Sample records for stimulation improved spatial

  1. Evaluation of focused multipolar stimulation for cochlear implants in acutely deafened cats

    NASA Astrophysics Data System (ADS)

    George, Shefin S.; Wise, Andrew K.; Shivdasani, Mohit N.; Shepherd, Robert K.; Fallon, James B.

    2014-12-01

    Objective. The conductive nature of the fluids and tissues of the cochlea can lead to broad activation of spiral ganglion neurons using contemporary cochlear implant stimulation configurations such as monopolar (MP) stimulation. The relatively poor spatial selectivity is thought to limit implant performance, particularly in noisy environments. Several current focusing techniques have been proposed to reduce the spread of activation with the aim towards achieving improved clinical performance. Approach. The present research evaluated the efficacy of focused multipolar (FMP) stimulation, a relatively new focusing technique in the cochlea, and compared its efficacy to both MP stimulation and tripolar (TP) stimulation. The spread of neural activity across the inferior colliculus (IC), measured by recording the spatial tuning curve, was used as a measure of spatial selectivity. Adult cats (n = 6) were acutely deafened and implanted with an intracochlear electrode array before multi-unit responses were recorded across the cochleotopic gradient of the contralateral IC. Recordings were made in response to acoustic and electrical stimulation using the MP, TP and FMP configurations. Main results. FMP and TP stimulation resulted in greater spatial selectivity than MP stimulation. However, thresholds were significantly higher (p < 0.001) for FMP and TP stimulation compared to MP stimulation. There were no differences found in spatial selectivity and threshold between FMP and TP stimulation. Significance. The greater spatial selectivity of FMP and TP stimulation would be expected to result in improved clinical performance. However, further research will be required to demonstrate the efficacy of these modes of stimulation after longer durations of deafness.

  2. Vestibular stimulation, spatial hemineglect and dysphasia, selective effects.

    PubMed

    Vallar, G; Papagno, C; Rusconi, M L; Bisiach, E

    1995-09-01

    The selectivity of the effects of vestibular stimulation was investigated in a left brain-damaged patient suffering from right visuo-spatial hemineglect and severe dysplasia. Vestibular stimulation temporarily improved the former but not the latter disorder. These results support the view that this treatment improves hemineglect by a specific effect, running counter the rightward distortion of egocentric co-ordinates, rather than by a general hemispheric activation.

  3. Mineralocorticoid receptor stimulation effects on spatial memory in healthy young adults: A study using the virtual Morris Water Maze task.

    PubMed

    Piber, Dominique; Schultebraucks, Katharina; Mueller, Sven C; Deuter, Christian Eric; Wingenfeld, Katja; Otte, Christian

    2016-12-01

    Stress hormones such as cortisol are known to influence a wide range of cognitive functions, including hippocampal based spatial memory. In the brain, cortisol acts via two different receptors: the glucocorticoid (GR) and the mineralocorticoid receptor (MR). As the MR has a high density in the hippocampus, we examined the effects of pharmacological MR stimulation on spatial memory. Eighty healthy participants (40 women, 40 men, mean age=23.9years±SD=3.3) completed the virtual Morris Water Maze (vMWM) task to test spatial encoding and spatial memory retrieval after receiving 0.4mg fludrocortisone, a MR agonist, or placebo. There was no effect of MR stimulation on spatial encoding during the vMWM task. However, participants who received fludrocortisone exhibited improved spatial memory retrieval performance. There was neither a main effect of sex nor a sex-by-treatment interaction. In young healthy participants, MR stimulation improved hippocampal based spatial memory retrieval in a virtual Morris Water Maze task. Our study not only confirms the importance of MR function in spatial memory, but suggests beneficial effects of acute MR stimulation on spatial memory retrieval in humans. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Cochlear-implant spatial selectivity with monopolar, bipolar and tripolar stimulation.

    PubMed

    Zhu, Ziyan; Tang, Qing; Zeng, Fan-Gang; Guan, Tian; Ye, Datian

    2012-01-01

    Sharp spatial selectivity is critical to auditory performance, particularly in pitch-related tasks. Most contemporary cochlear implants have employed monopolar stimulation that produces broad electric fields, which presumably contribute to poor pitch and pitch-related performance by implant users. Bipolar or tripolar stimulation can generate focused electric fields but requires higher current to reach threshold and, more interestingly, has not produced any apparent improvement in cochlear-implant performance. The present study addressed this dilemma by measuring psychophysical and physiological spatial selectivity with both broad and focused stimulations in the same cohort of subjects. Different current levels were adjusted by systematically measuring loudness growth for each stimulus, each stimulation mode, and in each subject. Both psychophysical and physiological measures showed that, although focused stimulation produced significantly sharper spatial tuning than monopolar stimulation, it could shift the tuning position or even split the tuning tips. The altered tuning with focused stimulation is interpreted as a result of poor electrode-to-neuron interface in the cochlea, and is suggested to be mainly responsible for the lack of consistent improvement in implant performance. A linear model could satisfactorily quantify the psychophysical and physiological data and derive the tuning width. Significant correlation was found between the individual physiological and psychophysical tuning widths, and the correlation was improved by log-linearly transforming the physiological data to predict the psychophysical data. Because the physiological measure took only one-tenth of the time of the psychophysical measure, the present model is of high clinical significance in terms of predicting and improving cochlear-implant performance. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Cochlear Implant Spatial Selectivity with Monopolar, Bipolar and Tripolar Stimulation

    PubMed Central

    Zhu, Ziyan; Tang, Qing; Zeng, Fan-Gang; Guan, Tian; Ye, Datian

    2011-01-01

    Sharp spatial selectivity is critical to auditory performance, particularly in pitch related tasks. Most contemporary cochlear implants have employed monopolar stimulation that produces broad electric fields, which presumably contribute to poor pitch and pitch-related performance by implant users. Bipolar or tripolar stimulation can generate focused electric fields but requires higher current to reach threshold and, more interestingly, has not produced any apparent improvement in cochlear implant performance. The present study addressed this dilemma by measuring psychophysical and physiological spatial selectivity with both broad and focused stimulations in the same cohort of subjects. Different current levels were adjusted by systematically measuring loudness growth for each stimulus, each stimulation mode, and in each subject. Both psychophysical and physiological measures showed that, although focused stimulation produced significantly sharper spatial tuning than monopolar stimulation, it could shift the tuning position or even split the tuning tips. The altered tuning with focused stimulation is interpreted as a result of poor electrode-to-neuron interface in the cochlea, and is suggested to be mainly responsible for the lack of consistent improvement in implant performance. A linear model could satisfactorily quantify the psychophysical and physiological data and derive the tuning width. Significant correlation was found between the individual physiological and psychophysical tuning widths, and the correlation was improved by log-linearly transforming the physiological data to predict the psychophysical data. Because the physiological measure took only one-tenth of the time of the psychophysical measure, the present model is of high clinical significance in terms of predicting and improving cochlear implant performance. PMID:22138630

  6. Identifying the appropriate time for deep brain stimulation to achieve spatial memory improvement on the Morris water maze.

    PubMed

    Jeong, Da Un; Lee, Jihyeon; Chang, Won Seok; Chang, Jin Woo

    2017-03-07

    The possibility of using deep brain stimulation (DBS) for memory enhancement has recently been reported, but the precise underlying mechanisms of its effects remain unknown. Our previous study suggested that spatial memory improvement by medial septum (MS)-DBS may be associated with cholinergic regulation and neurogenesis. However, the affected stage of memory could not be distinguished because the stimulation was delivered during the execution of all memory processes. Therefore, this study was performed to determine the stage of memory affected by MS-DBS. Rats were administered 192 IgG-saporin to lesion cholinergic neurons. Stimulation was delivered at different times in different groups of rats: 5 days before the Morris water maze test (pre-stimulation), 5 days during the training phase of the Morris water maze test (training-stimulation), and 2 h before the Morris water maze probe test (probe-stimulation). A fourth group of rats was lesioned but received no stimulation. These four groups were compared with a normal (control) group. The most effective memory restoration occurred in the pre-stimulation group. Moreover, the pre-stimulation group exhibited better recall of the platform position than the other stimulation groups. An increase in the level of brain derived neurotrophic factor (BDNF) was observed in the pre-stimulation group; this increase was maintained for 1 week. However, acetylcholinesterase activity in the pre-stimulation group was not significantly different from the lesion group. Memory impairment due to cholinergic denervation can be improved by DBS. The improvement is significantly correlated with the up-regulation of BDNF expression and neurogenesis. Based on the results of this study, the use of MS-DBS during the early stage of disease may restore spatial memory impairment.

  7. Subthalamic nucleus stimulation selectively improves motor and visual memory performance in Parkinson's disease.

    PubMed

    Mollion, Hélène; Dominey, Peter Ford; Broussolle, Emmanuel; Ventre-Dominey, Jocelyne

    2011-09-01

    Although the treatment of Parkinson's disease via subthalamic stimulation yields remarkable improvements in motor symptoms, its effects on memory function are less clear. In this context, we previously demonstrated dissociable effects of levodopa therapy on parkinsonian performance in spatial and nonspatial visual working memory. Here we used the same protocol with an additional, purely motor task to investigate visual memory and motor performance in 2 groups of patients with Parkinson's disease with or without subthalamic stimulation. In each stimulation condition, subjects performed a simple motor task and 3 successive cognitive tasks: 1 conditional color-response association task and 2 visual (spatial and nonspatial) working memory tasks. The Parkinson's groups were compared with a control group of age-matched healthy subjects. Our principal results demonstrated that (1) in the motor task, stimulated patients were significantly improved with respect to nonstimulated patients and did not differ significantly from healthy controls, and (2) in the cognitive tasks, stimulated patients were significantly improved with respect to nonstimulated patients, but both remained significantly impaired when compared with healthy controls. These results demonstrate selective effects of subthalamic stimulation on parkinsonian disorders of motor and visual memory functions, with clear motor improvement for stimulated patients and a partial improvement for their visual memory processing. Copyright © 2011 Movement Disorder Society.

  8. Direct Electrical Stimulation of the Human Entorhinal Region and Hippocampus Impairs Memory.

    PubMed

    Jacobs, Joshua; Miller, Jonathan; Lee, Sang Ah; Coffey, Tom; Watrous, Andrew J; Sperling, Michael R; Sharan, Ashwini; Worrell, Gregory; Berry, Brent; Lega, Bradley; Jobst, Barbara C; Davis, Kathryn; Gross, Robert E; Sheth, Sameer A; Ezzyat, Youssef; Das, Sandhitsu R; Stein, Joel; Gorniak, Richard; Kahana, Michael J; Rizzuto, Daniel S

    2016-12-07

    Deep brain stimulation (DBS) has shown promise for treating a range of brain disorders and neurological conditions. One recent study showed that DBS in the entorhinal region improved the accuracy of human spatial memory. Based on this line of work, we performed a series of experiments to more fully characterize the effects of DBS in the medial temporal lobe on human memory. Neurosurgical patients with implanted electrodes performed spatial and verbal-episodic memory tasks. During the encoding periods of both tasks, subjects received electrical stimulation at 50 Hz. In contrast to earlier work, electrical stimulation impaired memory performance significantly in both spatial and verbal tasks. Stimulation in both the entorhinal region and hippocampus caused decreased memory performance. These findings indicate that the entorhinal region and hippocampus are causally involved in human memory and suggest that refined methods are needed to use DBS in these regions to improve memory. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Caloric vestibular stimulation and postural control in patients with spatial neglect following stroke.

    PubMed

    Sturt, Ruth; Punt, T David

    2013-01-01

    The impact of spatial neglect remains a substantial challenge to patients undergoing rehabilitation following stroke. Beyond the relatively well-described implications for visuospatial function, neglect is increasingly shown to have a negative impact on the wider aspects of sensori-motor performance with corresponding implications for activities including gait and balance. Caloric vestibular stimulation (CVS) administered to the contralesional ear has previously been shown to improve performance in patients with spatial neglect. Here, in Experiment One, we investigated the effect of CVS on clinical measures of spatial neglect and postural control in three groups of patients following stroke; left brain damaged patients (LBD, n = 6), right brain damaged patients without neglect (RBD-, n = 6), and right brain damaged patients with neglect (RBD+ , n = 6). While post-stimulation scores demonstrated an improvement for participants with spatial neglect, further analysis of postural scores indicated that improvement was selective for asymmetrical activities, with symmetrical activities remaining unchanged. We interpret these results with reference to the related problem of extinction which predicts that activities demanding synchronous bilateral activity (symmetrical activities) would cause greater difficulties for patients with neglect. In Experiment Two, we tested a further six RBD+ patients on the same measures following CVS to the ipsilesional (right) ear. There was no significant improvement in perceptual or postural scores. Our findings are supportive of previous studies that demonstrate improvement in perception and movement for patients with spatial neglect following contralesional CVS and suggest that these improvements may have clinical benefits.

  10. Enhanced working memory performance via transcranial direct current stimulation: The possibility of near and far transfer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Trumbo, Michael C.; Matzen, Laura E.; Coffman, Brian A.

    Although working memory (WM) training programs consistently result in improvement on the trained task, benefit is typically short-lived and extends only to tasks very similar to the trained task (i.e., near transfer). It is possible that pairing repeated performance of a WM task with brain stimulation encourages plasticity in brain networks involved in WM task performance, thereby improving the training benefit. In the current study, transcranial direct current stimulation (tDCS) was paired with performance of a WM task (n-back). In Experiment 1, participants performed a spatial location-monitoring n-back during stimulation, while Experiment 2 used a verbal identity-monitoring n-back. In eachmore » experiment, participants received either active (2.0 mA) or sham (0.1 mA) stimulation with the anode placed over either the right or the left dorsolateral prefrontal cortex (DLPFC) and the cathode placed extracephalically. In Experiment 1, only participants receiving active stimulation with the anode placed over the right DLPFC showed marginal improvement on the trained spatial n-back, which did not extend to a near transfer (verbal n-back) or far transfer task (a matrix-reasoning task designed to measure fluid intelligence). Here, in Experiment 2, both left and right anode placements led to improvement, and right DLPFC stimulation resulted in numerical (though not sham-adjusted) improvement on the near transfer (spatial n-back) and far transfer (fluid intelligence) task. Results suggest that WM training paired with brain stimulation may result in cognitive enhancement that transfers to performance on other tasks, depending on the combination of training task and tDCS parameters used.« less

  11. Enhanced working memory performance via transcranial direct current stimulation: The possibility of near and far transfer

    DOE PAGES

    Trumbo, Michael C.; Matzen, Laura E.; Coffman, Brian A.; ...

    2016-10-15

    Although working memory (WM) training programs consistently result in improvement on the trained task, benefit is typically short-lived and extends only to tasks very similar to the trained task (i.e., near transfer). It is possible that pairing repeated performance of a WM task with brain stimulation encourages plasticity in brain networks involved in WM task performance, thereby improving the training benefit. In the current study, transcranial direct current stimulation (tDCS) was paired with performance of a WM task (n-back). In Experiment 1, participants performed a spatial location-monitoring n-back during stimulation, while Experiment 2 used a verbal identity-monitoring n-back. In eachmore » experiment, participants received either active (2.0 mA) or sham (0.1 mA) stimulation with the anode placed over either the right or the left dorsolateral prefrontal cortex (DLPFC) and the cathode placed extracephalically. In Experiment 1, only participants receiving active stimulation with the anode placed over the right DLPFC showed marginal improvement on the trained spatial n-back, which did not extend to a near transfer (verbal n-back) or far transfer task (a matrix-reasoning task designed to measure fluid intelligence). Here, in Experiment 2, both left and right anode placements led to improvement, and right DLPFC stimulation resulted in numerical (though not sham-adjusted) improvement on the near transfer (spatial n-back) and far transfer (fluid intelligence) task. Results suggest that WM training paired with brain stimulation may result in cognitive enhancement that transfers to performance on other tasks, depending on the combination of training task and tDCS parameters used.« less

  12. Enhanced working memory performance via transcranial direct current stimulation: The possibility of near and far transfer.

    PubMed

    Trumbo, Michael C; Matzen, Laura E; Coffman, Brian A; Hunter, Michael A; Jones, Aaron P; Robinson, Charles S H; Clark, Vincent P

    2016-12-01

    Although working memory (WM) training programs consistently result in improvement on the trained task, benefit is typically short-lived and extends only to tasks very similar to the trained task (i.e., near transfer). It is possible that pairing repeated performance of a WM task with brain stimulation encourages plasticity in brain networks involved in WM task performance, thereby improving the training benefit. In the current study, transcranial direct current stimulation (tDCS) was paired with performance of a WM task (n-back). In Experiment 1, participants performed a spatial location-monitoring n-back during stimulation, while Experiment 2 used a verbal identity-monitoring n-back. In each experiment, participants received either active (2.0mA) or sham (0.1mA) stimulation with the anode placed over either the right or the left dorsolateral prefrontal cortex (DLPFC) and the cathode placed extracephalically. In Experiment 1, only participants receiving active stimulation with the anode placed over the right DLPFC showed marginal improvement on the trained spatial n-back, which did not extend to a near transfer (verbal n-back) or far transfer task (a matrix-reasoning task designed to measure fluid intelligence). In Experiment 2, both left and right anode placements led to improvement, and right DLPFC stimulation resulted in numerical (though not sham-adjusted) improvement on the near transfer (spatial n-back) and far transfer (fluid intelligence) task. Results suggest that WM training paired with brain stimulation may result in cognitive enhancement that transfers to performance on other tasks, depending on the combination of training task and tDCS parameters used. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Evaluation of focused multipolar stimulation for cochlear implants in long-term deafened cats

    NASA Astrophysics Data System (ADS)

    George, Shefin S.; Wise, Andrew K.; Fallon, James B.; Shepherd, Robert K.

    2015-06-01

    Objective. Focused multipolar (FMP) stimulation has been shown to produce restricted neural activation using intracochlear stimulation in animals with a normal population of spiral ganglion neurons (SGNs). However, in a clinical setting, the widespread loss of SGNs and peripheral fibres following deafness is expected to influence the effectiveness of FMP. Approach. We compared the efficacy of FMP stimulation to both monopolar (MP) and tripolar (TP) stimulation in long-term deafened cat cochleae (n = 8). Unlike our previous study, these cochleae contained <10% of the normal SGN population adjacent to the electrode array. We also evaluated the effect of electrode position on stimulation modes by using either modiolar facing or lateral wall facing half-band electrodes. The spread of neural activity across the inferior colliculus, a major nucleus within the central auditory pathway, was used as a measure of spatial selectivity. Main results. In cochleae with significant SGN degeneration, we observed that FMP and TP stimulation resulted in greater spatial selectivity than MP stimulation (p < 0.001). However, thresholds were significantly higher for FMP and TP stimulation compared to MP stimulation (p < 0.001). No difference between FMP and TP stimulation was found in any measures. The high threshold levels for FMP stimulation was significantly reduced without compromising spatial selectivity by varying the degree of current focusing (referred as ‘partial-FMP’ stimulation). Spatial selectivity of all stimulation modes was unaffected by the electrode position. Finally, spatial selectivity in long-term deafened cochleae was significantly less than that of cochleae with normal SGN population (George S S et al 2014 J. Neural Eng. 11 065003). Significance. The present results indicate that the greater spatial selectivity of FMP and TP stimulation over MP stimulation is maintained in cochleae with significant neural degeneration and is not adversely affected by electrode position. The greater spatial selectivity of FMP and TP stimulation would be expected to result in improved clinical performance.

  14. Electro-triggering and electrochemical monitoring of dopamine exocytosis from a single cell by using ultrathin electrodes based on Au nanowires

    NASA Astrophysics Data System (ADS)

    Kang, Mijeong; Yoo, Seung Min; Gwak, Raekeun; Eom, Gayoung; Kim, Jihwan; Lee, Sang Yup; Kim, Bongsoo

    2015-12-01

    A sophisticated set of an Au nanowire (NW) stimulator-Au NW detector system is developed for electrical cell stimulation and electrochemical analysis of subsequent exocytosis with very high spatial resolution. Dopamine release from a rat pheochromocytoma cell is more stimulated by a more negative voltage pulse. This system could help to improve the therapeutic efficacy of electrotherapies by providing valuable information on their healing mechanism.A sophisticated set of an Au nanowire (NW) stimulator-Au NW detector system is developed for electrical cell stimulation and electrochemical analysis of subsequent exocytosis with very high spatial resolution. Dopamine release from a rat pheochromocytoma cell is more stimulated by a more negative voltage pulse. This system could help to improve the therapeutic efficacy of electrotherapies by providing valuable information on their healing mechanism. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06021d

  15. Transcranial magnetic stimulation: Improved coil design for deep brain investigation

    NASA Astrophysics Data System (ADS)

    Crowther, L. J.; Marketos, P.; Williams, P. I.; Melikhov, Y.; Jiles, D. C.; Starzewski, J. H.

    2011-04-01

    This paper reports on a design for a coil for transcranial magnetic stimulation. The design shows potential for improving the penetration depth of the magnetic field, allowing stimulation of subcortical structures within the brain. The magnetic and induced electric fields in the human head have been calculated with finite element electromagnetic modeling software and compared with empirical measurements. Results show that the coil design used gives improved penetration depth, but also indicates the likelihood of stimulation of additional tissue resulting from the spatial distribution of the magnetic field.

  16. Balanced bifrontal transcranial direct current stimulation enhances working memory in adults with high-functioning autism: a sham-controlled crossover study.

    PubMed

    van Steenburgh, J Jason; Varvaris, Mark; Schretlen, David J; Vannorsdall, Tracy D; Gordon, Barry

    2017-01-01

    Working memory (WM) often is impaired in autism spectrum disorder (ASD). Such impairment may underlie core deficits in cognition and social functioning. Transcranial direct current stimulation (tDCS) has been shown to enhance WM in both healthy adults and clinical populations, but its efficacy in ASD is unknown. We predicted that bifrontal tDCS would improve WM performances of adults with high-functioning autism during active stimulation compared to sham stimulation and that such enhancement would generalize to an untrained task. Twelve adults with high-functioning ASD engaged in a battery of WM tasks that included backward spatial span, backward digit span, spatial n -back and letter n -back. While engaged, 40 min of 1.5 mA bifrontal stimulation was applied over the left and the right dorsolateral prefrontal cortices (DLPFC). Using a single-blind crossover design, each participant received left anodal/right cathodal stimulation, right anodal/left cathodal stimulation, or sham stimulation, in randomized counterbalanced order on three separate days. Following tDCS, participants again engaged in letter and spatial n -back tasks before taking the Brief Test of Attention (BTA). We used repeated-measures ANOVA to compare overall performance on the WM battery as measured by a composite of z -scores for all five measures. Post hoc ANOVAs, t tests, Friedman's tests, and Wilcoxon signed-rank tests were used to measure the online and offline effects of tDCS and to assess performances on individual measures. Compared to sham stimulation, both left DLPFC anodal stimulation ( t 11  = 5.4, p  = 0.0002) and right DLPFC anodal stimulation ( t 11  = 3.57, p  = 0.004) improved overall WM performance. Left anodal stimulation ( t 11  = 3.9, p  = 0.003) and right anodal stimulation ( t 11  = 2.7, p  = 0.019) enhanced performances during stimulation. Enhancement transferred to an untrained task 50 min after right anodal stimulation (z 11  = 2.263, p  = 0.024). The tasks that showed the largest effects of active stimulation were spatial span backward ( z 11  = 2.39, p  = 0.017) and BTA ( z 11  = 2.263, p  = 0.024). In adults with high-functioning ASD, active bifrontal tDCS given during WM tasks appears to improve performance. TDCS benefits also transferred to an untrained task completed shortly after stimulation. These results suggest that tDCS can improve WM task performance and could reduce some core deficits of autism. NCT01602263.

  17. Recovery from Spatial Neglect with Intra- and Transhemispheric Functional Connectivity Changes in Vestibular and Visual Cortex Areas-A Case Study.

    PubMed

    Conrad, Julian; Boegle, Rainer; Ertl, Matthias; Brandt, Thomas; Dieterich, Marianne

    2018-01-01

    Vestibular signals are involved in higher cortical functions like spatial orientation and its disorders. Vestibular dysfunction contributes, for example, to spatial neglect which can be transiently improved by caloric stimulation. The exact roles and mechanisms of the vestibular and visual systems for the recovery of neglect are not yet known. Resting-state functional connectivity (fc) magnetic resonance imaging was recorded in a patient with hemispatial neglect during the acute phase and after recovery 6 months later following a right middle cerebral artery infarction before and after caloric vestibular stimulation. Seeds in the vestibular [parietal operculum (OP2)], the parietal [posterior parietal cortex (PPC); 7A, hIP3], and the visual cortex (VC) were used for the analysis. During the acute stage after caloric stimulation the fc of the right OP2 to the left OP2, the anterior cingulum, and the para/hippocampus was increased bilaterally (i.e., the vestibular network), while the interhemispheric fc was reduced between homologous regions in the VC. After 6 months, similar fc increases in the vestibular network were found without stimulation. In addition, fc increases of the OP2 to the PPC and the VC were seen; interhemispherically this was true for both PPCs and for the right PPC to both VCs. Improvement of neglect after caloric stimulation in the acute phase was associated with increased fc of vestibular cortex areas in both hemispheres to the para-hippocampus and the dorsal anterior cingulum, but simultaneously with reduced interhemispheric VC connectivity. This disclosed a, to some extent, similar but also distinct short-term mechanism (vestibular stimulation) of an improvement of spatial orientation compared to the long-term recovery of neglect.

  18. Acupuncture Stimulation Alleviates Corticosterone-Induced Impairments of Spatial Memory and Cholinergic Neurons in Rats

    PubMed Central

    Lee, Bombi; Sur, Bong-Jun; Kwon, Sunoh; Jung, Euntaek; Shim, Insop; Lee, Hyejung; Hahm, Dae-Hyun

    2012-01-01

    The purpose of this study was to examine whether acupuncture improves spatial cognitive impairment induced by repeated corticosterone (CORT) administration in rats. The effect of acupuncture on the acetylcholinergic system was also investigated in the hippocampus. Male rats were subcutaneously injected with CORT (5 mg/kg) once daily for 21 days. Acupuncture stimulation was performed at the HT7 (Sinmun) acupoint for 5 min before CORT injection. HT7 acupoint is located at the end of transverse crease of ulnar wrist of forepaw. In CORT-treated rats, reduced spatial cognitive function was associated with significant increases in plasma CORT level (+36%) and hippocampal CORT level (+204%) compared with saline-treated rats. Acupuncture stimulation improved the escape latency for finding the platform in the Morris water maze. Consistently, the acupuncture significantly alleviated memory-associated decreases in cholinergic immunoreactivity and mRNA expression of BDNF and CREB in the hippocampus. These findings demonstrate that stimulation of HT7 acupoint produced significant neuroprotective activity against the neuronal impairment and memory dysfunction. PMID:22216057

  19. Visual-spatial memory may be enhanced with theta burst deep brain stimulation of the fornix: a preliminary investigation with four cases.

    PubMed

    Miller, Jonathan P; Sweet, Jennifer A; Bailey, Christopher M; Munyon, Charles N; Luders, Hans O; Fastenau, Philip S

    2015-07-01

    Memory loss after brain injury can be a source of considerable morbidity, but there are presently few therapeutic options for restoring memory function. We have previously demonstrated that burst stimulation of the fornix is able to significantly improve memory in a rodent model of traumatic brain injury. The present study is a preliminary investigation with a small group of cases to explore whether theta burst stimulation of the fornix might improve memory in humans. Four individuals undergoing stereo-electroencephalography evaluation for drug-resistant epilepsy were enrolled. All participants were implanted with an electrode into the proximal fornix and dorsal hippocampal commissure on the language dominant (n = 3) or language non-dominant (n = 1) side, and stimulation of this electrode reliably produced a diffuse evoked potential in the head and body of the ipsilateral hippocampus. Each participant underwent testing of verbal memory (Rey Auditory-Verbal Learning Test), visual-spatial memory (Medical College of Georgia Complex Figure Test), and visual confrontational naming (Boston Naming Test Short Form) once per day over at least two consecutive days using novel test forms each day. For 50% of the trials, the fornix electrode was continuously stimulated using a burst pattern (200 Hz in 100 ms trains, five trains per second, 100 µs, 7 mA) and was compared with sham stimulation. Participants and examiners were blinded to whether stimulation was active or not, and the order of stimulation was randomized. The small sample size precluded use of inferential statistics; therefore, data were analysed using descriptive statistics and graphic analysis. Burst stimulation of the fornix was not perceived by any of the participants but was associated with a robust reversible improvement in immediate and delayed performance on the Medical College of Georgia Complex Figure Test. There were no apparent differences on either Rey Auditory-Verbal Learning Test or Boston Naming Test. There was no apparent relationship between performance and side of stimulation (language dominant or non-dominant). There were no complications. Preliminary evidence in this small sample of patients with drug-resistant epilepsy suggests that theta burst stimulation of the fornix may be associated with improvement in visual-spatial memory. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Prenatal complex rhythmic music sound stimulation facilitates postnatal spatial learning but transiently impairs memory in the domestic chick.

    PubMed

    Kauser, H; Roy, S; Pal, A; Sreenivas, V; Mathur, R; Wadhwa, S; Jain, S

    2011-01-01

    Early experience has a profound influence on brain development, and the modulation of prenatal perceptual learning by external environmental stimuli has been shown in birds, rodents and mammals. In the present study, the effect of prenatal complex rhythmic music sound stimulation on postnatal spatial learning, memory and isolation stress was observed. Auditory stimulation with either music or species-specific sounds or no stimulation (control) was provided to separate sets of fertilized eggs from day 10 of incubation. Following hatching, the chicks at age 24, 72 and 120 h were tested on a T-maze for spatial learning and the memory of the learnt task was assessed 24 h after training. In the posthatch chicks at all ages, the plasma corticosterone levels were estimated following 10 min of isolation. The chicks of all ages in the three groups took less (p < 0.001) time to navigate the maze over the three trials thereby showing an improvement with training. In both sound-stimulated groups, the total time taken to reach the target decreased significantly (p < 0.01) in comparison to the unstimulated control group, indicating the facilitation of spatial learning. However, this decline was more at 24 h than at later posthatch ages. When tested for memory after 24 h of training, only the music-stimulated chicks at posthatch age 24 h took a significantly longer (p < 0.001) time to traverse the maze, suggesting a temporary impairment in their retention of the learnt task. In both sound-stimulated groups at 24 h, the plasma corticosterone levels were significantly decreased (p < 0.001) and increased thereafter at 72 h (p < 0.001) and 120 h which may contribute to the differential response in spatial learning. Thus, prenatal auditory stimulation with either species-specific or complex rhythmic music sounds facilitates spatial learning, though the music stimulation transiently impairs postnatal memory. 2011 S. Karger AG, Basel.

  1. Deep Brain Stimulation using Magnetic Fields

    NASA Astrophysics Data System (ADS)

    Jiles, David; Williams, Paul; Crowther, Lawrence; Iowa State University Team; Wolfson CentreMagnetics Team

    2011-03-01

    New applications for transcranial magnetic stimulation are developing rapidly for both diagnostic and therapeutic purposes. Therefore so is the demand for improved performance, particularly in terms of their ability to stimulate deeper regions of the brain and to do so selectively. The coil designs that are used presently are limited in their ability to stimulate the brain at depth and with high spatial focality. Consequently, any improvement in coil performance would have a significant impact in extending the usefulness of TMS in both clinical applications and academic research studies. New and improved coil designs have then been developed, modeled and tested as a result of this work. A large magnetizing coil, 300mm in diameter and compatible with a commercial TMS system has been constructed to determine its feasibility for use as a deep brain stimulator. The results of this work have suggested directions that could be pursued in order to further improve the coil designs.

  2. Lasting improvements in left spatial neglect following a protocol combining neck-muscle vibration and voluntary arm movements: a case-study.

    PubMed

    Ceyte, Hadrien; Beis, Jean-Marie; Simon, Mathilde; Rémy, Ariane; Anxionnat, René; Paysant, Jean; Caudron, Sébastien

    2018-01-22

    Beyond promising experimental results of sensory passive stimulations in spatial cognition disorders, some questions still remain regarding interests of these stimulations during the daily activities in neglect. The aim of this case-study was to evaluate the effects of a protocol combining left neck-muscle vibration with daily simple movements, like arm pointing movements, on perceptivo-locomotor deficits in a left spatial neglect patient. Two neuropsychological tests, one subjective straight-ahead pointing (SSA) test and one wheelchair navigation test were carried out before the combination protocol, immediately after, 1 h later, and 24 h later. The results showed a reduction of neglect spatial bias following the protocol lasted at least 24 h in all the tests (except for the SSA test due to the unavailability of the pointing device). The range of improvements in the symptoms of spatial neglect suggests that this therapeutic intervention based on the combining neck-muscle vibration to voluntary arm movements could be a useful treatment for this condition. One of future investigation axes should be the development of a vibratory tool in order to facilitate the combining this proprioceptive stimulation to daily activities. Implications for rehabilitation Spatial neglect is a perplexing neuropsychological syndrome, affecting different domains of spatial cognition and impacting also the functional domain. The treatments based on neck-muscle vibration are simple to use, non-invasive and requires none active participation of patient. A therapeutic intervention based on the combining left neck-muscle vibration and voluntary arm movements in a left-spatial-neglect show a lasting reduction of symptoms especially in daily activities. The combination of treatments based on the Bottom-Up approach opens innovative perspectives in rehabilitation.

  3. [Stimulation of D2-receptors improves passive avoidance learning in female rats].

    PubMed

    Fedotova, Iu O

    2012-01-01

    The involvement of D2-receptors in learning/memory processes during ovary cycle was assessed in the adult female rats. Quinperole (0,1 mg/kg, i.p.), D2-receptor agonist and sulpiride (10,0 mg/kg, i.p.), D2-receptor antagonist were injected chronically to adult female rats. Learning of these animals was assessed in different models: passive avoidance performance and Morris water maze. Chronic quinperole administration to females resulted in the appearance of the passive avoidance performance in proestrous and estrous, as distinct from the control animals. Also, quinperole improved spatial learning in proestrous and stimulated it in estrous in Morris water maze. Chronic sulpiride administration similarly impaired non-spatial and spatial learning in females during all phases of ovary cycle. The results of the study suggest modulating role of D2-receptors in learning/memory processes during ovary cycle in the adult female rats.

  4. Vestibular-somatosensory interactions: effects of passive whole-body rotation on somatosensory detection.

    PubMed

    Ferrè, Elisa Raffaella; Kaliuzhna, Mariia; Herbelin, Bruno; Haggard, Patrick; Blanke, Olaf

    2014-01-01

    Vestibular signals are strongly integrated with information from several other sensory modalities. For example, vestibular stimulation was reported to improve tactile detection. However, this improvement could reflect either a multimodal interaction or an indirect interaction driven by vestibular effects on spatial attention and orienting. Here we investigate whether natural vestibular activation induced by passive whole-body rotation influences tactile detection. In particular, we assessed the ability to detect faint tactile stimuli to the fingertips of the left and right hand during spatially congruent or incongruent rotations. We found that passive whole-body rotations significantly enhanced sensitivity to faint shocks, without affecting response bias. Critically, this enhancement of somatosensory sensitivity did not depend on the spatial congruency between the direction of rotation and the hand stimulated. Thus, our results support a multimodal interaction, likely in brain areas receiving both vestibular and somatosensory signals.

  5. Ventromedial prefrontal cortex stimulation enhances memory and hippocampal neurogenesis in the middle-aged rats

    PubMed Central

    Liu, Albert; Jain, Neeraj; Vyas, Ajai; Lim, Lee Wei

    2015-01-01

    Memory dysfunction is a key symptom of age-related dementia. Although recent studies have suggested positive effects of electrical stimulation for memory enhancement, its potential targets remain largely unknown. In this study, we hypothesized that spatially targeted deep brain stimulation of ventromedial prefrontal cortex enhanced memory functions in a middle-aged rat model. Our results show that acute stimulation enhanced the short-, but not the long-term memory in the novel-object recognition task. Interestingly, after chronic high-frequency stimulation, both the short- and long-term memories were robustly improved in the novel-object recognition test and Morris water-maze spatial task compared to sham. Our results also demonstrated that chronic ventromedial prefrontal cortex high-frequency stimulation upregulated neurogenesis-associated genes along with enhanced hippocampal cell proliferation. Importantly, these memory behaviors were strongly correlated with the hippocampal neurogenesis. Overall, these findings suggest that chronic ventromedial prefrontal cortex high-frequency stimulation may serve as a novel effective therapeutic target for dementia-related disorders. DOI: http://dx.doi.org/10.7554/eLife.04803.001 PMID:25768425

  6. Electrical stimulation vs. pulsed and continuous-wave optical stimulation of the rat prostate cavernous nerves, in vivo

    NASA Astrophysics Data System (ADS)

    Perkins, William C.; Lagoda, Gwen A.; Burnett, Arthur; Fried, Nathaniel M.

    2015-07-01

    Identification and preservation of the cavernous nerves (CNs) during prostate cancer surgery is critical for post-operative sexual function. Electrical nerve stimulation (ENS) mapping has previously been tested as an intraoperative tool for CN identification, but was found to be unreliable. ENS is limited by the need for electrode-tissue contact, poor spatial precision from electrical current spreading, and stimulation artifacts interfering with detection. Alternatively, optical nerve stimulation (ONS) provides noncontact stimulation, improved spatial selectivity, and elimination of stimulation artifacts. This study compares ENS to pulsed/CW ONS to explore the ONS mechanism. A total of eighty stimulations were performed in 5 rats, in vivo. ENS (4 V, 5 ms, 10 Hz) was compared to ONS using a pulsed diode laser nerve stimulator (1873 nm, 5 ms, 10 Hz) or CW diode laser nerve stimulator (1455 nm). Intracavernous pressure (ICP) response and nerve compound action potentials (nCAPs) were measured. All three stimulation modes (ENS, ONS-CW, ONS-P) produced comparable ICP magnitudes. However, ENS demonstrated more rapid ICP response times and well defined nCAPs compared to unmeasurable nCAPs for ONS. Further experiments measuring single action potentials during ENS and ONS are warranted to further understand differences in the ENS and ONS mechanisms.

  7. High frequency repetitive sensory stimulation improves temporal discrimination in healthy subjects.

    PubMed

    Erro, Roberto; Rocchi, Lorenzo; Antelmi, Elena; Palladino, Raffaele; Tinazzi, Michele; Rothwell, John; Bhatia, Kailash P

    2016-01-01

    High frequency electrical stimulation of an area of skin on a finger improves two-point spatial discrimination in the stimulated area, likely depending on plastic changes in the somatosensory cortex. However, it is unknown whether improvement also applies to temporal discrimination. Twelve young and ten elderly volunteers underwent the stimulation protocol onto the palmar skin of the right index finger. Somatosensory temporal discrimination threshold (STDT) was evaluated before and immediately after stimulation as well as 2.5h and 24h later. There was a significant reduction in somatosensory temporal threshold only on the stimulated finger. The effect was reversible, with STDT returning to the baseline values within 24h, and was smaller in the elderly than in the young participants. High frequency stimulation of the skin focally improves temporal discrimination in the area of stimulation. Given previous suggestions that the perceptual effects rely on plastic changes in the somatosensory cortex, our results are consistent with the idea that the timing of sensory stimuli is, at least partially, encoded in the primary somatosensory cortex. Such a protocol could potentially be used as a therapeutic intervention to ameliorate physiological decline in the elderly or in other disorders of sensorimotor integration. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  8. Spread of cochlear excitation during stimulation with pulsed infrared radiation: inferior colliculus measurements

    NASA Astrophysics Data System (ADS)

    Richter, C.-P.; Rajguru, S. M.; Matic, A. I.; Moreno, E. L.; Fishman, A. J.; Robinson, A. M.; Suh, E.; Walsh, J. T., Jr.

    2011-10-01

    Infrared neural stimulation (INS) has received considerable attention over the last few years. It provides an alternative method to artificially stimulate neurons without electrical current or the introduction of exogenous chromophores. One of the primary benefits of INS could be the improved spatial selectivity when compared with electrical stimulation. In the present study, we have evaluated the spatial selectivity of INS in the acutely damaged cochlea of guinea pigs and compared it to stimulation with acoustic tone pips in normal-hearing animals. The radiation was delivered via a 200 µm diameter optical fiber, which was inserted through a cochleostomy into the scala tympani of the basal cochlear turn. The stimulated section along the cochlear spiral ganglion was estimated from the neural responses recorded from the central nucleus of the inferior colliculus (ICC). ICC responses were recorded in response to cochlear INS using a multichannel penetrating electrode array. Spatial tuning curves (STCs) were constructed from the responses. For INS, approximately 55% of the activation profiles showed a single maximum, ~22% had two maxima and ~13% had multiple maxima. The remaining 10% of the profiles occurred at the limits of the electrode array and could not be classified. The majority of ICC STCs indicated that the spread of activation evoked by optical stimuli is comparable to that produced by acoustic tone pips.

  9. Effects of anodal transcranial direct current stimulation (tDCS) on behavioral and spatial memory during the early stage of traumatic brain injury in the rats.

    PubMed

    Yoon, Kyung Jae; Lee, Yong-Taek; Chae, Seoung Wan; Park, Chae Ri; Kim, Dae Yul

    2016-03-15

    Transcranial direct current stimulation (tDCS) is a noninvasive technique to modulate the neural membrane potential. Its effects in the early stage of traumatic brain injury (TBI) have rarely been investigated. This study assessed the effects of anodal tDCS on behavioral and spatial memory in a rat model of traumatic brain injury. Thirty six rats underwent lateral fluid percussion and were then randomly assigned to one of three groups: control (n=12), five-day tDCS over peri-lesional cortex at one (1W, n=12), or two (2W, n=12) weeks post-injury. The Barnes maze (BM) and Rotarod (RR) tests were evaluated in a blind manner on day 1, week 3 and week 5 post-injury. After three weeks, both the 1W and 2W groups showed significant improvements in the BM ratio (P<0.05), whereas only group 2W obtained a significant improvement in the RR ratio compared with the control group (P<0.05). However, there were no significant differences between any of the groups at five weeks after TBI. Immunohistochemistry revealed that only group 2W had a significantly higher brain-derived neurotrophic factor (BDNF) expression in the peri-lesional cortex, which was significantly correlated with the improvement of the Rotarod test at 3-week post-injury. However, BDNF expression in the ipsi-lesional hippocampus was not significantly different among the three groups. Group 1W tended to have increased choline/creatine ratios, as measured by magnetic resonance spectroscopy in the peri-lesional cortex, than the control group (P=0.051). Neither regimen aggravated the lesion volume or brain edema measured by MRI. These beneficial effects were not observed with either regimen at five weeks post-injury. In conclusions, anodal tDCS ameliorated behavioral and spatial memory function in the early phase after TBI when it is delivered two weeks post-injury. Earlier stimulation (one week post-injury) improves spatial memory only. However, the beneficial effects did not persist after cessation of the anodal stimulation. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Low-frequency transcranial magnetic stimulation is beneficial for enhancing synaptic plasticity in the aging brain.

    PubMed

    Zhang, Zhan-Chi; Luan, Feng; Xie, Chun-Yan; Geng, Dan-Dan; Wang, Yan-Yong; Ma, Jun

    2015-06-01

    In the aging brain, cognitive function gradually declines and causes a progressive reduction in the structural and functional plasticity of the hippocampus. Transcranial magnetic stimulation is an emerging and novel neurological and psychiatric tool used to investigate the neurobiology of cognitive function. Recent studies have demonstrated that low-frequency transcranial magnetic stimulation (≤1 Hz) ameliorates synaptic plasticity and spatial cognitive deficits in learning-impaired mice. However, the mechanisms by which this treatment improves these deficits during normal aging are still unknown. Therefore, the current study investigated the effects of transcranial magnetic stimulation on the brain-derived neurotrophic factor signal pathway, synaptic protein markers, and spatial memory behavior in the hippocampus of normal aged mice. The study also investigated the downstream regulator, Fyn kinase, and the downstream effectors, synaptophysin and growth-associated protein 43 (both synaptic markers), to determine the possible mechanisms by which transcranial magnetic stimulation regulates cognitive capacity. Transcranial magnetic stimulation with low intensity (110% average resting motor threshold intensity, 1 Hz) increased mRNA and protein levels of brain-derived neurotrophic factor, tropomyosin receptor kinase B, and Fyn in the hippocampus of aged mice. The treatment also upregulated the mRNA and protein expression of synaptophysin and growth-associated protein 43 in the hippocampus of these mice. In conclusion, brain-derived neurotrophic factor signaling may play an important role in sustaining and regulating structural synaptic plasticity induced by transcranial magnetic stimulation in the hippocampus of aging mice, and Fyn may be critical during this regulation. These responses may change the structural plasticity of the aging hippocampus, thereby improving cognitive function.

  11. [Influence of stimulation and blockade of α4β2 nicotinic acetylcholine receptors on learning of female rats in basic phases of ovary cycle].

    PubMed

    Fedotova, Iu O

    2014-03-01

    The present work was devoted to the comparative analysis of α4β2 nicotinic acetylcholine receptors (nAChRs) in learning/memory processes during ovary cycle in the adult female rats. RJR-2403 (1.0 mg/kg, i. p.), α4β2 nAChRs agonist and mecamylamine (1.0 mg/kg, i. p.), α4β2 nAChRs antagonist were injected chronically during 14 days. The processes of learning/memory were assessed in different models of learning: passive avoidance performance and Morris water maze. Chronic RJR-2403 administration to females improved the passive avoidance performance in proestrous and estrous as compared to the control animals. Also, RJR-2403 restored spatial learning of rats during proestrous phases in Morris water maze, and stimulated the dynamics of spatial learning during estrous phases. On the contrary, the chronic mecamylamine administration impaired non-spatial, and especially, spatial learning in females during key phases of ovary cycle. The results of the study suggest positive effect of α4β2 nAChRs stimulation in learning/memory processes during ovary cycle in the adult female rats.

  12. Fornix deep brain stimulation induced long-term spatial memory independent of hippocampal neurogenesis.

    PubMed

    Hescham, Sarah; Temel, Yasin; Schipper, Sandra; Lagiere, Mélanie; Schönfeld, Lisa-Maria; Blokland, Arjan; Jahanshahi, Ali

    2017-03-01

    Deep brain stimulation (DBS) is an established symptomatic treatment modality for movement disorders and constitutes an emerging therapeutic approach for the treatment of memory impairment. In line with this, fornix DBS has shown to ameliorate cognitive decline associated with dementia. Nonetheless, mechanisms mediating clinical effects in demented patients or patients with other neurological disorders are largely unknown. There is evidence that DBS is able to modulate neurophysiological activity in targeted brain regions. We therefore hypothesized that DBS might be able to influence cognitive function via activity-dependent regulation of hippocampal neurogenesis. Using stimulation parameters, which were validated to restore memory loss in a previous behavioral study, we here assessed long-term effects of fornix DBS. To do so, we injected the thymidine analog, 5-bromo-2'-deoxyuridine (BrdU), after DBS and perfused the animals 6.5 weeks later. A week prior to perfusion, memory performance was assessed in the water maze. We found that acute stimulation of the fornix improved spatial memory performance in the water maze when the probe trial was performed 1 h after the last training session. However, no evidence for stimulation-induced neurogenesis was found in fornix DBS rats when compared to sham. Our results suggest that fornix DBS improves memory functions independent of hippocampal neurogenesis, possibly through other mechanisms such as synaptic plasticity and acute neurotransmitter release.

  13. Parkinsonian gait improves with bilateral subthalamic nucleus deep brain stimulation during cognitive multi-tasking.

    PubMed

    Chenji, Gaurav; Wright, Melissa L; Chou, Kelvin L; Seidler, Rachael D; Patil, Parag G

    2017-05-01

    Gait impairment in Parkinson's disease reduces mobility and increases fall risk, particularly during cognitive multi-tasking. Studies suggest that bilateral subthalamic deep brain stimulation, a common surgical therapy, degrades motor performance under cognitive dual-task conditions, compared to unilateral stimulation. To measure the impact of bilateral versus unilateral subthalamic deep brain stimulation on walking kinematics with and without cognitive dual-tasking. Gait kinematics of seventeen patients with advanced Parkinson's disease who had undergone bilateral subthalamic deep brain stimulation were examined off medication under three stimulation states (bilateral, unilateral left, unilateral right) with and without a cognitive challenge, using an instrumented walkway system. Consistent with earlier studies, gait performance declined for all six measured parameters under cognitive dual-task conditions, independent of stimulation state. However, bilateral stimulation produced greater improvements in step length and double-limb support time than unilateral stimulation, and achieved similar performance for other gait parameters. Contrary to expectations from earlier studies of dual-task motor performance, bilateral subthalamic deep brain stimulation may assist in maintaining temporal and spatial gait performance under cognitive dual-task conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Spatially restricted electrical activation of retinal ganglion cells in the rabbit retina by hexapolar electrode return configuration

    NASA Astrophysics Data System (ADS)

    Habib, Amgad G.; Cameron, Morven A.; Suaning, Gregg J.; Lovell, Nigel H.; Morley, John W.

    2013-06-01

    Objective. Visual prostheses currently in development aim to restore some form of vision to patients suffering from diseases such as age-related macular degeneration and retinitis pigmentosa. Most rely on electrically stimulating inner retinal cells via electrodes implanted on or near the retina, resulting in percepts of light termed ‘phosphenes’. Activation of spatially distinct populations of cells in the retina is key for pattern vision to be produced. To achieve this, the electrical stimulation must be localized, activating cells only in the direct vicinity of the stimulating electrode(s). With this goal in mind, a hexagonal return (hexapolar) configuration has been proposed as an alternative to the traditional monopolar or bipolar return configurations for electrically stimulating the retina. This study investigated the efficacy of the hexapolar configuration in localizing the activation of retinal ganglion cells (RGCs), compared to a monopolar configuration. Approach. Patch-clamp electrophysiology was used to measure the activation thresholds of RGCs in whole-mount rabbit retina to monopolar and hexapolar electrical stimulation, applied subretinally. Main results. Hexapolar activation thresholds for RGCs located outside the hex guard were found to be significantly (>2 fold) higher than those located inside the area of tissue bounded by the hex guard. The hexapolar configuration localized the activation of RGCs more effectively than its monopolar counterpart. Furthermore, no difference in hexapolar thresholds or localization was observed when using cathodic-first versus anodic-first stimulation. Significance. The hexapolar configuration may provide an improved method for electrically stimulating spatially distinct populations of cells in retinal tissue.

  15. Deactivating stimulation sites based on low-rate thresholds improves spectral ripple and speech reception thresholds in cochlear implant users.

    PubMed

    Zhou, Ning

    2017-03-01

    The study examined whether the benefit of deactivating stimulation sites estimated to have broad neural excitation was attributed to improved spectral resolution in cochlear implant users. The subjects' spatial neural excitation pattern was estimated by measuring low-rate detection thresholds across the array [see Zhou (2016). PLoS One 11, e0165476]. Spectral resolution, as assessed by spectral-ripple discrimination thresholds, significantly improved after deactivation of five high-threshold sites. The magnitude of improvement in spectral-ripple discrimination thresholds predicted the magnitude of improvement in speech reception thresholds after deactivation. Results suggested that a smaller number of relatively independent channels provide a better outcome than using all channels that might interact.

  16. Does participation in art classes influence performance on two different cognitive tasks?

    PubMed

    Schindler, Manuel; Maihöfner, Christian; Bolwerk, Anne; Lang, Frieder R

    2017-04-01

    Effects of two mentally stimulating art interventions on processing speed and visuo-spatial cognition were compared in three samples. In a randomized 10-week art intervention study with a pre-post follow-up design, 113 adults (27 healthy older adults with subjective memory complaints, 50 healthy older adults and 36 healthy younger adults) were randomly assigned to one of two groups: visual art production or cognitive art evaluation, where the participants either produced or evaluated art. ANOVAs with repeated measures were computed to observe effects on the Symbol-Digit Test, and the Stick Test. Significant Time effects were found with regard to processing speed and visuo-spatial cognition. Additionally, there was found a significant Time × Sample interaction for processing speed. The effects proved robust after testing for education and adding sex as additional factor. Mental stimulation by participation in art classes leads to an improvement of processing speed and visuo-spatial cognition. Further investigation is required to improve understanding of the potential impact of art intervention on cognitive abilities across adulthood.

  17. Spatial and temporal variability in response to hybrid electro-optical stimulation

    NASA Astrophysics Data System (ADS)

    Duke, Austin R.; Lu, Hui; Jenkins, Michael W.; Chiel, Hillel J.; Jansen, E. Duco

    2012-06-01

    Hybrid electro-optical neural stimulation is a novel paradigm combining the advantages of optical and electrical stimulation techniques while reducing their respective limitations. However, in order to fulfill its promise, this technique requires reduced variability and improved reproducibility. Here we used a comparative physiological approach to aid the further development of this technique by identifying the spatial and temporal factors characteristic of hybrid stimulation that may contribute to experimental variability and/or a lack of reproducibility. Using transient pulses of infrared light delivered simultaneously with a bipolar electrical stimulus in either the marine mollusk Aplysia californica buccal nerve or the rat sciatic nerve, we determined the existence of a finite region of excitability with size altered by the strength of the optical stimulus and recruitment dictated by the polarity of the electrical stimulus. Hybrid stimulation radiant exposures yielding 50% probability of firing (RE50) were shown to be negatively correlated with the underlying changes in electrical stimulation threshold over time. In Aplysia, but not in the rat sciatic nerve, increasing optical radiant exposures (J cm-2) beyond the RE50 ultimately resulted in inhibition of evoked potentials. Accounting for the sources of variability identified in this study increased the reproducibility of stimulation from 35% to 93% in Aplysia and 23% to 76% in the rat with reduced variability.

  18. A Rehabilitation Protocol for Empowering Spatial Orientation in MCI. A Pilot Study.

    PubMed

    Gadler, Erminia; Grassi, Alessandra; Riva, Giuseppe

    2009-01-01

    Spatial navigation is among the first cognitive functions to be impaired in Alzheimer's disease [1] and deficit in this domain is detectable earlier in patients with Mild Cognitive Impairment [2]. Since efficacy of cognitive training in persons with MCI was successfully assessed [3], we developed a multitasking training protocol using virtual environments for stimulating attention, perception and visuo-spatial cognition in order to empower spatial orientation in MCI. Two healthy elders were exposed to the training over a period of four weeks and both showed improved performances in attention and orientation after the end of the intervention.

  19. Effect of low frequency electrical stimulation on seizure-induced short- and long-term impairments in learning and memory in rats.

    PubMed

    Esmaeilpour, Khadijeh; Sheibani, Vahid; Shabani, Mohammad; Mirnajafi-Zadeh, Javad

    2017-01-01

    Kindled seizures can impair learning and memory. In the present study the effect of low-frequency electrical stimulation (LFS) on kindled seizure-induced impairment in spatial learning and memory was investigated and followed up to one month. Animals were kindled by electrical stimulation of hippocampal CA1 area in a semi-rapid manner (12 stimulations per day). One group of animals received four trials of LFS at 30s, 6h, 24h, and 30h following the last kindling stimulation. Each LFS trial was consisted of 4 packages at 5min intervals. Each package contained 200 monophasic square wave pulses of 0.1ms duration at 1Hz. The Open field, Morris water maze, and novel object recognition tests were done 48h, 1week, 2weeks, and one month after the last kindling stimulation respectively. Kindled animals showed a significant impairment in learning and memory compared to control rats. LFS decreased the kindling-induced learning and memory impairments at 24h and one week following its application, but not at 2week or 1month after kindling. In the group of animals that received the same 4 trials of LFS again one week following the last kindling stimulation, the improving effect of LFS was observed even after one month. Obtained results showed that application of LFS in fully kindled animals has a long-term improving effect on spatial learning and memory. This effect can remain for a long duration (one month in this study) by increasing the number of applied LFS. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. A novel control software that improves the experimental workflow of scanning photostimulation experiments.

    PubMed

    Bendels, Michael H K; Beed, Prateep; Leibold, Christian; Schmitz, Dietmar; Johenning, Friedrich W

    2008-10-30

    Optical uncaging of caged compounds is a well-established method to study the functional anatomy of a brain region on the circuit level. We present an alternative approach to existing experimental setups. Using a low-magnification objective we acquire images for planning the spatial patterns of stimulation. Then high-magnification objectives are used during laser stimulation providing a laser spot between 2 microm and 20 microm size. The core of this system is a video-based control software that monitors and controls the connected devices, allows for planning of the experiment, coordinates the stimulation process and manages automatic data storage. This combines a high-resolution analysis of neuronal circuits with flexible and efficient online planning and execution of a grid of spatial stimulation patterns on a larger scale. The software offers special optical features that enable the system to achieve a maximum degree of spatial reliability. The hardware is mainly built upon standard laboratory devices and thus ideally suited to cost-effectively complement existing electrophysiological setups with a minimal amount of additional equipment. Finally, we demonstrate the performance of the system by mapping the excitatory and inhibitory connections of entorhinal cortex layer II stellate neurons and present an approach for the analysis of photo-induced synaptic responses in high spontaneous activity.

  1. Intensity coding in electric hearing: effects of electrode configurations and stimulation waveforms.

    PubMed

    Chua, Tiffany Elise H; Bachman, Mark; Zeng, Fan-Gang

    2011-01-01

    Current cochlear implants typically stimulate the auditory nerve with biphasic pulses and monopolar electrode configurations. Tripolar stimulation can increase spatial selectivity and potentially improve place pitch related perception but requires higher current levels to elicit the same loudness as monopolar stimulation. The present study combined delayed pseudomonophonasic pulses, which produce lower thresholds, with tripolar stimulation in an attempt to solve the power-performance tradeoff problem. The present study systematically measured thresholds, dynamic range, loudness growth, and intensity discrimination using either biphasic or delayed pseudomonophonasic pulses under both monopolar and tripolar stimulation. Participants were five Clarion cochlear implant users. For each subject, data from apical, middle, and basal electrode positions were collected when possible. Compared with biphasic pulses, delayed pseudomonophonasic pulses increased the dynamic range by lowering thresholds while maintaining comparable maximum allowable levels under both electrode configurations. However, delayed pseudomonophonasic pulses did not change the shape of loudness growth function and actually increased intensity discrimination limens, especially at lower current levels. The present results indicate that delayed pseudomonophonasic pulses coupled with tripolar stimulation cannot provide significant power savings nor can it increase the functional dynamic range. Whether this combined stimulation could improve functional spectral resolution remains to be seen.

  2. Clinical Applications of Transcranial Magnetic Stimulation in Pediatric Neurology.

    PubMed

    Narayana, Shalini; Papanicolaou, Andrew C; McGregor, Amy; Boop, Frederick A; Wheless, James W

    2015-08-01

    Noninvasive brain stimulation is now an accepted technique that is used as a diagnostic aid and in the treatment of neuropsychiatric disorders in adults, and is being increasingly used in children. In this review, we will discuss the basic principles and safety of one noninvasive brain stimulation method, transcranial magnetic stimulation. Improvements in the spatial accuracy of transcranial magnetic stimulation are described in the context of image-guided transcranial magnetic stimulation. The article describes and provides examples of the current clinical applications of transcranial magnetic stimulation in children as an aid in the diagnosis and treatment of neuropsychiatric disorders and discusses future potential applications. Transcranial magnetic stimulation is a noninvasive tool that is safe for use in children and adolescents for functional mapping and treatment, and for many children it aids in the preoperative evaluation and the risk-benefit decision making. © The Author(s) 2014.

  3. Electrical receptive fields of retinal ganglion cells: Influence of presynaptic neurons

    PubMed Central

    Apollo, Nicholas V.; Garrett, David J.

    2018-01-01

    Implantable retinal stimulators activate surviving neurons to restore a sense of vision in people who have lost their photoreceptors through degenerative diseases. Complex spatial and temporal interactions occur in the retina during multi-electrode stimulation. Due to these complexities, most existing implants activate only a few electrodes at a time, limiting the repertoire of available stimulation patterns. Measuring the spatiotemporal interactions between electrodes and retinal cells, and incorporating them into a model may lead to improved stimulation algorithms that exploit the interactions. Here, we present a computational model that accurately predicts both the spatial and temporal nonlinear interactions of multi-electrode stimulation of rat retinal ganglion cells (RGCs). The model was verified using in vitro recordings of ON, OFF, and ON-OFF RGCs in response to subretinal multi-electrode stimulation with biphasic pulses at three stimulation frequencies (10, 20, 30 Hz). The model gives an estimate of each cell’s spatiotemporal electrical receptive fields (ERFs); i.e., the pattern of stimulation leading to excitation or suppression in the neuron. All cells had excitatory ERFs and many also had suppressive sub-regions of their ERFs. We show that the nonlinearities in observed responses arise largely from activation of presynaptic interneurons. When synaptic transmission was blocked, the number of sub-regions of the ERF was reduced, usually to a single excitatory ERF. This suggests that direct cell activation can be modeled accurately by a one-dimensional model with linear interactions between electrodes, whereas indirect stimulation due to summated presynaptic responses is nonlinear. PMID:29432411

  4. TMS of supplementary motor area (SMA) facilitates mental rotation performance: Evidence for sequence processing in SMA.

    PubMed

    Cona, G; Marino, G; Semenza, C

    2017-02-01

    In the present study we applied online transcranial magnetic stimulation (TMS) bursts at 10Hz to the supplementary motor area (SMA) and primary motor cortex to test whether these regions are causally involved in mental rotation. Furthermore, in order to investigate what is the specific role played by SMA and primary motor cortex, two mental rotation tasks were used, which included pictures of hands and abstract objects, respectively. While primary motor cortex stimulation did not affect mental rotation performance, SMA stimulation improved the performance in the task with object stimuli, and only for the pairs of stimuli that had higher angular disparity between each other (i.e., 100° and 150°). The finding that the effect of SMA stimulation was modulated by the amount of spatial orientation information indicates that SMA is causally involved in the very act of mental rotation. More specifically, we propose that SMA mediates domain-general sequence processes, likely required to accumulate and integrate information that are, in this context, spatial. The possible physiological mechanisms underlying the facilitation of performance due to SMA stimulation are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Deep brain stimulation modulates synchrony within spatially and spectrally distinct resting state networks in Parkinson's disease.

    PubMed

    Oswal, Ashwini; Beudel, Martijn; Zrinzo, Ludvic; Limousin, Patricia; Hariz, Marwan; Foltynie, Tom; Litvak, Vladimir; Brown, Peter

    2016-05-01

    Chronic dopamine depletion in Parkinson's disease leads to progressive motor and cognitive impairment, which is associated with the emergence of characteristic patterns of synchronous oscillatory activity within cortico-basal-ganglia circuits. Deep brain stimulation of the subthalamic nucleus is an effective treatment for Parkinson's disease, but its influence on synchronous activity in cortico-basal-ganglia loops remains to be fully characterized. Here, we demonstrate that deep brain stimulation selectively suppresses certain spatially and spectrally segregated resting state subthalamic nucleus-cortical networks. To this end we used a validated and novel approach for performing simultaneous recordings of the subthalamic nucleus and cortex using magnetoencephalography (during concurrent subthalamic nucleus deep brain stimulation). Our results highlight that clinically effective subthalamic nucleus deep brain stimulation suppresses synchrony locally within the subthalamic nucleus in the low beta oscillatory range and furthermore that the degree of this suppression correlates with clinical motor improvement. Moreover, deep brain stimulation relatively selectively suppressed synchronization of activity between the subthalamic nucleus and mesial premotor regions, including the supplementary motor areas. These mesial premotor regions were predominantly coupled to the subthalamic nucleus in the high beta frequency range, but the degree of deep brain stimulation-associated suppression in their coupling to the subthalamic nucleus was not found to correlate with motor improvement. Beta band coupling between the subthalamic nucleus and lateral motor areas was not influenced by deep brain stimulation. Motor cortical coupling with subthalamic nucleus predominantly involved driving of the subthalamic nucleus, with those drives in the higher beta frequency band having much shorter net delays to subthalamic nucleus than those in the lower beta band. These observations raise the possibility that cortical connectivity with the subthalamic nucleus in the high and low beta bands may reflect coupling mediated predominantly by the hyperdirect and indirect pathways to subthalamic nucleus, respectively, and that subthalamic nucleus deep brain stimulation predominantly suppresses the former. Yet only the change in strength of local subthalamic nucleus oscillations correlates with the degree of improvement during deep brain stimulation, compatible with the current view that a strengthened hyperdirect pathway is a prerequisite for locally generated beta activity but that it is the severity of the latter that may determine or index motor impairment. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

  6. Deep brain stimulation modulates synchrony within spatially and spectrally distinct resting state networks in Parkinson’s disease

    PubMed Central

    Oswal, Ashwini; Beudel, Martijn; Zrinzo, Ludvic; Limousin, Patricia; Hariz, Marwan; Foltynie, Tom; Litvak, Vladimir

    2016-01-01

    Abstract Chronic dopamine depletion in Parkinson’s disease leads to progressive motor and cognitive impairment, which is associated with the emergence of characteristic patterns of synchronous oscillatory activity within cortico-basal-ganglia circuits. Deep brain stimulation of the subthalamic nucleus is an effective treatment for Parkinson’s disease, but its influence on synchronous activity in cortico-basal-ganglia loops remains to be fully characterized. Here, we demonstrate that deep brain stimulation selectively suppresses certain spatially and spectrally segregated resting state subthalamic nucleus–cortical networks. To this end we used a validated and novel approach for performing simultaneous recordings of the subthalamic nucleus and cortex using magnetoencephalography (during concurrent subthalamic nucleus deep brain stimulation). Our results highlight that clinically effective subthalamic nucleus deep brain stimulation suppresses synchrony locally within the subthalamic nucleus in the low beta oscillatory range and furthermore that the degree of this suppression correlates with clinical motor improvement. Moreover, deep brain stimulation relatively selectively suppressed synchronization of activity between the subthalamic nucleus and mesial premotor regions, including the supplementary motor areas. These mesial premotor regions were predominantly coupled to the subthalamic nucleus in the high beta frequency range, but the degree of deep brain stimulation-associated suppression in their coupling to the subthalamic nucleus was not found to correlate with motor improvement. Beta band coupling between the subthalamic nucleus and lateral motor areas was not influenced by deep brain stimulation. Motor cortical coupling with subthalamic nucleus predominantly involved driving of the subthalamic nucleus, with those drives in the higher beta frequency band having much shorter net delays to subthalamic nucleus than those in the lower beta band. These observations raise the possibility that cortical connectivity with the subthalamic nucleus in the high and low beta bands may reflect coupling mediated predominantly by the hyperdirect and indirect pathways to subthalamic nucleus, respectively, and that subthalamic nucleus deep brain stimulation predominantly suppresses the former. Yet only the change in strength of local subthalamic nucleus oscillations correlates with the degree of improvement during deep brain stimulation, compatible with the current view that a strengthened hyperdirect pathway is a prerequisite for locally generated beta activity but that it is the severity of the latter that may determine or index motor impairment. PMID:27017189

  7. Spatial distribution of motor units recruited during electrical stimulation of the quadriceps muscle versus the femoral nerve.

    PubMed

    Rodriguez-Falces, Javier; Maffiuletti, Nicola A; Place, Nicolas

    2013-11-01

    In this study we investigated differences in the spatial recruitment of motor units (MUs) in the quadriceps when electrical stimulation is applied over the quadriceps belly versus the femoral nerve. M-waves and mechanical twitches were evoked using over-the-quadriceps and femoral nerve stimulation of gradually increasing intensity from 22 young, healthy subjects. Spatial recruitment was investigated using recruitment curves of M-waves recorded from the vastus medialis (VM) and vastus lateralis (VL) and of twitches recorded from the quadriceps. At maximal stimulation intensity (Imax), no differences were found between nerve and over-the-quadriceps stimulation. At submaximal intensities, VL M-wave amplitude was higher for over-the-quadriceps stimulation at 40% Imax, and peak twitch force was greater for nerve stimulation at 60% and 80% Imax. For the VM, MU spatial recruitment during nerve and over-the-quadriceps stimulation of increasing intensity occurred in a similar manner, whereas significant differences were observed for the VL. Copyright © 2013 Wiley Periodicals, Inc.

  8. RehAtt - scanning training for neglect enhanced by multi-sensory stimulation in Virtual Reality.

    PubMed

    Fordell, Helena; Bodin, Kenneth; Eklund, Anders; Malm, Jan

    2016-06-01

    There is a lack of effective treatment for neglect. We have developed a new training method, RehAtt™. The objective of this study was to determine whether RehAtt™ improves spatial attention in chronic neglect after stroke. RehAtt™ consists of a computer with monitor, 3D glasses, and a force feedback interface (Robotic pen) giving sensory motor activation to the contra-lesional arm. The software combines visual scanning training with multi-sensory stimulation in 3D virtual reality (VR) game environment. Fifteen stroke patients with chronic neglect (duration > 6 month) had repeated baseline evaluations to confirm stability of symptoms. There were no test-retest effects for any of the tests. Thereafter, all patients trained 15 h in RehAtt™ (3 × 1 h for 5 weeks). A neglect test battery and Catherine Bergego Scale, CBS, were used to assess behavioral outcome after intervention. CBS was also used at a 6-month follow-up. Using repeated measurement analysis improvements due to the training were found for Star cancellation test (p = 0.006), Baking tray task (p < 0.001), and Extinction test (p = 0.05). In the Posner task improvements were seen fewer missed targets (p = 0.024). CBS showed improvements in activities of daily life immediately after training (p < 0.01). After 6 months the patients still reported improvement in CBS. RehAtt™ is a new concept for rehabilitation of neglect. Training with the VR-method improved spatial attention and showed transfer to improved spatial attention in activities of daily living in chronic neglect. Our results are promising and merit further studies.

  9. Intensity coding in electric hearing: Effects of electrode configurations and stimulation waveforms

    PubMed Central

    Chua, Tiffany Elise H.; Bachman, Mark; Zeng, Fan-Gang

    2011-01-01

    Objectives Current cochlear implants typically stimulate the auditory nerve with biphasic pulses and monopolar electrode configurations. Tripolar stimulation can increase spatial selectivity and potentially improve place pitch related perception, but requires higher current levels to elicit the same loudness as monopolar stimulation. The present study combined delayed pseudomonophonasic pulses, which produce lower thresholds, with tripolar stimulation in an attempt to solve the power-performance tradeoff problem. Design The present study systematically measured thresholds, dynamic range, loudness growth, and intensity discrimination using either biphasic or delayed pseudomonophonasic pulses under both monopolar and tripolar stimulation. Participants were 5 Clarion cochlear implant users. For each subject, data from apical, middle and basal electrode positions were collected when possible. Results Compared with biphasic pulses, delayed pseudomonophonasic pulses increased the dynamic range by lowering thresholds while maintaining comparable maximum allowable levels under both electrode configurations. However, delayed pseudomonophonasic pulses did not change the shape of loudness growth function and actually increased intensity discrimination limens, especially at lower current levels. Conclusions The present results indicate that delayed pseudomonophonasic pulses coupled with tripolar stimulation cannot provide significant power savings, nor can it increase the functional dynamic range. Whether this combined stimulation could improve functional spectral resolution remains to be seen. PMID:21610498

  10. Spatial Disorientation Training - Demonstration and Avoidance (entrainement a la desorientation spatiale - Demonstration et reponse)

    DTIC Science & Technology

    2008-10-01

    INTRODUCTION RTO-TR-HFM-118 1 - 7 1.2.1.2 Acoustic HUD A three-dimensional auditory display presents sound from arbitrary directions spanning a...through the visual channel, use of the auditory channel shortens reaction times and is expected to reduce pilot workload, thus improving the overall...of vestibular stimulation using a rotating chair or suitable disorientation device to provide each student with a personal experience of some of

  11. Multi-images deconvolution improves signal-to-noise ratio on gated stimulated emission depletion microscopy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Castello, Marco; DIBRIS, University of Genoa, Via Opera Pia 13, Genoa 16145; Diaspro, Alberto

    2014-12-08

    Time-gated detection, namely, only collecting the fluorescence photons after a time-delay from the excitation events, reduces complexity, cost, and illumination intensity of a stimulated emission depletion (STED) microscope. In the gated continuous-wave- (CW-) STED implementation, the spatial resolution improves with increased time-delay, but the signal-to-noise ratio (SNR) reduces. Thus, in sub-optimal conditions, such as a low photon-budget regime, the SNR reduction can cancel-out the expected gain in resolution. Here, we propose a method which does not discard photons, but instead collects all the photons in different time-gates and recombines them through a multi-image deconvolution. Our results, obtained on simulated andmore » experimental data, show that the SNR of the restored image improves relative to the gated image, thereby improving the effective resolution.« less

  12. Improvement and decline in tactile discrimination behavior after cortical plasticity induced by passive tactile coactivation.

    PubMed

    Hodzic, Amra; Veit, Ralf; Karim, Ahmed A; Erb, Michael; Godde, Ben

    2004-01-14

    Perceptual learning can be induced by passive tactile coactivation without attention or reinforcement. We used functional MRI (fMRI) and psychophysics to investigate in detail the specificity of this type of learning for different tactile discrimination tasks and the underlying cortical reorganization. We found that a few hours of Hebbian coactivation evoked a significant increase of primary (SI) and secondary (SII) somatosensory cortical areas representing the stimulated body parts. The amount of plastic changes was strongly correlated with improvement in spatial discrimination performance. However, in the same subjects, frequency discrimination was impaired after coactivation, indicating that even maladaptive processes can be induced by intense passive sensory stimulation.

  13. Modeling the Electrode-Neuron Interface of Cochlear Implants: Effects of Neural Survival, Electrode Placement, and the Partial Tripolar Configuration

    PubMed Central

    Goldwyn, Joshua H.; Bierer, Steven M.; Bierer, Julie A.

    2010-01-01

    The partial tripolar electrode configuration is a relatively novel stimulation strategies that can generate more spatially focused electric fields than the commonly used monopolar configuration. Focused stimulation strategies should improve spectral resolution in cochlear implant users, but may also be more sensitive to local irregularities in the electrode-neuron interface. In this study, we develop a practical computer model of cochlear implant stimulation that can simulate neural activation in a simplified cochlear geometry and we relate the resulting patterns of neural activity to basic psychophysical measures. We examine how two types of local irregularities in the electrode-neuron interface, variations in spiral ganglion nerve density and electrode position within the scala tympani, affect the simulated neural activation patterns and how these patterns change with electrode configuration. The model shows that higher partial tripolar fractions activate more spatially restricted populations of neurons at all current levels and require higher current levels to excite a given number of neurons. We find that threshold levels are more sensitive at high partial tripolar fractions to both types of irregularities, but these effects are not independent. In particular, at close electrode-neuron distances, activation is typically more spatially localized which leads to a greater influence of neural dead regions. PMID:20580801

  14. Spatial channel interactions in cochlear implants

    NASA Astrophysics Data System (ADS)

    Tang, Qing; Benítez, Raul; Zeng, Fan-Gang

    2011-08-01

    The modern multi-channel cochlear implant is widely considered to be the most successful neural prosthesis owing to its ability to restore partial hearing to post-lingually deafened adults and to allow essentially normal language development in pre-lingually deafened children. However, the implant performance varies greatly in individuals and is still limited in background noise, tonal language understanding, and music perception. One main cause for the individual variability and the limited performance in cochlear implants is spatial channel interaction from the stimulating electrodes to the auditory nerve and brain. Here we systematically examined spatial channel interactions at the physical, physiological, and perceptual levels in the same five modern cochlear implant subjects. The physical interaction was examined using an electric field imaging technique, which measured the voltage distribution as a function of the electrode position in the cochlea in response to the stimulation of a single electrode. The physiological interaction was examined by recording electrically evoked compound action potentials as a function of the electrode position in response to the stimulation of the same single electrode position. The perceptual interactions were characterized by changes in detection threshold as well as loudness summation in response to in-phase or out-of-phase dual-electrode stimulation. To minimize potentially confounding effects of temporal factors on spatial channel interactions, stimulus rates were limited to 100 Hz or less in all measurements. Several quantitative channel interaction indexes were developed to define and compare the width, slope and symmetry of the spatial excitation patterns derived from these physical, physiological and perceptual measures. The electric field imaging data revealed a broad but uniformly asymmetrical intracochlear electric field pattern, with the apical side producing a wider half-width and shallower slope than the basal side. In contrast, the evoked compound action potential and perceptual channel interaction data showed much greater individual variability. It is likely that actual reduction in neural and higher level interactions, instead of simple sharpening of the electric current field, would be the key to predicting and hopefully improving the variable cochlear implant performance. The present results are obtained with auditory prostheses but can be applied to other neural prostheses, in which independent spatial channels, rather than a high stimulation rate, are critical to their performance.

  15. Repetitive deep transcranial magnetic stimulation improves verbal fluency and written language in a patient with primary progressive aphasia-logopenic variant (LPPA).

    PubMed

    Trebbastoni, Alessandro; Raccah, Ruggero; de Lena, Carlo; Zangen, Abraham; Inghilleri, Maurizio

    2013-07-01

    To date, no therapies are available for the logopenic variant of primary progressive aphasia (LPPA). Even though deep repetitive transcranial magnetic stimulation (rTMS) may improve cognitive functions in some neurodegenerative disorders, no previous studies investigated its effects in patients with LPPA. Our aim was to investigate the effects on cognitive function of high frequency rTMS (hf-rTMS) delivered over the left dorso-lateral prefrontal cortex (DLPFC) through a coil designed for deep rTMS, compared to a SHAM stimulation, in a right-handed patient with LPPA. The patient presented a progressive language impairment (phonological errors in speech and naming, impaired single word retrieval and sentences repetition) and predominant left perisylvian atrophy and hypoperfusion. He received four stimulation cycles (two REAL and two SHAM) each of whom lasted 20 min for 5 consecutive days. Patient's performances in frontal, visuo-spatial and linguistic tasks were evaluated before and after each stimulation session. Test scores after REAL were compared with those obtained at baseline and after SHAM. We found a temporary and highly significant improvement in the linguistic skills (both oral and written tasks) but not in the other cognitive domains tested, after REAL, but not SHAM stimulations. Hf-rTMS delivered over the DLPFC could improve language in LPPA by enhancing long-term potentiation and synaptic plasticity within the stimulated and interconnected areas involved in language network. Our findings might prompt future researches into the feasibility and efficacy of deep hf-rTMS as a therapeutic tool in progressive aphasia syndromes and other neurodegenerative disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Long lasting effects of daily theta burst rTMS sessions in the human amblyopic cortex.

    PubMed

    Clavagnier, Simon; Thompson, Benjamin; Hess, Robert F

    2013-11-01

    It has been reported that a single session of 1 Hz or 10 Hz repetitive transcranial magnetic stimulation (rTMS) of the visual cortex can temporarily improve contrast sensitivity in adults with amblyopia. More recently, continuous theta burst stimulation (cTBS) of the visual cortex has been found to improve contrast sensitivity in observers with normal vision. The aims of this study were to assess whether cTBS of the visual cortex could improve contrast sensitivity in adults with amblyopia and whether repeated sessions of cTBS would lead to more pronounced and/or longer lasting effects. cTBS was delivered to the visual cortex while patients viewed a high contrast stimulus with their non-amblyopic eye. This manipulation was designed to bias the effects of cTBS toward inputs from the amblyopic eye. Contrast sensitivity was measured before and after stimulation. The effects of one cTBS session were measured in five patients and the effects of five consecutive daily sessions were measured in four patients. Three patients were available for follow-up at varying intervals after the final session. cTBS improved amblyopic eye contrast sensitivity to high spatial frequencies (P < 0.05) and there was a cumulative improvement across sessions with asymptotic improvement occurring after 2 daily sessions of stimulation. The contrast sensitivity improvements were stable over a period of up to 78 days. These initial results in a small number of patients indicate the cTBS may allow for enduring visual function improvements in adults with amblyopia. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Cerebellar cathodal tDCS interferes with recalibration and spatial realignment during prism adaptation procedure in healthy subjects.

    PubMed

    Panico, Francesco; Sagliano, Laura; Grossi, Dario; Trojano, Luigi

    2016-06-01

    The aim of this study is to clarify the specific role of the cerebellum during prism adaptation procedure (PAP), considering its involvement in early prism exposure (i.e., in the recalibration process) and in post-exposure phase (i.e., in the after-effect, related to spatial realignment). For this purpose we interfered with cerebellar activity by means of cathodal transcranial direct current stimulation (tDCS), while young healthy individuals were asked to perform a pointing task on a touch screen before, during and after wearing base-left prism glasses. The distance from the target dot in each trial (in terms of pixels) on horizontal and vertical axes was recorded and served as an index of accuracy. Results on horizontal axis, that was shifted by prism glasses, revealed that participants who received cathodal stimulation showed increased rightward deviation from the actual position of the target while wearing prisms and a larger leftward deviation from the target after prisms removal. Results on vertical axis, in which no shift was induced, revealed a general trend in the two groups to improve accuracy through the different phases of the task, and a trend, more visible in cathodal stimulated participants, to worsen accuracy from the first to the last movements in each phase. Data on horizontal axis allow to confirm that the cerebellum is involved in all stages of PAP, contributing to early strategic recalibration process, as well as to spatial realignment. On vertical axis, the improving performance across the different stages of the task and the worsening accuracy within each task phase can be ascribed, respectively, to a learning process and to the task-related fatigue. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Microseismic Monitoring of Stimulating Shale Gas Reservoir in SW China: 2. Spatial Clustering Controlled by the Preexisting Faults and Fractures

    NASA Astrophysics Data System (ADS)

    Chen, Haichao; Meng, Xiaobo; Niu, Fenglin; Tang, Youcai; Yin, Chen; Wu, Furong

    2018-02-01

    Microseismic monitoring is crucial to improving stimulation efficiency of hydraulic fracturing treatment, as well as to mitigating potential induced seismic hazard. We applied an improved matching and locating technique to the downhole microseismic data set during one treatment stage along a horizontal well within the Weiyuan shale gas play inside Sichuan Basin in SW China, resulting in 3,052 well-located microseismic events. We employed this expanded catalog to investigate the spatiotemporal evolution of the microseismicity in order to constrain migration of the injected fluids and the associated dynamic processes. The microseismicity is generally characterized by two distinctly different clusters, both of which are highly correlated with the injection activity spatially and temporarily. The distant and well-confined cluster (cluster A) is featured by relatively large-magnitude events, with 40 events of M -1 or greater, whereas the cluster in the immediate vicinity of the wellbore (cluster B) includes two apparent lineations of seismicity with a NE-SW trending, consistent with the predominant orientation of natural fractures. We calculated the b-value and D-value, an index of fracture complexity, and found significant differences between the two seismicity clusters. Particularly, the distant cluster showed an extremely low b-value ( 0.47) and D-value ( 1.35). We speculate that the distant cluster is triggered by reactivation of a preexisting critically stressed fault, whereas the two lineations are induced by shear failures of optimally oriented natural fractures associated with fluid diffusion. In both cases, the spatially clustered microseismicity related to hydraulic stimulation is strongly controlled by the preexisting faults and fractures.

  19. Coherent optical adaptive technique improves the spatial resolution of STED microscopy in thick samples

    PubMed Central

    Yan, Wei; Yang, Yanlong; Tan, Yu; Chen, Xun; Li, Yang; Qu, Junle; Ye, Tong

    2018-01-01

    Stimulated emission depletion microscopy (STED) is one of far-field optical microscopy techniques that can provide sub-diffraction spatial resolution. The spatial resolution of the STED microscopy is determined by the specially engineered beam profile of the depletion beam and its power. However, the beam profile of the depletion beam may be distorted due to aberrations of optical systems and inhomogeneity of specimens’ optical properties, resulting in a compromised spatial resolution. The situation gets deteriorated when thick samples are imaged. In the worst case, the sever distortion of the depletion beam profile may cause complete loss of the super resolution effect no matter how much depletion power is applied to specimens. Previously several adaptive optics approaches have been explored to compensate aberrations of systems and specimens. However, it is hard to correct the complicated high-order optical aberrations of specimens. In this report, we demonstrate that the complicated distorted wavefront from a thick phantom sample can be measured by using the coherent optical adaptive technique (COAT). The full correction can effectively maintain and improve the spatial resolution in imaging thick samples. PMID:29400356

  20. Laser Speckle Imaging of Cerebral Blood Flow

    NASA Astrophysics Data System (ADS)

    Luo, Qingming; Jiang, Chao; Li, Pengcheng; Cheng, Haiying; Wang, Zhen; Wang, Zheng; Tuchin, Valery V.

    Monitoring the spatio-temporal characteristics of cerebral blood flow (CBF) is crucial for studying the normal and pathophysiologic conditions of brain metabolism. By illuminating the cortex with laser light and imaging the resulting speckle pattern, relative CBF images with tens of microns spatial and millisecond temporal resolution can be obtained. In this chapter, a laser speckle imaging (LSI) method for monitoring dynamic, high-resolution CBF is introduced. To improve the spatial resolution of current LSI, a modified LSI method is proposed. To accelerate the speed of data processing, three LSI data processing frameworks based on graphics processing unit (GPU), digital signal processor (DSP), and field-programmable gate array (FPGA) are also presented. Applications for detecting the changes in local CBF induced by sensory stimulation and thermal stimulation, the influence of a chemical agent on CBF, and the influence of acute hyperglycemia following cortical spreading depression on CBF are given.

  1. Target structures in the cochlea for infrared neural stimulation (INS)

    NASA Astrophysics Data System (ADS)

    Young, Hunter; Tan, Xiaodong; Richter, Claus-Peter

    2014-03-01

    Spatial selective infrared neural stimulation has potential to improve neural prostheses, including cochlear implants. The heating of a confined target volume depolarizes the cell membrane and results in an action potential. Tissue heating may also result in the generation of a stress relaxation wave causing mechanical stimulation of hair cells in the cochlea, creating an optoacoustic response. Data are presented that quantify the effect of an acoustical stimulus (noise masker) on the response obtained with INS in normal hearing, and chronic deaf animals. While in normal hearing animals an acoustic masker can reduce the response to INS, in chronic deaf animals this effect has not been detected. The responses to INS remain stable following the different degrees of cochlear damage.

  2. Improvement of uncorrected visual acuity and contrast sensitivity with perceptual learning and transcranial random noise stimulation in individuals with mild myopia

    PubMed Central

    Camilleri, Rebecca; Pavan, Andrea; Ghin, Filippo; Battaglini, Luca; Campana, Gianluca

    2014-01-01

    Perceptual learning has been shown to produce an improvement of visual acuity (VA) and contrast sensitivity (CS) both in subjects with amblyopia and refractive defects such as myopia or presbyopia. Transcranial random noise stimulation (tRNS) has proven to be efficacious in accelerating neural plasticity and boosting perceptual learning in healthy participants. In this study, we investigated whether a short behavioral training regime using a contrast detection task combined with online tRNS was as effective in improving visual functions in participants with mild myopia compared to a 2-month behavioral training regime without tRNS (Camilleri et al., 2014). After 2 weeks of perceptual training in combination with tRNS, participants showed an improvement of 0.15 LogMAR in uncorrected VA (UCVA) that was comparable with that obtained after 8 weeks of training with no tRNS, and an improvement in uncorrected CS (UCCS) at various spatial frequencies (whereas no UCCS improvement was seen after 8 weeks of training with no tRNS). On the other hand, a control group that trained for 2 weeks without stimulation did not show any significant UCVA or UCCS improvement. These results suggest that the combination of behavioral and neuromodulatory techniques can be fast and efficacious in improving sight in individuals with mild myopia. PMID:25400610

  3. Improving effect of mild foot electrical stimulation on pentylenetetrazole-induced impairment of learning and memory.

    PubMed

    Abasi-Moghadam, Monir; Ghasemi-Dehno, Arefe; Sadegh, Mehdi; Palizvan, Mohammad Reza

    2018-05-10

    Epilepsy is a common neurological disorder that affects learning and memory. Recently it has been shown that mild foot electrical stimulation (MFES) can increase learning and memory in normal rats. Pentylenetetrazole (PTZ) kindling is a model of human epilepsy. As with human epilepsy, PTZ kindling impairs learning and memory in rats. The purpose of this study was to investigate the effect MFES on kindling-induced learning and memory deficits in rats. Forty-nine male Wistar rats weighting 200 to 250 g were divided into the following seven groups: PTZ only, phenytoin only, MFES only, PTZ plus phenytoin, PTZ plus MFES, phenytoin plus MFES, and saline (control), with the treatments administered for 26 days. Forty-eight hours after the last injection, the animals performed the Morris water maze (MWM) task, and spatial learning and memory were measured. The results indicated that although chronic administration of phenytoin inhibited the development of PTZ kindling, it did not exert a protective effect against kindling-induced spatial learning and memory impairment in rats. On the other hand, pretreatment of PTZ-kindled animals with MFES significantly improved spatial working and reference memory. The results point to potential novel beneficial effects of MFES on learning and memory impairment induced by PTZ kindling in rats. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Strength and Aerobic Exercises Improve Spatial Memory in Aging Rats Through Stimulating Distinct Neuroplasticity Mechanisms.

    PubMed

    Vilela, Thais Ceresér; Muller, Alexandre Pastoris; Damiani, Adriani Paganini; Macan, Tamires Pavei; da Silva, Sabrina; Canteiro, Paula Bortoluzzi; de Sena Casagrande, Alisson; Pedroso, Giulia Dos Santos; Nesi, Renata Tiscoski; de Andrade, Vanessa Moraes; de Pinho, Ricardo Aurino

    2017-12-01

    Aging is associated with impaired cognition and memory and increased susceptibility to neurodegenerative disorders. Physical exercise is neuroprotective; however, the major evidence of this effect involves studies of only aerobic training in young animals. The benefits of other exercise protocols such as strength training in aged animals remains unknown. Here, we investigated the effect of aerobic and strength training on spatial memory and hippocampal plasticity in aging rats. Aging Wistar rats performed aerobic or strength training for 50 min 3 to 4 days/week for 8 weeks. Spatial memory and neurotrophic and glutamatergic signaling in the hippocampus of aged rats were evaluated after aerobic or strength training. Both aerobic and strength training improved cognition during the performance of a spatial memory task. Remarkably, the improvement in spatial memory was accompanied by an increase in synaptic plasticity proteins within the hippocampus after exercise training, with some differences in the intracellular functions of those proteins between the two exercise protocols. Moreover, neurotrophic signaling (CREB, BDNF, and the P75 NTR receptor) increased after training for both exercise protocols, and aerobic exercise specifically increased glutamatergic proteins (NMDA receptor and PSD-95). We also observed a decrease in DNA damage after aerobic training. In contrast, strength training increased levels of PKCα and the proinflammatory factors TNF-α and IL-1β. Overall, our results show that both aerobic and strength training improved spatial memory in aging rats through inducing distinct molecular mechanisms of neuroplasticity. Our findings extend the idea that exercise protocols can be used to improve cognition during aging.

