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Sample records for repetitive stimulation imaging

  1. 21 CFR 882.5805 - Repetitive transcranial magnetic stimulation system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Repetitive transcranial magnetic stimulation....5805 Repetitive transcranial magnetic stimulation system. (a) Identification. A repetitive transcranial magnetic stimulation system is an external device that delivers transcranial repetitive pulsed...

  2. 21 CFR 882.5805 - Repetitive transcranial magnetic stimulation system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Repetitive transcranial magnetic stimulation....5805 Repetitive transcranial magnetic stimulation system. (a) Identification. A repetitive transcranial magnetic stimulation system is an external device that delivers transcranial repetitive pulsed...

  3. 21 CFR 882.5805 - Repetitive transcranial magnetic stimulation system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Repetitive transcranial magnetic stimulation....5805 Repetitive transcranial magnetic stimulation system. (a) Identification. A repetitive transcranial magnetic stimulation system is an external device that delivers transcranial repetitive pulsed...

  4. Neuromodulatory effects of offline low-frequency repetitive transcranial magnetic stimulation of the motor cortex: A functional magnetic resonance imaging study

    PubMed Central

    Min, Yu-Sun; Park, Jang Woo; Jin, Seong Uk; Jang, Kyung Eun; Lee, Byung-Joo; Lee, Hui Joong; Lee, Jongmin; Lee, Yang-Soo; Chang, Yongmin; Jung, Tae-Du

    2016-01-01

    Repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) can modulate cortical excitability and is thought to influence activity in other brain areas. In this study, we investigated the anatomical and functional effects of rTMS of M1 and the time course of after-effects from a 1-Hz subthreshold rTMS to M1. Using an “offline” functional magnetic resonance imaging (fMRI)-rTMS paradigm, neural activation was mapped during simple finger movements after 1-Hz rTMS over the left M1 in a within-subjects repeated measurement design, including rTMS and sham stimulation. A significant decrease in the blood oxygen level dependent (BOLD) signal due to right hand motor activity during a simple finger-tapping task was observed in areas remote to the stimulated motor cortex after rTMS stimulation. This decrease in BOLD signal suggests that low frequency subthreshold rTMS may be sufficiently strong to elicit inhibitory modulation of remote brain regions. In addition, the time course patterns of BOLD activity showed this inhibitory modulation was maximal approximately 20 minutes after rTMS stimulation. PMID:27786301

  5. Clinical application of repetitive transcranial magnetic stimulation in stroke rehabilitation☆

    PubMed Central

    Shin, Joonho; Yang, EunJoo; Cho, KyeHee; Barcenas, Carmelo L; Kim, Woo Jin; Min, Yusun; Paik, Nam-Jong

    2012-01-01

    Proper stimulation to affected cerebral hemisphere would promote the functional recovery of patients with stroke. Effects of repetitive transcranial magnetic stimulation on cortical excitability can be can be altered by the stimulation frequency, intensity and duration. There has been no consistent recognition regarding the best stimulation frequency and intensity. This study reviews the intervention effects of repetitive transcranial stimulation on motor impairment, dysphagia, visuospatial neglect and aphasia, and summarizes the stimulation frequency, intensity and area for repetitive transcranial magnetic stimulation to yield the best therapeutic effects. PMID:25745455

  6. Neural dynamics during repetitive visual stimulation

    NASA Astrophysics Data System (ADS)

    Tsoneva, Tsvetomira; Garcia-Molina, Gary; Desain, Peter

    2015-12-01

    Objective. Steady-state visual evoked potentials (SSVEPs), the brain responses to repetitive visual stimulation (RVS), are widely utilized in neuroscience. Their high signal-to-noise ratio and ability to entrain oscillatory brain activity are beneficial for their applications in brain-computer interfaces, investigation of neural processes underlying brain rhythmic activity (steady-state topography) and probing the causal role of brain rhythms in cognition and emotion. This paper aims at analyzing the space and time EEG dynamics in response to RVS at the frequency of stimulation and ongoing rhythms in the delta, theta, alpha, beta, and gamma bands. Approach.We used electroencephalography (EEG) to study the oscillatory brain dynamics during RVS at 10 frequencies in the gamma band (40-60 Hz). We collected an extensive EEG data set from 32 participants and analyzed the RVS evoked and induced responses in the time-frequency domain. Main results. Stable SSVEP over parieto-occipital sites was observed at each of the fundamental frequencies and their harmonics and sub-harmonics. Both the strength and the spatial propagation of the SSVEP response seem sensitive to stimulus frequency. The SSVEP was more localized around the parieto-occipital sites for higher frequencies (>54 Hz) and spread to fronto-central locations for lower frequencies. We observed a strong negative correlation between stimulation frequency and relative power change at that frequency, the first harmonic and the sub-harmonic components over occipital sites. Interestingly, over parietal sites for sub-harmonics a positive correlation of relative power change and stimulation frequency was found. A number of distinct patterns in delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz) and beta (15-30 Hz) bands were also observed. The transient response, from 0 to about 300 ms after stimulation onset, was accompanied by increase in delta and theta power over fronto-central and occipital sites, which returned to baseline

  7. Repetitive transcranial magnetic stimulation and drug addiction.

    PubMed

    Barr, Mera S; Farzan, Faranak; Wing, Victoria C; George, Tony P; Fitzgerald, Paul B; Daskalakis, Zafiris J

    2011-10-01

    Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that is now being tested for its ability to treat addiction. This review discusses current research approaches and results of studies which measured the therapeutic use of rTMS to treat tobacco, alcohol and illicit drug addiction. The research in this area is limited and therefore all studies evaluating the therapeutic use of rTMS in tobacco, alcohol or illicit drug addiction were retained including case studies through NCBI PubMed ( http://www.ncbi.nlm.nih.gov ) and manual searches. A total of eight studies were identified that examined the ability of rTMS to treat tobacco, alcohol and cocaine addiction. The results of this review indicate that rTMS is effective in reducing the level of cravings for smoking, alcohol, and cocaine when applied at high frequencies to the dorsolateral prefrontal cortex (DLPFC). Furthermore, these studies suggest that repeated sessions of high frequency rTMS over the DLPFC may be most effective in reducing the level of smoking and alcohol consumption. Although work in this area is limited, this review indicates that rTMS is a promising modality for treating drug addiction.

  8. [Rehabilitation Using Repetitive Transcranial Magnetic Stimulation].

    PubMed

    Takeuchi, Naoyuki; Izumi, Shin-Ichi

    2017-03-01

    Various novel stroke rehabilitative methods have been developed based on findings in basic science and clinical research. Recently, many reports have shown that repetitive transcranial magnetic stimulation (rTMS) improves function in stroke patients by altering the excitability of the human cortex. The interhemispheric competition model proposes that deficits in stroke patients are due to reduced output from the affected hemisphere and excessive interhemispheric inhibition from the unaffected hemisphere to the affected hemisphere. The interhemispheric competition model indicates that improvement in deficits can be achieved either by increasing the excitability of the affected hemisphere using excitatory rTMS or by decreasing the excitability of the unaffected hemisphere using inhibitory rTMS. Recovery after stroke is related to neural plasticity, which involves developing new neural connections, acquiring new functions, and compensating for impairments. Artificially modulating the neural network by rTMS may induce a more suitable environment for use-dependent plasticity and also may interfere with maladaptive neural activation, which weakens function and limits recovery. There is potential, therefore, for rTMS to be used as an adjuvant therapy for developed neurorehabilitation techniques in stroke patients.

  9. [Repetitive transcranial magnetic stimulation: A potential therapy for cognitive disorders?

    PubMed

    Nouhaud, C; Sherrard, R M; Belmin, J

    2017-03-01

    Considering the limited effectiveness of drugs treatments in cognitive disorders, the emergence of noninvasive techniques to modify brain function is very interesting. Among these techniques, repetitive transcranial magnetic stimulation (rTMS) can modulate cortical excitability and have potential therapeutic effects on cognition and behaviour. These effects are due to physiological modifications in the stimulated cortical tissue and their associated circuits, which depend on the parameters of stimulation. The objective of this article is to specify current knowledge and efficacy of rTMS in cognitive disorders. Previous studies found very encouraging results with significant improvement of higher brain functions. Nevertheless, these few studies have limits: a few patients were enrolled, the lack of control of the mechanisms of action by brain imaging, insufficiently formalized technique and variability of cognitive tests. It is therefore necessary to perform more studies, which identify statistical significant improvement and to specify underlying mechanisms of action and the parameters of use of the rTMS to offer rTMS as a routine therapy for cognitive dysfunction.

  10. Modulation of sensorimotor cortex by repetitive peripheral magnetic stimulation

    PubMed Central

    Gallasch, Eugen; Christova, Monica; Kunz, Alexander; Rafolt, Dietmar; Golaszewski, Stefan

    2015-01-01

    This study examines with transcranial magnetic stimulation (TMS) and with functional magnetic resonance imaging (fMRI) whether 20 min of repetitive peripheral magnetic stimulation (rPMS) has a facilitating effect on associated motor controlling regions. Trains of rPMS with a stimulus intensity of 150% of the motor threshold (MT) were applied over right hand flexor muscles of healthy volunteers. First, with TMS, 10 vs. 25 Hz rPMS was examined and compared to a control group. Single and paired pulse motor evoked potentials (MEPs) from flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles were recorded at baseline (T0), post rPMS (T1), 30 min post (T2), 1 h post (T3) and 2 h post rPMS (T4). Then, with fMRI, 25 Hz rPMS was compared to sham stimulation by utilizing a finger tapping activation paradigm. Changes in bloodoxygen level dependent (BOLD) contrast were examined at baseline (PRE), post rPMS (POST1) and 1 h post rPMS (POST2). With TMS facilitation was observed in the target muscle (FCR) following 25 Hz rPMS: MEP recruitment curves (RCs) were increased at T1, T2 and T3, and intracortical facilitation (ICF) was increased at T1 and T2. No effects were observed following 10 Hz rPMS. With fMRI the BOLD contrast at the left sensorimotor area was increased at POST1. Compared to inductions protocols based on transcutaneous electrical stimulation and mechanical stimulation, the rPMS induced effects appeared shorter lasting. PMID:26236220

  11. Repetitive Transcranial Magnetic Stimulation Activates Specific Regions in Rat Brain

    NASA Astrophysics Data System (ADS)

    Ji, Ru-Rong; Schlaepfer, Thomas E.; Aizenman, Carlos D.; Epstein, Charles M.; Qiu, Dike; Huang, Justin C.; Rupp, Fabio

    1998-12-01

    Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique to induce electric currents in the brain. Although rTMS is being evaluated as a possible alternative to electroconvulsive therapy for the treatment of refractory depression, little is known about the pattern of activation induced in the brain by rTMS. We have compared immediate early gene expression in rat brain after rTMS and electroconvulsive stimulation, a well-established animal model for electroconvulsive therapy. Our result shows that rTMS applied in conditions effective in animal models of depression induces different patterns of immediate-early gene expression than does electroconvulsive stimulation. In particular, rTMS evokes strong neural responses in the paraventricular nucleus of the thalamus (PVT) and in other regions involved in the regulation of circadian rhythms. The response in PVT is independent of the orientation of the stimulation probe relative to the head. Part of this response is likely because of direct activation, as repetitive magnetic stimulation also activates PVT neurons in brain slices.