  5. Modeling the electrode-neuron interface of cochlear implants: effects of neural survival, electrode placement, and the partial tripolar configuration.

    PubMed

    Goldwyn, Joshua H; Bierer, Steven M; Bierer, Julie Arenberg

    2010-09-01

    The partial tripolar electrode configuration is a relatively novel stimulation strategy that can generate more spatially focused electric fields than the commonly used monopolar configuration. Focused stimulation strategies should improve spectral resolution in cochlear implant users, but may also be more sensitive to local irregularities in the electrode-neuron interface. In this study, we develop a practical computer model of cochlear implant stimulation that can simulate neural activation in a simplified cochlear geometry and we relate the resulting patterns of neural activity to basic psychophysical measures. We examine how two types of local irregularities in the electrode-neuron interface, variations in spiral ganglion nerve density and electrode position within the scala tympani, affect the simulated neural activation patterns and how these patterns change with electrode configuration. The model shows that higher partial tripolar fractions activate more spatially restricted populations of neurons at all current levels and require higher current levels to excite a given number of neurons. We find that threshold levels are more sensitive at high partial tripolar fractions to both types of irregularities, but these effects are not independent. In particular, at close electrode-neuron distances, activation is typically more spatially localized which leads to a greater influence of neural dead regions. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  6. Optically based quantification of absolute cerebral metabolic rate of oxygen (CMRO2) with high spatial resolution in rodents

    NASA Astrophysics Data System (ADS)

    Yaseen, Mohammad A.; Srinivasan, Vivek J.; Sakadžić, Sava; Vinogradov, Sergei A.; Boas, David A.

    2010-02-01

    Measuring oxygen delivery in brain tissue is important for identifying the pathophysiological changes associated with brain injury and various diseases such as cancer, stroke, and Alzheimer's disease. We have developed a multi-modal imaging system for minimally invasive measurement of cerebral oxygenation and blood flow in small animals with high spatial resolution. The system allows for simultaneous measurement of blood flow using Fourier-domain optical coherence tomography, and oxygen partial pressure (pO2) using either confocal or multiphoton phosphorescence lifetime imaging with exogenous porphyrin-based dyes sensitive to dissolved oxygen. Here we present the changes in pO2 and blood flow in superficial cortical vessels of Sprague Dawley rats in response to conditions such as hypoxia, hyperoxia, and functional stimulation. pO2 measurements display considerable heterogeneity over distances that cannot be resolved with more widely used oxygen-monitoring techniques such as BOLD-fMRI. Large increases in blood flow are observed in response to functional stimulation and hypoxia. Our system allows for quantification of cerebral metabolic rate of oxygen (CMRO2) with high spatial resolution, providing a better understanding of metabolic dynamics during functional stimulation and under various neuropathologies. Ultimately, better insight into the underlying mechanisms of neuropathologies will facilitate the development of improved therapeutic strategies to minimize damage to brain tissue.

  7. Neuropsychology of selective attention and magnetic cortical stimulation.

    PubMed

    Sabatino, M; Di Nuovo, S; Sardo, P; Abbate, C S; La Grutta, V

    1996-01-01

    Informed volunteers were asked to perform different neuropsychological tests involving selective attention under control conditions and during transcranial magnetic cortical stimulation. The tests chosen involved the recognition of a specific letter among different letters (verbal test) and the search for three different spatial orientations of an appendage to a square (visuo-spatial test). For each test the total time taken and the error rate were calculated. Results showed that cortical stimulation did not cause a worsening in performance. Moreover, magnetic stimulation of the temporal lobe neither modified completion time in both verbal and visuo-spatial tests nor changed error rate. In contrast, magnetic stimulation of the pre-frontal area induced a significant reduction in the performance time of both the verbal and visuo-spatial tests always without an increase in the number of errors. The experimental findings underline the importance of the pre-frontal area in performing tasks requiring a high level of controlled attention and suggest the need to adopt an interdisciplinary approach towards the study of neurone/mind interface mechanisms.

  8. Spatial Attention and the Effects of Frontoparietal Alpha Band Stimulation

    PubMed Central

    van Schouwenburg, Martine R.; Zanto, Theodore P.; Gazzaley, Adam

    2017-01-01

    A frontoparietal network has long been implicated in top-down control of attention. Recent studies have suggested that this network might communicate through coherence in the alpha band. Here we aimed to test the effect of coherent alpha (8–12 Hz) stimulation on the frontoparietal network. To this end, we recorded behavioral performance and electroencephalography (EEG) data while participants were engaged in a spatial attention task. Furthermore, participants received transcranial alternating current stimulation (tACS) over the right frontal and parietal cortex, which oscillated coherently in-phase within the alpha band. Compared to a group of participants that received sham stimulation, we found that coherent frontoparietal alpha band stimulation altered a behavioral spatial attention bias. Neurally, the groups showed hemispheric-specific differences in alpha coherence between the frontal and parietal-occipital cortex. These results provide preliminary evidence that alpha coherence in the frontoparietal network might play a role in top-down control of spatial attention. PMID:28174529

  9. Electrical Stimulation in Hippocampus and Entorhinal Cortex Impairs Spatial and Temporal Memory.

    PubMed

    Goyal, Abhinav; Miller, Jonathan; Watrous, Andrew J; Lee, Sang Ah; Coffey, Tom; Sperling, Michael R; Sharan, Ashwini; Worrell, Gregory; Berry, Brent; Lega, Bradley; Jobst, Barbara C; Davis, Kathryn A; Inman, Cory; Sheth, Sameer A; Wanda, Paul A; Ezzyat, Youssef; Das, Sandhitsu R; Stein, Joel; Gorniak, Richard; Jacobs, Joshua

    2018-05-09

    The medial temporal lobe (MTL) is widely implicated in supporting episodic memory and navigation, but its precise functional role in organizing memory across time and space remains elusive. Here we examine the specific cognitive processes implemented by MTL structures (hippocampus and entorhinal cortex) to organize memory by using electrical brain stimulation, leveraging its ability to establish causal links between brain regions and features of behavior. We studied neurosurgical patients of both sexes who performed spatial-navigation and verbal-episodic memory tasks while brain stimulation was applied in various regions during learning. During the verbal memory task, stimulation in the MTL disrupted the temporal organization of encoded memories such that items learned with stimulation tended to be recalled in a more randomized order. During the spatial task, MTL stimulation impaired subjects' abilities to remember items located far away from boundaries. These stimulation effects were specific to the MTL. Our findings thus provide the first causal demonstration in humans of the specific memory processes that are performed by the MTL to encode when and where events occurred. SIGNIFICANCE STATEMENT Numerous studies have implicated the medial temporal lobe (MTL) in encoding spatial and temporal memories, but they have not been able to causally demonstrate the nature of the cognitive processes by which this occurs in real-time. Electrical brain stimulation is able to demonstrate causal links between a brain region and a given function with high temporal precision. By examining behavior in a memory task as subjects received MTL stimulation, we provide the first causal evidence demonstrating the role of the MTL in organizing the spatial and temporal aspects of episodic memory. Copyright © 2018 the authors 0270-6474/18/384471-11$15.00/0.

  10. Interaction of visual and vestibular stimulation on spatial coordinates for eye movements in rabbits.

    PubMed

    Pettorossi, V E; Errico, P; Ferraresi, A; Minciotti, M; Barmack, N H

    1998-07-01

    Researchers investigated how vestibular and optokinetic signals alter the spatial transformation of the coordinate system that governs the spatial orientation of reflexive eye movements. Also examined were the effects of sensory stimulation when vestibular and optokinetic signals act synergistically and when the two signals are in conflict.

  11. WHOLE BODY VIBRATION IMPROVES ATTENTION AND MOTOR PERFORMANCE IN MICE DEPENDING ON THE DURATION OF THE WHOLE-BODY VIBRATION SESSION.

    PubMed

    Keijser, Jan N; van Heuvelen, Marieke J G; Nyakas, Csaba; Tóth, Kata; Schoemaker, Regien G; Zeinstra, Edzard; van der Zee, Eddy A

    2017-01-01

    Whole body vibration (WBV) is a form of physical stimulation via mechanical vibrations transmitted to a subject. It is assumed that WBV induces sensory stimulation in cortical brain regions through the activation of skin and muscle receptors responding to the vibration. The effects of WBV on muscle strength are well described. However, little is known about the impact of WBV on the brain. Recently, it was shown in humans that WBV improves attention in an acute WBV protocol. Preclinical research is needed to unravel the underlying brain mechanism. As a first step, we examined whether chronic WBV improves attention in mice. A custom made vibrating platform for mice with low intensity vibrations was used. Male CD1 mice (3 months of age) received five weeks WBV (30 Hz; 1.9 G), five days a week with sessions of five (n=12) or 30 (n=10) minutes. Control mice (pseudo-WBV; n=12 and 10 for the five and 30 minute sessions, respectively) were treated in a similar way, but did not receive the actual vibration. Object recognition tasks were used as an attention test (novel and spatial object recognition - the primary outcome measure). A Balance beam was used for motor performance, serving as a secondary outcome measure. WBV sessions of five (but not WBV sessions of 30 minutes) improved balance beam performance (mice gained 28% in time needed to cross the beam) and novel object recognition (mice paid significantly more attention to the novel object) as compared to pseudo WBV, but no change was found for spatial object performance (mice did not notice the relocation). Although 30 minutes WBV sessions were not beneficial, it did not impair either attention or motor performance. These results show that brief sessions of WBV improve, next to motor performance, attention for object recognition, but not spatial cues of the objects. The selective improvement of attention in mice opens the avenue to unravel the underlying brain mechanisms.

  12. Attention Modulates Visual-Tactile Interaction in Spatial Pattern Matching

    PubMed Central

    Göschl, Florian; Engel, Andreas K.; Friese, Uwe

    2014-01-01

    Factors influencing crossmodal interactions are manifold and operate in a stimulus-driven, bottom-up fashion, as well as via top-down control. Here, we evaluate the interplay of stimulus congruence and attention in a visual-tactile task. To this end, we used a matching paradigm requiring the identification of spatial patterns that were concurrently presented visually on a computer screen and haptically to the fingertips by means of a Braille stimulator. Stimulation in our paradigm was always bimodal with only the allocation of attention being manipulated between conditions. In separate blocks of the experiment, participants were instructed to (a) focus on a single modality to detect a specific target pattern, (b) pay attention to both modalities to detect a specific target pattern, or (c) to explicitly evaluate if the patterns in both modalities were congruent or not. For visual as well as tactile targets, congruent stimulus pairs led to quicker and more accurate detection compared to incongruent stimulation. This congruence facilitation effect was more prominent under divided attention. Incongruent stimulation led to behavioral decrements under divided attention as compared to selectively attending a single sensory channel. Additionally, when participants were asked to evaluate congruence explicitly, congruent stimulation was associated with better performance than incongruent stimulation. Our results extend previous findings from audiovisual studies, showing that stimulus congruence also resulted in behavioral improvements in visuotactile pattern matching. The interplay of stimulus processing and attentional control seems to be organized in a highly flexible fashion, with the integration of signals depending on both bottom-up and top-down factors, rather than occurring in an ‘all-or-nothing’ manner. PMID:25203102

  13. Opposite effects of lateralised transcranial alpha versus gamma stimulation on auditory spatial attention.

    PubMed

    Wöstmann, Malte; Vosskuhl, Johannes; Obleser, Jonas; Herrmann, Christoph S

    2018-04-06

    Spatial attention relatively increases the power of neural 10-Hz alpha oscillations in the hemisphere ipsilateral to attention, and decreases alpha power in the contralateral hemisphere. For gamma oscillations (>40 Hz), the opposite effect has been observed. The functional roles of lateralised oscillations for attention are currently unclear. If lateralised oscillations are functionally relevant for attention, transcranial stimulation of alpha versus gamma oscillations in one hemisphere should differentially modulate the accuracy of spatial attention to the ipsi-versus contralateral side. 20 human participants performed a dichotic listening task under continuous transcranial alternating current stimulation (tACS, vs sham) at alpha (10 Hz) or gamma (47 Hz) frequency. On each trial, participants attended to four spoken numbers on the left or right ear, while ignoring numbers on the other ear. In order to stimulate a left temporo-parietal cortex region, which is known to show marked modulations of alpha power during auditory spatial attention, tACS (1 mA peak-to-peak amplitude) was applied at electrode positions TP7 and FC5 over the left hemisphere. As predicted, unihemispheric alpha-tACS relatively decreased the recall of targets contralateral to stimulation, but increased recall of ipsilateral targets. Importantly, this spatial pattern of results was reversed for gamma-tACS. Results provide a proof of concept that transcranially stimulated oscillations can enhance spatial attention and facilitate attentional selection of speech. Furthermore, opposite effects of alpha versus gamma stimulation support the view that states of high alpha are incommensurate with active neural processing as reflected by states of high gamma. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Daily visual stimulation in the critical period enhances multiple aspects of vision through BDNF-mediated pathways in the mouse retina

    PubMed Central

    Mui, Amanda M.; Yang, Victoria; Aung, Moe H.; Fu, Jieming; Adekunle, Adewumi N.; Prall, Brian C.; Sidhu, Curran S.; Park, Han na; Boatright, Jeffrey H.; Iuvone, P. Michael

    2018-01-01

    Visual experience during the critical period modulates visual development such that deprivation causes visual impairments while stimulation induces enhancements. This study aimed to determine whether visual stimulation in the form of daily optomotor response (OMR) testing during the mouse critical period (1) improves aspects of visual function, (2) involves retinal mechanisms and (3) is mediated by brain derived neurotrophic factor (BDNF) and dopamine (DA) signaling pathways. We tested spatial frequency thresholds in C57BL/6J mice daily from postnatal days 16 to 23 (P16 to P23) using OMR testing. Daily OMR-treated mice were compared to littermate controls that were placed in the OMR chamber without moving gratings. Contrast sensitivity thresholds, electroretinograms (ERGs), visual evoked potentials, and pattern ERGs were acquired at P21. To determine the role of BDNF signaling, a TrkB receptor antagonist (ANA-12) was systemically injected 2 hours prior to OMR testing in another cohort of mice. BDNF immunohistochemistry was performed on retina and brain sections. Retinal DA levels were measured using high-performance liquid chromatography. Daily OMR testing enhanced spatial frequency thresholds and contrast sensitivity compared to controls. OMR-treated mice also had improved rod-driven ERG oscillatory potential response times, greater BDNF immunoreactivity in the retinal ganglion cell layer, and increased retinal DA content compared to controls. VEPs and pattern ERGs were unchanged. Systemic delivery of ANA-12 attenuated OMR-induced visual enhancements. Daily OMR testing during the critical period leads to general visual function improvements accompanied by increased DA and BDNF in the retina, with this process being requisitely mediated by TrkB activation. These results suggest that novel combination therapies involving visual stimulation and using both behavioral and molecular approaches may benefit degenerative retinal diseases or amblyopia. PMID:29408880

  15. Visual Evoked Cortical Potential (VECP) Elicited by Sinusoidal Gratings Controlled by Pseudo-Random Stimulation

    PubMed Central

    Araújo, Carolina S.; Souza, Givago S.; Gomes, Bruno D.; Silveira, Luiz Carlos L.

    2013-01-01

    The contributions of contrast detection mechanisms to the visual cortical evoked potential (VECP) have been investigated studying the contrast-response and spatial frequency-response functions. Previously, the use of m-sequences for stimulus control has been almost restricted to multifocal electrophysiology stimulation and, in some aspects, it substantially differs from conventional VECPs. Single stimulation with spatial contrast temporally controlled by m-sequences has not been extensively tested or compared to multifocal techniques. Our purpose was to evaluate the influence of spatial frequency and contrast of sinusoidal gratings on the VECP elicited by pseudo-random stimulation. Nine normal subjects were stimulated by achromatic sinusoidal gratings driven by pseudo random binary m-sequence at seven spatial frequencies (0.4–10 cpd) and three stimulus sizes (4°, 8°, and 16° of visual angle). At 8° subtence, six contrast levels were used (3.12–99%). The first order kernel (K1) did not provide a consistent measurable signal across spatial frequencies and contrasts that were tested–signal was very small or absent–while the second order kernel first (K2.1) and second (K2.2) slices exhibited reliable responses for the stimulus range. The main differences between results obtained with the K2.1 and K2.2 were in the contrast gain as measured in the amplitude versus contrast and amplitude versus spatial frequency functions. The results indicated that K2.1 was dominated by M-pathway, but for some stimulus condition some P-pathway contribution could be found, while the second slice reflected the P-pathway contribution. The present work extended previous findings of the visual pathways contribution to VECP elicited by pseudorandom stimulation for a wider range of spatial frequencies. PMID:23940546

  16. Programming social, cognitive, and neuroendocrine development by early exposure to novelty.

    PubMed

    Tang, Akaysha C; Akers, Katherine G; Reeb, Bethany C; Romeo, Russell D; McEwen, Bruce S

    2006-10-17

    Mildly stressful early life experiences can potentially impact a broad range of social, cognitive, and physiological functions in humans, nonhuman primates, and rodents. Recent rodent studies favor a maternal-mediation hypothesis that considers maternal-care differences induced by neonatal stimulation as the cause of individual differences in offspring development. Using neonatal novelty exposure, a neonatal stimulation paradigm that dissociates maternal individual differences from a direct stimulation effect on the offspring, we investigated the effect of early exposures to novelty on a diverse range of psychological functions using several assessment paradigms. Pups that received brief neonatal novelty exposures away from the home environment showed enhancement in spatial working memory, social competition, and corticosterone response to surprise during adulthood compared with their home-staying siblings. These functional enhancements in novelty-exposed rats occurred despite evidence that maternal care was directed preferentially toward home-staying instead of novelty-exposed pups, indicating that greater maternal care is neither necessary nor sufficient for these early stimulation-induced functional enhancements. We suggest a unifying maternal-modulation hypothesis, which distinguishes itself from the maternal-mediation hypothesis in that (i) neonatal stimulation can have direct effects on pups, cumulatively leading to long-term improvement in adult offspring; and (ii) maternal behavior can attenuate or potentiate these effects, thereby decreasing or increasing this long-term functional improvement.

  17. Laser Stimulation of Single Auditory Nerve Fibers

    PubMed Central

    Littlefield, Philip D.; Vujanovic, Irena; Mundi, Jagmeet; Matic, Agnella Izzo; Richter, Claus-Peter

    2011-01-01

    Objectives/Hypothesis One limitation with cochlear implants is the difficulty stimulating spatially discrete spiral ganglion cell groups because of electrode interactions. Multipolar electrodes have improved on this some, but also at the cost of much higher device power consumption. Recently, it has been shown that spatially selective stimulation of the auditory nerve is possible with a mid-infrared laser aimed at the spiral ganglion via the round window. However, these neurons must be driven at adequate rates for optical radiation to be useful in cochlear implants. We herein use single-fiber recordings to characterize the responses of auditory neurons to optical radiation. Study Design In vivo study using normal-hearing adult gerbils. Methods Two diode lasers were used for stimulation of the auditory nerve. They operated between 1.844 μm and 1.873 μm, with pulse durations of 35 μs to 1,000 μs, and at repetition rates up to 1,000 pulses per second (pps). The laser outputs were coupled to a 200-μm-diameter optical fiber placed against the round window membrane and oriented toward the spiral ganglion. The auditory nerve was exposed through a craniotomy, and recordings were taken from single fibers during acoustic and laser stimulation. Results Action potentials occurred 2.5 ms to 4.0 ms after the laser pulse. The latency jitter was up to 3 ms. Maximum rates of discharge averaged 97 ± 52.5 action potentials per second. The neurons did not strictly respond to the laser at stimulation rates over 100 pps. Conclusions Auditory neurons can be stimulated by a laser beam passing through the round window membrane and driven at rates sufficient for useful auditory information. Optical stimulation and electrical stimulation have different characteristics; which could be selectively exploited in future cochlear implants. Level of Evidence Not applicable. PMID:20830761

  18. Spatiotemporal neuromodulation therapies engaging muscle synergies improve motor control after spinal cord injury

    PubMed Central

    Wenger, Nikolaus; Moraud, Eduardo Martin; Gandar, Jerome; Musienko, Pavel; Capogrosso, Marco; Baud, Laetitia; Le Goff, Camille G.; Barraud, Quentin; Pavlova, Natalia; Dominici, Nadia; Minev, Ivan R.; Asboth, Leonie; Hirsch, Arthur; Duis, Simone; Kreider, Julie; Mortera, Andrea; Haverbeck, Oliver; Kraus, Silvio; Schmitz, Felix; DiGiovanna, Jack; van den Brand, Rubia; Bloch, Jocelyne; Detemple, Peter; Lacour, Stéphanie P.; Bézard, Erwan; Micera, Silvestro; Courtine, Grégoire

    2016-01-01

    Electrical neuromodulation of lumbar segments improves motor control after spinal cord injury in animal models and humans. However, the physiological principles underlying the effect of this intervention remain poorly understood, which has limited this therapeutic approach to continuous stimulation applied to restricted spinal cord locations. Here, we developed novel stimulation protocols that reproduce the natural dynamics of motoneuron activation during locomotion. For this, we computed the spatiotemporal activation pattern of muscle synergies during locomotion in healthy rats. Computer simulations identified optimal electrode locations to target each synergy through the recruitment of proprioceptive feedback circuits. This framework steered the design of spatially selective spinal implants and real–time control software that modulate extensor versus flexor synergies with precise temporal resolution. Spatiotemporal neuromodulation therapies improved gait quality, weight–bearing capacities, endurance and skilled locomotion in multiple rodent models of spinal cord injury. These new concepts are directly translatable to strategies to improve motor control in humans. PMID:26779815

  19. Individual differences in learning correlate with modulation of brain activity induced by transcranial direct current stimulation

    PubMed Central

    Falcone, Brian; Wada, Atsushi; Parasuraman, Raja

    2018-01-01

    Transcranial direct current stimulation (tDCS) has been shown to enhance cognitive performance on a variety of tasks. It is hypothesized that tDCS enhances performance by affecting task related cortical excitability changes in networks underlying or connected to the site of stimulation facilitating long term potentiation. However, many recent studies have called into question the reliability and efficacy of tDCS to induce modulatory changes in brain activity. In this study, our goal is to investigate the individual differences in tDCS induced modulatory effects on brain activity related to the degree of enhancement in performance, providing insight into this lack of reliability. In accomplishing this goal, we used functional magnetic resonance imaging (fMRI) concurrently with tDCS stimulation (1 mA, 30 minutes duration) using a visual search task simulating real world conditions. The experiment consisted of three fMRI sessions: pre-training (no performance feedback), training (performance feedback which included response accuracy and target location and either real tDCS or sham stimulation given), and post-training (no performance feedback). The right posterior parietal cortex was selected as the site of anodal tDCS based on its known role in visual search and spatial attention processing. Our results identified a region in the right precentral gyrus, known to be involved with visual spatial attention and orienting, that showed tDCS induced task related changes in cortical excitability that were associated with individual differences in improved performance. This same region showed greater activity during the training session for target feedback of incorrect (target-error feedback) over correct trials for the tDCS stim over sham group indicating greater attention to target features during training feedback when trials were incorrect. These results give important insight into the nature of neural excitability induced by tDCS as it relates to variability in individual differences in improved performance shedding some light the apparent lack of reliability found in tDCS research. PMID:29782510

  20. Visual Spatial Attention Training Improve Spatial Attention and Motor Control for Unilateral Neglect Patients.

    PubMed

    Wang, Wei; Ji, Xiangtong; Ni, Jun; Ye, Qian; Zhang, Sicong; Chen, Wenli; Bian, Rong; Yu, Cui; Zhang, Wenting; Shen, Guangyu; Machado, Sergio; Yuan, Tifei; Shan, Chunlei

    2015-01-01

    To compare the effect of visual spatial training on the spatial attention to that on motor control and to correlate the improvement of spatial attention to motor control progress after visual spatial training in subjects with unilateral spatial neglect (USN). 9 cases with USN after right cerebral stroke were randomly divided into Conventional treatment group + visual spatial attention and Conventional treatment group. The Conventional treatment group + visual spatial attention received conventional rehabilitation therapy (physical and occupational therapy) and visual spatial attention training (optokinetic stimulation and right half-field eye patching). The Conventional treatment group was only treated with conventional rehabilitation training (physical and occupational therapy). All patients were assessed by behavioral inattention test (BIT), Fugl-Meyer Assessment of motor function (FMA), equilibrium coordination test (ECT) and non-equilibrium coordination test (NCT) before and after 4 weeks treatment. Total scores in both groups (without visual spatial attention/with visual spatial attention) improved significantly (BIT: P=0.021/P=0.000, d=1.667/d=2.116, power=0.69/power=0.98, 95%CI[-0.8839,45.88]/95%CI=[16.96,92.64]; FMA: P=0.002/P=0.000, d=2.521/d=2.700, power=0.93/power=0.98, 95%CI[5.707,30.79]/95%CI=[16.06,53.94]; ECT: P=0.002/ P=0.000, d=2.031/d=1.354, power=0.90/power=0.17, 95%CI[3.380,42.61]/95%CI=[-1.478,39.08]; NCT: P=0.013/P=0.000, d=1.124/d=1.822, power=0.41/power=0.56, 95%CI[-7.980,37.48]/95%CI=[4.798,43.60],) after treatment. Among the 2 groups, the group with visual spatial attention significantly improved in BIT (P=0.003, d=3.103, power=1, 95%CI[15.68,48.92]), FMA of upper extremity (P=0.006, d=2.771, power=1, 95%CI[5.061,20.14]) and NCT (P=0.010, d=2.214, power=0.81-0.90, 95%CI[3.018,15.88]). Correlative analysis shows that the change of BIT scores is positively correlated to the change of FMA total score (r=0.77, P<;0.01), FMA of upper extremity (r=0.81, P<0.01), NCT (r=0.78, P<0.01). Four weeks visual spatial training could improve spatial attention as well as motor control functions in hemineglect patients. The improvement of motor function is positively correlated to the progresses of visual spatial functions after visual spatial attention training.

  1. Perception-action relationships reconsidered in light of spatial display instruments

    NASA Technical Reports Server (NTRS)

    Shebilske, Wayne L.

    1989-01-01

    Spatial display instruments convey information about both the identity and the location of objects in order to assist surgeons, astronauts, pilots, blind individuals, and others in identification, remote manipulations, navigation, and obstacle avoidance. Scientists believe that these instruments have not reached their full potential and that progress toward new applications, including the possibility of restoring sight to the blind, will be accelerated by advancing the understanding of perceptual processes. This stimulating challenge to basic researchers was advanced by Paul Bach-Y-Rita (1972) and by the National Academy of Science (1986) report on Electronic Aids for the Blind. Although progress has been made, new applications of spatial display instruments in medicine, space, aviation, and rehabilitation await improved theoretical and empirical foundations.

  2. Multi-Scale Modeling to Improve Single-Molecule, Single-Cell Experiments

    NASA Astrophysics Data System (ADS)

    Munsky, Brian; Shepherd, Douglas

    2014-03-01

    Single-cell, single-molecule experiments are producing an unprecedented amount of data to capture the dynamics of biological systems. When integrated with computational models, observations of spatial, temporal and stochastic fluctuations can yield powerful quantitative insight. We concentrate on experiments that localize and count individual molecules of mRNA. These high precision experiments have large imaging and computational processing costs, and we explore how improved computational analyses can dramatically reduce overall data requirements. In particular, we show how analyses of spatial, temporal and stochastic fluctuations can significantly enhance parameter estimation results for small, noisy data sets. We also show how full probability distribution analyses can constrain parameters with far less data than bulk analyses or statistical moment closures. Finally, we discuss how a systematic modeling progression from simple to more complex analyses can reduce total computational costs by orders of magnitude. We illustrate our approach using single-molecule, spatial mRNA measurements of Interleukin 1-alpha mRNA induction in human THP1 cells following stimulation. Our approach could improve the effectiveness of single-molecule gene regulation analyses for many other process.

  3. [Noopept improves the spatial memory and stimulates prefibrillar beta-amyloid(25-35) antibody production in mice].

    PubMed

    Bobkova, N V; Gruden', M A; Samokhin, A N; Medvinskaia, N I; Morozova-Roch, L; Uudasheva, T A; Ostrovskaia, R U; Seredinin, S B

    2005-01-01

    The effects of the novel proline-containing nootropic and neuroprotective dipeptide noopept (GVS-111, N-phenylacetyl-L-prolylglycine ethyl ester) were studied on NMRI mice upon olfactory bulbectomy, which had been previously shown to imitate the main morphological and biochemical signs of Alzheimer's disease (AD). The spatial memory was assessed using the Morris (water maze) test; the immunological status was characterized by ELISA with antibodies to prefibrillar beta-amyloid(25-35), S100b protein, and protofilaments of equine lysozyme, which are the molecular factors involved in the pathogenesis of AD. The control (sham-operated) animals during the Morris test preferred a sector where the safety platform was placed during the learning session. Bulbectomized animals treated with saline failed to recognize this sector, while bulbectomized animals treated with noopept (0.01 mg/kg for 21 days) restored this predominance, thus demonstrating the improvement of the spatial memory. These animals also demonstrated an increase in the level of antibodies to beta-amyloid(25-35)--the effect, which was more pronounced in the sham-operated than in bulbectomized mice. The latter demonstrated a profound decrease of immunological reactivity in a large number of tests. Noopept, stimulating the production of antibodies to beta-amyloid(25-35), can attenuate the well-known neurotoxic effects of beta-amyloid. The obtained data on the mnemotropic and immunostimulant effects noopept are indicative of good prospects for the clinical usage of this drug in the therapy of patients with neurodegenerative diseases.

  4. Measurement of Off-Body Velocity, Pressure, and Temperature in an Unseeded Supersonic Air Vortex by Stimulated Raman Scattering

    NASA Technical Reports Server (NTRS)

    Herring, Gregory C.

    2008-01-01

    A noninvasive optical method is used to make time-averaged (30 sec) off-body measurements in a supersonic airflow. Seeding of tracer particles is not required. One spatial component of velocity, static pressure, and static temperature are measured with stimulated Raman scattering. The three flow parameters are determined simultaneously from a common sample volume (0.3 by 0.3 by 15 mm) using concurrent measurements of the forward and backward scattered line shapes of a N2 vibrational Raman transition. The capability of this technique is illustrated with laboratory and large-scale wind tunnel testing that demonstrate 5-10% measurement uncertainties. Because the spatial resolution of the present work was improved to 1.5 cm (compared to 20 cm in previous work), it was possible to demonstrate a modest one-dimensional profiling of cross-flow velocity, pressure, and translational temperature through the low-density core of a stream-wise vortex (delta-wing model at Mach 2.8 in NASA Langley's Unitary Plan Wind Tunnel).

  5. Effect of Fiberoptic Collimation Technique on 808 nm Wavelength Laser Stimulation of Cochlear Neurons.

    PubMed

    Wang, Jingxuan; Lu, Jianren; Tian, Lan

    2016-06-01

    The purpose of this study was to evaluate the effects of fiberoptic collimation technique on auditory neural stimulation in the cochlea with 808 nm wavelength lasers. Recently, the pulsed near-infrared lasers in the 800-1000 nm wavelength range have been investigated as an emerging technique to trigger auditory neural response in the cochlea. A laser beam divergence in the optical stimulation pathway exists, which may affect stimulation efficiency and spatial selectivity. The fiberoptic collimation technique was proposed for cochlear neuron stimulation, and the C-lens element was designed as the collimation structure. The spiral ganglion cells in deafened guinea pigs' cochlea were irradiated with collimated and uncollimated near-infrared lasers. Optically evoked auditory brainstem response (OABR) under the two laser output modes were recorded. Laser with the collimation technique evoked an average 58% higher OABR amplitude than the uncollimated laser output. In addition, the collimated laser setup consumed on average 35.2% of laser energy compared with the uncollimated laser when evoking the same OABR amplitude. The fiberoptic collimation technique improved stimulation efficiency and reduced stimulating energy consumption in near-infrared neural stimulation in cochlea. The positive effects of laser collimation technique could benefit further research in optically based cochlear implants.

  6. Stimulation of the basolateral amygdala improves the acquisition of a motor skill.

    PubMed

    Bergado, Jorge A; Rojas, Yeneissy; Capdevila, Vladimir; González, Odalys; Almaguer-Melian, William

    2006-01-01

    We have previously shown that the stimulation of limbic structures related to affective life such as the amygdale can improve and reinforce neural plastic processes related to hippocampus-dependent forms of explicit memory, as spatial memory and LTP. We now assessed whether this effect is restricted to the mentioned structure and memory type, or represents a more general form of modulatory influence. Young, male Sprague Dawley rats were implanted stereotactically with one electrode in the basolateral amygdala (BLA) and trained to acquire a motor skill using their right anterior limb. A group of animals received 3 trains of 15 impulses at the BLA 15 minutes after each daily training session. A second group of implanted animals was handled in the same way, but not stimulated, while a third group was not implanted. After reaching the training criterion the left motor cortex was mapped by the observation of the movements induced by stimuli applied in discrete points of the cortex. Cortical representation of the anterior limb was increased in all trained animals, showing that the motor cortex is involved in the acquisition of the new skill. Animals receiving stimulation of the BLA showed similar cortical changes, but learned faster than non-stimulated controls. Reinforcement of neural plasticity by the activation of the amygdala is not restricted to hippocampus-dependent explicit memory, but it might represent a universal mechanism to modulate plasticity.

  7. Optimal number of stimulation contacts for coordinated reset neuromodulation

    PubMed Central

    Lysyansky, Borys; Popovych, Oleksandr V.; Tass, Peter A.

    2013-01-01

    In this computational study we investigate coordinated reset (CR) neuromodulation designed for an effective control of synchronization by multi-site stimulation of neuronal target populations. This method was suggested to effectively counteract pathological neuronal synchrony characteristic for several neurological disorders. We study how many stimulation sites are required for optimal CR-induced desynchronization. We found that a moderate increase of the number of stimulation sites may significantly prolong the post-stimulation desynchronized transient after the stimulation is completely switched off. This can, in turn, reduce the amount of the administered stimulation current for the intermittent ON–OFF CR stimulation protocol, where time intervals with stimulation ON are recurrently followed by time intervals with stimulation OFF. In addition, we found that the optimal number of stimulation sites essentially depends on how strongly the administered current decays within the neuronal tissue with increasing distance from the stimulation site. In particular, for a broad spatial stimulation profile, i.e., for a weak spatial decay rate of the stimulation current, CR stimulation can optimally be delivered via a small number of stimulation sites. Our findings may contribute to an optimization of therapeutic applications of CR neuromodulation. PMID:23885239

  8. [Effectivity of an occlusion-supporting PC-based visual training programme by horizontal drifting sinus gratings in children with amblyopia].

    PubMed

    Bau, V; Rose, K; Pollack, K; Spoerl, E; Pillunat, L E

    2012-10-01

    The studies of Kämpf et al. suggested an efficiency of a computer-based stimulation therapy by drifting sinus gratings in patients with anisometropic and/or strabismic amblyopia but provided no clear evidence. This is the first trial with amblyopic patients without previous treatment at the beginning of amblyopia therapy. A prospective, randomised, single-blinded, placebo-controlled study of n = 15 patients with anisometropic and/or strabismic amblyopia without previous treatment was performed. Age of the patients was between 4 and 10 years, mean 6.3 years (± 2.0), all after full correction of refraction errors and refractive adaptation. Stimulation therapy was performed 5 times a week over 4 weeks, respectively 2 × 20 min, a drifting sinus grating of constant spatial and temporal frequency was combined with computer games (n = 8). Control group had only computer games with a neutral background (n = 7). In both groups patching was only done in stimulation times. Stimulation and control group did not differ due to age, gender, and cause of amblyopie, baseline visual acuity, and time of wearing glasses. There was no significant difference in the development of visual acuity over the stimulation period between stimulation and control groups. Stimulation therapy with drifting sinus gratings did not improve the development of visual acuity in the first phase of amblyopia treatment combined with minimal occlusion therapy. Accordingly, the stimulation therapy is not adequate to replace sufficient occlusion therapy. Whether this therapy could support patching therapy and improve acuity development in later therapy phases cannot be assumed from this trial. Georg Thieme Verlag KG Stuttgart · New York.

  9. Continuous-wave optical stimulation of the rat prostate nerves using an all-single-mode 1455 nm diode laser and fiber system

    NASA Astrophysics Data System (ADS)

    Tozburun, Serhat; Lagoda, Gwen A.; Burnett, Arthur L.; Fried, Nathaniel M.

    2011-03-01

    Optical nerve stimulation (ONS) has recently been reported as a potential alternative to electrical nerve stimulation. Continuous-wave (CW) laser stimulation of the prostate cavernous nerves (CN) in a rat model, in vivo, has also been demonstrated in our previous studies. The objective of this study is to present a new all-single-mode-fiber configuration for ONS with the laser operating in CW mode for potential diagnostic applications. An infrared pigtailed single-mode diode laser (λ = 1455 nm) was used in this study for noncontact ONS. This new all-fiber approach introduces several advantages including: (1) a less expensive and more compact ONS system, (2) elimination of alignment of optical components, and (3) an improved spatial beam profile. Successful optical stimulation of the rat CN using this new design was observed after the CN reached a threshold temperature of ~ 41 °C with response times as short as 3 s. Upon further study, this configuration may be useful for identification and preservation of the cavernous nerves during prostate cancer surgery.

  10. Measurements and models of electric fields in the in vivo human brain during transcranial electric stimulation

    PubMed Central

    Huang, Yu; Liu, Anli A; Lafon, Belen; Friedman, Daniel; Dayan, Michael; Wang, Xiuyuan; Bikson, Marom; Doyle, Werner K; Devinsky, Orrin; Parra, Lucas C

    2017-01-01

    Transcranial electric stimulation aims to stimulate the brain by applying weak electrical currents at the scalp. However, the magnitude and spatial distribution of electric fields in the human brain are unknown. We measured electric potentials intracranially in ten epilepsy patients and estimated electric fields across the entire brain by leveraging calibrated current-flow models. When stimulating at 2 mA, cortical electric fields reach 0.8 V/m, the lower limit of effectiveness in animal studies. When individual whole-head anatomy is considered, the predicted electric field magnitudes correlate with the recorded values in cortical (r = 0.86) and depth (r = 0.88) electrodes. Accurate models require adjustment of tissue conductivity values reported in the literature, but accuracy is not improved when incorporating white matter anisotropy or different skull compartments. This is the first study to validate and calibrate current-flow models with in vivo intracranial recordings in humans, providing a solid foundation to target stimulation and interpret clinical trials. DOI: http://dx.doi.org/10.7554/eLife.18834.001 PMID:28169833

  11. Improving working memory in children with attention-deficit/hyperactivity disorder: the separate and combined effects of incentives and stimulant medication.

    PubMed

    Strand, Michael T; Hawk, Larry W; Bubnik, Michelle; Shiels, Keri; Pelham, William E; Waxmonsky, James G

    2012-10-01

    Working memory (WM) is considered a core deficit in Attention-Deficit/ Hyperactivity Disorder (ADHD), with numerous studies demonstrating impaired WM among children with ADHD. We tested the degree to which WM in children with ADHD was improved by performance-based incentives, an analog of behavioral intervention. In two studies, WM performance was assessed using a visuo-spatial n-back task. Study 1 compared children (ages 9-12 years) with ADHD-Combined type (n = 24) to a group of typically developing (TD) children (n = 32). Study 1 replicated WM deficits among children with ADHD. Incentives improved WM, particularly among children with ADHD. The provision of incentives reduced the ADHD-control group difference by approximately half but did not normalize WM. Study 2 examined the separate and combined effects of incentives and stimulant medication among 17 children with ADHD-Combined type. Both incentives and a moderate dose of long-acting methylphenidate (MPH; ~0.3 mg/kg t.i.d. equivalent) robustly improved WM relative to the no-incentive, placebo condition. The combination of incentives and medication improved WM significantly more than either incentives or MPH alone. These studies indicate that contingencies markedly improve WM among children with ADHD-Combined type, with effect sizes comparable to a moderate dose of stimulant medication. More broadly, this work calls attention to the role of motivation in studying cognitive deficits in ADHD and in testing multifactorial models of ADHD.

  12. Results on the spatial resolution of repetitive transcranial magnetic stimulation for cortical language mapping during object naming in healthy subjects.

    PubMed

    Sollmann, Nico; Hauck, Theresa; Tussis, Lorena; Ille, Sebastian; Maurer, Stefanie; Boeckh-Behrens, Tobias; Ringel, Florian; Meyer, Bernhard; Krieg, Sandro M

    2016-10-24

    The spatial resolution of repetitive navigated transcranial magnetic stimulation (rTMS) for language mapping is largely unknown. Thus, to determine a minimum spatial resolution of rTMS for language mapping, we evaluated the mapping sessions derived from 19 healthy volunteers for cortical hotspots of no-response errors. Then, the distances between hotspots (stimulation points with a high error rate) and adjacent mapping points (stimulation points with low error rates) were evaluated. Mean distance values of 13.8 ± 6.4 mm (from hotspots to ventral points, range 0.7-30.7 mm), 10.8 ± 4.8 mm (from hotspots to dorsal points, range 2.0-26.5 mm), 16.6 ± 4.8 mm (from hotspots to apical points, range 0.9-27.5 mm), and 13.8 ± 4.3 mm (from hotspots to caudal points, range 2.0-24.2 mm) were measured. According to the results, the minimum spatial resolution of rTMS should principally allow for the identification of a particular gyrus, and according to the literature, it is in good accordance with the spatial resolution of direct cortical stimulation (DCS). Since measurement was performed between hotspots and adjacent mapping points and not on a finer-grained basis, we only refer to a minimum spatial resolution. Furthermore, refinement of our results within the scope of a prospective study combining rTMS and DCS for resolution measurement during language mapping should be the next step.

  13. Comparison between treadmill training with rhythmic auditory stimulation and ground walking with rhythmic auditory stimulation on gait ability in chronic stroke patients: A pilot study.

    PubMed

    Park, Jin; Park, So-yeon; Kim, Yong-wook; Woo, Youngkeun

    2015-01-01

    Generally, treadmill training is very effective intervention, and rhythmic auditory stimulation is designed to feedback during gait training in stroke patients. The purpose of this study was to compare the gait abilities in chronic stroke patients following either treadmill walking training with rhythmic auditory stimulation (TRAS) or over ground walking training with rhythmic auditory stimulation (ORAS). Nineteen subjects were divided into two groups: a TRAS group (9 subjects) and an ORAS group (10 subjects). Temporal and spatial gait parameters and motor recovery ability were measured before and after the training period. Gait ability was measured by the Biodex Gait trainer treadmill system, Timed up and go test (TUG), 6 meter walking distance (6MWD) and Functional gait assessment (FGA). After the training periods, the TRAS group showed a significant improvement in walking speed, step cycle, step length of the unaffected limb, coefficient of variation, 6MWD, and, FGA when compared to the ORAS group (p <  0.05). Treadmill walking training during the rhythmic auditory stimulation may be useful for rehabilitation of patients with chronic stroke.

  14. Boosting Cognition: Effects of Multiple-Session Transcranial Direct Current Stimulation on Working Memory.

    PubMed

    Talsma, Lotte J; Kroese, Henryk A; Slagter, Heleen A

    2017-04-01

    Transcranial direct current stimulation (tDCS) is a promising tool for neurocognitive enhancement. Several studies have shown that just a single session of tDCS over the left dorsolateral pFC (lDLPFC) can improve the core cognitive function of working memory (WM) in healthy adults. Yet, recent studies combining multiple sessions of anodal tDCS over lDLPFC with verbal WM training did not observe additional benefits of tDCS in subsequent stimulation sessions nor transfer of benefits to novel WM tasks posttraining. Using an enhanced stimulation protocol as well as a design that included a baseline measure each day, the current study aimed to further investigate the effects of multiple sessions of tDCS on WM. Specifically, we investigated the effects of three subsequent days of stimulation with anodal (20 min, 1 mA) versus sham tDCS (1 min, 1 mA) over lDLPFC (with a right supraorbital reference) paired with a challenging verbal WM task. WM performance was measured with a verbal WM updating task (the letter n-back) in the stimulation sessions and several WM transfer tasks (different letter set n-back, spatial n-back, operation span) before and 2 days after stimulation. Anodal tDCS over lDLPFC enhanced WM performance in the first stimulation session, an effect that remained visible 24 hr later. However, no further gains of anodal tDCS were observed in the second and third stimulation sessions, nor did benefits transfer to other WM tasks at the group level. Yet, interestingly, post hoc individual difference analyses revealed that in the anodal stimulation group the extent of change in WM performance on the first day of stimulation predicted pre to post changes on both the verbal and the spatial transfer task. Notably, this relationship was not observed in the sham group. Performance of two individuals worsened during anodal stimulation and on the transfer tasks. Together, these findings suggest that repeated anodal tDCS over lDLPFC combined with a challenging WM task may be an effective method to enhance domain-independent WM functioning in some individuals, but not others, or can even impair WM. They thus call for a thorough investigation into individual differences in tDCS respondence as well as further research into the design of multisession tDCS protocols that may be optimal for boosting cognition across a wide range of individuals.

  15. An infrared optical pacing system for high-throughput screening of cardiac electrophysiology in human cardiomyocytes (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    McPheeters, Matt T.; Wang, Yves T.; Laurita, Kenneth R.; Jenkins, Michael W.

    2017-02-01

    Cardiomyocytes derived from human induced pluripotent stem cells (hiPS-HCM) have the potential to provide individualized therapies for patients and to test drug candidates for cardiac toxicity. In order for hiPS-CM to be useful for such applications, there is a need for high-throughput technology to rapidly assess cardiac electrophysiology parameters. Here, we designed and tested a fully contactless optical mapping (OM) and optical pacing (OP) system capable of imaging and point stimulation of hiPS-CM in small wells. OM allowed us to characterize cardiac electrophysiological parameters (conduction velocity, action potential duration, etc.) using voltage-sensitive dyes with high temporal and spatial resolution over the entire well. To improve OM signal-to-noise ratio, we tested a new voltage-sensitive dye (Fluovolt) for accuracy and phototoxicity. Stimulation is essential because most electrophysiological parameters are rate dependent; however, traditional methods utilizing electrical stimulation is difficult in small wells. To overcome this limitation, we utilized OP (λ = 1464 nm) to precisely control heart rate with spatial precision without the addition of exogenous agents. We optimized OP parameters (e.g., well size, pulse width, spot size) to achieve robust pacing and minimize the threshold radiant exposure. Finally, we tested system sensitivity using Flecainide, a drug with well described action on multiple electrophysiological properties.

  16. Charge-balanced biphasic electrical stimulation inhibits neurite extension of spiral ganglion neurons.

    PubMed

    Shen, Na; Liang, Qiong; Liu, Yuehong; Lai, Bin; Li, Wen; Wang, Zhengmin; Li, Shufeng

    2016-06-15

    Intracochlear application of exogenous or transgenic neurotrophins, such as neurotrophin-3 (NT-3) and brain derived neurotrophic factor (BDNF), could promote the resprouting of spiral ganglion neuron (SGN) neurites in deafened animals. These resprouting neurites might reduce the gap between cochlear implant electrodes and their targeting SGNs, allowing for an improvement of spatial resolution of electrical stimulation. This study is to investigate the impact of electrical stimulation employed in CI on the extension of resprouting SGN neurites. We established an in vitro model including the devices delivering charge-balanced biphasic electrical stimulation, and spiral ganglion (SG) dissociated culture treated with BDNF and NT-3. After electrical stimulation with varying durations and intensities, we quantified neurite lengths and Schwann cell densities in SG cultures. Stimulations that were greater than 50μA or longer than 8h significantly decreased SG neurite length. Schwann cell density under 100μA electrical stimulation for 48h was significantly lower compared to that in non-stimulated group. These electrical stimulation-induced decreases of neurite extension and Schwann cell density were attenuated by various types of voltage-dependent calcium channel (VDCC) blockers, or completely prevented by their combination, cadmium or calcium-free medium. Our study suggested that charge-balanced biphasic electrical stimulation inhibited the extension of resprouting SGN neurites and decreased Schwann cell density in vitro. Calcium influx through multiple types of VDCCs was involved in the electrical stimulation-induced inhibition. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Development of a multi-electrode array for spinal cord epidural stimulation to facilitate stepping and standing after a complete spinal cord injury in adult rats.

    PubMed

    Gad, Parag; Choe, Jaehoon; Nandra, Mandheerej Singh; Zhong, Hui; Roy, Roland R; Tai, Yu-Chong; Edgerton, V Reggie

    2013-01-21

    Stimulation of the spinal cord has been shown to have great potential for improving function after motor deficits caused by injury or pathological conditions. Using a wide range of animal models, many studies have shown that stimulation applied to the neural networks intrinsic to the spinal cord can result in a dramatic improvement of motor ability, even allowing an animal to step and stand after a complete spinal cord transection. Clinical use of this technology, however, has been slow to develop due to the invasive nature of the implantation procedures, the lack of versatility in conventional stimulation technology, and the difficulty of ascertaining specific sites of stimulation that would provide optimal amelioration of the motor deficits. Moreover, the development of tools available to control precise stimulation chronically via biocompatible electrodes has been limited. In this paper, we outline the development of this technology and its use in the spinal rat model, demonstrating the ability to identify and stimulate specific sites of the spinal cord to produce discrete motor behaviors in spinal rats using this array. We have designed a chronically implantable, rapidly switchable, high-density platinum based multi-electrode array that can be used to stimulate at 1-100 Hz and 1-10 V in both monopolar and bipolar configurations to examine the electrophysiological and behavioral effects of spinal cord epidural stimulation in complete spinal cord transected rats. In this paper, we have demonstrated the effectiveness of using high-resolution stimulation parameters in the context of improving motor recovery after a spinal cord injury. We observed that rats whose hindlimbs were paralyzed can stand and step when specific sets of electrodes of the array are stimulated tonically (40 Hz). Distinct patterns of stepping and standing were produced by stimulation of different combinations of electrodes on the array located at specific spinal cord levels and by specific stimulation parameters, i.e., stimulation frequency and intensity, and cathode/anode orientation. The array also was used to assess functional connectivity between the cord dorsum to interneuronal circuits and specific motor pools via evoked potentials induced at 1 Hz stimulation in the absence of any anesthesia. Therefore the high density electrode array allows high spatial resolution and the ability to selectively activate different neural pathways within the lumbosacral region of the spinal cord to facilitate standing and stepping in adult spinal rats and provides the capability to evoke motor potentials and thus a means for assessing connectivity between sensory circuits and specific motor pools and muscles.

  18. Improvements in Memory after Medial Septum Stimulation Are Associated with Changes in Hippocampal Cholinergic Activity and Neurogenesis

    PubMed Central

    Jeong, Da Un; Lee, Ji Eun; Lee, Sung Eun; Chang, Won Seok; Kim, Sung June; Chang, Jin Woo

    2014-01-01

    Deep brain stimulation (DBS) has been found to have therapeutic effects in patients with dementia, but DBS mechanisms remain elusive. To provide evidence for the effectiveness of DBS as a treatment for dementia, we performed DBS in a rat model of dementia with intracerebroventricular administration of 192 IgG-saporins. We utilized four groups of rats, group 1, unlesioned control; group 2, cholinergic lesion; group 3, cholinergic lesion plus medial septum (MS) electrode implantation (sham stimulation); group 4, cholinergic lesions plus MS electrode implantation and stimulation. During the probe test in the water maze, performance of the lesion group decreased for measures of time spent and the number of swim crossings over the previous platform location. Interestingly, the stimulation group showed an equivalent performance to the normal group on all measures. And these are partially reversed by the electrode implantation. Acetylcholinesterase activity in the hippocampus was decreased in lesion and implantation groups, whereas activity in the stimulation group was not different from the normal group. Hippocampal neurogenesis was increased in the stimulation group. Our results revealed that DBS of MS restores spatial memory after damage to cholinergic neurons. This effect is associated with an increase in hippocampal cholinergic activity and neurogenesis. PMID:25101288

  19. Spatially Uniform Tumor Treatment and Drug Penetration by Regulating Ultrasound with Microbubbles.

    PubMed

    Ho, Yi-Ju; Wang, Tzu-Chia; Fan, Ching-Hsiang; Yeh, Chih-Kuang

    2018-05-30

    Tumor microenvironment has different morphologies of vessels in the core and rim regions, which influences the efficacy of tumor therapy. Our study proposed to improve the spatial uniformity of the antivascular effect and drug penetration within the tumor core and rim in combination therapies by regulating ultrasound-stimulated microbubble destruction (USMD). Focused ultrasound at 2 MHz and lipid-shell microbubbles (1.12 ± 0.08 μm, mean ± standard deviation) were used to perform USMD. The efficiency of the antivascular effect was evaluated by intravital imaging to determine the optimal USMD parameters. Tumor perfusion and histological alterations in the tumor core and rim were used to analyze the spatial uniformity of the antivascular effect and liposomal-doxorubicin (5 mg/kg) penetration in the combination therapy. Tumor vessels of specific sizes were disrupted by regulating USMD: vessels with sizes of 11 ± 3, 14 ± 5, 19 ± 7, and 23 ± 10 μm were disrupted by stimulation at acoustic pressures of 3, 5, 7, and 9 MPa, respectively (each p < 0.05). The effective treatment time of USMD (at 2 × 10 7 microbubbles/mouse, 7 MPa, and three cycles) was 60-120 min, which resulted in the disruption of 21-44% of vessels smaller than 50 μm. The reductions in perfusion and vascular density after combination therapy did not differ significantly between the tumor core and rim. This study found that regulating USMD can result in homogeneous antivascular effects and drug penetration within tumors and thereby improve the efficacy of combination therapies.

  20. Improved selectivity from a wavelength addressable device for wireless stimulation of neural tissue

    PubMed Central

    Seymour, Elif Ç.; Freedman, David S.; Gökkavas, Mutlu; Özbay, Ekmel; Sahin, Mesut; Ünlü, M. Selim

    2014-01-01

    Electrical neural stimulation with micro electrodes is a promising technique for restoring lost functions in the central nervous system as a result of injury or disease. One of the problems related to current neural stimulators is the tissue response due to the connecting wires and the presence of a rigid electrode inside soft neural tissue. We have developed a novel, optically activated, microscale photovoltaic neurostimulator based on a custom layered compound semiconductor heterostructure that is both wireless and has a comparatively small volume (<0.01 mm3). Optical activation provides a wireless means of energy transfer to the neurostimulator, eliminating wires and the associated complications. This neurostimulator was shown to evoke action potentials and a functional motor response in the rat spinal cord. In this work, we extend our design to include wavelength selectivity and thus allowing independent activation of devices. As a proof of concept, we fabricated two different microscale devices with different spectral responsivities in the near-infrared region. We assessed the improved addressability of individual devices via wavelength selectivity as compared to spatial selectivity alone through on-bench optical measurements of the devices in combination with an in vivo light intensity profile in the rat cortex obtained in a previous study. We show that wavelength selectivity improves the individual addressability of the floating stimulators, thus increasing the number of devices that can be implanted in close proximity to each other. PMID:24600390

  1. Masking of infrared neural stimulation (INS) in hearing and deaf guinea pigs

    NASA Astrophysics Data System (ADS)

    Kadakia, Sama; Young, Hunter; Richter, Claus-Peter

    2013-03-01

    Spatial selective infrared neural stimulation has potential to improve neural prostheses, including cochlear implants. The heating of a confined target volume depolarizes the cell membrane and results in an action potential. Tissue heating may also results in thermal damage or the generation of a stress relaxation wave. Stress relaxation waves may result in a direct mechanical stimulation of remaining hair cells in the cochlea, so called optophony. Data are presented that quantify the effect of an acoustical stimulus (noise masker) on the response obtained with INS in normal hearing, acutely deafened, and chronic deaf animals. While in normal hearing animals an acoustic masker can reduce the response to INS, in acutely deafened animals the masking effect is reduced, and in chronic deaf animals this effect has not been detected. The responses to INS remain stable following the different degrees of cochlear damage.

  2. Stimulation from Cochlear Implant Electrodes Assists with Recovery from Asymmetric Perceptual Tilt: Evidence from the Subjective Visual Vertical Test

    PubMed Central

    Gnanasegaram, Joshua J.; Parkes, William J.; Cushing, Sharon L.; McKnight, Carmen L.; Papsin, Blake C.; Gordon, Karen A.

    2016-01-01

    Vestibular end organ impairment is highly prevalent in children who have sensorineural hearing loss (SNHL) rehabilitated with cochlear implants (CIs). As a result, spatial perception is likely to be impacted in this population. Of particular interest is the perception of visual vertical because it reflects a perceptual tilt in the roll axis and is sensitive to an imbalance in otolith function. The objectives of the present study were thus to identify abnormalities in perception of the vertical plane in children with SNHL and determine whether such abnormalities could be resolved with stimulation from the CI. Participants included 53 children (15.2 ± 4.0 years of age) with SNHL and vestibular loss, confirmed with vestibular evoked myogenic potential (VEMP) testing. Testing protocol was validated in a sample of nine young adults with normal hearing (28.8 ± 7.7 years). Perception of visual vertical was assessed using the static Subjective Visual Vertical (SVV) test performed with and without stimulation in the participants with cochleovestibular loss. Trains of electrical pulses were delivered by an electrode in the left and/or right ear. Asymmetric spatial orientation deficits were found in nearly half of the participants with CIs (24/53 [45%]). The abnormal perception in this cohort was exacerbated by visual tilts in the direction of their deficit. Electric pulse trains delivered using the CI shifted this abnormal perception towards center (i.e., normal; p = 0.007). Importantly, this benefit was realized regardless of which ear was stimulated. These results suggest a role for CI stimulation beyond the auditory system, in particular, for improving vestibular/balance function. PMID:27679562

  3. Patterned optogenetic modulation of neurovascular and metabolic signals

    PubMed Central

    Richner, Thomas J; Baumgartner, Ryan; Brodnick, Sarah K; Azimipour, Mehdi; Krugner-Higby, Lisa A; Eliceiri, Kevin W; Williams, Justin C; Pashaie, Ramin

    2015-01-01

    The hemodynamic and metabolic response of the cortex depends spatially and temporally on the activity of multiple cell types. Optogenetics enables specific cell types to be modulated with high temporal precision and is therefore an emerging method for studying neurovascular and neurometabolic coupling. Going beyond temporal investigations, we developed a microprojection system to apply spatial photostimulus patterns in vivo. We monitored vascular and metabolic fluorescence signals after photostimulation in Thy1-channelrhodopsin-2 mice. Cerebral arteries increased in diameter rapidly after photostimulation, while nearby veins showed a slower smaller response. The amplitude of the arterial response was depended on the area of cortex stimulated. The fluorescence signal emitted at 450/100 nm and excited with ultraviolet is indicative of reduced nicotinamide adenine dinucleotide, an endogenous fluorescent enzyme involved in glycolysis and the citric acid cycle. This fluorescence signal decreased quickly and transiently after optogenetic stimulation, suggesting that glucose metabolism is tightly locked to optogenetic stimulation. To verify optogenetic stimulation of the cortex, we used a transparent substrate microelectrode array to map cortical potentials resulting from optogenetic stimulation. Spatial optogenetic stimulation is a new tool for studying neurovascular and neurometabolic coupling. PMID:25388678

  4. Transcutaneous Electrical Nerve Stimulation Effects on Neglect: A Visual-Evoked Potential Study

    PubMed Central

    Pitzalis, Sabrina; Spinelli, Donatella; Vallar, Giuseppe; Di Russo, Francesco

    2013-01-01

    We studied the effects of transcutaneous electrical nerve stimulation (TENS) in six right-brain-damaged patients with left unilateral spatial neglect (USN), using both standard clinical tests (reading, line, and letter cancelation, and line bisection), and electrophysiological measures (steady-state visual-evoked potentials, SSVEP). TENS was applied on left neck muscles for 15′, and measures were recorded before, immediately after, and 60′ after stimulation. Behavioral results showed that the stimulation temporarily improved the deficit in all patients. In cancelation tasks, omissions and performance asymmetries between the two hand-sides were reduced, as well as the rightward deviation in line bisection. Before TENS, SSVEP average latency to stimuli displayed in the left visual half-field [LVF (160 ms)] was remarkably longer than to stimuli shown in the right visual half-field [RVF (120 ms)]. Immediately after TENS, latency to LVF stimuli was 130 ms; 1 h after stimulation the effect of TENS faded, with latency returning to baseline. TENS similarly affected also the latency SSVEP of 12 healthy participants, and their line bisection performance, with effects smaller in size. The present study, first, replicates evidence concerning the positive behavioral effects of TENS on the manifestations of left USN in right-brain-damaged patients; second, it shows putatively related electrophysiological effects on the SSVEP latency. These behavioral and novel electrophysiological results are discussed in terms of specific directional effects of left somatosensory stimulation on egocentric coordinates, which in USN patients are displaced toward the side of the cerebral lesion. Showing that visual-evoked potentials latency is modulated by proprioceptive stimulation, we provide electrophysiological evidence to the effect that TENS may improve some manifestations of USN, with implications for its rehabilitation. PMID:23966919

  5. Effects of transcranial direct current stimulation for treating depression: A modeling study.

    PubMed

    Csifcsák, Gábor; Boayue, Nya Mehnwolo; Puonti, Oula; Thielscher, Axel; Mittner, Matthias

    2018-07-01

    Transcranial direct current stimulation (tDCS) above the left dorsolateral prefrontal cortex (lDLPFC) has been widely used to improve symptoms of major depressive disorder (MDD). However, the effects of different stimulation protocols in the entire frontal lobe have not been investigated in a large sample including patient data. We used 38 head models created from structural magnetic resonance imaging data of 19 healthy adults and 19 MDD patients and applied computational modeling to simulate the spatial distribution of tDCS-induced electric fields (EFs) in 20 frontal regions. We evaluated effects of seven bipolar and two multi-electrode 4 × 1 tDCS protocols. For bipolar montages, EFs were of comparable strength in the lDLPFC and in the medial prefrontal cortex (MPFC). Depending on stimulation parameters, EF cortical maps varied to a considerable degree, but were found to be similar in controls and patients. 4 × 1 montages produced more localized, albeit weaker effects. White matter anisotropy was not modeled. The relationship between EF strength and clinical response to tDCS could not be evaluated. In addition to lDLPFC stimulation, excitability changes in the MPFC should also be considered as a potential mechanism underlying clinical efficacy of bipolar montages. MDD-associated anatomical variations are not likely to substantially influence current flow. Individual modeling of tDCS protocols can substantially improve cortical targeting. We make recommendations for future research to explicitly test the contribution of lDLPFC vs. MPFC stimulation to therapeutic outcomes of tDCS in this disorder. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chu, Zhaodong; Yang, Mengjin; Schulz, Philip

    Organic-inorganic perovskite solar cells have attracted tremendous attention because of their remarkably high power conversion efficiencies. To further improve device performance, it is imperative to obtain fundamental understandings on the photo-response and long-term stability down to the microscopic level. Here, we report the quantitative nanoscale photoconductivity imaging on two methylammonium lead triiodide thin films with different efficiencies by light-stimulated microwave impedance microscopy. The microwave signals are largely uniform across grains and grain boundaries, suggesting that microstructures do not lead to strong spatial variations of the intrinsic photo-response. In contrast, the measured photoconductivity and lifetime are strongly affected by bulk propertiesmore » such as the sample crystallinity. As visualized by the spatial evolution of local photoconductivity, the degradation process begins with the disintegration of grains rather than nucleation and propagation from visible boundaries between grains. In conclusion, our findings provide insights to improve the electro-optical properties of perovskite thin films towards large-scale commercialization.« less

  7. Orientation of human optokinetic nystagmus to gravity: a model-based approach

    NASA Technical Reports Server (NTRS)

    Gizzi, M.; Raphan, T.; Rudolph, S.; Cohen, B.

    1994-01-01

    Optokinetic nystagmus (OKN) was induced by having subjects watch a moving display in a binocular, head-fixed apparatus. The display was composed of 3.3 degrees stripes moving at 35 degrees/s for 45 s. It subtended 88 degrees horizontally by 72 degrees vertically of the central visual field and could be oriented to rotate about axes that were upright or tilted 45 degrees or 90 degrees. The head was held upright or was tilted 45 degrees left or right on the body during stimulation. Head-horizontal (yaw axis) and head-vertical (pitch axis) components of OKN were recorded with electro-oculography (EOG). Slow phase velocity vectors were determined and compared with the axis of stimulation and the spatial vertical (gravity axis). With the head upright, the axis of eye rotation during yaw axis OKN was coincident with the stimulus axis and the spatial vertical. With the head tilted, a significant vertical component of eye velocity appeared during yaw axis stimulation. As a result the axis of eye rotation shifted from the stimulus axis toward the spatial vertical. Vertical components developed within 1-2 s of stimulus onset and persisted until the end of stimulation. In the six subjects there was a mean shift of the axis of eye rotation during yaw axis stimulation of approximately 18 degrees with the head tilted 45 degrees on the body. Oblique optokinetic stimulation with the head upright was associated with a mean shift of the axis of eye rotation toward the spatial vertical of 9.2 degrees. When the head was tilted and the same oblique stimulation was given, the axis of eye rotation rotated to the other side of the spatial vertical by 5.4 degrees. This counterrotation of the axis of eye rotation is similar to the "Muller (E) effect," in which the perception of the upright is counterrotated to the opposite side of the spatial vertical when subjects are tilted in darkness. The data were simulated by a model of OKN with a "direct" and "indirect" pathway. It was assumed that the direct visual pathway is oriented in a body, not a spatial frame of reference. Despite the short optokinetic after-nystagmus time constants, strong horizontal to vertical cross-coupling could be produced if the horizontal and vertical time constants were in proper ratio and there were no suppression of nystagmus in directions orthogonal to the stimulus direction. The model demonstrates that the spatial orientation of OKN can be achieved by restructuring the system matrix of velocity storage. We conclude that an important function of velocity storage is to orient slow-phase velocity toward the spatial vertical during movement in a terrestrial environment.

  8. Nanostructured cavity devices for extracellular stimulation of HL-1 cells

    NASA Astrophysics Data System (ADS)

    Czeschik, Anna; Rinklin, Philipp; Derra, Ulrike; Ullmann, Sabrina; Holik, Peter; Steltenkamp, Siegfried; Offenhäusser, Andreas; Wolfrum, Bernhard

    2015-05-01

    Microelectrode arrays (MEAs) are state-of-the-art devices for extracellular recording and stimulation on biological tissue. Furthermore, they are a relevant tool for the development of biomedical applications like retina, cochlear and motor prostheses, cardiac pacemakers and drug screening. Hence, research on functional cell-sensor interfaces, as well as the development of new surface structures and modifications for improved electrode characteristics, is a vivid and well established field. However, combining single-cell resolution with sufficient signal coupling remains challenging due to poor cell-electrode sealing. Furthermore, electrodes with diameters below 20 µm often suffer from a high electrical impedance affecting the noise during voltage recordings. In this study, we report on a nanocavity sensor array for voltage-controlled stimulation and extracellular action potential recordings on cellular networks. Nanocavity devices combine the advantages of low-impedance electrodes with small cell-chip interfaces, preserving a high spatial resolution for recording and stimulation. A reservoir between opening aperture and electrode is provided, allowing the cell to access the structure for a tight cell-sensor sealing. We present the well-controlled fabrication process and the effect of cavity formation and electrode patterning on the sensor's impedance. Further, we demonstrate reliable voltage-controlled stimulation using nanostructured cavity devices by capturing the pacemaker of an HL-1 cell network.Microelectrode arrays (MEAs) are state-of-the-art devices for extracellular recording and stimulation on biological tissue. Furthermore, they are a relevant tool for the development of biomedical applications like retina, cochlear and motor prostheses, cardiac pacemakers and drug screening. Hence, research on functional cell-sensor interfaces, as well as the development of new surface structures and modifications for improved electrode characteristics, is a vivid and well established field. However, combining single-cell resolution with sufficient signal coupling remains challenging due to poor cell-electrode sealing. Furthermore, electrodes with diameters below 20 µm often suffer from a high electrical impedance affecting the noise during voltage recordings. In this study, we report on a nanocavity sensor array for voltage-controlled stimulation and extracellular action potential recordings on cellular networks. Nanocavity devices combine the advantages of low-impedance electrodes with small cell-chip interfaces, preserving a high spatial resolution for recording and stimulation. A reservoir between opening aperture and electrode is provided, allowing the cell to access the structure for a tight cell-sensor sealing. We present the well-controlled fabrication process and the effect of cavity formation and electrode patterning on the sensor's impedance. Further, we demonstrate reliable voltage-controlled stimulation using nanostructured cavity devices by capturing the pacemaker of an HL-1 cell network. Electronic supplementary information (ESI) available: Comparison of non-filtered and Savitzky-Golay filtered action potential recordings, electrical signals and corresponding optical signals. See DOI: 10.1039/c5nr01690h

  9. Improving fMRI reliability in presurgical mapping for brain tumours.

    PubMed

    Stevens, M Tynan R; Clarke, David B; Stroink, Gerhard; Beyea, Steven D; D'Arcy, Ryan Cn

    2016-03-01

    Functional MRI (fMRI) is becoming increasingly integrated into clinical practice for presurgical mapping. Current efforts are focused on validating data quality, with reliability being a major factor. In this paper, we demonstrate the utility of a recently developed approach that uses receiver operating characteristic-reliability (ROC-r) to: (1) identify reliable versus unreliable data sets; (2) automatically select processing options to enhance data quality; and (3) automatically select individualised thresholds for activation maps. Presurgical fMRI was conducted in 16 patients undergoing surgical treatment for brain tumours. Within-session test-retest fMRI was conducted, and ROC-reliability of the patient group was compared to a previous healthy control cohort. Individually optimised preprocessing pipelines were determined to improve reliability. Spatial correspondence was assessed by comparing the fMRI results to intraoperative cortical stimulation mapping, in terms of the distance to the nearest active fMRI voxel. The average ROC-r reliability for the patients was 0.58±0.03, as compared to 0.72±0.02 in healthy controls. For the patient group, this increased significantly to 0.65±0.02 by adopting optimised preprocessing pipelines. Co-localisation of the fMRI maps with cortical stimulation was significantly better for more reliable versus less reliable data sets (8.3±0.9 vs 29±3 mm, respectively). We demonstrated ROC-r analysis for identifying reliable fMRI data sets, choosing optimal postprocessing pipelines, and selecting patient-specific thresholds. Data sets with higher reliability also showed closer spatial correspondence to cortical stimulation. ROC-r can thus identify poor fMRI data at time of scanning, allowing for repeat scans when necessary. ROC-r analysis provides optimised and automated fMRI processing for improved presurgical mapping. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  10. Model-Based Comparison of Deep Brain Stimulation Array Functionality with Varying Number of Radial Electrodes and Machine Learning Feature Sets.

    PubMed

    Teplitzky, Benjamin A; Zitella, Laura M; Xiao, YiZi; Johnson, Matthew D

    2016-01-01

    Deep brain stimulation (DBS) leads with radially distributed electrodes have potential to improve clinical outcomes through more selective targeting of pathways and networks within the brain. However, increasing the number of electrodes on clinical DBS leads by replacing conventional cylindrical shell electrodes with radially distributed electrodes raises practical design and stimulation programming challenges. We used computational modeling to investigate: (1) how the number of radial electrodes impact the ability to steer, shift, and sculpt a region of neural activation (RoA), and (2) which RoA features are best used in combination with machine learning classifiers to predict programming settings to target a particular area near the lead. Stimulation configurations were modeled using 27 lead designs with one to nine radially distributed electrodes. The computational modeling framework consisted of a three-dimensional finite element tissue conductance model in combination with a multi-compartment biophysical axon model. For each lead design, two-dimensional threshold-dependent RoAs were calculated from the computational modeling results. The models showed more radial electrodes enabled finer resolution RoA steering; however, stimulation amplitude, and therefore spatial extent of the RoA, was limited by charge injection and charge storage capacity constraints due to the small electrode surface area for leads with more than four radially distributed electrodes. RoA shifting resolution was improved by the addition of radial electrodes when using uniform multi-cathode stimulation, but non-uniform multi-cathode stimulation produced equivalent or better resolution shifting without increasing the number of radial electrodes. Robust machine learning classification of 15 monopolar stimulation configurations was achieved using as few as three geometric features describing a RoA. The results of this study indicate that, for a clinical-scale DBS lead, more than four radial electrodes minimally improved in the ability to steer, shift, and sculpt axonal activation around a DBS lead and a simple feature set consisting of the RoA center of mass and orientation enabled robust machine learning classification. These results provide important design constraints for future development of high-density DBS arrays.

  11. Model-Based Comparison of Deep Brain Stimulation Array Functionality with Varying Number of Radial Electrodes and Machine Learning Feature Sets

    PubMed Central

    Teplitzky, Benjamin A.; Zitella, Laura M.; Xiao, YiZi; Johnson, Matthew D.

    2016-01-01

    Deep brain stimulation (DBS) leads with radially distributed electrodes have potential to improve clinical outcomes through more selective targeting of pathways and networks within the brain. However, increasing the number of electrodes on clinical DBS leads by replacing conventional cylindrical shell electrodes with radially distributed electrodes raises practical design and stimulation programming challenges. We used computational modeling to investigate: (1) how the number of radial electrodes impact the ability to steer, shift, and sculpt a region of neural activation (RoA), and (2) which RoA features are best used in combination with machine learning classifiers to predict programming settings to target a particular area near the lead. Stimulation configurations were modeled using 27 lead designs with one to nine radially distributed electrodes. The computational modeling framework consisted of a three-dimensional finite element tissue conductance model in combination with a multi-compartment biophysical axon model. For each lead design, two-dimensional threshold-dependent RoAs were calculated from the computational modeling results. The models showed more radial electrodes enabled finer resolution RoA steering; however, stimulation amplitude, and therefore spatial extent of the RoA, was limited by charge injection and charge storage capacity constraints due to the small electrode surface area for leads with more than four radially distributed electrodes. RoA shifting resolution was improved by the addition of radial electrodes when using uniform multi-cathode stimulation, but non-uniform multi-cathode stimulation produced equivalent or better resolution shifting without increasing the number of radial electrodes. Robust machine learning classification of 15 monopolar stimulation configurations was achieved using as few as three geometric features describing a RoA. The results of this study indicate that, for a clinical-scale DBS lead, more than four radial electrodes minimally improved in the ability to steer, shift, and sculpt axonal activation around a DBS lead and a simple feature set consisting of the RoA center of mass and orientation enabled robust machine learning classification. These results provide important design constraints for future development of high-density DBS arrays. PMID:27375470

  12. Associations between cognitively stimulating leisure activities, cognitive function and age-related cognitive decline.

    PubMed

    Ferreira, Nicola; Owen, Adrian; Mohan, Anita; Corbett, Anne; Ballard, Clive

    2015-04-01

    Emerging literature suggests that lifestyle factors may play an important role in reducing age-related cognitive decline. There have, however, been few studies investigating the role of cognitively stimulating leisure activities in maintaining cognitive health. This study sought to identify changes in cognitive performance with age and to investigate associations of cognitive performance with several key cognitively stimulating leisure activities. Over 65,000 participants provided demographic and lifestyle information and completed tests of grammatical reasoning, spatial working memory, verbal working memory and episodic memory. Regression analyses suggested that frequency of engaging in Sudoku or similar puzzles was significantly positively associated with grammatical reasoning, spatial working memory and episodic memory scores. Furthermore, for participants aged under 65 years, frequency of playing non-cognitive training computer games was also positively associated with performance in the same cognitive domains. The results also suggest that grammatical reasoning and episodic memory are particularly vulnerable to age-related decline. Further investigation to determine the potential benefits of participating in Sudoku puzzles and non-cognitive computer games is indicated, particularly as they are associated with grammatical reasoning and episodic memory, cognitive domains found to be strongly associated with age-related cognitive decline. Results of this study have implications for developing improved guidance for the public regarding the potential value of cognitively stimulating leisure activities. The results also suggest that grammatical reasoning and episodic memory should be targeted in developing appropriate outcome measures to assess efficacy of future interventions, and in developing cognitive training programmes to prevent or delay cognitive decline. Copyright © 2014 John Wiley & Sons, Ltd.

  13. Differential effects of tactile high- and low-frequency stimulation on tactile discrimination in human subjects.

    PubMed

    Ragert, Patrick; Kalisch, Tobias; Bliem, Barbara; Franzkowiak, Stephanie; Dinse, Hubert R

    2008-01-23

    Long-term potentiation (LTP) and long-term depression (LTD) play important roles in mediating activity-dependent changes in synaptic transmission and are believed to be crucial mechanisms underlying learning and cortical plasticity. In human subjects, however, the lack of adequate input stimuli for the induction of LTP and LTD makes it difficult to study directly the impact of such protocols on behavior. Using tactile high- and low-frequency stimulation protocols in humans, we explored the potential of such protocols for the induction of perceptual changes. We delivered tactile high-frequency and low-frequency stimuli (t-HFS, t-LFS) to skin sites of approximately 50 mm2 on the tip of the index finger. As assessed by 2-point discrimination, we demonstrate that 20 minutes of t-HFS improved tactile discrimination, while t-LFS impaired performance. T-HFS-effects were stable for at least 24 hours whereas t-LFS-induced changes recovered faster. While t-HFS changes were spatially very specific with no changes on the neighboring fingers, impaired tactile performance after t-LFS was also observed on the right middle-finger. A central finding was that for both t-LFS and t-HFS perceptual changes were dependent on the size of the stimulated skin area. No changes were observed when the stimulated area was very small (< 1 mm2) indicating special requirements for spatial summation. Our results demonstrate differential effects of such protocols in a frequency specific manner that might be related to LTP- and LTD-like changes in human subjects.

  14. Correlation of spatial intensity distribution of light reaching the retina and restoration of vision by optogenetic stimulation

    NASA Astrophysics Data System (ADS)

    Shivalingaiah, Shivaranjani; Gu, Ling; Mohanty, Samarendra K.

    2011-03-01

    Stimulation of retinal neuronal cells using optogenetics via use of chanelrhodopsin-2 (ChR2) and blue light has opened up a new direction for restoration of vision with respect to treatment of Retinitis pigmentosa (RP). In addition to delivery of ChR2 to specific retinal layer using genetic engineering, threshold level of blue light needs to be delivered onto the retina for generating action potential and successful behavioral outcome. We report measurement of intensity distribution of light reaching the retina of Retinitis pigmentosa (RP) mouse models and compared those results with theoretical simulations of light propagation in eye. The parameters for the stimulating source positioning in front of eye was determined for optimal light delivery to the retina. In contrast to earlier viral method based delivery of ChR2 onto retinal ganglion cells, in-vivo electroporation method was employed for retina-transfection of RP mice. The behavioral improvement in mice with Thy1-ChR2-YFP transfected retina, expressing ChR2 in retinal ganglion cells, was found to correlate with stimulation intensity.

  15. Active and placebo transcranial magnetic stimulation effects on external and internal auditory hallucinations of schizophrenia.

    PubMed

    Paillère-Martinot, M-L; Galinowski, A; Plaze, M; Andoh, J; Bartrés-Faz, D; Bellivier, F; Lefaucheur, J-P; Rivière, D; Gallarda, T; Martinot, J-L; Artiges, E

    2017-03-01

    Repetitive transcranial magnetic stimulation (rTMS) over the left temporo-parietal region has been proposed as a treatment for resistant auditory verbal hallucinations (AVH), but which patients are more likely to benefit from rTMS is still unclear. This study sought to assess the effects of rTMS on AVH, with a focus on hallucination phenomenology. Twenty-seven patients with schizophrenia and medication-resistant AVH participated to a randomized, double-blind, placebo-controlled, add-on rTMS study. The stimulation targeted a language-perception area individually determined using functional magnetic resonance imaging and a language recognition task. AVH were assessed using the hallucination subscale of the Scale for the Assessment of Positive Symptoms (SAPS). The spatial location of AVH was assessed using the Psychotic Symptom Rating Scales. A significant improvement in SAPS hallucination subscale score was observed in both actively treated and placebo-treated groups with no difference between both modalities. Patients with external AVH were significantly more improved than patients with internal AVH, with both modalities. A marked placebo effect of rTMS was observed in patients with resistant AVH. Patients with prominent external AVH may be more likely to benefit from both active and placebo interventions. Cortical effects related to non-magnetic stimulation of the auditory cortex are suggested. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Endogenous hippocampal LTD that is enabled by spatial object recognition requires activation of NMDA receptors and the metabotropic glutamate receptor, mGlu5.

    PubMed

    Goh, Jinzhong Jeremy; Manahan-Vaughan, Denise

    2013-02-01

    Learning-facilitated synaptic plasticity describes the ability of hippocampal synapses to respond with persistent plasticity to afferent stimulation when coupled with a spatial learning event, whereby the afferent stimulation normally produces short-term plasticity or no change in synaptic strength if given in the absence of novel learning. Recently, it was reported that in the mouse hippocampus intrinsic long-term depression (LTD > 24 h) occurs when test-pulse afferent stimulation is coupled with a novel spatial learning. It is not known to what extent this phenomenon shares molecular properties with synaptic plasticity that is typically induced by means of patterned electrical afferent stimulation. In previous work, we showed that a novel spatial object recognition task facilitates LTD at the Schaffer collateral-CA1 synapse of freely behaving adult mice, whereas reexposure to the familiar spatial configuration ∼24 h later elicited no such facilitation. Here we report that treatment with the NMDA receptor antagonist, (±)-3-(2-Carboxypiperazin-4-yl)-propanephosphonic acid (CPP), or antagonism of metabotropic glutamate (mGlu) receptor, mGlu5, using 2-methyl-6-(phenylethynyl) pyridine (MPEP), completely prevented LTD under the novel learning conditions. Behavioral assessment during re-exposure after application of the antagonists revealed that the animals did not remember the object during novel exposure and treated them as if they were novel. Under these circumstances, where the acquisition of novel spatial information was involved, LTD was facilitated. Our data support that the endogenous LTD that is enabled through novel spatial learning in adult mice is critically dependent on the activation of both the NMDA receptors and mGlu5. Copyright © 2012 Wiley Periodicals, Inc.

  17. Action video games improve reading abilities and visual-to-auditory attentional shifting in English-speaking children with dyslexia.

    PubMed

    Franceschini, Sandro; Trevisan, Piergiorgio; Ronconi, Luca; Bertoni, Sara; Colmar, Susan; Double, Kit; Facoetti, Andrea; Gori, Simone

    2017-07-19

    Dyslexia is characterized by difficulties in learning to read and there is some evidence that action video games (AVG), without any direct phonological or orthographic stimulation, improve reading efficiency in Italian children with dyslexia. However, the cognitive mechanism underlying this improvement and the extent to which the benefits of AVG training would generalize to deep English orthography, remain two critical questions. During reading acquisition, children have to integrate written letters with speech sounds, rapidly shifting their attention from visual to auditory modality. In our study, we tested reading skills and phonological working memory, visuo-spatial attention, auditory, visual and audio-visual stimuli localization, and cross-sensory attentional shifting in two matched groups of English-speaking children with dyslexia before and after they played AVG or non-action video games. The speed of words recognition and phonological decoding increased after playing AVG, but not non-action video games. Furthermore, focused visuo-spatial attention and visual-to-auditory attentional shifting also improved only after AVG training. This unconventional reading remediation program also increased phonological short-term memory and phoneme blending skills. Our report shows that an enhancement of visuo-spatial attention and phonological working memory, and an acceleration of visual-to-auditory attentional shifting can directly translate into better reading in English-speaking children with dyslexia.

  18. [Stimulation of D1-receptors improves passive avoidance learning of female rats during ovary cycle].

    PubMed

    Fedotova, Iu O; Sapronov, N S

    2012-01-01

    The involvement of D1-receptors in learning/memory processes during ovary cycle was assessed in the adult female rats. SKF-38393 (0,1 mg/kg, i.p.), D1-receptor agonist and SCH-23390 (0,1 mg/kg, i.p.), D1-receptor antagonist were injected chronically to adult female rats. Learning of these animals was assessed in different models: passive avoidance performance and Morris water maze. Chronic SKF-3839 administration to females resulted in the appearance of the passive avoidance performance in proestrous and estrous, as distinct from the control animals, but failed to change the dynamics of spatial learning in Morris water maze. Chronic SCH-23390 administration similarly impaired non-spatial and spatial learning in females during all phases of ovary cycle. The results of the study suggest modulating role of D1-receptors in learning/memory processes during ovary cycle in the adult female rats.

  19. On the temporal dynamics of spatial stimulus-response transfer between spatial incompatibility and Simon tasks

    PubMed Central

    Ivanoff, Jason; Blagdon, Ryan; Feener, Stefanie; McNeil, Melanie; Muir, Paul H.

    2014-01-01

    The Simon effect refers to the performance (response time and accuracy) advantage for responses that spatially correspond to the task-irrelevant location of a stimulus. It has been attributed to a natural tendency to respond toward the source of stimulation. When location is task-relevant, however, and responses are intentionally directed away (incompatible) or toward (compatible) the source of the stimulation, there is also an advantage for spatially compatible responses over spatially incompatible responses. Interestingly, a number of studies have demonstrated a reversed, or reduced, Simon effect following practice with a spatial incompatibility task. One interpretation of this finding is that practicing a spatial incompatibility task disables the natural tendency to respond toward stimuli. Here, the temporal dynamics of this stimulus-response (S-R) transfer were explored with speed-accuracy trade-offs (SATs). All experiments used the mixed-task paradigm in which Simon and spatial compatibility/incompatibility tasks were interleaved across blocks of trials. In general, bidirectional S-R transfer was observed: while the spatial incompatibility task had an influence on the Simon effect, the task-relevant S-R mapping of the Simon task also had a small impact on congruency effects within the spatial compatibility and incompatibility tasks. These effects were generally greater when the task contexts were similar. Moreover, the SAT analysis of performance in the Simon task demonstrated that the tendency to respond to the location of the stimulus was not eliminated because of the spatial incompatibility task. Rather, S-R transfer from the spatial incompatibility task appeared to partially mask the natural tendency to respond to the source of stimulation with a conflicting inclination to respond away from it. These findings support the use of SAT methodology to quantitatively describe rapid response tendencies. PMID:25191217

  20. Method to Reduce Muscle Fatigue During Transcutaneous Neuromuscular Electrical Stimulation in Major Knee and Ankle Muscle Groups.

    PubMed

    Sayenko, Dimitry G; Nguyen, Robert; Hirabayashi, Tomoyo; Popovic, Milos R; Masani, Kei

    2015-09-01

    A critical limitation with transcutaneous neuromuscular electrical stimulation as a rehabilitative approach is the rapid onset of muscle fatigue during repeated contractions. We have developed a method called spatially distributed sequential stimulation (SDSS) to reduce muscle fatigue by distributing the center of electrical field over a wide area within a single stimulation site, using an array of surface electrodes. To extend the previous findings and to prove feasibility of the method by exploring the fatigue-reducing ability of SDSS for lower limb muscle groups in the able-bodied population, as well as in individuals with spinal cord injury (SCI). SDSS was delivered through 4 active electrodes applied to the knee extensors and flexors, plantarflexors, and dorsiflexors, sending a stimulation pulse to each electrode one after another with 90° phase shift between successive electrodes. Isometric ankle torque was measured during fatiguing stimulations using SDSS and conventional single active electrode stimulation lasting 2 minutes. We demonstrated greater fatigue-reducing ability of SDSS compared with the conventional protocol, as revealed by larger values of fatigue index and/or torque peak mean in all muscles except knee flexors of able-bodied individuals, and in all muscles tested in individuals with SCI. Our study has revealed improvements in fatigue tolerance during transcutaneous neuromuscular electrical stimulation using SDSS, a stimulation strategy that alternates activation of subcompartments of muscles. The SDSS protocol can provide greater stimulation times with less decrement in mechanical output compared with the conventional protocol. © The Author(s) 2014.

  1. [Cognitive plasticity in Alzheimer's disease patients receiving cognitive stimulation programs].

    PubMed

    Zamarrón Cassinello, Ma Dolores; Tárraga Mestre, Luis; Fernández-Ballesteros, Rocío

    2008-08-01

    The main purpose of this article is to examine whether cognitive plasticity increases after cognitive training in Alzheimer's disease patients. Twenty six patients participated in this study, all of them diagnosed with mild Alzheimer's disease, 17 of them received a cognitive training program during 6 months, and the other 9 were assigned to the control group. Participants were assigned to experimental or control conditions for clinical reasons. In order to assess cognitive plasticity, all patients were assessed before and after treatment with three subtests from the "Bateria de Evaluación de Potencial de Aprendizaje en Demencias" [Assessment Battery of Learning Potential in Dementia] (BEPAD). After treatment, Alzheimer's disease patients improved their performance in all the tasks assessing cognitive plasticity: viso-spatial memory, audio-verbal memory and verbal fluency. However, the cognitive plasticity scores of the patients in the control group decreased. In conclusion, this study showed that cognitive stimulation programs can improve cognitive functioning in mildly demented patients, and patients who do not receive any cognitive interventions may reduce their cognitive functioning.

  2. Frontoparietal regions may become hypoactive after intermittent theta burst stimulation over the contralateral homologous cortex in humans.

    PubMed

    He, Xiaofei; Lan, Yue; Xu, Guangqing; Mao, Yurong; Chen, Zhenghong; Huang, Dongfeng; Pei, Zhong

    2013-12-01

    Brain injury to the dorsal frontoparietal networks, including the posterior parietal cortex (PPC) and dorsolateral prefrontal cortex (DLPFC), commonly cause spatial neglect. However, the interaction of these different regions in spatial attention is unclear. The aim of the present study was to investigate whether hyperexcitable neural networks can cause an abnormal interhemispheric inhibition. The Attention Network Test was used to test subjects following intermittent theta burst stimulation (iTBS) to the left or right frontoparietal networks. During the Attention Network Test task, all subjects tolerated each conditioning iTBS without any obvious iTBS-related side effects. Subjects receiving real-right-PPC iTBS showed significant enhancement in both alerting and orienting efficiency compared with those receiving either sham-right-PPC iTBS or real-left-PPC iTBS. Moreover, subjects exposed to the real-right-DLPFC iTBS exhibited significant improvement in both alerting and executive control efficiency, compared with those exposed to either the sham-right-DLPFC or real-left-DLPFC conditioning. Interestingly, compared with subjects exposed to the sham-left-PPC stimuli, subjects exposed to the real-left-PPC iTBS had a significant deficit in the orienting index. The present study indicates that iTBS over the contralateral homologous cortex may induce the hypoactivity of the right PPC through interhemispheric competition in spatial orienting attention.

  3. Structural plasticity in hippocampal cells related to the facilitative effect of intracranial self-stimulation on a spatial memory task.

    PubMed

    Chamorro-López, Jacobo; Miguéns, Miguel; Morgado-Bernal, Ignacio; Kastanauskaite, Asta; Selvas, Abraham; Cabané-Cucurella, Alberto; Aldavert-Vera, Laura; DeFelipe, Javier; Segura-Torres, Pilar

    2015-12-01

    Posttraining intracranial self-stimulation (SS) in the lateral hypothalamus facilitates the acquisition and retention of several implicit and explicit memory tasks. Here, intracellular injections of Lucifer yellow were used to assess morphological changes in hippocampal neurons that might be specifically related to the facilitative posttraining SS effect upon the acquisition and retention of a distributed spatial task in the Morris water maze. We examined the structure, size and branching complexity of cornus ammonis 1 (CA1) cells, and the spine density of CA1 pyramidal neurons and granular cells of the dentate gyrus (DG). Animals that received SS after each acquisition session performed faster and better than Sham ones--an improvement that was also evident in a probe trial 3 days after the last training session. The neuromorphological analysis revealed an increment in the size and branching complexity in apical CA1 dendritic arborization in SS-treated subjects as compared with Sham animals. Furthermore, increased spine density was observed in the CA1 field in SS animals, whereas no effects were observed in DG cells. Our results support the hypothesis that the facilitating effect of SS on the acquisition and retention of a spatial memory task could be related to structural plasticity in CA1 hippocampal cells. (c) 2015 APA, all rights reserved).

  4. Laser intensity scaling through stimulated scattering in optical fibers

    NASA Astrophysics Data System (ADS)

    Russell, Timothy H.

    The influence of stimulated scattering on laser intensity in fiber optic waveguides is examined. Stimulated Brillouin scattering (SBS) in long, multimode optical waveguides is found to generate a Stokes beam that propagates in the fiber LP01 mode. This characteristic of the Stokes beam was first applied to beam cleanup, where an aberrated pump generated a Gaussian-like Stokes beam. Additionally, the same process is found to combine multiple laser beams into a single spatially coherent source. The mean square difference between the two beams was used to measure the degree of spatial overlap, demonstrating spatial coherence between the Stokes beams even when the pump beams are not spatially correlated. This result is obtained regardless of whether the pump beams are at the same or different frequencies; producing two temporally coherent or incoherent Stokes beams respectively. Limitations in beam cleanup and combining are also examined to identify ways to overcome them. Output couplers are designed that could be used to spatially filter the Stokes beam from the pump, thus increasing the number of beams that could be combined. The combined power restriction induced by second order Stokes threshold is examined experimentally and theoretically and is not found to be a significant limitation. Finally, stimulated Raman scattering (SRS) beam cleanup is examined to overcome the stringent spectral requirements on the pump beams required by SBS. The last portion of the dissertation theoretically examines suppression of stimulated Raman scattering in fibers to eliminate the restriction this imposes on the power of a fiber laser or amplifier. The suppression was modeled using both a holmium dopant and adding a long period grating to the fiber. Both methods were shown to have a significant effect on the SRS threshold.

  5. How do stimulant treatments for ADHD work? Evidence for mediation by improved cognition.

    PubMed

    Hawk, Larry W; Fosco, Whitney D; Colder, Craig R; Waxmonsky, James G; Pelham, William E; Rosch, Keri S

    2018-05-07

    Stimulant medications such as methylphenidate (MPH) are the frontline treatment for Attention-Deficit/Hyperactivity Disorder (ADHD). Despite their well-documented efficacy, the mechanisms by which stimulants improve clinical outcomes are not clear. The current study evaluated whether MPH effects on classroom behavior were mediated by improved cognitive functioning. Children with ADHD (n = 82; 9-12 years old) participated in a week-long summer research camp, consisting of cognitive testing, classroom periods, and recreational activities. After a baseline day, participants completed a 3-day randomized, double-blind, placebo-controlled trial of MPH (at doses approximating 0.3 and 0.6 mg/kg of immediate-release MPH dosed TID). Cognitive domains included inhibitory control (Stop Signal Task and prepulse inhibition of startle), attention (Continuous Performance Task and reaction time variability), and working memory (forward and backward spatial span). Clinical outcomes included math seatwork productivity and teacher-rated classroom behavior. A within-subjects path-analytic approach was used to test mediation. MPH-placebo and dose-response contrasts were used to evaluate drug effects. Methylphenidate improved seatwork productivity and teacher ratings (ds = 1.4 and 1.1) and all domains of cognition (ds = 0.3-1.1). Inhibitory control (Stop Signal Task, SST) and working memory backward uniquely mediated the effect of MPH (vs. placebo) on productivity. Only working memory backward mediated the impact of MPH on teacher-rated behavior. The dose-response (0.6 vs. 0.3 mg/kg) effects were more modest for clinical outcomes (ds = 0.4 and 0.2) and cognition (ds = 0-0.3); there was no evidence of cognitive mediation of the clinical dose-response effects. These findings are novel in demonstrating that specific cognitive processes mediate clinical improvement with stimulant treatment for ADHD. They converge with work on ADHD theory, neurobiology, and treatment development in suggesting that inhibitory control and working memory may be mechanisms of stimulant treatment response in ADHD. More work is necessary to evaluate the degree to which these findings generalize to chronic treatment, a broader array of clinical outcomes, and nonstimulant treatments. © 2018 Association for Child and Adolescent Mental Health.

  6. Computational modeling of pedunculopontine nucleus deep brain stimulation

    NASA Astrophysics Data System (ADS)

    Zitella, Laura M.; Mohsenian, Kevin; Pahwa, Mrinal; Gloeckner, Cory; Johnson, Matthew D.

    2013-08-01

    Objective. Deep brain stimulation (DBS) near the pedunculopontine nucleus (PPN) has been posited to improve medication-intractable gait and balance problems in patients with Parkinson's disease. However, clinical studies evaluating this DBS target have not demonstrated consistent therapeutic effects, with several studies reporting the emergence of paresthesia and oculomotor side effects. The spatial and pathway-specific extent to which brainstem regions are modulated during PPN-DBS is not well understood. Approach. Here, we describe two computational models that estimate the direct effects of DBS in the PPN region for human and translational non-human primate (NHP) studies. The three-dimensional models were constructed from segmented histological images from each species, multi-compartment neuron models and inhomogeneous finite element models of the voltage distribution in the brainstem during DBS. Main Results. The computational models predicted that: (1) the majority of PPN neurons are activated with -3 V monopolar cathodic stimulation; (2) surgical targeting errors of as little as 1 mm in both species decrement activation selectivity; (3) specifically, monopolar stimulation in caudal, medial, or anterior PPN activates a significant proportion of the superior cerebellar peduncle (up to 60% in the human model and 90% in the NHP model at -3 V) (4) monopolar stimulation in rostral, lateral or anterior PPN activates a large percentage of medial lemniscus fibers (up to 33% in the human model and 40% in the NHP model at -3 V) and (5) the current clinical cylindrical electrode design is suboptimal for isolating the modulatory effects to PPN neurons. Significance. We show that a DBS lead design with radially-segmented electrodes may yield improved functional outcome for PPN-DBS.

  7. Cortical responses following simultaneous and sequential retinal neurostimulation with different return configurations.

    PubMed

    Barriga-Rivera, Alejandro; Morley, John W; Lovell, Nigel H; Suaning, Gregg J

    2016-08-01

    Researchers continue to develop visual prostheses towards safer and more efficacious systems. However limitations still exist in the number of stimulating channels that can be integrated. Therefore there is a need for spatial and time multiplexing techniques to provide improved performance of the current technology. In particular, bright and high-contrast visual scenes may require simultaneous activation of several electrodes. In this research, a 24-electrode array was suprachoroidally implanted in three normally-sighted cats. Multi-unit activity was recorded from the primary visual cortex. Four stimulation strategies were contrasted to provide activation of seven electrodes arranged hexagonally: simultaneous monopolar, sequential monopolar, sequential bipolar and hexapolar. Both monopolar configurations showed similar cortical activation maps. Hexapolar and sequential bipolar configurations activated a lower number of cortical channels. Overall, the return configuration played a more relevant role in cortical activation than time multiplexing and thus, rapid sequential stimulation may assist in reducing the number of channels required to activate large retinal areas.

  8. Porous media of the Red River Formation, Williston Basin, North Dakota: a possible Sedimentary Enhanced Geothermal System

    NASA Astrophysics Data System (ADS)

    Hartig, Caitlin M.

    2018-01-01

    Fracture-stimulated enhanced geothermal systems (EGS) can be developed in both crystalline rocks and sedimentary basins. The Red River Formation (Ordovician) is a viable site for development of a sedimentary EGS (SEGS) because the formation temperatures exceed 140 °C and the permeability is 0.1-38 mD; fracture stimulation can be utilized to improve permeability. The spatial variations of the properties of the Red River Formation were analyzed across the study area in order to understand the distribution of subsurface formation temperatures. Maps of the properties of the Red River Formation-including depth to the top of the formation, depth to the bottom of the formation, porosity, geothermal gradient, heat flow, and temperature-were produced by the Kriging interpolation method in ArcGIS. In the future, these results may be utilized to create a reservoir simulation model of an SEGS in the Red River Formation; the purpose of this model would be to ascertain the thermal response of the reservoir to fracture stimulation.

  9. Comprehensive Survey on Improved Focality and Penetration Depth of Transcranial Magnetic Stimulation Employing Multi-Coil Arrays.

    PubMed

    Wei, Xile; Li, Yao; Lu, Meili; Wang, Jiang; Yi, Guosheng

    2017-11-14

    Multi-coil arrays applied in transcranial magnetic stimulation (TMS) are proposed to accurately stimulate brain tissues and modulate neural activities by an induced electric field (EF). Composed of numerous independently driven coils, a multi-coil array has alternative energizing strategies to evoke EFs targeting at different cerebral regions. To improve the locating resolution and the stimulating focality, we need to fully understand the variation properties of induced EFs and the quantitative control method of the spatial arrangement of activating coils, both of which unfortunately are still unclear. In this paper, a comprehensive analysis of EF properties was performed based on multi-coil arrays. Four types of planar multi-coil arrays were used to study the relationship between the spatial distribution of EFs and the structure of stimuli coils. By changing coil-driven strategies in a basic 16-coil array, we find that an EF induced by compactly distributed coils decays faster than that induced by dispersedly distributed coils, but the former has an advantage over the latter in terms of the activated brain volume. Simulation results also indicate that the attenuation rate of an EF induced by the 36-coil dense array is 3 times and 1.5 times greater than those induced by the 9-coil array and the 16-coil array, respectively. The EF evoked by the 36-coil dispense array has the slowest decay rate. This result demonstrates that larger multi-coil arrays, compared to smaller ones, activate deeper brain tissues at the expense of decreased focality. A further study on activating a specific field of a prescribed shape and size was conducted based on EF variation. Accurate target location was achieved with a 64-coil array 18 mm in diameter. A comparison between the figure-8 coil, the planar array, and the cap-formed array was made and demonstrates an improvement of multi-coil configurations in the penetration depth and the focality. These findings suggest that there is a tradeoff between attenuation rate and focality in the application of multi-coil arrays. Coil-energizing strategies and array dimensions should be based on an adequate evaluation of these two important demands and the topological structure of target tissues.

  10. Analytical theory for extracellular electrical stimulation of nerve with focal electrodes. I. Passive unmyelinated axon.

    PubMed Central

    Rubinstein, J T; Spelman, F A

    1988-01-01

    The cable model of a passive, unmyelinated fiber in an applied extracellular field is derived. The solution is valid for an arbitrary, time-varying, applied field, which may be determined analytically or numerically. Simple analytical computations are presented. They explain a variety of known phenomena and predict some previously undescribed properties of extracellular electrical stimulation. The polarization of a fiber in an applied field behaves like the output of a spatial high-pass and temporal low-pass filter of the stimulus. High-frequency stimulation results in a more spatially restricted region of fiber excitation, effectively reducing current spread relative to that produced by low-frequency stimulation. Chronaxie measured extracellularly is a function of electrode position relative to the stimulated fiber, and its value may differ substantially from that obtained intracellularly. Frequency dependence of psychophysical threshold obtained by electrical stimulation of the macaque cochlea closely follows the frequency dependence of single-fiber passive response. PMID:3233274

  11. Recording and assessment of evoked potentials with electrode arrays.

    PubMed

    Miljković, N; Malešević, N; Kojić, V; Bijelić, G; Keller, T; Popović, D B

    2015-09-01

    In order to optimize procedure for the assessment of evoked potentials and to provide visualization of the flow of action potentials along the motor systems, we introduced array electrodes for stimulation and recording and developed software for the analysis of the recordings. The system uses a stimulator connected to an electrode array for the generation of evoked potentials, an electrode array connected to the amplifier, A/D converter and computer for the recording of evoked potentials, and a dedicated software application. The method has been tested for the assessment of the H-reflex on the triceps surae muscle in six healthy humans. The electrode array with 16 pads was positioned over the posterior aspect of the thigh, while the recording electrode array with 16 pads was positioned over the triceps surae muscle. The stimulator activated all the pads of the stimulation electrode array asynchronously, while the signals were recorded continuously at all the recording sites. The results are topography maps (spatial distribution of evoked potentials) and matrices (spatial visualization of nerve excitability). The software allows the automatic selection of the lowest stimulation intensity to achieve maximal H-reflex amplitude and selection of the recording/stimulation pads according to predefined criteria. The analysis of results shows that the method provides rich information compared with the conventional recording of the H-reflex with regard the spatial distribution.

  12. Prenatal Loud Music and Noise: Differential Impact on Physiological Arousal, Hippocampal Synaptogenesis and Spatial Behavior in One Day-Old Chicks

    PubMed Central

    Sanyal, Tania; Kumar, Vivek; Nag, Tapas Chandra; Jain, Suman; Sreenivas, Vishnu; Wadhwa, Shashi

    2013-01-01

    Prenatal auditory stimulation in chicks with species-specific sound and music at 65 dB facilitates spatial orientation and learning and is associated with significant morphological and biochemical changes in the hippocampus and brainstem auditory nuclei. Increased noradrenaline level due to physiological arousal is suggested as a possible mediator for the observed beneficial effects following patterned and rhythmic sound exposure. However, studies regarding the effects of prenatal high decibel sound (110 dB; music and noise) exposure on the plasma noradrenaline level, synaptic protein expression in the hippocampus and spatial behavior of neonatal chicks remained unexplored. Here, we report that high decibel music stimulation moderately increases plasma noradrenaline level and positively modulates spatial orientation, learning and memory of one day-old chicks. In contrast, noise at the same sound pressure level results in excessive increase of plasma noradrenaline level and impairs the spatial behavior. Further, to assess the changes at the molecular level, we have quantified the expression of functional synapse markers: synaptophysin and PSD-95 in the hippocampus. Compared to the controls, both proteins show significantly increased expressions in the music stimulated group but decrease in expressions in the noise group. We propose that the differential increase of plasma noradrenaline level and altered expression of synaptic proteins in the hippocampus are responsible for the observed behavioral consequences following prenatal 110 dB music and noise stimulation. PMID:23861759

  13. Closed-Loop Targeted Memory Reactivation during Sleep Improves Spatial Navigation.

    PubMed

    Shimizu, Renee E; Connolly, Patrick M; Cellini, Nicola; Armstrong, Diana M; Hernandez, Lexus T; Estrada, Rolando; Aguilar, Mario; Weisend, Michael P; Mednick, Sara C; Simons, Stephen B

    2018-01-01

    Sounds associated with newly learned information that are replayed during non-rapid eye movement (NREM) sleep can improve recall in simple tasks. The mechanism for this improvement is presumed to be reactivation of the newly learned memory during sleep when consolidation takes place. We have developed an EEG-based closed-loop system to precisely deliver sensory stimulation at the time of down-state to up-state transitions during NREM sleep. Here, we demonstrate that applying this technology to participants performing a realistic navigation task in virtual reality results in a significant improvement in navigation efficiency after sleep that is accompanied by increases in the spectral power especially in the fast (12-15 Hz) sleep spindle band. Our results show promise for the application of sleep-based interventions to drive improvement in real-world tasks.

  14. Spatiotemporal Pixelization to Increase the Recognition Score of Characters for Retinal Prostheses

    PubMed Central

    Kim, Hyun Seok; Park, Kwang Suk

    2017-01-01

    Most of the retinal prostheses use a head-fixed camera and a video processing unit. Some studies proposed various image processing methods to improve visual perception for patients. However, previous studies only focused on using spatial information. The present study proposes a spatiotemporal pixelization method mimicking fixational eye movements to generate stimulation images for artificial retina arrays by combining spatial and temporal information. Input images were sampled with a resolution that was four times higher than the number of pixel arrays. We subsampled this image and generated four different phosphene images. We then evaluated the recognition scores of characters by sequentially presenting phosphene images with varying pixel array sizes (6 × 6, 8 × 8 and 10 × 10) and stimulus frame rates (10 Hz, 15 Hz, 20 Hz, 30 Hz, and 60 Hz). The proposed method showed the highest recognition score at a stimulus frame rate of approximately 20 Hz. The method also significantly improved the recognition score for complex characters. This method provides a new way to increase practical resolution over restricted spatial resolution by merging the higher resolution image into high-frame time slots. PMID:29073735

  15. A Portable Ultrasound System for Non-Invasive Ultrasonic Neuro-Stimulation.

    PubMed

    Qiu, Weibao; Zhou, Juan; Chen, Yan; Su, Min; Li, Guofeng; Zhao, Huixia; Gu, Xianyi; Meng, De; Wang, Congzhi; Xiao, Yang; Lam, Kwok Ho; Dai, Jiyan; Zheng, Hairong

    2017-12-01

    Fundamental insights into the function of the neural circuits often follows from the advances in methodologies and tools for neuroscience. Electrode- and optical- based stimulation methods have been used widely for neuro-modulation with high resolution. However, they are suffering from inherent invasive surgical procedure. Ultrasound has been proved as a promising technology for neuro-stimulation in a non-invasive manner. However, no portable ultrasound system has been developed particularly for neuro-stimulation. The utilities used currently are assembled by traditional functional generator, power amplifier, and general transducer, therefore, resulting in lack of flexibility. This paper presents a portable system to achieve ultrasonic neuro-stimulation to satisfy various studies. The system incorporated a high voltage waveform generator and a matching circuit that were optimized for neuro-stimulation. A new switching mode power amplifier was designed and fabricated. The noise generated by the power amplifier was reduced (about 30 dB), and the size and weight were smaller in contrast with commercial equipment. In addition, a miniaturized ultrasound transducer was fabricated using Pb(Mg 1/3 Nb 2/3 )O 3 -PbTiO 3 (PMN-PT) 1-3 composite single crystal for the improved ultrasonic performance. The spatial peak temporal average pressure was higher than 250 kPa in the range of 0.5-5 MHz. In vitro and in vivo studies were conducted to show the performance of the system.

  16. Binaural release from masking with single- and multi-electrode stimulation in children with cochlear implantsa)

    PubMed Central

    Todd, Ann E.; Goupell, Matthew J.; Litovsky, Ruth Y.

    2016-01-01

    Cochlear implants (CIs) provide children with access to speech information from a young age. Despite bilateral cochlear implantation becoming common, use of spatial cues in free field is smaller than in normal-hearing children. Clinically fit CIs are not synchronized across the ears; thus binaural experiments must utilize research processors that can control binaural cues with precision. Research to date has used single pairs of electrodes, which is insufficient for representing speech. Little is known about how children with bilateral CIs process binaural information with multi-electrode stimulation. Toward the goal of improving binaural unmasking of speech, this study evaluated binaural unmasking with multi- and single-electrode stimulation. Results showed that performance with multi-electrode stimulation was similar to the best performance with single-electrode stimulation. This was similar to the pattern of performance shown by normal-hearing adults when presented an acoustic CI simulation. Diotic and dichotic signal detection thresholds of the children with CIs were similar to those of normal-hearing children listening to a CI simulation. The magnitude of binaural unmasking was not related to whether the children with CIs had good interaural time difference sensitivity. Results support the potential for benefits from binaural hearing and speech unmasking in children with bilateral CIs. PMID:27475132

  17. Binaural release from masking with single- and multi-electrode stimulation in children with cochlear implants.

    PubMed

    Todd, Ann E; Goupell, Matthew J; Litovsky, Ruth Y

    2016-07-01

    Cochlear implants (CIs) provide children with access to speech information from a young age. Despite bilateral cochlear implantation becoming common, use of spatial cues in free field is smaller than in normal-hearing children. Clinically fit CIs are not synchronized across the ears; thus binaural experiments must utilize research processors that can control binaural cues with precision. Research to date has used single pairs of electrodes, which is insufficient for representing speech. Little is known about how children with bilateral CIs process binaural information with multi-electrode stimulation. Toward the goal of improving binaural unmasking of speech, this study evaluated binaural unmasking with multi- and single-electrode stimulation. Results showed that performance with multi-electrode stimulation was similar to the best performance with single-electrode stimulation. This was similar to the pattern of performance shown by normal-hearing adults when presented an acoustic CI simulation. Diotic and dichotic signal detection thresholds of the children with CIs were similar to those of normal-hearing children listening to a CI simulation. The magnitude of binaural unmasking was not related to whether the children with CIs had good interaural time difference sensitivity. Results support the potential for benefits from binaural hearing and speech unmasking in children with bilateral CIs.

  18. Nanostructured cavity devices for extracellular stimulation of HL-1 cells.

    PubMed

    Czeschik, Anna; Rinklin, Philipp; Derra, Ulrike; Ullmann, Sabrina; Holik, Peter; Steltenkamp, Siegfried; Offenhäusser, Andreas; Wolfrum, Bernhard

    2015-01-01

    Microelectrode arrays (MEAs) are state-of-the-art devices for extracellular recording and stimulation on biological tissue. Furthermore, they are a relevant tool for the development of biomedical applications like retina, cochlear and motor prostheses, cardiac pacemakers and drug screening. Hence, research on functional cell-sensor interfaces, as well as the development of new surface structures and modifications for improved electrode characteristics, is a vivid and well established field. However, combining single-cell resolution with sufficient signal coupling remains challenging due to poor cell-electrode sealing. Furthermore, electrodes with diameters below 20 µm often suffer from a high electrical impedance affecting the noise during voltage recordings. In this study, we report on a nanocavity sensor array for voltage-controlled stimulation and extracellular action potential recordings on cellular networks. Nanocavity devices combine the advantages of low-impedance electrodes with small cell-chip interfaces, preserving a high spatial resolution for recording and stimulation. A reservoir between opening aperture and electrode is provided, allowing the cell to access the structure for a tight cell-sensor sealing. We present the well-controlled fabrication process and the effect of cavity formation and electrode patterning on the sensor's impedance. Further, we demonstrate reliable voltage-controlled stimulation using nanostructured cavity devices by capturing the pacemaker of an HL-1 cell network.

  19. Differential spatial activity patterns of acupuncture by a machine learning based analysis

    NASA Astrophysics Data System (ADS)

    You, Youbo; Bai, Lijun; Xue, Ting; Zhong, Chongguang; Liu, Zhenyu; Tian, Jie

    2011-03-01

    Acupoint specificity, lying at the core of the Traditional Chinese Medicine, underlies the theoretical basis of acupuncture application. However, recent studies have reported that acupuncture stimulation at nonacupoint and acupoint can both evoke similar signal intensity decreases in multiple regions. And these regions were spatially overlapped. We used a machine learning based Support Vector Machine (SVM) approach to elucidate the specific neural response pattern induced by acupuncture stimulation. Group analysis demonstrated that stimulation at two different acupoints (belong to the same nerve segment but different meridians) could elicit distinct neural response patterns. Our findings may provide evidence for acupoint specificity.

  20. Anodal tDCS applied during multitasking training leads to transferable performance gains.

    PubMed

    Filmer, Hannah L; Lyons, Maxwell; Mattingley, Jason B; Dux, Paul E

    2017-10-11

    Cognitive training can lead to performance improvements that are specific to the tasks trained. Recent research has suggested that transcranial direct current stimulation (tDCS) applied during training of a simple response-selection paradigm can broaden performance benefits to an untrained task. Here we assessed the impact of combined tDCS and training on multitasking, stimulus-response mapping specificity, response-inhibition, and spatial attention performance in a cohort of healthy adults. Participants trained over four days with concurrent tDCS - anodal, cathodal, or sham - applied to the left prefrontal cortex. Immediately prior to, 1 day after, and 2 weeks after training, performance was assessed on the trained multitasking paradigm, an untrained multitasking paradigm, a go/no-go inhibition task, and a visual search task. Training combined with anodal tDCS, compared with training plus cathodal or sham stimulation, enhanced performance for the untrained multitasking paradigm and visual search tasks. By contrast, there were no training benefits for the go/no-go task. Our findings demonstrate that anodal tDCS combined with multitasking training can extend to untrained multitasking paradigms as well as spatial attention, but with no extension to the domain of response inhibition.

  1. Revisiting synaptic vesicle pool localization in the Drosophila neuromuscular junction

    PubMed Central

    Denker, Annette; Kröhnert, Katharina; Rizzoli, Silvio O

    2009-01-01

    The synaptic vesicles are organized in distinct populations or ‘pools’: the readily releasable pool (the first vesicles released upon stimulation), the recycling pool (which maintains release under moderate stimulation) and the reserve pool (which is called into action only upon strong, often unphysiological stimulation). A major question in the field is whether the pools consist of biochemically different vesicles or whether the pool tag is a spatial one (with the recycling vesicles found next to the release sites, and the reserve ones farther away). A strong and stable spatial segregation has been proposed in the last decade in the Drosophila larval neuromuscular junction – albeit based solely on light microscopy experiments. We have tested here this hypothesis using electron microscopy (EM) photoconversion. We found the recycling and reserve pools to be thoroughly intermixed at the EM level, indicating that spatial location is irrelevant for the functional properties of the vesicle. PMID:19403600

  2. Impact of grain boundaries on efficiency and stability of organic-inorganic trihalide perovskites

    DOE PAGES

    Chu, Zhaodong; Yang, Mengjin; Schulz, Philip; ...

    2017-12-20

    Organic-inorganic perovskite solar cells have attracted tremendous attention because of their remarkably high power conversion efficiencies. To further improve device performance, it is imperative to obtain fundamental understandings on the photo-response and long-term stability down to the microscopic level. Here, we report the quantitative nanoscale photoconductivity imaging on two methylammonium lead triiodide thin films with different efficiencies by light-stimulated microwave impedance microscopy. The microwave signals are largely uniform across grains and grain boundaries, suggesting that microstructures do not lead to strong spatial variations of the intrinsic photo-response. In contrast, the measured photoconductivity and lifetime are strongly affected by bulk propertiesmore » such as the sample crystallinity. As visualized by the spatial evolution of local photoconductivity, the degradation process begins with the disintegration of grains rather than nucleation and propagation from visible boundaries between grains. In conclusion, our findings provide insights to improve the electro-optical properties of perovskite thin films towards large-scale commercialization.« less

  3. Optimization of return electrodes in neurostimulating arrays

    NASA Astrophysics Data System (ADS)

    Flores, Thomas; Goetz, Georges; Lei, Xin; Palanker, Daniel

    2016-06-01

    Objective. High resolution visual prostheses require dense stimulating arrays with localized inputs of individual electrodes. We study the electric field produced by multielectrode arrays in electrolyte to determine an optimal configuration of return electrodes and activation sequence. Approach. To determine the boundary conditions for computation of the electric field in electrolyte, we assessed current dynamics using an equivalent circuit of a multielectrode array with interleaved return electrodes. The electric field modeled with two different boundary conditions derived from the equivalent circuit was then compared to measurements of electric potential in electrolyte. To assess the effect of return electrode configuration on retinal stimulation, we transformed the computed electric fields into retinal response using a model of neural network-mediated stimulation. Main results. Electric currents at the capacitive electrode-electrolyte interface redistribute over time, so that boundary conditions transition from equipotential surfaces at the beginning of the pulse to uniform current density in steady state. Experimental measurements confirmed that, in steady state, the boundary condition corresponds to a uniform current density on electrode surfaces. Arrays with local return electrodes exhibit improved field confinement and can elicit stronger network-mediated retinal response compared to those with a common remote return. Connecting local return electrodes enhances the field penetration depth and allows reducing the return electrode area. Sequential activation of the pixels in large monopolar arrays reduces electrical cross-talk and improves the contrast in pattern stimulation. Significance. Accurate modeling of multielectrode arrays helps optimize the electrode configuration to maximize the spatial resolution, contrast and dynamic range of retinal prostheses.

  4. Suitability of the Binaural Interaction Component for Interaural Electrode Pairing of Bilateral Cochlear Implants.

    PubMed

    Hu, Hongmei; Kollmeier, Birger; Dietz, Mathias

    2016-01-01

    Although bilateral cochlear implants (BiCIs) have succeeded in improving the spatial hearing performance of bilateral CI users, the overall performance is still not comparable with normal hearing listeners. Limited success can be partially caused by an interaural mismatch of the place-of-stimulation in each cochlea. Pairing matched interaural CI electrodes and stimulating them with the same frequency band is expected to facilitate binaural functions such as binaural fusion, localization, or spatial release from masking. It has been shown in animal experiments that the magnitude of the binaural interaction component (BIC) derived from the wave-eV decreases for increasing interaural place of stimulation mismatch. This motivated the investigation of the suitability of an electroencephalography-based objective electrode-frequency fitting procedure based on the BIC for BiCI users. A 61 channel monaural and binaural electrically evoked auditory brainstem response (eABR) recording was performed in 7 MED-EL BiCI subjects so far. These BiCI subjects were directly stimulated at 60% dynamic range with 19.9 pulses per second via a research platform provided by the University of Innsbruck (RIB II). The BIC was derived for several interaural electrode pairs by subtracting the response from binaural stimulation from their summed monaural responses. The BIC based pairing results are compared with two psychoacoustic pairing methods: interaural pulse time difference sensitivity and interaural pitch matching. The results for all three methods analyzed as a function of probe electrode allow for determining a matched pair in more than half of the subjects, with a typical accuracy of ± 1 electrode. This includes evidence for statistically significant tuning of the BIC as a function of probe electrode in human subjects. However, results across the three conditions were sometimes not consistent. These discrepancies will be discussed in the light of pitch plasticity versus less plastic brainstem processing.

  5. Captured by the pain: pain steady-state evoked potentials are not modulated by selective spatial attention.

    PubMed

    Blöchl, Maria; Franz, Marcel; Miltner, Wolfgang H R; Weiss, Thomas

    2015-04-07

    Attention has been shown to affect the neural processing of pain. However, the exact mechanisms underlying this modulation remain unknown. Here, we used a new method called pain steady-state evoked potentials (PSSEPs) to investigate whether selective spatial attention affects EEG responses to tonic painful stimuli. In general, steady-state evoked potentials reflect changes in the EEG spectrum at a certain frequency that correspond to the frequency of a train of applied stimuli. In this study, high intensity transcutaneous electrical stimulation was delivered to both hands simultaneously with 31 Hz and 37 Hz, respectively. Subject׳s attention was directed to one of the two trains of stimulation in order to detect a small gap that was occasionally interspersed into the stimulus trains. Thereby, they had to ignore the stimulation applied to the other hand. Results show that PSSEPs were induced at 31 Hz and 37 Hz at frontal and central electrodes. PSSEPs occurred contralaterally to the respective hand stimulated with that frequency. Surprisingly, the magnitude of PSSEPs was not modulated by spatial attention towards one of the two stimuli. Our results indicate that attention can hardly be shifted between two simultaneously applied tonic painful stimulations. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Holographically generated structured illumination for cell stimulation in optogenetics

    NASA Astrophysics Data System (ADS)

    Schmieder, Felix; Büttner, Lars; Czarske, Jürgen; Torres, Maria Leilani; Heisterkamp, Alexander; Klapper, Simon; Busskamp, Volker

    2017-06-01

    In Optogenetics, cells, e.g. neurons or cardiac cells, are genetically altered to produce for example the lightsensitive protein Channelrhodopsin-2. Illuminating these cells induces action potentials or contractions and therefore allows to control electrical activity. Thus, light-induced cell stimulation can be used to gain insight to various biological processes. Many optogenetics studies, however, use only full field illumination and thus gain no local information about their specimen. But using modern spatial light modulators (SLM) in conjunction with computer-generated holograms (CGH), cells may be stimulated locally, thus enabling the research of the foundations of cell networks and cell communications. In our contribution, we present a digital holographic system for the patterned, spatially resolved stimulation of cell networks. We employ a fast ferroelectric liquid crystal on silicon SLM to display CGH at up to 1.7 kHz. With an effective working distance of 33 mm, we achieve a focus of 10 μm at a positioning accuracy of the individual foci of about 8 μm. We utilized our setup for the optogenetic stimulation of clusters of cardiac cells derived from induced pluripotent stem cells and were able to observe contractions correlated to both temporal frequency and spatial power distribution of the light incident on the cell clusters.

  7. Enhancing Working Memory Training with Transcranial Direct Current Stimulation.

    PubMed

    Au, Jacky; Katz, Benjamin; Buschkuehl, Martin; Bunarjo, Kimberly; Senger, Thea; Zabel, Chelsea; Jaeggi, Susanne M; Jonides, John

    2016-09-01

    Working memory (WM) is a fundamental cognitive ability that supports complex thought but is limited in capacity. Thus, WM training interventions have become very popular as a means of potentially improving WM-related skills. Another promising intervention that has gained increasing traction in recent years is transcranial direct current stimulation (tDCS), a noninvasive form of brain stimulation that can modulate cortical excitability and temporarily increase brain plasticity. As such, it has the potential to boost learning and enhance performance on cognitive tasks. This study assessed the efficacy of tDCS to supplement WM training. Sixty-two participants were randomized to receive either right prefrontal, left prefrontal, or sham stimulation with concurrent visuospatial WM training over the course of seven training sessions. Results showed that tDCS enhanced training performance, which was strikingly preserved several months after training completion. Furthermore, we observed stronger effects when tDCS was spaced over a weekend break relative to consecutive daily training, and we also demonstrated selective transfer in the right prefrontal group to nontrained tasks of visual and spatial WM. These findings shed light on how tDCS may be leveraged as a tool to enhance performance on WM-intensive learning tasks.

  8. Brain stimulation, mathematical, and numerical training: Contribution of core and noncore skills.

    PubMed

    Looi, C Y; Cohen Kadosh, R

    2016-01-01

    Mathematical abilities that are correlated with various life outcomes vary across individuals. One approach to improve mathematical abilities is by understanding the underlying cognitive functions. Theoretical and experimental evidence suggest that mathematical abilities are subserved by "core" and "noncore" skills. Core skills are commonly regarded as the "innate" capacity to attend to and process numerical information, while noncore skills are those that are important for mathematical cognition, but are not exclusive to the mathematical domain such as executive functions, spatial skills, and attention. In recent years, mathematical training has been combined with the application of noninvasive brain stimulation to further enhance training outcomes. However, the development of more strategic training paradigms is hindered by the lack of understanding on the contributory nature of core and noncore skills and their neural underpinnings. In the current review, we will examine the effects of brain stimulation with focus on transcranial electrical stimulation on core and noncore skills, and its impact on mathematical and numerical training. We will conclude with a discussion on the theoretical and experimental implications of these studies and directions for further research. © 2016 Elsevier B.V. All rights reserved.

  9. Desalted deep-sea water improves cognitive function in mice by increasing the production of insulin-like growth factor-I in the hippocampus.

    PubMed

    Harada, Naoaki; Zhao, Juan; Kurihara, Hiroki; Nakagata, Naomi; Okajima, Kenji

    2011-08-01

    The stimulation of sensory neurons in the gastrointestinal (GI) tract improves cognitive function by increasing the hippocampal production of insulin-like growth factor-I (IGF-I) in mice. In the current study, we examined whether oral administration of desalted deep-sea water (DSW) increases the hippocampal production of IGF-I by stimulating sensory neurons in the GI tract, thereby improving cognitive function in mice. Desalted DSW increased calcitonin gene-related peptide (CGRP) release from dorsal root ganglion (DRG) neurons isolated from wild-type (WT) mice by activating transient receptor potential vanilloid 1. The plasma levels of IGF-I and tissue levels of CGRP, IGF-I, and IGF-I mRNA in the hippocampus were increased by oral administration of desalted DSW in WT mice. In these animals, nociceptive information originating from the GI tract was transmitted to the hippocampus via the spinothalamic pathway. Improvement of spatial learning was observed in WT mice after administration of desalted DSW. Distilled DSW showed results similar to those of desalted DSW in vitro and in vivo. None of the effects of desalted DSW in WT mice were observed after the administration of desalted DSW in CGRP-knockout (CGRP-/-) mice. No volatile compounds were detected in distilled DSW on GC-MS analysis. These observations suggest that desalted DSW may increase the hippocampal IGF-I production via sensory neuron stimulation in the Gl tract, thereby improving cognitive function in mice. Such effects of desalted DSW might not be dependent on the minerals but are dependent on the function of the water molecule itself. Copyright © 2011 Mosby, Inc. All rights reserved.

  10. [Effects of the neurogenesis stimulator Ro 25-6981 upon formation of spatial skill in adult rats depend on the term of its administration and the animals' ability to learn].

    PubMed

    Solov'eva, O A; Storozheva, Z I; Proshin, A T; Sherstnev, V V

    2011-02-01

    Effect of administration of selective N-methyl-D-aspartate (NMDA) receptor antagonist Ro 25-6981 on learning and memory in a dose which is known to stimulate neoneurogenesis was assessed in adult rats with different abilities to formation of spatial skills in different time periods after the antagonist injection. Wistar male rats were trained to find hidden platform in the Morris water maze for 5 consecutive days. Rats' learning ability for spatial skill formation was evaluated depending on platform speed achievements. In re-training sessions (cues and platform location changed), it was found that all rats received Ro 25-6981 13 days before the re-training demonstrated impaired spatial memory. At the same time the inhibitor injected 29 days before re-training selectively facilitated the formation of spatial skill in animals with initially low learning abilities.

  11. Chemical stimulation of adherent cells by localized application of acetylcholine from a microfluidic system.

    PubMed

    Zibek, Susanne; Hagmeyer, Britta; Stett, Alfred; Stelzle, Martin

    2010-01-01

    Chemical stimulation of cells is inherently cell type selective in contrast to electro-stimulation. The availability of a system for localized application of minute amounts of chemical stimulants could be useful for dose related response studies to test new compounds. It could also bring forward the development of a novel type of neuroprostheses. In an experimental setup microdroplets of an acetylcholine solution were ejected from a fluidic microsystem and applied to the bottom of a nanoporous membrane. The solution traveled through the pores to the top of the membrane on which TE671 cells were cultivated. Calcium imaging was used to visualize cellular response with temporal and spatial resolution. Experimental demonstration of chemical stimulation for both threshold gated stimulation as well as accumulated dose-response was achieved by either employing acetylcholine as chemical stimulant or applying calcein uptake, respectively. Numerical modeling and simulation of transport mechanisms involved were employed to gain a theoretical understanding of the influence of pore size, concentration of stimulant and droplet volume on the spatial-temporal distribution of stimulant and on the cellular response. Diffusion, pressure driven flow and evaporation effects were taken into account. Fast stimulation kinetic is achieved with pores of 0.82 μm diameter, whereas sustained substance delivery is obtained with nanoporous membranes. In all cases threshold concentrations ranging from 0.01 to 0.015 μM acetylcholine independent of pore size were determined.

  12. Electrical stimulation site influences the spatial distribution of motor units recruited in tibialis anterior.

    PubMed

    Okuma, Yoshino; Bergquist, Austin J; Hong, Mandy; Chan, K Ming; Collins, David F

    2013-11-01

    To compare the spatial distribution of motor units recruited in tibialis anterior (TA) when electrical stimulation is applied over the TA muscle belly versus the common peroneal nerve trunk. Electromyography (EMG) was recorded from the surface and from fine wires in superficial and deep regions of TA. Separate M-wave recruitment curves were constructed for muscle belly and nerve trunk stimulation. During muscle belly stimulation, significantly more current was required to generate M-waves that were 5% of the maximal M-wave (M max; M5%max), 50% M max (M 50%max) and 95% M max (M 95%max) at the deep versus the superficial recording site. In contrast, during nerve trunk stimulation, there were no differences in the current required to reach M5%max, M 50%max or M 95%max between deep and superficial recording sites. Surface EMG reflected activity in both superficial and deep muscle regions. Stimulation over the muscle belly recruited motor units from superficial to deep with increasing stimulation amplitude. Stimulation over the nerve trunk recruited superficial and deep motor units equally, regardless of stimulation amplitude. These results support the idea that where electrical stimulation is applied markedly affects how contractions are produced and have implications for the interpretation of surface EMG data. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  13. Gaussian versus flat-top spatial beam profiles for optical stimulation of the prostate nerves

    NASA Astrophysics Data System (ADS)

    Tozburun, Serhat; Lagoda, Gwen A.; Burnett, Arthur L.; Fried, Nathaniel M.

    2010-02-01

    The cavernous nerves (CN) course along the prostate surface and are responsible for erectile function. Improved identification and preservation of the CN's is critical to maintaining sexual potency after prostate cancer surgery. Noncontact optical nerve stimulation (ONS) of the CN's was recently demonstrated in a rat model, in vivo, as a potential alternative to electrical nerve stimulation (ENS) for identification of the CN's during prostate surgery. However, the therapeutic window for ONS is narrow, so optimal design of the fiber optic delivery system is critical for safe, reproducible stimulation. This study describes modeling, assembly, and testing of an ONS probe for delivering a small, collimated, flat-top laser beam for uniform CN stimulation. A direct comparison of the magnitude and response time of the intracavernosal pressure (ICP) for both Gaussian and flat-top spatial beam profiles was performed. Thulium fiber laser radiation (λ=1870 nm) was delivered through a 200-μm fiber, with distal fiber tip chemically etched to convert a Gaussian to flat-top beam profile. The laser beam was collimated to a 1-mm-diameter spot using an aspheric lens. Computer simulations of light propagation were used to optimize the probe design. The 10-Fr (3.4-mm-OD) laparoscopic probe provided a constant radiant exposure at the CN surface. The probe was tested in four rats, in vivo. ONS of the CN's was performed with a 1-mm-diameter spot, 5-ms pulse duration, and pulse rate of 20 Hz for a duration of 15-30 s. The flat-top laser beam profile consistently produced a faster and higher ICP response at a lower radiant exposure than the Gaussian beam profile due, in part, to easier alignment of the more uniform beam with nerve. The threshold for ONS was approximately 0.14 J/cm2, corresponding to a temperature increase of 6-8°C at the CN surface after a stimulation time of 15 s. With further development, ONS may be used as a diagnostic tool for identification of CN's during prostate cancer surgery.

  14. Redesigning existing transcranial magnetic stimulation coils to reduce energy: application to low field magnetic stimulation

    NASA Astrophysics Data System (ADS)

    Wang, Boshuo; Shen, Michael R.; Deng, Zhi-De; Smith, J. Evan; Tharayil, Joseph J.; Gurrey, Clement J.; Gomez, Luis J.; Peterchev, Angel V.

    2018-06-01

    Objective. To present a systematic framework and exemplar for the development of a compact and energy-efficient coil that replicates the electric field (E-field) distribution induced by an existing transcranial magnetic stimulation coil. Approach. The E-field generated by a conventional low field magnetic stimulation (LFMS) coil was measured for a spherical head model and simulated in both spherical and realistic head models. Then, using a spherical head model and spatial harmonic decomposition, a spherical-shaped cap coil was synthesized such that its windings conformed to a spherical surface and replicated the E-field on the cortical surface while requiring less energy. A prototype coil was built and electrically characterized. The effect of constraining the windings to the upper half of the head was also explored via an alternative coil design. Main results. The LFMS E-field distribution resembled that of a large double-cone coil, with a peak field strength around 350 mV m‑1 in the cortex. The E-field distributions of the cap coil designs were validated against the original coil, with mean errors of 1%–3%. The cap coil required as little as 2% of the original coil energy and was significantly smaller in size. Significance. The redesigned LFMS coil is substantially smaller and more energy-efficient than the original, improving cost, power consumption, and portability. These improvements could facilitate deployment of LFMS in the clinic and potentially at home. This coil redesign approach can also be applied to other magnetic stimulation paradigms. Finally, the anatomically-accurate E-field simulation of LFMS can be used to interpret clinical LFMS data.

  15. Ginsenoside Rb1 improves spatial learning and memory by regulation of cell genesis in the hippocampal subregions of rats.

    PubMed

    Liu, Lei; Hoang-Gia, Trinh; Wu, Hui; Lee, Mi-Ra; Gu, Lijuan; Wang, Chunyan; Yun, Beom-Sik; Wang, Qijun; Ye, Shengquan; Sung, Chang-Keun

    2011-03-25

    Ginsenoside Rb1 (Rb1) is known to improve learning and memory in hippocampus-dependent tasks. However, the cellular mechanism remains unknown. Cell genesis in hippocampus is involved in spatial learning and memory. In the present study, Rb1 was orally administrated to adult rats for 30days. The behavioral training tests indicated that Rb1 improved spatial cognitive performance of rats in Morris water maze (MWM). Furthermore, we investigated the effects of Rb1 on cell genesis in adult rats' hippocampus, using thymidine analog bromodeoxyuridine (BrdU) as a marker for dividing cells. It has been shown that hippocampal cell genesis can be influenced by several factors such as learning and exercise. In order to avoid the effects of the interfering factors, only the rats treated with Rb1 without training in MWM were used to investigate cell genesis in hippocampus. When BrdU was given to the rats 30days prior to being killed, it was shown that oral administration of Rb1 significantly increased cell survival in dentate gyrus and hippocampal subregion CA3. However, when BrdU was injected 2h prior to sacrifice, the results indicated that Rb1 had no significant influence on cell proliferation in the hippocampal subregions. Thus, an increase of cell survival in hippocampus stimulated by Rb1 may be one of the mechanisms by which ginseng facilitates spatial learning and memory. Our study also indicates that Rb1 may be developed as a therapeutic agent for patients with memory impairment. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Role of cerebellar nodulus and uvula on the vestibular quick phase spatial constancy.

    PubMed

    Pettorossi, V E; Grassi, S; Errico, P; Barmack, N H

    2001-01-01

    We investigated the orientation of quick phases (QPs) of vestibularly-induced eye movements in rabbits in response to "off-vertical" sinusoidal vestibular stimulation. We also examined the possible role of the cerebellar nodulus and ventral uvula in controlling QP spatial orientation and modification. During "off-vertical" vestibular stimulation QPs remained aligned with the earth's horizontal plane, while the slow phases (SPs) were aligned with the plane of vestibular stimulation. This suggests that QPs are coded in gravito-inertial coordinates and SPs in head coordinates. When rabbits were oscillated in the light (20 degrees peak-to-peak; 0.2 Hz) about an "off-vertical" axis for 2 h, the QPs changed their trajectory, abandoning the earth's horizontal plane to approach the plane of the stimulus. By contrast, in the absence of conjunctive optokinetic stimulation, QPs remained fixed in the earth's horizontal plane even after 2 h of "off-vertical" stimulation. The conjunctive combination of optokinetic and vestibular stimulation caused QPs to change their plane of rotation. After lesion of the nodulus-uvula the ability of rabbits to reorient QPs during conjoint vestibular-optokinetic stimulation was maintained. We conclude that the space orientation and adaptation of QPs do not require cerebellar control.

  17. Proton spectral editing in the inhomogeneous radiofrequency field of a surface coil using modified stimulated echoes.

    PubMed

    Lahrech, H; Briguet, A

    1990-11-01

    It is shown that the modified stimulated echo sequence, [theta](+/- x +/- y)-t1-[theta](+ x)-t2/2-[2 theta](+ x)-t2/2- [theta](+ x)-t1-Acq(+/- x +/- y), denoted as MSTE[2 theta]x according to the exciter phase of the 2 theta pulse, is able to perform proton spectral editing without difference spectra. On the other hand, this sequence appears to be suitable for spatial localization. Sensitivity and spatial selectivity of MSTE and conventional stimulated echo sequence (STE) are briefly compared. MSTE is applied to editing lactate in the rat brain using the locally restricted excitation of a surface coil.

  18. Galvanic vestibular stimulation speeds visual memory recall.

    PubMed

    Wilkinson, David; Nicholls, Sophie; Pattenden, Charlotte; Kilduff, Patrick; Milberg, William

    2008-08-01

    The experiments of Alessandro Volta were amongst the first to indicate that visuo-spatial function can be altered by stimulating the vestibular nerves with galvanic current. Until recently, the beneficial effects of the procedure were masked by the high levels of electrical current applied, which induced nystagmus-related gaze deviation and spatial disorientation. However, several neuropsychological studies have shown that much weaker, imperceptible currents that do not elicit unpleasant side-effects can help overcome visual loss after stroke. Here, we show that visual processing in neurologically healthy individuals can also benefit from galvanic vestibular stimulation. Participants first learnt the names of eight unfamiliar faces and then after a short delay, answered questions from memory about how pairs of these faces differed. Mean correct reaction times were significantly shorter when sub-sensory, noise-enhanced anodal stimulation was administered to the left mastoid, compared to when no stimulation was administered at all. This advantage occurred with no loss in response accuracy, and raises the possibility that the procedure may constitute a more general form of cognitive enhancement.

  19. Using Transcranial Magnetic Stimulation to Evaluate the Motor Pathways After an Intraoperative Spinal Cord Injury and to Predict the Recovery of Intraoperative Transcranial Electrical Motor Evoked Potentials: A Case Report.

    PubMed

    Grover, Helen J; Thornton, Rachel; Lutchman, Lennel N; Blake, Julian C

    2016-06-01

    The authors report a case of unilateral loss of intraoperative transcranial electrical motor evoked potentials (TES MEP) associated with a spinal cord injury during scoliosis correction and the subsequent use of extraoperative transcranial magnetic stimulation to monitor the recovery of spinal cord function. The authors demonstrate the absence of TES MEPs and absent transcranial magnetic stimulation responses in the immediate postoperative period, and document the partial recovery of transcranial magnetic stimulation responses, which corresponded to partial recovery of TES MEPs. Intraoperative TES MEPs were enhanced using spatial facilitation technique, which enabled the patient to undergo further surgery to stabilize the spine and correct her scoliosis. This case report supports evidence of the use of extraoperative transcranial magnetic stimulation to predict the presence of intraoperative TES responses and demonstrates the usefulness of spatial facilitation to monitor TES MEPs in a patient with a preexisting spinal cord injury.

  20. Distinct roles of the intraparietal sulcus and temporoparietal junction in attentional capture from distractor features: An individual differences approach.

    PubMed

    Painter, David R; Dux, Paul E; Mattingley, Jason B

    2015-07-01

    Setting attention for an elementary visual feature, such as color or motion, results in greater spatial attentional "capture" from items with target compared with distractor features. Thus, capture is contingent on feature-based control settings. Neuroimaging studies suggest that this contingent attentional capture involves interactions between dorsal and ventral frontoparietal networks. To examine the distinct causal influences of these networks on contingent capture, we applied continuous theta-burst stimulation (cTBS) to alter neural excitability within the dorsal intraparietal sulcus (IPS), the ventral temporoparietal junction (TPJ) and a control site, visual area MT. Participants undertook an attentional capture task before and after stimulation, in which they made speeded responses to color-defined targets that were preceded by spatial cues in the target or distractor color. Cues appeared either at the target location (valid) or at a non-target location (invalid). Reaction times were slower for targets preceded by invalid compared with valid cues, demonstrating spatial attentional capture. Cues with the target color captured attention to a greater extent than those with the distractor color, consistent with contingent capture. Effects of cTBS were not evident at the group level, but emerged instead from analyses of individual differences. Target capture magnitude was positively correlated pre- and post-stimulation for all three cortical sites, suggesting that cTBS did not influence target capture. Conversely, distractor capture was positively correlated pre- and post-stimulation of MT, but uncorrelated for IPS and TPJ, suggesting that stimulation of IPS and TPJ selectively disrupted distractor capture. Additionally, the effects of IPS stimulation were predicted by pre-stimulation attentional capture, whereas the effects of TPJ stimulation were predicted by pre-stimulation distractor suppression. The results are consistent with the existence of distinct neural circuits underlying target and distractor capture, as well as distinct roles for the IPS and TPJ. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Engineering Data Compendium. Human Perception and Performance. Volume 2

    DTIC Science & Technology

    1988-01-01

    Stimulation 5.1014 5.1004 Auditory Detection in the Presence of Visual Stimulation 5.1015 5.1005 Tactual Detection and Discrimination in the Presence of...Accessory Stimulation 5.1016 5.1006 Tactile Versus Auditory Localization of Sound 5.1007 Spatial Localization in the Presence of Inter- 5.1017...York: Wiley. Cross References 5.1004 Auditory detection in the presence of visual stimulation ; 5.1005 Tactual detection and dis- crimination in

  2. Investigating brain functional evolution and plasticity using microelectrode array technology.

    PubMed

    Napoli, Alessandro; Obeid, Iyad

    2015-10-01

    The aim of this work was to investigate long and short-term plasticity responsible for memory formation in dissociated neuronal networks. In order to address this issue, a set of experiments was designed and implemented in which the microelectrode array electrode grid was divided into four quadrants, two of which were chronically stimulated, every two days for one hour with a stimulation paradigm that varied over time. Overall network and quadrant responses were then analyzed to quantify what level of plasticity took place in the network and how this was due to the stimulation interruption. The results demonstrate that there were no spatial differences in the stimulus-evoked activity within quadrants. Furthermore, the implemented stimulation protocol induced depression effects in the neuronal networks as demonstrated by the consistently lower network activity following stimulation sessions. Finally, the analysis demonstrated that the inhibitory effects of the stimulation decreased over time, thus suggesting a habituation phenomenon. These findings are sufficient to conclude that electrical stimulation is an important tool to interact with dissociated neuronal cultures, but localized stimuli are not enough to drive spatial synaptic potentiation or depression. On the contrary, the ability to modulate synaptic temporal plasticity was a feasible task to achieve by chronic network stimulation. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Electrophysiological channel interactions using focused multipolar stimulation for cochlear implants

    NASA Astrophysics Data System (ADS)

    George, Shefin S.; Shivdasani, Mohit N.; Wise, Andrew K.; Shepherd, Robert K.; Fallon, James B.

    2015-12-01

    Objective. Speech intelligibility with existing multichannel cochlear implants (CIs) is thought to be limited by poor spatial selectivity and interactions between CI channels caused by overlapping activation with monopolar (MP) stimulation. Our previous studies have shown that focused multipolar (FMP) and tripolar (TP) stimulation produce more restricted neural activation in the inferior colliculus (IC), compared to MP stimulation. Approach. This study explored interactions in the IC produced by simultaneous stimulation of two CI channels. We recorded multi-unit neural activity in the IC of anaesthetized cats with normal and severely degenerated spiral ganglion neuron populations in response to FMP, TP and MP stimulation from a 14 channel CI. Stimuli were applied to a ‘fixed’ CI channel, chosen toward the middle of the cochlear electrode array, and the effects of simultaneously stimulating a more apical ‘test’ CI channel were measured as a function of spatial separation between the two stimulation channels and stimulus level of the fixed channel. Channel interactions were quantified by changes in neural responses and IC threshold (i.e., threshold shift) elicited by simultaneous stimulation of two CI channels, compared to stimulation of the test channel alone. Main results. Channel interactions were significantly lower for FMP and TP than for MP stimulation (p < 0.001), whereas no significant difference was observed between FMP and TP stimulation. With MP stimulation, threshold shifts increased with decreased inter-electrode spacing and increased stimulus levels of the fixed channel. For FMP and TP stimulation, channel interactions were found to be similar for different inter-electrode spacing and stimulus levels of the fixed channel. Significance. The present study demonstrates how the degree of channel interactions in a CI can be controlled using stimulation configurations such as FMP and TP; such knowledge is essential in enhancing CI function in complex acoustic environments.

  4. Binaural Hearing Ability With Bilateral Bone Conduction Stimulation in Subjects With Normal Hearing: Implications for Bone Conduction Hearing Aids.

    PubMed

    Zeitooni, Mehrnaz; Mäki-Torkko, Elina; Stenfelt, Stefan

    The purpose of this study is to evaluate binaural hearing ability in adults with normal hearing when bone conduction (BC) stimulation is bilaterally applied at the bone conduction hearing aid (BCHA) implant position as well as at the audiometric position on the mastoid. The results with BC stimulation are compared with bilateral air conduction (AC) stimulation through earphones. Binaural hearing ability is investigated with tests of spatial release from masking and binaural intelligibility level difference using sentence material, binaural masking level difference with tonal chirp stimulation, and precedence effect using noise stimulus. In all tests, results with bilateral BC stimulation at the BCHA position illustrate an ability to extract binaural cues similar to BC stimulation at the mastoid position. The binaural benefit is overall greater with AC stimulation than BC stimulation at both positions. The binaural benefit for BC stimulation at the mastoid and BCHA position is approximately half in terms of decibels compared with AC stimulation in the speech based tests (spatial release from masking and binaural intelligibility level difference). For binaural masking level difference, the binaural benefit for the two BC positions with chirp signal phase inversion is approximately twice the benefit with inverted phase of the noise. The precedence effect results with BC stimulation at the mastoid and BCHA position are similar for low frequency noise stimulation but differ with high-frequency noise stimulation. The results confirm that binaural hearing processing with bilateral BC stimulation at the mastoid position is also present at the BCHA implant position. This indicates the ability for binaural hearing in patients with good cochlear function when using bilateral BCHAs.

  5. Nonlinear Focal Modulation Microscopy.

    PubMed

    Zhao, Guangyuan; Zheng, Cheng; Kuang, Cuifang; Zhou, Renjie; Kabir, Mohammad M; Toussaint, Kimani C; Wang, Wensheng; Xu, Liang; Li, Haifeng; Xiu, Peng; Liu, Xu

    2018-05-11

    We demonstrate nonlinear focal modulation microscopy (NFOMM) to achieve superresolution imaging. Traditional approaches to superresolution that utilize point scanning often rely on spatially reducing the size of the emission pattern by directly narrowing (e.g., through minimizing the detection pinhole in Airyscan, Zeiss) or indirectly peeling its outer profiles [e.g., through depleting the outer emission region in stimulated emission depletion (STED) microscopy]. We show that an alternative conceptualization that focuses on maximizing the optical system's frequency shifting ability offers advantages in further improving resolution while reducing system complexity. In NFOMM, a spatial light modulator and a suitably intense laser illumination are used to implement nonlinear focal-field modulation to achieve a transverse spatial resolution of ∼60  nm (∼λ/10). We show that NFOMM is comparable with STED microscopy and suitable for fundamental biology studies, as evidenced in imaging nuclear pore complexes, tubulin and vimentin in Vero cells. Since NFOMM is readily implemented as an add-on module to a laser-scanning microscope, we anticipate wide utility of this new imaging technique.

  6. Nonlinear Focal Modulation Microscopy

    NASA Astrophysics Data System (ADS)

    Zhao, Guangyuan; Zheng, Cheng; Kuang, Cuifang; Zhou, Renjie; Kabir, Mohammad M.; Toussaint, Kimani C.; Wang, Wensheng; Xu, Liang; Li, Haifeng; Xiu, Peng; Liu, Xu

    2018-05-01

    We demonstrate nonlinear focal modulation microscopy (NFOMM) to achieve superresolution imaging. Traditional approaches to superresolution that utilize point scanning often rely on spatially reducing the size of the emission pattern by directly narrowing (e.g., through minimizing the detection pinhole in Airyscan, Zeiss) or indirectly peeling its outer profiles [e.g., through depleting the outer emission region in stimulated emission depletion (STED) microscopy]. We show that an alternative conceptualization that focuses on maximizing the optical system's frequency shifting ability offers advantages in further improving resolution while reducing system complexity. In NFOMM, a spatial light modulator and a suitably intense laser illumination are used to implement nonlinear focal-field modulation to achieve a transverse spatial resolution of ˜60 nm (˜λ /10 ). We show that NFOMM is comparable with STED microscopy and suitable for fundamental biology studies, as evidenced in imaging nuclear pore complexes, tubulin and vimentin in Vero cells. Since NFOMM is readily implemented as an add-on module to a laser-scanning microscope, we anticipate wide utility of this new imaging technique.

  7. Structural Organization of the Corpus Callosum Predicts Attentional Shifts after Continuous Theta Burst Stimulation.

    PubMed

    Chechlacz, Magdalena; Humphreys, Glyn W; Sotiropoulos, Stamatios N; Kennard, Christopher; Cazzoli, Dario

    2015-11-18

    Repetitive transcranial magnetic stimulation (rTMS) applied over the right posterior parietal cortex (PPC) in healthy participants has been shown to trigger a significant rightward shift in the spatial allocation of visual attention, temporarily mimicking spatial deficits observed in neglect. In contrast, rTMS applied over the left PPC triggers a weaker or null attentional shift. However, large interindividual differences in responses to rTMS have been reported. Studies measuring changes in brain activation suggest that the effects of rTMS may depend on both interhemispheric and intrahemispheric interactions between cortical loci controlling visual attention. Here, we investigated whether variability in the structural organization of human white matter pathways subserving visual attention, as assessed by diffusion magnetic resonance imaging and tractography, could explain interindividual differences in the effects of rTMS. Most participants showed a rightward shift in the allocation of spatial attention after rTMS over the right intraparietal sulcus (IPS), but the size of this effect varied largely across participants. Conversely, rTMS over the left IPS resulted in strikingly opposed individual responses, with some participants responding with rightward and some with leftward attentional shifts. We demonstrate that microstructural and macrostructural variability within the corpus callosum, consistent with differential effects on cross-hemispheric interactions, predicts both the extent and the direction of the response to rTMS. Together, our findings suggest that the corpus callosum may have a dual inhibitory and excitatory function in maintaining the interhemispheric dynamics that underlie the allocation of spatial attention. The posterior parietal cortex (PPC) controls allocation of attention across left versus right visual fields. Damage to this area results in neglect, characterized by a lack of spatial awareness of the side of space contralateral to the brain injury. Transcranial magnetic stimulation over the PPC is used to study cognitive mechanisms of spatial attention and to examine the potential of this technique to treat neglect. However, large individual differences in behavioral responses to stimulation have been reported. We demonstrate that the variability in the structural organization of the corpus callosum accounts for these differences. Our findings suggest novel dual mechanism of the corpus callosum function in spatial attention and have broader implications for the use of stimulation in neglect rehabilitation. Copyright © 2015 the authors 0270-6474/15/3515353-16$15.00/0.

  8. Environmental enrichment decreases GABAergic inhibition and improves cognitive abilities, synaptic plasticity, and visual functions in a mouse model of Down syndrome

    PubMed Central

    Begenisic, Tatjana; Spolidoro, Maria; Braschi, Chiara; Baroncelli, Laura; Milanese, Marco; Pietra, Gianluca; Fabbri, Maria E.; Bonanno, Giambattista; Cioni, Giovanni; Maffei, Lamberto; Sale, Alessandro

    2011-01-01

    Down syndrome (DS) is the most common genetic disorder associated with mental retardation. It has been repeatedly shown that Ts65Dn mice, the prime animal model for DS, have severe cognitive and neural plasticity defects due to excessive inhibition. We report that increasing sensory-motor stimulation in adulthood through environmental enrichment (EE) reduces brain inhibition levels and promotes recovery of spatial memory abilities, hippocampal synaptic plasticity, and visual functions in adult Ts65Dn mice. PMID:22207837

  9. Midbrain Raphe Stimulation Improves Behavioral and Anatomical Recovery from Fluid-Percussion Brain Injury

    PubMed Central

    Carballosa Gonzalez, Melissa M.; Blaya, Meghan O.; Alonso, Ofelia F.; Bramlett, Helen M.

    2013-01-01

    Abstract The midbrain median raphe (MR) and dorsal raphe (DR) nuclei were tested for their capacity to regulate recovery from traumatic brain injury (TBI). An implanted, wireless self-powered stimulator delivered intermittent 8-Hz pulse trains for 7 days to the rat's MR or DR, beginning 4–6 h after a moderate parasagittal (right) fluid-percussion injury. MR stimulation was also examined with a higher frequency (24 Hz) or a delayed start (7 days after injury). Controls had sham injuries, inactive stimulators, or both. The stimulation caused no apparent acute responses or adverse long-term changes. In water-maze trials conducted 5 weeks post-injury, early 8-Hz MR and DR stimulation restored the rate of acquisition of reference memory for a hidden platform of fixed location. Short-term spatial working memory, for a variably located hidden platform, was restored only by early 8-Hz MR stimulation. All stimulation protocols reversed injury-induced asymmetry of spontaneous forelimb reaching movements tested 6 weeks post-injury. Post-mortem histological measurement at 8 weeks post-injury revealed volume losses in parietal-occipital cortex and decussating white matter (corpus callosum plus external capsule), but not hippocampus. The cortical losses were significantly reversed by early 8-Hz MR and DR stimulation, the white matter losses by all forms of MR stimulation. The generally most effective protocol, 8-Hz MR stimulation, was tested 3 days post-injury for its acute effect on forebrain cyclic adenosine monophosphate (cAMP), a key trophic signaling molecule. This procedure reversed injury-induced declines of cAMP levels in both cortex and hippocampus. In conclusion, midbrain raphe nuclei can enduringly enhance recovery from early disseminated TBI, possibly in part through increased signaling by cAMP in efferent targets. A neurosurgical treatment for TBI using interim electrical stimulation in raphe repair centers is suggested. PMID:22963112

  10. Neural and Hemodynamic Responses Elicited by Forelimb- and Photo-stimulation in Channelrhodopsin-2 Mice: Insights into the Hemodynamic Point Spread Function

    PubMed Central

    Vazquez, Alberto L.; Fukuda, Mitsuhiro; Crowley, Justin C.; Kim, Seong-Gi

    2014-01-01

    Hemodynamic responses are commonly used to map brain activity; however, their spatial limits have remained unclear because of the lack of a well-defined and malleable spatial stimulus. To examine the properties of neural activity and hemodynamic responses, multiunit activity, local field potential, cerebral blood volume (CBV)-sensitive optical imaging, and laser Doppler flowmetry were measured from the somatosensory cortex of transgenic mice expressing Channelrhodopsin-2 in cortex Layer 5 pyramidal neurons. The magnitude and extent of neural and hemodynamic responses were modulated using different photo-stimulation parameters and compared with those induced by somatosensory stimulation. Photo-stimulation-evoked spiking activity across cortical layers was similar to forelimb stimulation, although their activity originated in different layers. Hemodynamic responses induced by forelimb- and photo-stimulation were similar in magnitude and shape, although the former were slightly larger in amplitude and wider in extent. Altogether, the neurovascular relationship differed between these 2 stimulation pathways, but photo-stimulation-evoked changes in neural and hemodynamic activities were linearly correlated. Hemodynamic point spread functions were estimated from the photo-stimulation data and its full-width at half-maximum ranged between 103 and 175 µm. Therefore, submillimeter functional structures separated by a few hundred micrometers may be resolved using hemodynamic methods, such as optical imaging and functional magnetic resonance imaging. PMID:23761666

  11. EFFECTS OF MEDIAL SEPTAL LESION ON HIPPOCAMPAL EXTRACELLULAR GLUTAMATE AND GABA LEVELS DURING SPATIAL ALTERNATION TESTING.

    PubMed

    Mataradze, S; Naneishvili, T; Sephashvili, M; Mikeladze, D; Dashniani, M

    2016-10-01

    The present study investigated spatial working memory assessed in spontaneous alternation (SA) task and hippocampal glutamate and GABA release prior to, during, and after SA test in sham-operated and electrolytic medial septal (MS) lesioned rats. Also, have been investigated the effects of MS lesion on KCl-stimulated release of glutamate and GABA in the hippocampus. Behavioral study showed that electrolytic lesion of MS significantly impaired SA performance. Although both groups of animals had an insignificant rise in their respective hippocampal glutamate efflux during the SA, the rise of MS lesioned animals was blunted when compared with control animals. Hippocampal GABA levels did not change during behavioral testing in both groups. Most of control animals showed increase in KCl-stimulated glutamate release. By contrast, only one MS lesioned rat showed increase in glutamate release in response to KCl stimulation. Most of control and MS lesioned rats were non-responders in GABA release in response to KCl stimulation. Decreased glutamate release (upon stimulation) in the MS lesioned rats may contribute to spatial working memory impairment in these animals. We propose that SA testing coupled with in vivo microdialysis sampling represents a suitable approach to revealing the neurochemical correlates of hippocampal-dependent memory function, and thus could be a useful tool for better understanding of the neurochemical basis of cognitive decline associated with various disorders and neurodegenerative diseases.

  12. Where Is the Square? Activities to Stimulate Spatial Reasoning

    ERIC Educational Resources Information Center

    Obara, Samuel

    2013-01-01

    The National Council of Teachers of Mathematics (NCTM, 1989, 2000) and the new "Australian Curriculum: Mathematics" for senior secondary (ACARA, 2010) highlight the importance of teaching spatial reasoning as early as preschool when mathematics is introduced. Studies have shown that there is a relationship between spatial abilities and…

  13. Silicone Molding and Lifetime Testing of Peripheral Nerve Interfaces for Neuroprostheses

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gupte, Kimaya; Tolosa, Vanessa

    Implantable peripheral nerve cuffs have a large application in neuroprostheses as they can be used to restore sensation to those with upper limb amputations. Modern day prosthetics, while lessening the pain associated with phantom limb syndrome, have limited fine motor control and do not provide sensory feedback to patients. Sensory feedback with prosthetics requires communication between the nervous system and limbs, and is still a challenge to accomplish with amputees. Establishing this communication between the peripheral nerves in the arm and artificial limbs is vital as prosthetics research aims to provide sensory feedback to amputees. Peripheral nerve cuffs restore sensationmore » by electrically stimulating certain parts of the nerve in order to create feeling in the hand. Cuff electrodes have an advantage over standard electrodes as they have high selective stimulation by bringing the electrical interface close to the neural tissue in order to selectively activate targeted regions of a peripheral nerve. In order to further improve the selective stimulation of these nerve cuffs, there is need for finer spatial resolution among electrodes. One method to achieve a higher spatial resolution is to increase the electrode density on the cuff itself. Microfabrication techniques can be used to achieve this higher electrode density. Using L-Edit, a layout editor, microfabricated peripheral nerve cuffs were designed with a higher electrode density than the current model. This increase in electrode density translates to an increase in spatial resolution by at least one order of magnitude. Microfabricated devices also have two separate components that are necessary to understand before implantation: lifetime of the device and assembly to prevent nerve damage. Silicone molding procedures were optimized so that devices do not damage nerves in vivo, and lifetime testing was performed on test microfabricated devices to determine their lifetime in vivo. Future work of this project would include fabricating some of the designed devices and seeing how they compare to the current cuffs in terms of their electrical performance, lifetime, shape, and mechanical properties.« less

  14. A multi-pad electrode based functional electrical stimulation system for restoration of grasp

    PubMed Central

    2012-01-01

    Background Functional electrical stimulation (FES) applied via transcutaneous electrodes is a common rehabilitation technique for assisting grasp in patients with central nervous system lesions. To improve the stimulation effectiveness of conventional FES, we introduce multi-pad electrodes and a new stimulation paradigm. Methods The new FES system comprises an electrode composed of small pads that can be activated individually. This electrode allows the targeting of motoneurons that activate synergistic muscles and produce a functional movement. The new stimulation paradigm allows asynchronous activation of motoneurons and provides controlled spatial distribution of the electrical charge that is delivered to the motoneurons. We developed an automated technique for the determination of the preferred electrode based on a cost function that considers the required movement of the fingers and the stabilization of the wrist joint. The data used within the cost function come from a sensorized garment that is easy to implement and does not require calibration. The design of the system also includes the possibility for fine-tuning and adaptation with a manually controllable interface. Results The device was tested on three stroke patients. The results show that the multi-pad electrodes provide the desired level of selectivity and can be used for generating a functional grasp. The results also show that the procedure, when performed on a specific user, results in the preferred electrode configuration characteristics for that patient. The findings from this study are of importance for the application of transcutaneous stimulation in the clinical and home environments. PMID:23009589

  15. Mapping organelle motion reveals a vesicular conveyor belt spatially replenishing secretory vesicles in stimulated chromaffin cells.

    PubMed

    Maucort, Guillaume; Kasula, Ravikiran; Papadopulos, Andreas; Nieminen, Timo A; Rubinsztein-Dunlop, Halina; Meunier, Frederic A

    2014-01-01

    How neurosecretory cells spatially adjust their secretory vesicle pools to replenish those that have fused and released their hormonal content is currently unknown. Here we designed a novel set of image analyses to map the probability of tracked organelles undergoing a specific type of movement (free, caged or directed). We then applied our analysis to time-lapse z-stack confocal imaging of secretory vesicles from bovine Chromaffin cells to map the global changes in vesicle motion and directionality occurring upon secretagogue stimulation. We report a defined region abutting the cortical actin network that actively transports secretory vesicles and is dissipated by actin and microtubule depolymerizing drugs. The directionality of this "conveyor belt" towards the cell surface is activated by stimulation. Actin and microtubule networks therefore cooperatively probe the microenvironment to transport secretory vesicles to the periphery, providing a mechanism whereby cells globally adjust their vesicle pools in response to secretagogue stimulation.

  16. Effect of chronic and acute low-frequency repetitive transcranial magnetic stimulation on spatial memory in rats.

    PubMed

    Li, Wei; Yang, Yuye; Ye, Qing; Yang, Bo; Wang, Zhengrong

    2007-03-15

    Repetitive transcranial magnetic stimulation (rTMS) is a novel, non-invasive neurological and psychiatric tool. The low-frequency (1 Hz or less) rTMS is likely to play a particular role in its mechanism of action with different effects in comparison with high-frequency (>1 Hz) rTMS. There is limited information regarding the effect of low-frequency rTMS on spatial memory. In our study, each male Wistar rat was daily given 300 stimuli (1.0 T, 200 micros) at a rate of 0.5 Hz or sham stimulation. We investigated the effects of chronic and acute rTMS on reference/working memory process in Morris water maze test with the hypothesis that the effect would differ by chronic or acute condition. Chronic low-frequency rTMS impaired the retrieval of spatial short- and long-term spatial reference memory but not acquisition process and working memory, whereas acute low-frequency rTMS predominantly induced no deficits in acquisition or short-term spatial reference memory as well as working memory except for long-term reference memory. In summary, chronic 0.5 Hz rTMS disrupts spatial short- and long-term reference memory function, but acute rTMS differently affects reference memory. Chronic low-frequency rTMS may be used to modulate reference memory. Treatment protocols using low-frequency rTMS in neurological and psychiatric disorders need to take into account the potential effect of chronic low-frequency rTMS on memory and other cognitive functions.

  17. The right hemisphere is independent from the left hemisphere in allocating visuospatial attention.

    PubMed

    Zuanazzi, Arianna; Cattaneo, Luigi

    2017-07-28

    The capacity to allocate visuospatial attention is traditionally considered right-lateralized according to the effects of unilateral cerebral lesions. Contralateral hemi-spatial neglect occurs much more frequently after lesions of the right hemisphere, which has therefore been dubbed as 'dominant'. This pattern of symptoms is supported by functional models that postulate either independence or reciprocal influences between the two hemispheres. Here we specifically explored the dependency of the right hemisphere (RH) from the left hemisphere (LH) in spatial attention. We capitalized on the well-known effect of online transcranial magnetic stimulation (TMS) on the RH in healthy individuals, consisting in transient neglect-like manifestations in the left hemi-space. We assessed whether prior stimulation of the left posterior parietal cortex with a long-lasting neuromodulatory procedure (transcranial direct current stimulation - tDCS) affected the acute effects of TMS on the right posterior parietal cortex. We performed a within-subjects factorial study with two factors: LH tDCS (sham or real) and RH TMS (sham or real), resulting in a 2×2 design. The effects on spatial attention were examined separately for the two hemi-spaces by means of a modified line-bisection task. The results indicated that TMS over the RH produced a spatial attention deficit in the left hemi-space alone and the behavioural effects of TMS were not modulated by prior stimulation of the LH. Interestingly, additional analyses showed that tDCS over the LH alone produced a deficit in spatial attention to the right hemi-space. We interpret the current results as evidence for a largely independent contribution of each hemisphere to the allocation of visuospatial attention limited to the contralateral hemi-space. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Effective intracortical microstimulation parameters applied to primary motor cortex for evoking forelimb movements to stable spatial end points

    PubMed Central

    Van Acker, Gustaf M.; Amundsen, Sommer L.; Messamore, William G.; Zhang, Hongyu Y.; Luchies, Carl W.; Kovac, Anthony

    2013-01-01

    High-frequency, long-duration intracortical microstimulation (HFLD-ICMS) applied to motor cortex is recognized as a useful and informative method for corticomotor mapping by evoking natural-appearing movements of the limb to consistent stable end-point positions. An important feature of these movements is that stimulation of a specific site in motor cortex evokes movement to the same spatial end point regardless of the starting position of the limb. The goal of this study was to delineate effective stimulus parameters for evoking forelimb movements to stable spatial end points from HFLD-ICMS applied to primary motor cortex (M1) in awake monkeys. We investigated stimulation of M1 as combinations of frequency (30–400 Hz), amplitude (30–200 μA), and duration (0.5–2 s) while concurrently recording electromyographic (EMG) activity from 24 forelimb muscles and movement kinematics with a motion capture system. Our results suggest a range of parameters (80–140 Hz, 80–140 μA, and 1,000-ms train duration) that are effective and safe for evoking forelimb translocation with subsequent stabilization at a spatial end point. The mean time for stimulation to elicit successful movement of the forelimb to a stable spatial end point was 475.8 ± 170.9 ms. Median successful frequency and amplitude were 110 Hz and 110 μA, respectively. Attenuated parameters resulted in inconsistent, truncated, or undetectable movements, while intensified parameters yielded no change to movement end points and increased potential for large-scale physiological spread and adverse focal motor effects. Establishing cortical stimulation parameters yielding consistent forelimb movements to stable spatial end points forms the basis for a systematic and comprehensive mapping of M1 in terms of evoked movements and associated muscle synergies. Additionally, the results increase our understanding of how the central nervous system may encode movement. PMID:23741044

  19. Planar implantable sensor for in vivo measurement of cellular oxygen metabolism in brain tissue.

    PubMed

    Tsytsarev, Vassiliy; Akkentli, Fatih; Pumbo, Elena; Tang, Qinggong; Chen, Yu; Erzurumlu, Reha S; Papkovsky, Dmitri B

    2017-04-01

    Brain imaging methods are continually improving. Imaging of the cerebral cortex is widely used in both animal experiments and charting human brain function in health and disease. Among the animal models, the rodent cerebral cortex has been widely used because of patterned neural representation of the whiskers on the snout and relative ease of activating cortical tissue with whisker stimulation. We tested a new planar solid-state oxygen sensor comprising a polymeric film with a phosphorescent oxygen-sensitive coating on the working side, to monitor dynamics of oxygen metabolism in the cerebral cortex following sensory stimulation. Sensory stimulation led to changes in oxygenation and deoxygenation processes of activated areas in the barrel cortex. We demonstrate the possibility of dynamic mapping of relative changes in oxygenation in live mouse brain tissue with such a sensor. Oxygenation-based functional magnetic resonance imaging (fMRI) is very effective method for functional brain mapping but have high costs and limited spatial resolution. Optical imaging of intrinsic signal (IOS) does not provide the required sensitivity, and voltage-sensitive dye optical imaging (VSDi) has limited applicability due to significant toxicity of the voltage-sensitive dye. Our planar solid-state oxygen sensor imaging approach circumvents these limitations, providing a simple optical contrast agent with low toxicity and rapid application. The planar solid-state oxygen sensor described here can be used as a tool in visualization and real-time analysis of sensory-evoked neural activity in vivo. Further, this approach allows visualization of local neural activity with high temporal and spatial resolution. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Simplifications of the RELIEF flow tagging system for laboratory use. [Raman Excitation plus Laser Induced Electronic Fluorescence

    NASA Technical Reports Server (NTRS)

    Lempert, Walter R.; Zhang, Boying; Miles, Richard B.; Diskin, Glenn

    1991-01-01

    The use of an O2:He stimulated Raman cell to generate the Stokes beam for the Raman vibrational pumping step of the RELIEF (Raman Excitation plus Laser-Induced Electronic Fluorescence) flow tagging method is reported. Use of the Raman cell rather than a dye laser provides pump and Stokes beams which are automatically frequency matched and temporally and spatially overlapped. The Nd:YAG pump laser is operated multilongitudinal mode, which eliminates the need for injection seeding, resulting in decreased operation complexity and improved stability with respect to acoustic noise. Results are presented for 1st Stokes conversion efficiency and stimulated Brillouin backscattering loss and are compared to the case of pure O2. Scanning CARS measurements of the Q-branch lineshape for both pure O2 and the O2:He mixture are also presented.

  1. Vertically aligned carbon nanofiber as nano-neuron interface for monitoring neural function

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ericson, Milton Nance; McKnight, Timothy E; Melechko, Anatoli Vasilievich

    2012-01-01

    Neural chips, which are capable of simultaneous, multi-site neural recording and stimulation, have been used to detect and modulate neural activity for almost 30 years. As a neural interface, neural chips provide dynamic functional information for neural decoding and neural control. By improving sensitivity and spatial resolution, nano-scale electrodes may revolutionize neural detection and modulation at cellular and molecular levels as nano-neuron interfaces. We developed a carbon-nanofiber neural chip with lithographically defined arrays of vertically aligned carbon nanofiber electrodes and demonstrated its capability of both stimulating and monitoring electrophysiological signals from brain tissues in vitro and monitoring dynamic information ofmore » neuroplasticity. This novel nano-neuron interface can potentially serve as a precise, informative, biocompatible, and dual-mode neural interface for monitoring of both neuroelectrical and neurochemical activity at the single cell level and even inside the cell.« less

  2. Dynamic and Inherent B0 Correction for DTI Using Stimulated Echo Spiral Imaging

    PubMed Central

    Avram, Alexandru V.; Guidon, Arnaud; Truong, Trong-Kha; Liu, Chunlei; Song, Allen W.

    2013-01-01

    Purpose To present a novel technique for high-resolution stimulated echo (STE) diffusion tensor imaging (DTI) with self-navigated interleaved spirals (SNAILS) readout trajectories that can inherently and dynamically correct for image artifacts due to spatial and temporal variations in the static magnetic field (B0) resulting from eddy currents, tissue susceptibilities, subject/physiological motion, and hardware instabilities. Methods The Hahn spin echo formed by the first two 90° radio-frequency pulses is balanced to consecutively acquire two additional images with different echo times (TE) and generate an inherent field map, while the diffusion-prepared STE signal remains unaffected. For every diffusion-encoding direction, an intrinsically registered field map is estimated dynamically and used to effectively and inherently correct for off-resonance artifacts in the reconstruction of the corresponding diffusion-weighted image (DWI). Results After correction with the dynamically acquired field maps, local blurring artifacts are specifically removed from individual STE DWIs and the estimated diffusion tensors have significantly improved spatial accuracy and larger fractional anisotropy. Conclusion Combined with the SNAILS acquisition scheme, our new method provides an integrated high-resolution short-TE DTI solution with inherent and dynamic correction for both motion-induced phase errors and off-resonance effects. PMID:23630029

  3. Biomedical ontologies: toward scientific debate.

    PubMed

    Maojo, V; Crespo, J; García-Remesal, M; de la Iglesia, D; Perez-Rey, D; Kulikowski, C

    2011-01-01

    Biomedical ontologies have been very successful in structuring knowledge for many different applications, receiving widespread praise for their utility and potential. Yet, the role of computational ontologies in scientific research, as opposed to knowledge management applications, has not been extensively discussed. We aim to stimulate further discussion on the advantages and challenges presented by biomedical ontologies from a scientific perspective. We review various aspects of biomedical ontologies going beyond their practical successes, and focus on some key scientific questions in two ways. First, we analyze and discuss current approaches to improve biomedical ontologies that are based largely on classical, Aristotelian ontological models of reality. Second, we raise various open questions about biomedical ontologies that require further research, analyzing in more detail those related to visual reasoning and spatial ontologies. We outline significant scientific issues that biomedical ontologies should consider, beyond current efforts of building practical consensus between them. For spatial ontologies, we suggest an approach for building "morphospatial" taxonomies, as an example that could stimulate research on fundamental open issues for biomedical ontologies. Analysis of a large number of problems with biomedical ontologies suggests that the field is very much open to alternative interpretations of current work, and in need of scientific debate and discussion that can lead to new ideas and research directions.

  4. Noninvasive MRI measurement of the absolute cerebral blood volume-cerebral blood flow relationship during visual stimulation in healthy humans.

    PubMed

    Ciris, Pelin Aksit; Qiu, Maolin; Constable, R Todd

    2014-09-01

    The relationship between cerebral blood volume (CBV) and cerebral blood flow (CBF) underlies blood oxygenation level-dependent functional MRI signal. This study investigates the potential for improved characterization of the CBV-CBF relationship in humans, and examines sex effects as well as spatial variations in the CBV-CBF relationship. Healthy subjects were imaged noninvasively at rest and during visual stimulation, constituting the first MRI measurement of the absolute CBV-CBF relationship in humans with complete coverage of the functional areas of interest. CBV and CBF estimates were consistent with the literature, and their relationship varied both spatially and with sex. In a region of interest with stimulus-induced activation in CBV and CBF at a significance level of the P < 0.05, a power function fit resulted in CBV = 2.1 CBF(0.32) across all subjects, CBV = 0.8 CBF(0.51) in females and CBV = 4.4 CBF(0.15) in males. Exponents decreased in both sexes as ROIs were expanded to include less significantly activated regions. Consideration for potential sex-related differences, as well as regional variations under a range of physiological states, may reconcile some of the variation across literature and advance our understanding of the underlying cerebrovascular physiology. Copyright © 2013 Wiley Periodicals, Inc.

  5. Parietal stimulation destabilizes spatial updating across saccadic eye movements.

    PubMed

    Morris, Adam P; Chambers, Christopher D; Mattingley, Jason B

    2007-05-22

    Saccadic eye movements cause sudden and global shifts in the retinal image. Rather than causing confusion, however, eye movements expand our sense of space and detail. In macaques, a stable representation of space is embodied by neural populations in intraparietal cortex that redistribute activity with each saccade to compensate for eye displacement, but little is known about equivalent updating mechanisms in humans. We combined noninvasive cortical stimulation with a double-step saccade task to examine the contribution of two human intraparietal areas to transsaccadic spatial updating. Right hemisphere stimulation over the posterior termination of the intraparietal sulcus (IPSp) broadened and shifted the distribution of second-saccade endpoints, but only when the first-saccade was directed into the contralateral hemifield. By interleaving trials with and without cortical stimulation, we show that the shift in endpoints was caused by an enduring effect of stimulation on neural functioning (e.g., modulation of neuronal gain). By varying the onset time of stimulation, we show that the representation of space in IPSp is updated immediately after the first-saccade. In contrast, stimulation of an adjacent IPS site had no such effects on second-saccades. These experiments suggest that stimulation of IPSp distorts an eye position or displacement signal that updates the representation of space at the completion of a saccade. Such sensory-motor integration in IPSp is crucial for the ongoing control of action, and may contribute to visual stability across saccades.

  6. Optical stimulation of the prostate nerves: A potential diagnostic technique

    NASA Astrophysics Data System (ADS)

    Tozburun, Serhat

    There is wide variability in sexual potency rates (9--86%) after nerve-sparing prostate cancer surgery due to limited knowledge of the location of the cavernous nerves (CN's) on the prostate surface, which are responsible for erectile function. Thus, preservation of the CN's is critical in preserving a man's ability to have spontaneous erections following surgery. Nerve-mapping devices, utilizing conventional Electrical Nerve Stimulation (ENS) techniques, have been used as intra-operative diagnostic tools to assist in preservation of the CN. However, these technologies have proven inconsistent and unreliable in identifying the CN's due to the need for physical contact, the lack of spatial selectivity, and the presence of electrical artifacts in measurements. Optical Nerve Stimulation (ONS), using pulsed infrared laser radiation, is studied as an alternative to ENS. The objective of this study is sevenfold: (1) to develop a laparoscopic laser probe for ONS of the CN's in a rat model, in vivo; (2) to demonstrate faster ONS using continuous-wave infrared laser radiation; (3) to describe and characterize the mechanism of successful ONS using alternative laser wavelengths; (4) to test a compact, inexpensive all-single-mode fiber configuration for optical stimulation of the rat CN studies; (5) to implement fiber optic beam shaping methods for comparison of Gaussian and flat-top spatial beam profiles during ONS; (6) to demonstrate successful ONS of CN's through a thin layer of fascia placed over the nerve and prostate gland; and (7) to verify the experimentally determined therapeutic window for safe and reliable ONS without thermal damage to the CN's by comparison with a computational model for thermal damage. A 5.5-Watt Thulium fiber laser operated at 1870 nm and two pigtailed, single mode, near-IR diode lasers (150-mW, 1455-nm laser and 500-mW, 1550-nm laser) were used for non-contact stimulation of the rat CN's. Successful laser stimulation, as measured by an intracavernous pressure (ICP) response in the penis, was achieved with the laser operating in CW mode. CW optical nerve stimulation provides a significantly faster ICP response time using a lower laser power laser than conventional pulsed stimulation. An all-single-mode fiber design was successfully tested in a rat model. The CN reached a threshold temperature of ˜ 42 °C, with response times as short as 3 s, and ICP responses in the rat penis of up to 50 mmHg compared to a baseline of 5--10 mmHg. Chemical etching of the distal single-mode-fiber tip produced a concave shape and transformed the Gaussian to a flat-top spatial beam profile, resulting in simplified alignment of the laser beam with the nerve. This novel, all-single-mode-fiber laser nerve stimulation system introduces several advantages including: (1) a less expensive and more compact ONS configuration; (2) elimination of alignment and cleaning bulk optical components; and (3) improved spatial beam profile for simplified alignment. For the fascia layers over the CN's (240--600 microm), the 1550 nm laser with an optical penetration depth of ˜ 930 microm in water was substituted for the 1455 nm laser. Successful ONS was achieved, for the first time, in fascia layers up to 450 microm thick which is critical for future clinical translation of this method for intra-operative identification and preservation of CN's during prostate cancer surgery. In order to define the upper limit of the therapeutic window for ONS of CN in a rat model, in vivo, identification of the thermal damage threshold for the CN after laser irradiation was investigated by direct comparison of the visible thermal damage data with a theoretical thermal damage calculation utilizing a standard Arrhenius integral model.

  7. Instrumentation to Record Evoked Potentials for Closed-Loop Control of Deep Brain Stimulation

    PubMed Central

    Kent, Alexander R.; Grill, Warren M.