  12. Repetitive magnetic stimulation induces plasticity of inhibitory synapses

    PubMed Central

    Lenz, Maximilian; Galanis, Christos; Müller-Dahlhaus, Florian; Opitz, Alexander; Wierenga, Corette J.; Szabó, Gábor; Ziemann, Ulf; Deller, Thomas; Funke, Klaus; Vlachos, Andreas

    2016-01-01

    Repetitive transcranial magnetic stimulation (rTMS) is used as a therapeutic tool in neurology and psychiatry. While repetitive magnetic stimulation (rMS) has been shown to induce plasticity of excitatory synapses, it is unclear whether rMS can also modify structural and functional properties of inhibitory inputs. Here we employed 10-Hz rMS of entorhinohippocampal slice cultures to study plasticity of inhibitory neurotransmission on CA1 pyramidal neurons. Our experiments reveal a rMS-induced reduction in GABAergic synaptic strength (2–4 h after stimulation), which is Ca2+-dependent and accompanied by the remodelling of postsynaptic gephyrin scaffolds. Furthermore, we present evidence that 10-Hz rMS predominantly acts on dendritic, but not somatic inhibition. Consistent with this finding, a reduction in clustered gephyrin is detected in CA1 stratum radiatum of rTMS-treated anaesthetized mice. These results disclose that rTMS induces coordinated Ca2+-dependent structural and functional changes of specific inhibitory postsynapses on principal neurons. PMID:26743822

  13. Repetitive Transcranial Magnetic Stimulation Improves Handwriting in Parkinson's Disease

    PubMed Central

    Randhawa, Bubblepreet K.; Farley, Becky G.; Boyd, Lara A.

    2013-01-01

    Background. Parkinson disease (PD) is characterized by hypometric movements resulting from loss of dopaminergic neurons in the substantia nigra. PD leads to decreased activation of the supplementary motor area (SMA); the net result of these changes is a poverty of movement. The present study determined the impact of 5 Hz repetitive transcranial magnetic stimulation (rTMS) over the SMA on a fine motor movement, handwriting (writing cursive “l”s), and on cortical excitability, in individuals with PD. Methods. In a cross-over design, ten individuals with PD were randomized to receive either 5 Hz or control stimulation over the SMA. Immediately following brain stimulation right handed writing was assessed. Results. 5 Hz stimulation increased vertical size of handwriting and diminished axial pressure. In addition, 5 Hz rTMS significantly decreased the threshold for excitability in the primary motor cortex. Conclusions. These data suggest that in the short term 5 Hz rTMS benefits functional fine motor task performance, perhaps by altering cortical excitability across a network of brain regions. Further, these data may provide the foundation for a larger investigation of the effects of noninvasive brain stimulation over the SMA in individuals with PD. PMID:23841021

  14. Outcomes in spasticity after repetitive transcranial magnetic and transcranial direct current stimulations

    PubMed Central

    Gunduz, Aysegul; Kumru, Hatice; Pascual-Leone, Alvaro

    2014-01-01

    Non-invasive brain stimulations mainly consist of repetitive transcranial magnetic stimulation and transcranial direct current stimulation. Repetitive transcranial magnetic stimulation exhibits satisfactory outcomes in improving multiple sclerosis, stroke, spinal cord injury and cerebral palsy-induced spasticity. By contrast, transcranial direct current stimulation has only been studied in post-stroke spasticity. To better validate the efficacy of non-invasive brain stimulations in improving the spasticity post-stroke, more prospective cohort studies involving large sample sizes are needed. PMID:25206878

  15. Rehabilitation interventions for chronic motor deficits with repetitive transcranial magnetic stimulation.

    PubMed

    Paquette, C; Thiel, A

    2012-12-01

    Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive electrophysiological method to modulate cortical excitability. As such, rTMS can be used in conjunction with conventional physiotherapy or occupational therapy to facilitate rehabilitation of motor function in patients with focal brain lesions. This review summarizes the rationale for using rTMS in the rehabilitation of motor deficits as derived from imaging and electrophysiological studies of the human motor system. rTMS methodology and its various stimulation modalities are introduced and current evidence for rTMS as supportive therapy for the rehabilitation of chronic motor deficits is discussed.

  16. [Therapeutic application of repetitive transcranial magnetic stimulation for major depression].

    PubMed

    Nakamura, Motoaki

    2012-01-01

    It has been reported that approximately one third of patients with major depression are medication-resistant. In spite of partial responsiveness to antidepressants, most of the medication-resistant patients remain incompletely remitted without successful social reintegration. Symptom severity could be mild to moderate for many of them due to the incomplete remission, and, thus, electroconvulsive therapy is not applicable for them. However, they usually feel some difficulty performing cognitive behavioral therapy or social rehabilitation training due to residual symptoms such as thought inhibition and hypobulia. Under such conditions, those patients are longing for treatment options complementary to antidepressants, for less painful social reintegration. In October 2008, the Food and Drug Administration (FDA) of the United States finally approved repetitive Transcranial Magnetic Stimulation (rTMS) for medication-resistant patients with major depression. The main reason for the FDA approval was that rTMS had shown similar effectiveness (effect size around 0.39 in a recent meta-analysis) to antidepressants for medication-resistant patients without serious adverse effects. TMS is a brain stimulation methodology employing magnetic energy which can penetrate the skull bone without energy decay, and, thus, eddy currents induced by TMS can stimulate cerebral cortices effectively and locally. When TMS is repetitively delivered over several hundreds of pulses within a session, stimulation effects can be observed beyond the stimulation period as aftereffects. Moreover, when a daily rTMS session is repeated over several weeks, rTMS could have antidepressant effects. Clinical trials of rTMS for depression have employed two kinds of rTMS protocol of high-frequency (facilitatory) rTMS over the left Dorsolateral Prefrontal Cortex (DLPFC) and low-frequency (inhibitory) rTMS over the right DLPFC. Although the antidepressant action of rTMS over DLPFC has not been fully elucidated

  17. Use of Repetitive Transcranial Magnetic Stimulation for Treatment in Psychiatry

    PubMed Central

    2013-01-01

    The potential of noninvasive neurostimulation by repetitive transcranial magnetic stimulation (rTMS) for improving psychiatric disorders has been studied increasingly over the past two decades. This is especially the case for major depression and for auditory-verbal hallucinations in schizophrenia. The present review briefly describes the background of this novel treatment modality and summarizes evidence from clinical trials into the efficacy of rTMS for depression and hallucinations. Evidence for efficacy in depression is stronger than for hallucinations, although a number of studies have reported clinically relevant improvements for hallucinations too. Different stimulation parameters (frequency, duration, location of stimulation) are discussed. There is a paucity of research into other psychiatric disorders, but initial evidence suggests that rTMS may also hold promise for the treatment of negative symptoms in schizophrenia, obsessive compulsive disorder and post-traumatic stress disorder. It can be concluded that rTMS induces alterations in neural networks relevant for psychiatric disorders and that more research is needed to elucidate efficacy and underlying mechanisms of action. PMID:24023548

  18. Stimulated Raman photoacoustic imaging

    PubMed Central

    Yakovlev, Vladislav V.; Zhang, Hao F.; Noojin, Gary D.; Denton, Michael L.; Thomas, Robert J.; Scully, Marlan O.

    2010-01-01

    Achieving label-free, molecular-specific imaging with high spatial resolution in deep tissue is often considered the grand challenge of optical imaging. To accomplish this goal, significant optical scattering in tissues has to be overcome while achieving molecular specificity without resorting to extrinsic labeling. We demonstrate the feasibility of developing such an optical imaging modality by combining the molecularly specific stimulated Raman excitation with the photoacoustic detection. By employing two ultrashort excitation laser pulses, separated in frequency by the vibrational frequency of a targeted molecule, only the specific vibrational level of the target molecules in the illuminated tissue volume is excited. This targeted optical absorption generates ultrasonic waves (referred to as stimulated Raman photoacoustic waves) which are detected using a traditional ultrasonic transducer to form an image following the design of the established photoacoustic microscopy. PMID:21059930

  19. Role of repetitive transcranial magnetic stimulation in stroke rehabilitation.

    PubMed

    Pinter, Michaela M; Brainin, Michael

    2013-01-01

    In recent years, efforts have focused on investigating the neurophysiological changes that occur in the brain after stroke, and on developing novel strategies such as additional brain stimulation to enhance sensorimotor and cognitive recovery. In the 1990s, repetitive transcranial magnetic stimulation (rTMS) was introduced as a therapeutic tool for improving the efficacy of rehabilitation for recovery after stroke. It is evident that disturbances of interhemispheric processes after stroke result in a pathological hyperactivity of the intact hemisphere. The rationale of using rTMS as a complementary therapy is mainly to decrease the cortical excitability in regions that are presumed to hinder optimal recovery by low-frequency rTMS delivered to the unaffected hemisphere, while high-frequency rTMS delivered to the affected hemisphere facilitates cortical excitability. However, the exact mechanisms of how rTMS works are still under investigation. There is a growing body of research in stroke patients investigating the effect of rTMS on facilitating recovery by modifying cortical and subcortical networks. Clinical trials applying rTMS already yielded promising results in improving recovery of sensorimotor and cognitive functions. Altogether, in combination with conventional therapeutic approaches, rTMS has a potential to become a complementary strategy to enhance stroke recovery by modulating the excitability of targeted brain areas. In future studies, emphasis should be placed on selecting patient populations to determine whether treatment response depends on age, lesion acuteness, or stroke severity. Furthermore, it is important to identify parameters optimizing the beneficial effects of rTMS on stroke recovery, and to monitor their long-term effects.