    2012-01-01

    Closed-loop deep brain stimulation (DBS) systems offer promise in relieving the clinical burden of stimulus parameter selection and improving treatment outcomes. In such a system, a feedback signal is used to adjust automatically stimulation parameters and optimize the efficacy of stimulation. We explored the feasibility of recording electrically evoked compound action potentials (ECAPs) during DBS for use as a feedback control signal. A novel instrumentation system was developed to suppress the stimulus artifact and amplify the small magnitude, short latency ECAP response during DBS with clinically relevant parameters. In vitro testing demonstrated the capabilities to increase the gain by a factor of 1,000x over a conventional amplifier without saturation, reduce distortion of mock ECAP signals, and make high fidelity recordings of mock ECAPs at latencies of only 0.5 ms following DBS pulses of 50 to 100 μs duration. Subsequently, the instrumentation was used to make in vivo recordings of ECAPs during thalamic DBS in cats, without contamination by the stimulus artifact. The signal characteristics were similar across three experiments, suggesting common neural activation patterns. The ECAP recordings enabled with this novel instrumentation may provide insight into the type and spatial extent of neural elements activated during DBS, and could serve as feedback control signals for closed-loop systems. PMID:22255894

  8. New directions in the rational design of electrical and magnetic seizure therapies: individualized Low Amplitude Seizure Therapy (iLAST) and Magnetic Seizure Therapy (MST).

    PubMed

    Radman, Thomas; Lisanby, Sarah H

    2017-04-01

    Electroconvulsive therapy remains a key treatment option for severe cases of depression, but undesirable side-effects continue to limit its use. Innovations in the design of novel seizure therapies seek to improve its risk benefit ratio through enhanced control of the focality of stimulation. The design of seizure therapies with increased spatial precision is motivated by avoiding stimulation of deep brain structures implicated in memory retention, including the hippocampus. The development of two innovations in seizure therapy-individualized low-amplitude seizure therapy (iLAST) and magnetic seizure therapy (MST), are detailed. iLAST is a method of seizure titration involving reducing current spread in the brain by titrating current amplitude from the traditional fixed amplitudes. MST, which can be used in conjunction with iLAST dosing methods, involves the use of magnetic stimulation to reduce shunting and spreading of current by the scalp occurring during electrical stimulation. Evidence is presented on the rationale for increasing the focality of ECT in hopes of preserving its effectiveness, while reducing cognitive side-effects. Finally, the value of electric field and neural modelling is illustrated to explain observed clinical effects of modifications to ECT technique, and their utility in the rational design of the next generation of seizure therapies.

  9. Effects of Electrical Stimulation in the Inferior Colliculus on Frequency Discrimination by Rhesus Monkeys and Implications for the Auditory Midbrain Implant

    PubMed Central

    Ross, Deborah A.; Puñal, Vanessa M.; Agashe, Shruti; Dweck, Isaac; Mueller, Jerel; Grill, Warren M.; Wilson, Blake S.

    2016-01-01

    Understanding the relationship between the auditory selectivity of neurons and their contribution to perception is critical to the design of effective auditory brain prosthetics. These prosthetics seek to mimic natural activity patterns to achieve desired perceptual outcomes. We measured the contribution of inferior colliculus (IC) sites to perception using combined recording and electrical stimulation. Monkeys performed a frequency-based discrimination task, reporting whether a probe sound was higher or lower in frequency than a reference sound. Stimulation pulses were paired with the probe sound on 50% of trials (0.5–80 μA, 100–300 Hz, n = 172 IC locations in 3 rhesus monkeys). Electrical stimulation tended to bias the animals' judgments in a fashion that was coarsely but significantly correlated with the best frequency of the stimulation site compared with the reference frequency used in the task. Although there was considerable variability in the effects of stimulation (including impairments in performance and shifts in performance away from the direction predicted based on the site's response properties), the results indicate that stimulation of the IC can evoke percepts correlated with the frequency-tuning properties of the IC. Consistent with the implications of recent human studies, the main avenue for improvement for the auditory midbrain implant suggested by our findings is to increase the number and spatial extent of electrodes, to increase the size of the region that can be electrically activated, and to provide a greater range of evoked percepts. SIGNIFICANCE STATEMENT Patients with hearing loss stemming from causes that interrupt the auditory pathway after the cochlea need a brain prosthetic to restore hearing. Recently, prosthetic stimulation in the human inferior colliculus (IC) was evaluated in a clinical trial. Thus far, speech understanding was limited for the subjects and this limitation is thought to be partly due to challenges in harnessing the sound frequency representation in the IC. Here, we tested the effects of IC stimulation in monkeys trained to report the sound frequencies they heard. Our results indicate that the IC can be used to introduce a range of frequency percepts and suggest that placement of a greater number of electrode contacts may improve the effectiveness of such implants. PMID:27147659

  10. Chronic spatial working memory deficit associated with the superior longitudinal fasciculus: a study using voxel-based lesion-symptom mapping and intraoperative direct stimulation in right prefrontal glioma surgery.

    PubMed

    Kinoshita, Masashi; Nakajima, Riho; Shinohara, Harumichi; Miyashita, Katsuyoshi; Tanaka, Shingo; Okita, Hirokazu; Nakada, Mitsutoshi; Hayashi, Yutaka

    2016-10-01

    OBJECTIVE Although the right prefrontal region is regarded as a silent area, chronic deficits of the executive function, including working memory (WM), could occur after resection of a right prefrontal glioma. This may be overlooked by postoperative standard examinations, and the disabilities could affect the patient's professional life. The right prefrontal region is a part of the frontoparietal network and is subserved by the superior longitudinal fasciculus (SLF); however, the role of the SLF in spatial WM is unclear. This study investigated a persistent spatial WM deficit in patients who underwent right prefrontal glioma resection, and evaluated the relationship between the spatial WM deficit and the SLF. METHODS Spatial WM was examined in 24 patients who underwent prefrontal glioma resection (right, n = 14; left, n = 10) and in 14 healthy volunteers using a spatial 2-back task during the long-term postoperative period. The neural correlates of spatial WM were evaluated using lesion mapping and voxel-based lesion-symptom mapping. In addition, the spatial 2-back task was performed during surgery under direct subcortical electrical stimulation in 2 patients with right prefrontal gliomas. RESULTS Patients with a right prefrontal lesion had a significant chronic spatial WM deficit. Voxel-based lesion-symptom mapping analysis revealed a significant correlation between spatial WM deficit and the region that overlapped the first and second segments of the SLF (SLF I and SLF II). Two patients underwent awake surgery and had difficulties providing the correct responses in the spatial 2-back task with direct subcortical electrical stimulation on the SLF I, which was preserved and confirmed by postoperative diffusion tensor imaging tractography. These patients exhibited no spatial WM deficits during the postoperative immediate and long-term periods. CONCLUSIONS Spatial WM deficits may persist in patients who undergo resection of the tumor located in the right prefrontal brain parenchyma. Injury to the dorsal frontoparietal subcortical white matter pathway, i.e., the SLF I or SLF I and II, could play a causal role in this chronic deficit. A persistent spatial WM deficit, without motor and language deficits, could affect the professional life of the patient. In such cases, awake surgery would be useful to detect the spatial WM network with appropriate task during tumor exploration.

  11. Threshold and channel interaction in cochlear implant users: evaluation of the tripolar electrode configuration.

    PubMed

    Bierer, Julie Arenberg

    2007-03-01

    The efficacy of cochlear implants is limited by spatial and temporal interactions among channels. This study explores the spatially restricted tripolar electrode configuration and compares it to bipolar and monopolar stimulation. Measures of threshold and channel interaction were obtained from nine subjects implanted with the Clarion HiFocus-I electrode array. Stimuli were biphasic pulses delivered at 1020 pulses/s. Threshold increased from monopolar to bipolar to tripolar stimulation and was most variable across channels with the tripolar configuration. Channel interaction, quantified by the shift in threshold between single- and two-channel stimulation, occurred for all three configurations but was largest for the monopolar and simultaneous conditions. The threshold shifts with simultaneous tripolar stimulation were slightly smaller than with bipolar and were not as strongly affected by the timing of the two channel stimulation as was monopolar. The subjects' performances on clinical speech tests were correlated with channel-to-channel variability in tripolar threshold, such that greater variability was related to poorer performance. The data suggest that tripolar channels with high thresholds may reveal cochlear regions of low neuron survival or poor electrode placement.

  12. Multidimensionally encoded magnetic resonance imaging.

    PubMed

    Lin, Fa-Hsuan

    2013-07-01

    Magnetic resonance imaging (MRI) typically achieves spatial encoding by measuring the projection of a q-dimensional object over q-dimensional spatial bases created by linear spatial encoding magnetic fields (SEMs). Recently, imaging strategies using nonlinear SEMs have demonstrated potential advantages for reconstructing images with higher spatiotemporal resolution and reducing peripheral nerve stimulation. In practice, nonlinear SEMs and linear SEMs can be used jointly to further improve the image reconstruction performance. Here, we propose the multidimensionally encoded (MDE) MRI to map a q-dimensional object onto a p-dimensional encoding space where p > q. MDE MRI is a theoretical framework linking imaging strategies using linear and nonlinear SEMs. Using a system of eight surface SEM coils with an eight-channel radiofrequency coil array, we demonstrate the five-dimensional MDE MRI for a two-dimensional object as a further generalization of PatLoc imaging and O-space imaging. We also present a method of optimizing spatial bases in MDE MRI. Results show that MDE MRI with a higher dimensional encoding space can reconstruct images more efficiently and with a smaller reconstruction error when the k-space sampling distribution and the number of samples are controlled. Copyright © 2012 Wiley Periodicals, Inc.

  13. Life-long environmental enrichment counteracts spatial learning, reference and working memory deficits in middle-aged rats subjected to perinatal asphyxia

    PubMed Central

    Galeano, Pablo; Blanco, Eduardo; Logica Tornatore, Tamara M. A.; Romero, Juan I.; Holubiec, Mariana I.; Rodríguez de Fonseca, Fernando; Capani, Francisco

    2015-01-01

    Continuous environmental stimulation induced by exposure to enriched environment (EE) has yielded cognitive benefits in different models of brain injury. Perinatal asphyxia results from a lack of oxygen supply to the fetus and is associated with long-lasting neurological deficits. However, the effects of EE in middle-aged rats suffering perinatal asphyxia are unknown. Therefore, the aim of the present study was to assess whether life-long exposure to EE could counteract the cognitive and behavioral alterations in middle-aged asphyctic rats. Experimental groups consisted of rats born vaginally (CTL), by cesarean section (C+), or by C+ following 19 min of asphyxia at birth (PA). At weaning, rats were assigned to standard (SE) or enriched environment (EE) for 18 months. During the last month of housing, animals were submitted to a behavioral test battery including Elevated Plus Maze, Open Field, Novel Object Recognition and Morris water maze (MWM). Results showed that middle-aged asphyctic rats, reared in SE, exhibited an impaired performance in the spatial reference and working memory versions of the MWM. EE was able to counteract these cognitive impairments. Moreover, EE improved the spatial learning performance of middle-aged CTL and C+ rats. On the other hand, all groups reared in SE did not differ in locomotor activity and anxiety levels, while EE reduced locomotion and anxiety, regardless of birth condition. Recognition memory was altered neither by birth condition nor by housing environment. These results support the importance of environmental stimulation across the lifespan to prevent cognitive deficits induced by perinatal asphyxia. PMID:25601829

  14. Electrophysiological correlates of stimulus-driven reorienting deficits after interference with right parietal cortex during a spatial attention task: a TMS-EEG study

    PubMed Central

    Capotosto, Paolo; Corbetta, Maurizio; Romani, Gian Luca; Babiloni, Claudio

    2013-01-01

    Transcranial magnetic stimulation (TMS) interference over right intraparietal sulcus (IPS) causally disrupts behaviorally and electroencephalographic (EEG) rhythmic correlates of endogenous spatial orienting prior to visual target presentation (Capotosto et al. 2009; 2011). Here we combine data from our previous studies to examine whether right parietal TMS during spatial orienting also impairs stimulus-driven re-orienting or the ability to efficiently process unattended stimuli, i.e. stimuli outside the current focus of attention. Healthy subjects (N=24) performed a Posner spatial cueing task while their EEG activity was being monitored. Repetitive TMS (rTMS) was applied for 150 milliseconds (ms) simultaneously to the presentation of a central arrow directing spatial attention to the location of an upcoming visual target. Right IPS-rTMS impaired target detection, especially for stimuli presented at unattended locations; it also caused a modulation of the amplitude of parieto-occipital positive ERPs peaking at about 480 ms (P3) post-target. The P3 significantly decreased for unattended targets, and significantly increased for attended targets after right IPS-rTMS as compared to Sham stimulation. Similar effects were obtained for left IPS stimulation albeit in a smaller group of subjects. We conclude that disruption of anticipatory processes in right IPS has prolonged effects that persist during target processing. The P3 decrement may reflect interference with post-decision processes that are part of stimulus-driven re-orienting. Right IPS is a node of functional interaction between endogenous spatial orienting and stimulus-driven re-orienting processes in human vision. PMID:22905824

  15. Negative/positive chemotaxis of a droplet: Dynamic response to a stimulant gas

    NASA Astrophysics Data System (ADS)

    Sakuta, Hiroki; Magome, Nobuyuki; Mori, Yoshihito; Yoshikawa, Kenichi

    2016-05-01

    We report here the repulsive/attractive motion of an oil droplet floating on an aqueous phase caused by the application of a stimulant gas. A cm-sized droplet of oleic acid is repelled by ammonia vapor. In contrast, a droplet of aniline on an aqueous phase moves toward hydrochloric acid as a stimulant. The mechanisms of these characteristic behaviors of oil droplets are discussed in terms of the spatial gradient of the interfacial tension caused by the stimulant gas.

  16. Photovoltaic restoration of sight with high visual acuity

    PubMed Central

    Lorach, Henri; Goetz, Georges; Smith, Richard; Lei, Xin; Mandel, Yossi; Kamins, Theodore; Mathieson, Keith; Huie, Philip; Harris, James; Sher, Alexander; Palanker, Daniel

    2015-01-01

    Patients with retinal degeneration lose sight due to gradual demise of photoreceptors. Electrical stimulation of the surviving retinal neurons provides an alternative route for delivery of visual information. We demonstrate that subretinal arrays with 70 μm photovoltaic pixels provide highly localized stimulation, with electrical and visual receptive fields of comparable sizes in rat retinal ganglion cells. Similarly to normal vision, retinal response to prosthetic stimulation exhibits flicker fusion at high frequencies, adaptation to static images and non-linear spatial summation. In rats with retinal degeneration, these photovoltaic arrays provide spatial resolution of 64 ± 11 μm, corresponding to half of the normal visual acuity in pigmented rats. Ease of implantation of these wireless and modular arrays, combined with their high resolution opens the door to functional restoration of sight. PMID:25915832

  17. 3D finite element modeling of epiretinal stimulation: Impact of prosthetic electrode size and distance from the retina.

    PubMed

    Sui, Xiaohong; Huang, Yu; Feng, Fuchen; Huang, Chenhui; Chan, Leanne Lai Hang; Wang, Guoxing

    2015-05-01

    A novel 3-dimensional (3D) finite element model was established to systematically investigate the impact of the diameter (Φ) of disc electrodes and the electrode-to-retina distance on the effectiveness of stimulation. The 3D finite element model was established based on a disc platinum stimulating electrode and a 6-layered retinal structure. The ground electrode was placed in the extraocular space in direct attachment with sclera and treated as a distant return electrode. An established criterion of electric-field strength of 1000 Vm-1 was adopted as the activation threshold for RGCs. The threshold current (TC) increased linearly with increasing Φ and electrode-to-retina distance and remained almost unchanged with further increases in diameter. However, the threshold charge density (TCD) increased dramatically with decreasing electrode diameter. TCD exceeded the electrode safety limit for an electrode diameter of 50 µm at an electrode-to-retina distance of 50 to 200 μm. The electric field distributions illustrated that smaller electrode diameters and shorter electrode-to-retina distances were preferred due to more localized excitation of RGC area under stimulation of different threshold currents in terms of varied electrode size and electrode-to-retina distances. Under the condition of same-amplitude current stimulation, a large electrode exhibited an improved potential spatial selectivity at large electrode-to-retina distances. Modeling results were consistent with those reported in animal electrophysiological experiments and clinical trials, validating the 3D finite element model of epiretinal stimulation. The computational model proved to be useful in optimizing the design of an epiretinal stimulating electrode for prosthesis.

  18. Abnormal hemodynamic response to forepaw stimulation in rat brain after cocaine injection

    NASA Astrophysics Data System (ADS)

    Chen, Wei; Park, Kicheon; Choi, Jeonghun; Pan, Yingtian; Du, Congwu

    2015-03-01

    Simultaneous measurement of hemodynamics is of great importance to evaluate the brain functional changes induced by brain diseases such as drug addiction. Previously, we developed a multimodal-imaging platform (OFI) which combined laser speckle contrast imaging with multi-wavelength imaging to simultaneously characterize the changes in cerebral blood flow (CBF), oxygenated- and deoxygenated- hemoglobin (HbO and HbR) from animal brain. Recently, we upgraded our OFI system that enables detection of hemodynamic changes in response to forepaw electrical stimulation to study potential brain activity changes elicited by cocaine. The improvement includes 1) high sensitivity to detect the cortical response to single forepaw electrical stimulation; 2) high temporal resolution (i.e., 16Hz/channel) to resolve dynamic variations in drug-delivery study; 3) high spatial resolution to separate the stimulation-evoked hemodynamic changes in vascular compartments from those in tissue. The system was validated by imaging the hemodynamic responses to the forepaw-stimulations in the somatosensory cortex of cocaine-treated rats. The stimulations and acquisitions were conducted every 2min over 40min, i.e., from 10min before (baseline) to 30min after cocaine challenge. Our results show that the HbO response decreased first (at ~4min) followed by the decrease of HbR response (at ~6min) after cocaine, and both did not fully recovered for over 30min. Interestingly, while CBF decreased at 4min, it partially recovered at 18min after cocaine administration. The results indicate the heterogeneity of cocaine's effects on vasculature and tissue metabolism, demonstrating the unique capability of optical imaging for brain functional studies.

  19. Observations of Ocean Primary Productivity Using MODIS

    NASA Technical Reports Server (NTRS)

    Esaias, Wayne E.; Abbott, Mark R.; Koblinsky, Chester J. (Technical Monitor)

    2001-01-01

    Measuring the magnitude and variability of oceanic net primary productivity (NPP) represents a key advancement toward our understanding of the dynamics of marine ecosystems and the role of the ocean in the global carbon cycle. MODIS observations make two new contributions in addition to continuing the bio-optical time series begun with Orbview-2's SeaWiFS sensor. First, MODIS provides weekly estimates of global ocean net primary productivity on weekly and annual time periods, and annual empirical estimates of carbon export production. Second, MODIS provides additional insight into the spatial and temporal variations in photosynthetic efficiency through the direct measurements of solar-stimulated chlorophyll fluorescence. The two different weekly productivity indexes (first developed by Behrenfeld & Falkowski and by Yoder, Ryan and Howard) are used to derive daily productivity as a function of chlorophyll biomass, incident daily surface irradiance, temperature, euphotic depth, and mixed layer depth. Comparisons between these two estimates using both SeaWiFS and MODIS data show significant model differences in spatial distribution after allowance for the different integration depths. Both estimates are strongly dependence on the accuracy of the chlorophyll determination. In addition, an empirical approach is taken on annual scales to estimate global NPP and export production. Estimates of solar stimulated fluorescence efficiency from chlorophyll have been shown to be inversely related to photosynthetic efficiency by Abbott and co-workers. MODIS provides the first global estimates of oceanic chlorophyll fluorescence, providing an important proof of concept. MODIS observations are revealing spatial patterns of fluorescence efficiency which show expected variations with phytoplankton photo-physiological parameters as measured during in-situ surveys. This has opened the way for research into utilizing this information to improve our understanding of oceanic NPP variability. Deriving the ocean bio-optical properties places severe demands on instrument performance (especially band to band precision) and atmospheric correction. Improvements in MODIS instrument characterization and calibration over the first 16 mission months have greatly improved the accuracy of the chlorophyll input fields and FLH, and therefore the estimates of NPP and fluorescence efficiency. Annual estimates now show the oceanic NPP accounts for 40-50% of the global total NPP, with significant interannual variations related to large scale ocean processes. Spatial variations in ocean NPP, and exported production, have significant effects on exchange of CO2 between the ocean and atmosphere. Further work is underway to improve both the primary productivity model functions, and to refine our understanding of the relationships between fluorescence efficiency and NPP estimates. We expect that the MODIS instruments will prove extremely useful in assessing the time dependencies of oceanic carbon uptake and effects of iron enrichment, within the global carbon cycle.

  20. Selective attention within the foveola.

    PubMed

    Poletti, Martina; Rucci, Michele; Carrasco, Marisa

    2017-10-01

    Efficient control of attentional resources and high-acuity vision are both fundamental for survival. Shifts in visual attention are known to covertly enhance processing at locations away from the center of gaze, where visual resolution is low. It is unknown, however, whether selective spatial attention operates where the observer is already looking-that is, within the high-acuity foveola, the small yet disproportionally important rod-free region of the retina. Using new methods for precisely controlling retinal stimulation, here we show that covert attention flexibly improves and speeds up both detection and discrimination at loci only a fraction of a degree apart within the foveola. These findings reveal a surprisingly precise control of attention and its involvement in fine spatial vision. They show that the commonly studied covert shifts of attention away from the fovea are the expression of a global mechanism that exerts its action across the entire visual field.

  1. Selective attention within the foveola

    PubMed Central

    Poletti, Martina; Rucci, Michele; Carrasco, Marisa

    2018-01-01

    Efficient control of attentional resources and high-acuity vision are both fundamental for survival. Shifts in visual attention are known to covertly enhance processing at locations away from the center of gaze, where visual resolution is low. It is unknown, however, whether selective spatial attention operates where the observer already looks, i.e., within the high-acuity foveola, the small, yet disproportionally important rod-free region of the retina. Using new methods for precisely controlling retinal stimulation, here we show that covert attention flexibly improves and speeds-up both detection and discrimination at loci only a fraction of a degree apart within the foveola. These findings reveal a surprisingly precise control of attention and its involvement in fine spatial vision. They show that the commonly studied covert shifts of attention away from the fovea are the expression of a global mechanism that exerts its action across the entire visual field. PMID:28805816

  2. Binaural enhancement for bilateral cochlear implant users.

    PubMed

    Brown, Christopher A

    2014-01-01

    Bilateral cochlear implant (BCI) users receive limited binaural cues and, thus, show little improvement to speech intelligibility from spatial cues. The feasibility of a method for enhancing the binaural cues available to BCI users is investigated. This involved extending interaural differences of levels, which typically are restricted to high frequencies, into the low-frequency region. Speech intelligibility was measured in BCI users listening over headphones and with direct stimulation, with a target talker presented to one side of the head in the presence of a masker talker on the other side. Spatial separation was achieved by applying either naturally occurring binaural cues or enhanced cues. In this listening configuration, BCI patients showed greater speech intelligibility with the enhanced binaural cues than with naturally occurring binaural cues. In some situations, it is possible for BCI users to achieve greater speech intelligibility when binaural cues are enhanced by applying interaural differences of levels in the low-frequency region.

  3. LTP saturation and spatial learning disruption: effects of task variables and saturation levels.

    PubMed

    Barnes, C A; Jung, M W; McNaughton, B L; Korol, D L; Andreasson, K; Worley, P F

    1994-10-01

    The prediction that "saturation" of LTP/LTE at hippocampal synapses should impair spatial learning was reinvestigated in the light of a more specific consideration of the theory of Hebbian associative networks, which predicts a nonlinear relationship between LTP "saturation" and memory impairment. This nonlinearity may explain the variable results of studies that have addressed the effects of LTP "saturation" on behavior. The extent of LTP "saturation" in fascia dentata produced by the standard chronic LTP stimulation protocol was assessed both electrophysiologically and through the use of an anatomical marker (activation of the immediate-early gene zif268). Both methods point to the conclusion that the standard protocols used to induce LTP do not "saturate" the process at any dorsoventral level, and leave the ventral half of the hippocampus virtually unaffected. LTP-inducing, bilateral perforant path stimulation led to a significant deficit in the reversal of a well-learned spatial response on the Barnes circular platform task as reported previously, yet in the same animals produced no deficit in learning the Morris water task (for which previous results have been conflicting). The behavioral deficit was not a consequence of any after-discharge in the hippocampal EEG. In contrast, administration of maximal electroconvulsive shock led to robust zif268 activation throughout the hippocampus, enhancement of synaptic responses, occlusion of LTP produced by discrete high-frequency stimulation, and spatial learning deficits in the water task. These data provide further support for the involvement of LTP-like synaptic enhancement in spatial learning.

  4. Amygdala stimulation promotes recovery of behavioral performance in a spatial memory task and increases GAP-43 and MAP-2 in the hippocampus and prefrontal cortex of male rats.

    PubMed

    Mercerón-Martínez, D; Almaguer-Melian, W; Alberti-Amador, E; Bergado, J A

    2018-06-19

    The relationships between affective and cognitive processes are an important issue of present neuroscience. The amygdala, the hippocampus and the prefrontal cortex appear as main players in these mechanisms. We have shown that post-training electrical stimulation of the basolateral amygdala (BLA) speeds the acquisition of a motor skill, and produces a recovery in behavioral performance related to spatial memory in fimbria-fornix (FF) lesioned animals. BLA electrical stimulation rises bdnf RNA expression, BDNF protein levels, and arc RNA expression in the hippocampus. In the present paper we have measured the levels of one presynaptic protein (GAP-43) and one postsynaptic protein (MAP-2) both involved in synaptogenesis to assess whether structural neuroplastic mechanisms are involved in the memory enhancing effects of BLA stimulation. A single train of BLA stimulation produced in healthy animals an increase in the levels of GAP-43 and MAP-2 that lasted days in the hippocampus and the prefrontal cortex. In FF-lesioned rats, daily post-training stimulation of the BLA ameliorates the memory deficit of the animals and induces an increase in the level of both proteins. These results support the hypothesis that the effects of amygdala stimulation on memory recovery are sustained by an enhanced formation of new synapses. Copyright © 2018. Published by Elsevier Inc.

  5. Beyond the random phase approximation: Stimulated Brillouin backscatter for finite laser coherence times

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Korotkevich, Alexander O.; Lushnikov, Pavel M., E-mail: plushnik@math.unm.edu; Landau Institute for Theoretical Physics, 2 Kosygin Str., Moscow 119334

    2015-01-15

    We developed a linear theory of backward stimulated Brillouin scatter (BSBS) of a spatially and temporally random laser beam relevant for laser fusion. Our analysis reveals a new collective regime of BSBS (CBSBS). Its intensity threshold is controlled by diffraction, once cT{sub c} exceeds a laser speckle length, with T{sub c} the laser coherence time. The BSBS spatial gain rate is approximately the sum of that due to CBSBS, and a part which is independent of diffraction and varies linearly with T{sub c}. The CBSBS spatial gain rate may be reduced significantly by the temporal bandwidth of KrF-based laser systemsmore » compared to the bandwidth currently available to temporally smoothed glass-based laser systems.« less

  6. Development of optics with micro-LED arrays for improved opto-electronic neural stimulation

    NASA Astrophysics Data System (ADS)

    Chaudet, Lionel; Neil, Mark; Degenaar, Patrick; Mehran, Kamyar; Berlinguer-Palmini, Rolando; Corbet, Brian; Maaskant, Pleun; Rogerson, David; Lanigan, Peter; Bamberg, Ernst; Roska, Botond

    2013-03-01

    The breakthrough discovery of a nanoscale optically gated ion channel protein, Channelrhodopsin 2 (ChR2), and its combination with a genetically expressed ion pump, Halorhodopsin, allowed the direct stimulation and inhibition of individual action potentials with light alone. This work reports developments of ultra-bright elec­ tronically controlled optical array sources with enhanced light gated ion channels and pumps for use in systems to further our understanding of both brain and visual function. This work is undertaken as part of the European project, OptoNeuro. Micro-LED arrays permit spatio-temporal control of neuron stimulation on sub-millisecond timescales. However they are disadvantaged by their broad spatial light emission distribution and low fill factor. We present the design and implementation of a projection and micro-optics system for use with a micro-LED array consisting of a 16x16 matrix of 25 μm diameter micro-LEDs with 150 μm centre-to-centre spacing and an emission spectrum centred at 470 nm overlapping the peak sensitivity of ChR2 and its testing on biological samples. The projection system images the micro-LED array onto micro-optics to improve the fill-factor from ~2% to more than 78% by capturing a larger fraction of the LED emission and directing it correctly to the sample plane. This approach allows low fill factor arrays to be used effectively, which in turn has benefits in terms of thermal management and electrical drive from CMOS backplane electronics. The entire projection system is integrated into a microscope prototype to provide stimulation spots at the same size as the neuron cell body (μ10 pm).

  7. Model of diffusion-assisted direct laser writing by means of nanopolymerization in the presence of radical quencher

    NASA Astrophysics Data System (ADS)

    Pikulin, Alexander; Bityurin, Nikita; Sokolov, Viktor I.

    2015-12-01

    Diffusion-assisted direct laser writing (DA-DLW) by multiphoton polymerization has been recently shown to be one of the most promising methods for the high-resolution 3D nanofabrication [I. Sakellari, et al., ACS Nano 6, 2302 (2012)]. The improvement of the writing spatial resolution has been observed under certain conditions when the mobile radical quencher (polymerization inhibitor) is added to the photosensitive composition. In this work, we present a theoretical study of this method, focusing on the resolution capabilities and optimal writing parameters. The laser beam absorption in the polymerizable composition causes the localized depletion of the quencher molecules. If the quencher depletion is balanced by its diffusion from the outside of the focal volume, the quasi-stationary non-equillibrium concentration spatial profile with zero minimum can be obtained. The polymer is then effectively formed only in the domain where the quencher is depleted. The spatially-distributed quencher, in this case, has the effect similar to that of the vortex beam in STimulated Emission Microscopy (STED).

  8. Using a high spatial resolution tactile sensor for intention detection.

    PubMed

    Castellini, Claudio; Koiva, Risto

    2013-06-01

    Intention detection is the interpretation of biological signals with the aim of automatically, reliably and naturally understanding what a human subject desires to do. Although intention detection is not restricted to disabled people, such methods can be crucial in improving a patient's life, e.g., aiding control of a robotic wheelchair or of a self-powered prosthesis. Traditionally, intention detection is done using, e.g., gaze tracking, surface electromyography and electroencephalography. In this paper we present exciting initial results of an experiment aimed at intention detection using a high-spatial-resolution, high-dynamic-range tactile sensor. The tactile image of the ventral side of the forearm of 9 able-bodied participants was recorded during a variable-force task stimulated at the fingertip. Both the forces at the fingertip and at the forearm were synchronously recorded. We show that a standard dimensionality reduction technique (Principal Component Analysis) plus a Support Vector Machine attain almost perfect detection accuracy of the direction and the intensity of the intended force. This paves the way for high spatial resolution tactile sensors to be used as a means for intention detection.

  9. Model of diffusion-assisted direct laser writing by means of nanopolymerization in the presence of radical quencher

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pikulin, Alexander, E-mail: pikulin@ufp.appl.sci-nnov.ru; Bityurin, Nikita; Institute of Applied Physics of Russian Academy of Sciences, 46, Ul’yanov Str., Nizhniy Novgorod, 603950

    Diffusion-assisted direct laser writing (DA-DLW) by multiphoton polymerization has been recently shown to be one of the most promising methods for the high-resolution 3D nanofabrication [I. Sakellari, et al., ACS Nano 6, 2302 (2012)]. The improvement of the writing spatial resolution has been observed under certain conditions when the mobile radical quencher (polymerization inhibitor) is added to the photosensitive composition. In this work, we present a theoretical study of this method, focusing on the resolution capabilities and optimal writing parameters. The laser beam absorption in the polymerizable composition causes the localized depletion of the quencher molecules. If the quencher depletionmore » is balanced by its diffusion from the outside of the focal volume, the quasi-stationary non-equillibrium concentration spatial profile with zero minimum can be obtained. The polymer is then effectively formed only in the domain where the quencher is depleted. The spatially-distributed quencher, in this case, has the effect similar to that of the vortex beam in STimulated Emission Microscopy (STED)« less

  10. Uses of virtual reality for diagnosis, rehabilitation and study of unilateral spatial neglect: review and analysis.

    PubMed

    Tsirlin, Inna; Dupierrix, Eve; Chokron, Sylvie; Coquillart, Sabine; Ohlmann, Theophile

    2009-04-01

    Unilateral spatial neglect is a disabling condition frequently occurring after stroke. People with neglect suffer from various spatial deficits in several modalities, which in many cases impair everyday functioning. A successful treatment is yet to be found. Several techniques have been proposed in the last decades, but only a few showed long-lasting effects and none could completely rehabilitate the condition. Diagnostic methods of neglect could be improved as well. The disorder is normally diagnosed with pen-and-paper methods, which generally do not assess patients in everyday tasks and do not address some forms of the disorder. Recently, promising new methods based on virtual reality have emerged. Virtual reality technologies hold great opportunities for the development of effective assessment and treatment techniques for neglect because they provide rich, multimodal, and highly controllable environments. In order to stimulate advancements in this domain, we present a review and an analysis of the current work. We describe past and ongoing research of virtual reality applications for unilateral neglect and discuss the existing problems and new directions for development.

  11. Seismically active volume not a good indicator of the stimulated reservoir: evidence from Paralana

    NASA Astrophysics Data System (ADS)

    Riffault, J.; Dempsey, D. E.; Karra, S.; Archer, R.

    2017-12-01

    Hydraulic stimulation is routinely carried out in EGS projects in order to engineer the geothermal reservoir, triggering large amounts of seismicity. There is broad consensus that hydroshearing, the shear failure of existing fractures caused by pore pressure increasing above a critical value, is the mechanism primarily responsible for the seismicity. It is also often assumed to be the primary mechanism behind permeability enhancement and thus reservoir creation, although several other physical processes, such as thermal and chemical effects, and tensile failure, can also contribute. An extension of this assumption is that the seismically active volume reflects the extent of the stimulated reservoir. This may not always be the case. Hydraulic stimulation aims to improve injectivity, which we define as the ratio of injection rate to wellhead pressure. During the Paralana-2 EGS stimulation, undertaken in South Australia in 2011, injectivity increased linearly over time, implying permeability enhancement. Concurrently, 4754 micro-earthquakes were detected and located. We have spatially averaged hypocentre positions in order to image the spatio-temporally evolving seismicity cloud and its main features. Using an established correlation from a previous EGS experiment, we use hypocentre density as a proxy measure of pore pressure increase. Knowing then how pressure and injectivity evolve over time, we develop an inversion procedure based on reservoir simulation to infer how permeability has evolved around the well. Our results indicate that, although there is significant permeability enhancement close to the wellbore, this is largely uncoupled from the seismically active volume that extends much further away. In other words, for the Paralana stimulation, the seismicity cloud is a poor indicator of the stimulated reservoir volume. It further implies that hydroshearing itself is not the main cause of permeability enhancement at Paralana. Our study suggests that past stimulations may need to be revisited and a stronger case made for estimates of the stimulated reservoir.

  12. Non-invasive cortical stimulation improves post-stroke attention decline.

    PubMed

    Kang, Eun Kyoung; Baek, Min Jae; Kim, Sangyun; Paik, Nam-Jong

    2009-01-01

    Attention decline after stroke is common and hampers the rehabilitation process, and non-invasive transcranial direct current stimulation (tDCS) has the potential to elicit behavioral changes by modulating cortical excitability. The authors tested the hypothesis that a single session of non-invasive cortical stimulation with excitatory anodal tDCS applied to the left dorsolateral prefrontal cortex (DLPFC) can improve attention in stroke patients. Ten patients with post-stroke cognitive decline (MMSE 25) and 10 age-matched healthy controls participated in this double blind, sham-controlled, crossover study involving the administration of real (2 mA for 20 min) or sham stimulation (2 mA for 1 min) to the left DLPFC. Attention was measured using a computerized Go/No-Go test before and after intervention. Improvements in accuracy and speed after stimulation relative to baseline were compared for real and sham stimulations. In healthy controls, no significant improvement in Go/No-Go test was observed after either real or sham stimulation. However, in stroke patients, tDCS led to a significant improvement in response accuracy at 1 hour post-stimulation relative to baseline, and this improvement was maintained until 3 hours post-stimulation (P< 0.05), whereas sham stimulation did not lead to a significant improvement in response accuracy (P> 0.05). Changes in reaction times were comparable for the two stimulations (P> 0.05). Non invasive anodal tDCS applied to the left DLPFC was found to improve attention versus sham stimulation in stroke patients, which suggests that non-invasive cortical intervention could potentially be used during rehabilitative training to improve attention.

  13. Postmortem diffusion MRI of the human brainstem and thalamus for deep brain stimulator electrode localization

    PubMed Central

    Calabrese, Evan; Hickey, Patrick; Hulette, Christine; Zhang, Jingxian; Parente, Beth; Lad, Shivanand P.; Johnson, G. Allan

    2015-01-01

    Deep brain stimulation (DBS) is an established surgical therapy for medically refractory tremor disorders including essential tremor (ET) and is currently under investigation for use in a variety of other neurologic and psychiatric disorders. There is growing evidence that the anti-tremor effects of DBS for ET are directly related to modulation of the dentatorubrothalamic tract (DRT), a white matter pathway that connects the cerebellum, red nucleus, and ventral intermediate nucleus of the thalamus. Emerging white matter targets for DBS, like the DRT, will require improved 3D reference maps of deep brain anatomy and structural connectivity for accurate electrode targeting. High-resolution diffusion MRI of postmortem brain specimens can provide detailed volumetric images of important deep brain nuclei and 3D reconstructions of white matter pathways with probabilistic tractography techniques. We present a high spatial and angular resolution diffusion MRI template of the postmortem human brainstem and thalamus with 3D reconstructions of the nuclei and white matter tracts involved in ET circuitry. We demonstrate accurate registration of these data to in vivo, clinical images from patients receiving DBS therapy, and correlate electrode proximity to tractography of the DRT with improvement of ET symptoms. PMID:26043869

  14. Translational Rodent Models of Korsakoff Syndrome Reveal the Critical Neuroanatomical Substrates of Memory Dysfunction and Recovery

    PubMed Central

    Hall, Joseph M.; Resende, Leticia S.

    2016-01-01

    Investigation of the amnesic disorder Korsakoff Syndrome (KS) has been vital in elucidating the critical brain regions involved in learning and memory. Although the thalamus and mammillary bodies are the primary sites of neuropathology in KS, functional deactivation of the hippocampus and certain cortical regions also contributes to the chronic cognitive dysfunction reported in KS. The rodent pyrithiamine-induced thiamine deficiency (PTD) model has been used to study the extent of hippocampal and cortical neuroadaptations in KS. In the PTD model, the hippocampus, frontal and retrosplenial cortical regions display loss of cholinergic innervation, decreases in behaviorally stimulated acetylcholine release and reductions in neurotrophins. While PTD treatment results in significant impairment in measures of spatial learning and memory, other cognitive processes are left intact and may be recruited to improve cognitive outcome. In addition, behavioral recovery can be stimulated in the PTD model by increasing acetylcholine levels in the medial septum, hippocampus and frontal cortex, but not in the retrosplenial cortex. These data indicate that although the hippocampus and frontal cortex are involved in the pathogenesis of KS, these regions retain neuroplasticity and may be critical targets for improving cognitive outcome in KS. PMID:22528861

  15. Translational rodent models of Korsakoff syndrome reveal the critical neuroanatomical substrates of memory dysfunction and recovery.

    PubMed

    Savage, Lisa M; Hall, Joseph M; Resende, Leticia S

    2012-06-01

    Investigation of the amnesic disorder Korsakoff Syndrome (KS) has been vital in elucidating the critical brain regions involved in learning and memory. Although the thalamus and mammillary bodies are the primary sites of neuropathology in KS, functional deactivation of the hippocampus and certain cortical regions also contributes to the chronic cognitive dysfunction reported in KS. The rodent pyrithiamine-induced thiamine deficiency (PTD) model has been used to study the extent of hippocampal and cortical neuroadaptations in KS. In the PTD model, the hippocampus, frontal and retrosplenial cortical regions display loss of cholinergic innervation, decreases in behaviorally stimulated acetylcholine release and reductions in neurotrophins. While PTD treatment results in significant impairment in measures of spatial learning and memory, other cognitive processes are left intact and may be recruited to improve cognitive outcome. In addition, behavioral recovery can be stimulated in the PTD model by increasing acetylcholine levels in the medial septum, hippocampus and frontal cortex, but not in the retrosplenial cortex. These data indicate that although the hippocampus and frontal cortex are involved in the pathogenesis of KS, these regions retain neuroplasticity and may be critical targets for improving cognitive outcome in KS.

  16. Spatial Object Recognition Enables Endogenous LTD that Curtails LTP in the Mouse Hippocampus

    PubMed Central

    Goh, Jinzhong Jeremy

    2013-01-01

    Although synaptic plasticity is believed to comprise the cellular substrate for learning and memory, limited direct evidence exists that hippocampus-dependent learning actually triggers synaptic plasticity. It is likely, however, that long-term potentiation (LTP) works in concert with its counterpart, long-term depression (LTD) in the creation of spatial memory. It has been reported in rats that weak synaptic plasticity is facilitated into persistent plasticity if afferent stimulation is coupled with a novel spatial learning event. It is not known if this phenomenon also occurs in other species. We recorded from the hippocampal CA1 of freely behaving mice and observed that novel spatial learning triggers endogenous LTD. Specifically, we observed that LTD is enabled when test-pulse afferent stimulation is given during the learning of object constellations or during a spatial object recognition task. Intriguingly, LTP is significantly impaired by the same tasks, suggesting that LTD is the main cellular substrate for this type of learning. These data indicate that learning-facilitated plasticity is not exclusive to rats and that spatial learning leads to endogenous LTD in the hippocampus, suggesting an important role for this type of synaptic plasticity in the creation of hippocampus-dependent memory. PMID:22510536

  17. Using 3D spatial correlations to improve the noise robustness of multi component analysis of 3D multi echo quantitative T2 relaxometry data.

    PubMed

    Kumar, Dushyant; Hariharan, Hari; Faizy, Tobias D; Borchert, Patrick; Siemonsen, Susanne; Fiehler, Jens; Reddy, Ravinder; Sedlacik, Jan

    2018-05-12

    We present a computationally feasible and iterative multi-voxel spatially regularized algorithm for myelin water fraction (MWF) reconstruction. This method utilizes 3D spatial correlations present in anatomical/pathological tissues and underlying B1 + -inhomogeneity or flip angle inhomogeneity to enhance the noise robustness of the reconstruction while intrinsically accounting for stimulated echo contributions using T2-distribution data alone. Simulated data and in vivo data acquired using 3D non-selective multi-echo spin echo (3DNS-MESE) were used to compare the reconstruction quality of the proposed approach against those of the popular algorithm (the method by Prasloski et al.) and our previously proposed 2D multi-slice spatial regularization spatial regularization approach. We also investigated whether the inter-sequence correlations and agreements improved as a result of the proposed approach. MWF-quantifications from two sequences, 3DNS-MESE vs 3DNS-gradient and spin echo (3DNS-GRASE), were compared for both reconstruction approaches to assess correlations and agreements between inter-sequence MWF-value pairs. MWF values from whole-brain data of six volunteers and two multiple sclerosis patients are being reported as well. In comparison with competing approaches such as Prasloski's method or our previously proposed 2D multi-slice spatial regularization method, the proposed method showed better agreements with simulated truths using regression analyses and Bland-Altman analyses. For 3DNS-MESE data, MWF-maps reconstructed using the proposed algorithm provided better depictions of white matter structures in subcortical areas adjoining gray matter which agreed more closely with corresponding contrasts on T2-weighted images than MWF-maps reconstructed with the method by Prasloski et al. We also achieved a higher level of correlations and agreements between inter-sequence (3DNS-MESE vs 3DNS-GRASE) MWF-value pairs. The proposed algorithm provides more noise-robust fits to T2-decay data and improves MWF-quantifications in white matter structures especially in the sub-cortical white matter and major white matter tract regions. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Hemispheric differences in the voluntary control of spatial attention: direct evidence for a right-hemispheric dominance within frontal cortex.

    PubMed

    Duecker, Felix; Formisano, Elia; Sack, Alexander T

    2013-08-01

    Lesion studies in neglect patients have inspired two competing models of spatial attention control, namely, Heilman's "hemispatial" theory and Kinsbourne's "opponent processor" model. Both assume a functional asymmetry between the two hemispheres but propose very different mechanisms. Neuroimaging studies have identified a bilateral dorsal frontoparietal network underlying voluntary shifts of spatial attention. However, lateralization of attentional processes within this network has not been consistently reported. In the current study, we aimed to provide direct evidence concerning the functional asymmetry of the right and left FEF during voluntary shifts of spatial attention. To this end, we applied fMRI-guided neuronavigation to disrupt individual FEF activation foci with a longer-lasting inhibitory patterned TMS protocol followed by a spatial cueing task. Our results indicate that right FEF stimulation impaired the ability of shifting spatial attention toward both hemifields, whereas the effects of left FEF stimulation were limited to the contralateral hemifield. These results provide strong direct evidence for right-hemispheric dominance in spatial attention within frontal cortex supporting Heilman's "hemispatial" theory. This complements previous TMS studies that generally conform to Kinsbourne's "opponent processor" model after disruption of parietal cortex, and we therefore propose that both theories are not mutually exclusive.

  19. Biofunctionalized peptide-based hydrogels provide permissive scaffolds to attract neurite outgrowth from spiral ganglion neurons.

    PubMed

    Frick, Claudia; Müller, Marcus; Wank, Ute; Tropitzsch, Anke; Kramer, Benedikt; Senn, Pascal; Rask-Andersen, Helge; Wiesmüller, Karl-Heinz; Löwenheim, Hubert

    2017-01-01

    Cochlear implants (CI) allow for hearing rehabilitation in patients with sensorineural hearing loss or deafness. Restricted CI performance results from the spatial gap between spiral ganglion neurons and the CI, causing current spread that limits spatially restricted stimulation and impairs frequency resolution. This may be substantially improved by guiding peripheral processes of spiral ganglion neurons towards and onto the CI electrode contacts. An injectable, peptide-based hydrogel was developed which may provide a permissive scaffold to facilitate neurite growth towards the CI. To test hydrogel capacity to attract spiral ganglion neurites, neurite outgrowth was quantified in an in vitro model using a custom-designed hydrogel scaffold and PuraMatrix ® . Neurite attachment to native hydrogels is poor, but significantly improved by incorporation of brain-derived neurotrophic factor (BDNF), covalent coupling of the bioactive laminin epitope IKVAV and the incorporation a full length laminin to hydrogel scaffolds. Incorporation of full length laminin protein into a novel custom-designed biofunctionalized hydrogel (IKVAV-GGG-SIINFEKL) allows for neurite outgrowth into the hydrogel scaffold. The study demonstrates that peptide-based hydrogels can be specifically biofunctionalized to provide a permissive scaffold to attract neurite outgrowth from spiral ganglion neurons. Such biomaterials appear suitable to bridge the spatial gap between neurons and the CI. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Vertically aligned carbon nanofiber as nano-neuron interface for monitoring neural function.

    PubMed

    Yu, Zhe; McKnight, Timothy E; Ericson, M Nance; Melechko, Anatoli V; Simpson, Michael L; Morrison, Barclay

    2012-05-01

    Neural chips, which are capable of simultaneous multisite neural recording and stimulation, have been used to detect and modulate neural activity for almost thirty years. As neural interfaces, neural chips provide dynamic functional information for neural decoding and neural control. By improving sensitivity and spatial resolution, nano-scale electrodes may revolutionize neural detection and modulation at cellular and molecular levels as nano-neuron interfaces. We developed a carbon-nanofiber neural chip with lithographically defined arrays of vertically aligned carbon nanofiber electrodes and demonstrated its capability of both stimulating and monitoring electrophysiological signals from brain tissues in vitro and monitoring dynamic information of neuroplasticity. This novel nano-neuron interface may potentially serve as a precise, informative, biocompatible, and dual-mode neural interface for monitoring of both neuroelectrical and neurochemical activity at the single-cell level and even inside the cell. The authors demonstrate the utility of a neural chip with lithographically defined arrays of vertically aligned carbon nanofiber electrodes. The new device can be used to stimulate and/or monitor signals from brain tissue in vitro and for monitoring dynamic information of neuroplasticity both intracellularly and at the single cell level including neuroelectrical and neurochemical activities. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. The development and modeling of devices and paradigms for transcranial magnetic stimulation

    PubMed Central

    Goetz, Stefan M.; Deng, Zhi-De

    2017-01-01

    Magnetic stimulation is a noninvasive neurostimulation technique that can evoke action potentials and modulate neural circuits through induced electric fields. Biophysical models of magnetic stimulation have become a major driver for technological developments and the understanding of the mechanisms of magnetic neurostimulation and neuromodulation. Major technological developments involve stimulation coils with different spatial characteristics and pulse sources to control the pulse waveform. While early technological developments were the result of manual design and invention processes, there is a trend in both stimulation coil and pulse source design to mathematically optimize parameters with the help of computational models. To date, macroscopically highly realistic spatial models of the brain as well as peripheral targets, and user-friendly software packages enable researchers and practitioners to simulate the treatment-specific and induced electric field distribution in the brains of individual subjects and patients. Neuron models further introduce the microscopic level of neural activation to understand the influence of activation dynamics in response to different pulse shapes. A number of models that were designed for online calibration to extract otherwise covert information and biomarkers from the neural system recently form a third branch of modeling. PMID:28443696

  2. The development and modelling of devices and paradigms for transcranial magnetic stimulation.

    PubMed

    Goetz, Stefan M; Deng, Zhi-De

    2017-04-01

    Magnetic stimulation is a non-invasive neurostimulation technique that can evoke action potentials and modulate neural circuits through induced electric fields. Biophysical models of magnetic stimulation have become a major driver for technological developments and the understanding of the mechanisms of magnetic neurostimulation and neuromodulation. Major technological developments involve stimulation coils with different spatial characteristics and pulse sources to control the pulse waveform. While early technological developments were the result of manual design and invention processes, there is a trend in both stimulation coil and pulse source design to mathematically optimize parameters with the help of computational models. To date, macroscopically highly realistic spatial models of the brain, as well as peripheral targets, and user-friendly software packages enable researchers and practitioners to simulate the treatment-specific and induced electric field distribution in the brains of individual subjects and patients. Neuron models further introduce the microscopic level of neural activation to understand the influence of activation dynamics in response to different pulse shapes. A number of models that were designed for online calibration to extract otherwise covert information and biomarkers from the neural system recently form a third branch of modelling.

  3. Slow-Frequency Pulsed Transcranial Electrical Stimulation for Modulation of Cortical Plasticity Based on Reciprocity Targeting with Precision Electrical Head Modeling

    PubMed Central

    Luu, Phan; Essaki Arumugam, Easwara Moorthy; Anderson, Erik; Gunn, Amanda; Rech, Dennis; Turovets, Sergei; Tucker, Don M.

    2016-01-01

    In pain management as well as other clinical applications of neuromodulation, it is important to consider the timing parameters influencing activity-dependent plasticity, including pulsed versus sustained currents, as well as the spatial action of electrical currents as they polarize the complex convolutions of the cortical mantle. These factors are of course related; studying temporal factors is not possible when the spatial resolution of current delivery to the cortex is so uncertain to make it unclear whether excitability is increased or decreased with anodal vs. cathodal current flow. In the present study we attempted to improve the targeting of specific cortical locations by applying current through flexible source-sink configurations of 256 electrodes in a geodesic array. We constructed a precision electric head model for 12 healthy individuals. Extraction of the individual’s cortical surface allowed computation of the component of the induced current that is normal to the target cortical surface. In an effort to replicate the long-term depression (LTD) induced with pulsed protocols in invasive animal research and transcranial magnetic stimulation studies, we applied 100 ms pulses at 1.9 s intervals either in cortical-surface-anodal or cortical-surface-cathodal directions, with a placebo (sham) control. The results showed significant LTD of the motor evoked potential as a result of the cortical-surface-cathodal pulses in contrast to the placebo control, with a smaller but similar LTD effect for anodal pulses. The cathodal LTD after-effect was sustained over 90 min following current injection. These results support the feasibility of pulsed protocols with low total charge in non-invasive neuromodulation when the precision of targeting is improved with a dense electrode array and accurate head modeling. PMID:27531976

  4. Magnetic Stimulation Studies of Foveal Representation

    ERIC Educational Resources Information Center

    Lavidor, Michal; Walsh, Vincent

    2004-01-01

    The right and left visual fields each project to the contralateral cerebral hemispheres, but the extent of the functional overlap of the two hemifields along the vertical meridian is still under debate. After presenting the spatial, temporal, and functional specifications of Transcranial Magnetic Stimulation (TMS), we show that TMS is particularly…

  5. Artificial Walking Technologies to Improve Gait in Cerebral Palsy: Multichannel Neuromuscular Stimulation.

    PubMed

    Rose, Jessica; Cahill-Rowley, Katelyn; Butler, Erin E

    2017-11-01

    Cerebral palsy (CP) is the most common childhood motor disability and often results in debilitating walking abnormalities, such as flexed-knee and stiff-knee gait. Current medical and surgical treatments are only partially effective in improving gait abnormalities and may cause significant muscle weakness. However, emerging artificial walking technologies, such as step-initiated, multichannel neuromuscular electrical stimulation (NMES), can substantially improve gait patterns and promote muscle strength in children with spastic CP. NMES may also be applied to specific lumbar-sacral sensory roots to reduce spasticity. Development of tablet computer-based multichannel NMES can leverage lightweight, wearable wireless stimulators, advanced control design, and surface electrodes to activate lower-limb muscles. Musculoskeletal models have been used to characterize muscle contributions to unimpaired gait and identify high muscle demands, which can help guide multichannel NMES-assisted gait protocols. In addition, patient-specific NMES-assisted gait protocols based on 3D gait analysis can facilitate the appropriate activation of lower-limb muscles to achieve a more functional gait: stance-phase hip and knee extension and swing-phase sequence of hip and knee flexion followed by rapid knee extension. NMES-assisted gait treatment can be conducted as either clinic-based or home-based programs. Rigorous testing of multichannel NMES-assisted gait training protocols will determine optimal treatment dosage for future clinical trials. Evidence-based outcome evaluation using 3D kinematics or temporal-spatial gait parameters will help determine immediate neuroprosthetic effects and longer term neurotherapeutic effects of step-initiated, multichannel NMES-assisted gait in children with spastic CP. Multichannel NMES is a promising assistive technology to help children with spastic CP achieve a more upright, functional gait. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  6. Forniceal deep brain stimulation rescues hippocampal memory in Rett syndrome mice

    PubMed Central

    Hao, Shuang; Tang, Bin; Wu, Zhenyu; Ure, Kerstin; Sun, Yaling; Tao, Huifang; Gao, Yan; Patel, Akash J.; Curry, Daniel J.; Samaco, Rodney C.; Zoghbi, Huda Y.; Tang, Jianrong

    2016-01-01

    Deep brain stimulation (DBS) has improved the prospects for many individuals with diseases affecting motor control, and recently it has shown promise for improving cognitive function as well. Several studies in individuals with Alzheimer disease and in amnestic rats have demonstrated that DBS targeted to the fimbria-fornix1-3, the region that appears to regulate hippocampal activity, can mitigate defects in hippocampus-dependent memory3-5. Despite these promising results, DBS has not been tested for its ability to improve cognition in any childhood intellectual disability disorder (IDD). IDDs are a pressing concern: they affect as much as 3% of the population and involve hundreds of different genes. We hypothesized that stimulating the neural circuits that underlie learning and memory might provide a more promising route to treating these otherwise intractable disorders than seeking to adjust levels of one molecule at a time. We therefore studied the effects of forniceal DBS in a well-characterized mouse model of Rett Syndrome (RTT), which is a leading cause of intellectual disability in females. Caused by mutations that impair the function of MeCP26, RTT appears by the second year of life, causing profound impairment in cognitive, motor, and social skills along with an array of neurological features7; RTT mice, which reproduce the broad phenotype of this disorder, also show clear deficits in hippocampus-dependent learning and memory and hippocampal synaptic plasticity8-11. Here we show that forniceal DBS in RTT mice rescued contextual fear memory as well as spatial learning and memory. In parallel, forniceal DBS restored in vivo hippocampal long-term potentiation (LTP) and hippocampal neurogenesis. These results indicate that forniceal DBS might mitigate cognitive dysfunction in RTT. PMID:26469053

  7. Fiber-optic two-photon optogenetic stimulation.

    PubMed

    Dhakal, K; Gu, L; Black, B; Mohanty, S K

    2013-06-01

    Optogenetic stimulation of genetically targeted cells is proving to be a powerful tool in the study of cellular systems, both in vitro and in vivo. However, most opsins are activated in the visible spectrum, where significant absorption and scattering of stimulating light occurs, leading to low penetration depth and less precise stimulation. Since we first (to the best of our knowledge) demonstrated two-photon optogenetic stimulation (TPOS), it has gained considerable interest in the probing of cellular circuitry by precise spatial modulation. However, all existing methods use microscope objectives and complex scanning beam geometries. Here, we report a nonscanning method based on multimode fiber to accomplish fiber-optic TPOS of cells.

  8. Cortical activation changes underlying stimulation-induced behavioural gains in chronic stroke

    PubMed Central

    Bachtiar, Velicia; O'Shea, Jacinta; Allman, Claire; Bosnell, Rosemary Ann; Kischka, Udo; Matthews, Paul McMahan; Johansen-Berg, Heidi

    2012-01-01

    Transcranial direct current stimulation, a form of non-invasive brain stimulation, is showing increasing promise as an adjunct therapy in rehabilitation following stroke. However, although significant behavioural improvements have been reported in proof-of-principle studies, the underlying mechanisms are poorly understood. The rationale for transcranial direct current stimulation as therapy for stroke is that therapeutic stimulation paradigms increase activity in ipsilesional motor cortical areas, but this has not previously been directly tested for conventional electrode placements. This study was performed to test directly whether increases in ipsilesional cortical activation with transcranial direct current stimulation are associated with behavioural improvements in chronic stroke patients. Patients at least 6 months post-first stroke participated in a behavioural experiment (n = 13) or a functional magnetic resonance imaging experiment (n = 11), each investigating the effects of three stimulation conditions in separate sessions: anodal stimulation to the ipsilesional hemisphere; cathodal stimulation to the contralesional hemisphere; and sham stimulation. Anodal (facilitatory) stimulation to the ipsilesional hemisphere led to significant improvements (5–10%) in response times with the affected hand in both experiments. This improvement was associated with an increase in movement-related cortical activity in the stimulated primary motor cortex and functionally interconnected regions. Cathodal (inhibitory) stimulation to the contralesional hemisphere led to a functional improvement only when compared with sham stimulation. We show for the first time that the significant behavioural improvements produced by anodal stimulation to the ipsilesional hemisphere are associated with a functionally relevant increase in activity within the ipsilesional primary motor cortex in patients with a wide range of disabilities following stroke. PMID:22155982

  9. Value and Efficacy of Transcranial Direct Current Stimulation in the Cognitive Rehabilitation: A Critical Review Since 2000

    PubMed Central

    Cappon, Davide; Jahanshahi, Marjan; Bisiacchi, Patrizia

    2016-01-01

    Non-invasive brain stimulation techniques, including transcranial direct current stimulation (t-DCS) have been used in the rehabilitation of cognitive function in a spectrum of neurological disorders. The present review outlines methodological communalities and differences of t-DCS procedures in neurocognitive rehabilitation. We consider the efficacy of tDCS for the management of specific cognitive deficits in four main neurological disorders by providing a critical analysis of recent studies that have used t-DCS to improve cognition in patients with Parkinson's Disease, Alzheimer's Disease, Hemi-spatial Neglect, and Aphasia. The evidence from this innovative approach to cognitive rehabilitation suggests that tDCS can influence cognition. However, the results show a high variability between studies both in terms of the methodological approach adopted and the cognitive functions targeted. The review also focuses both on methodological issues such as technical aspects of the stimulation (electrode position and dimension; current intensity; duration of protocol) and on the inclusion of appropriate assessment tools for cognition. A further aspect considered is the optimal timing for administration of tDCS: before, during or after cognitive rehabilitation. We conclude that more studies using common methodology are needed to gain a better understanding of the efficacy of tDCS as a new tool for rehabilitation of cognitive disorders in a range of neurological disorders. PMID:27147949

  10. Value and Efficacy of Transcranial Direct Current Stimulation in the Cognitive Rehabilitation: A Critical Review Since 2000.

    PubMed

    Cappon, Davide; Jahanshahi, Marjan; Bisiacchi, Patrizia

    2016-01-01

    Non-invasive brain stimulation techniques, including transcranial direct current stimulation (t-DCS) have been used in the rehabilitation of cognitive function in a spectrum of neurological disorders. The present review outlines methodological communalities and differences of t-DCS procedures in neurocognitive rehabilitation. We consider the efficacy of tDCS for the management of specific cognitive deficits in four main neurological disorders by providing a critical analysis of recent studies that have used t-DCS to improve cognition in patients with Parkinson's Disease, Alzheimer's Disease, Hemi-spatial Neglect, and Aphasia. The evidence from this innovative approach to cognitive rehabilitation suggests that tDCS can influence cognition. However, the results show a high variability between studies both in terms of the methodological approach adopted and the cognitive functions targeted. The review also focuses both on methodological issues such as technical aspects of the stimulation (electrode position and dimension; current intensity; duration of protocol) and on the inclusion of appropriate assessment tools for cognition. A further aspect considered is the optimal timing for administration of tDCS: before, during or after cognitive rehabilitation. We conclude that more studies using common methodology are needed to gain a better understanding of the efficacy of tDCS as a new tool for rehabilitation of cognitive disorders in a range of neurological disorders.

  11. Non-target adjacent stimuli classification improves performance of classical ERP-based brain computer interface

    NASA Astrophysics Data System (ADS)

    Ceballos, G. A.; Hernández, L. F.

    2015-04-01

    Objective. The classical ERP-based speller, or P300 Speller, is one of the most commonly used paradigms in the field of Brain Computer Interfaces (BCI). Several alterations to the visual stimuli presentation system have been developed to avoid unfavorable effects elicited by adjacent stimuli. However, there has been little, if any, regard to useful information contained in responses to adjacent stimuli about spatial location of target symbols. This paper aims to demonstrate that combining the classification of non-target adjacent stimuli with standard classification (target versus non-target) significantly improves classical ERP-based speller efficiency. Approach. Four SWLDA classifiers were trained and combined with the standard classifier: the lower row, upper row, right column and left column classifiers. This new feature extraction procedure and the classification method were carried out on three open databases: the UAM P300 database (Universidad Autonoma Metropolitana, Mexico), BCI competition II (dataset IIb) and BCI competition III (dataset II). Main results. The inclusion of the classification of non-target adjacent stimuli improves target classification in the classical row/column paradigm. A gain in mean single trial classification of 9.6% and an overall improvement of 25% in simulated spelling speed was achieved. Significance. We have provided further evidence that the ERPs produced by adjacent stimuli present discriminable features, which could provide additional information about the spatial location of intended symbols. This work promotes the searching of information on the peripheral stimulation responses to improve the performance of emerging visual ERP-based spellers.

  12. Simultaneously driven linear and nonlinear spatial encoding fields in MRI.

    PubMed

    Gallichan, Daniel; Cocosco, Chris A; Dewdney, Andrew; Schultz, Gerrit; Welz, Anna; Hennig, Jürgen; Zaitsev, Maxim

    2011-03-01

    Spatial encoding in MRI is conventionally achieved by the application of switchable linear encoding fields. The general concept of the recently introduced PatLoc (Parallel Imaging Technique using Localized Gradients) encoding is to use nonlinear fields to achieve spatial encoding. Relaxing the requirement that the encoding fields must be linear may lead to improved gradient performance or reduced peripheral nerve stimulation. In this work, a custom-built insert coil capable of generating two independent quadratic encoding fields was driven with high-performance amplifiers within a clinical MR system. In combination with the three linear encoding fields, the combined hardware is capable of independently manipulating five spatial encoding fields. With the linear z-gradient used for slice-selection, there remain four separate channels to encode a 2D-image. To compare trajectories of such multidimensional encoding, the concept of a local k-space is developed. Through simulations, reconstructions using six gradient-encoding strategies were compared, including Cartesian encoding separately or simultaneously on both PatLoc and linear gradients as well as two versions of a radial-based in/out trajectory. Corresponding experiments confirmed that such multidimensional encoding is practically achievable and demonstrated that the new radial-based trajectory offers the PatLoc property of variable spatial resolution while maintaining finite resolution across the entire field-of-view. Copyright © 2010 Wiley-Liss, Inc.

  13. The role of multisensory interplay in enabling temporal expectations.

    PubMed

    Ball, Felix; Michels, Lara E; Thiele, Carsten; Noesselt, Toemme

    2018-01-01

    Temporal regularities can guide our attention to focus on a particular moment in time and to be especially vigilant just then. Previous research provided evidence for the influence of temporal expectation on perceptual processing in unisensory auditory, visual, and tactile contexts. However, in real life we are often exposed to a complex and continuous stream of multisensory events. Here we tested - in a series of experiments - whether temporal expectations can enhance perception in multisensory contexts and whether this enhancement differs from enhancements in unisensory contexts. Our discrimination paradigm contained near-threshold targets (subject-specific 75% discrimination accuracy) embedded in a sequence of distractors. The likelihood of target occurrence (early or late) was manipulated block-wise. Furthermore, we tested whether spatial and modality-specific target uncertainty (i.e. predictable vs. unpredictable target position or modality) would affect temporal expectation (TE) measured with perceptual sensitivity (d ' ) and response times (RT). In all our experiments, hidden temporal regularities improved performance for expected multisensory targets. Moreover, multisensory performance was unaffected by spatial and modality-specific uncertainty, whereas unisensory TE effects on d ' but not RT were modulated by spatial and modality-specific uncertainty. Additionally, the size of the temporal expectation effect, i.e. the increase in perceptual sensitivity and decrease of RT, scaled linearly with the likelihood of expected targets. Finally, temporal expectation effects were unaffected by varying target position within the stream. Together, our results strongly suggest that participants quickly adapt to novel temporal contexts, that they benefit from multisensory (relative to unisensory) stimulation and that multisensory benefits are maximal if the stimulus-driven uncertainty is highest. We propose that enhanced informational content (i.e. multisensory stimulation) enables the robust extraction of temporal regularities which in turn boost (uni-)sensory representations. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Cathodal Transcranial Direct Current Stimulation (tDCS) to the Right Cerebellar Hemisphere Affects Motor Adaptation During Gait.

    PubMed

    Fernandez, Lara; Albein-Urios, Natalia; Kirkovski, Melissa; McGinley, Jennifer L; Murphy, Anna T; Hyde, Christian; Stokes, Mark A; Rinehart, Nicole J; Enticott, Peter G

    2017-02-01

    The cerebellum appears to play a key role in the development of internal rules that allow fast, predictive adjustments to novel stimuli. This is crucial for adaptive motor processes, such as those involved in walking, where cerebellar dysfunction has been found to increase variability in gait parameters. Motor adaptation is a process that results in a progressive reduction in errors as movements are adjusted to meet demands, and within the cerebellum, this seems to be localised primarily within the right hemisphere. To examine the role of the right cerebellar hemisphere in adaptive gait, cathodal transcranial direct current stimulation (tDCS) was administered to the right cerebellar hemisphere of 14 healthy adults in a randomised, double-blind, crossover study. Adaptation to a series of distinct spatial and temporal templates was assessed across tDCS condition via a pressure-sensitive gait mat (ProtoKinetics Zeno walkway), on which participants walked with an induced 'limp' at a non-preferred pace. Variability was assessed across key spatial-temporal gait parameters. It was hypothesised that cathodal tDCS to the right cerebellar hemisphere would disrupt adaptation to the templates, reflected in a failure to reduce variability following stimulation. In partial support, adaptation was disrupted following tDCS on one of the four spatial-temporal templates used. However, there was no evidence for general effects on either the spatial or temporal domain. This suggests, under specific conditions, a coupling of spatial and temporal processing in the right cerebellar hemisphere and highlights the potential importance of task complexity in cerebellar function.

  15. Inhibitory Mechanisms in Primary Somatosensory Cortex Mediate the Effects of Peripheral Electrical Stimulation on Tactile Spatial Discrimination.

    PubMed

    Saito, Kei; Otsuru, Naofumi; Inukai, Yasuto; Kojima, Sho; Miyaguchi, Shota; Tsuiki, Shota; Sasaki, Ryoki; Onishi, Hideaki

    2018-06-01

    Selective afferent activation can be used to improve somatosensory function, possibly by altering cortical inhibitory circuit activity. Peripheral electrical stimulation (PES) is widely used to induce selective afferent activation, and its effect may depend on PES intensity. Therefore, we investigated the effects of high- and low-intensity PES applied to the right index finger on tactile discrimination performance and cortical sensory-evoked potential paired-pulse depression (SEP-PPD) in 25 neurologically healthy subjects. In Experiment 1, a grating orientation task (GOT) was performed before and immediately after local high- and low-intensity PES (both delivered as 1-s, 20-Hz trains of 0.2-ms electrical pulses at 5-s intervals). In Experiment 2, PPD of SEP components N20/P25_SEP-PPD and N20_SEP-PPD, respectively, were assessed before and immediately after high- and low-intensity PES. Improved GOT discrimination performance after high-intensity PES (reduced discrimination threshold) was associated with lower baseline performance (higher baseline discrimination threshold). Subjects were classified into low and high (baseline) GOT performance groups. Improved GOT discrimination performance in the low GOT performance group was significantly associated with a greater N20_SEP-PPD decrease (weaker PPD). Subjects were also classified into GOT improvement and GOT decrement groups. High-intensity PES decreased N20_SEP-PPD in the GOT improvement group but increased N20_SEP-PPD in the GOT decrement group. Furthermore, a greater decrease in GOT discrimination threshold was significantly associated with a greater N20_SEP-PPD decrease in the GOT improvement group. These results suggest that high-intensity PES can improve sensory perception in subjects with low baseline function by modulating cortical inhibitory circuits in primary somatosensory cortex. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  16. Surmounting retraining limits in musicians' dystonia by transcranial stimulation.

    PubMed

    Furuya, Shinichi; Nitsche, Michael A; Paulus, Walter; Altenmüller, Eckart

    2014-05-01

    Abnormal cortical excitability is evident in various movement disorders that compromise fine motor control. Here we tested whether skilled finger movements can be restored in musicians with focal hand dystonia through behavioral training assisted by transcranial direct current stimulation to the motor cortex of both hemispheres. The bilateral motor cortices of 20 pianists (10 with focal dystonia, 10 healthy controls) were electrically stimulated noninvasively during bimanual mirrored finger movements. We found improvement in the rhythmic accuracy of sequential finger movements with the affected hand during and after cathodal stimulation over the affected cortex and simultaneous anodal stimulation over the unaffected cortex. The improvement was retained 4 days after intervention. Neither a stimulation with the reversed montage of electrodes nor sham stimulation yielded any improvement. Furthermore, the amount of improvement was positively correlated with the severity of the symptoms. Bihemispheric stimulation without concurrent motor training failed to improve fine motor control, underlining the importance of combined retraining and stimulation for restoring the dystonic symptoms. For the healthy pianists, none of the stimulation protocols enhanced movement accuracy. These results suggest a therapeutic potential of behavioral training assisted by bihemispheric, noninvasive brain stimulation in restoring fine motor control in focal dystonia. © 2014 American Neurological Association.

  17. Regional acidosis locally inhibits but remotely stimulates Ca2+ waves in ventricular myocytes

    PubMed Central

    Ford, Kerrie L.; Moorhouse, Emma L.; Bortolozzi, Mario; Richards, Mark A.; Swietach, Pawel; Vaughan-Jones, Richard D.

    2017-01-01

    Abstract Aims Spontaneous Ca2+ waves in cardiomyocytes are potentially arrhythmogenic. A powerful controller of Ca2+ waves is the cytoplasmic H+ concentration ([H+]i), which fluctuates spatially and temporally in conditions such as myocardial ischaemia/reperfusion. H+-control of Ca2+ waves is poorly understood. We have therefore investigated how [H+]i co-ordinates their initiation and frequency. Methods and results Spontaneous Ca2+ waves were imaged (fluo-3) in rat isolated ventricular myocytes, subjected to modest Ca2+-overload. Whole-cell intracellular acidosis (induced by acetate-superfusion) stimulated wave frequency. Pharmacologically blocking sarcolemmal Na+/H+ exchange (NHE1) prevented this stimulation, unveiling inhibition by H+. Acidosis also increased Ca2+ wave velocity. Restricting acidosis to one end of a myocyte, using a microfluidic device, inhibited Ca2+ waves in the acidic zone (consistent with ryanodine receptor inhibition), but stimulated wave emergence elsewhere in the cell. This remote stimulation was absent when NHE1 was selectively inhibited in the acidic zone. Remote stimulation depended on a locally evoked, NHE1-driven rise of [Na+]i that spread rapidly downstream. Conclusion Acidosis influences Ca2+ waves via inhibitory Hi+ and stimulatory Nai+ signals (the latter facilitating intracellular Ca2+-loading through modulation of sarcolemmal Na+/Ca2+ exchange activity). During spatial [H+]i-heterogeneity, Hi+-inhibition dominates in acidic regions, while rapid Nai+ diffusion stimulates waves in downstream, non-acidic regions. Local acidosis thus simultaneously inhibits and stimulates arrhythmogenic Ca2+-signalling in the same myocyte. If the principle of remote H+-stimulation of Ca2+ waves also applies in multicellular myocardium, it raises the possibility of electrical disturbances being driven remotely by adjacent ischaemic areas, which are known to be intensely acidic. PMID:28339694

  18. Regional acidosis locally inhibits but remotely stimulates Ca2+ waves in ventricular myocytes.

    PubMed

    Ford, Kerrie L; Moorhouse, Emma L; Bortolozzi, Mario; Richards, Mark A; Swietach, Pawel; Vaughan-Jones, Richard D

    2017-07-01

    Spontaneous Ca2+ waves in cardiomyocytes are potentially arrhythmogenic. A powerful controller of Ca2+ waves is the cytoplasmic H+ concentration ([H+]i), which fluctuates spatially and temporally in conditions such as myocardial ischaemia/reperfusion. H+-control of Ca2+ waves is poorly understood. We have therefore investigated how [H+]i co-ordinates their initiation and frequency. Spontaneous Ca2+ waves were imaged (fluo-3) in rat isolated ventricular myocytes, subjected to modest Ca2+-overload. Whole-cell intracellular acidosis (induced by acetate-superfusion) stimulated wave frequency. Pharmacologically blocking sarcolemmal Na+/H+ exchange (NHE1) prevented this stimulation, unveiling inhibition by H+. Acidosis also increased Ca2+ wave velocity. Restricting acidosis to one end of a myocyte, using a microfluidic device, inhibited Ca2+ waves in the acidic zone (consistent with ryanodine receptor inhibition), but stimulated wave emergence elsewhere in the cell. This remote stimulation was absent when NHE1 was selectively inhibited in the acidic zone. Remote stimulation depended on a locally evoked, NHE1-driven rise of [Na+]i that spread rapidly downstream. Acidosis influences Ca2+ waves via inhibitory Hi+ and stimulatory Nai+ signals (the latter facilitating intracellular Ca2+-loading through modulation of sarcolemmal Na+/Ca2+ exchange activity). During spatial [H+]i-heterogeneity, Hi+-inhibition dominates in acidic regions, while rapid Nai+ diffusion stimulates waves in downstream, non-acidic regions. Local acidosis thus simultaneously inhibits and stimulates arrhythmogenic Ca2+-signalling in the same myocyte. If the principle of remote H+-stimulation of Ca2+ waves also applies in multicellular myocardium, it raises the possibility of electrical disturbances being driven remotely by adjacent ischaemic areas, which are known to be intensely acidic. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Cardiology.

  19. Tactile exploration of virtual objects for blind and sighted people: the role of beta 1 EEG band in sensory substitution and supramodal mental mapping

    PubMed Central

    Brayda, L.; De Carli, F.; Chellali, R.; Famà, F.; Bruzzo, C.; Lucagrossi, L.; Rodriguez, G.

    2012-01-01

    The neural correlates of exploration and cognitive mapping in blindness remain elusive. The role of visuo-spatial pathways in blind vs. sighted subjects is still under debate. In this preliminary study, we investigate, as a possible estimation of the activity in the visuo-spatial pathways, the EEG patterns of blind and blindfolded-sighted subjects during the active tactile construction of cognitive maps from virtual objects compared with rest and passive tactile stimulation. Ten blind and ten matched, blindfolded-sighted subjects participated in the study. Events were defined as moments when the finger was only stimulated (passive stimulation) or the contour of a virtual object was touched (during active exploration). Event-related spectral power and coherence perturbations were evaluated within the beta 1 band (14–18 Hz). They were then related to a subjective cognitive-load estimation required by the explorations [namely, perceived levels of difficulty (PLD)]. We found complementary cues for sensory substitution and spatial processing in both groups: both blind and sighted subjects showed, while exploring, late power decreases and early power increases, potentially associated with motor programming and touch, respectively. The latter involved occipital areas only for blind subjects (long-term plasticity) and only during active exploration, thus supporting tactile-to-visual sensory substitution. In both groups, coherences emerged among the fronto-central, centro-parietal, and occipito-temporal derivations associated with visuo-spatial processing. This seems in accordance with mental map construction involving spatial processing, sensory-motor processing, and working memory. The observed involvement of the occipital regions suggests that a substitution process also occurs in sighted subjects. Only during explorations did coherence correlate positively with PLD for both groups and in derivations, which can be related to visuo-spatial processing, supporting the existence of supramodal spatial processing independently of vision capabilities. PMID:22338024

  20. A fast stimulability screening protocol for neuronal cultures on microelectrode arrays.

    PubMed

    Kapucu, Fikret E; Tanskanen, Jarno M A; Yuan, Yuting; Hyttinen, Jari A K

    2015-01-01

    Microelectrode arrays (MEAs) are used to study the electrical activity in brain slices and neuronal cultures. MEA experiments for the analysis of electrical stimulation responses require the tissue or culture to be prone to stimulation. For brain slices, potential stimulation sites may be directly visible in microscope, in which case the determination of stimulability at those locations is sufficient. In unstructured neuronal cultures, potential stimulation sites may not be known a priori, and spatial stimulability screening should be performed. Considering, e.g., 59 microelectrode sites, each to be stimulated several times, may result in long screening times, unacceptable with a MEA system without an integrated CO2 incubator, or in high stimulation effects on the networks. Here, we describe an implementation of a fast stimulation protocol employing pseudorandom stimulation site switching aiming at alleviating the network effects of the stimulability screening. In this paper, we show the usability of the proposed protocol by first detecting stimulable locations and subsequently apply repeated stimulation on the identified potentially stimulable locations to observe an exemplary neuronal pathway.

  1. Brain networks modulated by subthalamic nucleus deep brain stimulation.

    PubMed

    Accolla, Ettore A; Herrojo Ruiz, Maria; Horn, Andreas; Schneider, Gerd-Helge; Schmitz-Hübsch, Tanja; Draganski, Bogdan; Kühn, Andrea A

    2016-09-01

    Deep brain stimulation of the subthalamic nucleus is an established treatment for the motor symptoms of Parkinson's disease. Given the frequent occurrence of stimulation-induced affective and cognitive adverse effects, a better understanding about the role of the subthalamic nucleus in non-motor functions is needed. The main goal of this study is to characterize anatomical circuits modulated by subthalamic deep brain stimulation, and infer about the inner organization of the nucleus in terms of motor and non-motor areas. Given its small size and anatomical intersubject variability, functional organization of the subthalamic nucleus is difficult to investigate in vivo with current methods. Here, we used local field potential recordings obtained from 10 patients with Parkinson's disease to identify a subthalamic area with an analogous electrophysiological signature, namely a predominant beta oscillatory activity. The spatial accuracy was improved by identifying a single contact per macroelectrode for its vicinity to the electrophysiological source of the beta oscillation. We then conducted whole brain probabilistic tractography seeding from the previously identified contacts, and further described connectivity modifications along the macroelectrode's main axis. The designated subthalamic 'beta' area projected predominantly to motor and premotor cortical regions additional to connections to limbic and associative areas. More ventral subthalamic areas showed predominant connectivity to medial temporal regions including amygdala and hippocampus. We interpret our findings as evidence for the convergence of different functional circuits within subthalamic nucleus' portions deemed to be appropriate as deep brain stimulation target to treat motor symptoms in Parkinson's disease. Potential clinical implications of our study are illustrated by an index case where deep brain stimulation of estimated predominant non-motor subthalamic nucleus induced hypomanic behaviour. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. The effect of functional electrical stimulation cycling on late functional improvement in patients with chronic incomplete spinal cord injury.

    PubMed

    Yaşar, E; Yılmaz, B; Göktepe, S; Kesikburun, S

    2015-12-01

    Prospective single-arm study. To investigate the effect of functional electrical stimulation (FES) cycling on late functional recovery, spasticity, gait parameters and oxygen consumption during walking in patients with chronic incomplete spinal cord injury (SCI). Turkish Armed Forces Rehabilitation Center, Ankara, Turkey. Ten patients with chronic (duration of more than 2 years) incomplete SCI who could ambulate at least 10 m independently or with the assistance of a cane or walker, but no hip-knee-ankle-foot orthosis. The subjects underwent 1-h FES cycling sessions three times a week for 16 weeks. Outcome measures including the total motor score, the Functional Independence Measure (FIM) score, the Modified Ashworth Scale for knee spasticity, temporal spatial gait parameters and oxygen consumption rate during walking were assessed at baseline, 3 and 6 months after the baseline. There were statistically significant improvements in total motor scores, the FIM scores and spasticity level at the 6-month follow-up (P<0.01). The changes in gait parameters reached no significant level (P>0.05). Oxygen consumption rate of the patients showed significant reduction at only 6 months compared with baseline (P<0.01). The results suggest that FES cycling may provide some functional improvements in the late period of SCI. The study was supported by The Scientific and Technological Research Council of Turkey (TUBITAK).

  3. Optogenetic control of ATP release

    NASA Astrophysics Data System (ADS)

    Lewis, Matthew A.; Joshi, Bipin; Gu, Ling; Feranchak, Andrew; Mohanty, Samarendra K.

    2013-03-01

    Controlled release of ATP can be used for understanding extracellular purinergic signaling. While coarse mechanical forces and hypotonic stimulation have been utilized in the past to initiate ATP release from cells, these methods are neither spatially accurate nor temporally precise. Further, these methods cannot be utilized in a highly effective cell-specific manner. To mitigate the uncertainties regarding cellular-specificity and spatio-temporal release of ATP, we herein demonstrate use of optogenetics for ATP release. ATP release in response to optogenetic stimulation was monitored by Luciferin-Luciferase assay (North American firefly, photinus pyralis) using luminometer as well as mesoscopic bioluminescence imaging. Our result demonstrates repetitive release of ATP subsequent to optogenetic stimulation. It is thus feasible that purinergic signaling can be directly detected via imaging if the stimulus can be confined to single cell or in a spatially-defined group of cells. This study opens up new avenue to interrogate the mechanisms of purinergic signaling.

  4. Effect of hindpaw electrical stimulation on capillary flow heterogeneity and oxygen delivery (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Li, Yuandong; Wei, Wei; Li, Chenxi; Wang, Ruikang K.

    2017-02-01

    We report a novel use of optical coherence tomography (OCT) based angiography to visualize and quantify dynamic response of cerebral capillary flow pattern in mice upon hindpaw electrical stimulation through the measurement of the capillary transit-time heterogeneity (CTH) and capillary mean transit time (MTT) in a wide dynamic range of a great number of vessels in vivo. The OCT system was developed to have a central wavelength of 1310 nm, a spatial resolution of 8 µm and a system dynamic range of 105 dB at an imaging rate of 92 kHz. The mapping of dynamic cerebral microcirculations was enabled by optical microangiography protocol. From the imaging results, the spatial homogenization of capillary velocity (decreased CTH) was observed in the region of interest (ROI) corresponding to the stimulation, along with an increase in the MTT in the ROI to maintain sufficient oxygen exchange within the brain tissue during functional activation. We validated the oxygen consumption due to an increase of the MTT through demonstrating an increase in the deoxygenated hemoglobin (HbR) during the stimulation by the use of laser speckle contrast imaging.

  5. Transcranial direct current stimulation of dorsolateral prefrontal cortex during encoding improves recall but not recognition memory

    DOE PAGES

    Leshikar, Eric D.; Leach, Ryan C.; McCurdy, Matthew P.; ...

    2017-10-19

    Prior work demonstrates that application of transcranial direct current stimulation (tDCS) improves memory. In this study, we investigated tDCS effects on face-name associative memory using both recall and recognition tests. Participants encoded face-name pairs under either active (1.5 mA) or sham (.1 mA) stimulation applied to the scalp adjacent to the left dorsolateral prefrontal cortex (dlPFC), an area known to support associative memory. Participants’ memory was then tested after study (day one) and then again after a 24-h delay (day two), to assess both immediate and delayed stimulation effects on memory. Results indicated that active relative to sham stimulation ledmore » to substantially improved recall (more than 50%) at both day one and day two. Recognition memory performance did not differ between stimulation groups at either time point. These results suggest that stimulation at encoding improves memory performance by enhancing memory for details that enable a rich recollective experience, but that these improvements are evident only under some testing conditions, especially those that rely on recollection. Altogether, stimulation of the dlPFC could have led to recall improvement through enhanced encoding from stimulation or from carryover effects of stimulation that influenced retrieval processes, or both.« less

  6. Transcranial direct current stimulation of dorsolateral prefrontal cortex during encoding improves recall but not recognition memory

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Leshikar, Eric D.; Leach, Ryan C.; McCurdy, Matthew P.

    Prior work demonstrates that application of transcranial direct current stimulation (tDCS) improves memory. In this study, we investigated tDCS effects on face-name associative memory using both recall and recognition tests. Participants encoded face-name pairs under either active (1.5 mA) or sham (.1 mA) stimulation applied to the scalp adjacent to the left dorsolateral prefrontal cortex (dlPFC), an area known to support associative memory. Participants’ memory was then tested after study (day one) and then again after a 24-h delay (day two), to assess both immediate and delayed stimulation effects on memory. Results indicated that active relative to sham stimulation ledmore » to substantially improved recall (more than 50%) at both day one and day two. Recognition memory performance did not differ between stimulation groups at either time point. These results suggest that stimulation at encoding improves memory performance by enhancing memory for details that enable a rich recollective experience, but that these improvements are evident only under some testing conditions, especially those that rely on recollection. Altogether, stimulation of the dlPFC could have led to recall improvement through enhanced encoding from stimulation or from carryover effects of stimulation that influenced retrieval processes, or both.« less

  7. One-shot percutaneous electrical nerve stimulation vs. transcutaneous electrical nerve stimulation for low back pain: comparison of therapeutic effects.

    PubMed

    Hsieh, Ru-Lan; Lee, Wen-Chung

    2002-11-01

    To investigate the therapeutic effects of one shot of low-frequency percutaneous electrical nerve stimulation one shot of transcutaneous electrical nerve stimulation in patients with low back pain. In total, 133 low back pain patients were recruited for this randomized, control study. Group 1 patients received medication only. Group 2 patients received medication plus one shot of percutaneous electrical nerve stimulation. Group 3 patients received medication plus one shot of transcutaneous electrical nerve stimulation. Therapeutic effects were measured using a visual analog scale, body surface score, pain pressure threshold, and the Quebec Back Pain Disability Scale. Immediately after one-shot treatment, the visual analog scale improved 1.53 units and the body surface score improved 3.06 units in the percutaneous electrical nerve stimulation group. In the transcutaneous electrical nerve stimulation group, the visual analog scale improved 1.50 units and the body surface score improved 3.98 units. The improvements did not differ between the two groups. There were no differences in improvement at 3 days or 1 wk after the treatment among the three groups. Simple one-shot treatment with percutaneous electrical nerve stimulation or transcutaneous electrical nerve stimulation provided immediate pain relief for low back pain patients. One-shot transcutaneous electrical nerve stimulation treatment is recommended due to the rarity of side effects and its convenient application.

  8. Spatial Working Memory Effects in Early Visual Cortex

    ERIC Educational Resources Information Center

    Munneke, Jaap; Heslenfeld, Dirk J.; Theeuwes, Jan

    2010-01-01

    The present study investigated how spatial working memory recruits early visual cortex. Participants were required to maintain a location in working memory while changes in blood oxygen level dependent (BOLD) signals were measured during the retention interval in which no visual stimulation was present. We show working memory effects during the…

  9. Noninvasive transcranial focused ultrasonic-magnetic stimulation for modulating brain oscillatory activity

    NASA Astrophysics Data System (ADS)

    Yuan, Yi; Chen, Yudong; Li, Xiaoli

    2016-02-01

    A novel technique, transcranial focused ultrasonic-magnetic stimulation (tFUMS), has been developed for noninvasive brain modulation in vivo. tFUMS has a higher spatial resolution (<2 mm) and a higher penetration depth than other noninvasive neuromodulation methods. The in vivo animal experimental results show that tFUMS can not only increase the power of local field potentials and the firing rate of the neurons, but also enhance the effect of transcranial focused ultrasound stimulation on the neuromodulation. The results demonstrate that tFUMS can modulate brain oscillatory activities by stimulating brain tissues.

  10. Neuronal and Astrocytic Monoacylglycerol Lipase Limit the Spread of Endocannabinoid Signaling in the Cerebellum.

    PubMed

    Chen, Yao; Liu, Xiaojie; Vickstrom, Casey R; Liu, Michelle J; Zhao, Li; Viader, Andreu; Cravatt, Benjamin F; Liu, Qing-Song

    2016-01-01

    Endocannabinoids are diffusible lipophilic molecules that may spread to neighboring synapses. Monoacylglycerol lipase (MAGL) is the principal enzyme that degrades the endocannabinoid 2-arachidonoylglycerol (2-AG). Using knock-out mice in which MAGL is deleted globally or selectively in neurons and astrocytes, we investigated the extent to which neuronal and astrocytic MAGL limit the spread of 2-AG-mediated retrograde synaptic depression in cerebellar slices. A brief tetanic stimulation of parallel fibers in the molecular layer induced synaptically evoked suppression of excitation (SSE) in Purkinje cells, and both neuronal and astrocytic MAGL contribute to the termination of this form of endocannabinoid-mediated synaptic depression. The spread of SSE among Purkinje cells occurred only after global knock-out of MAGL or pharmacological blockade of either MAGL or glutamate uptake, but no spread was detected following neuron- or astrocyte-specific deletion of MAGL. The spread of endocannabinoid signaling was also influenced by the spatial pattern of synaptic stimulation, because it did not occur at spatially dispersed parallel fiber synapses induced by stimulating the granular layer. The tetanic stimulation of parallel fibers did not induce endocannabinoid-mediated synaptic suppression in Golgi cells even after disruption of MAGL and glutamate uptake, suggesting that heightened release of 2-AG by Purkinje cells does not spread the retrograde signal to parallel fibers that innervate Golgi cells. These results suggest that both neuronal and astrocytic MAGL limit the spatial diffusion of 2-AG and confer synapse-specificity of endocannabinoid signaling.

  11. EDITORIAL: Special issue on optical neural engineering: advances in optical stimulation technology Special issue on optical neural engineering: advances in optical stimulation technology

    NASA Astrophysics Data System (ADS)

    Shoham, Shy; Deisseroth, Karl

    2010-08-01

    Neural engineering, itself an 'emerging interdisciplinary research area' [1] has undergone a sea change over the past few years with the emergence of exciting new optical technologies for monitoring, stimulating, inhibiting and, more generally, modulating neural activity. To a large extent, this change is driven by the realization of the promise and complementary strengths that emerging photo-stimulation tools offer to add to the neural engineer's toolbox, which has been almost exclusively based on electrical stimulation technologies. Notably, photo-stimulation is non-contact, can in some cases be genetically targeted to specific cell populations, can achieve high spatial specificity (cellular or even sub-cellular) in two or three dimensions, and opens up the possibility of large-scale spatial-temporal patterned stimulation. It also offers a seamless solution to the problem of cross-talk generated by simultaneous electrical stimulation and recording. As in other biomedical optics phenomena [2], photo-stimulation includes multiple possible modes of interaction between light and the target neurons, including a variety of photo-physical and photo-bio-chemical effects with various intrinsic components or exogenous 'sensitizers' which can be loaded into the tissue or genetically expressed. Early isolated reports of neural excitation with light date back to the late 19th century [3] and to Arvanitaki and Chalazonitis' work five decades ago [4]; however, the mechanism by which these and other direct photo-stimulation, inhibition and modulation events [5-7] took place is yet unclear, as is their short- and long-term safety profile. Photo-chemical photolysis of covalently 'caged' neurotransmitters [8, 9] has been widely used in cellular neuroscience research for three decades, including for exciting or inhibiting neural activity, and for mapping neural circuits. Technological developments now allow neurotransmitters to be uncaged with exquisite spatial specificity (down to a single spine, with two-photon uncaging) and in rapid, flexible spatial-temporal patterns [10-14]. Nevertheless, current technology generally requires damaging doses of UV or violet illumination and the continuous re-introduction of the caged compound, which, despite interest, makes for a difficult transition beyond in vitro preparations. Thus, the tremendous progress in the in vivo application of photo-stimulation tools over the past five years has been largely facilitated by two 'exciting' new photo-stimulation technologies: photo-biological stimulation of a rapidly increasing arsenal of light-sensitive ion channels and pumps ('optogenetic' probes[15-18]) and direct photo-thermal stimulation of neural tissue with an IR laser [19-21]. The Journal of Neural Engineering has dedicated a special section in this issue to highlight advances in optical stimulation technology, which includes original peer-reviewed contributions dealing with the design of modern optical systems for spatial-temporal control of optical excitation patterns and with the biophysics of neural-thermal interaction mediated by electromagnetic waves. The paper by Nikolenko, Peterka and Yuste [22] presents a compact design of a microscope-photo-stimulator based on a transmissive phase-modulating spatial-light modulator (SLM). Computer-generated holographic photo-stimulation using SLMs [12-14, 23] allows the efficient parallel projection of intense sparse patterns of light, and the welcome development of compact, user-friendly systems will likely reduce the barrier to its widespread adoption. The paper by Losavio et al [24] presents the design and functional characteristics of their acousto-optical deflector (AOD) systems for studying spatial-temporal dendritic integration in single neurons in vitro. Both single-photon (UV) and two-photon (femtosecond pulsed IR) AOD uncaging systems are described in detail. The paper presents an excellent overview of the current state of the art and limitations of this technology, which is increasingly being applied for both photo- stimulation and imaging [25, 26]. Finally, the paper by Pikov et al [27] studies the modulatory biophysical effects exerted by low power millimeter waves on neuronal excitability and membrane properties of cortical pyramidal neurons in vitro. These extensive neuro-modulatory effects seem to include a thermal component (related to the photo-thermal effects observed under laser illumination [28]) as well as a more specific effect exerted by these lower frequency (sub-THz) electromagnetic waves. These new contributions augment five previous manuscripts published by the journal on optical stimulation technology, which reported the development of a fiber-based system for in vivo optogenetic cortical stimulation [29], patterned stimulation systems based on computer-generated holography [23] and on arrays of micro-LEDs [30] designed for an optical retina neuroprosthetic [31], and an integrated system for optical stimulation with microelectrode array recording [32]. Without doubt, many more will quickly follow as neural engineers and neuroscientists increasingly tackle the many challenges that this exciting area poses. We can all expect to hear much more in the near future about the biophysics and implementation of photo-physical neural-interaction mechanisms, the design of new optogenetic probes and patterned-stimulation systems (including stand-alone and implantable systems), further integration of electrodes and optical components into electro-optical neurostimulation systems, and rapid progress towards multiple medical applications for alleviating neurological disabilities and improving human health. References [1] Durand D M 2006 What is neural engineering? J. Neural Eng. 4 (4) [2] Niemz M H 2007 Laser-Tissue Interactions: Fundamentals and Applications 3rd edn (Berlin: Springer) [3] Arsonval A D 1891 La fibre musculaire est directement excitable par la lumiere C. R. Soc. Biol. 43 318-20 [4] Arvanitaki A and Chalazonitis N 1961 Excitatiory and inhibitory processes initiated by light and infra-red radiations in single identifiable nerve cells Nervous Inhibition ed. E Florey (New York: Pergamon) pP 194-231 [5] Fork R L 1971 Laser stimulation of nerve cells in Aplysia Science 171 907-8 [6] Allegre G, Avrillier S and Albe-Fessard D 1994 Stimulation in the rat of a nerve fiber bundle by a short UV pulse from an excimer laser Neurosci. Lett. 180 261-4 [7] Hirase H, Nikolenko V, Goldberg J H and Yuste R 2002 Multiphoton stimulation of neurons J. Neurobiol. 51 237-47 [8] Callaway E M and Yuste R 2002 Stimulating neurons with light Curr. Opin. Neurobiol. 12 587-92 [9] Ellis-Davies G C 2007 Caged compounds: photorelease technology for control of cellular chemistry and physiology Nat. Methods 4 619-28 [10] Shoham S, O'Connor D H, Sarkisov D V and Wang S S 2005 Rapid neurotransmitter uncaging in spatially defined patterns Nat. Methods 2 837-43 [11] Nikolenko V, Poskanzer K E and Yuste R 2007 Two-photon photostimulation and imaging of neural circuits Nat. Methods 4 943-50 [12] Lutz C, Otis T S, DeSars V, Charpak S, DiGregorio D A and Emiliani V 2008 Holographic photolysis of caged neurotransmitters Nat. Methods 5 821-7 [13] Nikolenko V, Watson B O, Araya R, Woodruff A, Peterka D S and Yuste R 2008 SLM microscopy: scanless two-photon imaging and photostimulation with spatial light modulators Front. Neural Circuits 2 5 [14] Zahid M, Velez-Fort M, Papagiakoumou E, Ventalon C, Angulo M C and Emiliani V Holographic photolysis for multiple cell stimulation in mouse hippocampal slices PLoS One 5 e9431 [15] Boyden E S, Zhang F, Bamberg E, Nagel G and Deisseroth K 2005 Millisecond-timescale, genetically targeted optical control of neural activity Nat. Neurosci. 8 1263-8 [16] Zhang F, Aravanis A M, Adamantidis A, de Lecea L and Deisseroth K 2007 Circuit-breakers: optical technologies for probing neural signals and systems Nat. Rev. Neurosci. 8 577-81 [17] Gradinaru V, Zhang F, Ramakrishnan C, Mattis J, Prakash R, Diester I, Goshen I, Thompson K R, Deisseroth K 2010 Molecular and cellular approaches for diversifying and extending optogenetics Cell 141 154-65 [18] Zhang F, Gradinaru V, Adamantidis A R, Durand R, Airan R D, de Lecea L and Deisseroth K 2010 Optogenetic interrogation of neural circuits: technology for probing mammalian brain structures Nat. Protoc. 5 439-56 [19] Wells J, Kao C, Mariappan K, Albea J, Duco Jansen E, Konrad P and Mahadevan-Jansen A 2005 Optical stimulation of neural tissue in vivo Opt. Lett. 30 504-6 [20] Izzo A D, Richter C P, Jansen E D and Walsh J T Jr 2006 Laser stimulation of the auditory nerve Lasers Surg. Med. 38 745-53 [21] Richter C P, Izzo A D, Wells J, Jansen E D and Walsh J T Jr 2010 Neural stimulation with optical radiation Laser Photonics Rev. available at doi:10.1002/lpor.200900044 [22] Nikolenko V, Peterka D S and Yuste R 2010 A portable laser photostimulation and imaging microscope J. Neural Eng. 7 045001 [23] Golan L, Reutsky I, Farah N and Shoham S 2009 Design and characteristics of holographic neural photo-stimulation systems J. Neural Eng. 6 066004 [24] Losavio B E, Iyer V, Patel S and Saggau P 2010 Acousto-optical laser scanning for multi-site photo-stimulation of single neurons in vitro J. Neural Eng. 7 045002 [25] Duemani Reddy G, Kelleher K, Fink R and Saggau P 2008 Three-dimensional random access multiphoton microscopy for functional imaging of neuronal activity Nat. Neurosci. 11 713-20 [26] Grewe B F, Langer D, Kasper H, Kampa B M and Helmchen F 2010 High-speed in vivo calcium imaging reveals neuronal network activity with near-millisecond precision Nat. Methods 7 399-405 [27] Pikov V, Arakaki X, Harrington M, Fraser S E and Siegel P H 2010 Modulation of neuronal activity and plasma membrane propertiess with low-power millimeter waves in organotypic cortical slices J. Neural Eng. 7 045003 [28] Liang S et al 2009 Temperature-dependent activation of neurons by continuous near-infrared laser Cell Biochem. Biophys. 53 33-42 [29] Aravanis A M, Wang L-P, ZhangF, Meltzer L A, Mogri M Z, Schneider M B and Deisseroth K 2007 An optical neural interface: in vivo control of rodent motor cortex with integrated fiberoptic and optogenetic technology J. Neural Eng. 4 S143-56 [30] Grossman N et al 2010 Multi-site optical excitation using ChR2 and micro-LED array J. Neural Eng. 7 016004 [31] Degenaar P, Grossman N, Memon M A, Burrone J, Dawson M, Drakakis E, Neil M and Nikolic K 2009 Optobionic vision—a new genetically enhanced light on retinal prosthesis J. Neural Eng. 6 035007 [32] Zhang J et al 2009 Integrated device for optical stimulation and spatiotemporal electrical recording of neural activity in light-sensitized brain tissue J. Neural Eng. 6 055007

  12. Effiectiveness and safety of transcranial direct current stimulation in fibromyalgia: A systematic review and meta-analysis.

    PubMed

    Zhu, Chang-E; Yu, Bo; Zhang, Wen; Chen, Wen-Hua; Qi, Qi; Miao, Yun

    2017-01-19

    To evaluate the effectiveness and safety of transcranial direct current stimulation for fibro-myalgia. Databases, conference records and registered trials were searched for articles published from the date of establishment of the database through to October 2015. Six randomized controlled trials (n=192) of transcranial direct current stimulation for fibromyalgia were included in the current study. Two researchers independently screened the literature, assessed methodological quality using the Cochrane Collaboration's tool, and extracted data. Studies were divided into 3 groups for meta-analysis according to stimulation site and polarity. Significant improvement in pain and general fibromyalgia-related function was seen with anodal transcranial direct current stimulation over the primary motor cortex (p<0.05). However, the pressure pain threshold did not improve (p>0.05). Anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex did not significantly reduce pain or improve general fibromyalgia-related function compared with sham stimulation (p>0.05). Cathodal transcranial direct current stimulation over the primary motor cortex did not improve the pressure pain threshold compared with sham stimulation (p>0.05). No significant adverse effects were seen. Anodal transcranial direct current stimulation over the primary motor cortex is more likely than sham transcranial direct current stimulation to relieve pain and improve general fibromyalgia-related function.

  13. Spatial characterization of innervation zones under electrically elicited M-wave.

    PubMed

    Zhang, C; Peng, Y; Li, S; Zhou, P; Munoz, A; Tang, D; Zhang, Y

    2016-08-01

    The three dimensional (3D) innervation zone (IZ) imaging approach (3DIZI) has been developed in our group to localize the IZ of a particular motor unit (MU) from its motor unit action potentials decomposed from high-density surface electromyography (EMG) recordings. In this study, the developed 3DIZI approach was combined with electrical stimulation to investigate global distributions of IZs in muscles from electrically elicited M-wave recordings. Electrical stimulations were applied to the musculocutaneous nerve to activate supramaximal muscle response of the biceps brachii in one healthy subject, and high-density (128 channels) surface EMG signals of the biceps brachii muscles were recorded. The 3DIZI approach was then employed to image the IZ distribution of IZs in the 3D space of the biceps brachii. The performance of the M-wave based 3DIZI approach was evaluated with different stimulation intensities. Results show that the reconstructed IZs under supramaximal stimulation are spatially distributed in the center region of muscle belly which is consistent with previous studies. With sub-maximal stimulation intensity, the imaged IZ centers became more proximally and deeply located. The proposed M-wave based 3DIZI approach demonstrated its capability of imaging global distribution of IZs in muscles, which provide valuable information for clinical applications such as guiding botulinum toxin injection in treating muscle spasticity.

  14. Modulation of Memory by Vestibular Lesions and Galvanic Vestibular Stimulation

    PubMed Central

    Smith, Paul F.; Geddes, Lisa H.; Baek, Jean-Ha; Darlington, Cynthia L.; Zheng, Yiwen

    2010-01-01

    For decades it has been speculated that there is a close association between the vestibular system and spatial memories constructed by areas of the brain such as the hippocampus. While many animal studies have been conducted which support this relationship, only in the last 10 years have detailed quantitative studies been carried out in patients with vestibular disorders. The majority of these studies suggest that complete bilateral vestibular loss results in spatial memory deficits that are not simply due to vestibular reflex dysfunction, while the effects of unilateral vestibular damage are more complex and subtle. Very recently, reports have emerged that sub-threshold, noisy galvanic vestibular stimulation can enhance memory in humans, although this has not been investigated for spatial memory as yet. These studies add to the increasing evidence that suggests a connection between vestibular sensory information and memory in humans. PMID:21173897

  15. Focal Hemodynamic Responses in the Stimulated Hemisphere During High-Definition Transcranial Direct Current Stimulation.

    PubMed

    Muthalib, Makii; Besson, Pierre; Rothwell, John; Perrey, Stéphane

    2017-07-17

    High-definition transcranial direct current stimulation (HD-tDCS) using a 4 × 1 electrode montage has been previously shown using modeling and physiological studies to constrain the electric field within the spatial extent of the electrodes. The aim of this proof-of-concept study was to determine if functional near-infrared spectroscopy (fNIRS) neuroimaging can be used to determine a hemodynamic correlate of this 4 × 1 HD-tDCS electric field on the brain. In a three session cross-over study design, 13 healthy males received one sham (2 mA, 30 sec) and two real (HD-tDCS-1 and HD-tDCS-2, 2 mA, 10 min) anodal HD-tDCS targeting the left M1 via a 4 × 1 electrode montage (anode on C3 and 4 return electrodes 3.5 cm from anode). The two real HD-tDCS sessions afforded a within-subject replication of the findings. fNIRS was used to measure changes in brain hemodynamics (oxygenated hemoglobin integral-O 2 Hb int ) during each 10 min session from two regions of interest (ROIs) in the stimulated left hemisphere that corresponded to "within" (L in ) and "outside" (L out ) the spatial extent of the 4 × 1 electrode montage, and two corresponding ROIs (R in and R out ) in the right hemisphere. The ANOVA showed that both real anodal HD-tDCS compared to sham induced a significantly greater O 2 Hb int in the L in than L out ROIs of the stimulated left hemisphere; while there were no significant differences between the real and sham sessions for the right hemisphere ROIs. Intra-class correlation coefficients showed "fair-to-good" reproducibility for the left stimulated hemisphere ROIs. The greater O 2 Hb int "within" than "outside" the spatial extent of the 4 × 1 electrode montage represents a hemodynamic correlate of the electrical field distribution, and thus provides a prospective reliable method to determine the dose of stimulation that is necessary to optimize HD-tDCS parameters in various applications. © 2017 International Neuromodulation Society.

  16. Effect of microgravity on spatial orientation and posture regulation during Coriolis stimulation.

    PubMed

    Takahashi, Masahiro; Sekine, Motoki; Ikeda, Takuo; Watanuki, Koichi; Hakuta, Shuzo; Takeoka, Hajime

    2004-05-01

    To elucidate spatial orientation and posture regulation under conditions of microgravity. Coriolis stimulation was done with five normal subjects on the ground (1 g) and onboard an aircraft (under conditions of microgravity during parabolic flight). Subjects were asked to tilt their heads forward during rotation at speeds of 0, 50, 100 and 150 degrees/s on the ground and 100 degrees/s during flight. Body sway was recorded using a 3D linear accelerometer and eye movements using an infrared charge-coupled device video camera. Flight experiments were performed on 5 consecutive days, and 11-16 parabolic maneuvers were done during each flight. Two subjects boarded each flight and were examined alternately at least five times. Coriolis stimulation at 1 g caused body sway, nystagmus and a movement sensation in accordance with inertial inputs at 1 g. Neither body sway, excepting a minute sway due to the Coriolis force, nor a movement sensation occurred in microgravity, but nystagmus was recorded. Posture, eye movement and sensation at 1 g are controlled with reference to spatial coordinates that represent the external world in the brain. Normal spatial coordinates are not relevant in microgravity because there is no Z-axis, and the posture regulation and sensation that depend on them collapse. The discrepancy in responses between posture and eye movement under conditions of microgravity may be caused by a different constitution of the effectors which adjust posture and gaze.

  17. Spatial and temporal characteristics of V1 microstimulation during chronic implantation of a microelectrode array in a behaving macaque

    NASA Astrophysics Data System (ADS)

    Davis, T. S.; Parker, R. A.; House, P. A.; Bagley, E.; Wendelken, S.; Normann, R. A.; Greger, B.

    2012-12-01

    Objective. It has been hypothesized that a vision prosthesis capable of evoking useful visual percepts can be based upon electrically stimulating the primary visual cortex (V1) of a blind human subject via penetrating microelectrode arrays. As a continuation of earlier work, we examined several spatial and temporal characteristics of V1 microstimulation. Approach. An array of 100 penetrating microelectrodes was chronically implanted in V1 of a behaving macaque monkey. Microstimulation thresholds were measured using a two-alternative forced choice detection task. Relative locations of electrically-evoked percepts were measured using a memory saccade-to-target task. Main results. The principal finding was that two years after implantation we were able to evoke behavioural responses to electric stimulation across the spatial extent of the array using groups of contiguous electrodes. Consistent responses to stimulation were evoked at an average threshold current per electrode of 204 ± 49 µA (mean ± std) for groups of four electrodes and 91 ± 25 µA for groups of nine electrodes. Saccades to electrically-evoked percepts using groups of nine electrodes showed that the animal could discriminate spatially distinct percepts with groups having an average separation of 1.6 ± 0.3 mm (mean ± std) in cortex and 1.0° ± 0.2° in visual space. Significance. These results demonstrate chronic perceptual functionality and provide evidence for the feasibility of a cortically-based vision prosthesis for the blind using penetrating microelectrodes.

  18. Temporal information entropy of the Blood-Oxygenation Level-Dependent signals increases in the activated human primary visual cortex

    NASA Astrophysics Data System (ADS)

    DiNuzzo, Mauro; Mascali, Daniele; Moraschi, Marta; Bussu, Giorgia; Maraviglia, Bruno; Mangia, Silvia; Giove, Federico

    2017-02-01

    Time-domain analysis of blood-oxygenation level-dependent (BOLD) signals allows the identification of clusters of voxels responding to photic stimulation in primary visual cortex (V1). However, the characterization of information encoding into temporal properties of the BOLD signals of an activated cluster is poorly investigated. Here, we used Shannon entropy to determine spatial and temporal information encoding in the BOLD signal within the most strongly activated area of the human visual cortex during a hemifield photic stimulation. We determined the distribution profile of BOLD signals during epochs at rest and under stimulation within small (19-121 voxels) clusters designed to include only voxels driven by the stimulus as highly and uniformly as possible. We found consistent and significant increases (2-4% on average) in temporal information entropy during activation in contralateral but not ipsilateral V1, which was mirrored by an expected loss of spatial information entropy. These opposite changes coexisted with increases in both spatial and temporal mutual information (i.e. dependence) in contralateral V1. Thus, we showed that the first cortical stage of visual processing is characterized by a specific spatiotemporal rearrangement of intracluster BOLD responses. Our results indicate that while in the space domain BOLD maps may be incapable of capturing the functional specialization of small neuronal populations due to relatively low spatial resolution, some information encoding may still be revealed in the temporal domain by an increase of temporal information entropy.

  19. Spatially divergent cardiac responses to nicotinic stimulation of ganglionated plexus neurons in the canine heart.

    PubMed

    Cardinal, René; Pagé, Pierre; Vermeulen, Michel; Ardell, Jeffrey L; Armour, J Andrew

    2009-01-28

    Ganglionated plexuses (GPs) are major constituents of the intrinsic cardiac nervous system, the final common integrator of regional cardiac control. We hypothesized that nicotinic stimulation of individual GPs exerts divergent regional influences, affecting atrial as well as ventricular functions. In 22 anesthetized canines, unipolar electrograms were recorded from 127 atrial and 127 ventricular epicardial loci during nicotine injection (100 mcg in 0.1 ml) into either the 1) right atrial (RA), 2) dorsal atrial, 3) left atrial, 4) inferior vena cava-inferior left atrial, 5) right ventricular, 6) ventral septal ventricular or 7) cranial medial ventricular (CMV) GP. In addition to sinus and AV nodal function, neural effects on atrial and ventricular repolarization were identified as changes in the area subtended by unipolar recordings under basal conditions and at maximum neurally-induced effects. Animals were studied with intact AV node or following ablation to achieve ventricular rate control. Atrial rate was affected in response to stimulation of all 7 GPs with an incidence of 50-95% of the animals among the different GPs. AV conduction was affected following stimulation of 6/7 GP with an incidence of 22-75% among GPs. Atrial and ventricular repolarization properties were affected by atrial as well as ventricular GP stimulation. Distinct regional patterns of repolarization changes were identified in response to stimulation of individual GPs. RAGP predominantly affected the RA and posterior right ventricular walls whereas CMVGP elicited biatrial and biventricular repolarization changes. Spatially divergent and overlapping cardiac regions are affected in response to nicotinic stimulation of neurons in individual GPs.

  20. Temporal and spatial tuning of dorsal lateral geniculate nucleus neurons in unanesthetized rats

    PubMed Central

    Sriram, Balaji; Meier, Philip M.

    2016-01-01

    Visual response properties of neurons in the dorsolateral geniculate nucleus (dLGN) have been well described in several species, but not in rats. Analysis of responses from the unanesthetized rat dLGN will be needed to develop quantitative models that account for visual behavior of rats. We recorded visual responses from 130 single units in the dLGN of 7 unanesthetized rats. We report the response amplitudes, temporal frequency, and spatial frequency sensitivities in this population of cells. In response to 2-Hz visual stimulation, dLGN cells fired 15.9 ± 11.4 spikes/s (mean ± SD) modulated by 10.7 ± 8.4 spikes/s about the mean. The optimal temporal frequency for full-field stimulation ranged from 5.8 to 19.6 Hz across cells. The temporal high-frequency cutoff ranged from 11.7 to 33.6 Hz. Some cells responded best to low temporal frequency stimulation (low pass), and others were strictly bandpass; most cells fell between these extremes. At 2- to 4-Hz temporal modulation, the spatial frequency of drifting grating that drove cells best ranged from 0.008 to 0.18 cycles per degree (cpd) across cells. The high-frequency cutoff ranged from 0.01 to 1.07 cpd across cells. The majority of cells were driven best by the lowest spatial frequency tested, but many were partially or strictly bandpass. We conclude that single units in the rat dLGN can respond vigorously to temporal modulation up to at least 30 Hz and spatial detail up to 1 cpd. Tuning properties were heterogeneous, but each fell along a continuum; we found no obvious clustering into discrete cell types along these dimensions. PMID:26936980

  1. Repeated cognitive stimulation alleviates memory impairments in an Alzheimer's disease mouse model.

    PubMed

    Martinez-Coria, Hilda; Yeung, Stephen T; Ager, Rahasson R; Rodriguez-Ortiz, Carlos J; Baglietto-Vargas, David; LaFerla, Frank M

    2015-08-01

    Alzheimer's disease is a neurodegenerative disease associated with progressive memory and cognitive decline. Previous studies have identified the benefits of cognitive enrichment on reducing disease pathology. Additionally, epidemiological and clinical data suggest that repeated exercise, and cognitive and social enrichment, can improve and/or delay the cognitive deficiencies associated with aging and neurodegenerative diseases. In the present study, 3xTg-AD mice were exposed to a rigorous training routine beginning at 3 months of age, which consisted of repeated training in the Morris water maze spatial recognition task every 3 months, ending at 18 months of age. At the conclusion of the final Morris water maze training session, animals subsequently underwent testing in another hippocampus-dependent spatial task, the Barnes maze task, and on the more cortical-dependent novel object recognition memory task. Our data show that periodic cognitive enrichment throughout aging, via multiple learning episodes in the Morris water maze task, can improve the memory performance of aged 3xTg-AD mice in a separate spatial recognition task, and in a preference memory task, when compared to naïve aged matched 3xTg-AD mice. Furthermore, we observed that the cognitive enrichment properties of Morris water maze exposer, was detectable in repeatedly trained animals as early as 6 months of age. These findings suggest early repeated cognitive enrichment can mitigate the diverse cognitive deficits observed in Alzheimer's disease. Published by Elsevier Inc.

  2. Postmortem diffusion MRI of the human brainstem and thalamus for deep brain stimulator electrode localization.

    PubMed

    Calabrese, Evan; Hickey, Patrick; Hulette, Christine; Zhang, Jingxian; Parente, Beth; Lad, Shivanand P; Johnson, G Allan

    2015-08-01

    Deep brain stimulation (DBS) is an established surgical therapy for medically refractory tremor disorders including essential tremor (ET) and is currently under investigation for use in a variety of other neurologic and psychiatric disorders. There is growing evidence that the anti-tremor effects of DBS for ET are directly related to modulation of the dentatorubrothalamic tract (DRT), a white matter pathway that connects the cerebellum, red nucleus, and ventral intermediate nucleus of the thalamus. Emerging white matter targets for DBS, like the DRT, will require improved three-dimensional (3D) reference maps of deep brain anatomy and structural connectivity for accurate electrode targeting. High-resolution diffusion MRI of postmortem brain specimens can provide detailed volumetric images of important deep brain nuclei and 3D reconstructions of white matter pathways with probabilistic tractography techniques. We present a high spatial and angular resolution diffusion MRI template of the postmortem human brainstem and thalamus with 3D reconstructions of the nuclei and white matter tracts involved in ET circuitry. We demonstrate registration of these data to in vivo, clinical images from patients receiving DBS therapy, and correlate electrode proximity to tractography of the DRT with improvement of ET symptoms. © 2015 Wiley Periodicals, Inc.

  3. Assessing a 3D smoothed seismicity model of induced earthquakes

    NASA Astrophysics Data System (ADS)

    Zechar, Jeremy; Király, Eszter; Gischig, Valentin; Wiemer, Stefan

    2016-04-01

    As more energy exploration and extraction efforts cause earthquakes, it becomes increasingly important to control induced seismicity. Risk management schemes must be improved and should ultimately be based on near-real-time forecasting systems. With this goal in mind, we propose a test bench to evaluate models of induced seismicity based on metrics developed by the CSEP community. To illustrate the test bench, we consider a model based on the so-called seismogenic index and a rate decay; to produce three-dimensional forecasts, we smooth past earthquakes in space and time. We explore four variants of this model using the Basel 2006 and Soultz-sous-Forêts 2004 datasets to make short-term forecasts, test their consistency, and rank the model variants. Our results suggest that such a smoothed seismicity model is useful for forecasting induced seismicity within three days, and giving more weight to recent events improves forecast performance. Moreover, the location of the largest induced earthquake is forecast well by this model. Despite the good spatial performance, the model does not estimate the seismicity rate well: it frequently overestimates during stimulation and during the early post-stimulation period, and it systematically underestimates around shut-in. In this presentation, we also describe a robust estimate of information gain, a modification that can also benefit forecast experiments involving tectonic earthquakes.

  4. Transparent, conformable, active multielectrode array using organic electrochemical transistors.

    PubMed

    Lee, Wonryung; Kim, Dongmin; Matsuhisa, Naoji; Nagase, Masae; Sekino, Masaki; Malliaras, George G; Yokota, Tomoyuki; Someya, Takao

    2017-10-03

    Mechanically flexible active multielectrode arrays (MEA) have been developed for local signal amplification and high spatial resolution. However, their opaqueness limited optical observation and light stimulation during use. Here, we show a transparent, ultraflexible, and active MEA, which consists of transparent organic electrochemical transistors (OECTs) and transparent Au grid wirings. The transparent OECT is made of Au grid electrodes and has shown comparable performance with OECTs with nontransparent electrodes/wirings. The transparent active MEA realizes the spatial mapping of electrocorticogram electrical signals from an optogenetic rat with 1-mm spacing and shows lower light artifacts than noise level. Our active MEA would open up the possibility of precise investigation of a neural network system with direct light stimulation.

  5. Potential Benefits of an Integrated Electric-Acoustic Sound Processor with Children: A Preliminary Report.

    PubMed

    Wolfe, Jace; Neumann, Sara; Schafer, Erin; Marsh, Megan; Wood, Mark; Baker, R Stanley

    2017-02-01

    A number of published studies have demonstrated the benefits of electric-acoustic stimulation (EAS) over conventional electric stimulation for adults with functional low-frequency acoustic hearing and severe-to-profound high-frequency hearing loss. These benefits potentially include better speech recognition in quiet and in noise, better localization, improvements in sound quality, better music appreciation and aptitude, and better pitch recognition. There is, however, a paucity of published reports describing the potential benefits and limitations of EAS for children with functional low-frequency acoustic hearing and severe-to-profound high-frequency hearing loss. The objective of this study was to explore the potential benefits of EAS for children. A repeated measures design was used to evaluate performance differences obtained with EAS stimulation versus acoustic- and electric-only stimulation. Seven users of Cochlear Nucleus Hybrid, Nucleus 24 Freedom, CI512, and CI422 implants were included in the study. Sentence recognition (assayed using the pediatric version of the AzBio sentence recognition test) was evaluated in quiet and at three fixed signal-to-noise ratios (SNR) (0, +5, and +10 dB). Functional hearing performance was also evaluated with the use of questionnaires, including the comparative version of the Speech, Spatial, and Qualities, the Listening Inventory for Education Revised, and the Children's Home Inventory for Listening Difficulties. Speech recognition in noise was typically better with EAS compared to participants' performance with acoustic- and electric-only stimulation, particularly when evaluated at the less favorable SNR. Additionally, in real-world situations, children generally preferred to use EAS compared to electric-only stimulation. Also, the participants' classroom teachers observed better hearing performance in the classroom with the use of EAS. Use of EAS provided better speech recognition in quiet and in noise when compared to performance obtained with use of acoustic- and electric-only stimulation, and children responded favorably to the use of EAS implemented in an integrated sound processor for real-world use. American Academy of Audiology

  6. Improved detection following Neuro-Eye Therapy in patients with post-geniculate brain damage.

    PubMed

    Sahraie, Arash; Macleod, Mary-Joan; Trevethan, Ceri T; Robson, Siân E; Olson, John A; Callaghan, Paula; Yip, Brigitte

    2010-09-01

    Damage to the optic radiation or the occipital cortex results in loss of vision in the contralateral visual field, termed partial cortical blindness or hemianopia. Previously, we have demonstrated that stimulation in the field defect using visual stimuli with optimal properties for blindsight detection can lead to increases in visual sensitivity within the blind field of a group of patients. The present study was aimed to extend the previous work by investigating the effect of positive feedback on recovery of visual sensitivity. Patients' abilities for detection of a range of spatial frequencies within their field defect were determined using a temporal two-alternative forced-choice technique, before and after a period of visual training (n = 4). Patients underwent Neuro-Eye Therapy which involved detection of temporally modulated spatial grating patches at specific retinal locations within their field defect. Three patients showed improved detection ability following visual training. Based on our previous studies, we had hypothesised that should the occipital brain lesion extend anteriorly to the thalamus, little recovery would be expected. Here, we describe one such case who showed no improvements after extensive training. The present study provides further evidence that recovery (a) can be gradual and may require a large number of training sessions (b) can be accelerated using positive feedback and (c) may be less likely to take place if the occipital damage extends anteriorly to the thalamus.

  7. Integrated trimodal SSEP experimental setup for visual, auditory and tactile stimulation

    NASA Astrophysics Data System (ADS)

    Kuś, Rafał; Spustek, Tomasz; Zieleniewska, Magdalena; Duszyk, Anna; Rogowski, Piotr; Suffczyński, Piotr

    2017-12-01

    Objective. Steady-state evoked potentials (SSEPs), the brain responses to repetitive stimulation, are commonly used in both clinical practice and scientific research. Particular brain mechanisms underlying SSEPs in different modalities (i.e. visual, auditory and tactile) are very complex and still not completely understood. Each response has distinct resonant frequencies and exhibits a particular brain topography. Moreover, the topography can be frequency-dependent, as in case of auditory potentials. However, to study each modality separately and also to investigate multisensory interactions through multimodal experiments, a proper experimental setup appears to be of critical importance. The aim of this study was to design and evaluate a novel SSEP experimental setup providing a repetitive stimulation in three different modalities (visual, tactile and auditory) with a precise control of stimuli parameters. Results from a pilot study with a stimulation in a particular modality and in two modalities simultaneously prove the feasibility of the device to study SSEP phenomenon. Approach. We developed a setup of three separate stimulators that allows for a precise generation of repetitive stimuli. Besides sequential stimulation in a particular modality, parallel stimulation in up to three different modalities can be delivered. Stimulus in each modality is characterized by a stimulation frequency and a waveform (sine or square wave). We also present a novel methodology for the analysis of SSEPs. Main results. Apart from constructing the experimental setup, we conducted a pilot study with both sequential and simultaneous stimulation paradigms. EEG signals recorded during this study were analyzed with advanced methodology based on spatial filtering and adaptive approximation, followed by statistical evaluation. Significance. We developed a novel experimental setup for performing SSEP experiments. In this sense our study continues the ongoing research in this field. On the other hand, the described setup along with the presented methodology is a considerable improvement and an extension of methods constituting the state-of-the-art in the related field. Device flexibility both with developed analysis methodology can lead to further development of diagnostic methods and provide deeper insight into information processing in the human brain.

  8. Groundwater–surface water mixing shifts ecological assembly processes and stimulates organic carbon turnover

    DOE PAGES

    Stegen, James C.; Fredrickson, James K.; Wilkins, Michael J.; ...

    2016-04-07

    Environmental transition zones are associated with geochemical gradients that overcome energy limitations to microbial metabolism, resulting in biogeochemical hot spots and moments. Riverine systems where groundwater mixes with surface water (the hyporheic zone) are spatially complex and temporally dynamic, making development of predictive models challenging. Spatial and temporal variations in hyporheic zone microbial communities are a key, but understudied, component of riverine biogeochemical function. To investigate the coupling among groundwater-surface water mixing, microbial communities, and biogeochemistry we applied ecological theory, aqueous biogeochemistry, DNA sequencing, and ultra-high resolution organic carbon profiling to field samples collected across times and locations representing amore » broad range of mixing conditions. Mixing of groundwater and surface water resulted in a shift from transport-driven stochastic dynamics to a deterministic microbial structure associated with elevated biogeochemical rates. While the dynamics of the hyporheic make predictive modeling a challenge, we provide new knowledge that can improve the tractability of such models.« less

  9. Predicting successful tactile mapping of virtual objects.

    PubMed

    Brayda, Luca; Campus, Claudio; Gori, Monica

    2013-01-01

    Improving spatial ability of blind and visually impaired people is the main target of orientation and mobility (O&M) programs. In this study, we use a minimalistic mouse-shaped haptic device to show a new approach aimed at evaluating devices providing tactile representations of virtual objects. We consider psychophysical, behavioral, and subjective parameters to clarify under which circumstances mental representations of spaces (cognitive maps) can be efficiently constructed with touch by blindfolded sighted subjects. We study two complementary processes that determine map construction: low-level perception (in a passive stimulation task) and high-level information integration (in an active exploration task). We show that jointly considering a behavioral measure of information acquisition and a subjective measure of cognitive load can give an accurate prediction and a practical interpretation of mapping performance. Our simple TActile MOuse (TAMO) uses haptics to assess spatial ability: this may help individuals who are blind or visually impaired to be better evaluated by O&M practitioners or to evaluate their own performance.

  10. Promotion of Myogenic Maturation by Timely Application of Electric Field Along the Topographical Alignment.

    PubMed

    Ko, Ung Hyun; Park, Sukhee; Bang, Hyunseung; Kim, Mina; Shin, Hyunjun; Shin, Jennifer H

    2018-05-01

    Engineered muscular substitutes can restore the impaired muscle functions when integrated properly into the host tissue. To generate functional muscles with sufficient contractility at the site of transplant, the in vitro construction of fully differentiated muscle fibers would be desired. Many previous reports have identified either topographical alignment or electrical stimulation as an effective tool to promote myogenic differentiation. However, optimization of spatial and temporal arrangement of these two physical cues for better differentiation and maturation of skeletal muscles has not been investigated. In this article, we introduce a novel cell culture system that allows simultaneous application of these two independent directional cues at both orthogonal and parallel arrangements. We then show that the parallel arrangement of the aligned topography and the electric field synergistically facilitates better differentiation and maturation of C2C12, generating myotubes with more fused nuclei. Addition of the electric stimulation at the late stage of myogenic differentiation is found to further improve cell fusion to form multinucleate myotubes through a phosphatidylinositol-3-OH-kinase-dependent pathway. As such, we successfully demonstrated that the combined stimulation of topographical and electrical cues could effectively enhance both myogenic differentiation and maturation in a temporal and orientation-dependent manner, providing the basis for therapeutic strategies for regenerative tissue engineering.

  11. Cerebral correlates of visuospatial neglect: a direct cerebral stimulation study.

    PubMed

    Vallar, Giuseppe; Bello, Lorenzo; Bricolo, Emanuela; Castellano, Antonella; Casarotti, Alessandra; Falini, Andrea; Riva, Marco; Fava, Enrica; Papagno, Costanza

    2014-04-01

    To assess the role of the superior longitudinal fascicle, the inferior fronto-occipital fascicle, and the posterior parietal lobe in visuospatial attention in humans during awake brain surgery. Seven patients with hemispheric gliomas (six in the right hemisphere) entered the study. During surgery in asleep/awake anesthesia, guided by Diffusion Tensor Imaging Fiber Tractography, visuospatial neglect was assessed during direct electrical stimulation by computerized line bisection. A rightward deviation, indicating left visuospatial neglect, was induced in six of seven patients by stimulation of the parietofrontal connections, in a location consistent with the trajectory of the second branch of the superior longitudinal fascicle. Stimulation of the medial and dorsal white matter of the superior parietal lobule (corresponding to the first branch of the superior longitudinal fascicle), of the ventral and lateral white matter of the supramarginal gyrus (corresponding to the third branch of the superior longitudinal fascicle), and of the inferior occipitofrontal fasciculus, was largely ineffective. Stimulation of the superior parietal lobule (Brodmann's area 7) caused a marked rightward deviation in all of the six assessed patients, while stimulation of Brodmann's areas 5 and 19 was ineffective. The parietofrontal connections of the dorso-lateral fibers of the superior longitudinal fascicle (i.e., the second branch of the fascicle), and the posterior superior parietal lobe (Brodmann's area 7) are involved in the orientation of spatial attention. Spatial neglect should be assessed systematically during awake brain surgery, particularly when the right parietal lobe may be involved by the neurosurgical procedure. Copyright © 2013 Wiley Periodicals, Inc.

  12. Neural time course of visually enhanced echo suppression.

    PubMed

    Bishop, Christopher W; London, Sam; Miller, Lee M

    2012-10-01

    Auditory spatial perception plays a critical role in day-to-day communication. For instance, listeners utilize acoustic spatial information to segregate individual talkers into distinct auditory "streams" to improve speech intelligibility. However, spatial localization is an exceedingly difficult task in everyday listening environments with numerous distracting echoes from nearby surfaces, such as walls. Listeners' brains overcome this unique challenge by relying on acoustic timing and, quite surprisingly, visual spatial information to suppress short-latency (1-10 ms) echoes through a process known as "the precedence effect" or "echo suppression." In the present study, we employed electroencephalography (EEG) to investigate the neural time course of echo suppression both with and without the aid of coincident visual stimulation in human listeners. We find that echo suppression is a multistage process initialized during the auditory N1 (70-100 ms) and followed by space-specific suppression mechanisms from 150 to 250 ms. Additionally, we find a robust correlate of listeners' spatial perception (i.e., suppressing or not suppressing the echo) over central electrode sites from 300 to 500 ms. Contrary to our hypothesis, vision's powerful contribution to echo suppression occurs late in processing (250-400 ms), suggesting that vision contributes primarily during late sensory or decision making processes. Together, our findings support growing evidence that echo suppression is a slow, progressive mechanism modifiable by visual influences during late sensory and decision making stages. Furthermore, our findings suggest that audiovisual interactions are not limited to early, sensory-level modulations but extend well into late stages of cortical processing.

  13. Gait training assisted by multi-channel functional electrical stimulation early after stroke: study protocol for a randomized controlled trial.

    PubMed

    van Bloemendaal, Maijke; Bus, Sicco A; de Boer, Charlotte E; Nollet, Frans; Geurts, Alexander C H; Beelen, Anita

    2016-10-01

    Many stroke survivors suffer from paresis of lower limb muscles, resulting in compensatory gait patterns characterised by asymmetries in spatial and temporal parameters and reduced walking capacity. Functional electrical stimulation has been used to improve walking capacity, but evidence is mostly limited to the orthotic effects of peroneal functional electrical stimulation in the chronic phase after stroke. The aim of this study is to investigate the therapeutic effects of up to 10 weeks of multi-channel functional electrical stimulation (MFES)-assisted gait training on the restoration of spatiotemporal gait symmetry and walking capacity in subacute stroke patients. In a proof-of-principle study with a randomised controlled design, 40 adult patients with walking deficits who are admitted for inpatient rehabilitation within 31 days since the onset of stroke are randomised to either MFES-assisted gait training or conventional gait training. Gait training is delivered in 30-minute sessions each workday for up to 10 weeks. The step length symmetry ratio is the primary outcome. Blinded assessors conduct outcome assessments at baseline, every 2 weeks during the intervention period, immediately post intervention and at 3-month follow-up. This study aims to provide preliminary evidence for the feasibility and effectiveness of MFES-assisted gait rehabilitation early after stroke. Results will inform the design of a larger multi-centre trial. This trial is registered at the Netherlands Trial Register (number NTR4762 , registered 28 August 2014).

  14. Nanosecond laser pulse stimulation of spiral ganglion neurons and model cells.

    PubMed

    Rettenmaier, Alexander; Lenarz, Thomas; Reuter, Günter

    2014-04-01

    Optical stimulation of the inner ear has recently attracted attention, suggesting a higher frequency resolution compared to electrical cochlear implants due to its high spatial stimulation selectivity. Although the feasibility of the effect is shown in multiple in vivo experiments, the stimulation mechanism remains open to discussion. Here we investigate in single-cell measurements the reaction of spiral ganglion neurons and model cells to irradiation with a nanosecond-pulsed laser beam over a broad wavelength range from 420 nm up to 1950 nm using the patch clamp technique. Cell reactions were wavelength- and pulse-energy-dependent but too small to elicit action potentials in the investigated spiral ganglion neurons. As the applied radiant exposure was much higher than the reported threshold for in vivo experiments in the same laser regime, we conclude that in a stimulation paradigm with nanosecond-pulses, direct neuronal stimulation is not the main cause of optical cochlea stimulation.

  15. Spatial factors and muscle spindle input influence the generation of neuromuscular responses to stimulation of the human foot

    NASA Astrophysics Data System (ADS)

    Layne, Charles S.; Forth, Katharine E.; Abercromby, Andrew F. J.

    2005-05-01

    Removal of the mechanical pressure gradient on the soles leads to physiological adaptations that ultimately result in neuromotor degradation during spaceflight. We propose that mechanical stimulation of the soles serves to partially restore the afference associated with bipedal loading and assists in attenuating the negative neuromotor consequences of spaceflight. A dynamic foot stimulus device was used to stimulate the soles in a variety of conditions with different stimulation locations, stimulation patterns and muscle spindle input. Surface electromyography revealed the lateral side of the sole elicited the greatest neuromuscular response in ankle musculature, followed by the medial side, then the heel. These responses were modified by preceding stimulation. Neuromuscular responses were also influenced by the level of muscle spindle input. These results provide important information that can be used to guide the development of a "passive" countermeasure that relies on sole stimulation and can supplement existing exercise protocols during spaceflight.

  16. Intermittent θ burst stimulation modulates resting-state functional connectivity in the attention network and promotes behavioral recovery in patients with visual spatial neglect.

    PubMed

    Cao, Lei; Fu, Wei; Zhang, Yanming; Huo, Su; Du, JuBao; Zhu, Lin; Song, Weiqun

    2016-12-07

    Functional connectivity changes in the attention network are viewed as a physiological signature of visual spatial neglect (VSN). The left dorsal lateral prefrontal cortex (LDLPFC) is known to initiate and monitor top-down attentional control and dynamically adjust behavioral performance. This study aimed to investigate whether increasing the activity of the LDLPFC through intermittent θ burst stimulation (iTBS) could modulate the resting-state functional connectivity in the attention network and facilitate recovery from VSN. Patients with right hemisphere stroke and VSN were randomly assigned to two groups matched for clinical characteristics and given a 10-day treatment. On each day, all patients underwent visual scanning training and motor function training and received iTBS over the LDLPFC either at 80% resting motor threshold (RMT) or at 40% RMT before the trainings. MRI, the line bisection test, and the star cancelation test were performed before and after treatment. Patients who received iTBS at 80% RMT showed a large-scale reduction in the resting-state functional connectivity extent, largely in the right attention network, and more significant improvement of behavioral performance compared with patients who received iTBS at 40% RMT. These results support that the LDLPFC potentially plays a key role in the modulation of attention networks in neglect. Increasing the activity of the LDPLPFC through iTBS can facilitate recovery from VSN in patients with stroke.

  17. Combining physical training with transcranial direct current stimulation to improve gait in Parkinson's disease: a pilot randomized controlled study.

    PubMed

    Kaski, D; Dominguez, R O; Allum, J H; Islam, A F; Bronstein, A M

    2014-11-01

    To improve gait and balance in patients with Parkinson's disease by combining anodal transcranial direct current stimulation with physical training. In a double-blind design, one group (physical training; n = 8) underwent gait and balance training during transcranial direct current stimulation (tDCS; real/sham). Real stimulation consisted of 15 minutes of 2 mA transcranial direct current stimulation over primary motor and premotor cortex. For sham, the current was switched off after 30 seconds. Patients received the opposite stimulation (sham/real) with physical training one week later; the second group (No physical training; n = 8) received stimulation (real/sham) but no training, and also repeated a sequential transcranial direct current stimulation session one week later (sham/real). Hospital Srio Libanes, Buenos Aires, Argentina. Sixteen community-dwelling patients with Parkinson's disease. Transcranial direct current stimulation with and without concomitant physical training. Gait velocity (primary gait outcome), stride length, timed 6-minute walk test, Timed Up and Go Test (secondary outcomes), and performance on the pull test (primary balance outcome). Transcranial direct current stimulation with physical training increased gait velocity (mean = 29.5%, SD = 13; p < 0.01) and improved balance (pull test: mean = 50.9%, SD = 37; p = 0.01) compared with transcranial direct current stimulation alone. There was no isolated benefit of transcranial direct current stimulation alone. Although physical training improved gait velocity (mean = 15.5%, SD = 12.3; p = 0.03), these effects were comparatively less than with combined tDCS + physical therapy (p < 0.025). Greater stimulation-related improvements were seen in patients with more advanced disease. Anodal transcranial direct current stimulation during physical training improves gait and balance in patients with Parkinson's disease. Power calculations revealed that 14 patients per treatment arm (α = 0.05; power = 0.8) are required for a definitive trial. © The Author(s) 2014.

  18. The Effect of Visual-Spatial Stimulation on Emergent Readers at Risk for Specific Learning Disability in Reading

    ERIC Educational Resources Information Center

    Zascavage, Victoria Selden; McKenzie, Ginger Kelley; Buot, Max; Woods, Carol; Orton-Gillingham, Fellow

    2012-01-01

    This study compared word recognition for words written in a traditional flat font to the same words written in a three-dimensional appearing font determined to create a right hemispheric stimulation. The participants were emergent readers enrolled in Montessori schools in the United States learning to read basic CVC (consonant, vowel, consonant)…

  19. Silicon chip with capacitors and transistors for interfacing organotypic brain slice of rat hippocampus.

    PubMed

    Hutzler, Michael; Fromherz, Peter

    2004-04-01

    Probing projections between brain areas and their modulation by synaptic potentiation requires dense arrays of contacts for noninvasive electrical stimulation and recording. Semiconductor technology is able to provide planar arrays with high spatial resolution to be used with planar neuronal structures such as organotypic brain slices. To address basic methodical issues we developed a silicon chip with simple arrays of insulated capacitors and field-effect transistors for stimulation of neuronal activity and recording of evoked field potentials. Brain slices from rat hippocampus were cultured on that substrate. We achieved local stimulation of the CA3 region by applying defined voltage pulses to the chip capacitors. Recording of resulting local field potentials in the CA1 region was accomplished with transistors. The relationship between stimulation and recording was rationalized by a sheet conductor model. By combining a row of capacitors with a row of transistors we determined a simple stimulus-response matrix from CA3 to CA1. Possible contributions of inhomogeneities of synaptic projection, of tissue structure and of neuroelectronic interfacing were considered. The study provides the basis for a development of semiconductor chips with high spatial resolution that are required for long-term studies of topographic mapping.

  20. Transverse tripolar stimulation of peripheral nerve: a modelling study of spatial selectivity.

    PubMed

    Deurloo, K E; Holsheimer, J; Boom, H B

    1998-01-01

    Various anode-cathode configurations in a nerve cuff are modelled to predict their spatial selectivity characteristics for functional nerve stimulation. A 3D volume conductor model of a monofascicular nerve is used for the computation of stimulation-induced field potentials, whereas a cable model of myelinated nerve fibre is used for the calculation of the excitation thresholds of fibres. As well as the usual configurations (monopole, bipole, longitudinal tripole, 'steering' anode), a transverse tripolar configuration (central cathode) is examined. It is found that the transverse tripole is the only configuration giving convex recruitment contours and therefore maximises activation selectivity for a small (cylindrical) bundle of fibres in the periphery of a monofascicular nerve trunk. As the electrode configuration is changed to achieve greater selectivity, the threshold current increases. Therefore threshold currents for fibre excitation with a transverse tripole are relatively high. Inverse recruitment is less extreme than for the other configurations. The influences of several geometrical parameters and model conductivities of the transverse tripole on selectivity and threshold current are analysed. In chronic implantation, when electrodes are encapsulated by a layer of fibrous tissue, threshold currents are low, whereas the shape of the recruitment contours in transverse tripolar stimulation does not change.

  1. Electric crosstalk impairs spatial resolution of multi-electrode arrays in retinal implants

    NASA Astrophysics Data System (ADS)

    Wilke, R. G. H.; Khalili Moghadam, G.; Lovell, N. H.; Suaning, G. J.; Dokos, S.

    2011-08-01

    Active multi-electrode arrays are used in vision prostheses, including optic nerve cuffs and cortical and retinal implants for stimulation of neural tissue. For retinal implants, arrays with up to 1500 electrodes are used in clinical trials. The ability to convey information with high spatial resolution is critical for these applications. To assess the extent to which spatial resolution is impaired by electric crosstalk, finite-element simulation of electric field distribution in a simplified passive tissue model of the retina is performed. The effects of electrode size, electrode spacing, distance to target cells, and electrode return configuration (monopolar, tripolar, hexagonal) on spatial resolution is investigated in the form of a mathematical model of electric field distribution. Results show that spatial resolution is impaired with increased distance from the electrode array to the target cells. This effect can be partly compensated by non-monopolar electrode configurations and larger electrode diameters, albeit at the expense of lower pixel densities due to larger covering areas by each stimulation electrode. In applications where multi-electrode arrays can be brought into close proximity to target cells, as presumably with epiretinal implants, smaller electrodes in monopolar configuration can provide the highest spatial resolution. However, if the implantation site is further from the target cells, as is the case in suprachoroidal approaches, hexagonally guarded electrode return configurations can convey higher spatial resolution. This paper was originally submitted for the special issue containing contributions from the Sixth Biennial Research Congress of The Eye and the Chip.

  2. Frontal and parietal theta burst TMS impairs working memory for visual-spatial conjunctions

    PubMed Central

    Morgan, Helen M.; Jackson, Margaret C.; van Koningsbruggen, Martijn G.; Shapiro, Kimron L.; Linden, David E.J.

    2013-01-01

    In tasks that selectively probe visual or spatial working memory (WM) frontal and posterior cortical areas show a segregation, with dorsal areas preferentially involved in spatial (e.g. location) WM and ventral areas in visual (e.g. object identity) WM. In a previous fMRI study [1], we showed that right parietal cortex (PC) was more active during WM for orientation, whereas left inferior frontal gyrus (IFG) was more active during colour WM. During WM for colour-orientation conjunctions, activity in these areas was intermediate to the level of activity for the single task preferred and non-preferred information. To examine whether these specialised areas play a critical role in coordinating visual and spatial WM to perform a conjunction task, we used theta burst transcranial magnetic stimulation (TMS) to induce a functional deficit. Compared to sham stimulation, TMS to right PC or left IFG selectively impaired WM for conjunctions but not single features. This is consistent with findings from visual search paradigms, in which frontal and parietal TMS selectively affects search for conjunctions compared to single features, and with combined TMS and functional imaging work suggesting that parietal and frontal regions are functionally coupled in tasks requiring integration of visual and spatial information. Our results thus elucidate mechanisms by which the brain coordinates spatially segregated processing streams and have implications beyond the field of working memory. PMID:22483548

  3. Frontal and parietal theta burst TMS impairs working memory for visual-spatial conjunctions.

    PubMed

    Morgan, Helen M; Jackson, Margaret C; van Koningsbruggen, Martijn G; Shapiro, Kimron L; Linden, David E J

    2013-03-01

    In tasks that selectively probe visual or spatial working memory (WM) frontal and posterior cortical areas show a segregation, with dorsal areas preferentially involved in spatial (e.g. location) WM and ventral areas in visual (e.g. object identity) WM. In a previous fMRI study [1], we showed that right parietal cortex (PC) was more active during WM for orientation, whereas left inferior frontal gyrus (IFG) was more active during colour WM. During WM for colour-orientation conjunctions, activity in these areas was intermediate to the level of activity for the single task preferred and non-preferred information. To examine whether these specialised areas play a critical role in coordinating visual and spatial WM to perform a conjunction task, we used theta burst transcranial magnetic stimulation (TMS) to induce a functional deficit. Compared to sham stimulation, TMS to right PC or left IFG selectively impaired WM for conjunctions but not single features. This is consistent with findings from visual search paradigms, in which frontal and parietal TMS selectively affects search for conjunctions compared to single features, and with combined TMS and functional imaging work suggesting that parietal and frontal regions are functionally coupled in tasks requiring integration of visual and spatial information. Our results thus elucidate mechanisms by which the brain coordinates spatially segregated processing streams and have implications beyond the field of working memory. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Effect of subaperture beamforming on phase coherence imaging.

    PubMed

    Hasegawa, Hideyuki; Kanai, Hiroshi

    2014-11-01

    High-frame-rate echocardiography using unfocused transmit beams and parallel receive beamforming is a promising method for evaluation of cardiac function, such as imaging of rapid propagation of vibration of the heart wall resulting from electrical stimulation of the myocardium. In this technique, high temporal resolution is realized at the expense of spatial resolution and contrast. The phase coherence factor has been developed to improve spatial resolution and contrast in ultrasonography. It evaluates the variance in phases of echo signals received by individual transducer elements after delay compensation, as in the conventional delay-andsum beamforming process. However, the phase coherence factor suppresses speckle echoes because phases of speckle echoes fluctuate as a result of interference of echoes. In the present study, the receiving aperture was divided into several subapertures, and conventional delay-and-sum beamforming was performed with respect to each subaperture to suppress echoes from scatterers except for that at a focal point. After subaperture beamforming, the phase coherence factor was obtained from beamformed RF signals from respective subapertures. By means of this procedure, undesirable echoes, which can interfere with the echo from a focal point, can be suppressed by subaperture beamforming, and the suppression of the phase coherence factor resulting from phase fluctuation caused by such interference can be avoided. In the present study, the effect of subaperture beamforming in high-frame-rate echocardiography with the phase coherence factor was evaluated using a phantom. By applying subaperture beamforming, the average intensity of speckle echoes from a diffuse scattering medium was significantly higher (-39.9 dB) than that obtained without subaperture beamforming (-48.7 dB). As for spatial resolution, the width at half-maximum of the lateral echo amplitude profile obtained without the phase coherence factor was 1.06 mm. By using the phase coherence factor, spatial resolution was improved significantly, and subaperture beamforming achieved a better spatial resolution of 0.75 mm than that of 0.78 mm obtained without subaperture beamforming.

  5. Spatial variations in the consumption of illicit stimulant drugs across Australia: A nationwide application of wastewater-based epidemiology.

    PubMed

    Lai, Foon Yin; O'Brien, Jake; Bruno, Raimondo; Hall, Wayne; Prichard, Jeremy; Kirkbride, Paul; Gartner, Coral; Thai, Phong; Carter, Steve; Lloyd, Belinda; Burns, Lucy; Mueller, Jochen

    2016-10-15

    Obtaining representative information on illicit drug use and patterns across a country remains difficult using surveys because of low response rates and response biases. A range of studies have used wastewater-based epidemiology (WBE) as a complementary approach to monitor community-wide illicit drug use. In Australia, no large-scale WBE studies have been conducted to date to reveal illicit drug use profiles in a national context. In this study, we performed the first Australia-wide WBE monitoring to examine spatial patterns in the use of three illicit stimulants (cocaine, as its human metabolite benzoylecgonine; methamphetamine; and 3,4-methylendioxymethamphetamine (MDMA)). A total of 112 daily composite wastewater samples were collected from 14 wastewater treatment plants across four states and two territories. These covered approximately 40% of the Australian population. We identified and quantified illicit drug residues using liquid chromatography coupled with tandem mass spectrometry. There were distinctive spatial patterns of illicit stimulant use in Australia. Multivariate analyses showed that consumption of cocaine and MDMA was higher in the large cities than in rural areas. Also, cocaine consumption differed significantly between different jurisdictions. Methamphetamine consumption was more similar between urban and rural locations. Only a few cities had elevated levels of use. Extrapolation of the WBE estimates suggested that the annual consumption was 3tonnes for cocaine and 9tonnes combined for methamphetamine and MDMA, which outweighed the annual seizure amount by 25 times and 45 times, respectively. These ratios imply the difficulty of detecting the trafficking of these stimulants in Australia, possibly more so for methamphetamine than cocaine. The obtained spatial pattern of use was compared with that in the most recent national household survey. Together both WBE and survey methods provide a more comprehensive evaluation of drug use that can assist governments in developing policies to reduce drug use and harm in the communities. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Auditory cortical activity after intracortical microstimulation and its role for sensory processing and learning.

    PubMed

    Deliano, Matthias; Scheich, Henning; Ohl, Frank W

    2009-12-16

    Several studies have shown that animals can learn to make specific use of intracortical microstimulation (ICMS) of sensory cortex within behavioral tasks. Here, we investigate how the focal, artificial activation by ICMS leads to a meaningful, behaviorally interpretable signal. In natural learning, this involves large-scale activity patterns in widespread brain-networks. We therefore trained gerbils to discriminate closely neighboring ICMS sites within primary auditory cortex producing evoked responses largely overlapping in space. In parallel, during training, we recorded electrocorticograms (ECoGs) at high spatial resolution. Applying a multivariate classification procedure, we identified late spatial patterns that emerged with discrimination learning from the ongoing poststimulus ECoG. These patterns contained information about the preceding conditioned stimulus, and were associated with a subsequent correct behavioral response by the animal. Thereby, relevant pattern information was mainly carried by neuron populations outside the range of the lateral spatial spread of ICMS-evoked cortical activation (approximately 1.2 mm). This demonstrates that the stimulated cortical area not only encoded information about the stimulation sites by its focal, stimulus-driven activation, but also provided meaningful signals in its ongoing activity related to the interpretation of ICMS learned by the animal. This involved the stimulated area as a whole, and apparently required large-scale integration in the brain. However, ICMS locally interfered with the ongoing cortical dynamics by suppressing pattern formation near the stimulation sites. The interaction between ICMS and ongoing cortical activity has several implications for the design of ICMS protocols and cortical neuroprostheses, since the meaningful interpretation of ICMS depends on this interaction.

  7. Nutrient load summaries for major lakes and estuaries of the Eastern United States, 2002

    USGS Publications Warehouse

    Moorman, Michelle C.; Hoos, Anne B.; Bricker, Suzanne B.; Moore, Richard B.; García, Ana María; Ator, Scott W.

    2014-01-01

    Nutrient enrichment of lakes and estuaries across the Nation is widespread. Nutrient enrichment can stimulate excessive plant and algal growth and cause a number of undesirable effects that impair aquatic life and recreational activities and can also result in economic effects. Understanding the amount of nutrients entering lakes and estuaries, the physical characteristics affecting the nutrient processing within these receiving waterbodies, and the natural and manmade sources of nutrients is fundamental to the development of effective nutrient reduction strategies. To improve this understanding, sources and stream transport of nutrients to 255 major lakes and 64 estuaries in the Eastern United States were estimated using Spatially Referenced Regression on Watershed attributes (SPARROW) nutrient models.

  8. Visual spatial attention enhances the amplitude of positive and negative fMRI responses to visual stimulation in an eccentricity-dependent manner

    PubMed Central

    Bressler, David W.; Fortenbaugh, Francesca C.; Robertson, Lynn C.; Silver, Michael A.

    2013-01-01

    Endogenous visual spatial attention improves perception and enhances neural responses to visual stimuli at attended locations. Although many aspects of visual processing differ significantly between central and peripheral vision, little is known regarding the neural substrates of the eccentricity dependence of spatial attention effects. We measured amplitudes of positive and negative fMRI responses to visual stimuli as a function of eccentricity in a large number of topographically-organized cortical areas. Responses to each stimulus were obtained when the stimulus was attended and when spatial attention was directed to a stimulus in the opposite visual hemifield. Attending to the stimulus increased both positive and negative response amplitudes in all cortical areas we studied: V1, V2, V3, hV4, VO1, LO1, LO2, V3A/B, IPS0, TO1, and TO2. However, the eccentricity dependence of these effects differed considerably across cortical areas. In early visual, ventral, and lateral occipital cortex, attentional enhancement of positive responses was greater for central compared to peripheral eccentricities. The opposite pattern was observed in dorsal stream areas IPS0 and putative MT homolog TO1, where attentional enhancement of positive responses was greater in the periphery. Both the magnitude and the eccentricity dependence of attentional modulation of negative fMRI responses closely mirrored that of positive responses across cortical areas. PMID:23562388

  9. [The effect of the new nootropic dipeptide GVS-111 in different functional disorders of the escape reaction].

    PubMed

    Inozemtsev, A N; Trofimov, S S; Borlikova, G G; Firova, F A; Pragina, L L; Gudasheva, T A; Ostrovskaia, R U; Tushmalova, N A; Voronina, T A

    1998-01-01

    The authors studied the effect of a new nootropic agent with anxiolytic properties GVS-111 (ethyl ether N-phenylacetyl-L-prolylglycine) on formation of the avoidance reaction (AR) in rats and its functional disorders which were induced by two methods. In one case the stereotype of the relations between the stimulus, reaction and its consequence which developed during the experiment were urgently disturbed: the change of the animal to the other half of the chamber in response to a conditioned stimulus did not lead to its cutting off and prevention of the electropain stimulation for three successive combinations (AR error). In another case the spatial stereotype of the experiment was altered by changing the place of the opening through which the animal avoided the stimulus (spatial remodeling). Intraperitoneal injection of GVS-111 (0.1 mg/kg/day) improved the learning, but the effect differed from experiment to experiment. Along with this, the dipeptide prevented AR disturbance during the error and quickened restoration of the habit in spatial remodeling. It was shown earlier that AR disorders during an error are prevented by anxiolytics and nootropic agents but during spatial remodeling only by nootropic agents. It may be assumed that the positive effect of GSV-111 on AR in functional disorders is due to its nootropic effect.

  10. Design analysis of an MPI human functional brain scanner

    PubMed Central

    Mason, Erica E.; Cooley, Clarissa Z.; Cauley, Stephen F.; Griswold, Mark A.; Conolly, Steven M.; Wald, Lawrence L.

    2017-01-01

    MPI’s high sensitivity makes it a promising modality for imaging brain function. Functional contrast is proposed based on blood SPION concentration changes due to Cerebral Blood Volume (CBV) increases during activation, a mechanism utilized in fMRI studies. MPI offers the potential for a direct and more sensitive measure of SPION concentration, and thus CBV, than fMRI. As such, fMPI could surpass fMRI in sensitivity, enhancing the scientific and clinical value of functional imaging. As human-sized MPI systems have not been attempted, we assess the technical challenges of scaling MPI from rodent to human brain. We use a full-system MPI simulator to test arbitrary hardware designs and encoding practices, and we examine tradeoffs imposed by constraints that arise when scaling to human size as well as safety constraints (PNS and central nervous system stimulation) not considered in animal scanners, thereby estimating spatial resolutions and sensitivities achievable with current technology. Using a projection FFL MPI system, we examine coil hardware options and their implications for sensitivity and spatial resolution. We estimate that an fMPI brain scanner is feasible, although with reduced sensitivity (20×) and spatial resolution (5×) compared to existing rodent systems. Nonetheless, it retains sufficient sensitivity and spatial resolution to make it an attractive future instrument for studying the human brain; additional technical innovations can result in further improvements. PMID:28752130

  11. Late Enrichment Maintains Accurate Recent and Remote Spatial Memory Only in Aged Rats That Were Unimpaired When Middle Aged

    ERIC Educational Resources Information Center

    Fuchs, Fanny; Herbeaux, Karine; Aufrere, Noémie; Kelche, Christian; Mathis, Chantal; Barbelivien, Alexandra; Majchrzak, Monique

    2016-01-01

    Exposure of rodents to a stimulating environment has beneficial effects on some cognitive functions that are impaired during physiological aging, and especially spatial reference memory. The present study investigated whether environmental enrichment rescues these functions in already declining subjects and/or protects them from subsequent…

  12. Optimization of multifocal transcranial current stimulation for weighted cortical pattern targeting from realistic modeling of electric fields

    PubMed Central

    Ruffini, Giulio; Fox, Michael D.; Ripolles, Oscar; Miranda, Pedro Cavaleiro; Pascual-Leone, Alvaro

    2014-01-01

    Recently, multifocal transcranial current stimulation (tCS) devices using several relatively small electrodes have been used to achieve more focal stimulation of specific cortical targets. However, it is becoming increasingly recognized that many behavioral manifestations of neurological and psychiatric disease are not solely the result of abnormality in one isolated brain region but represent alterations in brain networks. In this paper we describe a method for optimizing the configuration of multifocal tCS for stimulation of brain networks, represented by spatially extended cortical targets. We show how, based on fMRI, PET, EEG or other data specifying a target map on the cortical surface for excitatory, inhibitory or neutral stimulation and a constraint of the maximal number of electrodes, a solution can be produced with the optimal currents and locations of the electrodes. The method described here relies on a fast calculation of multifocal tCS electric fields (including components normal and tangential to the cortical boundaries) using a five layer finite element model of a realistic head. Based on the hypothesis that the effects of current stimulation are to first order due to the interaction of electric fields with populations of elongated cortical neurons, it is argued that the optimization problem for tCS stimulation can be defined in terms of the component of the electric field normal to the cortical surface. Solutions are found using constrained least squares to optimize current intensities, while electrode number and their locations are selected using a genetic algorithm. For direct current tCS (tDCS) applications, we provide some examples of this technique using an available tCS system providing 8 small Ag/AgCl stimulation electrodes. We demonstrate the approach both for localized and spatially extended targets defined using rs-fcMRI and PET data, with clinical applications in stroke and depression. Finally, we extend these ideas to more general stimulation protocols, such as alternating current tCS (tACS). PMID:24345389

  13. Modulation of attentional processing by deep brain stimulation of the pedunculopontine nucleus region in patients with parkinsonian disorders.

    PubMed

    Fischer, Julia; Schwiecker, Kati; Bittner, Verena; Heinze, Hans-Jochen; Voges, Jürgen; Galazky, Imke; Zaehle, Tino

    2015-07-01

    Low-frequency electrical stimulation of the pedunculopontine nucleus (PPN) is a therapeutic approach aiming to improve motor symptoms such as freezing of gate and postural instability in parkinsonian disorders. Because the PPN is a component of the reticular activating system, we tested whether PPN stimulation directly affects attention and consciousness. Eight patients with parkinsonian disorders and implanted with electrodes in the bilateral PPN underwent computerized assessment of attention. Performance in 3 standard reaction time (RT) tasks was assessed at 5 different stimulation frequencies in 5 consecutive sessions. Stimulation of the PPN at low (8 Hz) and therapeutic (20 Hz) frequencies led to a significant improvement of performance in a simple RT task. Patients' RTs were significantly faster at stimulation frequencies of 8 Hz and 20 Hz relative to no stimulation. Stimulation did not affect patients' performance in more complex attentional tasks. Low-frequent stimulation of PPN improves basal attentional processing in patients with parkinsonian disorders, leading to an improved tonic alertness. As successful performance in this task requires the intrinsic ability to build up and keep a certain level of attention, this might be interpreted as attentional augmentation related to stimulation features. Stimulation had no effect on more complex attentional processing. Our results suggest an influence of the PPN on certain aspects of attention, supporting attentional augmentation as one possible mechanism to improve motor action and gait in patients with parkinsonian disorders. (c) 2015 APA, all rights reserved).

  14. Investigation of the cerebral hemodynamic response function in single blood vessels by functional photoacoustic microscopy

    PubMed Central

    Liao, Lun-De; Lin, Chin-Teng; Shih, Yen-Yu I.; Lai, Hsin-Yi; Zhao, Wan-Ting; Duong, Timothy Q.; Chang, Jyh-Yeong; Chen, You-Yin

    2012-01-01

    Abstract. The specificity of the hemodynamic response function (HRF) is determined spatially by the vascular architecture and temporally by the evolution of hemodynamic changes. Here, we used functional photoacoustic microscopy (fPAM) to investigate single cerebral blood vessels of rats after left forepaw stimulation. In this system, we analyzed the spatiotemporal evolution of the HRFs of the total hemoglobin concentration (HbT), cerebral blood volume (CBV), and hemoglobin oxygen saturation (SO2). Changes in specific cerebral vessels corresponding to various electrical stimulation intensities and durations were bilaterally imaged with 36×65-μm2 spatial resolution. Stimulation intensities of 1, 2, 6, and 10 mA were applied for periods of 5 or 15 s. Our results show that the relative functional changes in HbT, CBV, and SO2 are highly dependent not only on the intensity of the stimulation, but also on its duration. Additionally, the duration of the stimulation has a strong influence on the spatiotemporal characteristics of the HRF as shorter stimuli elicit responses only in the local vasculature (smaller arterioles), whereas longer stimuli lead to greater vascular supply and drainage. This study suggests that the current fPAM system is reliable for studying relative cerebral hemodynamic changes, as well as for offering new insights into the dynamics of functional cerebral hemodynamic changes in small animals. PMID:22734740

  15. Transcranial direct current stimulation over left inferior frontal cortex improves speech fluency in adults who stutter.

    PubMed

    Chesters, Jennifer; Möttönen, Riikka; Watkins, Kate E

    2018-04-01

    See Crinion (doi:10.1093/brain/awy075) for a scientific commentary on this article.Stuttering is a neurodevelopmental condition affecting 5% of children, and persisting in 1% of adults. Promoting lasting fluency improvement in adults who stutter is a particular challenge. Novel interventions to improve outcomes are of value, therefore. Previous work in patients with acquired motor and language disorders reported enhanced benefits of behavioural therapies when paired with transcranial direct current stimulation. Here, we report the results of the first trial investigating whether transcranial direct current stimulation can improve speech fluency in adults who stutter. We predicted that applying anodal stimulation to the left inferior frontal cortex during speech production with temporary fluency inducers would result in longer-lasting fluency improvements. Thirty male adults who stutter completed a randomized, double-blind, controlled trial of anodal transcranial direct current stimulation over left inferior frontal cortex. Fifteen participants received 20 min of 1-mA stimulation on five consecutive days while speech fluency was temporarily induced using choral and metronome-timed speech. The other 15 participants received the same speech fluency intervention with sham stimulation. Speech fluency during reading and conversation was assessed at baseline, before and after the stimulation on each day of the 5-day intervention, and at 1 and 6 weeks after the end of the intervention. Anodal stimulation combined with speech fluency training significantly reduced the percentage of disfluent speech measured 1 week after the intervention compared with fluency intervention alone. At 6 weeks after the intervention, this improvement was maintained during reading but not during conversation. Outcome scores at both post-intervention time points on a clinical assessment tool (the Stuttering Severity Instrument, version 4) also showed significant improvement in the group receiving transcranial direct current stimulation compared with the sham group, in whom fluency was unchanged from baseline. We conclude that transcranial direct current stimulation combined with behavioural fluency intervention can improve fluency in adults who stutter. Transcranial direct current stimulation thereby offers a potentially useful adjunct to future speech therapy interventions for this population, for whom fluency therapy outcomes are currently limited.

  16. Current density distributions, field distributions and impedance analysis of segmented deep brain stimulation electrodes

    NASA Astrophysics Data System (ADS)

    Wei, Xuefeng F.; Grill, Warren M.

    2005-12-01

    Deep brain stimulation (DBS) electrodes are designed to stimulate specific areas of the brain. The most widely used DBS electrode has a linear array of 4 cylindrical contacts that can be selectively turned on depending on the placement of the electrode and the specific area of the brain to be stimulated. The efficacy of DBS therapy can be improved by localizing the current delivery into specific populations of neurons and by increasing the power efficiency through a suitable choice of electrode geometrical characteristics. We investigated segmented electrode designs created by sectioning each cylindrical contact into multiple rings. Prototypes of these designs, made with different materials and larger dimensions than those of clinical DBS electrodes, were evaluated in vitro and in simulation. A finite element model was developed to study the effects of varying the electrode characteristics on the current density and field distributions in an idealized electrolytic medium and in vitro experiments were conducted to measure the electrode impedance. The current density over the electrode surface increased towards the edges of the electrode, and multiple edges increased the non-uniformity of the current density profile. The edge effects were more pronounced over the end segments than over the central segments. Segmented electrodes generated larger magnitudes of the second spatial difference of the extracellular potentials, and thus required lower stimulation intensities to achieve the same level of neuronal activation as solid electrodes. For a fixed electrode conductive area, increasing the number of segments (edges) decreased the impedance compared to a single solid electrode, because the average current density over the segments increased. Edge effects played a critical role in determining the current density distributions, neuronal excitation patterns, and impedance of cylindrical electrodes, and segmented electrodes provide a means to increase the efficiency of DBS.

  17. Improved Discrimination of Visual Stimuli Following Repetitive Transcranial Magnetic Stimulation

    PubMed Central

    Waterston, Michael L.; Pack, Christopher C.

    2010-01-01

    Background Repetitive transcranial magnetic stimulation (rTMS) at certain frequencies increases thresholds for motor-evoked potentials and phosphenes following stimulation of cortex. Consequently rTMS is often assumed to introduce a “virtual lesion” in stimulated brain regions, with correspondingly diminished behavioral performance. Methodology/Principal Findings Here we investigated the effects of rTMS to visual cortex on subjects' ability to perform visual psychophysical tasks. Contrary to expectations of a visual deficit, we find that rTMS often improves the discrimination of visual features. For coarse orientation tasks, discrimination of a static stimulus improved consistently following theta-burst stimulation of the occipital lobe. Using a reaction-time task, we found that these improvements occurred throughout the visual field and lasted beyond one hour post-rTMS. Low-frequency (1 Hz) stimulation yielded similar improvements. In contrast, we did not find consistent effects of rTMS on performance in a fine orientation discrimination task. Conclusions/Significance Overall our results suggest that rTMS generally improves or has no effect on visual acuity, with the nature of the effect depending on the type of stimulation and the task. We interpret our results in the context of an ideal-observer model of visual perception. PMID:20442776

  18. Nanomaterial-Enabled Neural Stimulation

    PubMed Central

    Wang, Yongchen; Guo, Liang

    2016-01-01

    Neural stimulation is a critical technique in treating neurological diseases and investigating brain functions. Traditional electrical stimulation uses electrodes to directly create intervening electric fields in the immediate vicinity of neural tissues. Second-generation stimulation techniques directly use light, magnetic fields or ultrasound in a non-contact manner. An emerging generation of non- or minimally invasive neural stimulation techniques is enabled by nanotechnology to achieve a high spatial resolution and cell-type specificity. In these techniques, a nanomaterial converts a remotely transmitted primary stimulus such as a light, magnetic or ultrasonic signal to a localized secondary stimulus such as an electric field or heat to stimulate neurons. The ease of surface modification and bio-conjugation of nanomaterials facilitates cell-type-specific targeting, designated placement and highly localized membrane activation. This review focuses on nanomaterial-enabled neural stimulation techniques primarily involving opto-electric, opto-thermal, magneto-electric, magneto-thermal and acousto-electric transduction mechanisms. Stimulation techniques based on other possible transduction schemes and general consideration for these emerging neurotechnologies are also discussed. PMID:27013938

  19. Autistic spectrum disorder, epilepsy, and vagus nerve stimulation.

    PubMed

    Hull, Mariam Mettry; Madhavan, Deepak; Zaroff, Charles M

    2015-08-01

    In individuals with a comorbid autistic spectrum disorder and medically refractory epilepsy, vagus nerve stimulation may offer the potential of seizure control and a positive behavioral side effect profile. We aimed to examine the behavioral side effect profile using longitudinal and quantitative data and review the potential mechanisms behind behavioral changes. We present a case report of a 10-year-old boy with autistic spectrum disorder and epilepsy, who underwent vagus nerve stimulation subsequent to unsuccessful treatment with antiepileptic medication. Following vagus nerve stimulation implantation, initial, if temporary, improvement was observed in seizure control. Modest improvements were also observed in behavior and development, improvements which were observed independent of seizure control. Vagus nerve stimulation in autistic spectrum disorder is associated with modest behavioral improvement, with unidentified etiology, although several candidates for this improvement are evident.

  20. Model-based Vestibular Afferent Stimulation: Modular Workflow for Analyzing Stimulation Scenarios in Patient Specific and Statistical Vestibular Anatomy.

    PubMed

    Handler, Michael; Schier, Peter P; Fritscher, Karl D; Raudaschl, Patrik; Johnson Chacko, Lejo; Glueckert, Rudolf; Saba, Rami; Schubert, Rainer; Baumgarten, Daniel; Baumgartner, Christian

    2017-01-01

    Our sense of balance and spatial orientation strongly depends on the correct functionality of our vestibular system. Vestibular dysfunction can lead to blurred vision and impaired balance and spatial orientation, causing a significant decrease in quality of life. Recent studies have shown that vestibular implants offer a possible treatment for patients with vestibular dysfunction. The close proximity of the vestibular nerve bundles, the facial nerve and the cochlear nerve poses a major challenge to targeted stimulation of the vestibular system. Modeling the electrical stimulation of the vestibular system allows for an efficient analysis of stimulation scenarios previous to time and cost intensive in vivo experiments. Current models are based on animal data or CAD models of human anatomy. In this work, a (semi-)automatic modular workflow is presented for the stepwise transformation of segmented vestibular anatomy data of human vestibular specimens to an electrical model and subsequently analyzed. The steps of this workflow include (i) the transformation of labeled datasets to a tetrahedra mesh, (ii) nerve fiber anisotropy and fiber computation as a basis for neuron models, (iii) inclusion of arbitrary electrode designs, (iv) simulation of quasistationary potential distributions, and (v) analysis of stimulus waveforms on the stimulation outcome. Results obtained by the workflow based on human datasets and the average shape of a statistical model revealed a high qualitative agreement and a quantitatively comparable range compared to data from literature, respectively. Based on our workflow, a detailed analysis of intra- and extra-labyrinthine electrode configurations with various stimulation waveforms and electrode designs can be performed on patient specific anatomy, making this framework a valuable tool for current optimization questions concerning vestibular implants in humans.

  1. Spatial temperature distribution in human hairy and glabrous skin after infrared CO2 laser radiation

    PubMed Central

    2010-01-01

    Background CO2 lasers have been used for several decades as an experimental non-touching pain stimulator. The laser energy is absorbed by the water content in the most superficial layers of the skin. The deeper located nociceptors are activated by passive conduction of heat from superficial to deeper skin layers. Methods In the current study, a 2D axial finite element model was developed and validated to describe the spatial temperature distribution in the skin after infrared CO2 laser stimulation. The geometry of the model was based on high resolution ultrasound scans. The simulations were compared to the subjective pain intensity ratings from 16 subjects and to the surface skin temperature distributions measured by an infrared camera. Results The stimulations were sensed significantly slower and less intense in glabrous skin than they were in hairy skin (MANOVA, p < 0.001). The model simulations of superficial temperature correlated with the measured skin surface temperature (r > 0.90, p < 0.001). Of the 16 subjects tested; eight subjects reported pricking pain in the hairy skin following a stimulus of 0.6 J/cm2 (5 W, 0.12 s, d1/e2 = 11.4 mm) only two reported pain to glabrous skin stimulation using the same stimulus intensity. The temperature at the epidermal-dermal junction (depth 50 μm in hairy and depth 133 μm in glabrous skin) was estimated to 46°C for hairy skin stimulation and 39°C for glabrous skin stimulation. Conclusions As compared to previous one dimensional heat distribution models, the current two dimensional model provides new possibilities for detailed studies regarding CO2 laser stimulation intensity, temperature levels and nociceptor activation. PMID:21059226

  2. High-frequency electroacupuncture evidently reinforces hippocampal synaptic transmission in Alzheimer's disease rats

    PubMed Central

    Li, Wei; Kong, Li-hong; Wang, Hui; Shen, Feng; Wang, Ya-wen; Zhou, Hua; Sun, Guo-jie

    2016-01-01

    The frequency range of electroacupuncture in treatment of Alzheimer's disease in rats is commonly 2–5 Hz (low frequency) and 50–100 Hz (high frequency). We established a rat model of Alzheimer's disease by injecting β-amyloid 1–42 (Aβ1–42) into the bilateral hippocampal dentate gyrus to verify which frequency may be better suited in treatment. Electroacupuncture at 2 Hz or 50 Hz was used to stimulate Baihui (DU20) and Shenshu (BL23) acupoints. The water maze test and electrophysiological studies demonstrated that spatial memory ability was apparently improved, and the ranges of long-term potentiation and long-term depression were increased in Alzheimer's disease rats after electroacupuncture treatment. Moreover, the effects of electroacupuncture at 50 Hz were better than that at 2 Hz. These findings suggest that high-frequency electroacupuncture may enhance hippocampal synaptic transmission and potentially improve memory disorders in Alzheimer's disease rats. PMID:27335565

  3. The Iterative Research Cycle: Process-Based Model Evaluation

    NASA Astrophysics Data System (ADS)

    Vrugt, J. A.

    2014-12-01

    The ever increasing pace of computational power, along with continued advances in measurement technologies and improvements in process understanding has stimulated the development of increasingly complex physics based models that simulate a myriad of processes at different spatial and temporal scales. Reconciling these high-order system models with perpetually larger volumes of field data is becoming more and more difficult, particularly because classical likelihood-based fitting methods lack the power to detect and pinpoint deficiencies in the model structure. In this talk I will give an overview of our latest research on process-based model calibration and evaluation. This approach, rooted in Bayesian theory, uses summary metrics of the calibration data rather than the data itself to help detect which component(s) of the model is (are) malfunctioning and in need of improvement. A few case studies involving hydrologic and geophysical models will be used to demonstrate the proposed methodology.

  4. A physiologically-inspired model reproducing the speech intelligibility benefit in cochlear implant listeners with residual acoustic hearing.

    PubMed

    Zamaninezhad, Ladan; Hohmann, Volker; Büchner, Andreas; Schädler, Marc René; Jürgens, Tim

    2017-02-01

    This study introduces a speech intelligibility model for cochlear implant users with ipsilateral preserved acoustic hearing that aims at simulating the observed speech-in-noise intelligibility benefit when receiving simultaneous electric and acoustic stimulation (EA-benefit). The model simulates the auditory nerve spiking in response to electric and/or acoustic stimulation. The temporally and spatially integrated spiking patterns were used as the final internal representation of noisy speech. Speech reception thresholds (SRTs) in stationary noise were predicted for a sentence test using an automatic speech recognition framework. The model was employed to systematically investigate the effect of three physiologically relevant model factors on simulated SRTs: (1) the spatial spread of the electric field which co-varies with the number of electrically stimulated auditory nerves, (2) the "internal" noise simulating the deprivation of auditory system, and (3) the upper bound frequency limit of acoustic hearing. The model results show that the simulated SRTs increase monotonically with increasing spatial spread for fixed internal noise, and also increase with increasing the internal noise strength for a fixed spatial spread. The predicted EA-benefit does not follow such a systematic trend and depends on the specific combination of the model parameters. Beyond 300 Hz, the upper bound limit for preserved acoustic hearing is less influential on speech intelligibility of EA-listeners in stationary noise. The proposed model-predicted EA-benefits are within the range of EA-benefits shown by 18 out of 21 actual cochlear implant listeners with preserved acoustic hearing. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Effects of background stimulation upon eye-movement information.

    PubMed

    Nakamura, S

    1996-04-01

    To investigate the effects of background stimulation upon eye-movement information (EMI), the perceived deceleration of the target motion during pursuit eye movement (Aubert-Fleishl paradox) was analyzed. In the experiment, a striped pattern was used as a background stimulus with various brightness contrasts and spatial frequencies for serially manipulating the attributions of the background stimulus. Analysis showed that the retinal-image motion of the background stimulus (optic flow) affected eye-movement information and that the effects of optic flow became stronger when high contrast and low spatial frequency stripes were presented as the background stimulus. In conclusion, optic flow is one source of eye-movement information in determining real object motion, and the effectiveness of optic flow depends on the attributes of the background stimulus.

  6. Transparent, conformable, active multielectrode array using organic electrochemical transistors

    PubMed Central

    Lee, Wonryung; Kim, Dongmin; Matsuhisa, Naoji; Nagase, Masae; Sekino, Masaki; Malliaras, George G.; Yokota, Tomoyuki; Someya, Takao

    2017-01-01

    Mechanically flexible active multielectrode arrays (MEA) have been developed for local signal amplification and high spatial resolution. However, their opaqueness limited optical observation and light stimulation during use. Here, we show a transparent, ultraflexible, and active MEA, which consists of transparent organic electrochemical transistors (OECTs) and transparent Au grid wirings. The transparent OECT is made of Au grid electrodes and has shown comparable performance with OECTs with nontransparent electrodes/wirings. The transparent active MEA realizes the spatial mapping of electrocorticogram electrical signals from an optogenetic rat with 1-mm spacing and shows lower light artifacts than noise level. Our active MEA would open up the possibility of precise investigation of a neural network system with direct light stimulation. PMID:28923928

  7. Photopolymerized materials and patterning for improved performance of neural prosthetics

    NASA Astrophysics Data System (ADS)

    Tuft, Bradley William

    Neural prosthetics are used to replace or substantially augment remaining motor and sensory functions of neural pathways that were lost or damaged due to physical trauma, disease, or genetics. However, due to poor spatial signal resolution, neural prostheses fail to recapitulate the intimate, precise interactions inherent to neural networks. Designing materials and interfaces that direct de novo nerve growth to spatially specific stimulating elements is, therefore, a promising method to enhance signal specificity and performance of prostheses such as the successful cochlear implant (CI) and the developing retinal implant. In this work, the spatial and temporal reaction control inherent to photopolymerization was used to develop methods to generate micro and nanopatterned materials that direct neurite growth from prosthesis relevant neurons. In particular, neurite growth and directionality has been investigated in response to physical, mechanical, and chemical cues on photopolymerized surfaces. Spiral ganglion neurons (SGNs) serve as the primary neuronal model as they are the principal target for CI stimulation. The objective of the research is to rationally design materials that spatially direct neurite growth and to translate fundamental understanding of nerve cell-material interactions into methods of nerve regeneration that improve neural prosthetic performance. A rapid, single-step photopolymerization method was developed to fabricate micro and nanopatterned physical cues on methacrylate surfaces by selectively blocking light with photomasks. Feature height is readily tuned by modulating parameters of the photopolymerizaiton including initiator concentration and species, light intensity, separation distance from the photomask, and radiation exposure time. Alignment of neural elements increases significantly with increasing feature amplitude and constant periodicity, as well as with decreasing periodicity and constant amplitude. SGN neurite alignment strongly correlates with the maximum feature slope. Neurite alignment is compared on unpatterned, unidirectional, and multidirectional photopolymerized micropatterns. The effect of substrate rigidity on neurite alignment to physical cues was determined by maintaining equivalent pattern microfeatures, afforded by the reaction control of photopolymerization, while concomitantly altering the composition of several copolymer platforms to tune matrix stiffness. For each platform, neurite alignment to unidirectional patterns increases with increasing substrate rigidity. Interestingly, SGN neurites respond to material stiffness cues that are orders of magnitude higher (GPa) than what is typically ascribed to neural environments (kPa). Finally, neurite behavior at bioactive borders of various adhesion modulating molecules was evaluated on micropatterned materials to determine which cues took precedence in establishing neurite directionality. At low microfeatures aspect ratios, neurites align to the pattern direction but are then caused to turn and repel from or turn and align to bioactive borders. Conversely, physical cues dominate neurite path-finding as pattern feature slope increases, i.e. aspect ratio of sloping photopolymerized features increases, causing neurites to readily cross bioactive borders. The photopolymerization method developed in this work to generate micro and nanopatterned materials serves as an additional surface engineering tool that enables investigation of cell-material interactions including directed de novo neurite growth. The results of this interdisciplinary effort contribute substantially to polymer neural regeneration technology and will lead to development of advanced biomaterials that improve neural prosthetic tissue integration and performance by spatially directing nerve growth.