  20. Repetitive transcranial magnetic stimulator with controllable pulse parameters.

    PubMed

    Peterchev, Angel V; Murphy, David L; Lisanby, Sarah H

    2011-06-01

    The characteristics of transcranial magnetic stimulation (TMS) pulses influence the physiological effect of TMS. However, available TMS devices allow very limited adjustment of the pulse parameters. We describe a novel TMS device that uses a circuit topology incorporating two energy storage capacitors and two insulated-gate bipolar transistor (IGBT) modules to generate near-rectangular electric field pulses with adjustable number, polarity, duration, and amplitude of the pulse phases. This controllable pulse parameter TMS (cTMS) device can induce electric field pulses with phase widths of 10-310 µs and positive/negative phase amplitude ratio of 1-56. Compared to conventional monophasic and biphasic TMS, cTMS reduces energy dissipation up to 82% and 57% and decreases coil heating up to 33% and 41%, respectively. We demonstrate repetitive TMS trains of 3000 pulses at frequencies up to 50 Hz with electric field pulse amplitude and width variability less than the measurement resolution (1.7% and 1%, respectively). Offering flexible pulse parameter adjustment and reduced power consumption and coil heating, cTMS enhances existing TMS paradigms, enables novel research applications and could lead to clinical applications with potentially enhanced potency.

  1. Repetitive Transcranial Magnetic Stimulator with Controllable Pulse Parameters

    PubMed Central

    Peterchev, Angel V; Murphy, David L; Lisanby, Sarah H

    2013-01-01

    The characteristics of transcranial magnetic stimulation (TMS) pulses influence the physiological effect of TMS. However, available TMS devices allow very limited adjustment of the pulse parameters. We describe a novel TMS device that uses a circuit topology incorporating two energy storage capacitors and two insulated-gate bipolar transistor (IGBT) modules to generate near-rectangular electric field pulses with adjustable number, polarity, duration, and amplitude of the pulse phases. This controllable pulse parameter TMS (cTMS) device can induce electric field pulses with phase widths of 10–310 μs and positive/negative phase amplitude ratio of 1–56. Compared to conventional monophasic and biphasic TMS, cTMS reduces energy dissipation by up to 82% and 57%, and decreases coil heating by up to 33% and 41%, respectively. We demonstrate repetitive TMS trains of 3,000 pulses at frequencies up to 50 Hz with electric field pulse amplitude and width variability less than the measurement resolution (1.7% and 1%, respectively). Offering flexible pulse parameter adjustment and reduced power consumption and coil heating, cTMS enhances existing TMS paradigms, enables novel research applications, and could lead to clinical applications with potentially enhanced potency. PMID:21540487

  2. Repetitive transcranial magnetic stimulator with controllable pulse parameters

    NASA Astrophysics Data System (ADS)

    Peterchev, Angel V.; Murphy, David L.; Lisanby, Sarah H.

    2011-06-01

    The characteristics of transcranial magnetic stimulation (TMS) pulses influence the physiological effect of TMS. However, available TMS devices allow very limited adjustment of the pulse parameters. We describe a novel TMS device that uses a circuit topology incorporating two energy storage capacitors and two insulated-gate bipolar transistor (IGBT) modules to generate near-rectangular electric field pulses with adjustable number, polarity, duration, and amplitude of the pulse phases. This controllable pulse parameter TMS (cTMS) device can induce electric field pulses with phase widths of 10-310 µs and positive/negative phase amplitude ratio of 1-56. Compared to conventional monophasic and biphasic TMS, cTMS reduces energy dissipation up to 82% and 57% and decreases coil heating up to 33% and 41%, respectively. We demonstrate repetitive TMS trains of 3000 pulses at frequencies up to 50 Hz with electric field pulse amplitude and width variability less than the measurement resolution (1.7% and 1%, respectively). Offering flexible pulse parameter adjustment and reduced power consumption and coil heating, cTMS enhances existing TMS paradigms, enables novel research applications and could lead to clinical applications with potentially enhanced potency.

  3. The interaction between duration, velocity and repetitive auditory stimulation.

    PubMed

    Makin, Alexis D J; Poliakoff, Ellen; Dillon, Joe; Perrin, Aimee; Mullet, Thomas; Jones, Luke A

    2012-03-01

    Repetitive auditory stimulation (with click trains) and visual velocity signals both have intriguing effects on the subjective passage of time. Previous studies have established that prior presentation of auditory clicks increases the subjective duration of subsequent sensory input, and that faster moving stimuli are also judged to have been presented for longer (the time dilation effect). However, the effect of clicks on velocity estimation is unknown, and the nature of the time dilation effect remains ambiguous. Here were present a series of five experiments to explore these phenomena in more detail. Participants viewed a rightward moving grating which traveled at velocities ranging from 5 to 15°/s and which lasted for durations of 500 to 1500 ms. Gratings were preceded by clicks, silence or white noise. It was found that both clicks and higher velocities increased subjective duration. It was also found that the time dilation effect was a constant proportion of stimulus duration. This implies that faster velocity increases the rate of the pacemaker component of the internal clock. Conversely, clicks increased subjective velocity, but the magnitude of this effect was not proportional to actual velocity. Through considerations of these results, we conclude that clicks independently affect velocity and duration representations.

  4. [Repetitive transcranial magnetic stimulation in depression; stimulation of the brain in order to cure the psyche].

    PubMed

    Helmich, R C; Snijders, A H; Verkes, R J; Bloem, B R

    2004-02-28

    Transcranial magnetic stimulation (TMS) is a non-invasive approach to briefly stimulate or inhibit cortical brain areas. A novel approach entails the delivery of repetitive TMS pulses (rTMS) at a fixed frequency. In rTMS cortical activity is altered beyond the period of actual stimulation. The changes occur locally as well as at a distance in functionally connected brain areas. These features render rTMS a suitable tool to study normal brain functions and the pathophysiology of brain diseases. Furthermore, it is expected that rTMS could be used as a novel therapy for neurological or psychiatric diseases characterised by abnormal cortical activation. This possibility has been studied mostly in patients suffering from depression, where rTMS has been used to restore normal activity in the hypoactive prefrontal cortex. Despite statistically significant therapeutic effects in small sized trials, the clinical implications are still limited.

  5. Repetitive Transcranial Magnetic Stimulation of the Primary Somatosensory Cortex Modulates Perception of the Tendon Vibration Illusion.

    PubMed

    Huh, D C; Lee, J M; Oh, S M; Lee, J-H; Van Donkelaar, P; Lee, D H

    2016-10-01

    The effect of repetitive transcranial magnetic stimulation on kinesthetic perception, when applied to the somatosensory cortex, was examined. Further, the facilitatory and inhibitory effects of repetitive transcranial magnetic stimulation using different stimulation frequencies were tested. Six female (M age = 32.0 years, SD = 6.7) and nine male (M age = 32.9 years, SD = 6.6) participants were asked to perceive the tendon vibration illusion of the left wrist joint and to replicate the illusion with their right hand. When comparing changes in the corresponding movement amplitude and velocity after three different repetitive transcranial magnetic stimulation protocols (sham, 1 Hz inhibitory, and 5 Hz facilitatory repetitive transcranial magnetic stimulation), the movement amplitude was found to decrease with the inhibitory repetitive transcranial magnetic stimulation, while the movement velocity respectively increased and decreased with the facilitatory and inhibitory repetitive transcranial magnetic stimulation. These results confirmed the modulating effects of repetitive transcranial magnetic stimulation on kinesthetic perception in a single experimental paradigm.

  6. A feasible repetitive transcranial magnetic stimulation clinical protocol in migraine prevention

    PubMed Central

    Zardouz, Shawn; Shi, Lei; Leung, Albert

    2016-01-01

    Objective: This case series was conducted to determine the clinical feasibility of a repetitive transcranial magnetic stimulation protocol for the prevention of migraine (with and without aura). Methods: Five patients with migraines underwent five repetitive transcranial magnetic stimulation sessions separated in 1- to 2-week intervals for a period of 2 months at a single tertiary medical center. Repetitive transcranial magnetic stimulation was applied to the left motor cortex with 2000 pulses (20 trains with 1s inter-train interval) delivered per session, at a frequency of 10 Hz and 80% resting motor threshold. Pre- and post-treatment numerical rating pain scales were collected, and percent reductions in intensity, frequency, and duration were generated. Results: An average decrease in 37.8%, 32.1%, and 31.2% were noted in the intensity, frequency, and duration of migraines post-repetitive transcranial magnetic stimulation, respectively. A mean decrease in 1.9±1.0 (numerical rating pain scale ± standard deviation; range: 0.4–2.8) in headache intensity scores was noted after the repetitive transcranial magnetic stimulation sessions. Conclusion: The tested repetitive transcranial magnetic stimulation protocol is a well-tolerated, safe, and effective method for migraine prevention. PMID:27826448

  7. Repetitive transcranial magnetic stimulation and transcranial direct current stimulation in motor rehabilitation after stroke: an update.

    PubMed

    Klomjai, W; Lackmy-Vallée, A; Roche, N; Pradat-Diehl, P; Marchand-Pauvert, V; Katz, R

    2015-09-01

    Stroke is a leading cause of adult motor disability. The number of stroke survivors is increasing in industrialized countries, and despite available treatments used in rehabilitation, the recovery of motor functions after stroke is often incomplete. Studies in the 1980s showed that non-invasive brain stimulation (mainly repetitive transcranial magnetic stimulation [rTMS] and transcranial direct current stimulation [tDCS]) could modulate cortical excitability and induce plasticity in healthy humans. These findings have opened the way to the therapeutic use of the 2 techniques for stroke. The mechanisms underlying the cortical effect of rTMS and tDCS differ. This paper summarizes data obtained in healthy subjects and gives a general review of the use of rTMS and tDCS in stroke patients with altered motor functions. From 1988 to 2012, approximately 1400 publications were devoted to the study of non-invasive brain stimulation in humans. However, for stroke patients with limb motor deficit, only 141 publications have been devoted to the effects of rTMS and 132 to those of tDCS. The Cochrane review devoted to the effects of rTMS found 19 randomized controlled trials involving 588 patients, and that devoted to tDCS found 18 randomized controlled trials involving 450 patients. Without doubt, rTMS and tDCS contribute to physiological and pathophysiological studies in motor control. However, despite the increasing number of studies devoted to the possible therapeutic use of non-invasive brain stimulation to improve motor recovery after stroke, further studies will be necessary to specify their use in rehabilitation.