  8. Electro-acupuncture stimulation acts on the basal ganglia output pathway to ameliorate motor impairment in Parkinsonian model rats.

    PubMed

    Jia, Jun; Li, Bo; Sun, Zuo-Li; Yu, Fen; Wang, Xuan; Wang, Xiao-Min

    2010-04-01

    The role of electro-acupuncture (EA) stimulation on motor symptoms in Parkinson's disease (PD) has not been well studied. In a rat hemiparkinsonian model induced by unilateral transection of the medial forebrain bundle (MFB), EA stimulation improved motor impairment in a frequency-dependent manner. Whereas EA stimulation at a low frequency (2 Hz) had no effect, EA stimulation at a high frequency (100 Hz) significantly improved motor coordination. However, neither low nor high EA stimulation could significantly enhance dopamine levels in the striatum. EA stimulation at 100 Hz normalized the MFB lesion-induced increase in midbrain GABA content, but it had no effect on GABA content in the globus pallidus. These results suggest that high-frequency EA stimulation improves motor impairment in MFB-lesioned rats by increasing GABAergic inhibition in the output structure of the basal ganglia.

  9. Hippocampal Gαq/₁₁ but not Gαo-coupled receptors are altered in aging.

    PubMed

    McQuail, Joseph A; Davis, Kathleen N; Miller, Frances; Hampson, Robert E; Deadwyler, Samuel A; Howlett, Allyn C; Nicolle, Michelle M

    2013-07-01

    Normal aging may limit the signaling efficacy of certain GPCRs by disturbing the function of specific Gα-subunits and leading to deficient modulation of intracellular functions that subserve synaptic plasticity, learning and memory. Evidence suggests that Gαq/₁₁ is more sensitive to the effects of aging relative to other Gα-subunits, including Gαo. To test this hypothesis, the functionality of Gαq/₁₁ and Gαo were compared in the hippocampus of young (6 months) and aged (24 months) F344 × BNF₁ hybrid rats assessed for spatial learning ability. Basal GTPγS-binding to Gαq/₁₁ was significantly elevated in aged rats relative to young and but not reliably associated with spatial learning. mAChR stimulation of Gαq/₁₁ with oxotremorine-M produced equivocal GTPγS-binding between age groups although values tended to be lower in the aged hippocampus and were inversely related to basal activity. Downstream Gαq/₁₁ function was measured in hippocampal subregion CA₁ by determining changes in [Ca(2+)]i after mAChR and mGluR (DHPG) stimulation. mAChR-stimulated peak change in [Ca(2+)]i was lower in aged CA₁ relative to young while mGluR-mediated integrated [Ca(2+)]i responses tended to be larger in aged. GPCR modulation of [Ca(2+)]i was observed to depend on intracellular stores to a greater degree in aged than young. In contrast, measures of Gαo-mediated GTPγS-binding were stable across age, including basal, mAChR-, GABABR (baclofen)-stimulated levels. Overall, the data indicate that aging selectively modulates the activity of Gαq/₁₁ within the hippocampus leading to deficient modulation of [Ca(2+)]i following stimulation of mAChRs but these changes are not related to spatial learning. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Periodic Visuotactile Stimulation Slowly Enhances the Rubber Hand Illusion in Individuals with High Autistic Traits

    PubMed Central

    Ide, Masakazu; Wada, Makoto

    2016-01-01

    In a rubber hand illusion (RHI) task, synchronous brush stroking of a rubber hand and a participant's hidden hand induces body ownership of the rubber hand. The effects of spatial distances and temporal lags on the RHI have been extensively examined; however, the effect of periodicity of the stimuli on illusory body ownership has not been examined. Meanwhile, the occurrence of RHI tends to be weak in individuals with autism-spectrum disorders (ASD) and high autistic traits. Preference for stimulus having regularity of tempo is generally observed in individuals with ASD, and thus, periodic stimulation might be more effective to elicit the body ownership illusion in individuals with high autistic traits. Hence, we investigated whether stimulus periodicity influenced RHI as well as its association with participant's autistic traits. Brush strokes were applied to a participant's own hand and the rubber hand periodically (2 s) or non-periodically (1–3 s), either synchronously or asynchronously. Two blocks were performed in each condition. We found that periodic stimulation enhanced the spatial updating of tactile sensation induced by RHI in the subsequent block in participants with high autistic traits, whereas both periodic and non-periodic stimulation strongly elicited RHI in blocks 1 and 2. These results indicate that the periodicity of stimulation has different effects based on an individual's autistic traits. Since individuals with ASD are known to sustain their focus on interoceptive sensations (heartbeats), a periodic stimulation that is potentially correlated with heartbeats might be effective to enhance the visuotactile integration during RHI in individuals with high autistic traits. PMID:27375441

  11. The effect of surface electrical stimulation on swallowing in dysphagic Parkinson patients.

    PubMed

    Baijens, Laura W J; Speyer, Renée; Passos, Valeria Lima; Pilz, Walmari; Roodenburg, Nel; Clavé, Père

    2012-12-01

    Surface electrical stimulation has been applied on a large scale to treat oropharyngeal dysphagia. Patients suffering from oropharyngeal dysphagia in the presence of Parkinson's disease have been treated with surface electrical stimulation. Because of controversial reports on this treatment, a pilot study was set up. This study describes the effects of a single session of surface electrical stimulation using different electrode positions in ten patients with idiopathic Parkinson's disease (median Hoehn and Yahr score: II) and oropharyngeal dysphagia compared to ten age- and gender-matched healthy control subjects during videofluoroscopy of swallowing. Three different electrode positions were applied in random order per subject. For each electrode position, the electrical current was respectively turned "on" and "off" in random order. Temporal, spatial, and visuoperceptual variables were scored by experienced raters who were blinded to the group, electrode position, and status (on/off) of the electrical current. Interrater and interrater reliabilities were calculated. Only a few significant effects of a single session of surface electrical stimulation using different electrode positions in dysphagic Parkinson patients could be observed in this study. Furthermore, significant results for temporal and spatial variables were found regardless of the status of the electrical current in both groups suggesting placebo effects. Following adjustment for electrical current status as well as electrode positions (both not significant, P > 0.05) in the statistical model, significant group differences between Parkinson patients and healthy control subjects emerged. Further studies are necessary to evaluate the potential therapeutic effect and mechanism of electrical stimulation in dysphagic patients with Parkinson's disease.

  12. Brain plasticity after implanted peroneal nerve electrical stimulation to improve gait in chronic stroke patients: Two case reports.

    PubMed

    Thibaut, Aurore; Moissenet, Florent; Di Perri, Carol; Schreiber, Céline; Remacle, Angélique; Kolanowski, Elisabeth; Chantraine, Frédéric; Bernard, Claire; Hustinx, Roland; Tshibanda, Jean-Flory; Filipetti, Paul; Laureys, Steven; Gosseries, Olivia

    2017-01-01

    Recent studies have shown that stimulation of the peroneal nerve using an implantable 4-channel peroneal nerve stimulator could improve gait in stroke patients. To assess structural cortical and regional cerebral metabolism changes associated with an implanted peroneal nerve electrical stimulator to correct foot drop related to a central nervous system lesion. Two stroke patients presenting a foot drop related to a central nervous system lesion were implanted with an implanted peroneal nerve electrical stimulator. Both patients underwent clinical evaluations before implantation and one year after the activation of the stimulator. Structural magnetic resonance imaging (MRI) and [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) were acquired before and one year after the activation of the stimulator. Foot drop was corrected for both patients after the implantation of the stimulator. After one year of treatment, patient 1 improved in three major clinical tests, while patient 2 only improved in one test. Prior to treatment, FDG-PET showed a significant hypometabolism in premotor, primary and supplementary motor areas in both patients as compared to controls, with patient 2 presenting more widespread hypometabolism. One year after the activation of the stimulator, both patients showed significantly less hypometabolism in the damaged motor cortex. No difference was observed on the structural MRI. Clinical improvement of gait under peroneal nerve electrical stimulation in chronic stroke patients presenting foot drop was paralleled to metabolic changes in the damaged motor cortex.

  13. Autism-like behavior caused by deletion of vaccinia-related kinase 3 is improved by TrkB stimulation

    PubMed Central

    Kang, Myung-Su; Lee, Dohyun; Lee, Seung-Hyun

    2017-01-01

    Vaccinia-related kinases (VRKs) are multifaceted serine/threonine kinases that play essential roles in various aspects of cell signaling, cell cycle progression, apoptosis, and neuronal development and differentiation. However, the neuronal function of VRK3 is still unknown despite its etiological potential in human autism spectrum disorder (ASD). Here, we report that VRK3-deficient mice exhibit typical symptoms of autism-like behavior, including hyperactivity, stereotyped behaviors, reduced social interaction, and impaired context-dependent spatial memory. A significant decrease in dendritic spine number and arborization were identified in the hippocampus CA1 of VRK3-deficient mice. These mice also exhibited a reduced rectification of AMPA receptor–mediated current and changes in expression of synaptic and signaling proteins, including tyrosine receptor kinase B (TrkB), Arc, and CaMKIIα. Notably, TrkB stimulation with 7,8-dihydroxyflavone reversed the altered synaptic structure and function and successfully restored autism-like behavior in VRK3-deficient mice. These results reveal that VRK3 plays a critical role in neurodevelopmental disorders and suggest a potential therapeutic strategy for ASD. PMID:28899869

  14. Autism-like behavior caused by deletion of vaccinia-related kinase 3 is improved by TrkB stimulation.

    PubMed

    Kang, Myung-Su; Choi, Tae-Yong; Ryu, Hye Guk; Lee, Dohyun; Lee, Seung-Hyun; Choi, Se-Young; Kim, Kyong-Tai

    2017-10-02

    Vaccinia-related kinases (VRKs) are multifaceted serine/threonine kinases that play essential roles in various aspects of cell signaling, cell cycle progression, apoptosis, and neuronal development and differentiation. However, the neuronal function of VRK3 is still unknown despite its etiological potential in human autism spectrum disorder (ASD). Here, we report that VRK3 -deficient mice exhibit typical symptoms of autism-like behavior, including hyperactivity, stereotyped behaviors, reduced social interaction, and impaired context-dependent spatial memory. A significant decrease in dendritic spine number and arborization were identified in the hippocampus CA1 of VRK3 -deficient mice. These mice also exhibited a reduced rectification of AMPA receptor-mediated current and changes in expression of synaptic and signaling proteins, including tyrosine receptor kinase B (TrkB), Arc, and CaMKIIα. Notably, TrkB stimulation with 7,8-dihydroxyflavone reversed the altered synaptic structure and function and successfully restored autism-like behavior in VRK3 -deficient mice. These results reveal that VRK3 plays a critical role in neurodevelopmental disorders and suggest a potential therapeutic strategy for ASD. © 2017 Kang et al.

  15. Ultrawidefield microscope for high-speed fluorescence imaging and targeted optogenetic stimulation.

    PubMed

    Werley, Christopher A; Chien, Miao-Ping; Cohen, Adam E

    2017-12-01

    The rapid increase in the number and quality of fluorescent reporters and optogenetic actuators has yielded a powerful set of tools for recording and controlling cellular state and function. To achieve the full benefit of these tools requires improved optical systems with high light collection efficiency, high spatial and temporal resolution, and patterned optical stimulation, in a wide field of view (FOV). Here we describe our 'Firefly' microscope, which achieves these goals in a Ø6 mm FOV. The Firefly optical system is optimized for simultaneous photostimulation and fluorescence imaging in cultured cells. All but one of the optical elements are commercially available, yet the microscope achieves 10-fold higher light collection efficiency at its design magnification than the comparable commercially available microscope using the same objective. The Firefly microscope enables all-optical electrophysiology ('Optopatch') in cultured neurons with a throughput and information content unmatched by other neuronal phenotyping systems. This capability opens possibilities in disease modeling and phenotypic drug screening. We also demonstrate applications of the system to voltage and calcium recordings in human induced pluripotent stem cell derived cardiomyocytes.

  16. Ultrawidefield microscope for high-speed fluorescence imaging and targeted optogenetic stimulation

    PubMed Central

    Werley, Christopher A.; Chien, Miao-Ping; Cohen, Adam E.

    2017-01-01

    The rapid increase in the number and quality of fluorescent reporters and optogenetic actuators has yielded a powerful set of tools for recording and controlling cellular state and function. To achieve the full benefit of these tools requires improved optical systems with high light collection efficiency, high spatial and temporal resolution, and patterned optical stimulation, in a wide field of view (FOV). Here we describe our ‘Firefly’ microscope, which achieves these goals in a Ø6 mm FOV. The Firefly optical system is optimized for simultaneous photostimulation and fluorescence imaging in cultured cells. All but one of the optical elements are commercially available, yet the microscope achieves 10-fold higher light collection efficiency at its design magnification than the comparable commercially available microscope using the same objective. The Firefly microscope enables all-optical electrophysiology (‘Optopatch’) in cultured neurons with a throughput and information content unmatched by other neuronal phenotyping systems. This capability opens possibilities in disease modeling and phenotypic drug screening. We also demonstrate applications of the system to voltage and calcium recordings in human induced pluripotent stem cell derived cardiomyocytes. PMID:29296505

  17. Beyond time and space: The effect of a lateralized sustained attention task and brain stimulation on spatial and selective attention.

    PubMed

    Shalev, Nir; De Wandel, Linde; Dockree, Paul; Demeyere, Nele; Chechlacz, Magdalena

    2017-10-03

    The Theory of Visual Attention (TVA) provides a mathematical formalisation of the "biased competition" account of visual attention. Applying this model to individual performance in a free recall task allows the estimation of 5 independent attentional parameters: visual short-term memory (VSTM) capacity, speed of information processing, perceptual threshold of visual detection; attentional weights representing spatial distribution of attention (spatial bias), and the top-down selectivity index. While the TVA focuses on selection in space, complementary accounts of attention describe how attention is maintained over time, and how temporal processes interact with selection. A growing body of evidence indicates that different facets of attention interact and share common neural substrates. The aim of the current study was to modulate a spatial attentional bias via transfer effects, based on a mechanistic understanding of the interplay between spatial, selective and temporal aspects of attention. Specifically, we examined here: (i) whether a single administration of a lateralized sustained attention task could prime spatial orienting and lead to transferable changes in attentional weights (assigned to the left vs right hemi-field) and/or other attentional parameters assessed within the framework of TVA (Experiment 1); (ii) whether the effects of such spatial-priming on TVA parameters could be further enhanced by bi-parietal high frequency transcranial random noise stimulation (tRNS) (Experiment 2). Our results demonstrate that spatial attentional bias, as assessed within the TVA framework, was primed by sustaining attention towards the right hemi-field, but this spatial-priming effect did not occur when sustaining attention towards the left. Furthermore, we show that bi-parietal high-frequency tRNS combined with the rightward spatial-priming resulted in an increased attentional selectivity. To conclude, we present a novel, theory-driven method for attentional modulation providing important insights into how the spatial and temporal processes in attention interact with attentional selection. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Long-term effects of stimulant treatment on ADHD symptoms, social-emotional functioning, and cognition.

    PubMed

    Schweren, Lizanne; Hoekstra, Pieter; van Lieshout, Marloes; Oosterlaan, Jaap; Lambregts-Rommelse, Nanda; Buitelaar, Jan; Franke, Barbara; Hartman, Catharina

    2018-03-13

    Methodological and ethical constraints have hampered studies into long-term lasting outcomes of stimulant treatment in individuals with attention-deficit/hyperactivity disorder (ADHD). Lasting effects may be beneficial (i.e. improved functioning even when treatment is temporarily ceased) or detrimental (i.e. worse functioning while off medication), but both hypotheses currently lack empirical support. Here we investigate whether stimulant treatment history predicts long-term development of ADHD symptoms, social-emotional functioning or cognition, measured after medication wash-out. ADHD symptoms, social-emotional functioning and cognitive test performance were measured twice, 6 years apart, in two ADHD groups (stimulant-treated versus not stimulant-treated between baseline and follow-up). Groups were closely matched on baseline clinical and demographic variables (n = 148, 58% male, age = 11.1). A matched healthy control group was included for reference. All but two outcome measures (emotional problems and prosocial behaviour) improved between baseline and follow-up. Improvement over time in the stimulant-treated group did not differ from improvement in the not stimulant-treated group on any outcome measure. Stimulant treatment is not associated with the long-term developmental course of ADHD symptoms, social-emotional functioning, motor control, timing or verbal working memory. Adolescence is characterised by clinical improvement regardless of stimulant treatment during that time. These findings are an important source to inform the scientific and public debate.

  19. Microscopic magnetic stimulation of neural tissue

    PubMed Central

    Bonmassar, Giorgio; Lee, Seung Woo; Freeman, Daniel K.; Polasek, Miloslav; Fried, Shelley I.; Gale, John T.

    2012-01-01

    Electrical stimulation is currently used to treat a wide range of cardiovascular, sensory and neurological diseases. Despite its success, there are significant limitations to its application, including incompatibility with magnetic resonance imaging, limited control of electric fields and decreased performance associated with tissue inflammation. Magnetic stimulation overcomes these limitations but existing devices (that is, transcranial magnetic stimulation) are large, reducing their translation to chronic applications. In addition, existing devices are not effective for deeper, sub-cortical targets. Here we demonstrate that sub-millimeter coils can activate neuronal tissue. Interestingly, the results of both modelling and physiological experiments suggest that different spatial orientations of the coils relative to the neuronal tissue can be used to generate specific neural responses. These results raise the possibility that micro-magnetic stimulation coils, small enough to be implanted within the brain parenchyma, may prove to be an effective alternative to existing stimulation devices. PMID:22735449

  20. Bio-heat transfer model of deep brain stimulation-induced temperature changes

    NASA Astrophysics Data System (ADS)

    Elwassif, Maged M.; Kong, Qingjun; Vazquez, Maribel; Bikson, Marom

    2006-12-01

    There is a growing interest in the use of chronic deep brain stimulation (DBS) for the treatment of medically refractory movement disorders and other neurological and psychiatric conditions. Fundamental questions remain about the physiologic effects of DBS. Previous basic research studies have focused on the direct polarization of neuronal membranes by electrical stimulation. The goal of this paper is to provide information on the thermal effects of DBS using finite element models to investigate the magnitude and spatial distribution of DBS-induced temperature changes. The parameters investigated include stimulation waveform, lead selection, brain tissue electrical and thermal conductivities, blood perfusion, metabolic heat generation during the stimulation and lead thermal conductivity/heat dissipation through the electrode. Our results show that clinical DBS protocols will increase the temperature of surrounding tissue by up to 0.8 °C depending on stimulation/tissue parameters.

  1. Toward rational design of electrical stimulation strategies for epilepsy control

    PubMed Central

    Sunderam, Sridhar; Gluckman, Bruce; Reato, Davide; Bikson, Marom

    2009-01-01

    Electrical stimulation is emerging as a viable alternative for epilepsy patients whose seizures are not alleviated by drugs or surgery. Its attractions are temporal and spatial specificity of action, flexibility of waveform parameters and timing, and the perception that its effects are reversible unlike resective surgery. However, despite significant advances in our understanding of mechanisms of neural electrical stimulation, clinical electrotherapy for seizures relies heavily on empirical tuning of parameters and protocols. We highlight concurrent treatment goals with potentially conflicting design constraints that must be resolved when formulating rational strategies for epilepsy electrotherapy: namely seizure reduction versus cognitive impairment, stimulation efficacy versus tissue safety, and mechanistic insight versus clinical pragmatism. First, treatment markers, objectives, and metrics relevant to electrical stimulation for epilepsy are discussed from a clinical perspective. Then the experimental perspective is presented, with the biophysical mechanisms and modalities of open-loop electrical stimulation, and the potential benefits of closed-loop control for epilepsy. PMID:19926525

  2. Visual-Manipulative Response Strategies in Infant Operant Conditioning with Spatially Displaced Feedback.

    ERIC Educational Resources Information Center

    Millar, W. Stuart; Schaffer, H. Rudolph

    Six- and nine-month-old infants were exposed to contingent or non-contingent perceptual stimulation from a source which was spatially displaced at 60 from the infant's midline. Reliable operant acquisition was observed in the case of the nine-month-old infants, but not in the case of the six-month-old infants whose performance was similar to that…

  3. Making sense of human ecology mapping: an overview of approaches to integrating socio-spatial data into environmental planning

    Treesearch

    Rebecca McLain; Melissa R. Poe; Kelly Biedenweg; Lee K. Cerveny; Diane Besser; Dale J. Blahna

    2013-01-01

    Ecosystem-based planning and management have stimulated the need to gather sociocultural values and human uses of land in formats accessible to diverse planners and researchers. Human Ecology Mapping (HEM) approaches offer promising spatial data gathering and analytical tools, while also addressing important questions about human-landscape connections. This article...

  4. Knowing what and where: TMS evidence for the dual neural basis of geographical knowledge.

    PubMed

    Hoffman, Paul; Crutch, Sebastian

    2016-02-01

    All animals acquire knowledge about the topography of their immediate environment through direct exploration. Uniquely, humans also acquire geographical knowledge indirectly through exposure to maps and verbal information, resulting in a rich database of global geographical knowledge. We used transcranial magnetic stimulation to investigate the structure and neural basis of this critical but poorly understood component of semantic knowledge. Participants completed tests of geographical knowledge that probed either information about spatial locations (e.g., France borders Spain) or non-spatial taxonomic information (e.g., France is a country). TMS applied to the anterior temporal lobe, a region that codes conceptual knowledge for words and objects, had a general disruptive effect on the geographical tasks. In contrast, stimulation of the intraparietal sulcus (IPS), a region involved in the coding of spatial and numerical information, had a highly selective effect on spatial geographical decisions but no effect on taxonomic judgements. Our results establish that geographical concepts lie at the intersection of two distinct neural representation systems, and provide insights into how the interaction of these systems shape our understanding of the world. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Electrical and optical co-stimulation in the deaf white cat

    NASA Astrophysics Data System (ADS)

    Cao, Zhiping; Xu, Yingyue; Tan, Xiaodong; Suematsu, Naofumi; Robinson, Alan; Richter, Claus-Peter

    2018-02-01

    Spatial selectivity of neural stimulation with photons, such as infrared neural stimulation (INS) is higher than the selectivity obtained with electrical stimulation. To obtain more independent channels for stimulation in neural prostheses, INS may be implemented to better restore the fidelity of the damaged neural system. However, irradiation with infrared light also bares the risk of heat accumulation in the target tissue with subsequent neural damage. Lowering the threshold for stimulation could reduce the amount of heat delivered to the tissue and the risk for subsequent tissue damage. It has been shown in the rat sciatic nerve that simultaneous irradiation with infrared light and the delivery of biphasic sub-threshold electrical pulses can reduce the threshold for INS [1]. In this study, deaf white cats have been used to test whether opto-electrical co-stimulation can reduce the stimulation threshold for INS in the auditory system too. The cochleae of the deaf white cats have largely reduced spiral ganglion neuron counts and significant degeneration of the organ of Corti and do not respond to acoustic stimuli. Combined electrical and optical stimulation was used to demonstrate that simultaneous stimulation with infrared light and biphasic electrical pulses can reduce the threshold for stimulation.

  6. Engineering an improved light-induced dimer (iLID) for controlling the localization and activity of signaling proteins

    DOE PAGES

    Guntas, Gurkan; Hallett, Ryan A.; Zimmerman, Seth P.; ...

    2014-12-22

    The discovery of light-inducible protein–protein interactions has allowed for the spatial and temporal control of a variety of biological processes. To be effective, a photodimerizer should have several characteristics: it should show a large change in binding affinity upon light stimulation, it should not cross-react with other molecules in the cell, and it should be easily used in a variety of organisms to recruit proteins of interest to each other. In this study, to create a switch that meets these criteria we have embedded the bacterial SsrA peptide in the C-terminal helix of a naturally occurring photoswitch, the light-oxygen-voltage 2more » (LOV2) domain from Avena sativa. In the dark the SsrA peptide is sterically blocked from binding its natural binding partner, SspB. When activated with blue light, the C-terminal helix of the LOV2 domain undocks from the protein, allowing the SsrA peptide to bind SspB. Without optimization, the switch exhibited a twofold change in binding affinity for SspB with light stimulation. Here, we describe the use of computational protein design, phage display, and high-throughput binding assays to create an improved light inducible dimer (iLID) that changes its affinity for SspB by over 50-fold with light stimulation. A crystal structure of iLID shows a critical interaction between the surface of the LOV2 domain and a phenylalanine engineered to more tightly pin the SsrA peptide against the LOV2 domain in the dark. Finally, we demonstrate the functional utility of the switch through light-mediated subcellular localization in mammalian cell culture and reversible control of small GTPase signaling.« less

  7. The role of spatial organization of Ca2+ release sites in the generation of arrhythmogenic diastolic Ca2+ release in myocytes from failing hearts

    PubMed Central

    Ho, Hsiang-Ting; Bonilla, Ingrid M.; Terentyeva, Radmila; Schober, Karsten E.; Terentyev, Dmitry; Carnes, Cynthia A.

    2018-01-01

    In heart failure (HF), dysregulated cardiac ryanodine receptors (RyR2) contribute to the generation of diastolic Ca2+ waves (DCWs), thereby predisposing adrenergically stressed failing hearts to life-threatening arrhythmias. However, the specific cellular, subcellular, and molecular defects that account for cardiac arrhythmia in HF remain to be elucidated. Patch-clamp techniques and confocal Ca2+ imaging were applied to study spatially defined Ca2+ handling in ventricular myocytes isolated from normal (control) and failing canine hearts. Based on their activation time upon electrical stimulation, Ca2+ release sites were categorized as coupled, located in close proximity to the sarcolemmal Ca2+ channels, and uncoupled, the Ca2+ channel-free non-junctional Ca2+ release units. In control myocytes, stimulation of β-adrenergic receptors with isoproterenol (Iso) resulted in a preferential increase in Ca2+ spark rate at uncoupled sites. This site-specific effect of Iso was eliminated by the phosphatase inhibitor okadaic acid, which caused similar facilitation of Ca2+ sparks at coupled and uncoupled sites. Iso-challenged HF myocytes exhibited increased predisposition to DCWs compared to control myocytes. In addition, the overall frequency of Ca2+ sparks was increased in HF cells due to preferential stimulation of coupled sites. Furthermore, coupled sites exhibited accelerated recovery from functional refractoriness in HF myocytes compared to control myocytes. Spatially resolved subcellular Ca2+ mapping revealed that DCWs predominantly originated from coupled sites. Inhibition of CaMK∏ suppressed DCWs and prevented preferential stimulation of coupled sites in Iso-challenged HF myocytes. These results suggest that CaMK∏-(and phosphatase)-dependent dysregulation of junctional Ca2+ release sites contributes to Ca2+-dependent arrhythmogenesis in HF. PMID:28612155

  8. The MDS-UPDRS tracks motor and non-motor improvement due to subthalamic nucleus deep brain stimulation in Parkinson disease.

    PubMed

    Chou, Kelvin L; Taylor, Jennifer L; Patil, Parag G

    2013-11-01

    The Movement Disorders Society revision of the Unified Parkinson Disease Rating Scale (MDS-UPDRS) improves upon the original UPDRS by adding more non-motor items, making it a more robust tool to evaluate the severity of motor and non-motor symptoms of Parkinson disease. Previous studies on deep brain stimulation have not used the MDS-UPDRS. To determine if the MDS-UPDRS could detect improvement in both motor and non-motor symptoms after bilateral subthalamic nucleus deep brain stimulation for Parkinson disease. We compared scores on the entire MDS-UPDRS prior to surgery (baseline) and approximately six months following the initial programming visit in twenty subjects (12M/8F) with Parkinson disease undergoing bilateral subthalamic nucleus deep brain stimulation. STN DBS significantly improved the scores for every section of the MDS-UPDRS at the 6 month follow-up. Part I improved by 3.1 points (22%), Part II by 5.3 points (29%), Part III by 13.1 points (29%) with stimulation alone, and Part IV by 7.1 points (74%). Individual non-motor items in Part I that improved significantly were constipation, light-headedness, and fatigue. Both motor and non-motor symptoms, as assessed by the MDS-UPDRS, improve with bilateral subthalamic nucleus stimulation six months after the stimulator is turned on. We recommend that the MDS-UPDRS be utilized in future deep brain stimulation studies because of the advantage of detecting change in non-motor symptoms. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Fronto-Parietal Brain Responses to Visuotactile Congruence in an Anatomical Reference Frame

    PubMed Central

    Limanowski, Jakub; Blankenburg, Felix

    2018-01-01

    Spatially and temporally congruent visuotactile stimulation of a fake hand together with one’s real hand may result in an illusory self-attribution of the fake hand. Although this illusion relies on a representation of the two touched body parts in external space, there is tentative evidence that, for the illusion to occur, the seen and felt touches also need to be congruent in an anatomical reference frame. We used functional magnetic resonance imaging and a somatotopical, virtual reality-based setup to isolate the neuronal basis of such a comparison. Participants’ index or little finger was synchronously touched with the index or little finger of a virtual hand, under congruent or incongruent orientations of the real and virtual hands. The left ventral premotor cortex responded significantly more strongly to visuotactile co-stimulation of the same versus different fingers of the virtual and real hand. Conversely, the left anterior intraparietal sulcus responded significantly more strongly to co-stimulation of different versus same fingers. Both responses were independent of hand orientation congruence and of spatial congruence of the visuotactile stimuli. Our results suggest that fronto-parietal areas previously associated with multisensory processing within peripersonal space and with tactile remapping evaluate the congruence of visuotactile stimulation on the body according to an anatomical reference frame. PMID:29556183

  10. Microfluidic platform for single cell analysis under dynamic spatial and temporal stimulation.

    PubMed

    Song, Jiyoung; Ryu, Hyunryul; Chung, Minhwan; Kim, Youngtaek; Blum, Yannick; Lee, Sung Sik; Pertz, Olivier; Jeon, Noo Li

    2018-05-01

    Recent research on cellular responses is shifting from static observations recorded under static stimuli to real-time monitoring in a dynamic environment. Since cells sense and interact with their surrounding microenvironment, an experimental platform where dynamically changing cellular microenvironments should be recreated in vitro. There has been a lack of microfluidic devices to support spatial and temporal stimulations in a simple and robust manner. Here, we describe a microfluidic device that generates dynamic chemical gradients and pulses in both space and time using a single device. This microfluidic device provides at least 12h of continuous stimulations that can be used to observe responses from mammalian cells. Combination of the microfluidic de-vice with live-cell imaging facilitates real-time observation of dynamic cellular response at single cell level. Using stable HEK cells with biosensors, ERK (Extracellular signal-Regulated Kinase) activities were observed un-der the pulsatile and ramping stimulations of EGF (Epidermal Growth Factor). We quantified ERK activation even at extremely low EGF concentration (0.0625µg/ml), which can not be observed using conventional techniques such as western blot. Cytoskeleton re-arrangement of the 3T3 fibroblast (stable transfection with Lifeact-GFP) was compared under abrupt and gradually changing gradient of PDGF. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Fronto-Parietal Brain Responses to Visuotactile Congruence in an Anatomical Reference Frame.

    PubMed

    Limanowski, Jakub; Blankenburg, Felix

    2018-01-01

    Spatially and temporally congruent visuotactile stimulation of a fake hand together with one's real hand may result in an illusory self-attribution of the fake hand. Although this illusion relies on a representation of the two touched body parts in external space, there is tentative evidence that, for the illusion to occur, the seen and felt touches also need to be congruent in an anatomical reference frame. We used functional magnetic resonance imaging and a somatotopical, virtual reality-based setup to isolate the neuronal basis of such a comparison. Participants' index or little finger was synchronously touched with the index or little finger of a virtual hand, under congruent or incongruent orientations of the real and virtual hands. The left ventral premotor cortex responded significantly more strongly to visuotactile co-stimulation of the same versus different fingers of the virtual and real hand. Conversely, the left anterior intraparietal sulcus responded significantly more strongly to co-stimulation of different versus same fingers. Both responses were independent of hand orientation congruence and of spatial congruence of the visuotactile stimuli. Our results suggest that fronto-parietal areas previously associated with multisensory processing within peripersonal space and with tactile remapping evaluate the congruence of visuotactile stimulation on the body according to an anatomical reference frame.

  12. Preservation of visual cortical function following retinal pigment epithelium transplantation in the RCS rat using optical imaging techniques.

    PubMed

    Gias, Carlos; Jones, Myles; Keegan, David; Adamson, Peter; Greenwood, John; Lund, Ray; Martindale, John; Johnston, David; Berwick, Jason; Mayhew, John; Coffey, Peter

    2007-04-01

    The aim of this study was to determine the extent of cortical functional preservation following retinal pigment epithelium (RPE) transplantation in the Royal College of Surgeons (RCS) rat using single-wavelength optical imaging and spectroscopy. The cortical responses to visual stimulation in transplanted rats at 6 months post-transplantation were compared with those from age-matched untreated dystrophic and non-dystrophic rats. Our results show that cortical responses were evoked in non-dystrophic rats to both luminance changes and pattern stimulation, whereas no response was found in untreated dystrophic animals to any of the visual stimuli tested. In contrast, a cortical response was elicited in most of the transplanted rats to luminance changes and in many of those a response was also evoked to pattern stimulation. Although the transplanted rats did not respond to high spatial frequency information we found evidence of preservation in the cortical processing of luminance changes and low spatial frequency stimulation. Anatomical sections of transplanted rat retinas confirmed the capacity of RPE transplantation to rescue photoreceptors. Good correlation was found between photoreceptor survival and the extent of cortical function preservation determined with optical imaging techniques. This study determined the efficacy of RPE transplantation to preserve visual cortical processing and established optical imaging as a powerful technique for its assessment.

  13. Local probing and stimulation of neuronal cells by optical manipulation

    NASA Astrophysics Data System (ADS)

    Cojoc, Dan

    2014-09-01

    During development and in the adult brain, neurons continuously explore the environment searching for guidance cues, leading to the appropriate connections. Elucidating these mechanisms represents a gold goal in neurobiology. Here, I discuss our recent achievements developing new approaches to locally probe the growth cones and stimulate neuronal cell compartments with high spatial and temporal resolution. Optical tweezers force spectroscopy applied in conjunction with metabolic inhibitors reveals new properties of the cytoskeleton dynamics. On the other hand, using optically manipulated microvectors as functionalized beads or filled liposomes, we demonstrate focal stimulation of neurons by small number of signaling molecules.

  14. An intra-neural microstimulation system for ultra-high field magnetic resonance imaging and magnetoencephalography.

    PubMed

    Glover, Paul M; Watkins, Roger H; O'Neill, George C; Ackerley, Rochelle; Sanchez-Panchuelo, Rosa; McGlone, Francis; Brookes, Matthew J; Wessberg, Johan; Francis, Susan T

    2017-10-01

    Intra-neural microstimulation (INMS) is a technique that allows the precise delivery of low-current electrical pulses into human peripheral nerves. Single unit INMS can be used to stimulate individual afferent nerve fibres during microneurography. Combining this with neuroimaging allows the unique monitoring of central nervous system activation in response to unitary, controlled tactile input, with functional magnetic resonance imaging (fMRI) providing exquisite spatial localisation of brain activity and magnetoencephalography (MEG) high temporal resolution. INMS systems suitable for use within electrophysiology laboratories have been available for many years. We describe an INMS system specifically designed to provide compatibility with both ultra-high field (7T) fMRI and MEG. Numerous technical and safety issues are addressed. The system is fully analogue, allowing for arbitrary frequency and amplitude INMS stimulation. Unitary recordings obtained within both the MRI and MEG screened-room environments are comparable with those obtained in 'clean' electrophysiology recording environments. Single unit INMS (current <7μA, 200μs pulses) of individual mechanoreceptive afferents produces appropriate and robust responses during fMRI and MEG. This custom-built MRI- and MEG-compatible stimulator overcomes issues with existing INMS approaches; it allows well-controlled switching between recording and stimulus mode, prevents electrical shocks because of long cable lengths, permits unlimited patterns of stimulation, and provides a system with improved work-flow and participant comfort. We demonstrate that the requirements for an INMS-integrated system, which can be used with both fMRI and MEG imaging systems, have been fully met. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  15. Exercise leads to the re-emergence of the cholinergic/nestin neuronal phenotype within the medial septum/diagonal band and subsequent rescue of both hippocampal ACh efflux and spatial behavior.

    PubMed

    Hall, Joseph M; Savage, Lisa M

    2016-04-01

    Exercise has been shown to improve cognitive functioning in a range of species, presumably through an increase in neurotrophins throughout the brain, but in particular the hippocampus. The current study assessed the ability of exercise to restore septohippocampal cholinergic functioning in the pyrithiamine-induced thiamine deficiency (PTD) rat model of the amnestic disorder Korsakoff Syndrome. After voluntary wheel running or sedentary control conditions (stationary wheel attached to the home cage), PTD and control rats were behaviorally tested with concurrent in vivo microdialysis, at one of two time points: 24-h or 2-weeks post-exercise. It was found that only after the 2-week adaption period did exercise lead to an interrelated sequence of events in PTD rats that included: (1) restored spatial working memory; (2) rescued behaviorally-stimulated hippocampal acetylcholine efflux; and (3) within the medial septum/diagonal band, the re-emergence of the cholinergic (choline acetyltransferase [ChAT+]) phenotype, with the greatest change occurring in the ChAT+/nestin+ neurons. Furthermore, in control rats, exercise followed by a 2-week adaption period improved hippocampal acetylcholine efflux and increased the number of neurons co-expressing the ChAT and nestin phenotype. These findings demonstrate a novel mechanism by which exercise can modulate the mature cholinergic/nestin neuronal phenotype leading to improved neurotransmitter function as well as enhanced learning and memory. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Increasing spatial resolution and comparison of MR imaging sequences for the inner ear

    NASA Astrophysics Data System (ADS)

    Snyder, Carl J.; Bolinger, Lizann; Rubinstein, Jay T.; Wang, Ge

    2002-04-01

    The size and location of the cochlea and cochlear nerve are needed to assess the feasibility of cochlea implantation, provide information for surgical planning, and aid in construction of cochlear models. Models of implant stimulation incorporating anatomical and physiological information are likely to provide a better understanding of the biophysics of information transferred with cochlear implants and aid in electrode design and arrangement on cochlear implants. Until recently MR did not provide the necessary image resolution and suffered from long acquisition times. The purpose of this study was to optimize both Fast Spin Echo (FSE) and Steady State Free Precession (FIESTA) imaging scan parameters for the inner ear and comparatively examine both for improved image quality and increased spatial resolution. Image quality was determined by two primary measurements, signal to noise ratio (SNR), and image sharpness. Optimized parameters for FSE were 120ms, 3000ms, 64, and 32.25kHz for the TE, TR, echo train length, and bandwidth, respectively. FIESTA parameters were optimized to 2.7, 5.5ms, 70 degree(s), and 62.5kHz, for TE, TR, flip angle, and bandwidth, respectively. While both had the same in-plane spatial resolution, 0.625mm, FIESTA data shows higher SNR per acquisition time and better edge sharpness.

  17. High-Resolution Analysis of Seismicity Induced at Berlín Geothermal Field, El Salvador

    NASA Astrophysics Data System (ADS)

    Kwiatek, G.; Bulut, F.; Dresen, G. H.; Bohnhoff, M.

    2012-12-01

    We investigate induced microseismic activity monitored at Berlín Geothermal Field, El Salvador, during a hydraulic stimulation. The site was monitored for a time period of 17 months using thirteen 3-component seismic stations located in shallow boreholes. Three stimulations were performed in the well TR8A with a maximum injection rate and well head pressure of 160l/s and 130bar, respectively. For the entire time period of our analysis, the acquisition system recorded 581 events with moment magnitudes ranging between -0.5 and 3.7. The initial seismic catalog provided by the operator was substantially improved: 1) We re-picked P- and S-wave onsets and relocated the seismic events using the double-difference relocation algorithm based on cross-correlation derived differential arrival time data. Forward modeling was performed using a local 1D velocity model instead of homogeneous full-space. 2) We recalculated source parameters using the spectral fitting method and refined the results applying the spectral ratio method. We investigated the source parameters and spatial and temporal changes of the seismic activity based on the refined dataset and studied the correlation between seismic activity and production. The achieved hypocentral precision allowed resolving the spatiotemporal changes in seismic activity down to a scale of a few meters. The application of spectral ratio method significantly improved the quality of source parameters in a high-attenuating and complex geological environment. Of special interest is the largest event (Mw3.7) and its nucleation process. We investigate whether the refined seismic data display any signatures that the largest event is triggered by the shut-in of the well. We found seismic activity displaying clear spatial and temporal patterns that could be easily related to the amount of water injected into the well TR8A and other reinjection wells in the investigated area. The migration of seismicity outside of injection point is observed while injection rate is increasing. The locations of migrating seismic events are related to the existing fault system that is independently supported by calculated focal mechanisms. We found that the event migration occurs until the shut-in of the well. We observe that the large magnitude events are observed right after the shut-in, located in undamaged parts of the fault system. Results show that the following stimulation episodes require increased injection rate level (or increased well head pressure) to re-activate the seismic activity (Kaiser Effect, "Crustal memory" effect). The static stress drop values increase with the distance from injection point that is interpreted to be related to pore pressure perturbations introduced by stimulation of the injection well.

  18. Electrotactile EMG feedback improves the control of prosthesis grasping force

    NASA Astrophysics Data System (ADS)

    Schweisfurth, Meike A.; Markovic, Marko; Dosen, Strahinja; Teich, Florian; Graimann, Bernhard; Farina, Dario

    2016-10-01

    Objective. A drawback of active prostheses is that they detach the subject from the produced forces, thereby preventing direct mechanical feedback. This can be compensated by providing somatosensory feedback to the user through mechanical or electrical stimulation, which in turn may improve the utility, sense of embodiment, and thereby increase the acceptance rate. Approach. In this study, we compared a novel approach to closing the loop, namely EMG feedback (emgFB), to classic force feedback (forceFB), using electrotactile interface in a realistic task setup. Eleven intact-bodied subjects and one transradial amputee performed a routine grasping task while receiving emgFB or forceFB. The two feedback types were delivered through the same electrotactile interface, using a mixed spatial/frequency coding to transmit 8 discrete levels of the feedback variable. In emgFB, the stimulation transmitted the amplitude of the processed myoelectric signal generated by the subject (prosthesis input), and in forceFB the generated grasping force (prosthesis output). The task comprised 150 trials of routine grasping at six forces, randomly presented in blocks of five trials (same force). Interquartile range and changes in the absolute error (AE) distribution (magnitude and dispersion) with respect to the target level were used to assess precision and overall performance, respectively. Main results. Relative to forceFB, emgFB significantly improved the precision of myoelectric commands (min/max of the significant levels) for 23%/36% as well as the precision of force control for 12%/32%, in intact-bodied subjects. Also, the magnitude and dispersion of the AE distribution were reduced. The results were similar in the amputee, showing considerable improvements. Significance. Using emgFB, the subjects therefore decreased the uncertainty of the forward pathway. Since there is a correspondence between the EMG and force, where the former anticipates the latter, the emgFB allowed for predictive control, as the subjects used the feedback to adjust the desired force even before the prosthesis contacted the object. In conclusion, the online emgFB was superior to the classic forceFB in realistic conditions that included electrotactile stimulation, limited feedback resolution (8 levels), cognitive processing delay, and time constraints (fast grasping).

  19. Optical responses evoked by white matter stimulation in rat visual cortical slices and their relation to neural activities.

    PubMed

    Tanifuji, M; Yamanaka, A; Sunaba, R; Terakawa, S; Toyama, K

    1996-10-28

    To characterize optical responses (ORs) evoked by white matter (WM) stimulation in slices of rat visual cortex (VC) stained with voltage sensitive dyes, time course of ORs in each layer was investigated by recording ORs with a linearly aligned photodiode array, and the spatial patterns of the ORs at specified time after stimulation were investigated by a CCD camera in combination with stroboscopic illumination. The ORs recorded by the photodiode array were an increase in absorption at 700 nm and a decrease in the wavelength below 650 nm, suggesting that the ORs were dye related. The ORs were compared with field potentials (FPs) to clarify that neural events were represented by the ORs, and in support of this view, we found that the first order spatial differentials of ORs and that of FPs were in good agreement. We further compared ORs with intracellular responses, and found that the ORs mainly represent postsynaptic potentials (PSPs) of VC neurons except for the deeper part of layer VI, where a component representing action potentials in fibers stimulated directly was observed. The time-lapse imaging of ORs showed that excitation first propagated vertically up to layer I and subsequently in the horizontal direction along layers II-III and V-VI as in previous investigations. Spatio-temporal patterns of ORs under blockade of synaptic transmission were also investigated to reveal activity of fibers evoked by WM stimulation which produced such patterns of propagation.

  20. Magnetothermal genetic deep brain stimulation of motor behaviors in awake, freely moving mice

    PubMed Central

    Zhang, Qian; Castellanos Rubio, Idoia; del Pino, Pablo

    2017-01-01

    Establishing how neurocircuit activation causes particular behaviors requires modulating the activity of specific neurons. Here, we demonstrate that magnetothermal genetic stimulation provides tetherless deep brain activation sufficient to evoke motor behavior in awake mice. The approach uses alternating magnetic fields to heat superparamagnetic nanoparticles on the neuronal membrane. Neurons, heat-sensitized by expressing TRPV1 are activated with magnetic field application. Magnetothermal genetic stimulation in the motor cortex evoked ambulation, deep brain stimulation in the striatum caused rotation around the body-axis, and stimulation near the ridge between ventral and dorsal striatum caused freezing-of-gait. The duration of the behavior correlated tightly with field application. This approach provides genetically and spatially targetable, repeatable and temporarily precise activation of deep-brain circuits without the need for surgical implantation of any device. PMID:28826470

  1. Improving Speech Perception in Noise with Current Focusing in Cochlear Implant Users

    PubMed Central

    Srinivasan, Arthi G.; Padilla, Monica; Shannon, Robert V.; Landsberger, David M.

    2013-01-01

    Cochlear implant (CI) users typically have excellent speech recognition in quiet but struggle with understanding speech in noise. It is thought that broad current spread from stimulating electrodes causes adjacent electrodes to activate overlapping populations of neurons which results in interactions across adjacent channels. Current focusing has been studied as a way to reduce spread of excitation, and therefore, reduce channel interactions. In particular, partial tripolar stimulation has been shown to reduce spread of excitation relative to monopolar stimulation. However, the crucial question is whether this benefit translates to improvements in speech perception. In this study, we compared speech perception in noise with experimental monopolar and partial tripolar speech processing strategies. The two strategies were matched in terms of number of active electrodes, microphone, filterbanks, stimulation rate and loudness (although both strategies used a lower stimulation rate than typical clinical strategies). The results of this study showed a significant improvement in speech perception in noise with partial tripolar stimulation. All subjects benefited from the current focused speech processing strategy. There was a mean improvement in speech recognition threshold of 2.7 dB in a digits in noise task and a mean improvement of 3 dB in a sentences in noise task with partial tripolar stimulation relative to monopolar stimulation. Although the experimental monopolar strategy was worse than the clinical, presumably due to different microphones, frequency allocations and stimulation rates, the experimental partial-tripolar strategy, which had the same changes, showed no acute deficit relative to the clinical. PMID:23467170

  2. Optical cell stimulation for neuronal excitation (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Johannsmeier, Sonja; Heeger, Patrick; Terakawa, Mitsuhiro; Heisterkamp, Alexander; Ripken, Tammo; Heinemann, Dag

    2017-02-01

    Optical manipulation of cellular functions represents a growing field in biomedical sciences. The possibility to modulate specific targets with high spatial and temporal precision in a contactless manner allows a broad range of applications. Here, we present a study on stimulation of neuronal cells by optical means. As a long-term objective, we seek to improve the performance of current electric neurostimulation, especially in the context of cochlear implants. Firstly, we tested a gold nanoparticle mediated approach to modulate transmembrane conductivity by irradiation using a picosecond pulsed Nd:YAG laser at 532 nm for 40 ms in a neuroblastoma cell line (N2A) and primary murine neurons. The light absorption leads to a rapid temperature increase of the gold nanoparticles, which can induce an increased permeabilisation of the cellular membrane. Calcium transients were recorded as an indicator of neuronal activity. Although calcium signals were reliably detected upon laser irradiation, the temporal behavior did not resemble action potentials. The origin of these signals was investigated by an inhibitor study. These results indicate calcium induced calcium release (CICR) as the major source of the calcium transients. Consecutively, we tested alternative approaches for cell stimulation, such as glutamate release and optogenetics, and evaluated the potential of these methods for the application in a cochlear implant. Compared to the gold nanoparticle approach, both techniques induce less cellular stress and reliably produce action potentials.

  3. Individual differences and specificity of prefrontal gamma frequency-tACS on fluid intelligence capabilities.

    PubMed

    Santarnecchi, E; Muller, T; Rossi, S; Sarkar, A; Polizzotto, N R; Rossi, A; Cohen Kadosh, R

    2016-02-01

    Emerging evidence suggests that transcranial alternating current stimulation (tACS) is an effective, frequency-specific modulator of endogenous brain oscillations, with the potential to alter cognitive performance. Here, we show that reduction in response latencies to solve complex logic problem indexing fluid intelligence is obtained through 40 Hz-tACS (gamma band) applied to the prefrontal cortex. This improvement in human performance depends on individual ability, with slower performers at baseline receiving greater benefits. The effect could have not being explained by regression to the mean, and showed task and frequency specificity: it was not observed for trials not involving logical reasoning, as well as with the application of low frequency 5 Hz-tACS (theta band) or non-periodic high frequency random noise stimulation (101-640 Hz). Moreover, performance in a spatial working memory task was not affected by brain stimulation, excluding possible effects on fluid intelligence enhancement through an increase in memory performance. We suggest that such high-level cognitive functions are dissociable by frequency-specific neuromodulatory effects, possibly related to entrainment of specific brain rhythms. We conclude that individual differences in cognitive abilities, due to acquired or developmental origins, could be reduced during frequency-specific tACS, a finding that should be taken into account for future individual cognitive rehabilitation studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Lateralized Contribution of Prefrontal Cortex in Controlling Task-Irrelevant Information during Verbal and Spatial Working Memory Tasks: rTMS Evidence

    ERIC Educational Resources Information Center

    Sandrini, Marco; Rossini, Paolo Maria; Miniussi, Carlo

    2008-01-01

    The functional organization of working memory (WM) in the human prefrontal cortex remains unclear. The present study used repetitive transcranial magnetic stimulation (rTMS) to clarify the role of the dorsolateral prefrontal cortex (dlPFC) both in the types of information (verbal vs. spatial), and the types of processes (maintenance vs.…

  5. Use of Vagus Nerve Stimulator on Children With Primary Generalized Epilepsy.

    PubMed

    Welch, William P; Sitwat, Bilal; Sogawa, Yoshimi

    2018-06-01

    To describe the response to vagus nerve stimulator (VNS) in otherwise neurotypical children with medically intractable primary generalized epilepsy. Retrospective chart review of patients who underwent vagus nerve stimulator surgery between January 2011 and December 2015. Eleven patients were identified. Median follow-up duration was 2.5 years (1.2-8.4 years). Prior to vagus nerve stimulator surgery, all patients had at least 1 seizure per week, and 7/11 (64%) had daily seizures. At 1-year follow-up after vagus nerve stimulator, 7/11 (64%) reported improved seizure frequency and 6/11 (55%) reported fewer than 1 seizure per month. Three patients (27%) reported complications related to vagus nerve stimulator surgery, and no patients required device removal. In children with medically intractable primary generalized epilepsy, vagus nerve stimulator is well tolerated and appears to lead to improvement in seizure frequency. Improvement was not attributable to epilepsy classification, age at vagus nerve stimulator implantation, output current, duty cycle, or follow-up duration.

  6. What Exactly Are the Benefits of Stimulants for ADHD?

    ERIC Educational Resources Information Center

    Advokat, Claire

    2009-01-01

    Stimulant drugs (methylphenidate and amphetamine) have been used successfully for decades to improve the behavioral impairments of hyperactivity, impulsivity, and inattention in children diagnosed with attention-deficit/hyperactivity disorder (ADHD). A voluminous literature supports the benefits of stimulants for improving classroom manageability…

  7. Utility of bilateral acoustic hearing in combination with electrical stimulation provided by the cochlear implant.

    PubMed

    Plant, Kerrie; Babic, Leanne

    2016-01-01

    The aim of the study was to quantify the benefit provided by having access to amplified acoustic hearing in the implanted ear for use in combination with contralateral acoustic hearing and the electrical stimulation provided by the cochlear implant. Measures of spatial and non-spatial hearing abilities were obtained to compare performance obtained with different configurations of acoustic hearing in combination with electrical stimulation. In the combined listening condition participants had access to bilateral acoustic hearing whereas the bimodal condition used acoustic hearing contralateral to the implanted ear only. Experience was provided with each of the listening conditions using a repeated-measures A-B-B-A experimental design. Sixteen post-linguistically hearing-impaired adults participated in the study. Group mean benefit was obtained with use of the combined mode on measures of speech recognition in coincident speech in noise, localization ability, subjective ratings of real-world benefit, and musical sound quality ratings. Access to bilateral acoustic hearing after cochlear implantation provides significant benefit on a range of functional measures.

  8. Blood flow variation in human muscle during electrically stimulated exercise bouts.

    PubMed

    Vanderthommen, Marc; Depresseux, Jean-Claude; Dauchat, Luc; Degueldre, Christian; Croisier, Jean-Louis; Crielaard, Jean-Michel

    2002-07-01

    To evaluate, with a high spatial resolution, the blood flow variations in human skeletal muscle during neuromuscular electric stimulation (NMES) and hence to gain better understanding of the mechanisms of muscle spatial recruitment during NMES. One thigh was submitted to 3 stimulation bouts of different durations (S1=4min, S2=8min, S3=12min) with a workload corresponding to 10% of quadriceps maximal isometric voluntary torque. A cyclotron research center at a Belgian university. Ten healthy male volunteers. Not applicable. Participants were studied with positron emission tomography and H(2)(15)O. Tissue blood flow was evaluated during the last 4 minutes of each stimulation bout in multiple regions of interest (ROIs) selected in the transverse section of the stimulated thigh. Mean tissue blood flow was significantly lower during S1 (5.9+/-1.3mL. min(-1). 100g(-1)) than during S2 (10.6+/-3.4mL. min(-1). 100g(-1)) and S3 (11.6+/-3.7mL. min(-1). 100g(-1)) (P<.05). For each ROI, an arbitrary tissue blood flow activation level of 5mLmin(-1)100g(-1) was fixed. The mean percentage of activated ROIs reached 42.4%, 62.7%, and 63.6% during S1, S2, and S3, respectively. Between S1 and S3, the newly recruited ROIs were preferentially located far from the electrode. During NMES, new muscular regions situated far from the stimulation site are recruited. These recruitment mechanisms are particular and contrast with the recruitment of motor units seen during voluntary contraction. Copyright 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

  9. Visual spatial attention enhances the amplitude of positive and negative fMRI responses to visual stimulation in an eccentricity-dependent manner.

    PubMed

    Bressler, David W; Fortenbaugh, Francesca C; Robertson, Lynn C; Silver, Michael A

    2013-06-07

    Endogenous visual spatial attention improves perception and enhances neural responses to visual stimuli at attended locations. Although many aspects of visual processing differ significantly between central and peripheral vision, little is known regarding the neural substrates of the eccentricity dependence of spatial attention effects. We measured amplitudes of positive and negative fMRI responses to visual stimuli as a function of eccentricity in a large number of topographically-organized cortical areas. Responses to each stimulus were obtained when the stimulus was attended and when spatial attention was directed to a stimulus in the opposite visual hemifield. Attending to the stimulus increased both positive and negative response amplitudes in all cortical areas we studied: V1, V2, V3, hV4, VO1, LO1, LO2, V3A/B, IPS0, TO1, and TO2. However, the eccentricity dependence of these effects differed considerably across cortical areas. In early visual, ventral, and lateral occipital cortex, attentional enhancement of positive responses was greater for central compared to peripheral eccentricities. The opposite pattern was observed in dorsal stream areas IPS0 and putative MT homolog TO1, where attentional enhancement of positive responses was greater in the periphery. Both the magnitude and the eccentricity dependence of attentional modulation of negative fMRI responses closely mirrored that of positive responses across cortical areas. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Multiday Transcranial Direct Current Stimulation Causes Clinically Insignificant Changes in Childhood Dystonia: A Pilot Study.

    PubMed

    Bhanpuri, Nasir H; Bertucco, Matteo; Young, Scott J; Lee, Annie A; Sanger, Terence D

    2015-10-01

    Abnormal motor cortex activity is common in dystonia. Cathodal transcranial direct current stimulation may alter cortical activity by decreasing excitability while anodal stimulation may increase motor learning. Previous results showed that a single session of cathodal transcranial direct current stimulation can improve symptoms in childhood dystonia. Here we performed a 5-day, sham-controlled, double-blind, crossover study, where we measured tracking and muscle overflow in a myocontrol-based task. We applied cathodal and anodal transcranial direct current stimulation (2 mA, 9 minutes per day). For cathodal transcranial direct current stimulation (7 participants), 3 subjects showed improvements whereas 2 showed worsening in overflow or tracking error. The effect size was small (about 1% of maximum voluntary contraction) and not clinically meaningful. For anodal transcranial direct current stimulation (6 participants), none showed improvement, whereas 5 showed worsening. Thus, multiday cathodal transcranial direct current stimulation reduced symptoms in some children but not to a clinically meaningful extent, whereas anodal transcranial direct current stimulation worsened symptoms. Our results do not support transcranial direct current stimulation as clinically viable for treating childhood dystonia. © The Author(s) 2015.

  11. Using Stimulant Drugs in the Classroom.

    ERIC Educational Resources Information Center

    Barkley, Russell A.

    1979-01-01

    Research is reviewed on the effects of stimulant drugs on the classroom behavior and academic achievement of hyperactive children. Results indicate that stimulant drugs do not appreciably improve academic achievement, but are effective in improving attention span, on-task behavior, activity level, and disruptive behavior. (Author/MH)

  12. Studies for improved understanding of lipid distributions in human skin by combining stimulated and spontaneous Raman microscopy.

    PubMed

    Klossek, A; Thierbach, S; Rancan, F; Vogt, A; Blume-Peytavi, U; Rühl, E

    2017-07-01

    Advanced Raman techniques, such as stimulated Raman spectroscopy (SRS), have become a valuable tool for investigations of distributions of substances in biological samples. However, these techniques lack spectral information and are therefore highly affected by cross-sensitivities, which are due to blended Raman bands. One typical example is the symmetric CH 2 stretching vibration of lipids, which is blended with the more intense Raman band of proteins. We report in this work an approach to reduce such cross-sensitivities by a factor of 8 in human skin samples. This is accomplished by careful spectral deconvolutions revealing the neat spectra of skin lipids. Extensive Raman studies combining the complementary advantages of fast mapping and scanning, i.e. SRS, as well as spectral information provided by spontaneous Raman spectroscopy, were performed on the same skin regions. In addition, an approach for correcting artifacts is reported, which are due to transmission and reflection geometries in Raman microscopy as well as scattering of radiation from rough and highly structured skin samples. As a result, these developments offer improved results obtained from label-free spectromicroscopy provided by Raman techniques. These yield substance specific information from spectral regimes in which blended bands dominate. This improvement is illustrated by studies on the asymmetric CH 2 stretching vibration of lipids, which was previously difficult to identify due to the strong background signal from proteins. The advantage of the correction procedures is demonstrated by higher spatial resolution permitting to perform more detailed investigations on lipids and their composition in skin. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Organic electrode coatings for next-generation neural interfaces

    PubMed Central

    Aregueta-Robles, Ulises A.; Woolley, Andrew J.; Poole-Warren, Laura A.; Lovell, Nigel H.; Green, Rylie A.

    2014-01-01

    Traditional neuronal interfaces utilize metallic electrodes which in recent years have reached a plateau in terms of the ability to provide safe stimulation at high resolution or rather with high densities of microelectrodes with improved spatial selectivity. To achieve higher resolution it has become clear that reducing the size of electrodes is required to enable higher electrode counts from the implant device. The limitations of interfacing electrodes including low charge injection limits, mechanical mismatch and foreign body response can be addressed through the use of organic electrode coatings which typically provide a softer, more roughened surface to enable both improved charge transfer and lower mechanical mismatch with neural tissue. Coating electrodes with conductive polymers or carbon nanotubes offers a substantial increase in charge transfer area compared to conventional platinum electrodes. These organic conductors provide safe electrical stimulation of tissue while avoiding undesirable chemical reactions and cell damage. However, the mechanical properties of conductive polymers are not ideal, as they are quite brittle. Hydrogel polymers present a versatile coating option for electrodes as they can be chemically modified to provide a soft and conductive scaffold. However, the in vivo chronic inflammatory response of these conductive hydrogels remains unknown. A more recent approach proposes tissue engineering the electrode interface through the use of encapsulated neurons within hydrogel coatings. This approach may provide a method for activating tissue at the cellular scale, however, several technological challenges must be addressed to demonstrate feasibility of this innovative idea. The review focuses on the various organic coatings which have been investigated to improve neural interface electrodes. PMID:24904405

  14. Optimization of multifocal transcranial current stimulation for weighted cortical pattern targeting from realistic modeling of electric fields.

    PubMed

    Ruffini, Giulio; Fox, Michael D; Ripolles, Oscar; Miranda, Pedro Cavaleiro; Pascual-Leone, Alvaro

    2014-04-01

    Recently, multifocal transcranial current stimulation (tCS) devices using several relatively small electrodes have been used to achieve more focal stimulation of specific cortical targets. However, it is becoming increasingly recognized that many behavioral manifestations of neurological and psychiatric disease are not solely the result of abnormality in one isolated brain region but represent alterations in brain networks. In this paper we describe a method for optimizing the configuration of multifocal tCS for stimulation of brain networks, represented by spatially extended cortical targets. We show how, based on fMRI, PET, EEG or other data specifying a target map on the cortical surface for excitatory, inhibitory or neutral stimulation and a constraint on the maximal number of electrodes, a solution can be produced with the optimal currents and locations of the electrodes. The method described here relies on a fast calculation of multifocal tCS electric fields (including components normal and tangential to the cortical boundaries) using a five layer finite element model of a realistic head. Based on the hypothesis that the effects of current stimulation are to first order due to the interaction of electric fields with populations of elongated cortical neurons, it is argued that the optimization problem for tCS stimulation can be defined in terms of the component of the electric field normal to the cortical surface. Solutions are found using constrained least squares to optimize current intensities, while electrode number and their locations are selected using a genetic algorithm. For direct current tCS (tDCS) applications, we provide some examples of this technique using an available tCS system providing 8 small Ag/AgCl stimulation electrodes. We demonstrate the approach both for localized and spatially extended targets defined using rs-fcMRI and PET data, with clinical applications in stroke and depression. Finally, we extend these ideas to more general stimulation protocols, such as alternating current tCS (tACS). Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Manipulation of Pre-Target Activity on the Right Frontal Eye Field Enhances Conscious Visual Perception in Humans

    PubMed Central

    Chanes, Lorena; Chica, Ana B.; Quentin, Romain; Valero-Cabré, Antoni

    2012-01-01

    The right Frontal Eye Field (FEF) is a region of the human brain, which has been consistently involved in visuo-spatial attention and access to consciousness. Nonetheless, the extent of this cortical site’s ability to influence specific aspects of visual performance remains debated. We hereby manipulated pre-target activity on the right FEF and explored its influence on the detection and categorization of low-contrast near-threshold visual stimuli. Our data show that pre-target frontal neurostimulation has the potential when used alone to induce enhancements of conscious visual detection. More interestingly, when FEF stimulation was combined with visuo-spatial cues, improvements remained present only for trials in which the cue correctly predicted the location of the subsequent target. Our data provide evidence for the causal role of the right FEF pre-target activity in the modulation of human conscious vision and reveal the dependence of such neurostimulatory effects on the state of activity set up by cue validity in the dorsal attentional orienting network. PMID:22615759

  16. Experience-dependent plasticity from eye opening enables lasting, visual cortex-dependent enhancement of motion vision.

    PubMed

    Prusky, Glen T; Silver, Byron D; Tschetter, Wayne W; Alam, Nazia M; Douglas, Robert M

    2008-09-24

    Developmentally regulated plasticity of vision has generally been associated with "sensitive" or "critical" periods in juvenile life, wherein visual deprivation leads to loss of visual function. Here we report an enabling form of visual plasticity that commences in infant rats from eye opening, in which daily threshold testing of optokinetic tracking, amid otherwise normal visual experience, stimulates enduring, visual cortex-dependent enhancement (>60%) of the spatial frequency threshold for tracking. The perceptual ability to use spatial frequency in discriminating between moving visual stimuli is also improved by the testing experience. The capacity for inducing enhancement is transitory and effectively limited to infancy; however, enhanced responses are not consolidated and maintained unless in-kind testing experience continues uninterrupted into juvenile life. The data show that selective visual experience from infancy can alone enable visual function. They also indicate that plasticity associated with visual deprivation may not be the only cause of developmental visual dysfunction, because we found that experientially inducing enhancement in late infancy, without subsequent reinforcement of the experience in early juvenile life, can lead to enduring loss of function.

  17. Stimulation of the human auditory nerve with optical radiation

    NASA Astrophysics Data System (ADS)

    Fishman, Andrew; Winkler, Piotr; Mierzwinski, Jozef; Beuth, Wojciech; Izzo Matic, Agnella; Siedlecki, Zygmunt; Teudt, Ingo; Maier, Hannes; Richter, Claus-Peter

    2009-02-01

    A novel, spatially selective method to stimulate cranial nerves has been proposed: contact free stimulation with optical radiation. The radiation source is an infrared pulsed laser. The Case Report is the first report ever that shows that optical stimulation of the auditory nerve is possible in the human. The ethical approach to conduct any measurements or tests in humans requires efficacy and safety studies in animals, which have been conducted in gerbils. This report represents the first step in a translational research project to initiate a paradigm shift in neural interfaces. A patient was selected who required surgical removal of a large meningioma angiomatum WHO I by a planned transcochlear approach. Prior to cochlear ablation by drilling and subsequent tumor resection, the cochlear nerve was stimulated with a pulsed infrared laser at low radiation energies. Stimulation with optical radiation evoked compound action potentials from the human auditory nerve. Stimulation of the auditory nerve with infrared laser pulses is possible in the human inner ear. The finding is an important step for translating results from animal experiments to human and furthers the development of a novel interface that uses optical radiation to stimulate neurons. Additional measurements are required to optimize the stimulation parameters.

  18. New stimulation pattern design to improve P300-based matrix speller performance at high flash rate

    NASA Astrophysics Data System (ADS)

    Polprasert, Chantri; Kukieattikool, Pratana; Demeechai, Tanee; Ritcey, James A.; Siwamogsatham, Siwaruk

    2013-06-01

    Objective. We propose a new stimulation pattern design for the P300-based matrix speller aimed at increasing the minimum target-to-target interval (TTI). Approach. Inspired by the simplicity and strong performance of the conventional row-column (RC) stimulation, the proposed stimulation is obtained by modifying the RC stimulation through alternating row and column flashes which are selected based on the proposed design rules. The second flash of the double-flash components is then delayed for a number of flashing instants to increase the minimum TTI. The trade-off inherited in this approach is the reduced randomness within the stimulation pattern. Main results. We test the proposed stimulation pattern and compare its performance in terms of selection accuracy, raw and practical bit rates with the conventional RC flashing paradigm over several flash rates. By increasing the minimum TTI within the stimulation sequence, the proposed stimulation has more event-related potentials that can be identified compared to that of the conventional RC stimulations, as the flash rate increases. This leads to significant performance improvement in terms of the letter selection accuracy, the raw and practical bit rates over the conventional RC stimulation. Significance. These studies demonstrate that significant performance improvement over the RC stimulation is obtained without additional testing or training samples to compensate for low P300 amplitude at high flash rate. We show that our proposed stimulation is more robust to reduced signal strength due to the increased flash rate than the RC stimulation.

  19. Vagus Nerve Stimulation Delivered During Motor Rehabilitation Improves Recovery in a Rat Model of Stroke

    PubMed Central

    Khodaparast, Navid; Hays, Seth A.; Sloan, Andrew M.; Fayyaz, Tabbassum; Hulsey, Daniel R.; Rennaker, Robert L.; Kilgard, Michael P.

    2014-01-01

    Neural plasticity is widely believed to support functional recovery following brain damage. Vagus nerve stimulation paired with different forelimb movements causes long-lasting map plasticity in rat primary motor cortex that is specific to the paired movement. We tested the hypothesis that repeatedly pairing vagus nerve stimulation with upper forelimb movements would improve recovery of motor function in a rat model of stroke. Rats were separated into three groups: vagus nerve stimulation during rehab, vagus nerve stimulation after rehab, and rehab alone. Animals underwent 4 training stages: shaping (motor skill learning), pre-lesion training, post-lesion training, and therapeutic training. Rats were given a unilateral ischemic lesion within motor cortex and implanted with a left vagus nerve cuff. Animals were allowed one week of recovery before post-lesion baseline training. During the therapeutic training stage, rats received vagus nerve stimulation paired with each successful trial. All seventeen trained rats demonstrated significant contralateral forelimb impairment when performing a bradykinesia assessment task. Forelimb function was recovered completely to pre-lesion levels when vagus nerve stimulation was delivered during rehab training. Alternatively, intensive rehab training alone (without stimulation) failed to restore function to pre-lesion levels. Delivering the same amount of stimulation after rehab training did not yield improvements compared to rehab alone. These results demonstrate that vagus nerve stimulation repeatedly paired with successful forelimb movements can improve recovery after motor cortex ischemia and may be a viable option for stroke rehabilitation. PMID:24553102

  20. Reducing the Disruptive Effects of Interruptions With Noninvasive Brain Stimulation.

    PubMed

    Blumberg, Eric J; Foroughi, Cyrus K; Scheldrup, Melissa R; Peterson, Matthew S; Boehm-Davis, Debbie A; Parasuraman, Raja

    2015-09-01

    The authors determine whether transcranial direct current stimulation (tDCS) can reduce resumption time when an ongoing task is interrupted. Interruptions are common and disruptive. Working memory capacity has been shown to predict resumption lag (i.e., time to successfully resume a task after interruption). Given that tDCS applied to brain areas associated with working memory can enhance performance, tDCS has the potential to improve resumption lag when a task is interrupted. Participants were randomly assigned to one of four groups that received anodal (active) stimulation of 2 mA tDCS to one of two target brain regions, left and right dorsolateral prefrontal cortex (DLPFC), or to one of two control areas, active stimulation of the left primary motor cortex or sham stimulation of the right DLPFC, while completing a financial management task that was intermittently interrupted with math problem solving. Anodal stimulation to the right and left DLPFC significantly reduced resumption lags compared to the control conditions (sham and left motor cortex stimulation). Additionally, there was no speed-accuracy tradeoff (i.e., the improvement in resumption time was not accompanied by an increased error rate). Noninvasive brain stimulation can significantly decrease resumption lag (improve performance) after a task is interrupted. Noninvasive brain stimulation offers an easy-to-apply tool that can significantly improve interrupted task performance. © 2014, Human Factors and Ergonomics Society.

  1. Deep brain stimulation of the pedunculopontine nucleus for treatment of gait and balance disorder in progressive supranuclear palsy: Effects of frequency modulations and clinical outcome.

    PubMed

    Galazky, Imke; Kaufmann, Jörn; Lorenzl, Stefan; Ebersbach, Georg; Gandor, Florin; Zaehle, Tino; Specht, Sylke; Stallforth, Sabine; Sobieray, Uwe; Wirkus, Edyta; Casjens, Franziska; Heinze, Hans-Jochen; Kupsch, Andreas; Voges, Jürgen

    2018-05-01

    The pedunculopontine nucleus has been suggested as a potential deep brain stimulation target for axial symptoms such as gait and balance impairment in idiopathic Parkinson's disease as well as atypical Parkinsonian disorders. Seven consecutive patients with progressive supranuclear palsy received bilateral pedunculopontine nucleus deep brain stimulation. Inclusion criteria comprised of the clinical diagnosis of progressive supranuclear palsy, a levodopa-resistant gait and balance disorder, age <75 years, and absence of dementia or major psychiatric co-morbidities. Effects of stimulation frequencies at 8, 20, 60 and 130 Hz on motor scores and gait were assessed. Motor scores were followed up for two years postoperatively. Activities of daily living, frequency of falls, health-related quality of life, cognition and mood at 12 months were compared to baseline parameters. Surgical and stimulation related adverse events were assessed. Bilateral pedunculopontine nucleus deep brain stimulation at 8 Hz significantly improved axial motor symptoms and cyclic gait parameters, while high frequency stimulation did not ameliorate gait and balance but improved hypokinesia. This improvement however did not translate into clinically relevant benefits. Frequency of falls was not reduced. Activities of daily living, quality of life and frontal cognitive functions declined, while mood remained unchanged. Bilateral pedunculopontine nucleus deep brain stimulation in progressive supranuclear palsy generates frequency-dependent effects with improvement of cyclic gait parameters at low frequency and amelioration of hypokinesia at high frequency stimulation. However, these effects do not translate into a clinically important improvement. Copyright © 2018. Published by Elsevier Ltd.

  2. Improving speech perception in noise with current focusing in cochlear implant users.

    PubMed

    Srinivasan, Arthi G; Padilla, Monica; Shannon, Robert V; Landsberger, David M

    2013-05-01

    Cochlear implant (CI) users typically have excellent speech recognition in quiet but struggle with understanding speech in noise. It is thought that broad current spread from stimulating electrodes causes adjacent electrodes to activate overlapping populations of neurons which results in interactions across adjacent channels. Current focusing has been studied as a way to reduce spread of excitation, and therefore, reduce channel interactions. In particular, partial tripolar stimulation has been shown to reduce spread of excitation relative to monopolar stimulation. However, the crucial question is whether this benefit translates to improvements in speech perception. In this study, we compared speech perception in noise with experimental monopolar and partial tripolar speech processing strategies. The two strategies were matched in terms of number of active electrodes, microphone, filterbanks, stimulation rate and loudness (although both strategies used a lower stimulation rate than typical clinical strategies). The results of this study showed a significant improvement in speech perception in noise with partial tripolar stimulation. All subjects benefited from the current focused speech processing strategy. There was a mean improvement in speech recognition threshold of 2.7 dB in a digits in noise task and a mean improvement of 3 dB in a sentences in noise task with partial tripolar stimulation relative to monopolar stimulation. Although the experimental monopolar strategy was worse than the clinical, presumably due to different microphones, frequency allocations and stimulation rates, the experimental partial-tripolar strategy, which had the same changes, showed no acute deficit relative to the clinical. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Evaluation of the effectiveness of transcranial direct current stimulation (tDCS) and psychosensory stimulation through DOCS scale in a minimally conscious subject.

    PubMed

    Dimitri, Danilo; De Filippis, Daniela; Galetto, Valentina; Zettin, Marina

    2017-04-01

    The aim of our study was to assess the effectiveness of transcranial direct current stimulation (tDCS) on alertness improvement in a patient in a minimally conscious state (MCS) by means of disorders of consciousness scale combined with psycho-sensory stimulation. The effects of tDCS on muscle hypertonia through the Ashworth scale were also examined. tDCS was performed through a two-channel intra-cephalic stimulator. After stimulation, the patient followed a psychosensory stimulation training. Results pointed out an increase in DOCunit score, as well as an increase in alertness maintenance and an improvement in muscle hypertonia, although a MCS state persisted.

  4. Nigral stimulation for resistant axial motor impairment in Parkinson's disease? A randomized controlled trial.

    PubMed

    Weiss, Daniel; Walach, Margarete; Meisner, Christoph; Fritz, Melanie; Scholten, Marlieke; Breit, Sorin; Plewnia, Christian; Bender, Benjamin; Gharabaghi, Alireza; Wächter, Tobias; Krüger, Rejko

    2013-07-01

    Gait and balance disturbances typically emerge in advanced Parkinson's disease with generally limited response to dopaminergic medication and subthalamic nucleus deep brain stimulation. Therefore, advanced programming with interleaved pulses was put forward to introduce concomittant nigral stimulation on caudal contacts of a subthalamic lead. Here, we hypothesized that the combined stimulation of subthalamic nucleus and substantia nigra pars reticulata improves axial symptoms compared with standard subthalamic nucleus stimulation. Twelve patients were enrolled in this 2 × 2 cross-over double-blind randomized controlled clinical trial and both the safety and efficacy of combined subthalamic nucleus and substantia nigra pars reticulata stimulation were evaluated compared with standard subthalamic nucleus stimulation. The primary outcome measure was the change of a broad-scaled cumulative axial Unified Parkinson's Disease Rating Scale score (Scale II items 13-15, Scale III items 27-31) at '3-week follow-up'. Secondary outcome measures specifically addressed freezing of gait, balance, quality of life, non-motor symptoms and neuropsychiatric symptoms. For the primary outcome measure no statistically significant improvement was observed for combined subthalamic nucleus and substantia nigra pars reticulata stimulation at the '3-week follow-up'. The secondary endpoints, however, revealed that the combined stimulation of subthalamic nucleus and substantia nigra pars reticulata might specifically improve freezing of gait, whereas balance impairment remained unchanged. The combined stimulation of subthalamic nucleus and substantia nigra pars reticulata was safe, and of note, no clinically relevant neuropsychiatric adverse effect was observed. Patients treated with subthalamic nucleus and substantia nigra pars reticulata stimulation revealed no 'global' effect on axial motor domains. However, this study opens the perspective that concomittant stimulation of the substantia nigra pars reticulata possibly improves otherwise resistant freezing of gait and, therefore, highly warrants a subsequent phase III randomized controlled trial.

  5. Seeing ahead: experience and language in spatial perspective.

    PubMed

    Alloway, Tracy Packiam; Corley, Martin; Ramscar, Michael

    2006-03-01

    Spatial perspective can be directed by various reference frames, as well as by the direction of motion. In the present study, we explored how ambiguity in spatial tasks can be resolved. Participants were presented with virtual reality environments in order to stimulate a spatialreference frame based on motion. They interacted with an ego-moving spatial system in Experiment 1 and an object-moving spatial system in Experiment 2. While interacting with the virtual environment, the participants were presented with either a question representing a motion system different from that of the virtual environment or a nonspatial question relating to physical features of the virtual environment. They then performed the target task assign the label front in an ambiguous spatial task. The findings indicate that the disambiguation of spatial terms can be influenced by embodied experiences, as represented by the virtual environment, as well as by linguistic context.

  6. Vector solitons in coupled nonlinear Schrödinger equations with spatial stimulated scattering and inhomogeneous dispersion

    NASA Astrophysics Data System (ADS)

    Gromov, E. M.; Malomed, B. A.; Tyutin, V. V.

    2018-01-01

    The dynamics of two-component solitons is studied, analytically and numerically, in the framework of a system of coupled extended nonlinear Schrödinger equations, which incorporate the cross-phase modulation, pseudo-stimulated-Raman-scattering (pseudo-SRS), cross-pseudo-SRS, and spatially inhomogeneous second-order dispersion (SOD). The system models co-propagation of electromagnetic waves with orthogonal polarizations in plasmas. It is shown that the soliton's wavenumber downshift, caused by pseudo-SRS, may be compensated by an upshift, induced by the inhomogeneous SOD, to produce stable stationary two-component solitons. The corresponding approximate analytical solutions for stable solitons are found. Analytical results are well confirmed by their numerical counterparts. Further, the evolution of inputs composed of spatially even and odd components is investigated by means of systematic simulations, which reveal three different outcomes: formation of a breather which keeps opposite parities of the components; splitting into a pair of separating vector solitons; and spreading of the weak odd component into a small-amplitude pedestal with an embedded dark soliton.

  7. Opposite monosynaptic scaling of BLP–vCA1 inputs governs hopefulness- and helplessness-modulated spatial learning and memory

    PubMed Central

    Yang, Ying; Wang, Zhi-Hao; Jin, Sen; Gao, Di; Liu, Nan; Chen, Shan-Ping; Zhang, Sinan; Liu, Qing; Liu, Enjie; Wang, Xin; Liang, Xiao; Wei, Pengfei; Li, Xiaoguang; Li, Yin; Yue, Chenyu; Li, Hong-lian; Wang, Ya-Li; Wang, Qun; Ke, Dan; Xie, Qingguo; Xu, Fuqiang; Wang, Liping; Wang, Jian-Zhi

    2016-01-01

    Different emotional states lead to distinct behavioural consequences even when faced with the same challenging events. Emotions affect learning and memory capacities, but the underlying neurobiological mechanisms remain elusive. Here we establish models of learned helplessness (LHL) and learned hopefulness (LHF) by exposing animals to inescapable foot shocks or with anticipated avoidance trainings. The LHF animals show spatial memory potentiation with excitatory monosynaptic upscaling between posterior basolateral amygdale (BLP) and ventral hippocampal CA1 (vCA1), whereas the LHL show memory deficits with an attenuated BLP–vCA1 connection. Optogenetic disruption of BLP–vCA1 inputs abolishes the effects of LHF and impairs synaptic plasticity. By contrast, targeted BLP–vCA1 stimulation rescues the LHL-induced memory deficits and mimics the effects of LHF. BLP–vCA1 stimulation increases synaptic transmission and dendritic plasticity with the upregulation of CREB and intrasynaptic AMPA receptors in CA1. These findings indicate that opposite excitatory monosynaptic scaling of BLP–vCA1 controls LHF- and LHL-modulated spatial memory, revealing circuit-specific mechanisms linking emotions to memory. PMID:27411738

  8. Opposite monosynaptic scaling of BLP-vCA1 inputs governs hopefulness- and helplessness-modulated spatial learning and memory.

    PubMed

    Yang, Ying; Wang, Zhi-Hao; Jin, Sen; Gao, Di; Liu, Nan; Chen, Shan-Ping; Zhang, Sinan; Liu, Qing; Liu, Enjie; Wang, Xin; Liang, Xiao; Wei, Pengfei; Li, Xiaoguang; Li, Yin; Yue, Chenyu; Li, Hong-Lian; Wang, Ya-Li; Wang, Qun; Ke, Dan; Xie, Qingguo; Xu, Fuqiang; Wang, Liping; Wang, Jian-Zhi

    2016-07-14

    Different emotional states lead to distinct behavioural consequences even when faced with the same challenging events. Emotions affect learning and memory capacities, but the underlying neurobiological mechanisms remain elusive. Here we establish models of learned helplessness (LHL) and learned hopefulness (LHF) by exposing animals to inescapable foot shocks or with anticipated avoidance trainings. The LHF animals show spatial memory potentiation with excitatory monosynaptic upscaling between posterior basolateral amygdale (BLP) and ventral hippocampal CA1 (vCA1), whereas the LHL show memory deficits with an attenuated BLP-vCA1 connection. Optogenetic disruption of BLP-vCA1 inputs abolishes the effects of LHF and impairs synaptic plasticity. By contrast, targeted BLP-vCA1 stimulation rescues the LHL-induced memory deficits and mimics the effects of LHF. BLP-vCA1 stimulation increases synaptic transmission and dendritic plasticity with the upregulation of CREB and intrasynaptic AMPA receptors in CA1. These findings indicate that opposite excitatory monosynaptic scaling of BLP-vCA1 controls LHF- and LHL-modulated spatial memory, revealing circuit-specific mechanisms linking emotions to memory.

  9. Nanoscale Spatiotemporal Diffusion Modes Measured by Simultaneous Confocal and Stimulated Emission Depletion Nanoscopy Imaging.

    PubMed

    Schneider, Falk; Waithe, Dominic; Galiani, Silvia; Bernardino de la Serna, Jorge; Sezgin, Erdinc; Eggeling, Christian

    2018-06-19

    The diffusion dynamics in the cellular plasma membrane provide crucial insights into molecular interactions, organization, and bioactivity. Beam-scanning fluorescence correlation spectroscopy combined with super-resolution stimulated emission depletion nanoscopy (scanning STED-FCS) measures such dynamics with high spatial and temporal resolution. It reveals nanoscale diffusion characteristics by measuring the molecular diffusion in conventional confocal mode and super-resolved STED mode sequentially for each pixel along the scanned line. However, to directly link the spatial and the temporal information, a method that simultaneously measures the diffusion in confocal and STED modes is needed. Here, to overcome this problem, we establish an advanced STED-FCS measurement method, line interleaved excitation scanning STED-FCS (LIESS-FCS), that discloses the molecular diffusion modes at different spatial positions with a single measurement. It relies on fast beam-scanning along a line with alternating laser illumination that yields, for each pixel, the apparent diffusion coefficients for two different observation spot sizes (conventional confocal and super-resolved STED). We demonstrate the potential of the LIESS-FCS approach with simulations and experiments on lipid diffusion in model and live cell plasma membranes. We also apply LIESS-FCS to investigate the spatiotemporal organization of glycosylphosphatidylinositol-anchored proteins in the plasma membrane of live cells, which, interestingly, show multiple diffusion modes at different spatial positions.

  10. A STED-FLIM microscope applied to imaging the natural killer cell immune synapse

    NASA Astrophysics Data System (ADS)

    Lenz, M. O.; Brown, A. C. N.; Auksorius, E.; Davis, D. M.; Dunsby, C.; Neil, M. A. A.; French, P. M. W.

    2011-03-01

    We present a stimulated emission depletion (STED) fluorescence lifetime imaging (FLIM) microscope, excited by a microstructured optical fibre supercontinuum source that is pumped by a femtosecond Ti:Sapphire-laser, which is also used for depletion. Implemented using a piezo-scanning stage on a laser scanning confocal fluorescence microscope system with FLIM realised using time correlated single photon counting (TCSPC), this provides convenient switching between confocal and STED-FLIM with spatial resolution down to below 60 nm. We will present our design considerations to make a robust instrument for biological applications including a comparison between fixed phase plate and spatial light modulator (SLM) approaches to shape the STED beam and the correlation of STED and confocal FLIM microscopy. Following our previous application of FLIM-FRET to study intercellular signalling at the immunological synapse (IS), we are employing STED microscopy to characterize the spatial distribution of cellular molecules with subdiffraction resolution at the IS. In particular, we are imaging cytoskeletal structure at the Natural Killer cell activated immune synapse. We will also present our progress towards multilabel STED microscopy to determine how relative spatial molecular organization, previously undetectable by conventional microscopy techniques, is important for NK cell cytotoxic function. Keywords: STED, Stimulated Emission Depletion Microscopy, Natural Killer (NK) cell, Fluorescence lifetime imaging, FLIM, Super resolution microscopy.

  11. Evaluation of stimulation parameters on aortomyoplasty, using Latissimus Dorsi muscle in a goat model: an acute study.

    PubMed

    Hakami, A; Santamore, W P; Stremel, R W; Tobin, G; Hjortdal, V E

    1999-08-01

    Dynamic aortomyoplasty using Latissimus Dorsi muscle (LDM) has been shown to improve myocardial function. However, systematic examination of the effects of stimulation parameters on aortic wrap function has not been done. Thus, the present study measures the direct effect of stimulation voltage, pulse train duration, frequency of the pulses, and the duration of the stimulation delay from R wave on the aortic wrap function. In eight female goats, the left LDM was wrapped around the descending aorta. The muscle was then subjected to electrical stimulation, altering frequency of stimulation pulses (16.6, 20, 25, 33 and 50 Hz), amplitude (2, 4, 6, 8 and 10 V), and number of pulses (2, 4, 6, 8 and 10 pulses) in a train stimulation. Left ventricular, aortic pressure, and pressure generated by LDM on aorta (wrap pressure) was measured. The changes in hemodynamic parameters mentioned above were calculated and compared for different stimulation parameters during unassisted and assisted cardiac cycles. Aortomyoplasty counterpulsation using LDM provided significant improvement in wrap pressure (78 mmHg +/- 2), aortic diastolic pressure, and changes in aortic diastolic pressure from 2 to 4 V (P < 0.05). Further increase in amplitude did not make any significant improvements of the above mentioned parameters. Significant augmentation of wrap pressure (82 mmHg +/- 2), aortic diastolic pressure (79 mmHg +/- 3) and changes in aortic diastolic pressure (12 mmHg +/- 1) occurred at 6 pulses (P < 0.05). Other changes in number of pulses did not show any significant improvements. Significant improvement of wrap pressure (80 mmHg +/- 2), aortic diastolic pressure (73 mmHg +/- 3) and changes in aortic diastolic pressure (12 mmHg +/- 1) was observed with a frequency of 33 Hz. To examine a wide range of delays from the onset of the QRS complex to LDM stimulation, stimulation was delivered randomly. The exact delay was determined from the ECG signal and superimposed LDM stimulation pulses. In this study we present a new measurement, wrap pressure. We also present that in aortomyoplasty using LDM, the most significant improvement in wrap pressure, aortic diastolic pressure and changes in aortic diastolic pressure occurs when the stimulation consists of an amplitude of 4 V, a frequency of 33 Hz and a train stimulation of 6 pulses.

  12. Transient finite element modeling of functional electrical stimulation.

    PubMed

    Filipovic, Nenad D; Peulic, Aleksandar S; Zdravkovic, Nebojsa D; Grbovic-Markovic, Vesna M; Jurisic-Skevin, Aleksandra J

    2011-03-01

    Transcutaneous functional electrical stimulation is commonly used for strengthening muscle. However, transient effects during stimulation are not yet well explored. The effect of an amplitude change of the stimulation can be described by static model, but there is no differency for different pulse duration. The aim of this study is to present the finite element (FE) model of a transient electrical stimulation on the forearm. Discrete FE equations were derived by using a standard Galerkin procedure. Different tissue conductive and dielectric properties are fitted using least square method and trial and error analysis from experimental measurement. This study showed that FE modeling of electrical stimulation can give the spatial-temporal distribution of applied current in the forearm. Three different cases were modeled with the same geometry but with different input of the current pulse, in order to fit the tissue properties by using transient FE analysis. All three cases were compared with experimental measurements of intramuscular voltage on one volunteer.