  8. Normalization of sensorimotor integration by repetitive transcranial magnetic stimulation in cervical dystonia.

    PubMed

    Zittel, S; Helmich, R C; Demiralay, C; Münchau, A; Bäumer, T

    2015-08-01

    Previous studies indicated that sensorimotor integration and plasticity of the sensorimotor system are impaired in dystonia patients. We investigated motor evoked potential amplitudes and short latency afferent inhibition to examine corticospinal excitability and cortical sensorimotor integration, before and after inhibitory 1 Hz repetitive transcranial magnetic stimulation over primary sensory and primary motor cortex in patients with cervical dystonia (n = 12). Motor evoked potentials were recorded from the right first dorsal interosseous muscle after application of unconditioned transcranial magnetic test stimuli and after previous conditioning electrical stimulation of the right index finger at short interstimulus intervals of 25, 30 and 40 ms. Results were compared to a group of healthy age-matched controls. At baseline, motor evoked potential amplitudes did not differ between groups. Short latency afferent inhibition was reduced in cervical dystonia patients compared to healthy controls. Inhibitory 1 Hz sensory cortex repetitive transcranial magnetic stimulation but not motor cortex repetitive transcranial magnetic stimulation increased motor evoked potential amplitudes in cervical dystonia patients. Additionally, both 1 Hz repetitive transcranial magnetic stimulation over primary sensory and primary motor cortex normalized short latency afferent inhibition in these patients. In healthy subjects, sensory repetitive transcranial magnetic stimulation had no influence on motor evoked potential amplitudes and short latency afferent inhibition. Plasticity of sensorimotor circuits is altered in cervical dystonia patients.

  9. Brain topological correlates of motor performance changes after repetitive transcranial magnetic stimulation.

    PubMed

    Park, Chang-hyun; Chang, Won Hyuk; Yoo, Woo-Kyoung; Shin, Yong-Il; Kim, Sung Tae; Kim, Yun-Hee

    2014-05-01

    Repetitive transcranial magnetic stimulation (rTMS) influences the brain temporally beyond the stimulation period and spatially beyond the stimulation site. Application of rTMS over the primary motor cortex (M1) has been shown to lead to plastic changes in interregional connectivity over the motor system as well as alterations in motor performance. With a sequential combination of rTMS over the M1 and functional magnetic resonance imaging (fMRI), we sought changes in the topology of brain networks and specifically the association of brain topological changes with motor performance changes. In a sham-controlled parallel group experimental design, real or sham rTMS was administered to each of the 15 healthy subjects without prior motor-related dysfunctions, over the right M1 at a high frequency of 10 Hz. Before and after the intervention, fMRI data were acquired during a sequential finger motor task using the left, nondominant hand. Changes in the topology of brain networks were assessed in terms of global and local efficiency, which measures the efficiency in transporting information at global and local scales, respectively, provided by graph-theoretical analysis. Greater motor performance changes toward improvements after real rTMS were shown in individuals who exhibited more increases in global efficiency and more decreases in local efficiency. The enhancement of motor performance after rTMS is supposed to be associated with brain topological changes, such that global information exchange is facilitated, while local information exchange is restricted.

  10. Influence of repetitive peripheral magnetic stimulation on neural plasticity in the motor cortex related to swallowing.

    PubMed

    Momosaki, Ryo; Kakuda, Wataru; Yamada, Naoki; Abo, Masahiro

    2016-09-01

    The aim of this study was to evaluate the effect of repetitive peripheral magnetic stimulation at two different frequencies (20 and 30 Hz) on cortical excitability in motor areas related to swallowing in healthy individuals. The study participants were 10 healthy normal volunteers (two women and eight men, age range 25-36 years). Repetitive peripheral magnetic stimulation was applied to the submandibular muscle using a parabolic coil at the site where contraction of the suprahyoid muscles was elicited. Stimulation was continued for 10 min (total 1200 pulses) at 20 Hz on 1 day and at 30 Hz on another day, with the stimulation strength set at 90% of the intensity that elicited pain. The motor-evoked potential amplitude of suprahyoid muscles was assessed before, immediately after, and 30 min after stimulation. Stimulations at both 20 and 30 Hz significantly increased motor-evoked potential amplitude (P<0.05), with the increase maintained until 30 min after stimulation. The motor-evoked potential amplitude immediately after stimulation was not significantly different between the 20 and 30 Hz frequencies. The results indicated that repetitive magnetic stimulation increased motor-evoked potential amplitude of swallowing muscles, suggesting facilitation of the motor cortex related to swallowing in healthy individuals.

  11. Immediate Effects of Repetitive Magnetic Stimulation on Single Cortical Pyramidal Neurons

    PubMed Central

    Banerjee, Jineta; Sorrell, Mary E.; Celnik, Pablo A.; Pelled, Galit

    2017-01-01

    Repetitive Transcranial Magnetic Stimulation (rTMS) has been successfully used as a non-invasive therapeutic intervention for several neurological disorders in the clinic as well as an investigative tool for basic neuroscience. rTMS has been shown to induce long-term changes in neuronal circuits in vivo. Such long-term effects of rTMS have been investigated using behavioral, imaging, electrophysiological, and molecular approaches, but there is limited understanding of the immediate effects of TMS on neurons. We investigated the immediate effects of high frequency (20 Hz) rTMS on the activity of cortical neurons in an effort to understand the underlying cellular mechanisms activated by rTMS. We used whole-cell patch-clamp recordings in acute rat brain slices and calcium imaging of cultured primary neurons to examine changes in neuronal activity and intracellular calcium respectively. Our results indicate that each TMS pulse caused an immediate and transient activation of voltage gated sodium channels (9.6 ± 1.8 nA at -45 mV, p value < 0.01) in neurons. Short 500 ms 20 Hz rTMS stimulation induced action potentials in a subpopulation of neurons, and significantly increased the steady state current of the neurons at near threshold voltages (at -45 mV: before TMS: I = 130 ± 17 pA, during TMS: I = 215 ± 23 pA, p value = 0.001). rTMS stimulation also led to a delayed increase in intracellular calcium (153.88 ± 61.94% increase from baseline). These results show that rTMS has an immediate and cumulative effect on neuronal activity and intracellular calcium levels, and suggest that rTMS may enhance neuronal responses when combined with an additional motor, sensory or cognitive stimulus. Thus, these results could be translated to optimize rTMS protocols for clinical as well as basic science applications. PMID:28114421

  12. Repetitive Transcranial Magnetic Stimulation to the Primary Motor Cortex Interferes with Motor Learning by Observing

    ERIC Educational Resources Information Center

    Brown, Liana E.; Wilson, Elizabeth T.; Gribble, Paul L.

    2009-01-01

    Neural representations of novel motor skills can be acquired through visual observation. We used repetitive transcranial magnetic stimulation (rTMS) to test the idea that this "motor learning by observing" is based on engagement of neural processes for learning in the primary motor cortex (M1). Human subjects who observed another person learning…

  13. Repetitive Transcranial Magnetic Stimulation in Resistant Visual Hallucinations in a Woman With Schizophrenia: A Case Report

    PubMed Central

    Ghanbari Jolfaei, Atefeh; Naji, Borzooyeh; Nasr Esfehani, Mehdi

    2016-01-01

    A 29-year-old woman with schizophrenia introduced for application of repetitive transcranial magnetic stimulation for refractory visual hallucinations. Following inhibitory rTMS on visual cortex she reported significant reduction in severity and simplification of complexity of hallucinations, which lasted for three months. rTMS can be considered as a possibly potent treatment for visual hallucinations. PMID:27284279

  14. Repetitive transcranial magnetic stimulation for clinical applications in neurological and psychiatric disorders: an overview.

    PubMed

    Machado, Sergio; Arias-Carrión, Oscar; Paes, Flávia; Vieira, Renata Teles; Caixeta, Leonardo; Novaes, Felipe; Marinho, Tamires; Almada, Leonardo Ferreira; Silva, Adriana Cardoso; Nardi, Antonio Egidio

    2013-10-01

    Neurological and psychiatric disorders are characterized by several disabling symptoms for which effective, mechanism-based treatments remain elusive. Consequently, more advanced non-invasive therapeutic methods are required. A method that may modulate brain activity and be viable for use in clinical practice is repetitive transcranial magnetic stimulation (rTMS). It is a non-invasive procedure whereby a pulsed magnetic field stimulates electrical activity in the brain. Here, we focus on the basic foundation of rTMS, the main stimulation parametters, the factors that influence individual responses to rTMS and the experimental advances of rTMS that may become a viable clinical application to treat neurological and psychiatric disorders. The findings showed that rTMS can improve some symptoms associated with these conditions and might be useful for promoting cortical plasticity in patients with neurological and psychiatric disorders. However, these changes are transient and it is premature to propose these applications as realistic therapeutic options, even though the rTMS technique has been evidenced as a potential modulator of sensorimotor integration and neuroplasticity. Functional imaging of the region of interest could highlight the capacity of rTMS to bring about plastic changes of the cortical circuitry and hint at future novel clinical interventions. Thus, we recommend that further studies clearly determine the role of rTMS in the treatment of these conditions. Finally, we must remember that however exciting the neurobiological mechanisms might be, the clinical usefulness of rTMS will be determined by its ability to provide patients with neurological and psychiatric disorders with safe, long-lasting and substantial improvements in quality of life.