  13. The consequences of neural degeneration regarding optimal cochlear implant position in scala tympani: a model approach.

    PubMed

    Briaire, Jeroen J; Frijns, Johan H M

    2006-04-01

    Cochlear implant research endeavors to optimize the spatial selectivity, threshold and dynamic range with the objective of improving the speech perception performance of the implant user. One of the ways to achieve some of these goals is by electrode design. New cochlear implant electrode designs strive to bring the electrode contacts into close proximity to the nerve fibers in the modiolus: this is done by placing the contacts on the medial side of the array and positioning the implant against the medial wall of scala tympani. The question remains whether this is the optimal position for a cochlea with intact neural fibers and, if so, whether it is also true for a cochlea with degenerated neural fibers. In this study a computational model of the implanted human cochlea is used to investigate the optimal position of the array with respect to threshold, dynamic range and spatial selectivity for a cochlea with intact nerve fibers and for degenerated nerve fibers. In addition, the model is used to evaluate the predictive value of eCAP measurements for obtaining peri-operative information on the neural status. The model predicts improved threshold, dynamic range and spatial selectivity for the peri-modiolar position at the basal end of the cochlea, with minimal influence of neural degeneration. At the apical end of the array (1.5 cochlear turns), the dynamic range and the spatial selectivity are limited due to the occurrence of cross-turn stimulation, with the exception of the condition without neural degeneration and with the electrode array along the lateral wall of scala tympani. The eCAP simulations indicate that a large P(0) peak occurs before the N(1)P(1) complex when the fibers are not degenerated. The absence of this peak might be used as an indicator for neural degeneration.

  14. Improvement of language functions in a chronic non-fluent post-stroke aphasic patient following bilateral sequential theta burst magnetic stimulation.

    PubMed

    Vuksanović, Jasmina; Jelić, Milan B; Milanović, Sladjan D; Kačar, Katarina; Konstantinović, Ljubica; Filipović, Saša R

    2015-01-01

    In chronic non-fluent aphasia patients, inhibition of the intact right hemisphere (RH), by transcranial magnetic stimulation (TMS) or similar methods, can induce improvement in language functions. The supposed mechanism behind this improvement is a release of preserved left hemisphere (LH) language networks from RH transcallosal inhibition. Direct stimulation of the damaged LH can sometimes bring similar results too. Therefore, we developed a novel treatment approach that combined direct LH (Broca's area (BA)) stimulation, by intermittent theta burst stimulation (TBS), with homologue RH area's inhibition, by continuous TBS. We present the results of application of 15 daily sessions of the described treatment approach in a right-handed patient with chronic post-stroke non-fluent aphasia. The intervention appeared to improve several language functions, but most notably propositional speech, semantic fluency, short-term verbal memory, and verbal learning. Bilateral TBS modulation of activation of the language-related areas of both hemispheres seems to be a feasible and promising way to induce recovery in chronic aphasic patients. Due to potentially cumulative physiological effects of bilateral stimulation, the improvements may be even greater than following unilateral interventions.

  15. Stimulated Raman and Brillouin scattering of polarization-smoothed and temporally smoothed laser beams

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Berger, R.L.; Lefebvre, E.; Langdon, A.B.

    1999-04-01

    Control of filamentation and stimulated Raman and Brillouin scattering is shown to be possible by use of both spatial and temporal smoothing schemes. The spatial smoothing is accomplished by the use of phase plates [Y. Kato and K. Mima, Appl. Phys. {bold 329}, 186 (1982)] and polarization smoothing [Lefebvre {ital et al.}, Phys. Plasmas {bold 5}, 2701 (1998)] in which the plasma is irradiated with two orthogonally polarized, uncorrelated speckle patterns. The temporal smoothing considered here is smoothing by spectral dispersion [Skupsky {ital et al.}, J. Appl. Phys. {bold 66}, 3456 (1989)] in which the speckle pattern changes on themore » laser coherence time scale. At the high instability gains relevant to laser fusion experiments, the effect of smoothing must include the competition among all three instabilities. {copyright} {ital 1999 American Institute of Physics.}« less

  16. Heterogeneous 3D optrode with variable spatial resolution for optogenetic stimulation and electrophysiological recording.

    PubMed

    Ayub, Suleman; Barz, Falk; Paul, Oliver; Ruther, Patrick

    2016-08-01

    We report on the concept, development, and geometrical, optical as well as electrical characterization of the first three-dimensional (3D) optrode. This new device allows to optically interact with neuronal cells and simultaneously record their response with a high spatial resolution. Our design is based on a single-shank optical stimulation component and a multi-shank recording probe stacked together in a delicate assembly process. The electrical connection of both components is ensured by using flexible polyimide (PI) ribbon cables. The highly accurate relative positioning and precise alignment of the optical and electrical components in 3D with an optical output power at 460 nm well above 5 mW/mm2 and an all-electrical interface makes this device a promising tool for optogenetic experiments in neuroscientific research.

  17. Bacterial Community Succession During in situ Uranium Bioremediation: Spatial Similarities Along Controlled Flow Paths

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hwang, Chiachi; Wu, Weimin; Gentry, Terry J.

    2009-05-22

    Bacterial community succession was investigated in a field-scale subsurface reactor formed by a series of wells that received weekly ethanol additions to re-circulating groundwater. Ethanol additions stimulated denitrification, metal reduction, sulfate reduction, and U(VI) reduction to sparingly soluble U(IV). Clone libraries of SSU rRNA gene sequences from groundwater samples enabled tracking of spatial and temporal changes over a 1.5 y period. Analyses showed that the communities changed in a manner consistent with geochemical variations that occurred along temporal and spatial scales. Canonical correspondence analysis revealed that the levels of nitrate, uranium, sulfide, sulfate, and ethanol strongly correlated with particular bacterialmore » populations. As sulfate and U(VI) levels declined, sequences representative of sulfate-reducers and metal-reducers were detected at high levels. Ultimately, sequences associated with sulfate-reducing populations predominated, and sulfate levels declined as U(VI) remained at low levels. When engineering controls were compared to the population variation via canonical ordination, changes could be related to dissolved oxygen control and ethanol addition. The data also indicated that the indigenous populations responded differently to stimulation for bio-reduction; however, the two bio-stimulated communities became more similar after different transitions in an idiosyncratic manner. The strong associations between particular environmental variables and certain populations provide insight into the establishment of practical and successful remediation strategies in radionuclide-contaminated environments with respect to engineering controls and microbial ecology.« less

  18. Improving Sensorimotor Function Using Stochastic Vestibular Stimulation

    NASA Technical Reports Server (NTRS)

    Galvan, R. C.; Clark, T. K.; Merfeld, D. M.; Bloomberg, J. J.; Mulavara, A. P.; Oman, C. M.

    2014-01-01

    Astronauts experience sensorimotor changes during spaceflight, particularly during G-transition phases. Post flight sensorimotor changes may include postural and gait instability, spatial disorientation, and visual performance decrements, all of which can degrade operational capabilities of the astronauts and endanger the crew. Crewmember safety would be improved if these detrimental effects of spaceflight could be mitigated by a sensorimotor countermeasure and even further if adaptation to baseline could be facilitated. The goal of this research is to investigate the potential use of stochastic vestibular stimulation (SVS) as a technology to improve sensorimotor function. We hypothesize that low levels of SVS will improve sensorimotor performance through stochastic resonance (SR). The SR phenomenon occurs when the response of a nonlinear system to a weak input signal is optimized by the application of a particular nonzero level of noise. Two studies have been initiated to investigate the beneficial effects and potential practical usage of SVS. In both studies, electrical vestibular stimulation is applied via electrodes on the mastoid processes using a constant current stimulator. The first study aims to determine the repeatability of the effect of vestibular stimulation on sensorimotor performance and perception in order to better understand the practical use of SVS. The beneficial effect of low levels of SVS on balance performance has been shown in the past. This research uses the same balance task repeated multiple times within a day and across days to study the repeatability of the stimulation effects. The balance test consists of 50 sec trials in which the subject stands with his or her feet together, arms crossed, and eyes closed on compliant foam. Varying levels of SVS, ranging from 0-700 micro A, are applied across different trials. The subject-specific optimal SVS level is that which results in the best balance performance as measured by inertial measurement units placed on the upper and lower torso of the subjects. Additionally, each individual’s threshold for illusory motion perception of suprasensory electrical vestibular stimulation is measured multiple times within and across days to better understand how multiple SVS test methods compare. The second study aims to demonstrate stochastic resonance in the vestibular system using a perception based motion recognition task. This task measures an individual’s velocity threshold of motion recognition using a 6-degree of freedom Stewart platform and a 3-down/1-up staircase procedure. For this study, thresholds are determined using 150 trials in the upright, head-centered roll tilt motion direction at a 0.2 Hz frequency. We aim to demonstrate the characteristic bell shaped curve associated with stochastic resonance with each subject’s motion recognition thresholds at varying SVS levels ranging from 0 to 1500 micro A. The curve includes the individual’s baseline threshold with no SVS, optimal or minimal threshold at some mid-level of SVS, and finally degraded or increased threshold at a high SVS level. An additional aim is to formally retest each subject at his or her individual optimal SVS level on a different day than the original testing for additional validity. The overall purpose of this research is to further quantify the effects of SVS on various sensorimotor tasks and investigate the practical implications of its use in the context of human space flight so that it may be implemented in the future as a component of a comprehensive countermeasure plan for adaptation to G-transitions.

  19. Effect of neuromuscular electrical stimulation on facial muscle strength and oral function in stroke patients with facial palsy

    PubMed Central

    Choi, Jong-Bae

    2016-01-01

    [Purpose] The aim of this study was to investigate the effect of neuromuscular electrical stimulation on facial muscle strength and oral function in stroke patients with facial palsy. [Subjects and Methods] Nine subjects received the electrical stimulation and traditional dysphagia therapy. Electrical stimulation was applied to stimulate each subject’s facial muscles 30 minutes a day, 5 days a week, for 4 weeks. [Results] Subjects showed significant improvement in cheek and lip strength and oral function after the intervention. [Conclusion] This study demonstrates that electrical stimulation improves facial muscle strength and oral function in stroke patients with dysphagia. PMID:27799689

  20. Two-photon absorption induced stimulated Rayleigh-Bragg scattering

    NASA Astrophysics Data System (ADS)

    He, Guang S.; Prasad, Paras N.

    2005-01-01

    A frequency-unshifted and backward stimulated scattering can be efficiently generated in one-photon-absorption free but two-photon absorbing materials. Using a number of novel two-photon absorbing dye solutions as the scattering media and nanosecond pulsed laser as the pump beams, a highly directional backward stimulated scattering at the exact pump wavelength can be readily observed once the pump intensity is higher than a certain threshold level. The spectral and spatial structures as well as the temporal behavior and optical phase-conjugation property of this new type of backward stimulated scattering have been experimentally studied. This stimulated scattering phenomenon can be explained by using a model of two-photon-excitation enhanced standing-wave Bragg grating initially formed by the strong forward pump beam and much weaker backward Rayleigh scattering beam; the partial reflection of the pump beam from this grating provides an positive feedback to the initial backward Rayleigh scattering beam without suffering linear attenuation influence. Comparing to other known stimulated (Raman, Brillouin, Rayleigh-wing, and Kerr) scattering effects, the stimulated Rayleigh-Bragg scattering exhibits the advantages of no frequency-shift, low pump threshold, and low spectral linewidth requirement.

  1. Dyscalculia and vestibular function.

    PubMed

    Smith, P F

    2012-10-01

    A few studies in humans suggest that changes in stimulation of the balance organs of the inner ear (the 'vestibular system') can disrupt numerical cognition, resulting in 'dyscalculia', the inability to manipulate numbers. Many studies have also demonstrated that patients with vestibular dysfunction exhibit deficits in spatial memory. It is suggested that there may be a connection between spatial memory deficits resulting from vestibular dysfunction and the occurrence of dyscalculia, given the evidence that numerosity is coupled to the processing of spatial information (e.g., the 'spatial numerical association of response codes ('SNARC') effect'). The evidence supporting this hypothesis is summarised and potential experiments to test it are proposed. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Pilot Errors Involving Head-Up Displays (HUDs), Helmet-Mounted Displays (HMDs), and Night Vision Goggles (NVGs)

    DTIC Science & Technology

    1992-01-01

    results in stimulation of spatial-motion-location visual processes, which are known to take precedence over any other sensor or cognitive stimuli. In...or version he is flying. This was initially an observation that stimulated the birth of the human-factors engineering discipline during World War H...collisions with the surface, the pilot needs inputs to sensory channels other than the focal visual system. Properly designed auditory and

  3. Determinants of the electric field during transcranial direct current stimulation.

    PubMed

    Opitz, Alexander; Paulus, Walter; Will, Susanne; Antunes, Andre; Thielscher, Axel

    2015-04-01

    Transcranial direct current stimulation (tDCS) causes a complex spatial distribution of the electric current flow in the head which hampers the accurate localization of the stimulated brain areas. In this study we show how various anatomical features systematically shape the electric field distribution in the brain during tDCS. We constructed anatomically realistic finite element (FEM) models of two individual heads including conductivity anisotropy and different skull layers. We simulated a widely employed electrode montage to induce motor cortex plasticity and moved the stimulating electrode over the motor cortex in small steps to examine the resulting changes of the electric field distribution in the underlying cortex. We examined the effect of skull thickness and composition on the passing currents showing that thinner skull regions lead to higher electric field strengths. This effect is counteracted by a larger proportion of higher conducting spongy bone in thicker regions leading to a more homogenous current over the skull. Using a multiple regression model we could identify key factors that determine the field distribution to a significant extent, namely the thicknesses of the cerebrospinal fluid and the skull, the gyral depth and the distance to the anode and cathode. These factors account for up to 50% of the spatial variation of the electric field strength. Further, we demonstrate that individual anatomical factors can lead to stimulation "hotspots" which are partly resistant to electrode positioning. Our results give valuable novel insights in the biophysical foundation of tDCS and highlight the importance to account for individual anatomical factors when choosing an electrode montage. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Electrical Microstimulation of the Pulvinar Biases Saccade Choices and Reaction Times in a Time-Dependent Manner

    PubMed Central

    2017-01-01

    The pulvinar complex is interconnected extensively with brain regions involved in spatial processing and eye movement control. Recent inactivation studies have shown that the dorsal pulvinar (dPul) plays a role in saccade target selection; however, it remains unknown whether it exerts effects on visual processing or at planning/execution stages. We used electrical microstimulation of the dPul while monkeys performed saccade tasks toward instructed and freely chosen targets. Timing of stimulation was varied, starting before, at, or after onset of target(s). Stimulation affected saccade properties and target selection in a time-dependent manner. Stimulation starting before but overlapping with target onset shortened saccadic reaction times (RTs) for ipsiversive (to the stimulation site) target locations, whereas stimulation starting at and after target onset caused systematic delays for both ipsiversive and contraversive locations. Similarly, stimulation starting before the onset of bilateral targets increased ipsiversive target choices, whereas stimulation after target onset increased contraversive choices. Properties of dPul neurons and stimulation effects were consistent with an overall contraversive drive, with varying outcomes contingent upon behavioral demands. RT and choice effects were largely congruent in the visually-guided task, but stimulation during memory-guided saccades, while influencing RTs and errors, did not affect choice behavior. Together, these results show that the dPul plays a primary role in action planning as opposed to visual processing, that it exerts its strongest influence on spatial choices when decision and action are temporally close, and that this choice effect can be dissociated from motor effects on saccade initiation and execution. SIGNIFICANCE STATEMENT Despite a recent surge of interest, the core function of the pulvinar, the largest thalamic complex in primates, remains elusive. This understanding is crucial given the central role of the pulvinar in current theories of integrative brain functions supporting cognition and goal-directed behaviors, but electrophysiological and causal interference studies of dorsal pulvinar (dPul) are rare. Building on our previous studies that pharmacologically suppressed dPul activity for several hours, here we used transient electrical microstimulation at different periods while monkeys performed instructed and choice eye movement tasks, to determine time-specific contributions of pulvinar to saccade generation and decision making. We show that stimulation effects depend on timing and behavioral state and that effects on choices can be dissociated from motor effects. PMID:28119401

  5. Beneficial effects of multisensory and cognitive stimulation on age-related cognitive decline in long-term-care institutions

    PubMed Central

    De Oliveira, Thaís Cristina Galdino; Soares, Fernanda Cabral; De Macedo, Liliane Dias E Dias; Diniz, Domingos Luiz Wanderley Picanço; Bento-Torres, Natáli Valim Oliver; Picanço-Diniz, Cristovam Wanderley

    2014-01-01

    The aim of the present report was to evaluate the effectiveness and impact of multisensory and cognitive stimulation on improving cognition in elderly persons living in long-term-care institutions (institutionalized [I]) or in communities with their families (noninstitutionalized [NI]). We compared neuropsychological performance using language and Mini-Mental State Examination (MMSE) test scores before and after 24 and 48 stimulation sessions. The two groups were matched by age and years of schooling. Small groups of ten or fewer volunteers underwent the stimulation program, twice a week, over 6 months (48 sessions in total). Sessions were based on language and memory exercises, as well as visual, olfactory, auditory, and ludic stimulation, including music, singing, and dance. Both groups were assessed at the beginning (before stimulation), in the middle (after 24 sessions), and at the end (after 48 sessions) of the stimulation program. Although the NI group showed higher performance in all tasks in all time windows compared with I subjects, both groups improved their performance after stimulation. In addition, the improvement was significantly higher in the I group than the NI group. Language tests seem to be more efficient than the MMSE to detect early changes in cognitive status. The results suggest the impoverished environment of long-term-care institutions may contribute to lower cognitive scores before stimulation and the higher improvement rate of this group after stimulation. In conclusion, language tests should be routinely adopted in the neuropsychological assessment of elderly subjects, and long-term-care institutions need to include regular sensorimotor, social, and cognitive stimulation as a public health policy for elderly persons. PMID:24600211

  6. New modalities of brain stimulation for stroke rehabilitation

    PubMed Central

    Lucas, T. H.; Carey, J. R.; Fetz, E. E.

    2014-01-01

    Stroke is a leading cause of disability, and the number of stroke survivors continues to rise. Traditional neurorehabilitation strategies aimed at restoring function to weakened limbs provide only modest benefit. New brain stimulation techniques designed to augment traditional neurorehabilitation hold promise for reducing the burden of stroke-related disability. Investigators discovered that repetitive transcranial magnetic stimulation (rTMS), trans-cranial direct current stimulation (tDCS), and epidural cortical stimulation (ECS) can enhance neural plasticity in the motor cortex post-stroke. Improved outcomes may be obtained with activity-dependent stimulation, in which brain stimulation is contingent on neural or muscular activity during normal behavior. We review the evidence for improved motor function in stroke patients treated with rTMS, tDCS, and ECS and discuss the mediating physiological mechanisms. We compare these techniques to activity-dependent stimulation, discuss the advantages of this newer strategy for stroke rehabilitation, and suggest future applications for activity-dependent brain stimulation. PMID:23192336

  7. Effectiveness of transcranial direct current stimulation and visual illusion on neuropathic pain in spinal cord injury

    PubMed Central

    Kumru, Hatice; Pelayo, Raul; Vidal, Joan; Tormos, Josep Maria; Fregni, Felipe; Navarro, Xavier; Pascual-Leone, Alvaro

    2010-01-01

    The aim of this study was to evaluate the analgesic effect of transcranial direct current stimulation of the motor cortex and techniques of visual illusion, applied isolated or combined, in patients with neuropathic pain following spinal cord injury. In a sham controlled, double-blind, parallel group design, 39 patients were randomized into four groups receiving transcranial direct current stimulation with walking visual illusion or with control illusion and sham stimulation with visual illusion or with control illusion. For transcranial direct current stimulation, the anode was placed over the primary motor cortex. Each patient received ten treatment sessions during two consecutive weeks. Clinical assessment was performed before, after the last day of treatment, after 2 and 4 weeks follow-up and after 12 weeks. Clinical assessment included overall pain intensity perception, Neuropathic Pain Symptom Inventory and Brief Pain Inventory. The combination of transcranial direct current stimulation and visual illusion reduced the intensity of neuropathic pain significantly more than any of the single interventions. Patients receiving transcranial direct current stimulation and visual illusion experienced a significant improvement in all pain subtypes, while patients in the transcranial direct current stimulation group showed improvement in continuous and paroxysmal pain, and those in the visual illusion group improved only in continuous pain and dysaesthesias. At 12 weeks after treatment, the combined treatment group still presented significant improvement on the overall pain intensity perception, whereas no improvements were reported in the other three groups. Our results demonstrate that transcranial direct current stimulation and visual illusion can be effective in the management of neuropathic pain following spinal cord injury, with minimal side effects and with good tolerability. PMID:20685806

  8. Repetitive transcranial magnetic stimulation improves consciousness disturbance in stroke patients: A quantitative electroencephalography spectral power analysis.

    PubMed

    Xie, Ying; Zhang, Tong

    2012-11-05

    Repetitive transcranial magnetic stimulation is a noninvasive treatment technique that can directly alter cortical excitability and improve cerebral functional activity in unconscious patients. To investigate the effects and the electrophysiological changes of repetitive transcranial magnetic stimulation cortical treatment, 10 stroke patients with non-severe brainstem lesions and with disturbance of consciousness were treated with repetitive transcranial magnetic stimulation. A quantitative electroencephalography spectral power analysis was also performed. The absolute power in the alpha band was increased immediately after the first repetitive transcranial magnetic stimulation treatment, and the energy was reduced in the delta band. The alpha band relative power values slightly decreased at 1 day post-treatment, then increased and reached a stable level at 2 weeks post-treatment. Glasgow Coma Score and JFK Coma Recovery Scale-Revised score were improved. Relative power value in the alpha band was positively related to Glasgow Coma Score and JFK Coma Recovery Scale-Revised score. These data suggest that repetitive transcranial magnetic stimulation is a noninvasive, safe, and effective treatment technology for improving brain functional activity and promoting awakening in unconscious stroke patients.

  9. Noninvasive and painless magnetic stimulation of nerves improved brain motor function and mobility in a cerebral palsy case.

    PubMed

    Flamand, Véronique H; Schneider, Cyril

    2014-10-01

    Motor deficits in cerebral palsy disturb functional independence. This study tested whether noninvasive and painless repetitive peripheral magnetic stimulation could improve motor function in a 7-year-old boy with spastic hemiparetic cerebral palsy. Stimulation was applied over different nerves of the lower limbs for 5 sessions. We measured the concurrent aftereffects of this intervention on ankle motor control, gait (walking velocity, stride length, cadence, cycle duration), and function of brain motor pathways. We observed a decrease of ankle plantar flexors resistance to stretch, an increase of active dorsiflexion range of movement, and improvements of corticospinal control of ankle dorsiflexors. Joint mobility changes were still present 15 days after the end of stimulation, when all gait parameters were also improved. Resistance to stretch was still lower than prestimulation values 45 days after the end of stimulation. This case illustrates the sustained effects of repetitive peripheral magnetic stimulation on brain plasticity, motor function, and gait. It suggests a potential impact for physical rehabilitation in cerebral palsy. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  10. Urban Public Space Context and Cognitive Psychology Evolution in Information Environment

    NASA Astrophysics Data System (ADS)

    Feng, Chen; Xu, Hua-wei

    2017-11-01

    The rapid development of information technology has had a great impact on the understanding of urban environment, which brings different spatially psychological experience. Information and image transmission has been full with the streets, both the physical space and virtual space have been unprecedentedly blended together through pictures, images, electronic media and other tools, which also stimulates people’s vision and psychology and gives birth to a more complex form of urban space. Under the dual role of spatial mediumlization and media spatialization, the psychological cognitive pattern of urban public space context is changing.

  11. Hormonal control of growth in the wing imaginal disks of Junonia coenia: the relative contributions of insulin and ecdysone.

    PubMed

    Nijhout, H Frederik; Laub, Emily; Grunert, Laura W

    2018-03-19

    The wing imaginal disks of Lepidoptera can be grown in tissue culture, but require both insulin and ecdysone to grow normally. Here, we investigate the contributions the two hormones make to growth. Ecdysone is required to maintain mitoses, whereas in the presence of insulin alone mitoses stop. Both ecdysone and insulin stimulate protein synthesis, but only ecdysone stimulates DNA synthesis. Insulin stimulates primarily cytoplasmic growth and an increase in cell size, whereas ecdysone, by virtue of its stimulation of DNA synthesis and mitosis, stimulates growth by an increase in cell number. Although both hormones stimulate protein synthesis, they do so in different spatial patterns. Both hormones stimulate protein synthesis in the inter-vein regions, but ecdysone stimulates synthesis more strongly in the veins and in the margin of the wing disk. We propose that the balance of insulin and ecdysone signaling must be regulated to maintain normal growth, and when growth appears to be due primarily to an increase in cell number, or an increase in cell size, this may indicate growth occurred under conditions that favored a stronger role for ecdysone, or insulin, respectively. © 2018. Published by The Company of Biologists Ltd.

  12. Optogenetic stimulation of dentate gyrus engrams restores memory in Alzheimer's disease mice.

    PubMed

    Perusini, Jennifer N; Cajigas, Stephanie A; Cohensedgh, Omid; Lim, Sean C; Pavlova, Ina P; Donaldson, Zoe R; Denny, Christine A

    2017-10-01

    Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by amyloid-beta (Aβ) plaques and tau neurofibrillary tangles. APPswe/PS1dE9 (APP/PS1) mice have been developed as an AD model and are characterized by plaque formation at 4-6 months of age. Here, we sought to better understand AD-related cognitive decline by characterizing various types of memory. In order to better understand how memory declines with AD, APP/PS1 mice were bred with ArcCreER T2 mice. In this line, neural ensembles activated during memory encoding can be indelibly tagged and directly compared with neural ensembles activated during memory retrieval (i.e., memory traces/engrams). We first administered a battery of tests examining depressive- and anxiety-like behaviors, as well as spatial, social, and cognitive memory to APP/PS1 × ArcCreER T2 × channelrhodopsin (ChR2)-enhanced yellow fluorescent protein (EYFP) mice. Dentate gyrus (DG) neural ensembles were then optogenetically stimulated in these mice to improve memory impairment. AD mice had the most extensive differences in fear memory, as assessed by contextual fear conditioning (CFC), which was accompanied by impaired DG memory traces. Optogenetic stimulation of DG neural ensembles representing a CFC memory increased memory retrieval in the appropriate context in AD mice when compared with control (Ctrl) mice. Moreover, optogenetic stimulation facilitated reactivation of the neural ensembles that were previously activated during memory encoding. These data suggest that activating previously learned DG memory traces can rescue cognitive impairments and point to DG manipulation as a potential target to treat memory loss commonly seen in AD. © 2017 Wiley Periodicals, Inc.

  13. Anodal transcranial direct current stimulation of the left dorsolateral prefrontal cortex enhances emotion recognition in depressed patients and controls.

    PubMed

    Brennan, Sean; McLoughlin, Declan M; O'Connell, Redmond; Bogue, John; O'Connor, Stephanie; McHugh, Caroline; Glennon, Mark

    2017-05-01

    Transcranial direct current stimulation (tDCS) can enhance a range of neuropsychological functions but its efficacy in addressing clinically significant emotion recognition deficits associated with depression is largely untested. A randomized crossover placebo controlled study was used to investigate the effects of tDCS over the left dorsolateral prefrontal cortex (L-DLPFC) on a range of neuropsychological variables associated with depression as well as neural activity in the associated brain region. A series of computerized tests was administered to clinical (n = 17) and control groups (n = 20) during sham and anodal (1.5 mA) stimulation. Anodal tDCS led to a significant main effect for overall emotion recognition (p = .02), with a significant improvement in the control group (p = .04). Recognition of disgust was significantly greater in the clinical group (p = .01). Recognition of anger was significantly improved for the clinical group (p = .04) during anodal stimulation. Differences between groups for each of the six emotions at varying levels of expression found that at 40% during anodal stimulation, happy recognition significantly improved for the clinical group (p = .01). Anger recognition at 80% during anodal stimulation significantly improved for the clinical group (p = .02). These improvements were observed in the absence of any change in psychomotor speed or trail making ability during anodal stimulation. Working memory significantly improved during anodal stimulation for the clinical group but not for controls (p = .03). The tentative findings of this study indicate that tDCS can have a neuromodulatory effect on a range of neuropsychological variables. However, it is clear that there was a wide variation in responses to tDCS and that individual difference and different approaches to testing and stimulation have a significant impact on final outcomes. Nonetheless, tDCS remains a promising tool for future neuropsychological research.

  14. Early Warning Signals of Ecological Transitions: Methods for Spatial Patterns

    PubMed Central

    Brock, William A.; Carpenter, Stephen R.; Ellison, Aaron M.; Livina, Valerie N.; Seekell, David A.; Scheffer, Marten; van Nes, Egbert H.; Dakos, Vasilis

    2014-01-01

    A number of ecosystems can exhibit abrupt shifts between alternative stable states. Because of their important ecological and economic consequences, recent research has focused on devising early warning signals for anticipating such abrupt ecological transitions. In particular, theoretical studies show that changes in spatial characteristics of the system could provide early warnings of approaching transitions. However, the empirical validation of these indicators lag behind their theoretical developments. Here, we summarize a range of currently available spatial early warning signals, suggest potential null models to interpret their trends, and apply them to three simulated spatial data sets of systems undergoing an abrupt transition. In addition to providing a step-by-step methodology for applying these signals to spatial data sets, we propose a statistical toolbox that may be used to help detect approaching transitions in a wide range of spatial data. We hope that our methodology together with the computer codes will stimulate the application and testing of spatial early warning signals on real spatial data. PMID:24658137

  15. Shielded Coaxial Optrode Arrays for Neurophysiology

    PubMed Central

    Naughton, Jeffrey R.; Connolly, Timothy; Varela, Juan A.; Lundberg, Jaclyn; Burns, Michael J.; Chiles, Thomas C.; Christianson, John P.; Naughton, Michael J.

    2016-01-01

    Recent progress in the study of the brain has been greatly facilitated by the development of new tools capable of minimally-invasive, robust coupling to neuronal assemblies. Two prominent examples are the microelectrode array (MEA), which enables electrical signals from large numbers of neurons to be detected and spatiotemporally correlated, and optogenetics, which enables the electrical activity of cells to be controlled with light. In the former case, high spatial density is desirable but, as electrode arrays evolve toward higher density and thus smaller pitch, electrical crosstalk increases. In the latter, finer control over light input is desirable, to enable improved studies of neuroelectronic pathways emanating from specific cell stimulation. Here, we introduce a coaxial electrode architecture that is uniquely suited to address these issues, as it can simultaneously be utilized as an optical waveguide and a shielded electrode in dense arrays. Using optogenetically-transfected cells on a coaxial MEA, we demonstrate the utility of the architecture by recording cellular currents evoked from optical stimulation. We also show the capability for network recording by radiating an area of seven individually-addressed coaxial electrode regions with cultured cells covering a section of the extent. PMID:27375415

  16. Multiple sensor integration for seizure onset detection in human patients comparing conventional disc versus novel tripolar concentric ring electrodes.

    PubMed

    Makeyev, Oleksandr; Ding, Quan; Martínez-Juárez, Iris E; Gaitanis, John; Kay, Steven M; Besio, Walter G

    2013-01-01

    As epilepsy affects approximately one percent of the world population, electrical stimulation of the brain has recently shown potential for additive seizure control therapy. Closed-loop systems that apply electrical stimulation when seizure onset is automatically detected require high accuracy of automatic seizure detection based on electrographic brain activity. To improve this accuracy we propose to use noninvasive tripolar concentric ring electrodes that have been shown to have significantly better signal-to-noise ratio, spatial selectivity, and mutual information compared to conventional disc electrodes. The proposed detection methodology is based on integration of multiple sensors using exponentially embedded family (EEF). In this preliminary study it is validated on over 26.3 hours of data collected using both tripolar concentric ring and conventional disc electrodes concurrently each from 7 human patients with epilepsy including five seizures. For a cross-validation based group model EEF correctly detected 100% and 80% of seizures respectively with <0.76 and <1.56 false positive detections per hour respectively for the two electrode modalities. These results clearly suggest the potential of seizure onset detection based on data from tripolar concentric ring electrodes.

  17. Selecting electrode configurations for image-guided cochlear implant programming using template matching.

    PubMed

    Zhang, Dongqing; Zhao, Yiyuan; Noble, Jack H; Dawant, Benoit M

    2018-04-01

    Cochlear implants (CIs) are neural prostheses that restore hearing using an electrode array implanted in the cochlea. After implantation, the CI processor is programmed by an audiologist. One factor that negatively impacts outcomes and can be addressed by programming is cross-electrode neural stimulation overlap (NSO). We have proposed a system to assist the audiologist in programming the CI that we call image-guided CI programming (IGCIP). IGCIP permits using CT images to detect NSO and recommend deactivation of a subset of electrodes to avoid NSO. We have shown that IGCIP significantly improves hearing outcomes. Most of the IGCIP steps are robustly automated but electrode configuration selection still sometimes requires manual intervention. With expertise, distance-versus-frequency curves, which are a way to visualize the spatial relationship learned from CT between the electrodes and the nerves they stimulate, can be used to select the electrode configuration. We propose an automated technique for electrode configuration selection. A comparison between this approach and one we have previously proposed shows that our method produces results that are as good as those obtained with our previous method while being generic and requiring fewer parameters.

  18. Incorporation of fiber optic beam shaping into a laparoscopic probe for laser stimulation of the cavernous nerves

    NASA Astrophysics Data System (ADS)

    Tozburun, Serhat; Lagoda, Gwen A.; Mayeh, Mona; Burnett, Arthur L.; Farahi, Faramarz; Fried, Nathaniel M.

    2010-02-01

    The cavernous nerves (CN) course along the prostate surface and are responsible for erectile function. Improved identification and preservation of the CN's is critical to maintaining sexual potency after prostate cancer surgery. Noncontact optical nerve stimulation (ONS) of the CN's was recently demonstrated in a rat model, in vivo, as a potential alternative to electrical nerve stimulation (ENS) for identification of the CN's during prostate surgery. However, the therapeutic window for ONS is narrow, so optimal design of the fiber optic delivery system is critical for safe, reproducible stimulation. This study describes modeling, assembly, and testing of an ONS probe for delivering a small, collimated, flat-top laser beam for uniform CN stimulation. A direct comparison of the magnitude and response time of the intracavernosal pressure (ICP) for both Gaussian and flat-top spatial beam profiles was performed. Thulium fiber laser radiation (λ=1870 nm) was delivered through a 200-μm fiber, with distal fiber tip chemically etched to convert a Gaussian to flat-top beam profile. The laser beam was collimated to a 1-mm-diameter spot using an aspheric lens. Computer simulations of light propagation were used to optimize the probe design. The 10-Fr (3.4-mm-OD) laparoscopic probe provided a constant radiant exposure at the nerve surface. The probe was tested in four rats, in vivo. ONS of the CN's was performed with a 1-mm-diameter spot, 5- ms pulse duration, and pulse rate of 20 Hz for a duration of 15-30 s. The flat-top laser beam profile consistently produced a faster and higher ICP response at a lower radiant exposure than the Gaussian beam profile due, in part, to easier alignment of the more uniform beam with nerve. With further development, ONS may be used as a diagnostic tool for identification of the CN's during laparoscopic and robotic nerve-sparing prostate cancer surgery.

  19. Effects of payments for ecosystem services on wildlife habitat recovery.

    PubMed

    Tuanmu, Mao-Ning; Viña, Andrés; Yang, Wu; Chen, Xiaodong; Shortridge, Ashton M; Liu, Jianguo

    2016-08-01

    Conflicts between local people's livelihoods and conservation have led to many unsuccessful conservation efforts and have stimulated debates on policies that might simultaneously promote sustainable management of protected areas and improve the living conditions of local people. Many government-sponsored payments-for-ecosystem-services (PES) schemes have been implemented around the world. However, few empirical assessments of their effectiveness have been conducted, and even fewer assessments have directly measured their effects on ecosystem services. We conducted an empirical and spatially explicit assessment of the conservation effectiveness of one of the world's largest PES programs through the use of a long-term empirical data set, a satellite-based habitat model, and spatial autoregressive analyses on direct measures of change in an ecosystem service (i.e., the provision of wildlife species habitat). Giant panda (Ailuropoda melanoleuca) habitat improved in Wolong Nature Reserve of China after the implementation of the Natural Forest Conservation Program. The improvement was more pronounced in areas monitored by local residents than those monitored by the local government, but only when a higher payment was provided. Our results suggest that the effectiveness of a PES program depends on who receives the payment and on whether the payment provides sufficient incentives. As engagement of local residents has not been incorporated in many conservation strategies elsewhere in China or around the world, our results also suggest that using an incentive-based strategy as a complement to command-and-control, community- and norm-based strategies may help achieve greater conservation effectiveness and provide a potential solution for the park versus people conflict. © 2016 Society for Conservation Biology.

  20. Spatial orientation of caloric nystagmus in semicircular canal-plugged monkeys.

    PubMed

    Arai, Yasuko; Yakushin, Sergei B; Cohen, Bernard; Suzuki, Jun-Ichi; Raphan, Theodore

    2002-08-01

    We studied caloric nystagmus before and after plugging all six semicircular canals to determine whether velocity storage contributed to the spatial orientation of caloric nystagmus. Monkeys were stimulated unilaterally with cold ( approximately 20 degrees C) water while upright, supine, prone, right-side down, and left-side down. The decline in the slow phase velocity vector was determined over the last 37% of the nystagmus, at a time when the response was largely due to activation of velocity storage. Before plugging, yaw components varied with the convective flow of endolymph in the lateral canals in all head orientations. Plugging blocked endolymph flow, eliminating convection currents. Despite this, caloric nystagmus was readily elicited, but the horizontal component was always toward the stimulated (ipsilateral) side, regardless of head position relative to gravity. When upright, the slow phase velocity vector was close to the yaw and spatial vertical axes. Roll components became stronger in supine and prone positions, and vertical components were enhanced in side down positions. In each case, this brought the velocity vectors toward alignment with the spatial vertical. Consistent with principles governing the orientation of velocity storage, when the yaw component of the velocity vector was positive, the cross-coupled pitch or roll components brought the vector upward in space. Conversely, when yaw eye velocity vector was downward in the head coordinate frame, i.e., negative, pitch and roll were downward in space. The data could not be modeled simply by a reduction in activity in the ipsilateral vestibular nerve, which would direct the velocity vector along the roll direction. Since there is no cross coupling from roll to yaw, velocity storage alone could not rotate the vector to fit the data. We postulated, therefore, that cooling had caused contraction of the endolymph in the plugged canals. This contraction would deflect the cupula toward the plug, simulating ampullofugal flow of endolymph. Inhibition and excitation induced by such cupula deflection fit the data well in the upright position but not in lateral or prone/supine conditions. Data fits in these positions required the addition of a spatially orientated, velocity storage component. We conclude, therefore, that three factors produce cold caloric nystagmus after canal plugging: inhibition of activity in ampullary nerves, contraction of endolymph in the stimulated canals, and orientation of eye velocity to gravity through velocity storage. Although the response to convection currents dominates the normal response to caloric stimulation, velocity storage probably also contributes to the orientation of eye velocity.

  1. Monitoring Change in Temperate Coniferous Forest Ecosystems

    NASA Technical Reports Server (NTRS)

    Williams, Darrel (Technical Monitor); Woodcock, Curtis E.

    2004-01-01

    The primary goal of this research was to improve monitoring of temperate forest change using remote sensing. In this context, change includes both clearing of forest due to effects such as fire, logging, or land conversion and forest growth and succession. The Landsat 7 ETM+ proved an extremely valuable research tool in this domain. The Landsat 7 program has generated an extremely valuable transformation in the land remote sensing community by making high quality images available for relatively low cost. In addition, the tremendous improvements in the acquisition strategy greatly improved the overall availability of remote sensing images. I believe that from an historical prespective, the Landsat 7 mission will be considered extremely important as the improved image availability will stimulate the use of multitemporal imagery at resolutions useful for local to regional mapping. Also, Landsat 7 has opened the way to global applications of remote sensing at spatial scales where important surface processes and change can be directly monitored. It has been a wonderful experience to have participated on the Landsat 7 Science Team. The research conducted under this project led to contributions in four general domains: I. Improved understanding of the information content of images as a function of spatial resolution; II. Monitoring Forest Change and Succession; III. Development and Integration of Advanced Analysis Methods; and IV. General support of the remote sensing of forests and environmental change. This report is organized according to these topics. This report does not attempt to provide the complete details of the research conducted with support from this grant. That level of detail is provided in the 16 peer reviewed journal articles, 7 book chapters and 5 conference proceedings papers published as part of this grant. This report attempts to explain how the various publications fit together to improve our understanding of how forests are changing and how to monitor forest change with remote sensing. There were no new inventions that resulted from this grant.

  2. Gradient and shim technologies for ultra high field MRI

    PubMed Central

    Winkler, Simone A.; Schmitt, Franz; Landes, Hermann; DeBever, Josh; Wade, Trevor; Alejski, Andrew

    2017-01-01

    Ultra High Field (UHF) MRI requires improved gradient and shim performance to fully realize the promised gains (SNR as well as spatial, spectral, diffusion resolution) that higher main magnetic fields offer. Both the more challenging UHF environment by itself, as well as the higher currents used in high performance coils, require a deeper understanding combined with sophisticated engineering modeling and construction, to optimize gradient and shim hardware for safe operation and for highest image quality. This review summarizes the basics of gradient and shim technologies, and outlines a number of UHF-related challenges and solutions. In particular, Lorentz forces, vibroacoustics, eddy currents, and peripheral nerve stimulation are discussed. Several promising UHF-relevant gradient concepts are described, including insertable gradient coils aimed at higher performance neuroimaging. PMID:27915120

  3. A quantitative method for determining spatial discriminative capacity.

    PubMed

    Zhang, Zheng; Tannan, Vinay; Holden, Jameson K; Dennis, Robert G; Tommerdahl, Mark

    2008-03-10

    The traditional two-point discrimination (TPD) test, a widely used tactile spatial acuity measure, has been criticized as being imprecise because it is based on subjective criteria and involves a number of non-spatial cues. The results of a recent study showed that as two stimuli were delivered simultaneously, vibrotactile amplitude discrimination became worse when the two stimuli were positioned relatively close together and was significantly degraded when the probes were within a subject's two-point limen. The impairment of amplitude discrimination with decreasing inter-probe distance suggested that the metric of amplitude discrimination could possibly provide a means of objective and quantitative measurement of spatial discrimination capacity. A two alternative forced-choice (2AFC) tracking procedure was used to assess a subject's ability to discriminate the amplitude difference between two stimuli positioned at near-adjacent skin sites. Two 25 Hz flutter stimuli, identical except for a constant difference in amplitude, were delivered simultaneously to the hand dorsum. The stimuli were initially spaced 30 mm apart, and the inter-stimulus distance was modified on a trial-by-trial basis based on the subject's performance of discriminating the stimulus with higher intensity. The experiment was repeated via sequential, rather than simultaneous, delivery of the same vibrotactile stimuli. Results obtained from this study showed that the performance of the amplitude discrimination task was significantly degraded when the stimuli were delivered simultaneously and were near a subject's two-point limen. In contrast, subjects were able to correctly discriminate between the amplitudes of the two stimuli when they were sequentially delivered at all inter-probe distances (including those within the two-point limen), and improved when an adapting stimulus was delivered prior to simultaneously delivered stimuli. Subjects' capacity to discriminate the amplitude difference between two vibrotactile stimulations was degraded as the inter-stimulus distance approached the limit of their two-point spatial discriminative capacity. This degradation of spatial discriminative capacity lessened when an adapting stimulus was used. Performance of the task, as well as improvement on the task with adaptation, would most likely be impaired if the cortical information processing capacity of a subject or subject population were systemically altered, and thus, the methods described could be effective measures for use in clinical or clinical research applications.

  4. Enhanced neural function in highly aberrated eyes following perceptual learning with adaptive optics.

    PubMed

    Sabesan, Ramkumar; Barbot, Antoine; Yoon, Geunyoung

    2017-03-01

    Highly aberrated keratoconic (KC) eyes do not elicit the expected visual advantage from customized optical corrections. This is attributed to the neural insensitivity arising from chronic visual experience with poor retinal image quality, dominated by low spatial frequencies. The goal of this study was to investigate if targeted perceptual learning with adaptive optics (AO) can stimulate neural plasticity in these highly aberrated eyes. The worse eye of 2 KC subjects was trained in a contrast threshold test under AO correction. Prior to training, tumbling 'E' visual acuity and contrast sensitivity at 4, 8, 12, 16, 20, 24 and 28 c/deg were measured in both the trained and untrained eyes of each subject with their routine prescription and with AO correction for a 6mm pupil. The high spatial frequency requiring 50% contrast for detection with AO correction was picked as the training frequency. Subjects were required to train on a contrast detection test with AO correction for 1h for 5 consecutive days. During each training session, threshold contrast measurement at the training frequency with AO was conducted. Pre-training measures were repeated after the 5 training sessions in both eyes (i.e., post-training). After training, contrast sensitivity under AO correction improved on average across spatial frequency by a factor of 1.91 (range: 1.77-2.04) and 1.75 (1.22-2.34) for the two subjects. This improvement in contrast sensitivity transferred to visual acuity with the two subjects improving by 1.5 and 1.3 lines respectively with AO following training. One of the two subjects denoted an interocular transfer of training and an improvement in performance with their routine prescription post-training. This training-induced visual benefit demonstrates the potential of AO as a tool for neural rehabilitation in patients with abnormal corneas. Moreover, it reveals a sufficient degree of neural plasticity in normally developed adults who have a long history of abnormal visual experience due to optical imperfections. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Comparison of Thermo-Elastic and Poro-Elastic Effects during Shear Stimulation of Desert Peak EGS Well 27-15 Using a Coupled Thermal-Hydrological-Mechanical Simulator

    NASA Astrophysics Data System (ADS)

    Kelkar, S.; Dempsey, D.; Hickman, S. H.; Davatzes, N. C.; Moos, D.; Zemach, E.

    2013-12-01

    High-temperature rock formations at moderate depths with low permeability are candidates for Enhanced Geothermal Systems (EGS) projects. Hydraulic stimulation can be employed in such systems to create flow paths with low hydraulic impedance while maintaining significant heat transfer area to avoid premature cooling of the formation and the creation of short-circuit flow paths. Here we present results from a coupled thermal-hydrological-mechanical numerical model of a successful EGS stimulation in well 27-15 at the Desert Peak Geothermal Field, Nevada. This stimulation was carried out over two different depth intervals and multiple injection pressures, beginning in September 2010. The subject of this study is the initial shear stimulation phase, which was carried out at depths of 0.9 to 1.1 km over a period of about 100 days. The reservoir temperature at these depths is ~182 to 195° C. This treatment consisted of injection of 20 to 30° C water at wellhead pressures (WHP) of 1.5, 2.2, 3.1 and 3.7 MPa followed by periods of shut-in. To avoid hydraulic fracturing, these pressure steps were intentionally selected to stay below the minimum principal stress measured in the well. The injectivity did not change at WHP steps of 1.5 and 2.2 MPa, but improved significantly during injection at 3.1 MPa, from about 0.1 to 1.5 kg s-1 MPa-1. This improvement was attributed to self-propping shear failure of pre-existing natural fractures. The model incorporates physical processes thought to be important during this low-pressure shear stimulation phase. The relatively long periods of injection of water that was significantly cooler than the ambient formation temperature required incorporating in the model both thermo-mechanical and poroelastic effects, which were coupled to fluid flow via Mohr-Coulomb failure and shear-induced increases in fracture permeability. This model resulted in a good match to the wellhead injection data recorded during the stimulation. This numerical model was also used to separate the thermo-mechanical and poroelastic effects, compare their spatial and temporal evolution and carry out sensitivity analyses. To varying degrees, model results depended on variations in permeability anisotropy, elastic and thermal rock properties, Mohr-Coulomb parameters of static and dynamic friction and cohesion, shear-dilatation parameters, injection pressure and length of the injection zone. The thermoelastic and poroelastic effects are realized over different time scales, and their magnitudes are governed by different material properties; in general, model results show greater sensitivity to variations in the coefficient of thermal expansion than in the Biot poroelastic factor. Both thermal and poroelastic contributions to stressing of fractures significantly impact the onset as well as the magnitude of shear-induced permeability gains realized during this low-pressure stimulation.

  6. A spatially collocated sound thrusts a flash into awareness

    PubMed Central

    Aller, Máté; Giani, Anette; Conrad, Verena; Watanabe, Masataka; Noppeney, Uta

    2015-01-01

    To interact effectively with the environment the brain integrates signals from multiple senses. It is currently unclear to what extent spatial information can be integrated across different senses in the absence of awareness. Combining dynamic continuous flash suppression (CFS) and spatial audiovisual stimulation, the current study investigated whether a sound facilitates a concurrent visual flash to elude flash suppression and enter perceptual awareness depending on audiovisual spatial congruency. Our results demonstrate that a concurrent sound boosts unaware visual signals into perceptual awareness. Critically, this process depended on the spatial congruency of the auditory and visual signals pointing towards low level mechanisms of audiovisual integration. Moreover, the concurrent sound biased the reported location of the flash as a function of flash visibility. The spatial bias of sounds on reported flash location was strongest for flashes that were judged invisible. Our results suggest that multisensory integration is a critical mechanism that enables signals to enter conscious perception. PMID:25774126

  7. Auditory spatial processing in the human cortex.

    PubMed

    Salminen, Nelli H; Tiitinen, Hannu; May, Patrick J C

    2012-12-01

    The auditory system codes spatial locations in a way that deviates from the spatial representations found in other modalities. This difference is especially striking in the cortex, where neurons form topographical maps of visual and tactile space but where auditory space is represented through a population rate code. In this hemifield code, sound source location is represented in the activity of two widely tuned opponent populations, one tuned to the right and the other to the left side of auditory space. Scientists are only beginning to uncover how this coding strategy adapts to various spatial processing demands. This review presents the current understanding of auditory spatial processing in the cortex. To this end, the authors consider how various implementations of the hemifield code may exist within the auditory cortex and how these may be modulated by the stimulation and task context. As a result, a coherent set of neural strategies for auditory spatial processing emerges.

  8. STC1 interference on calcitonin family of receptors signaling during osteoblastogenesis via adenylate cyclase inhibition.

    PubMed

    Terra, Silvia R; Cardoso, João Carlos R; Félix, Rute C; Martins, Leo Anderson M; Souza, Diogo Onofre G; Guma, Fatima C R; Canário, Adelino Vicente M; Schein, Vanessa

    2015-03-05

    Stanniocalcin 1 (STC1) and calcitonin gene-related peptide (CGRP) are involved in bone formation/remodeling. Here we investigate the effects of STC1 on functional heterodimer complex CALCRL/RAMP1, expression and activity during osteoblastogenesis. STC1 did not modify CALCRL and ramp1 gene expression during osteoblastogenesis when compared to controls. However, plasma membrane spatial distribution of CALCRL/RAMP1 was modified in 7-day pre-osteoblasts exposed to either CGRP or STC1, and both peptides induced CALCRL and RAMP1 assembly. CGRP, but not STC1 stimulated cAMP accumulation in 7-day osteoblasts and in CALCRL/RAMP1 transfected HEK293 cells. Furthermore, STC1 inhibited forskolin stimulated cAMP accumulation of HEK293 cells, but not in CALCRL/RAMP1 transfected HEK293 cells. However, STC1 inhibited cAMP accumulation in calcitonin receptor (CTR) HEK293 transfected cells stimulated by calcitonin. In conclusion, STC1 signals through inhibitory G-protein modulates CGRP receptor spatial localization during osteoblastogenesis and may function as a regulatory factor interacting with calcitonin peptide members during bone formation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Spatial Disorientation in Military Vehicles: Causes, Consequences and Cures (Desorientation spaiale dans les vehicules militaires: causes, consequences et remedes)

    DTIC Science & Technology

    2003-02-01

    servcice warfighters (Training devices and protocols, Onboard equipment, Cognitive and sensorimotor aids, Visual and auditory symbology, Peripheral visual...vestibular stimulation causing a decrease in cerebral blood pressure with the consequent reduction in G-tolerance and increased likelihood of ALOC or GLOC...tactile stimulators (e.g. one providing a sensation of movement) or of displays with a more complex coding (e.g. by increase in the number of tactors, or

  10. Calcium signals in olfactory neurons.

    PubMed

    Tareilus, E; Noé, J; Breer, H

    1995-11-09

    Laser scanning confocal microscopy in combination with the fluorescent calcium indicators Fluo-3 and Fura-Red was employed to estimate the intracellular concentration of free calcium ions in individual olfactory receptor neurons and to monitor temporal and spatial changes in the Ca(2+)-level upon stimulation. The chemosensory cells responded to odorants with a significant increase in the calcium concentration, preferentially in the dendritic knob. Applying various stimulation paradigma, it was found that in a population of isolated cells, subsets of receptor neurons display distinct patterns of responsiveness.

  11. Noninvasive transcranial direct current stimulation (tDCS) for the treatment of orofacial pain.

    PubMed

    Fricova, Jitka; Englerova, Katerina; Rokyta, Richard

    2016-10-01

    tDCS is a promising method for the treatment of chronic pain. Electrode placement locations must be chosen in accordance with the density and the time course of the current in order to prevent pathological changes in the underlying tissue. In order to reduce current spatial variability, more electrodes of the same polarity are placed in a circle around the second electrode of the opposite polarity. The applied current produced the greatest changes directly beneath the electrodes: the cathode reduces the excitability of cortical neurons, while the anode has the opposite effect. Based on inclusion criteria, 10 patients with chronic orofacial pain, secondary trigeminal neuralgia after oral surgery, were enrolled and underwent both anode and cathode stimulation. Before the first session we measured pain intensity on a numeric pain rating scale and tactile and thermal stimulation were used to assess somatosensory status. tDCS was applied for five consecutive days. At the end of tDCS application, somatosensory status was assessed again. From our results we can conclude that the application of tDCS improves the perception of some types of pain. When we increase our sample size, we would expect confirmation not only on our positive results, but also some additional findings for explaining the pathophysiology of orofacial pain. These pathophysiological findings and explanations are very important for the application of tDCS in the treatment of orofacial pain and also for other types of neuropathic pain.

  12. Controversy: Noninvasive and invasive cortical stimulation show efficacy in treating stroke patients.

    PubMed

    Hummel, Friedhelm C; Celnik, Pablo; Pascual-Leone, Alvero; Fregni, Felipe; Byblow, Winston D; Buetefisch, Cathrin M; Rothwell, John; Cohen, Leonardo G; Gerloff, Christian

    2008-10-01

    Stroke is the leading cause of disability in the adult population of western industrialized countries. Despite significant improvements of acute stroke care, two thirds of stroke survivors have to cope with persisting neurologic deficits. Adjuvant brain stimulation is a novel approach to improving the treatment of residual deficits after stroke. Transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and epidural electrical stimulation have been used in first trials on small cohorts of stroke patients. Effect sizes in the order of 8% to 30% of functional improvement have been reported, but a publication bias toward presenting "promising" but not negative results is likely. Many questions regarding underlying mechanisms, optimal stimulation parameters, combination with other types of interventions, among others, are open. This review addresses six controversies related to the experimental application of brain stimulation techniques to stroke patients. Cortical stimulation after stroke will need to be individually tailored and a thorough patient stratification according to type and extent of clinical deficit, lesion location, lesion size, comorbidities, time in the recovery process, and perhaps also age and gender will be necessary. There is consensus that cortical stimulation in stroke patients is still experimental and should only be applied in the frame of scientific studies.

  13. Improved transcranial magnetic stimulation coil design with realistic head modeling

    NASA Astrophysics Data System (ADS)

    Crowther, Lawrence; Hadimani, Ravi; Jiles, David

    2013-03-01

    We are investigating Transcranial magnetic stimulation (TMS) as a noninvasive technique based on electromagnetic induction which causes stimulation of the neurons in the brain. TMS can be used as a pain-free alternative to conventional electroconvulsive therapy (ECT) which is still widely implemented for treatment of major depression. Development of improved TMS coils capable of stimulating subcortical regions could also allow TMS to replace invasive deep brain stimulation (DBS) which requires surgical implantation of electrodes in the brain. Our new designs allow new applications of the technique to be established for a variety of diagnostic and therapeutic applications of psychiatric disorders and neurological diseases. Calculation of the fields generated inside the head is vital for the use of this method for treatment. In prior work we have implemented a realistic head model, incorporating inhomogeneous tissue structures and electrical conductivities, allowing the site of neuronal activation to be accurately calculated. We will show how we utilize this model in the development of novel TMS coil designs to improve the depth of penetration and localization of stimulation produced by stimulator coils.

  14. An improved genetic algorithm for designing optimal temporal patterns of neural stimulation

    NASA Astrophysics Data System (ADS)

    Cassar, Isaac R.; Titus, Nathan D.; Grill, Warren M.

    2017-12-01

    Objective. Electrical neuromodulation therapies typically apply constant frequency stimulation, but non-regular temporal patterns of stimulation may be more effective and more efficient. However, the design space for temporal patterns is exceedingly large, and model-based optimization is required for pattern design. We designed and implemented a modified genetic algorithm (GA) intended for design optimal temporal patterns of electrical neuromodulation. Approach. We tested and modified standard GA methods for application to designing temporal patterns of neural stimulation. We evaluated each modification individually and all modifications collectively by comparing performance to the standard GA across three test functions and two biophysically-based models of neural stimulation. Main results. The proposed modifications of the GA significantly improved performance across the test functions and performed best when all were used collectively. The standard GA found patterns that outperformed fixed-frequency, clinically-standard patterns in biophysically-based models of neural stimulation, but the modified GA, in many fewer iterations, consistently converged to higher-scoring, non-regular patterns of stimulation. Significance. The proposed improvements to standard GA methodology reduced the number of iterations required for convergence and identified superior solutions.

  15. Transcranial Direct Current Stimulation Potentiates Improvements in Functional Ability in Patients With Chronic Stroke Receiving Constraint-Induced Movement Therapy.

    PubMed

    Figlewski, Krystian; Blicher, Jakob Udby; Mortensen, Jesper; Severinsen, Kåre Eg; Nielsen, Jørgen Feldbæk; Andersen, Henning

    2017-01-01

    Transcranial direct current stimulation may enhance effect of rehabilitation in patients with chronic stroke. The objective was to evaluate the efficacy of anodal transcranial direct current stimulation combined with constraint-induced movement therapy of the paretic upper limb. A total of 44 patients with stroke were randomly allocated to receive 2 weeks of constraint-induced movement therapy with either anodal or sham transcranial direct current stimulation. The primary outcome measure, Wolf Motor Function Test, was assessed at baseline and after the intervention by blinded investigators. Both groups improved significantly on all Wolf Motor Function Test scores. Group comparison showed improvement on Wolf Motor Function Test in the anodal group compared with the sham group. Anodal transcranial direct current stimulation combined with constraint-induced movement therapy resulted in improvement of functional ability of the paretic upper limb compared with constraint-induced movement therapy alone. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01983319. © 2016 American Heart Association, Inc.

  16. Nigral stimulation for resistant axial motor impairment in Parkinson’s disease? A randomized controlled trial

    PubMed Central

    Walach, Margarete; Meisner, Christoph; Fritz, Melanie; Scholten, Marlieke; Breit, Sorin; Plewnia, Christian; Bender, Benjamin; Gharabaghi, Alireza; Wächter, Tobias

    2013-01-01

    Gait and balance disturbances typically emerge in advanced Parkinson’s disease with generally limited response to dopaminergic medication and subthalamic nucleus deep brain stimulation. Therefore, advanced programming with interleaved pulses was put forward to introduce concomittant nigral stimulation on caudal contacts of a subthalamic lead. Here, we hypothesized that the combined stimulation of subthalamic nucleus and substantia nigra pars reticulata improves axial symptoms compared with standard subthalamic nucleus stimulation. Twelve patients were enrolled in this 2 × 2 cross-over double-blind randomized controlled clinical trial and both the safety and efficacy of combined subthalamic nucleus and substantia nigra pars reticulata stimulation were evaluated compared with standard subthalamic nucleus stimulation. The primary outcome measure was the change of a broad-scaled cumulative axial Unified Parkinson’s Disease Rating Scale score (Scale II items 13–15, Scale III items 27–31) at ‘3-week follow-up’. Secondary outcome measures specifically addressed freezing of gait, balance, quality of life, non-motor symptoms and neuropsychiatric symptoms. For the primary outcome measure no statistically significant improvement was observed for combined subthalamic nucleus and substantia nigra pars reticulata stimulation at the ‘3-week follow-up’. The secondary endpoints, however, revealed that the combined stimulation of subthalamic nucleus and substantia nigra pars reticulata might specifically improve freezing of gait, whereas balance impairment remained unchanged. The combined stimulation of subthalamic nucleus and substantia nigra pars reticulata was safe, and of note, no clinically relevant neuropsychiatric adverse effect was observed. Patients treated with subthalamic nucleus and substantia nigra pars reticulata stimulation revealed no ‘global’ effect on axial motor domains. However, this study opens the perspective that concomittant stimulation of the substantia nigra pars reticulata possibly improves otherwise resistant freezing of gait and, therefore, highly warrants a subsequent phase III randomized controlled trial. PMID:23757762

  17. Groundwater–surface water mixing shifts ecological assembly processes and stimulates organic carbon turnover

    PubMed Central

    Stegen, James C.; Fredrickson, James K.; Wilkins, Michael J.; Konopka, Allan E.; Nelson, William C.; Arntzen, Evan V.; Chrisler, William B.; Chu, Rosalie K.; Danczak, Robert E.; Fansler, Sarah J.; Kennedy, David W.; Resch, Charles T.; Tfaily, Malak

    2016-01-01

    Environmental transitions often result in resource mixtures that overcome limitations to microbial metabolism, resulting in biogeochemical hotspots and moments. Riverine systems, where groundwater mixes with surface water (the hyporheic zone), are spatially complex and temporally dynamic, making development of predictive models challenging. Spatial and temporal variations in hyporheic zone microbial communities are a key, but understudied, component of riverine biogeochemical function. Here, to investigate the coupling among groundwater–surface water mixing, microbial communities and biogeochemistry, we apply ecological theory, aqueous biogeochemistry, DNA sequencing and ultra-high-resolution organic carbon profiling to field samples collected across times and locations representing a broad range of mixing conditions. Our results indicate that groundwater–surface water mixing in the hyporheic zone stimulates heterotrophic respiration, alters organic carbon composition, causes ecological processes to shift from stochastic to deterministic and is associated with elevated abundances of microbial taxa that may degrade a broad suite of organic compounds. PMID:27052662

  18. Groundwater-surface water mixing shifts ecological assembly processes and stimulates organic carbon turnover.

    PubMed

    Stegen, James C; Fredrickson, James K; Wilkins, Michael J; Konopka, Allan E; Nelson, William C; Arntzen, Evan V; Chrisler, William B; Chu, Rosalie K; Danczak, Robert E; Fansler, Sarah J; Kennedy, David W; Resch, Charles T; Tfaily, Malak

    2016-04-07

    Environmental transitions often result in resource mixtures that overcome limitations to microbial metabolism, resulting in biogeochemical hotspots and moments. Riverine systems, where groundwater mixes with surface water (the hyporheic zone), are spatially complex and temporally dynamic, making development of predictive models challenging. Spatial and temporal variations in hyporheic zone microbial communities are a key, but understudied, component of riverine biogeochemical function. Here, to investigate the coupling among groundwater-surface water mixing, microbial communities and biogeochemistry, we apply ecological theory, aqueous biogeochemistry, DNA sequencing and ultra-high-resolution organic carbon profiling to field samples collected across times and locations representing a broad range of mixing conditions. Our results indicate that groundwater-surface water mixing in the hyporheic zone stimulates heterotrophic respiration, alters organic carbon composition, causes ecological processes to shift from stochastic to deterministic and is associated with elevated abundances of microbial taxa that may degrade a broad suite of organic compounds.

  19. Microseismic Event Grouping Based on PageRank Linkage at the Newberry Volcano Geothermal Site

    NASA Astrophysics Data System (ADS)

    Aguiar, A. C.; Myers, S. C.

    2016-12-01

    The Newberry Volcano DOE FORGE site in Central Oregon has been stimulated two times using high-pressure fluid injection to study the Enhanced Geothermal Systems (EGS) technology. Several hundred microseismic events were generated during the first stimulation in the fall of 2012. Initial locations of this microseismicity do not show well defined subsurface structure in part because event location uncertainties are large (Foulger and Julian, 2013). We focus on this stimulation to explore the spatial and temporal development of microseismicity, which is key to understanding how subsurface stimulation modifies stress, fractures rock, and increases permeability. We use PageRank, Google's initial search algorithm, to determine connectivity within the events (Aguiar and Beroza, 2014) and assess signal-correlation topology for the micro-earthquakes. We then use this information to create signal families and compare these to the spatial and temporal proximity of associated earthquakes. We relocate events within families (identified by PageRank linkage) using the Bayesloc approach (Myers et al., 2007). Preliminary relocations show tight spatial clustering of event families as well as evidence of events relocating to a different cluster than originally reported. We also find that signal similarity (linkage) at several stations, not just one or two, is needed in order to determine that events are in close proximity to one another. We show that indirect linkage of signals using PageRank is a reliable way to increase the number of events that are confidently determined to be similar to one another, which may lead to efficient and effective grouping of earthquakes with similar physical characteristics, such as focal mechanisms and stress drop. Our ultimate goal is to determine whether changes in the state of stress and/or changes in the generation of subsurface fracture networks can be detected using PageRank topology as well as aid in the event relocation to obtain more accurate subsurface structure. Prepared by LLNL under Contract DE-AC52-07NA27344. LLNL-ABS-699142.

  20. Modulation of left primary motor cortex excitability after bimanual training and intermittent theta burst stimulation to left dorsal premotor cortex.

    PubMed

    Neva, Jason L; Vesia, Michael; Singh, Amaya M; Staines, W Richard

    2014-03-15

    Bimanual visuomotor movement training (BMT) enhances the excitability of human preparatory premotor and primary motor (M1) cortices compared to unimanual movement. This occurs when BMT involves mirror symmetrical movements of both upper-limbs (in-phase) but not with non-symmetrical movements (anti-phase). The neural mechanisms mediating the effect of BMT is unclear, but may involve interhemispheric connections between homologous M1 representations as well as the dorsal premotor cortices (PMd). The purpose of this study is to assess how intermittent theta burst stimulation (iTBS) of the left PMd affects left M1 excitability, and the possible combined effects of iTBS to left PMd applied before a single session of BMT. Left M1 excitability was quantified using transcranial magnetic stimulation (TMS) in terms of both the amplitudes and spatial extent of motor evoked potentials (MEPs) for the extensor carpi radialis (ECR) before and multiple time points following (1) BMT, (2) iTBS to left PMd or (3) iTBS to left PMd and BMT. Although there was not a greater increase in either specific measure of M1 excitability due to the combination of the interventions, iTBS applied before BMT showed that both the spatial extent and global MEP amplitude for the ECR became larger in parallel, whereas the spatial extent was enhanced with BMT alone and global MEP amplitude was enhanced with iTBS to left PMd alone. These results suggest that the modulation of rapid functional M1 excitability associated with BMT and iTBS of the left PMd could operate under related early markers of neuro-plastic mechanisms, which may be expressed in concurrent and distinct patterns of M1 excitability. Critically, this work may guide rehabilitation training and stimulation techniques that modulate cortical excitability after brain injury. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Long-Term Paired Associative Stimulation Enhances Motor Output of the Tetraplegic Hand.

    PubMed

    Tolmacheva, Aleksandra; Savolainen, Sarianna; Kirveskari, Erika; Lioumis, Pantelis; Kuusela, Linda; Brandstack, Nina; Ylinen, Aarne; Mäkelä, Jyrki P; Shulga, Anastasia

    2017-09-15

    A large proportion of spinal cord injuries (SCI) are incomplete. Even in clinically complete injuries, silent non-functional connections can be present. Therapeutic approaches that can strengthen transmission in weak neural connections to improve motor performance are needed. Our aim was to determine whether long-term delivery of paired associative stimulation (PAS, a combination of transcranial magnetic stimulation [TMS] with peripheral nerve stimulation [PNS]) can enhance motor output in the hands of patients with chronic traumatic tetraplegia, and to compare this technique with long-term PNS. Five patients (4 males; age 38-68, mean 48) with no contraindications to TMS received 4 weeks (16 sessions) of stimulation. PAS was given to one hand and PNS combined with sham TMS to the other hand. Patients were blinded to the treatment. Hands were selected randomly. The patients were evaluated by a physiotherapist blinded to the treatment. The follow-up period was 1 month. Patients were evaluated with Daniels and Worthingham's Muscle Testing (0-5 scale) before the first stimulation session, after the last stimulation session, and 1 month after the last stimulation session. One month after the last stimulation session, the improvement in the PAS-treated hand was 1.02 ± 0.17 points (p < 0.0001, n = 100 muscles from 5 patients). The improvement was significantly higher in PAS-treated than in PNS-treated hands (176 ± 29%, p = 0.046, n = 5 patients). Long-term PAS might be an effective tool for improving motor performance in incomplete chronic SCI patients. Further studies on PAS in larger patient cohorts, with longer stimulation duration and at earlier stages after the injury, are warranted.

  2. Characterization and role of the immune response during ligament healing

    NASA Astrophysics Data System (ADS)

    Chamberlain, Connie S.

    Scar formation of ligaments after rupture remains a great challenge. Ligament healing involves a complex, coordinated series of events that form a neo-ligament, which is more disorganized and fibrotic in character than the native tissue. The repair process may extend from months to years, and the injured ligament never fully recovers its original mechanical properties. With little intrinsic healing potential, ruptures of the anterior cruciate ligament (ACL) are usually reconstructed. The "healed" tissues, however, do not regenerate native tissues or recapitulate their mechanical function. ACL grafts often lengthen (incidents range from 40-100%) and their strength can drop by ˜50% after remodeling. Reconstructed knees are often less stable and fail to restore normal joint kinematics. Our overall goal is to improve healing, making ligaments more regenerative. The first 2 studies characterized ligament healing in a spatial and temporal manner over 28 days. The experiments demonstrated creeping substitution and the potential role of the immune system to control the repair and/or regenerative process. From these studies, macrophages were identified as significant players during healing. Macrophages paralleled creeping substitution, were abundant within the healing ligament, and potentially played a destructive role via matrix phagocytosis. The role of macrophages during early ligament healing was then evaluated using liposome-encapsulated clodronate to inhibit phagocytosing macrophages. Clodronate attenuated the early infiltration of macrophages, resulting in delayed structural and functional healing. Macrophage re-infiltration into the wound resulted in continued ligament healing. These results suggested that early inhibition of phagocytosing macrophages is detrimental to ligament healing. The final experiment evaluated the effects of interleukin-4 on ligament healing. Interleukin-4 (IL-4) is reported to stimulate the Th2 lymphocyte/M2 macrophage pathway, reducing inflammation and stimulating remodeling. IL-4 dose- and time-dependently stimulated early ligament regeneration but was unable to maintain the response during later healing. In summary, this work demonstrated the association between the immune cells and ligament healing, indicating a potential for obtaining a more regenerative response by modulating the immune response in a time, dose, and spatial manner.

  3. Effects of Childhood Gymnastics Program on Spatial Working Memory.

    PubMed

    Hsieh, Shu-Shih; Lin, Chih-Chien; Chang, Yu-Kai; Huang, Chung-Ju; Hung, Tsung-Min

    2017-12-01

    A growing body of evidence has demonstrated the positive effects of physical exercise on cognition in children, and recent studies have specifically investigated the cognitive benefits of exercises involving cognitive-motor interactions, such as gymnastics. This study examined the effect of 8 wk of gymnastics training on behavioral and neurophysiological measures of spatial working memory in children. Forty-four children age 7 to 10 yr were recruited. The experimental group (n = 24; age, 8.7 ± 1.1 yr) was recruited from Yilan County in Taiwan, while the control group (n = 20; age, 8.6 ± 1.1 yr) resided in Taipei City. The experimental group undertook 8 wk of after-school gymnastics training (2 sessions per week, 90 min per session), whereas the control group received no intervention and were instructed to maintain their routine daily activities. Working memory was assessed by performance on a modified delayed match-to-sample test and by event-related potential including the P3 component. Data were collected before and after treatment for the experimental group and at the same time interval for the control group. Response accuracy improved after the experimental intervention regardless of working memory demands. Likewise, the P3 amplitude was larger at the parietal site after gymnastics training regardless of the task difficulty. Our results suggest that a short period of gymnastics training had a general facilitative effect on spatial working memory at both behavioral and neurophysiological levels in children. These finding highlight the potential importance of exercise programs involving cognitive-motor interactions in stimulating development of spatial cognition during childhood.

  4. Encouraging Spatial Talk: Using Children's Museums to Bolster Spatial Reasoning

    ERIC Educational Resources Information Center

    Polinsky, Naomi; Perez, Jasmin; Grehl, Mora; McCrink, Koleen

    2017-01-01

    Longitudinal spatial language intervention studies have shown that greater exposure to spatial language improves children's performance on spatial tasks. Can short naturalistic, spatial language interactions also evoke improved spatial performance? In this study, parents were asked to interact with their child at a block wall exhibit in a…

  5. Non-invasive stimulation of the vibrissal pad improves recovery of whisking function after simultaneous lesion of the facial and infraorbital nerves in rats.

    PubMed

    Bendella, H; Pavlov, S P; Grosheva, M; Irintchev, A; Angelova, S K; Merkel, D; Sinis, N; Kaidoglou, K; Skouras, E; Dunlop, S A; Angelov, Doychin N

    2011-07-01

    We have recently shown that manual stimulation of target muscles promotes functional recovery after transection and surgical repair to pure motor nerves (facial: whisking and blink reflex; hypoglossal: tongue position). However, following facial nerve repair, manual stimulation is detrimental if sensory afferent input is eliminated by, e.g., infraorbital nerve extirpation. To further understand the interplay between sensory input and motor recovery, we performed simultaneous cut-and-suture lesions on both the facial and the infraorbital nerves and examined whether stimulation of the sensory afferents from the vibrissae by a forced use would improve motor recovery. The efficacy of 3 treatment paradigms was assessed: removal of the contralateral vibrissae to ensure a maximal use of the ipsilateral ones (vibrissal stimulation; Group 2), manual stimulation of the ipsilateral vibrissal muscles (Group 3), and vibrissal stimulation followed by manual stimulation (Group 4). Data were compared to controls which underwent surgery but did not receive any treatment (Group 1). Four months after surgery, all three treatments significantly improved the amplitude of vibrissal whisking to 30° versus 11° in the controls of Group 1. The three treatments also reduced the degree of polyneuronal innervation of target muscle fibers to 37% versus 58% in Group 1. These findings indicate that forced vibrissal use and manual stimulation, either alone or sequentially, reduce target muscle polyinnervation and improve recovery of whisking function when both the sensory and the motor components of the trigemino-facial system regenerate.

  6. Biomarkers and Stimulation Algorithms for Adaptive Brain Stimulation

    PubMed Central

    Hoang, Kimberly B.; Cassar, Isaac R.; Grill, Warren M.; Turner, Dennis A.

    2017-01-01

    The goal of this review is to describe in what ways feedback or adaptive stimulation may be delivered and adjusted based on relevant biomarkers. Specific treatment mechanisms underlying therapeutic brain stimulation remain unclear, in spite of the demonstrated efficacy in a number of nervous system diseases. Brain stimulation appears to exert widespread influence over specific neural networks that are relevant to specific disease entities. In awake patients, activation or suppression of these neural networks can be assessed by either symptom alleviation (i.e., tremor, rigidity, seizures) or physiological criteria, which may be predictive of expected symptomatic treatment. Secondary verification of network activation through specific biomarkers that are linked to symptomatic disease improvement may be useful for several reasons. For example, these biomarkers could aid optimal intraoperative localization, possibly improve efficacy or efficiency (i.e., reduced power needs), and provide long-term adaptive automatic adjustment of stimulation parameters. Possible biomarkers for use in portable or implanted devices span from ongoing physiological brain activity, evoked local field potentials (LFPs), and intermittent pathological activity, to wearable devices, biochemical, blood flow, optical, or magnetic resonance imaging (MRI) changes, temperature changes, or optogenetic signals. First, however, potential biomarkers must be correlated directly with symptom or disease treatment and network activation. Although numerous biomarkers are under consideration for a variety of stimulation indications the feasibility of these approaches has yet to be fully determined. Particularly, there are critical questions whether the use of adaptive systems can improve efficacy over continuous stimulation, facilitate adjustment of stimulation interventions and improve our understanding of the role of abnormal network function in disease mechanisms. PMID:29066947

  7. Transplantation of in vitro cultured endothelial progenitor cells repairs the blood-brain barrier and improves cognitive function of APP/PS1 transgenic AD mice.

    PubMed

    Zhang, Shishuang; Zhi, Yongle; Li, Fei; Huang, Shan; Gao, Huabin; Han, Zhaoli; Ge, Xintong; Li, Dai; Chen, Fanglian; Kong, Xiaodong; Lei, Ping

    2018-04-15

    To date, the pathogenesis of Alzheimer's disease (AD) remains unclear. It is well-known that excessive deposition of Aβ in the brain is a crucial part of the pathogenesis of AD. In recent years, the AD neurovascular unit hypothesis has attracted much attention. Impairment of the blood-brain barrier (BBB) leads to abnormal amyloid-β (Aβ) transport, and chronic cerebral hypoperfusion causes Aβ deposition throughout the onset and progression of AD. Endothelial progenitor cells (EPCs) are the universal cells for repairing blood vessels. Our previous studies have shown that a reduced number of EPCs in the peripheral blood results in cerebral vascular repair disorder, cerebral hypoperfusion and neurodegeneration, which might be related to the cognitive dysfunction of AD patients. This study was designed to confirm whether EPCs transplantation could repair the blood-brain barrier, stimulate angiogenesis and reduce Aβ deposition in AD. The expression of ZO-1, Occludin and Claudin-5 was up-regulated in APP/PS1 transgenic mice after hippocampal transplantation of EPCs. Consistent with previous studies, EPC transplants also increased the microvessel density. We observed that Aβ senile plaque deposition was decreased and hippocampal cell apoptosis was reduced after EPCs transplantation. The Morris water maze test showed that spatial learning and memory functions were significantly improved in mice transplanted with EPCs. Consequently, EPCs could up-regulate the expression of tight junction proteins, repair BBB tight junction function, stimulate angiogenesis, promote Aβ clearance, and decrease neuronal loss, ultimately improve cognitive function. Taken together, these data demonstrate EPCs may play an important role in the therapeutic implications for vascular dysfunction in AD. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Induction of cortical plasticity and improved motor performance following unilateral and bilateral transcranial direct current stimulation of the primary motor cortex.

    PubMed

    Kidgell, Dawson J; Goodwill, Alicia M; Frazer, Ashlyn K; Daly, Robin M

    2013-07-01

    Transcranial direct current stimulation (tDCS) is a non-invasive technique that modulates the excitability of neurons within the primary motor cortex (M1). Research shows that anodal-tDCS applied over the non-dominant M1 (i.e. unilateral stimulation) improves motor function of the non-dominant hand. Similarly, previous studies also show that applying cathodal tDCS over the dominant M1 improves motor function of the non-dominant hand, presumably by reducing interhemispheric inhibition. In the present study, one condition involved anodal-tDCS over the non-dominant M1 (unilateral stimulation) whilst a second condition involved applying cathodal-tDCS over the dominant M1 and anodal-tDCS over non-dominant M1 (bilateral stimulation) to determine if unilateral or bilateral stimulation differentially modulates motor function of the non-dominant hand. Using a randomized, cross-over design, 11 right-handed participants underwent three stimulation conditions: 1) unilateral stimulation, that involved anodal-tDCS applied over the non-dominant M1, 2) bilateral stimulation, whereby anodal-tDCS was applied over the non-dominant M1, and cathodal-tDCS over the dominant M1, and 3) sham stimulation. Transcranial magnetic stimulation (TMS) was performed before, immediately after, 30 and 60 minutes after stimulation to elucidate the neural mechanisms underlying any potential after-effects on motor performance. Motor function was evaluated by the Purdue pegboard test. There were significant improvements in motor function following unilateral and bilateral stimulation when compared to sham stimulation at all-time points (all P < 0.05); however there was no difference across time points between unilateral and bilateral stimulation. There was also a similar significant increase in corticomotor excitability with both unilateral and bilateral stimulation immediately post, 30 minutes and 60 minutes compared to sham stimulation (all P < 0.05). Unilateral and bilateral stimulation reduced short-interval intracortical inhibition (SICI) immediately post and at 30 minutes (all P < 0.05), but returned to baseline in both conditions at 60 minutes. There was no difference between unilateral and bilateral stimulation for SICI (P > 0.05). Furthermore, changes in corticomotor plasticity were not related to changes in motor performance. These results indicate that tDCS induced behavioural changes in the non-dominant hand as a consequence of mechanisms associated with use-dependant cortical plasticity that is independent of the electrode arrangement.

  9. Procedural Factors That Affect Psychophysical Measures of Spatial Selectivity in Cochlear Implant Users

    PubMed Central

    Deeks, John M.; Carlyon, Robert P.

    2015-01-01

    Behavioral measures of spatial selectivity in cochlear implants are important both for guiding the programing of individual users’ implants and for the evaluation of different stimulation methods. However, the methods used are subject to a number of confounding factors that can contaminate estimates of spatial selectivity. These factors include off-site listening, charge interactions between masker and probe pulses in interleaved masking paradigms, and confusion effects in forward masking. We review the effects of these confounds and discuss methods for minimizing them. We describe one such method in which the level of a 125-pps masker is adjusted so as to mask a 125-pps probe, and where the masker and probe pulses are temporally interleaved. Five experiments describe the method and evaluate the potential roles of the different potential confounding factors. No evidence was obtained for off-site listening of the type observed in acoustic hearing. The choice of the masking paradigm was shown to alter the measured spatial selectivity. For short gaps between masker and probe pulses, both facilitation and refractory mechanisms had an effect on masking; this finding should inform the choice of stimulation rate in interleaved masking experiments. No evidence for confusion effects in forward masking was revealed. It is concluded that the proposed method avoids many potential confounds but that the choice of method should depend on the research question under investigation. PMID:26420785

  10. Spatial memory during the tropism of maize (Zea mays L.) coleoptiles.

    PubMed

    Nick, P; Schafer, E

    1988-09-01

    Photo- or gravitropic stimulation of graminean coleoptiles involves the formation of putative tropistic transverse polarities. It had been postulated that these polarities can be extended by stabilization to developmentally active polarities. Such polarities are known from unicellular spores and zygotes of lower plants and regeneration experiments in dicotyledonous plants. In coleoptiles, photo- or gravitropic stimulation results in stability to counterstimulation of equal strength (with only transient bending in the direction of the second stimulus), as a result of a directional memory, if the time interval between both stimuli exceeds 90 min. This directional memory develops from a labile precursor, which is present from at least 20 min after induction. Once it is stable, spatial memory is conserved for many hours. The formation of spatial memory involves at least one step not present in the common tropistic transduction chain. The spatial expression of memory as curvature is restricted to three distinct responses: (i) curving in the direction of the first stimulus (for time intervals exceeding 90 min); (ii) curving in the direction of the second stimulus (for time intervals shorter than 65 min); and (iii) zero-curvature (for time intervals between 65 and 90 min). This can be interpreted in terms of a stable transverse polarity, which is not identical with the putative tropistic transverse polarity, but might be an extension of it.

  11. Validation of finite element model of transcranial electrical stimulation using scalp potentials: implications for clinical dose

    NASA Astrophysics Data System (ADS)

    Datta, Abhishek; Zhou, Xiang; Su, Yuzhou; Parra, Lucas C.; Bikson, Marom

    2013-06-01

    Objective. During transcranial electrical stimulation, current passage across the scalp generates voltage across the scalp surface. The goal was to characterize these scalp voltages for the purpose of validating subject-specific finite element method (FEM) models of current flow. Approach. Using a recording electrode array, we mapped skin voltages resulting from low-intensity transcranial electrical stimulation. These voltage recordings were used to compare the predictions obtained from the high-resolution model based on the subject undergoing transcranial stimulation. Main results. Each of the four stimulation electrode configurations tested resulted in a distinct distribution of scalp voltages; these spatial maps were linear with applied current amplitude (0.1 to 1 mA) over low frequencies (1 to 10 Hz). The FEM model accurately predicted the distinct voltage distributions and correlated the induced scalp voltages with current flow through cortex. Significance. Our results provide the first direct model validation for these subject-specific modeling approaches. In addition, the monitoring of scalp voltages may be used to verify electrode placement to increase transcranial electrical stimulation safety and reproducibility.

  12. A new brain stimulation method: Noninvasive transcranial magneto-acoustical stimulation

    NASA Astrophysics Data System (ADS)

    Yuan, Yi; Chen, Yu-Dong; Li, Xiao-Li

    2016-08-01

    We investigate transcranial magneto-acoustical stimulation (TMAS) for noninvasive brain neuromodulation in vivo. TMAS as a novel technique uses an ultrasound wave to induce an electric current in the brain tissue in the static magnetic field. It has the advantage of high spatial resolution and penetration depth. The mechanism of TMAS onto a neuron is analyzed by combining the TMAS principle and Hodgkin-Huxley neuron model. The anesthetized rats are stimulated by TMAS, resulting in the local field potentials which are recorded and analyzed. The simulation results show that TMAS can induce neuronal action potential. The experimental results indicate that TMAS can not only increase the amplitude of local field potentials but also enhance the effect of focused ultrasound stimulation on the neuromodulation. In summary, TMAS can accomplish brain neuromodulation, suggesting a potentially powerful noninvasive stimulation method to interfere with brain rhythms for diagnostic and therapeutic purposes. Project supported by the National Natural Science Foundation of China (Grant Nos. 61503321 and 61273063) and the Natural Science Foundation of Hebei Province, China (Grant No. F2014203161).

  13. Combined motor point associative stimulation (MPAS) and transcranial direct current stimulation (tDCS) improves plateaued manual dexterity performance.

    PubMed

    Hoseini, Najmeh; Munoz-Rubke, Felipe; Wan, Hsuan-Yu; Block, Hannah J

    2016-10-28

    Motor point associative stimulation (MPAS) in hand muscles is known to modify motor cortex excitability and improve learning rate, but not plateau of performance, in manual dexterity tasks. Central stimulation of motor cortex, such as transcranial direct current stimulation (tDCS), can have similar effects if accompanied by motor practice, which can be difficult and tiring for patients. Here we asked whether adding tDCS to MPAS could improve manual dexterity in healthy individuals who are already performing at their plateau, with no motor practice during stimulation. We hypothesized that MPAS could provide enough coordinated muscle activity to make motor practice unnecessary, and that this combination of stimulation techniques could yield improvements even in subjects at or near their peak. If so, this approach could have a substantial effect on patients with impaired dexterity, who are far from their peak. MPAS was applied for 30min to two right hand muscles important for manual dexterity. tDCS was simultaneously applied over left sensorimotor cortex. The motor cortex input/output (I/O) curve was assessed with transcranial magnetic stimulation (TMS), and manual dexterity was assessed with the Purdue Pegboard Test. Compared to sham or cathodal tDCS combined with MPAS, anodal tDCS combined with MPAS significantly increased the plateau of manual dexterity. This result suggests that MPAS has the potential to substitute for motor practice in mediating a beneficial effect of tDCS on manual dexterity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Selective Stimulation of Penumbral Cones Reveals Perception in the Shadow of Retinal Blood Vessels

    PubMed Central

    Spitschan, Manuel; Aguirre, Geoffrey K.; Brainard, David H.

    2015-01-01

    In 1819, Johann Purkinje described how a moving light source that displaces the shadow of the retinal blood vessels to adjacent cones can produce the entopic percept of a branching tree. Here, we describe a novel method for producing a similar percept. We used a device that mixes 56 narrowband primaries under computer control, in conjunction with the method of silent substitution, to present observers with a spectral modulation that selectively targeted penumbral cones in the shadow of the retinal blood vessels. Such a modulation elicits a clear Purkinje-tree percept. We show that the percept is specific to penumbral L and M cone stimulation and is not produced by selective penumbral S cone stimulation. The Purkinje-tree percept was strongest at 16 Hz and fell off at lower (8 Hz) and higher (32 Hz) temporal frequencies. Selective stimulation of open-field cones that are not in shadow, with penumbral cones silenced, also produced the percept, but it was not seen when penumbral and open-field cones were modulated together. This indicates the need for spatial contrast between penumbral and open-field cones to create the Purkinje-tree percept. Our observation provides a new means for studying the response of retinally stabilized images and demonstrates that penumbral cones can support spatial vision. Further, the result illustrates a way in which silent substitution techniques can fail to be silent. We show that inadvertent penumbral cone stimulation can accompany melanopsin-directed modulations that are designed only to silence open-field cones. This in turn can result in visual responses that might be mistaken as melanopsin-driven. PMID:25897842

  15. Comparison of electric field strength and spatial distribution of electroconvulsive therapy and magnetic seizure therapy in a realistic human head model

    PubMed Central

    Lee, Won Hee; Lisanby, Sarah H.; Laine, Andrew F.; Peterchev, Angel V.

    2017-01-01

    Background This study examines the strength and spatial distribution of the electric field induced in the brain by electroconvulsive therapy (ECT) and magnetic seizure therapy (MST). Methods The electric field induced by standard (bilateral, right unilateral, and bifrontal) and experimental (focal electrically administered seizure therapy and frontomedial) ECT electrode configurations as well as a circular MST coil configuration was simulated in an anatomically realistic finite element model of the human head. Maps of the electric field strength relative to an estimated neural activation threshold were used to evaluate the stimulation strength and focality in specific brain regions of interest for these ECT and MST paradigms and various stimulus current amplitudes. Results The standard ECT configurations and current amplitude of 800–900 mA produced the strongest overall stimulation with median of 1.8–2.9 times neural activation threshold and more than 94% of the brain volume stimulated at suprathreshold level. All standard ECT electrode placements exposed the hippocampi to suprathreshold electric field, although there were differences across modalities with bilateral and right unilateral producing respectively the strongest and weakest hippocampal stimulation. MST stimulation is up to 9 times weaker compared to conventional ECT, resulting in direct activation of only 21% of the brain. Reducing the stimulus current amplitude can make ECT as focal as MST. Conclusions The relative differences in electric field strength may be a contributing factor for the cognitive sparing observed with right unilateral compared to bilateral ECT, and MST compared to right unilateral ECT. These simulations could help understand the mechanisms of seizure therapies and develop interventions with superior risk/benefit ratio. PMID:27318858

  16. Local Hotspots In The Gulf Of Maine: Spatial Overlap Between Dynamic Aggregations Of Primary Productivity And Fish Abundance

    NASA Astrophysics Data System (ADS)

    Ribera, M.

    2016-02-01

    Identification of biological hotspots may be a necessary step toward ecosystem-based management goals, as these often signal underlying processes that aggregate or stimulate resources in a particular location. However, previously used metrics to locate these hotspots are not easily adapted to local marine datasets, in part due to the high spatial and temporal variability of phytoplankton populations. While most fish species in temperate regions are well adapted to the seasonal variability of phytoplankton abundance, it is the variability beyond this predictable pattern (i.e. anomalies) that may heavily impact the abundance and spatial distribution of organisms higher up the food chain. The objective of this study was to identify local-scale biological hotspots in a region in the western side of the Gulf of Maine using remote sensing chlorophyll-a data (from MERIS sensor), and to study the spatial overlap between these hotspots and high concentrations of fish abundance (derived from VTR dataset). For this reason, we defined a new hotspot metric that identified as a hotspot any area that consistently exhibited high-magnitude anomalies through time, a sign of highly dynamic communities. We improved on previous indices by minimizing the effect that different means and variances across space may have on the results, a situation that often occurs when comparing coastal and offshore systems. Results show a significant spatial correlation between pelagic fish abundance and aggregations of primary productivity. Spatial correlations were also significant between benthic fish abundance and primary productivity hotspots, but only during spring months. We argue that this new hotspot index compliments existing global measures as it helps managers understand the dynamic characteristics of a complex marine system. It also provides a unique metric that is easily compared across space and between different trophic levels, which may facilitate future ecosystem-wide studies.

  17. Local Hotspots In The Gulf Of Maine: Spatial Overlap Between Dynamic Aggregations Of Primary Productivity And Fish Abundance

    NASA Astrophysics Data System (ADS)

    Ribera, M.

    2016-12-01

    Identification of biological hotspots may be a necessary step toward ecosystem-based management goals, as these often signal underlying processes that aggregate or stimulate resources in a particular location. However, previously used metrics to locate these hotspots are not easily adapted to local marine datasets, in part due to the high spatial and temporal variability of phytoplankton populations. While most fish species in temperate regions are well adapted to the seasonal variability of phytoplankton abundance, it is the variability beyond this predictable pattern (i.e. anomalies) that may heavily impact the abundance and spatial distribution of organisms higher up the food chain. The objective of this study was to identify local-scale biological hotspots in a region in the western side of the Gulf of Maine using remote sensing chlorophyll-a data (from MERIS sensor), and to study the spatial overlap between these hotspots and high concentrations of fish abundance (derived from VTR dataset). For this reason, we defined a new hotspot metric that identified as a hotspot any area that consistently exhibited high-magnitude anomalies through time, a sign of highly dynamic communities. We improved on previous indices by minimizing the effect that different means and variances across space may have on the results, a situation that often occurs when comparing coastal and offshore systems. Results show a significant spatial correlation between pelagic fish abundance and aggregations of primary productivity. Spatial correlations were also significant between benthic fish abundance and primary productivity hotspots, but only during spring months. We argue that this new hotspot index compliments existing global measures as it helps managers understand the dynamic characteristics of a complex marine system. It also provides a unique metric that is easily compared across space and between different trophic levels, which may facilitate future ecosystem-wide studies.

  18. Experimental assessment of thermal effects of high power density light stimulation for optogenetics control of deep brain structures (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Senova, Suhan; Scisniak, Ilona; Chiang, Chih Chieh; Doignon, Isabelle; Martin, Claire; Palfi, Stephane; Chaillet, Antoine; Pain, Frederic

    2016-03-01

    2D surface maps of light distribution and temperature increase were recorded in wild type anesthetized rats brains during 90s light stimulation at 478nm (blue) and 638nm (red) with continuous or pulsed optical stimulations with corresponding power ranging from 100 up to 1200 mW/mm² at the output of an optical fiber. Post mortem maps were recorded in the same animals to assess the cooling effect of blood flow. Post mortem histological analysis were carried out to assess whether high power light stimulations had phototoxic effects or could trigger non physiological functional activation. Temperature increase remains below physiological changes (0,5 -1°) for stimulations up to 400mW/mm² at 40Hz. . Histology did not show significant irreversible modifications or damage to the tissues. The spatial profile of light distribution and heat were correlated and demonstrate as expected a rapid attenuation with diatnce to the fiber.

  19. Optogenetic control of contractile function in skeletal muscle

    PubMed Central

    Bruegmann, Tobias; van Bremen, Tobias; Vogt, Christoph C.; Send, Thorsten; Fleischmann, Bernd K.; Sasse, Philipp

    2015-01-01

    Optogenetic stimulation allows activation of cells with high spatial and temporal precision. Here we show direct optogenetic stimulation of skeletal muscle from transgenic mice expressing the light-sensitive channel Channelrhodopsin-2 (ChR2). Largest tetanic contractions are observed with 5-ms light pulses at 30 Hz, resulting in 84% of the maximal force induced by electrical stimulation. We demonstrate the utility of this approach by selectively stimulating with a light guide individual intralaryngeal muscles in explanted larynges from ChR2-transgenic mice, which enables selective opening and closing of the vocal cords. Furthermore, systemic injection of adeno-associated virus into wild-type mice provides sufficient ChR2 expression for optogenetic opening of the vocal cords. Thus, direct optogenetic stimulation of skeletal muscle generates large force and provides the distinct advantage of localized and cell-type-specific activation. This technology could be useful for therapeutic purposes, such as restoring the mobility of the vocal cords in patients suffering from laryngeal paralysis. PMID:26035411

  20. Focused intracochlear electric stimulation with phased array channels.

    PubMed

    van den Honert, Chris; Kelsall, David C

    2007-06-01

    A method is described for producing focused intracochlear electric stimulation using an array of N electrodes. For each electrode site, N weights are computed that define the ratios of positive and negative electrode currents required to produce cancellation of the voltage within scala tympani at all of the N-1 other sites. Multiple sites can be stimulated simultaneously by superposition of their respective current vectors. The method allows N independent stimulus waveforms to be delivered to each of the N electrode sites without spatial overlap. Channel interaction from current spread associated with monopolar stimulation is substantially eliminated. The method operates by inverting the spread functions of individual monopoles as measured with the other electrodes. The method was implemented and validated with data from three human subjects implanted with 22-electrode perimodiolar arrays. Results indicate that (1) focusing is realizable with realistic precision; (2) focusing comes at the cost of increased total stimulation current; (3) uncanceled voltages that arise beyond the ends of the array are weak except when stimulating the two end channels; and (4) close perimodiolar positioning of the electrodes may be important for minimizing stimulation current and sensitivity to measurement errors.

  1. Spatial dynamics of action potentials estimated by dendritic Ca(2+) signals in insect projection neurons.

    PubMed

    Ogawa, Hiroto; Mitani, Ruriko

    2015-11-13

    The spatial dynamics of action potentials, including their propagation and the location of spike initiation zone (SIZ), are crucial for the computation of a single neuron. Compared with mammalian central neurons, the spike dynamics of invertebrate neurons remain relatively unknown. Thus, we examined the spike dynamics based on single spike-induced Ca(2+) signals in the dendrites of cricket mechanosensory projection neurons, known as giant interneurons (GIs). The Ca(2+) transients induced by a synaptically evoked single spike were larger than those induced by an antidromic spike, whereas subthreshold synaptic potentials caused no elevation of Ca(2+). These results indicate that synaptic activity enhances the dendritic Ca(2+) influx through voltage-gated Ca(2+) channels. Stimulation of the presynaptic sensory afferents ipsilateral to the recording site evoked a dendritic spike with higher amplitude than contralateral stimulation, thereby suggesting that alteration of the spike waveform resulted in synaptic enhancement of the dendritic Ca(2+) transients. The SIZ estimated from the spatial distribution of the difference in the Ca(2+) amplitude was distributed throughout the right and left dendritic branches across the primary neurite connecting them in GIs. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Comparison of dysphagia before and after deep brain stimulation in Parkinson's disease.

    PubMed

    Silbergleit, Alice K; LeWitt, Peter; Junn, Fred; Schultz, Lonni R; Collins, Denise; Beardsley, Tausha; Hubert, Meghan; Trosch, Richard; Schwalb, Jason M

    2012-12-01

    Although dysphagia is a common problem for many Parkinson's disease (PD) patients, the effect of deep brain stimulation (DBS) on swallowing is unclear. Fourteen subjects with advanced PD underwent videofluorographic swallowing studies prior to bilateral DBS of the subthalamic nucleus (STN) and at 3 and 12 months postprocedure. They were tested under several stimulation and medication conditions. Subjects completed the Dysphagia Handicap Index at each time. There was a strong trend toward improved swallowing response for solid intake in the medication-free condition with the stimulator on compared with the stimulator off (P = .0107). Also, there was a trend toward improved oral preparation of thin liquids (P = .0368) in the medication-free condition when the stimulator was on versus off 12 months later. The remaining swallowing parameters showed no change or worsening of swallowing function regardless of stimulator or medication status. Results of the Dysphagia Handicap Index revealed significant improvement in subject self-perception of swallowing 3 and 12 months following the procedure compared with baseline on the functional subscale (P = .020 and P = .010, respectively), the emotional subscale (P = .013 and P = .003, respectively), and the total score (P = .025 and P = .003, respectively). These data suggest that bilateral STN-DBS does not substantively impair swallowing in PD. In addition, it may improve motor sequencing of the oropharyngeal swallow for solid consistencies (which are known to provide increased sensory feedback to assist motor planning of the oropharyngeal swallow). Subjects with advanced PD who are undergoing DBS may perceive significant improvement in swallowing ability despite the lack of objective improvements in swallowing function. Copyright © 2012 Movement Disorder Society.

  3. Subthalamic nucleus deep brain stimulation for Parkinson's disease: evidence for effectiveness and limitations from 12 years' experience.

    PubMed

    Chan, Anne Y Y; Yeung, Jonas H M; Mok, Vincent C T; Ip, Vincent H L; Wong, Adrian; Kuo, S H; Chan, Danny T M; Zhu, X L; Wong, Edith; Lau, Claire K Y; Wong, Rosanna K M; Tang, Venus; Lau, Christine; Poon, W S

    2014-12-01

    To present the result and experience of subthalamic nucleus deep brain stimulation for Parkinson's disease. Case series. Prince of Wales Hospital, Hong Kong. A cohort of patients with Parkinson's disease received subthalamic nucleus deep brain stimulation from September 1998 to January 2010. Patient assessment data before and after the operation were collected prospectively. Forty-one patients (21 male and 20 female) with Parkinson's disease underwent bilateral subthalamic nucleus deep brain stimulation and were followed up for a median interval of 12 months. For the whole group, the mean improvements of Unified Parkinson's Disease Rating Scale (UPDRS) parts II and III were 32.5% and 31.5%, respectively (P<0.001). Throughout the years, a multidisciplinary team was gradually built. The deep brain stimulation protocol evolved and was substantiated by updated patient selection criteria and outcome assessment, integrated imaging and neurophysiological targeting, refinement of surgical technique as well as the accumulation of experience in deep brain stimulation programming. Most of the structural improvement occurred before mid-2005. Patients receiving the operation before June 2005 (19 cases) and after (22 cases) were compared; the improvements in UPDRS part III were 13.2% and 55.2%, respectively (P<0.001). There were three operative complications (one lead migration, one cerebral haematoma, and one infection) in the group operated on before 2005. There was no operative mortality. The functional state of Parkinson's disease patients with motor disabilities refractory to best medical treatment improved significantly after subthalamic nucleus deep brain stimulation. A dedicated multidisciplinary team building, refined protocol for patient selection and assessment, improvement of targeting methods, meticulous surgical technique, and experience in programming are the key factors contributing to the improved outcome.

  4. Design and performance characteristics of a mechanically driven vestibular stimulator.

    DOT National Transportation Integrated Search

    1964-01-01

    In order to determine basic response characteristics of mammalian vestibular systems, the sytems so important for spatial orientation, a device to provide programs of controlled angular accelerations about the vertical axis was required. The small ro...

  5. Vision restoration therapy does not benefit from costimulation: A pilot study.

    PubMed

    Kasten, Erich; Bunzenthal, Ulrike; Müller-Oehring, Eva M; Mueller, Iris; Sabel, Bernhard A

    2007-08-01

    Visual field deficits in patients have long been considered to be nontreatable, but in previous studies we have found an enlargement of the intact visual field following vision restoration therapy (VRT). In the present pilot study, we wished to determine whether a double-stimulation approach would facilitate visual field enlargements beyond those achieved by the single-stimulus paradigm used in standard VRT. This was motivated by the findings that following visual cortex injury in animals, the size of receptive fields could be enlarged by systematic costimulation, where two stimuli were used to excite visual cortex neurons (Eysel, Eyding, & Schweigart, 1998). Patients (n = 23) with stable homonymous field deficits after trauma, cerebral ischemia, or hemorrhage (lesion age > 6 months) carried out either (a) standard VRT with a single stimulation (n = 9), or vision therapy with (b) a parallel costimulation (n = 7) or (c) a moving costimulation paradigm (n = 7). Training was carried out twice daily for 30 min over a 3-month period. Before and after therapy, visual fields were tested with 30 degrees and 90 degrees Tübinger automatic perimetry (TAP) and with high-resolution perimetry (HRP). Eye movements were recorded with an eye tracking system. When data of all three types of visual field training were pooled, we found significant improvements of stimulus detection in HRP (4.2%) and fewer misses within the central 30 degrees perimetrically (-3.7% right eye, OD, or -4.4% left eye, OS). However, the type of training did not make any difference such that the three training groups profited equally. A more detailed analysis of trained versus untrained visual field areas in 16 patients revealed a superiority of the trained area of only 1.1% in HRP and between 3.5% (OS) and 4.4% (OD) in TAP. Spatial attention and alertness improved significantly in all three groups and correlated significantly with visual field enlargements. While vision training had no influence on the patient's testimonials concerning their visual abilities, the patients significantly improved in a practical paper-and-pencil number tracking task (Zahlen-Verbindungs Test; ZVT). Visual field enlargement does not benefit from a double-stimulation paradigm, but visual attention seems to play an important role in vision restoration. The improvements in trained as well as in untrained areas are explained by top-down attentional control mechanisms interacting with local visual cortex plasticity.

  6. Imaging Fractures Through Relative Velocity Change Using Ambient Seismic Noise And Distributed Acoustic Sensing (DAS): A SUBTER Pilot Study At Blue Canyon Dome, Socorro NM

    NASA Astrophysics Data System (ADS)

    James, S. R.; Knox, H. A.; Ajo Franklin, J. B.; Johnson, T. C.; Morris, J.; Grubelich, M. C.; King, D. K.

    2016-12-01

    Knowledge of fracture systems, including locations, morphology, and evolution, is critical for groundwater management, contaminant transport, and energy applications such as reservoir development (i.e. tight shale and geothermal) and reservoir management (i.e. carbon sequestration and wastewater injection). It has long been understood that the presence of fractures reduces bulk seismic velocity, with waves traveling perpendicular to fracture planes experiencing the strongest velocity reduction. We present results from seismic interferometry using ambient seismic noise to detect velocity changes following fracture emplacement from two energetic stimulations. Distributed Acoustic Sensing (DAS) using fiber optic cables was used to record seismic arrivals at high spatial resolution ( 3 ft). Cables were grouted in the annulus of four cased monitoring boreholes surrounding the stimulation borehole at a radius of 4 feet. Ambient noise was recorded before and after each stimulation for 12-hour time periods. We used the Python package MSNoise to compute cross-correlations of all near-horizontal (less than 60°) channel pairs between boreholes and calculated the velocity change of each time period relative to initial conditions prior to stimulation. Results show an average velocity decrease of approximately 6% following the first fracturing event. Variations between channel pairs suggest some are more strongly affected than others, which is supported by evaluation of other geophysical data. These results show promise for locating fractures based on spatial variation in velocity changes. Unsurprisingly, results following the second stimulation are generally more scattered. Some velocities are further reduced compared to those after the first stimulation while others show a relative velocity increase. These results are roughly consistent with time-lapse seismic measurements conducted using active sources and classical sensors (e.g. hydrophones). Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

  7. Reduced mastication stimulates impairment of spatial memory and degeneration of hippocampal neurons in aged SAMP8 mice.

    PubMed

    Onozuka, M; Watanabe, K; Mirbod, S M; Ozono, S; Nishiyama, K; Karasawa, N; Nagatsu, I

    1999-04-24

    The involvement of reduced mastication in senile dementia was evaluated by examining the effect of cutting off the upper molars (molarless) on spatial memory and numbers of hippocampal neurons in aged SAMP8 mice. Molarless mice showed a decrease in both learning ability in a water maze and neuron density in the hippocampal CA1 region compared with control mice. These changes increased the longer the molarless condition persisted. The data suggest a possible link between reduced mastication and hippocampal neuron loss that may be one risk factor for senile impairment of spatial memory. Copyright 1999 Elsevier Science B.V.

  8. Focal clonus elicited by electrical stimulation of the motor cortex in humans.

    PubMed

    Hamer, Hajo M; Lüders, Hans O; Rosenow, Felix; Najm, Imad

    2002-09-01

    Focal clonic seizures are a frequent epileptic phenomenon. However, there are little data about their pathomechanism. In four patients with focal epilepsy and subdural electrodes, focal clonus was elicited by electrical stimulation of the motor cortex. Three additional patients underwent intraoperative stimulation of the spinal cord. Rhythmic clonic muscle responses were elicited by cortical stimulation with 20-50 Hz. The clonus consisted of simultaneous trains of compound muscle action potentials (CMAP) in agonistic and antagonistic muscles alternating with periods of muscular silence despite continuous stimulation. Clonus frequency decreased from 4.0-8.0 Hz at 50 Hz stimulation to 3.0-3.5 Hz at 20 Hz paralleled by a prolongation of the trains of CMAP. The stimulation frequency correlated with the number of stimuli blocked during relaxation. During the stable stimulation periods, the clonus frequency decreased over time. The number of stimuli which formed a train of CMAP and which were blocked during relaxation increased towards the end of the stimulation periods. Increasing intensity of stimulation at the same frequency converted a clonic to a tonic response. There was always an 1:1 relationship between stimulus and CMAP during spinal cord stimulation. We hypothesize that during cortical stimulation, clonus is elicited by synchronous activation of pyramidal tract (PT) neurons which results in excitation of intracortical GABA(B)ergic interneurons by recurrent axon-collaterals. This leads to stepwise hyperpolarization of PT neurons intermittently suppressing the output of PT neurons despite continuous stimulation. This mechanism can explain our finding that temporal and spatial summation of the stimuli were needed for clonus generation. Copyright 2002 Elsevier Science B.V.

  9. Synergistic effect of combined transcranial direct current stimulation/constraint-induced movement therapy in children and young adults with hemiparesis: study protocol.

    PubMed

    Gillick, Bernadette; Menk, Jeremiah; Mueller, Bryon; Meekins, Gregg; Krach, Linda E; Feyma, Timothy; Rudser, Kyle

    2015-11-12

    Perinatal stroke occurs in more than 1 in 2,500 live births and resultant congenital hemiparesis necessitates investigation into interventions which may improve long-term function and decreased burden of care beyond current therapies ( http://www.cdc.gov/ncbddd/cp/data.html ). Constraint-Induced Movement Therapy (CIMT) is recognized as an effective hemiparesis rehabilitation intervention. Transcranial direct current stimulation as an adjunct treatment to CIMT may potentiate neuroplastic responses and improve motor function. The methodology of a clinical trial in children designed as a placebo-controlled, serial -session, non-invasive brain stimulation trial incorporating CIMT is described here. The primary hypotheses are 1) that no serious adverse events will occur in children receiving non-invasive brain stimulation and 2) that children in the stimulation intervention group will show significant improvements in hand motor function compared to children in the placebo stimulation control group. A randomized, controlled, double-blinded clinical trial. Twenty children and/or young adults (ages 8-21) with congenital hemiparesis, will be enrolled. The intervention group will receive ten 2-hour sessions of transcranial direct current stimulation combined with constraint-induced movement therapy and the control group will receive sham stimulation with CIMT. The primary outcome measure is safety assessment of transcranial direct current stimulation by physician evaluation, vital sign monitoring and symptom reports. Additionally, hand function will be evaluated using the Assisting Hand Assessment, grip strength and assessment of goals using the Canadian Occupational Performance Measure. Neuroimaging will confirm diagnoses, corticospinal tract integrity and cortical activation. Motor cortical excitability will also be examined using transcranial magnetic stimulation techniques. Combining non-invasive brain stimulation and CIMT interventions has the potential to improve motor function in children with congenital hemiparesis beyond each intervention independently. Such a combined intervention has the potential to benefit an individual throughout their lifetime. Clinicaltrials.gov, NCT02250092 Registered 18 September 2014.

  10. Enhanced control of electrochemical response in metallic materials in neural stimulation electrode applications

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Watkins, K.G.; Steen, W.M.; Manna, I.

    New means have been investigated for the production of electrode devices (stimulation electrodes) which could be implanted in the human body in order to control pain, activate paralysed limbs or provide electrode arrays for cochlear implants for the deaf or for the relief of tinitus. To achieve this ion implantation and laser materials processing techniques were employed. Ir was ion implanted in Ti-6Al-4V alloy and the surface subsequently enriched in the noble metal by dissolution in sulphuric acid. For laser materials processing techniques, investigation has been carried out on the laser cladding and laser alloying of Ir in Ti wire.more » A particular aim has been the determination of conditions required for the formation of a two phase Ir, Ir-rich, and Ti-rich microstructure which would enable subsequent removal of the non-noble phase to leave a highly porous noble metal with large real surface area and hence improved charge carrying capacity compared with conventional non porous electrodes. Evaluation of the materials produced has been carried out using repetitive cyclic voltammetry, amongst other techniques. For laser alloyed Ir on Ti wire, it has been found that differences in the melting point and density of the materials makes control of the cladding or alloying process difficult. Investigation of laser process parameters for the control of alloying and cladding in this system was carried out and a set of conditions for the successful production of two phase Ir-rich and Ti-rich components in a coating layer with strong metallurgical bonding to the Ti alloy substrate was derived. The laser processed material displays excellent potential for further development in providing stimulation electrodes with the current carrying capacity of Ir but in a form which is malleable and hence capable of formation into smaller electrodes with improved spatial resolution compared with presently employed electrodes.« less

  11. Therapeutic Effects of Caloric Stimulation and Optokinetic Stimulation on Hemispatial Neglect

    PubMed Central

    Moon, SY; Lee, BH

    2006-01-01

    Hemispatial neglect refers to a cognitive disorder in which patients with unilateral brain injury cannot recognize or respond to stimuli located in the contralesional hemispace. Hemispatial neglect in stroke patients is an important predictor for poor functional outcome. Therefore, there is a need for effective treatment for this condition. A number of interventions for hemispatial neglect have been proposed, although an approach resulting in persistent improvement is not available. Of these interventions, our review is focused on caloric stimulation and optokinetic stimulation. These lateralized or direction-specific stimulations of peripheral sensory systems can temporarily improve hemispatial neglect. According to recent functional MRI and PET studies, this improvement might result from the partial (re)activation of a distributed, multisensory vestibular network in the lesioned hemisphere, which is a part of a system that codes ego-centered space. However, much remain unknown regarding exact signal timing and directional selectivity of the network. PMID:20396481

  12. A sensorimotor stimulation program for rehabilitation of chronic stroke patients.

    PubMed

    de Diego, Cristina; Puig, Silvia; Navarro, Xavier

    2013-01-01

    The hypothesis of this study is that intensive therapy by means of a sensory and motor stimulation program of the upper limb in patients with chronic hemiparesis and severe disability due to stroke increases mobility and sensibility, and improves the use of the affected limb in activities of daily living (ADL). The program consists of 16 sessions of sensory stimulation and functional activity training in the rehabilitation center, and daily sessions of tactile stimulation, mental imaginery and practice of ADL at home, during 8 weeks. An experimental group (EG) of 12 patients followed this program, compared with a control group (CG) of 9 patients under standard rehabilitation. The efficacy of the program was evaluated by Fugl Meyer Assessment (FMA), Motor Activity Log (MAL) and Stroke Impact Scale-16 (SIS-16) scores, and a battery of sensory tests. The results show that in both groups, the motor FMA and the SIS-16 improved during the 8 weeks, this improvement being higher in the EG. Significant improvements were observed for the sensory tests in the EG. The intensive sensorimotor stimulation program for the upper extremity may be an efficacious method for improving function and use of the affected limb in ADL in chronic stroke patients.

  13. Memory improvement via slow-oscillatory stimulation during sleep in older adults.

    PubMed

    Westerberg, Carmen E; Florczak, Susan M; Weintraub, Sandra; Mesulam, M-Marsel; Marshall, Lisa; Zee, Phyllis C; Paller, Ken A

    2015-09-01

    We examined the intriguing but controversial idea that disrupted sleep-dependent consolidation contributes to age-related memory decline. Slow-wave activity during sleep may help strengthen neural connections and provide memories with long-term stability, in which case decreased slow-wave activity in older adults could contribute to their weaker memories. One prediction from this account is that age-related memory deficits should be reduced by artificially enhancing slow-wave activity. In young adults, applying transcranial current oscillating at a slow frequency (0.75 Hz) during sleep improves memory. Here, we tested whether this procedure can improve memory in older adults. In 2 sessions separated by 1 week, we applied either slow-oscillatory stimulation or sham stimulation during an afternoon nap in a double-blind, crossover design. Memory tests were administered before and after sleep. A larger improvement in word-pair recall and higher slow-wave activity was observed with slow-oscillatory stimulation than with sham stimulation. This is the first demonstration that this procedure can improve memory in older adults, suggesting that declarative memory performance in older adults is partly dependent on slow-wave activity during sleep. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Stridor and dysphagia associated with subthalamic nucleus stimulation in Parkinson disease.

    PubMed

    Fagbami, Oluwakemi Y; Donato, Anthony A

    2011-11-01

    Refractory symptoms in Parkinson disease show good response to deep brain stimulation (DBS). This procedure improves United Parkinson's Disease Rating Scale scores and reduces dyskinesias, whereas speech and swallowing dysfunction typically do not improve and may even worsen. Rarely, DBS can cause idiosyncratic dystonias of muscle groups, including those of the neck and throat. The authors describe a patient experiencing stridor and dysphagia with confirmed pulmonary restriction and aspiration following subthalamic nucleus deep brain stimulator adjustment, with a resolution of symptoms and signs when the stimulator was switched off.

  15. Adaptive deep brain stimulation in advanced Parkinson disease.

    PubMed

    Little, Simon; Pogosyan, Alex; Neal, Spencer; Zavala, Baltazar; Zrinzo, Ludvic; Hariz, Marwan; Foltynie, Thomas; Limousin, Patricia; Ashkan, Keyoumars; FitzGerald, James; Green, Alexander L; Aziz, Tipu Z; Brown, Peter

    2013-09-01

    Brain-computer interfaces (BCIs) could potentially be used to interact with pathological brain signals to intervene and ameliorate their effects in disease states. Here, we provide proof-of-principle of this approach by using a BCI to interpret pathological brain activity in patients with advanced Parkinson disease (PD) and to use this feedback to control when therapeutic deep brain stimulation (DBS) is delivered. Our goal was to demonstrate that by personalizing and optimizing stimulation in real time, we could improve on both the efficacy and efficiency of conventional continuous DBS. We tested BCI-controlled adaptive DBS (aDBS) of the subthalamic nucleus in 8 PD patients. Feedback was provided by processing of the local field potentials recorded directly from the stimulation electrodes. The results were compared to no stimulation, conventional continuous stimulation (cDBS), and random intermittent stimulation. Both unblinded and blinded clinical assessments of motor effect were performed using the Unified Parkinson's Disease Rating Scale. Motor scores improved by 66% (unblinded) and 50% (blinded) during aDBS, which were 29% (p = 0.03) and 27% (p = 0.005) better than cDBS, respectively. These improvements were achieved with a 56% reduction in stimulation time compared to cDBS, and a corresponding reduction in energy requirements (p < 0.001). aDBS was also more effective than no stimulation and random intermittent stimulation. BCI-controlled DBS is tractable and can be more efficient and efficacious than conventional continuous neuromodulation for PD. Copyright © 2013 American Neurological Association.

  16. Did I Do That? Expectancy Effects of Brain Stimulation on Error-related Negativity and Sense of Agency.

    PubMed

    Hoogeveen, Suzanne; Schjoedt, Uffe; van Elk, Michiel

    2018-06-19

    This study examines the effects of expected transcranial stimulation on the error(-related) negativity (Ne or ERN) and the sense of agency in participants who perform a cognitive control task. Placebo transcranial direct current stimulation was used to elicit expectations of transcranially induced cognitive improvement or impairment. The improvement/impairment manipulation affected both the Ne/ERN and the sense of agency (i.e., whether participants attributed errors to oneself or the brain stimulation device): Expected improvement increased the ERN in response to errors compared with both impairment and control conditions. Expected impairment made participants falsely attribute errors to the transcranial stimulation. This decrease in sense of agency was correlated with a reduced ERN amplitude. These results show that expectations about transcranial stimulation impact users' neural response to self-generated errors and the attribution of responsibility-especially when actions lead to negative outcomes. We discuss our findings in relation to predictive processing theory according to which the effect of prior expectations on the ERN reflects the brain's attempt to generate predictive models of incoming information. By demonstrating that induced expectations about transcranial stimulation can have effects at a neural level, that is, beyond mere demand characteristics, our findings highlight the potential for placebo brain stimulation as a promising tool for research.

  17. Anodal tDCS to V1 blocks visual perceptual learning consolidation.

    PubMed

    Peters, Megan A K; Thompson, Benjamin; Merabet, Lotfi B; Wu, Allan D; Shams, Ladan

    2013-06-01

    This study examined the effects of visual cortex transcranial direct current stimulation (tDCS) on visual processing and learning. Participants performed a contrast detection task on two consecutive days. Each session consisted of a baseline measurement followed by measurements made during active or sham stimulation. On the first day, one group received anodal stimulation to primary visual cortex (V1), while another received cathodal stimulation. Stimulation polarity was reversed for these groups on the second day. The third (control) group of subjects received sham stimulation on both days. No improvements or decrements in contrast sensitivity relative to the same-day baseline were observed during real tDCS, nor was any within-session learning trend observed. However, task performance improved significantly from Day 1 to Day 2 for the participants who received cathodal tDCS on Day 1 and for the sham group. No such improvement was found for the participants who received anodal stimulation on Day 1, indicating that anodal tDCS blocked overnight consolidation of visual learning, perhaps through engagement of inhibitory homeostatic plasticity mechanisms or alteration of the signal-to-noise ratio within stimulated cortex. These results show that applying tDCS to the visual cortex can modify consolidation of visual learning. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. An independent brain-computer interface using covert non-spatial visual selective attention

    NASA Astrophysics Data System (ADS)

    Zhang, Dan; Maye, Alexander; Gao, Xiaorong; Hong, Bo; Engel, Andreas K.; Gao, Shangkai

    2010-02-01

    In this paper, a novel independent brain-computer interface (BCI) system based on covert non-spatial visual selective attention of two superimposed illusory surfaces is described. Perception of two superimposed surfaces was induced by two sets of dots with different colors rotating in opposite directions. The surfaces flickered at different frequencies and elicited distinguishable steady-state visual evoked potentials (SSVEPs) over parietal and occipital areas of the brain. By selectively attending to one of the two surfaces, the SSVEP amplitude at the corresponding frequency was enhanced. An online BCI system utilizing the attentional modulation of SSVEP was implemented and a 3-day online training program with healthy subjects was carried out. The study was conducted with Chinese subjects at Tsinghua University, and German subjects at University Medical Center Hamburg-Eppendorf (UKE) using identical stimulation software and equivalent technical setup. A general improvement of control accuracy with training was observed in 8 out of 18 subjects. An averaged online classification accuracy of 72.6 ± 16.1% was achieved on the last training day. The system renders SSVEP-based BCI paradigms possible for paralyzed patients with substantial head or ocular motor impairments by employing covert attention shifts instead of changing gaze direction.

  19. High wall shear stress and spatial gradients in vascular pathology: a review.

    PubMed

    Dolan, Jennifer M; Kolega, John; Meng, Hui

    2013-07-01

    Cardiovascular pathologies such as intracranial aneurysms (IAs) and atherosclerosis preferentially localize to bifurcations and curvatures where hemodynamics are complex. While extensive knowledge about low wall shear stress (WSS) has been generated in the past, due to its strong relevance to atherogenesis, high WSS (typically >3 Pa) has emerged as a key regulator of vascular biology and pathology as well, receiving renewed interests. As reviewed here, chronic high WSS not only stimulates adaptive outward remodeling, but also contributes to saccular IA formation (at bifurcation apices or outer curves) and atherosclerotic plaque destabilization (in stenosed vessels). Recent advances in understanding IA pathogenesis have shed new light on the role of high WSS in pathological vascular remodeling. In complex geometries, high WSS can couple with significant spatial WSS gradient (WSSG). A combination of high WSS and positive WSSG has been shown to trigger aneurysm initiation. Since endothelial cells (ECs) are sensors of WSS, we have begun to elucidate EC responses to high WSS alone and in combination with WSSG. Understanding such responses will provide insight into not only aneurysm formation, but also plaque destabilization and other vascular pathologies and potentially lead to improved strategies for disease management and novel targets for pharmacological intervention.

  20. An independent brain-computer interface using covert non-spatial visual selective attention.

    PubMed

    Zhang, Dan; Maye, Alexander; Gao, Xiaorong; Hong, Bo; Engel, Andreas K; Gao, Shangkai

    2010-02-01

    In this paper, a novel independent brain-computer interface (BCI) system based on covert non-spatial visual selective attention of two superimposed illusory surfaces is described. Perception of two superimposed surfaces was induced by two sets of dots with different colors rotating in opposite directions. The surfaces flickered at different frequencies and elicited distinguishable steady-state visual evoked potentials (SSVEPs) over parietal and occipital areas of the brain. By selectively attending to one of the two surfaces, the SSVEP amplitude at the corresponding frequency was enhanced. An online BCI system utilizing the attentional modulation of SSVEP was implemented and a 3-day online training program with healthy subjects was carried out. The study was conducted with Chinese subjects at Tsinghua University, and German subjects at University Medical Center Hamburg-Eppendorf (UKE) using identical stimulation software and equivalent technical setup. A general improvement of control accuracy with training was observed in 8 out of 18 subjects. An averaged online classification accuracy of 72.6 +/- 16.1% was achieved on the last training day. The system renders SSVEP-based BCI paradigms possible for paralyzed patients with substantial head or ocular motor impairments by employing covert attention shifts instead of changing gaze direction.

  1. How do I provide leukapheresis products? Blood center experience and evidence for process improvement.

    PubMed

    Ginzburg, Yelena; Kessler, Debra; Narici, Manlio; Caltabiano, Melinda; Rebosa, Mark; Strauss, Donna; Shaz, Beth

    2013-10-01

    The past few decades have seen a resurgence of interest in leukapheresis products to improve the survival of infected patients with neutropenia. These products have a short shelf life and require donor stimulation with dexamethasone before collection. Additionally, a system with good communications and logistical support is essential. A recent survey of blood centers in North America revealed that the majority of centers collecting leukapheresis products use steroid-stimulated donors. The survey results suggested that an analysis of the process and potential process improvement would be of interest to the transfusion medicine community. Data from 2008 to 2011 regarding donor selection, donor dexamethasone stimulation, leukapheresis collection, and correlations between potentially pertinent variables for process improvement were analyzed. Results from an analysis of cost are also included. We evaluate 432 leukapheresis donations and demonstrate correlations between 1) pre- and poststimulation white blood cell (WBC) count (p<0.0001), 2) interval (donor stimulation to collection) and poststimulation WBC count (p<0.0001), and 3) poststimulation WBC count and leukapheresis product granulocyte yield (p<0.0001). Significant improvement in granulocyte quality and yield can be accomplished in dexamethasone-stimulated donors, by selecting eligible donors with relatively high normal prestimulation WBC counts and/or previously good responses to dexamethasone, increasing the duration between dexamethasone stimulation and granulocyte collection, and maintaining optimal hematocrit (5%-10%) in granulocyte collections. Because the majority of surveyed blood centers collecting stimulated granulocytes use steroids alone, modifications presented here may prove useful. Further assessment of correlation between granulocyte yield and clinical outcome will await results of additional studies. © 2012 American Association of Blood Banks.

  2. New possibilities of improving the function of the hand of patients with spastic hemiplegia.

    PubMed

    Kiwerski, J

    1984-01-01

    The report presents a therapeutic proposal aiming at the improvement of the functions of the paretic hand in spastic hemiplegics. To achieve this aim the author suggests a combination of phenolization of the medial and ulnar nerves and the stimulation training of the wrist and fingers extensors. An implanted stimulator is used; the stimulator electrodes are fixed to the radial nerve. The strengthening of the extensors during the period of increased muscular tension of the flexors makes it possible to improve the functions of the paretic upper extremity.

  3. Acute effects of unilateral whole body vibration training on single leg vertical jump height and symmetry in healthy men.

    PubMed

    Shin, Seungho; Lee, Kyeongjin; Song, Changho

    2015-12-01

    [Purpose] The aim of the present study was to investigate the acute effects of unilateral whole body vibration training on height and symmetry of the single leg vertical jump in healthy men. [Subjects] Thirty males with no history of lower limb dysfunction participated in this study. [Methods] The participants were randomly allocated to one of three groups: the unilateral vibratory stimulation group (n=10), bilateral vibratory stimulation group (n=10), and, no vibratory stimulation group (n=10). The subjects in the unilateral and bilateral stimulation groups participated in one session of whole body vibration training at 26 Hz for 3 min. The no vibratory stimulation group subjects underwent the same training for 3 min without whole body vibration. All participants performed the single leg vertical jump for each lower limb, to account for the strong and weak sides. The single leg vertical jump height and symmetry were measured before and after the intervention. [Results] The single leg vertical jump height of the weak lower limb significantly improved in the unilateral vibratory stimulation group, but not in the other groups. The single leg vertical jump height of the strong lower limb significantly improved in the bilateral vibratory stimulation group, but not in the other groups. The single leg vertical jump symmetry significantly improved in the unilateral vibratory stimulation group, but not in the other groups. [Conclusion] Therefore, the present study found that the effects of whole body vibration training were different depending on the type of application. To improve the single leg vertical jump height in the weak lower limbs as well as limb symmetry, unilateral vibratory stimulation might be more desirable.

  4. Network-targeted cerebellar transcranial magnetic stimulation improves attentional control

    PubMed Central

    Esterman, Michael; Thai, Michelle; Okabe, Hidefusa; DeGutis, Joseph; Saad, Elyana; Laganiere, Simon E.; Halko, Mark A.

    2018-01-01

    Developing non-invasive brain stimulation interventions to improve attentional control is extremely relevant to a variety of neurologic and psychiatric populations, yet few studies have identified reliable biomarkers that can be readily modified to improve attentional control. One potential biomarker of attention is functional connectivity in the core cortical network supporting attention - the dorsal attention network (DAN). We used a network-targeted cerebellar transcranial magnetic stimulation (TMS) procedure, intended to enhance cortical functional connectivity in the DAN. Specifically, in healthy young adults we administered intermittent theta burst TMS (iTBS) to the midline cerebellar node of the DAN and, as a control, the right cerebellar node of the default mode network (DMN). These cerebellar targets were localized using individual resting-state fMRI scans. Participants completed assessments of both sustained (gradual onset continuous performance task, gradCPT) and transient attentional control (attentional blink) immediately before and after stimulation, in two sessions (cerebellar DAN and DMN). Following cerebellar DAN stimulation, participants had significantly fewer attentional lapses (lower commission error rates) on the gradCPT. In contrast, stimulation to the cerebellar DMN did not affect gradCPT performance. Further, in the DAN condition, individuals with worse baseline gradCPT performance showed the greatest enhancement in gradCPT performance. These results suggest that temporarily increasing functional connectivity in the DAN via network-targeted cerebellar stimulation can enhance sustained attention, particularly in those with poor baseline performance. With regard to transient attention, TMS stimulation improved attentional blink performance across both stimulation sites, suggesting increasing functional connectivity in both networks can enhance this aspect of attention. These findings have important implications for intervention applications of TMS and theoretical models of functional connectivity. PMID:28495634

  5. Interference effects of transcranial direct current stimulation over the right frontal cortex and adrenergic system on conditioned fear.

    PubMed

    Nasehi, Mohammad; Soltanpour, Reyhaneh; Ebrahimi-Ghiri, Mohaddeseh; Zarrabian, Shahram; Zarrindast, Mohammad-Reza

    2017-11-01

    The effects of pharmacological interventions on fear memory have widely been studied, but there are very few studies about the effects of brain electrical stimulation on fear memory function. Therefore, our aim was to determine whether anodal/cathodal transcranial direct current stimulation (tDCS) over the right frontal cortex would modify propranolol-induced contextual and auditory fear memory deficits, before or after training. The adult NMRI male mice were randomly assigned into three groups: the sham group, the anodal tDCS group, and the cathodal tDCS group. Fear memories were evaluated using a classical fear conditioning apparatus. While the anodal stimulation did not affect fear retrieval, post-training cathodal stimulation improved fear memory retrieval. Regardless of when propranolol (0.1 mg/kg) was administered, it impaired fear memory retrieval. However, when anodal stimulation and propranolol were applied prior to the training, contextual fear memory retrieval was increased and auditory fear memory was reversed. An enhanced contextual retrieval was also observed when propranolol was administered prior to the training and stimulation occurred after the training. Only when the stimulation occurred prior to the training and propranolol was administered after the training was there a selective improvement in contextual fear memory retrieval, leaving the auditory fear memory retrieval impaired. Interestingly, cathodal stimulation improved the effects of propranolol on auditory fear memory only when it occurred prior to the training. The results highlight possible improving effects for anodal/cathodal tDCS on propranolol-induced deficits on fear memories. The timing of the interventions related to the specific phases of memory formation is important in modulating fear behaviors.

  6. Stuttering in Parkinson's disease after deep brain stimulation: A note on dystonia and low-frequency stimulation.

    PubMed

    Mendonça, Marcelo D; Barbosa, Raquel; Seromenho-Santos, Alexandra; Reizinho, Carla; Bugalho, Paulo

    2018-04-01

    Stuttering, a speech fluency disorder, is a rare complication of Deep Brain Stimulation (DBS) in Parkinson's Disease (PD). We report a 61 years-old patient with PD, afflicted by severe On and Off dystonia, treated with Subthalamic Nucleus DBS that developed post-DBS stuttering while on 130 Hz stimulation. Stuttering reduction was noted when frequency was changed to 80 Hz, but the previously observed dystonia improvement was lost. There are no reports in literature on patients developing stuttering with low-frequency stimulation. We question if low-frequency stimulation could have a role for managing PD's post-DBS stuttering, and notice that stuttering improvement was associated with dystonia worsening suggesting that they are distinct phenomena. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Cerebellar contribution to mental rotation: a cTBS study.

    PubMed

    Picazio, Silvia; Oliveri, Massimiliano; Koch, Giacomo; Caltagirone, Carlo; Petrosini, Laura

    2013-12-01

    A cerebellar role in spatial information processing has been advanced even in the absence of physical manipulation, as occurring in mental rotation. The present study was aimed at investigating the specific involvement of left and right cerebellar hemispheres in two tasks of mental rotation. We used continuous theta burst stimulation to downregulate cerebellar hemisphere excitability in healthy adult subjects performing two mental rotation tasks: an Embodied Mental Rotation (EMR) task, entailing an egocentric strategy, and an Abstract Mental Rotation (AMR) task entailing an allocentric strategy. Following downregulation of left cerebellar hemisphere, reaction times were slower in comparison to sham stimulation in both EMR and AMR tasks. Conversely, identical reaction times were obtained in both tasks following right cerebellar hemisphere and sham stimulations. No effect of cerebellar stimulation side was found on response accuracy. The present findings document a specialization of the left cerebellar hemisphere in mental rotation regardless of the kind of stimulus to be rotated.

  8. Natural stimulation of the nonclassical receptive field increases information transmission efficiency in V1.

    PubMed

    Vinje, William E; Gallant, Jack L

    2002-04-01

    We have investigated how the nonclassical receptive field (nCRF) affects information transmission by V1 neurons during simulated natural vision in awake, behaving macaques. Stimuli were centered over the classical receptive field (CRF) and stimulus size was varied from one to four times the diameter of the CRF. Stimulus movies reproduced the spatial and temporal stimulus dynamics of natural vision while maintaining constant CRF stimulation across all sizes. In individual neurons, stimulation of the nCRF significantly increases the information rate, the information per spike, and the efficiency of information transmission. Furthermore, the population averages of these quantities also increase significantly with nCRF stimulation. These data demonstrate that the nCRF increases the sparseness of the stimulus representation in V1, suggesting that the nCRF tunes V1 neurons to match the highly informative components of the natural world.

  9. The Effect of Electrical Stimulation in Improving Muscle Tone (Clinical)

    NASA Astrophysics Data System (ADS)

    Azman, M. F.; Azman, A. W.

    2017-11-01

    Electrical stimulation (ES) and also known as neuromuscular electrical stimulation (NMES) and transcutaneous electrical stimulation (TES) involves the use of electrical current to stimulate the nerves or nerve endings that innervate muscle beneath the skin. Electrical stimulation may be applied superficially on the skin (transcutaneously) or directly into a muscle or muscles (intramuscularly) for the primary purpose of enhancing muscle function. The basic theoretical premise is that if the peripheral nerve can be stimulated, the resulting excitation impulse will be transmitted along the nerve to the motor endplates in the muscle, producing a muscle contraction. In this work, the effect of mere electrical stimulation to the muscle bulk and strength are tested. This paper explains how electrical stimulation can affect the muscle bulk, muscle size, muscle tone, muscle atrophy and muscle strength. The experiment and data collection are performed on 5 subjects and the results obtained are analyzed. This research aims to understand the full potential of electrical stimulation and identifying its possible benefits or disadvantages to the muscle properties. The results indicated that electrical stimulation alone able to improve muscle properties but with certain limits and precautions which might be useful in rehabilitation programme.

  10. Combination of Transcranial Direct Current Stimulation and Neuromuscular Electrical Stimulation Improves Gait Ability in a Patient in Chronic Stage of Stroke.

    PubMed

    Satow, Takeshi; Kawase, Tomotaka; Kitamura, Atsushi; Kajitani, Yuki; Yamaguchi, Takuya; Tanabe, Nobuhiko; Otoi, Reiko; Komuro, Taro; Kobayashi, Akira; Nagata, Hirokazu; Mima, Tatsuya

    2016-01-01

    Walking ability is important in stroke patients to maintain daily life. Nevertheless, its improvement is limited with conventional physical therapy in chronic stage. We report the case of a chronic stroke patient showing a remarkable improvement in gait function after a new neurorehabilitation protocol using transcranial direct current stimulation (tDCS) and neuromuscular electrical stimulation (NMES). A 62-year-old male with left putaminal hemorrhage suffered from severe right hemiparesis. He could move by himself with a wheelchair 1 year after the ictus. Anodal tDCS at the vertex (2 mA, 20 min) with NMES at the anterior tibialis muscle had been applied for 3 weeks. The Timed Up and Go test and 10-meter walk test improved after the intervention, which had been maintained for at least 1 month. This single case suggests the possibility that tDCS with NMES could be a new rehabilitation approach to improve the gait ability in chronic stroke patients.

  11. Improved field localization in transcranial magnetic stimulation of the brain with the utilization of a conductive shield plate in the stimulator.

    PubMed

    Kim, Dong-Hun; Georghiou, George E; Won, Chulho

    2006-04-01

    In this paper, a carefully designed conductive shield plate is presented, which helps to improve localization of the electric field distribution induced by transcranial magnetic stimulation for neuron stimulation. The shield plate is introduced between a figure-of-eight coil and the head. In order to accurately predict the field distribution inside the brain and to examine the effects of the shield plate, a realistic head model is constructed from magnetic resonance image data with the help of image processing tools and the finite-element method in three dimensions is employed. Finally, to show the improvements obtained, the results are compared with two conventional coil designs. It is found that an incorporation of the shield plate into the coil, effectively improves the induced field localization by more than 50%, and prevents other parts of the brain from exposure to high pulsed magnetic fields.

  12. Effects of Sensory Modality Stimulation on the Dysarthria of Cerebral Palsy.

    ERIC Educational Resources Information Center

    Love, Russel J.

    To explore the efficacy of improving the dysarthria of cerebral palsy under conditions of aural stimulation, visual stimulation, and combined aural-visual stimulation, 22 subjects (aged 7.6 to 19.0 years) received intensive stimulation for word limitation for 22 consecutive school days. The 87 words of the Irwin Integrated Articulation Test were…

  13. [Supportive amblyopia treatment by means of computer games with background stimulation; a placebo controlled pilot study of 10 days].

    PubMed

    Kämpf, U; Muchamedjarow, F; Seiler, T

    2001-04-01

    Computer programmes for visual stimulation may give new impulses to the field of amblyopia treatment by offering an option to shift the apparative visual training into the domestic sphere. Regarding this aspect we report on a placebo controlled study on a newly developed vision training consisting of a background stimulation by a drifting sinusoidal grating combined with a foreground game aimed to maintain the attention. Fourteen amblyopia patients aged from 6 to 13 years participated in the study. Seven were allocated to a placebo and seven to a treatment group. Both groups had to train at the computer for a period of 10 working days by two sessions of about 20 minutes daily. Whilst the placebo group played in front of a neutral background, the treatment group did this with a drifting sinusoidal grating in the background. The treatment condition resulted in a greater increase of visual acuity than the placebo condition. Near vision improved in the treatment group from 0.20 (SD +/- 4.51 steps) to 0.39 (SD +/- 3.06 steps), i.e. by 3.0 steps of visual acuity (SD +/- 1.8 steps), in the placebo group from 0.14 (SD +/- 6.02 steps) to 0.17 (SD +/- 5.85 steps), i.e. by 0.8 steps of visual acuity (SD +/- 1.6 steps). Far vision improved in the treatment group from 0.29 (SD +/- 2.57 steps) to 0.44 (SD +/- 3.16 steps), i.e. by 1.9 steps of visual acuity (SD +/- 1.3 steps), in the placebo group from 0.24 (SD +/- 5.20 steps) to 0.28 (SD +/- 5.51 steps), i.e. by 0.7 steps of visual acuity (SD +/- 1.1 steps). Stimulation with drifting sinusoidal gratings improves the visual acuity of amblyopic eyes in a specific way. The effect might be accounted for by a synergy of spatial and temporal frequency in form vs. motion channels. A preliminary hypothesis is discussed and will be the subject of ongoing research. The presented method has been developed for the treatment of "delayed" amblyopia in the elder child. It is aimed to support and complement occlusion therapy. However, the reported results obtained over 10 days should be estimated only within the context of evaluation. By no means should the results be interpreted as a renewed pledge for a short-term treatment of amblyopia.

  14. Mild cognitive impairment in Parkinson's disease is improved by transcranial direct current stimulation combined with physical therapy.

    PubMed

    Manenti, Rosa; Brambilla, Michela; Benussi, Alberto; Rosini, Sandra; Cobelli, Chiara; Ferrari, Clarissa; Petesi, Michela; Orizio, Italo; Padovani, Alessandro; Borroni, Barbara; Cotelli, Maria

    2016-05-01

    Parkinson's disease (PD) is characterized by both motor and cognitive deficits. In PD, physical exercise has been found to improve physical functioning. Recent studies demonstrated that repeated sessions of transcranial direct current stimulation led to an increased performance in cognitive and motor tasks in patients with PD. The present study investigated the effects of anodal transcranial direct current stimulation applied over the dorsolateral prefrontal cortex and combined with physical therapy in PD patients. A total of 20 patients with PD were assigned to 1 of 2 study groups: group 1, anodal transcranial direct current stimulation plus physical therapy (n = 10) or group 2, placebo transcranial direct current stimulation plus physical therapy (n = 10). The 2 weeks of treatment consisted of daily direct current stimulation application for 25 minutes during physical therapy. Long-term effects of treatment were evaluated on clinical, neuropsychological, and motor task performance at 3-month follow-up. An improvement in motor abilities and a reduction of depressive symptoms were observed in both groups after the end of treatment and at 3-month follow-up. The Parkinson's Disease Cognitive Rating Scale and verbal fluency test performances increased only in the anodal direct current stimulation group with a stable effect at follow-up. The application of anodal transcranial direct current stimulation may be a relevant tool to improve cognitive abilities in PD and might be a novel therapeutic strategy for PD patients with mild cognitive impairment. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

  15. Stimulated Brillouin scattering in the field of a two-dimensionally localized pumping wave

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Solikhov, D. K., E-mail: davlat56@mail.ru; Dvinin, S. A., E-mail: dvinin@phys.msu.ru

    2016-06-15

    Stimulated Brillouin scattering of electromagnetic waves in the field of a two-dimensionally localized pump wave at arbitrary scattering angles in the regime of forward scattering is analyzed. Spatial variations in the amplitudes of interacting waves are studied for different values of the pump field and different dimensions of the pump wave localization region. The intensity of scattered radiation is determined as a function of the scattering angle and the dimensions of the pump wave localization region. It is shown that the intensity increases with increasing scattering angle.

  16. A microprocessor-based multichannel subsensory stochastic resonance electrical stimulator.

    PubMed

    Chang, Gwo-Ching

    2013-01-01

    Stochastic resonance electrical stimulation is a novel intervention which provides potential benefits for improving postural control ability in the elderly, those with diabetic neuropathy, and stroke patients. In this paper, a microprocessor-based subsensory white noise electrical stimulator for the applications of stochastic resonance stimulation is developed. The proposed stimulator provides four independent programmable stimulation channels with constant-current output, possesses linear voltage-to-current relationship, and has two types of stimulation modes, pulse amplitude and width modulation.

  17. Interleaving subthalamic nucleus deep brain stimulation to avoid side effects while achieving satisfactory motor benefits in Parkinson disease: A report of 12 cases.

    PubMed

    Zhang, Shizhen; Zhou, Peizhi; Jiang, Shu; Wang, Wei; Li, Peng

    2016-12-01

    Deep brain stimulation (DBS) of the subthalamic nucleus is an effective treatment for advanced Parkinson disease (PD). However, achieving ideal outcomes by conventional programming can be difficult in some patients, resulting in suboptimal control of PD symptoms and stimulation-induced adverse effects. Interleaving stimulation (ILS) is a newer programming technique that can individually optimize the stimulation area, thereby improving control of PD symptoms while alleviating stimulation-induced side effects after conventional programming fails to achieve the desired results. We retrospectively reviewed PD patients who received DBS programming during the previous 4 years in our hospital. We collected clinical and demographic data from 12 patients who received ILS because of incomplete alleviation of PD symptoms or stimulation-induced adverse effects after conventional programming had proven ineffective or intolerable. Appropriate lead location was confirmed with postoperative reconstruction images. The rationale and clinical efficacy of ILS was analyzed. We divided our patients into 4 groups based on the following symptoms: stimulation-induced dysarthria and choreoathetoid dyskinesias, gait disturbance, and incomplete control of parkinsonism. After treatment with ILS, patients showed satisfactory improvement in PD symptoms and alleviation of stimulation-induced side effects, with a mean improvement in Unified PD Rating Scale motor scores of 26.9%. ILS is a newer choice and effective programming strategy to maximize symptom control in PD while decreasing stimulation-induced adverse effects when conventional programming fails to achieve satisfactory outcome. However, we should keep in mind that most DBS patients are routinely treated with conventional stimulation and that not all patients benefit from ILS. ILS is not recommended as the first choice of programming, and it is recommended only when patients have unsatisfactory control of PD symptoms or stimulation-induced side effects after multiple treatments with conventional stimulation. A return to conventional stimulation may be required if ILS induces new side effects or the needs of the patient change.

  18. Interleaving subthalamic nucleus deep brain stimulation to avoid side effects while achieving satisfactory motor benefits in Parkinson disease

    PubMed Central

    Zhang, Shizhen; Zhou, Peizhi; Jiang, Shu; Wang, Wei; Li, Peng

    2016-01-01

    Abstract Background: Deep brain stimulation (DBS) of the subthalamic nucleus is an effective treatment for advanced Parkinson disease (PD). However, achieving ideal outcomes by conventional programming can be difficult in some patients, resulting in suboptimal control of PD symptoms and stimulation-induced adverse effects. Interleaving stimulation (ILS) is a newer programming technique that can individually optimize the stimulation area, thereby improving control of PD symptoms while alleviating stimulation-induced side effects after conventional programming fails to achieve the desired results. Methods: We retrospectively reviewed PD patients who received DBS programming during the previous 4 years in our hospital. We collected clinical and demographic data from 12 patients who received ILS because of incomplete alleviation of PD symptoms or stimulation-induced adverse effects after conventional programming had proven ineffective or intolerable. Appropriate lead location was confirmed with postoperative reconstruction images. The rationale and clinical efficacy of ILS was analyzed. Results: We divided our patients into 4 groups based on the following symptoms: stimulation-induced dysarthria and choreoathetoid dyskinesias, gait disturbance, and incomplete control of parkinsonism. After treatment with ILS, patients showed satisfactory improvement in PD symptoms and alleviation of stimulation-induced side effects, with a mean improvement in Unified PD Rating Scale motor scores of 26.9%. Conclusions: ILS is a newer choice and effective programming strategy to maximize symptom control in PD while decreasing stimulation-induced adverse effects when conventional programming fails to achieve satisfactory outcome. However, we should keep in mind that most DBS patients are routinely treated with conventional stimulation and that not all patients benefit from ILS. ILS is not recommended as the first choice of programming, and it is recommended only when patients have unsatisfactory control of PD symptoms or stimulation-induced side effects after multiple treatments with conventional stimulation. A return to conventional stimulation may be required if ILS induces new side effects or the needs of the patient change. PMID:27930569

  19. Novel nootropic drug sunifiram improves cognitive deficits via CaM kinase II and protein kinase C activation in olfactory bulbectomized mice.

    PubMed

    Moriguchi, Shigeki; Tanaka, Tomoya; Tagashira, Hideaki; Narahashi, Toshio; Fukunaga, Kohji

    2013-04-01

    Alzheimer's disease (AD) shows degeneration of the cholinergic system in the medial septum, thereby eliciting down-regulation of the olfactory function in patients. We have previously reported that olfactory bulbectomized (OBX) mice show hippocampus-dependent memory impairment as assessed by memory-related behavioral tasks and hippocampal long-term potentiation (LTP). In the present study, we focused whether novel pyrrolidone nootropic drug sunifiram improves both memory impairment and depression observed in OBX mice. OBX mice were administered once a day for 7-12 days with sunifiram (0.01-1.0mg/kg p.o.) from 10 days after operation with or without gavestinel (10mg/kg i.p.), which is glycine-binding site inhibitor of N-methyl-d-aspartate receptor (NMDAR). The spatial reference memory assessed by Y-maze and short-term memory assessed by novel object recognition task were significantly improved by sunifiram treatment in OBX mice. Sunifiram also restored hippocampal LTP injured in OBX mice without treatment with gavestinel. By contrast, sunifiram treatment did not ameliorate the depressive behaviors assessed by tail suspension task in OBX mice. Notably, sunifiram treatment restored CaMKIIα (Thr-286) autophosphorylation and GluR1 (Ser-831) phosphorylation in the hippocampal CA1 region from OBX mice to the levels of control mice. Likewise, sunifiram treatment improved PKCα (Ser-657) autophosphorylation and NR1 (Ser-896) phosphorylation to the control levels. Stimulation of CaMKII and PKC autophosphorylation by sunifiram was significantly inhibited by pre-treatment with gavestinel. However, sunifiram treatment did not affect the phosphorylation of CaMKIV (Thr-196) and ERK. Taken together, sunifiram ameliorates OBX-induced deficits of memory-related behaviors and impaired LTP in the hippocampal CA1 region via stimulation of glycine-binding site of NMDAR. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. An RCT into the effects of neurofeedback on neurocognitive functioning compared to stimulant medication and physical activity in children with ADHD.

    PubMed

    Geladé, Katleen; Bink, Marleen; Janssen, Tieme W P; van Mourik, Rosa; Maras, Athanasios; Oosterlaan, Jaap

    2017-04-01

    Neurofeedback (NFB) is a potential alternative treatment for children with ADHD that aims to optimize brain activity. Whereas most studies into NFB have investigated behavioral effects, less attention has been paid to the effects on neurocognitive functioning. The present randomized controlled trial (RCT) compared neurocognitive effects of NFB to (1) optimally titrated methylphenidate (MPH) and (2) a semi-active control intervention, physical activity (PA), to control for non-specific effects. Using a multicentre three-way parallel group RCT design, children with ADHD, aged 7-13, were randomly allocated to NFB (n = 39), MPH (n = 36) or PA (n = 37) over a period of 10-12 weeks. NFB comprised theta/beta training at CZ. The PA intervention was matched in frequency and duration to NFB. MPH was titrated using a double-blind placebo controlled procedure to determine the optimal dose. Neurocognitive functioning was assessed using parameters derived from the auditory oddball-, stop-signal- and visual spatial working memory task. Data collection took place between September 2010 and March 2014. Intention-to-treat analyses showed improved attention for MPH compared to NFB and PA, as reflected by decreased response speed during the oddball task [η p 2  = 0.21, p < 0.001], as well as improved inhibition, impulsivity and attention, as reflected by faster stop signal reaction times, lower commission and omission error rates during the stop-signal task (range η p 2  = 0.09-0.18, p values <0.008). Working memory improved over time, irrespective of received treatment (η p 2  = 0.17, p < 0.001). Overall, stimulant medication showed superior effects over NFB to improve neurocognitive functioning. Hence, the findings do not support theta/beta training applied as a stand-alone treatment in children with ADHD.

  1. A Simple Method for Constructing Artificial Promoters Activated in Response to Ultrasound Stimulation.

    PubMed

    Ogawa, Ryohei; Kagiya, Go; Watanabe, Akihiko; Morii, Akihiro; Cui, Zheng-Guo; Kondo, Takashi

    2017-01-01

    It has been pointed out that ultrasound could be used as a controller for bioprocesses including gene expression since its energy can noninvasively reach deep in the body. Gene expression may be timely and spatially controlled by ultrasound, thus providing necessary bioactive proteins for the targeted tissue in a timely fashion. Although there are many processes involved in gene expression control, one of the most important processes is transcription, and the promoter plays an essential role in it. There are several promoters known to be activated in response to ultrasound irradiation . However, in our opinion, an artificial promoter is more suitable for clinical use. We herein describe simple methods to construct promoters that are responsive to ultrasound irradiation by randomly combining cis-elements (transcription factor binding motifs) and thereby improve its reactivity to ultrasound irradiation .

  2. In vivo molecular photoacoustic tomography of melanomas targeted by bioconjugated gold nanocages.

    PubMed

    Kim, Chulhong; Cho, Eun Chul; Chen, Jingyi; Song, Kwang Hyun; Au, Leslie; Favazza, Christopher; Zhang, Qiang; Cobley, Claire M; Gao, Feng; Xia, Younan; Wang, Lihong V

    2010-08-24

    Early diagnosis, accurate staging, and image-guided resection of melanomas remain crucial clinical objectives for improving patient survival and treatment outcomes. Conventional techniques cannot meet this demand because of the low sensitivity, low specificity, poor spatial resolution, shallow penetration, and/or ionizing radiation. Here we overcome such limitations by combining high-resolution photoacoustic tomography (PAT) with extraordinarily optical absorbing gold nanocages (AuNCs). When bioconjugated with [Nle(4),D-Phe(7)]-alpha-melanocyte-stimulating hormone, the AuNCs can serve as a novel contrast agent for in vivo molecular PAT of melanomas with both exquisite sensitivity and high specificity. The bioconjugated AuNCs enhanced contrast approximately 300% more than the control, PEGylated AuNCs. The in vivo PAT quantification of the amount of AuNCs accumulated in melanomas was further validated with inductively coupled plasma mass spectrometry (ICP-MS).

  3. Investigation of shape, position, and permeability of shielding material in quadruple butterfly coil for focused transcranial magnetic stimulation

    NASA Astrophysics Data System (ADS)

    Rastogi, Priyam; Zhang, Bowen; Tang, Yalun; Lee, Erik G.; Hadimani, Ravi L.; Jiles, David C.

    2018-05-01

    Transcranial magnetic stimulation has been gaining popularity in the therapy for several neurological disorders. A time-varying magnetic field is used to generate electric field in the brain. As the development of TMS methods takes place, emphasis on the coil design increases in order to improve focal stimulation. Ideally reduction of stimulation of neighboring regions of the target area is desired. This study, focused on the improvement of the focality of the Quadruple Butterfly Coil (QBC) with supplemental use of different passive shields. Parameters such as shape, position and permeability of the shields have been explored to improve the focus of stimulation. Results have been obtained with the help of computer modelling of a MRI derived heterogeneous head model over the vertex position and the dorsolateral prefrontal cortex position using a finite element tool. Variables such as maximum electric field induced on the grey matter and scalp, volume and area of stimulation above half of the maximum value of electric field on the grey matter, and ratio of the maximum electric field in the brain versus the scalp have been investigated.

  4. It's all in the timing: modeling isovolumic contraction through development and disease with a dynamic dual electromechanical bioreactor system.

    PubMed

    Morgan, Kathy Ye; Black, Lauren Deems

    2014-01-01

    This commentary discusses the rationale behind our recently reported work entitled "Mimicking isovolumic contraction with combined electromechanical stimulation improves the development of engineered cardiac constructs," introduces new data supporting our hypothesis, and discusses future applications of our bioreactor system. The ability to stimulate engineered cardiac tissue in a bioreactor system that combines both electrical and mechanical stimulation offers a unique opportunity to simulate the appropriate dynamics between stretch and contraction and model isovolumic contraction in vitro. Our previous study demonstrated that combined electromechanical stimulation that simulated the timing of isovolumic contraction in healthy tissue improved force generation via increased contractile and calcium handling protein expression and improved hypertrophic pathway activation. In new data presented here, we further demonstrate that modification of the timing between electrical and mechanical stimulation to mimic a non-physiological process negatively impacts the functionality of the engineered constructs. We close by exploring the various disease states that have altered timing between the electrical and mechanical stimulation signals as potential future directions for the use of this system.

  5. Electric stimulation and decimeter wave therapy improve the recovery of injured sciatic nerves

    PubMed Central

    Zhao, Feng; He, Wei; Zhang, Yingze; Tian, Dehu; Zhao, Hongfang; Yu, Kunlun; Bai, Jiangbo

    2013-01-01

    Drug treatment, electric stimulation and decimeter wave therapy have been shown to promote the repair and regeneration of the peripheral nerves at the injured site. This study prepared a Mackinnon's model of rat sciatic nerve compression. Electric stimulation was given immediately after neurolysis, and decimeter wave radiation was performed at 1 and 12 weeks post-operation. Histological observation revealed that intraoperative electric stimulation and decimeter wave therapy could improve the local blood circulation of repaired sites, alleviate hypoxia of compressed nerves, and lessen adhesion of compressed nerves, thereby decreasing the formation of new entrapments and enhancing compressed nerve regeneration through an improved microenvironment for regeneration. Immunohistochemical staining results revealed that intraoperative electric stimulation and decimeter wave could promote the expression of S-100 protein. Motor nerve conduction velocity and amplitude, the number and diameter of myelinated nerve fibers, and sciatic functional index were significantly increased in the treated rats. These results verified that intraoperative electric stimulation and decimeter wave therapy contributed to the regeneration and the recovery of the functions in the compressed nerves. PMID:25206506

  6. Transcranial Direct Current Stimulation Improves Executive Dysfunctions in ADHD: Implications for Inhibitory Control, Interference Control, Working Memory, and Cognitive Flexibility.

    PubMed

    Nejati, Vahid; Salehinejad, Mohammad Ali; Nitsche, Michael A; Najian, Asal; Javadi, Amir-Homayoun

    2017-09-01

    This study examined effects of transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) on major executive functions (EFs), including response inhibition, executive control, working memory (WM), and cognitive flexibility/task switching in ADHD. ADHD children received (a) left anodal/right cathodal DLPFC tDCS and (b) sham stimulation in Experiment 1 and (a) left anodal DLPFC/right cathodal OFC tDCS, (b) left cathodal DLPFC/right anodal OFC tDCS, and (c) sham stimulation in Experiment 2. The current intensity was 1 mA for 15 min with a 72-hr interval between sessions. Participants underwent Go/No-Go task, N-back test, Wisconsin Card Sorting Test (WCST), and Stroop task after each tDCS condition. Anodal left DLPFC tDCS most clearly affected executive control functions (e.g., WM, interference inhibition), while cathodal left DLPFC tDCS improved inhibitory control. Cognitive flexibility/task switching benefited from combined DLPFC-OFC, but not DLPFC stimulation alone. Task-specific stimulation protocols can improve EFs in ADHD.

  7. Improved reading measures in adults with dyslexia following transcranial direct current stimulation treatment.

    PubMed

    Heth, Inbahl; Lavidor, Michal

    2015-04-01

    To better understand the contribution of the dorsal system to word reading, we explored transcranial direct current stimulation (tDCS) effects when adults with developmental dyslexia received active stimulation over the visual extrastriate area MT/V5, which is dominated by magnocellular input. Stimulation was administered in 5 sessions spread over two weeks, and reading speed and accuracy as well as reading fluency were assessed before, immediately after, and a week after the end of the treatment. A control group of adults with developmental dyslexia matched for age, gender, reading level, vocabulary and block-design WAIS-III sub-tests and reading level was exposed to the same protocol but with sham stimulation. The results revealed that active, but not sham stimulation, significantly improved reading speed and fluency. This finding suggests that the dorsal stream may play a role in efficient retrieval from the orthographic input lexicon in the lexical route. It also underscores the potential of tDCS as an intervention tool for improving reading speed, at least in adults with developmental dyslexia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Non-invasive brain stimulation: a new strategy to improve neurorehabilitation after stroke?

    PubMed

    Hummel, Friedhelm C; Cohen, Leonardo G

    2006-08-01

    Motor impairment resulting from chronic stroke can have extensive physical, psychological, financial, and social implications despite available neurorehabilitative treatments. Recent studies in animals showed that direct epidural stimulation of the primary motor cortex surrounding a small infarct in the lesioned hemisphere (M1(lesioned hemisphere)) elicits improvements in motor function. In human beings, proof of principle studies from different laboratories showed that non-invasive transcranial magnetic stimulation and direct current stimulation that upregulate excitability within M1(lesioned hemisphere) or downregulate excitability in the intact hemisphere (M1(intact hemisphere)) results in improvement in motor function in patients with stroke. Possible mechanisms mediating these effects can include the correction of abnormally persistent interhemispheric inhibitory drive from M1(intact hemisphere) to M1(lesioned hemisphere) in the process of generation of voluntary movements by the paretic hand, a disorder correlated with the magnitude of impairment. In this paper we review these mechanistically oriented interventional approaches. WHAT NEXT?: These findings suggest that transcranial magnetic stimulation and transcranial direct current stimulation could develop into useful adjuvant strategies in neurorehabilitation but have to be further assessed in multicentre clinical trials.

  9. State of the Art: Novel Applications for Cortical Stimulation.

    PubMed

    De Ridder, Dirk; Perera, Sanjaya; Vanneste, Sven

    2017-04-01

    Electrical stimulation via implanted electrodes that overlie the cortex of the brain is an upcoming neurosurgical technique that was hindered for a long time by insufficient knowledge of how the brain functions in a dynamic, physiological, and pathological way, as well as by technological limitations of the implantable stimulation devices. This paper provides an overview of cortex stimulation via implantable devices and introduces future possibilities to improve cortex stimulation. Cortex stimulation was initially used preoperatively as a technique to localize functions in the brain and only later evolved into a treatment technique. It was first used for pain, but more recently a multitude of pathologies are being targeted by cortex stimulation. These disorders are being treated by stimulating different cortical areas of the brain. Risks and complications are essentially similar to those related to deep brain stimulation and predominantly include haemorrhage, seizures, infection, and hardware failures. For cortex stimulation to fully mature, further technological development is required to predict its outcomes and improve stimulation designs. This includes the development of network science-based functional connectivity approaches, genetic analyses, development of navigated high definition transcranial alternating current stimulation, and development of pseudorandom stimulation designs for preventing habituation. In conclusion, cortex stimulation is a nascent but very promising approach to treating a variety of diseases, but requires further technological development for predicting outcomes, such as network science based functional connectivity approaches, genetic analyses, development of navigated transcranial electrical stimulation, and development of pseudorandom stimulation designs for preventing habituation. © 2017 International Neuromodulation Society.

  10. Imaging Cajal’s neuronal avalanche: how wide-field optical imaging of the point-spread advanced the understanding of neocortical structure–function relationship

    PubMed Central

    Frostig, Ron D.; Chen-Bee, Cynthia H.; Johnson, Brett A.; Jacobs, Nathan S.

    2017-01-01

    Abstract. This review brings together a collection of studies that specifically use wide-field high-resolution mesoscopic level imaging techniques (intrinsic signal optical imaging; voltage-sensitive dye optical imaging) to image the cortical point spread (PS): the total spread of cortical activation comprising a large neuronal ensemble evoked by spatially restricted (point) stimulation of the sensory periphery (e.g., whisker, pure tone, point visual stimulation). The collective imaging findings, combined with supporting anatomical and electrophysiological findings, revealed some key aspects about the PS including its very large (radius of several mm) and relatively symmetrical spatial extent capable of crossing cytoarchitectural borders and trespassing into other cortical areas; its relationship with underlying evoked subthreshold activity and underlying anatomical system of long-range horizontal projections within gray matter, both also crossing borders; its contextual modulation and plasticity; the ability of its relative spatiotemporal profile to remain invariant to major changes in stimulation parameters; its potential role as a building block for integrative cortical activity; and its ubiquitous presence across various cortical areas and across mammalian species. Together, these findings advance our understanding about the neocortex at the mesoscopic level by underscoring that the cortical PS constitutes a fundamental motif of neocortical structure–function relationship. PMID:28630879

  11. Imaging Cajal's neuronal avalanche: how wide-field optical imaging of the point-spread advanced the understanding of neocortical structure-function relationship.

    PubMed

    Frostig, Ron D; Chen-Bee, Cynthia H; Johnson, Brett A; Jacobs, Nathan S

    2017-07-01

    This review brings together a collection of studies that specifically use wide-field high-resolution mesoscopic level imaging techniques (intrinsic signal optical imaging; voltage-sensitive dye optical imaging) to image the cortical point spread (PS): the total spread of cortical activation comprising a large neuronal ensemble evoked by spatially restricted (point) stimulation of the sensory periphery (e.g., whisker, pure tone, point visual stimulation). The collective imaging findings, combined with supporting anatomical and electrophysiological findings, revealed some key aspects about the PS including its very large (radius of several mm) and relatively symmetrical spatial extent capable of crossing cytoarchitectural borders and trespassing into other cortical areas; its relationship with underlying evoked subthreshold activity and underlying anatomical system of long-range horizontal projections within gray matter, both also crossing borders; its contextual modulation and plasticity; the ability of its relative spatiotemporal profile to remain invariant to major changes in stimulation parameters; its potential role as a building block for integrative cortical activity; and its ubiquitous presence across various cortical areas and across mammalian species. Together, these findings advance our understanding about the neocortex at the mesoscopic level by underscoring that the cortical PS constitutes a fundamental motif of neocortical structure-function relationship.

  12. An integrated multi-electrode-optrode array for in vitro optogenetics

    PubMed Central

    Welkenhuysen, Marleen; Hoffman, Luis; Luo, Zhengxiang; De Proft, Anabel; Van den Haute, Chris; Baekelandt, Veerle; Debyser, Zeger; Gielen, Georges; Puers, Robert; Braeken, Dries

    2016-01-01

    Modulation of a group of cells or tissue needs to be very precise in order to exercise effective control over the cell population under investigation. Optogenetic tools have already demonstrated to be of great value in the study of neuronal circuits and in neuromodulation. Ideally, they should permit very accurate resolution, preferably down to the single cell level. Further, to address a spatially distributed sample, independently addressable multiple optical outputs should be present. In current techniques, at least one of these requirements is not fulfilled. In addition to this, it is interesting to directly monitor feedback of the modulation by electrical registration of the activity of the stimulated cells. Here, we present the fabrication and characterization of a fully integrated silicon-based multi-electrode-optrode array (MEOA) for in vitro optogenetics. We demonstrate that this device allows for artifact-free electrical recording. Moreover, the MEOA was used to reliably elicit spiking activity from ChR2-transduced neurons. Thanks to the single cell resolution stimulation capability, we could determine spatial and temporal activation patterns and spike latencies of the neuronal network. This integrated approach to multi-site combined optical stimulation and electrical recording significantly advances today’s tool set for neuroscientists in their search to unravel neuronal network dynamics. PMID:26832455

  13. Modulation of gut perception in humans by spatial summation phenomena

    PubMed Central

    Serra, Jordi; Azpiroz, Fernando; Malagelada, Juan-R

    1998-01-01

    We have recently shown that perception of intestinal stimuli increases by spatial summation phenomena. Our aim was to determine in humans whether intestinal perception depends on (a) the length of gut stimulated, and (b) the distance between stimuli. In a first series of studies, we compared perception of isobaric intestinal distensions applied over a 3 cm segment and a 36 cm segment by means of two separate barostats (n = 8). In a second series of studies we compared perception of intestinal distensions applied simultaneously by two balloons sited 3, 12 or 48 cm apart (n = 6). Distension of the 36 cm segment induced significantly greater perception than distension of the 3 cm intestinal segment (discomfort perceived at 20 ± 2 mmHg and 31 ± 2 mmHg, respectively; P < 0.05). Perception of intestinal balloon distension increased when a second stimulus was simultaneously applied, independently of the distance between the two balloons (the discomfort thresholds were 30 ± 11, 20 ± 6 and 28 ± 7% lower with simultaneous distensions 3, 12 and 48 cm apart, respectively). We conclude that perception of intestinal distension is determined by the extension of the field of stimulation, and the summation effect is similar whether adjacent or distant fields are stimulated. PMID:9490880

  14. Nonmonotonic spatial structure of interneuronal correlations in prefrontal microcircuits

    PubMed Central

    Safavi, Shervin; Dwarakanath, Abhilash; Kapoor, Vishal; Werner, Joachim; Hatsopoulos, Nicholas G.; Logothetis, Nikos K.; Panagiotaropoulos, Theofanis I.

    2018-01-01

    Correlated fluctuations of single neuron discharges, on a mesoscopic scale, decrease as a function of lateral distance in early sensory cortices, reflecting a rapid spatial decay of lateral connection probability and excitation. However, spatial periodicities in horizontal connectivity and associational input as well as an enhanced probability of lateral excitatory connections in the association cortex could theoretically result in nonmonotonic correlation structures. Here, we show such a spatially nonmonotonic correlation structure, characterized by significantly positive long-range correlations, in the inferior convexity of the macaque prefrontal cortex. This functional connectivity kernel was more pronounced during wakefulness than anesthesia and could be largely attributed to the spatial pattern of correlated variability between functionally similar neurons during structured visual stimulation. These results suggest that the spatial decay of lateral functional connectivity is not a common organizational principle of neocortical microcircuits. A nonmonotonic correlation structure could reflect a critical topological feature of prefrontal microcircuits, facilitating their role in integrative processes. PMID:29588415

  15. Reduction of pain thresholds in fibromyalgia after very low-intensity magnetic stimulation: a double-blinded, randomized placebo-controlled clinical trial.

    PubMed

    Maestú, Ceferino; Blanco, Manuel; Nevado, Angel; Romero, Julia; Rodríguez-Rubio, Patricia; Galindo, Javier; Bautista Lorite, Juan; de las Morenas, Francisco; Fernández-Argüelles, Pedro

    2013-01-01

    Exposure to electromagnetic fields has been reported to have analgesic and antinociceptive effects in several organisms. To test the effect of very low-intensity transcranial magnetic stimulation on symptoms associated with fibromyalgia syndrome. A double-blinded, placebo-controlled clinical trial was performed in the Sagrado Corazón Hospital, Seville, Spain. Female fibromyalgia patients (22 to 50 years of age) were randomly assigned to either a stimulation group or a sham group. The stimulation group (n=28) was stimulated using 8 Hz pulsed magnetic fields of very low intensity, while the sham group (n=26) underwent the same protocol without stimulation. Pressure pain thresholds before and after stimulation were determined using an algometer during the eight consecutive weekly sessions of the trial. In addition, blood serotonin levels were measured and patients completed questionnaires to monitor symptom evolution. A repeated-measures ANOVA indicated statistically significant improvement in the stimulation group compared with the control group with respect to somatosensory pain thresholds, ability to perform daily activities, perceived chronic pain and sleep quality. While improvement in pain thresholds was apparent after the first stimulation session, improvement in the other three measures occurred after the sixth week. No significant between-group differences were observed in scores of depression, fatigue, severity of headaches or serotonin levels. No adverse side effects were reported in any of the patients. Very low-intensity magnetic stimulation may represent a safe and effective treatment for chronic pain and other symptoms associated with fibromyalgia.

  16. Reduction of pain thresholds in fibromyalgia after very low-intensity magnetic stimulation: A double-blinded, randomized placebo-controlled clinical trial

    PubMed Central

    Maestú, Ceferino; Blanco, Manuel; Nevado, Angel; Romero, Julia; Rodríguez-Rubio, Patricia; Galindo, Javier; Lorite, Juan Bautista; de las Morenas, Francisco; Fernández-Argüelles, Pedro

    2013-01-01

    BACKGROUND: Exposure to electromagnetic fields has been reported to have analgesic and antinociceptive effects in several organisms. OBJECTIVE: To test the effect of very low-intensity transcranial magnetic stimulation on symptoms associated with fibromyalgia syndrome. METHODS: A double-blinded, placebo-controlled clinical trial was performed in the Sagrado Corazón Hospital, Seville, Spain. Female fibromyalgia patients (22 to 50 years of age) were randomly assigned to either a stimulation group or a sham group. The stimulation group (n=28) was stimulated using 8 Hz pulsed magnetic fields of very low intensity, while the sham group (n=26) underwent the same protocol without stimulation. Pressure pain thresholds before and after stimulation were determined using an algometer during the eight consecutive weekly sessions of the trial. In addition, blood serotonin levels were measured and patients completed questionnaires to monitor symptom evolution. RESULTS: A repeated-measures ANOVA indicated statistically significant improvement in the stimulation group compared with the control group with respect to somatosensory pain thresholds, ability to perform daily activities, perceived chronic pain and sleep quality. While improvement in pain thresholds was apparent after the first stimulation session, improvement in the other three measures occurred after the sixth week. No significant between-group differences were observed in scores of depression, fatigue, severity of headaches or serotonin levels. No adverse side effects were reported in any of the patients. CONCLUSIONS: Very low-intensity magnetic stimulation may represent a safe and effective treatment for chronic pain and other symptoms associated with fibromyalgia. PMID:24308025

  17. Electrical stimulation of the motor cortex enhances treatment outcome in post-stroke aphasia.

    PubMed

    Meinzer, Marcus; Darkow, Robert; Lindenberg, Robert; Flöel, Agnes

    2016-04-01

    Transcranial direct current stimulation has shown promise to improve recovery in patients with post-stroke aphasia, but previous studies have only assessed stimulation effects on impairment parameters, and evidence for long-term maintenance of transcranial direct current stimulation effects from randomized, controlled trials is lacking. Moreover, due to the variability of lesions and functional language network reorganization after stroke, recent studies have used advanced functional imaging or current modelling to determine optimal stimulation sites in individual patients. However, such approaches are expensive, time consuming and may not be feasible outside of specialized research centres, which complicates incorporation of transcranial direct current stimulation in day-to-day clinical practice. Stimulation of an ancillary system that is functionally connected to the residual language network, namely the primary motor system, would be more easily applicable, but effectiveness of such an approach has not been explored systematically. We conducted a randomized, parallel group, sham-controlled, double-blind clinical trial and 26 patients with chronic aphasia received a highly intensive naming therapy over 2 weeks (8 days, 2 × 1.5 h/day). Concurrently, anodal-transcranial direct current stimulation was administered to the left primary motor cortex twice daily at the beginning of each training session. Naming ability for trained items (n = 60 pictures that could not be named during repeated baseline assessments), transfer to untrained items (n = 284 pictures) and generalization to everyday communication were assessed immediately post-intervention and 6 months later. Naming ability for trained items was significantly improved immediately after the end of the intervention in both the anodal (Cohen's d = 3.67) and sham-transcranial direct current stimulation groups (d = 2.10), with a trend for larger gains in the anodal-transcranial direct current stimulation group (d = 0.71). Treatment effects for trained items were significantly better maintained in the anodal-transcranial direct current stimulation group 6 months later (d = 1.19). Transfer to untrained items was significantly larger in the anodal-transcranial direct current stimulation group after the training (d = 1.49) and during the 6 month follow-up assessment (d = 3.12). Transfer effects were only maintained in the anodal-transcranial direct current stimulation group. Functional communication was significantly more improved in the anodal-transcranial direct current stimulation group at both time points compared to patients treated with sham-transcranial direct current stimulation (d = 0.75-0.99). Our results provide the first evidence from a randomized, controlled trial that transcranial direct current stimulation can improve both function and activity-related outcomes in chronic aphasia, with medium to large effect sizes, and that these effects are maintained over extended periods of time. These effects were achieved with an easy-to-implement and thus clinically feasible motor-cortex montage that may represent a promising 'backdoor' approach to improve language recovery after stroke. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Neuroimaging Mechanisms of Therapeutic Transcranial Magnetic Stimulation for Major Depressive Disorder.

    PubMed

    Philip, Noah S; Barredo, Jennifer; Aiken, Emily; Carpenter, Linda L

    2018-03-01

    Research into therapeutic transcranial magnetic stimulation (TMS) for major depression has dramatically increased in the last decade. Understanding the mechanism of action of TMS is crucial to improve efficacy and develop the next generation of therapeutic stimulation. Early imaging research provided initial data supportive of widely held assumptions about hypothesized inhibitory or excitatory consequences of stimulation. Early work also indicated that while TMS modulated brain activity under the stimulation site, effects at deeper regions, in particular, the subgenual anterior cingulate cortex, were associated with clinical improvement. Concordant with earlier findings, functional connectivity studies also demonstrated that clinical improvements were related to changes distal, rather than proximal, to the site of stimulation. Moreover, recent work suggests that TMS modulates and potentially normalizes functional relationships between neural networks. An important observation that emerged from this review is that similar patterns of connectivity changes are observed across studies regardless of TMS parameters. Though promising, we stress that these imaging findings must be evaluated cautiously given the widespread reliance on modest sample sizes and little implementation of statistical validation. Additional limitations included use of imaging before and after a course of TMS, which provided little insight into changes that might occur during the weeks of stimulation. Furthermore, as studies to date have focused on depression, it is unclear whether our observations were related to mechanisms of action of TMS for depression or represented broader patterns of functional brain changes associated with clinical improvement. Published by Elsevier Inc.

  19. Transfer of Cognitive Training across Magnitude Dimensions Achieved with Concurrent Brain Stimulation of the Parietal Lobe

    PubMed Central

    Gessaroli, Erica; Hithersay, Rosalyn; Mitolo, Micaela; Didino, Daniele; Kanai, Ryota; Cohen Kadosh, Roi; Walsh, Vincent

    2013-01-01

    Improvement in performance following cognitive training is known to be further enhanced when coupled with brain stimulation. Here we ask whether training-induced changes can be maintained long term and, crucially, whether they can extend to other related but untrained skills. We trained overall 40 human participants on a simple and well established paradigm assessing the ability to discriminate numerosity–or the number of items in a set–which is thought to rely on an “approximate number sense” (ANS) associated with parietal lobes. We coupled training with parietal stimulation in the form of transcranial random noise stimulation (tRNS), a noninvasive technique that modulates neural activity. This yielded significantly better and longer lasting improvement (up to 16 weeks post-training) of the precision of the ANS compared with cognitive training in absence of stimulation, stimulation in absence of cognitive training, and cognitive training coupled to stimulation to a control site (motor areas). Critically, only ANS improvement induced by parietal tRNS + Training transferred to proficiency in other parietal lobe-based quantity judgment, i.e., time and space discrimination, but not to quantity-unrelated tasks measuring attention, executive functions, and visual pattern recognition. These results indicate that coupling intensive cognitive training with tRNS to critical brain regions resulted not only in the greatest and longer lasting improvement of numerosity discrimination, but importantly in this enhancement being transferable when trained and untrained abilities are carefully chosen to share common cognitive and neuronal components. PMID:24027289

  20. Transfer of cognitive training across magnitude dimensions achieved with concurrent brain stimulation of the parietal lobe.

    PubMed

    Cappelletti, Marinella; Gessaroli, Erica; Hithersay, Rosalyn; Mitolo, Micaela; Didino, Daniele; Kanai, Ryota; Cohen Kadosh, Roi; Walsh, Vincent

    2013-09-11

    Improvement in performance following cognitive training is known to be further enhanced when coupled with brain stimulation. Here we ask whether training-induced changes can be maintained long term and, crucially, whether they can extend to other related but untrained skills. We trained overall 40 human participants on a simple and well established paradigm assessing the ability to discriminate numerosity--or the number of items in a set--which is thought to rely on an "approximate number sense" (ANS) associated with parietal lobes. We coupled training with parietal stimulation in the form of transcranial random noise stimulation (tRNS), a noninvasive technique that modulates neural activity. This yielded significantly better and longer lasting improvement (up to 16 weeks post-training) of the precision of the ANS compared with cognitive training in absence of stimulation, stimulation in absence of cognitive training, and cognitive training coupled to stimulation to a control site (motor areas). Critically, only ANS improvement induced by parietal tRNS + Training transferred to proficiency in other parietal lobe-based quantity judgment, i.e., time and space discrimination, but not to quantity-unrelated tasks measuring attention, executive functions, and visual pattern recognition. These results indicate that coupling intensive cognitive training with tRNS to critical brain regions resulted not only in the greatest and longer lasting improvement of numerosity discrimination, but importantly in this enhancement being transferable when trained and untrained abilities are carefully chosen to share common cognitive and neuronal components.

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