  15. Repetitive Transcranial Magnetic Stimulation for Clinical Applications in Neurological and Psychiatric Disorders: An Overview

    PubMed Central

    Machado, Sergio; Arias-Carrión, Oscar; Paes, Flávia; Vieira, Renata Teles; Caixeta, Leonardo; Novaes, Felipe; Marinho, Tamires; Almada, Leonardo Ferreira; Silva, Adriana Cardoso; Nardi, Antonio Egidio

    2013-01-01

    Neurological and psychiatric disorders are characterized by several disabling symptoms for which effective, mechanism-based treatments remain elusive. Consequently, more advanced non-invasive therapeutic methods are required. A method that may modulate brain activity and be viable for use in clinical practice is repetitive transcranial magnetic stimulation (rTMS). It is a non-invasive procedure whereby a pulsed magnetic field stimulates electrical activity in the brain. Here, we focus on the basic foundation of rTMS, the main stimulation parametters, the factors that influence individual responses to rTMS and the experimental advances of rTMS that may become a viable clinical application to treat neurological and psychiatric disorders. The findings showed that rTMS can improve some symptoms associated with these conditions and might be useful for promoting cortical plasticity in patients with neurological and psychiatric disorders. However, these changes are transient and it is premature to propose these applications as realistic therapeutic options, even though the rTMS technique has been evidenced as a potential modulator of sensorimotor integration and neuroplasticity. Functional imaging of the region of interest could highlight the capacity of rTMS to bring about plastic changes of the cortical circuitry and hint at future novel clinical interventions. Thus, we recommend that further studies clearly determine the role of rTMS in the treatment of these conditions. Finally, we must remember that however exciting the neurobiological mechanisms might be, the clinical usefulness of rTMS will be determined by its ability to provide patients with neurological and psychiatric disorders with safe, long-lasting and substantial improvements in quality of life. PMID:25610279

  16. Repetitive transcranial magnetic stimulation over the supplementary motor area modifies breathing pattern in response to inspiratory loading in normal humans

    PubMed Central

    Nierat, Marie-Cécile; Hudson, Anna L.; Chaskalovic, Joël; Similowski, Thomas; Laviolette, Louis

    2015-01-01

    In awake humans, breathing depends on automatic brainstem pattern generators. It is also heavily influenced by cortical networks. For example, functional magnetic resonance imaging and electroencephalographic data show that the supplementary motor area becomes active when breathing is made difficult by inspiratory mechanical loads like resistances or threshold valves, which is associated with perceived respiratory discomfort. We hypothesized that manipulating the excitability of the supplementary motor area with repetitive transcranial magnetic stimulation would modify the breathing pattern response to an experimental inspiratory load and possibly respiratory discomfort. Seven subjects (three men, age 25 ± 4) were studied. Breathing pattern and respiratory discomfort during inspiratory loading were described before and after conditioning the supplementary motor area with repetitive stimulation, using an excitatory paradigm (5 Hz stimulation), an inhibitory paradigm, or sham stimulation. No significant change in breathing pattern during loading was observed after sham conditioning. Excitatory conditioning shortened inspiratory time (p = 0.001), decreased tidal volume (p = 0.016), and decreased ventilation (p = 0.003), as corroborated by an increased end-tidal expired carbon dioxide (p = 0.013). Inhibitory conditioning did not affect ventilation, but lengthened expiratory time (p = 0.031). Respiratory discomfort was mild under baseline conditions, and unchanged after conditioning of the supplementary motor area. This is the first study to show that repetitive transcranial magnetic stimulation conditioning of the cerebral cortex can alter breathing pattern. A 5 Hz conditioning protocol, known to enhance corticophrenic excitability, can reduce the amount of hyperventilation induced by inspiratory threshold loading. Further studies are needed to determine whether and under what circumstances rTMS can have an effect on dyspnoea. PMID:26483701

  17. Remodeling Brain Activity by Repetitive Cervicothoracic Transspinal Stimulation after Human Spinal Cord Injury

    PubMed Central

    Murray, Lynda M.; Knikou, Maria

    2017-01-01

    Interventions that can produce targeted brain plasticity after human spinal cord injury (SCI) are needed for restoration of impaired movement in these patients. In this study, we tested the effects of repetitive cervicothoracic transspinal stimulation in one person with cervical motor incomplete SCI on cortical and corticospinal excitability, which were assessed via transcranial magnetic stimulation with paired and single pulses, respectively. We found that repetitive cervicothoracic transspinal stimulation potentiated intracortical facilitation in flexor and extensor wrist muscles, recovered intracortical inhibition in the more impaired wrist flexor muscle, increased corticospinal excitability bilaterally, and improved voluntary muscle strength. These effects may have been mediated by improvements in cortical integration of ascending sensory inputs and strengthening of corticospinal connections. Our novel therapeutic intervention opens new avenues for targeted brain neuromodulation protocols in individuals with cervical motor incomplete SCI. PMID:28265259

  18. Repetitive transcranial magnetic stimulation for the treatment of chronic tinnitus after traumatic brain injury: a case study.

    PubMed

    Kreuzer, Peter Michael; Landgrebe, Michael; Frank, Elmar; Langguth, Berthold

    2013-01-01

    Tinnitus is a frequent symptom of traumatic brain injury, which is difficult to treat. Repetitive transcranial magnetic stimulation has shown beneficial effects in some forms of tinnitus. However, traumatic brain injury in the past has been considered as a relative contraindication for repetitive transcranial magnetic stimulation because of the increased risk of seizures. Here we present the case of a 53-year-old male patient suffering from severe tinnitus after traumatic brain injury with comorbid depression and alcohol abuse, who received 5 treatment series of repetitive transcranial magnetic stimulation (1 Hz stimulation protocol over left primary auditory cortex, 10 sessions of 2000 stimuli each, stimulation intensity 110% resting motor threshold). Repetitive transcranial magnetic stimulation was tolerated without any side effects and tinnitus complaints (measured by a validated tinnitus questionnaire and numeric rating scales) were improved in a replicable way throughout 5 courses of transcranial magnetic stimulation up to now.

  19. Non-invasive mapping of calculation function by repetitive navigated transcranial magnetic stimulation.

    PubMed

    Maurer, Stefanie; Tanigawa, Noriko; Sollmann, Nico; Hauck, Theresa; Ille, Sebastian; Boeckh-Behrens, Tobias; Meyer, Bernhard; Krieg, Sandro M

    2016-11-01

    Concerning calculation function, studies have already reported on localizing computational function in patients and volunteers by functional magnetic resonance imaging and transcranial magnetic stimulation. However, the development of accurate repetitive navigated TMS (rTMS) with a considerably higher spatial resolution opens a new field in cognitive neuroscience. This study was therefore designed to evaluate the feasibility of rTMS for locating cortical calculation function in healthy volunteers, and to establish this technique for future scientific applications as well as preoperative mapping in brain tumor patients. Twenty healthy subjects underwent rTMS calculation mapping using 5 Hz/10 pulses. Fifty-two previously determined cortical spots of the whole hemispheres were stimulated on both sides. The subjects were instructed to perform the calculation task composed of 80 simple arithmetic operations while rTMS pulses were applied. The highest error rate (80 %) for all errors of all subjects was observed in the right ventral precentral gyrus. Concerning division task, a 45 % error rate was achieved in the left middle frontal gyrus. The subtraction task showed its highest error rate (40 %) in the right angular gyrus (anG). In the addition task a 35 % error rate was observed in the left anterior superior temporal gyrus. Lastly, the multiplication task induced a maximum error rate of 30 % in the left anG. rTMS seems feasible as a way to locate cortical calculation function. Besides language function, the cortical localizations are well in accordance with the current literature for other modalities or lesion studies.

  20. The effect of 10 Hz repetitive transcranial magnetic stimulation of posterior parietal cortex on visual attention.

    PubMed

    Dombrowe, Isabel; Juravle, Georgiana; Alavash, Mohsen; Gießing, Carsten; Hilgetag, Claus C

    2015-01-01

    Repetitive transcranial magnetic stimulation (rTMS) of the posterior parietal cortex (PPC) at frequencies lower than 5 Hz transiently inhibits the stimulated area. In healthy participants, such a protocol can induce a transient attentional bias to the visual hemifield ipsilateral to the stimulated hemisphere. This bias might be due to a relatively less active stimulated hemisphere and a relatively more active unstimulated hemisphere. In a previous study, Jin and Hilgetag (2008) tried to switch the attention bias from the hemifield ipsilateral to the hemifield contralateral to the stimulated hemisphere by applying high frequency rTMS. High frequency rTMS has been shown to excite, rather than inhibit, the stimulated brain area. However, the bias to the ipsilateral hemifield was still present. The participants' performance decreased when stimuli were presented in the hemifield contralateral to the stimulation site. In the present study we tested if this unexpected result was related to the fact that participants were passively resting during stimulation rather than performing a task. Using a fully crossed factorial design, we compared the effects of high frequency rTMS applied during a visual detection task and high frequency rTMS during passive rest on the subsequent offline performance in the same detection task. Our results were mixed. After sham stimulation, performance was better after rest than after task. After active 10 Hz rTMS, participants' performance was overall better after task than after rest. However, this effect did not reach statistical significance. The comparison of performance after rTMS with task and performance after sham stimulation with task showed that 10 Hz stimulation significantly improved performance in the whole visual field. Thus, although we found a trend to better performance after rTMS with task than after rTMS during rest, we could not reject the hypothesis that high frequency rTMS with task and high frequency rTMS during rest

  1. The Effect of 10 Hz Repetitive Transcranial Magnetic Stimulation of Posterior Parietal Cortex on Visual Attention

    PubMed Central

    Dombrowe, Isabel; Juravle, Georgiana; Alavash, Mohsen; Gießing, Carsten; Hilgetag, Claus C.

    2015-01-01

    Repetitive transcranial magnetic stimulation (rTMS) of the posterior parietal cortex (PPC) at frequencies lower than 5 Hz transiently inhibits the stimulated area. In healthy participants, such a protocol can induce a transient attentional bias to the visual hemifield ipsilateral to the stimulated hemisphere. This bias might be due to a relatively less active stimulated hemisphere and a relatively more active unstimulated hemisphere. In a previous study, Jin and Hilgetag (2008) tried to switch the attention bias from the hemifield ipsilateral to the hemifield contralateral to the stimulated hemisphere by applying high frequency rTMS. High frequency rTMS has been shown to excite, rather than inhibit, the stimulated brain area. However, the bias to the ipsilateral hemifield was still present. The participants’ performance decreased when stimuli were presented in the hemifield contralateral to the stimulation site. In the present study we tested if this unexpected result was related to the fact that participants were passively resting during stimulation rather than performing a task. Using a fully crossed factorial design, we compared the effects of high frequency rTMS applied during a visual detection task and high frequency rTMS during passive rest on the subsequent offline performance in the same detection task. Our results were mixed. After sham stimulation, performance was better after rest than after task. After active 10 Hz rTMS, participants’ performance was overall better after task than after rest. However, this effect did not reach statistical significance. The comparison of performance after rTMS with task and performance after sham stimulation with task showed that 10 Hz stimulation significantly improved performance in the whole visual field. Thus, although we found a trend to better performance after rTMS with task than after rTMS during rest, we could not reject the hypothesis that high frequency rTMS with task and high frequency rTMS during rest

  2. Repetitive transcranial magnetic stimulation to improve mood and motor function in Parkinson's disease.

    PubMed

    Helmich, Rick C; Siebner, Hartwig R; Bakker, Maaike; Münchau, Alexander; Bloem, Bastiaan R

    2006-10-25

    Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that can produce lasting changes in excitability and activity in cortical regions underneath the stimulation coil (local effect), but also within functionally connected cortical or subcortical regions (remote effects). Since the clinical presentation of Parkinson's disease (PD) is related to abnormal neuronal activity within the basal ganglia and cortical regions, including the primary motor cortex, the premotor cortex and the prefrontal cortex, several studies have used rTMS to improve brain function in PD. Here, we review the studies that have investigated the possible therapeutic effects of rTMS on mood and motor function in PD patients. We highlight some methodological inconsistencies and problems, including the difficulty to define the most effective protocol for rTMS or to establish an appropriate placebo condition. We finally propose future directions of research that may help to improve the therapeutic efficacy of rTMS in PD.

  3. Repetitive Transcranial Magnetic Stimulation in Cervical Dystonia: Effect of Site and Repetition in a Randomized Pilot Trial

    PubMed Central

    Pirio Richardson, Sarah; Tinaz, Sule; Chen, Robert

    2015-01-01

    Dystonia is characterized by abnormal posturing due to sustained muscle contraction, which leads to pain and significant disability. New therapeutic targets are needed in this disorder. The objective of this randomized, sham-controlled, blinded exploratory study is to identify a specific motor system target for non-invasive neuromodulation and to evaluate this target in terms of safety and tolerability in the cervical dystonia (CD) population. Eight CD subjects were given 15-minute sessions of low-frequency (0.2 Hz) repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (MC), dorsal premotor cortex (dPM), supplementary motor area (SMA), anterior cingulate cortex (ACC) and a sham condition with each session separated by at least two days. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) score was rated in a blinded fashion immediately pre- and post-intervention. Secondary outcomes included physiology and tolerability ratings. The mean change in TWSTRS severity score by site was 0.25 ± 1.7 (ACC), -2.9 ± 3.4 (dPM), -3.0 ± 4.8 (MC), -0.5 ± 1.1 (SHAM), and -1.5 ± 3.2 (SMA) with negative numbers indicating improvement in symptom control. TWSTRS scores decreased from Session 1 (15.1 ± 5.1) to Session 5 (11.0 ± 7.6). The treatment was tolerable and safe. Physiology data were acquired on 6 of 8 subjects and showed no change over time. These results suggest rTMS can modulate CD symptoms. Both dPM and MC are areas to be targeted in further rTMS studies. The improvement in TWSTRS scores over time with multiple rTMS sessions deserves further evaluation. Trial Registration ClinicalTrials.gov NCT01859247 PMID:25923718

  4. [Repetitive Transcranial Magnetic Stimulation (rTMS) for Higher Brain Function Deficits].

    PubMed

    Inoue, Yukichi

    2016-12-01

    The management of higher brain dysfunctions such as stroke-induced unilateral spatial neglect (USN) or aphasia is crucial because these dysfunctions have devastating neurological repercussions on the patients' daily life and quality of life. Impairment of the physiological interhemispheric rivalry is often the result of brain insults such as strokes or traumatic injuries, and it may lead to USN or aphasia. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation method, is a promising tool for restoring the pathological imbalance in interhemispheric rivalry by either suppressing the hyperactivity of the unaffected hemisphere or facilitating hypoactivity in the affected hemisphere. The concept of paradoxical functional facilitation (Kapur, 1996) has important clinical implications when coupled with rTMS applications. In addition to conventional rTMS (c-rTMS), other clinically relevant protocols of patterned rTMS (p-rTMS) have been developed: the theta burst stimulation (TBS), the paired associative stimulation (PAS), and the quadripulse stimulation (QPS). TBS is commonly used in the rehabilitation of patients with post-stroke USN and those with non-fluent aphasia because of its prolonged beneficial effects and the short duration of stimulation. TBS may be considered an effective and safe protocol of rTMS. We foresee broader clinical applications of p-rTMS (TBS) and c-rTMS in the treatment of various neurological deficits.

  5. Repetitive Transcranial Magnetic Stimulation for Wernicke-Korsakoff Syndrome: A Case Report.

    PubMed

    Chung, So Won; Park, Shin Who; Seo, Young Jae; Kim, Jae-Hyung; Lee, Chan Ho; Lim, Jong Youb

    2017-02-01

    A 57-year-old man who was diagnosed with Wernicke-Korsakoff syndrome showed severe impairment of cognitive function and a craving for alcohol, even after sufficient supplementation with thiamine. After completing 10 sessions of 10 Hz repetitive transcranial magnetic stimulation (rTMS) at 100% of the resting motor threshold over the left dorsolateral prefrontal cortex, dramatic improvement in cognitive function and a reduction in craving for alcohol were noted. This is the first case report of the efficacy of a high-frequency rTMS in the treatment of Wernicke-Korsakoff syndrome.

  6. Repetitive Transcranial Magnetic Stimulation for Wernicke-Korsakoff Syndrome: A Case Report

    PubMed Central

    2017-01-01

    A 57-year-old man who was diagnosed with Wernicke-Korsakoff syndrome showed severe impairment of cognitive function and a craving for alcohol, even after sufficient supplementation with thiamine. After completing 10 sessions of 10 Hz repetitive transcranial magnetic stimulation (rTMS) at 100% of the resting motor threshold over the left dorsolateral prefrontal cortex, dramatic improvement in cognitive function and a reduction in craving for alcohol were noted. This is the first case report of the efficacy of a high-frequency rTMS in the treatment of Wernicke-Korsakoff syndrome. PMID:28289650

  7. Effect of Epidural Electrical Stimulation and Repetitive Transcranial Magnetic Stimulation in Rats With Diffuse Traumatic Brain Injury

    PubMed Central

    Yoon, Yong-Soon; Cho, Kang Hee; Kim, Eun-Sil; Lee, Mi-Sook

    2015-01-01

    Objective To evaluate the effects of epidural electrical stimulation (EES) and repetitive transcranial magnetic stimulation (rTMS) on motor recovery and brain activity in a rat model of diffuse traumatic brain injury (TBI) compared to the control group. Methods Thirty rats weighing 270-285 g with diffuse TBI with 45 kg/cm2 using a weight-drop model were assigned to one of three groups: the EES group (ES) (anodal electrical stimulation at 50 Hz), the rTMS group (MS) (magnetic stimulation at 10 Hz, 3-second stimulation with 6-second intervals, 4,000 total stimulations per day), and the sham-treated control group (sham) (no stimulation). They were pre-trained to perform a single-pellet reaching task (SPRT) and a rotarod test (RRT) for 14 days. Diffuse TBI was then induced and an electrode was implanted over the dominant motor cortex. The changes in SPRT success rate, RRT performance time rate and the expression of c-Fos after two weeks of EES or rTMS were tracked. Results SPRT improved significantly from day 8 to day 12 in the ES group and from day 4 to day 14 in the MS group (p<0.05) compared to the sham group. RRT improved significantly from day 6 to day 11 in ES and from day 4 to day 9 in MS compared to the sham group. The ES and MS groups showed increased expression of c-Fos in the cerebral cortex compared to the sham group. Conclusion ES or MS in a rat model of diffuse TBI can be used to enhance motor recovery and brain activity. PMID:26161348

  8. Stimulated Brillouin Scattering Microscopic Imaging

    PubMed Central

    Ballmann, Charles W.; Thompson, Jonathan V.; Traverso, Andrew J.; Meng, Zhaokai; Scully, Marlan O.; Yakovlev, Vladislav V.

    2015-01-01

    Two-dimensional stimulated Brillouin scattering microscopy is demonstrated for the first time using low power continuous-wave lasers tunable around 780 nm. Spontaneous Brillouin spectroscopy has much potential for probing viscoelastic properties remotely and non-invasively on a microscopic scale. Nonlinear Brillouin scattering spectroscopy and microscopy may provide a way to tremendously accelerate the data aquisition and improve spatial resolution. This general imaging setup can be easily adapted for specific applications in biology and material science. The low power and optical wavelengths in the water transparency window used in this setup provide a powerful bioimaging technique for probing the mechanical properties of hard and soft tissue. PMID:26691398

  9. [Repetitive transcranial magnetic stimulation. A method in the treatment of depressions].

    PubMed

    Hansen, P E

    2000-04-17

    Transcranial magnetic stimulation (TMS) has been used as a diagnostic tool in neurology for more than a decade. Recent research indicates that it when applied repeatedly as repetitive transcranial magnetic stimulation (rTMS) has an antidepressant effect. RTMS is based on the principle of electro-magnetism. An electromagnetic coil placed on the scalp produces a time-varying magnetic field, which gives rise to a current in the proximity of the cerebral cortex. Unlike electroconvulsive therapy (ECT) rTMS does normally not give rise to epileptic seizures and does not require anaesthesia. This review covers a critical summary of the literature on the subject. The results of recent placebo-controlled, randomized trials are promising. However, further investigations are required, before rTMS can be fully integrated in the antidepressant therapeutic armamentarium.

  10. Daily left prefrontal repetitive transcranial magnetic stimulation for medication-resistant burning mouth syndrome.

    PubMed

    Umezaki, Y; Badran, B W; Gonzales, T S; George, M S

    2015-08-01

    Burning mouth syndrome (BMS) is a persistent and chronic burning sensation in the mouth in the absence of any abnormal organic findings. The pathophysiology of BMS is unclear and its treatment is not fully established. Although antidepressant medication is commonly used for treatment, there are some medication-resistant patients, and a new treatment for medication-resistant BMS is needed. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technology approved by the US Food and Drug Administration (FDA) for the treatment of depression. Recent studies have found beneficial effects of TMS for the treatment of pain. A case of BMS treated successfully with daily left prefrontal rTMS over a 2-week period is reported here. Based on this patient's clinical course and a recent pain study, the mechanism by which TMS may act to decrease the burning pain is discussed.

  11. Modulation of N400 in Chronic Non-Fluent Aphasia Using Low Frequency Repetitive Transcranial Magnetic Stimulation (rTMS)

    ERIC Educational Resources Information Center

    Barwood, Caroline H. S.; Murdoch, Bruce E.; Whelan, Brooke-Mai; Lloyd, David; Riek, Stephan; O'Sullivan, John D.; Coulthard, Alan; Wong, Andrew

    2011-01-01

    Low frequency Repetitive Transcranial Magnetic Stimulation (rTMS) has previously been applied to language homologues in non-fluent populations of persons with aphasia yielding significant improvements in behavioral language function up to 43 months post stimulation. The present study aimed to investigate the electrophysiological correlates…

  12. Effects of low-frequency repetitive transcranial magnetic stimulation on event-related potential P300

    NASA Astrophysics Data System (ADS)

    Torii, Tetsuya; Sato, Aya; Iwahashi, Masakuni; Iramina, Keiji

    2012-04-01

    The present study analyzed the effects of repetitive transcranial magnetic stimulation (rTMS) on brain activity. P300 latency of event-related potential (ERP) was used to evaluate the effects of low-frequency and short-term rTMS by stimulating the supramarginal gyrus (SMG), which is considered to be the related area of P300 origin. In addition, the prolonged stimulation effects on P300 latency were analyzed after applying rTMS. A figure-eight coil was used to stimulate left-right SMG, and intensity of magnetic stimulation was 80% of motor threshold. A total of 100 magnetic pulses were applied for rTMS. The effects of stimulus frequency at 0.5 or 1 Hz were determined. Following rTMS, an odd-ball task was performed and P300 latency of ERP was measured. The odd-ball task was performed at 5, 10, and 15 min post-rTMS. ERP was measured prior to magnetic stimulation as a control. Electroencephalograph (EEG) was measured at Fz, Cz, and Pz that were indicated by the international 10-20 electrode system. Results demonstrated that different effects on P300 latency occurred between 0.5-1 Hz rTMS. With 1 Hz low-frequency magnetic stimulation to the left SMG, P300 latency decreased. Compared to the control, the latency time difference was approximately 15 ms at Cz. This decrease continued for approximately 10 min post-rTMS. In contrast, 0.5 Hz rTMS resulted in delayed P300 latency. Compared to the control, the latency time difference was approximately 20 ms at Fz, and this delayed effect continued for approximately 15 min post-rTMS. Results demonstrated that P300 latency varied according to rTMS frequency. Furthermore, the duration of the effect was not similar for stimulus frequency of low-frequency rTMS.

  13. Repetitive transcranial magnetic stimulation induces long-lasting changes in protein expression and histone acetylation

    PubMed Central

    Etiévant, Adeline; Manta, Stella; Latapy, Camille; Magno, Luiz Alexandre V.; Fecteau, Shirley; Beaulieu, Jean-Martin

    2015-01-01

    The use of non-invasive brain stimulation like repetitive transcranial magnetic stimulation (rTMS) is an increasingly popular set of methods with promising results for the treatment of neurological and psychiatric disorders. Despite great enthusiasm, the impact of non-invasive brain stimulation on its neuronal substrates remains largely unknown. Here we show that rTMS applied over the frontal cortex of awaken mice induces dopamine D2 receptor dependent persistent changes of CDK5 and PSD-95 protein levels specifically within the stimulated brain area. Importantly, these modifications were associated with changes of histone acetylation at the promoter of these genes and prevented by administration of the histone deacetylase inhibitor MS-275. These findings show that, like several other psychoactive treatments, repeated rTMS sessions can exert long-lasting effects on neuronal substrates. This underscores the need of understanding these effects in the development of future clinical applications as well as in the establishment of improved guidelines to use rTMS in non-medical settings. PMID:26585834

  14. Treating Clinical Depression with Repetitive Deep Transcranial Magnetic Stimulation Using the Brainsway H1-coil

    PubMed Central

    Feifel, David; Pappas, Katherine

    2016-01-01

    Repetitive transcranial magnetic stimulation (rTMS) is an emerging non-pharmacological approach to treating many brain-based disorders. rTMS uses electromagnetic coils to stimulate areas of the brain non-invasively. Deep transcranial magnetic stimulation (dTMS) with the Brainsway H1-coil system specifically is a type of rTMS indicated for treating patients with major depressive disorder (MDD) who are resistant to medication. The unique H1-coil design of this device is able to stimulate neuronal pathways that lie deeper in the targeted brain areas than those reached by conventional rTMS coils. dTMS is considered to be low-risk and well tolerated, making it a viable treatment option for people who have not responded to medication or psychotherapy trials for their depression. Randomized, sham-control studies have demonstrated that dTMS produces significantly greater improvement in depressive symptoms than sham dTMS treatment in patients with major depression that has not responded to antidepressant medication. In this paper, we will review the methodology for treating major depression with dTMS using an H1-coil. PMID:27768049

  15. Repetitive nerve stimulation decreases the acetylcholine content of quanta at the frog neuromuscular junction.

    PubMed

    Naves, L A; Van der Kloot, W

    2001-05-01

    We investigated how elevated quantal release produced by motor nerve stimulation affects the size of the quanta. The motor nerve was stimulated at 10 Hz in preparations in which excitation-contraction coupling was disrupted. Two hundred stimuli reduced the size of the time integrals of the miniature endplate currents ([integral]MEPCs), measured at the same junction immediately after stimulation, by 16 %. Three thousand stimuli reduced size by 23 %. When the solution contained 10 microM neostigmine (NEO) 3000 stimuli reduced [integral]MEPCs by 60 %, because with acetylcholinesterase (AChE) inhibited, [integral]MEPC size is more sensitive to changes in acetylcholine (ACh) content. Similar decreases in miniature endplate potential size ([integral]MEPP) followed repetitive stimulation of contracting preparations. The depolarization produced by iontophoretic pulses of ACh was scarcely changed by 3000 nerve stimuli at 10 Hz, suggesting that the decreases in miniature sizes are largely due to less ACh released per quantum. Following 3000 stimuli at 10 Hz the sizes of the [integral]MEPCs increased back to pre-stimulus values with a half-time of 8-10 min. Recovery was blocked by (-)-vesamicol (VES), by hemicholinium-3 (HC3) and by nicotinic cholinergic agonists - all of which inhibit ACh loading into synaptic vesicles. The number of quanta in the total store was estimated by releasing them with carbonyl cyanide m-chlorophenylhydrazone (CCCP). CCCP releases fewer quanta after stimulation than from unstimulated controls. After resting for hours following stimulation, the releasable number increased, even when ACh loading inhibitors were present. We conclude that the inhibitors do not block a significant fraction of the ACh loading into reformed reserve vesicles and propose that ACh can be loaded in a series of steps.

  16. Enhanced accuracy in novel mirror drawing after repetitive transcranial magnetic stimulation-induced proprioceptive deafferentation.

    PubMed

    Balslev, Daniela; Christensen, Lars O D; Lee, Ji-Hang; Law, Ian; Paulson, Olaf B; Miall, R Christopher

    2004-10-27

    When performing visually guided actions under conditions of perturbed visual feedback, e.g., in a mirror or a video camera, there is a spatial conflict between visual and proprioceptive information. Recent studies have shown that subjects without proprioception avoid this conflict and show a performance benefit. In this study, we tested whether deafferentation induced by repetitive transcranial magnetic stimulation (rTMS) can improve mirror tracing skills in normal subjects. Hand trajectory error during novel mirror drawing was compared across two groups of subjects that received either 1 Hz rTMS over the somatosensory cortex contralateral to the hand or sham stimulation. Mirror tracing was more accurate after rTMS than after sham stimulation. Using a position-matching task, we confirmed that rTMS reduced proprioceptive acuity and that this reduction was largest when the coil was placed at an anterior parietal site. It is thus possible, with rTMS, to enhance motor performance in tasks involving a visuoproprioceptive conflict, presumably by reducing the excitability of somatosensory cortical areas that contribute to the sense of hand position.

  17. Repetitive Electric Stimulation Elicits Enduring Improvement of Sensorimotor Performance in Seniors

    PubMed Central

    Kalisch, Tobias; Tegenthoff, Martin; Dinse, Hubert R.

    2010-01-01

    Age-related changes occur on all stages of the human somatosensory pathway, thereby deteriorating tactile, haptic, and sensorimotor performance. However, recent studies show that age-related changes are not irreversible but treatable through peripheral stimulation paradigms based on neuroplasticity mechanisms. We here applied repetitive electric stimulation (rES) to the fingers on a bi-weekly basis for 4 weeks to induce enduring amelioration of age-related changes in healthy individuals aged 60–85 years. Tactile, haptic, and motor performance gradually improved over time of intervention. After termination of rES, tactile acuity recovered to baseline within 2 weeks, while the gains in haptic and motor performance were preserved for 2 weeks. Sham stimulation showed no comparable changes. Our data indicate that age-related decline of sensorimotor performance can be ameliorated by rES and can be stabilized by the repeated application. Thus, long-term application of rES appears as a prime candidate for maintaining sensorimotor functions in elderly individuals. PMID:20414332

  18. Repetitive Transcranial Magnetic Stimulation (rTMS)-Induced Trigeminal Autonomic Cephalalgia

    PubMed Central

    DURMAZ, Onur; ATEŞ, Mehmet Alpay; ŞENOL, Mehmet Güney

    2015-01-01

    Repetitive transcranial magnetic stimulation (rTMS) is an effective and novel treatment method that has been approved for the treatment of refractory depression by the U.S. Food and Drug Administration. The most common side effects of rTMS are a transient headache that usually responds to simple analgesics, local discomfort in the stimulation area, dizziness, ipsilateral lacrimation and, very rarely, generalized seizure. TMS is also regarded as a beneficial tool for investigating mechanisms underlying headache. Although rTMS has considerable benefits in terms of headache, there is the potential for rare side effects. In this report, we present the case of a patient with no history of autonomic headache who underwent a course of rTMS for refractory unipolar depression caused by an inadequate response to pharmacotherapy. After his fourth rTMS session, the patient developed sudden headaches with characteristics of trigeminal autonomic cephalalgia on the stimulated side, representing a noteworthy example of the potential side effects of rTMS. PMID:28360729

  19. Lateralized effects of prefrontal repetitive transcranial magnetic stimulation on emotional working memory.

    PubMed

    Weigand, Anne; Grimm, Simone; Astalosch, Antje; Guo, Jia Shen; Briesemeister, Benny B; Lisanby, Sarah H; Luber, Bruce; Bajbouj, Malek

    2013-05-01

    Little is known about the neural correlates underlying the integration of working memory and emotion processing. We investigated the effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) applied over the left or right dorsolateral prefrontal cortex (DLPFC) on emotional working memory. In a sham-controlled crossover design, participants performed an emotional 3-back task (EMOBACK) at baseline and after stimulation (1 Hz, 15 min, 110 % of the resting motor threshold) in two subsequent sessions. Stimuli were words assigned to the distinct emotion categories fear and anger as well as neutral words. We found lateralized rTMS effects in the EMOBACK task accuracy for fear-related words, with enhanced performance after rTMS applied over the right DLPFC and impaired performance after rTMS applied over the left DLPFC. No significant stimulation effect could be found for anger-related and neutral words. Our findings are the first to demonstrate a causal role of the right DLPFC in working memory for negative, withdrawal-related words and provide further support for a hemispheric lateralization of emotion processing.

  20. History, Studies and Specific Uses of Repetitive Transcranial Magnetic Stimulation (rTMS) in Treating Epilepsy

    PubMed Central

    NOOHI, Sima; AMIRSALARI, Susan

    2016-01-01

    Objective In this study, repetitive Transcranial Magnetic Stimulation (rTMS) and its specific use for treating epilepsy were carefully scrutinized. Materials & Methods Target researches such as review articles, case reports, books and theses, which had to do with therapeutic method of rTMS were surveyed. It is worth mentioning that until the final stages, the search for records and documents related to rTMS went on and in the end, the collected data underwent a qualitative analysis. Results As the literature review suggests, TMS principally applies electromagnetic induction to generate an electric current inside the brain without physical contact. The therapeutic uses of rTMS are for a wide range of mental disorders, namely epilepsy, chronic pains, motor disorders and so on. Conclusion Despite safety concerns and possible side effects, many researchers subscribe to rTMS and see a bright future for it. PMID:27057180

  1. Local GABA Concentration Predicts Perceptual Improvements After Repetitive Sensory Stimulation in Humans.

    PubMed

    Heba, Stefanie; Puts, Nicolaas A J; Kalisch, Tobias; Glaubitz, Benjamin; Haag, Lauren M; Lenz, Melanie; Dinse, Hubert R; Edden, Richard A E; Tegenthoff, Martin; Schmidt-Wilcke, Tobias

    2016-03-01

    Learning mechanisms are based on synaptic plasticity processes. Numerous studies on synaptic plasticity suggest that the regulation of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) plays a central role maintaining the delicate balance of inhibition and excitation. However, in humans, a link between learning outcome and GABA levels has not been shown so far. Using magnetic resonance spectroscopy of GABA prior to and after repetitive tactile stimulation, we show here that baseline GABA+ levels predict changes in perceptual outcome. Although no net changes in GABA+ are observed, the GABA+ concentration prior to intervention explains almost 60% of the variance in learning outcome. Our data suggest that behavioral effects can be predicted by baseline GABA+ levels, which provide new insights into the role of inhibitory mechanisms during perceptual learning.

  2. Repetitive transcranial magnetic stimulation to treat substance use disorders and compulsive behavior.

    PubMed

    Protasio, Maria I B; da Silva, João P L; Arias-Carrión, Oscar; Nardi, Antonio E; Machado, Sergio; Cruz, Marcelo S

    2015-01-01

    Compulsions, like pathological gambling, binge-eating disorder, alcohol, tobacco or cocaine abuse and compulsive shopping have similar neurophysiological processing. This study aimed to examine the efficacy of repetitive transcranial magnetic stimulation (rTMS) in improving patient control over compulsive behavior. The rTMS modulatory role in cortical mesolimbic pathways possibly implies improvement of the inhibitory control system and compulsive consumption drive. Thus, craving reduction would be a component for control achievement. Within this context, 17 studies were found. Most studies applied rTMS over the left dorsolateral prefrontal cortex. Craving reduction was observed in 10 studies and was associated with improved control of compulsion in two of them. In one study reduction in consumption was found without reduction in craving. In addition, improvement in decision making was found in one study.

  3. Repetitive transcranial magnetic stimulation of human MT+ reduces apparent motion perception.

    PubMed

    Matsuyoshi, Daisuke; Hirose, Nobuyuki; Mima, Tatsuya; Fukuyama, Hidenao; Osaka, Naoyuki

    2007-12-18

    We investigated the effects of repetitive transcranial magnetic stimulation (rTMS) over the human cerebral cortex on apparent motion perception. Previous studies have shown that human extrastriate visual area MT+ (V5) processes not only real but also apparent motion. However, the functional relevance of MT+ on long-range apparent motion perception remains unclear. Here, we show direct evidence for the involvement of MT+ in apparent motion perception using rTMS, which is known to temporarily inhibit a localized region in the cerebral cortex. The results showed that apparent motion perception decreased after applying rTMS over MT+, but not after applying rTMS over the control region (inferior temporal gyrus). The decrease in performance caused by applying rTMS to MT+ suggests that MT+ is a causally responsible region for apparent motion perception, and thus, further supports the idea that MT+ plays a major role in the perception of motion.

  4. Repetitive Noninvasive Brain Stimulation to Modulate Cognitive Functions in Schizophrenia: A Systematic Review of Primary and Secondary Outcomes.

    PubMed

    Hasan, Alkomiet; Strube, Wolfgang; Palm, Ulrich; Wobrock, Thomas

    2016-07-01

    Despite many years of research, there is still an urgent need for new therapeutic options for the treatment of cognitive deficits in schizophrenia. Noninvasive brain stimulation (NIBS) has been proposed to be such a novel add-on treatment option. The main objective of this review was to systematically evaluate the cognitive effects of repetitive NIBS in schizophrenia. As most studies have not been specifically designed to investigate cognition as primary outcome, we have focused on both, primary and secondary outcomes. The PubMed/MEDLINE database (1985-2015) was systematically searched for interventional studies investigating the effects of repetitive NIBS on schizophrenia symptoms. All interventional clinical trials using repetitive transcranial stimulation, transcranial theta burst stimulation, and transcranial direct current stimulation for the treatment of schizophrenia were extracted and analyzed with regard to cognitive measures as primary or secondary outcomes. Seventy-six full-text articles were assessed for eligibility of which 33 studies were included in the qualitative synthesis. Of these 33 studies, only 4 studies included cognition as primary outcome, whereas 29 studies included cognitive measures as secondary outcomes. A beneficial effect of frontal NIBS could not be clearly established. No evidence for a cognitive disruptive effect of NIBS (temporal lobe) in schizophrenia could be detected. Finally, a large heterogeneity between studies in terms of inclusion criteria, stimulation parameters, applied cognitive measures, and follow-up intervals was observed. This review provides the first systematic overview regarding cognitive effects of repetitive NIBS in schizophrenia.

  5. Stroke recovery can be enhanced by using repetitive transcranial magnetic stimulation (rTMS).

    PubMed

    Lefaucheur, J-P

    2006-01-01

    Post-stroke recovery is based on plastic changes in the central nervous system that can compensate the loss of activity in affected brain regions. In particular, monohemispheric stroke is thought to result in disinhibition of the contralesional unaffected hemisphere. Neurorehabilitation programs improve function partly by enhancing cortical reorganization. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive way of producing potent changes in cortical excitability. Therefore, the application of rTMS was recently proposed to promote functional recovery in stroke patients, owing to the induced neuroplasticity. This review discusses the first clinical results that were obtained by rTMS in patients with post-stroke motor deficit, visuospatial neglect, or aphasia. These results are promising and depend on the site and frequency of stimulation. In summary, functional recovery might be obtained either when rTMS is applied at low-frequency (around 1 Hz) over the disinhibited, unaffected hemisphere in order to restore defective inhibition or when rTMS is applied at high-frequency (5 Hz or more) over the affected hemisphere in order to reactivate hypoactive regions. The overall procedure remains to be optimized, in particular regarding the number of rTMS sessions and the time of rTMS application after stroke. Cortical stimulation is an exciting perspective for improving functional recovery from stroke. Transient application of non-invasive transcranial stimulation during the time of the rehabilitation process will be preferable to the temporary implantation of epidural cortical electrodes, as recently proposed. Therefore, in the future, acute or recent stroke might be a major indication of rTMS in neurological practice.

  6. Effects of Repetitive Transcranial Magnetic Stimulation on Behavioral Recovery during Early Stage of Traumatic Brain Injury in Rats.

    PubMed

    Yoon, Kyung Jae; Lee, Yong-Taek; Chung, Pil-Wook; Lee, Yun Kyung; Kim, Dae Yul; Chun, Min Ho

    2015-10-01

    Repetitive transcranial magnetic stimulation (rTMS) is a promising technique that modulates neural networks. However, there were few studies evaluating the effects of rTMS in traumatic brain injury (TBI). Herein, we assessed the effectiveness of rTMS on behavioral recovery and metabolic changes using brain magnetic resonance spectroscopy (MRS) in a rat model of TBI. We also evaluated the safety of rTMS by measuring brain swelling with brain magnetic resonance imaging (MRI). Twenty male Sprague-Dawley rats underwent lateral fluid percussion and were randomly assigned to the sham (n=10) or the rTMS (n=10) group. rTMS was applied on the fourth day after TBI and consisted of 10 daily sessions for 2 weeks with 10 Hz frequency (total pulses=3,000). Although the rTMS group showed an anti-apoptotic effect around the peri-lesional area, functional improvements were not significantly different between the two groups. Additionally, rTMS did not modulate brain metabolites in MRS, nor was there any change of brain lesion or edema after magnetic stimulation. These data suggest that rTMS did not have beneficial effects on motor recovery during early stages of TBI, although an anti-apoptosis was observed in the peri-lesional area.

  7. Test-retest assessment of cortical activation induced by repetitive transcranial magnetic stimulation with brain atlas-guided optical topography

    NASA Astrophysics Data System (ADS)

    Tian, Fenghua; Kozel, F. Andrew; Yennu, Amarnath; Croarkin, Paul E.; McClintock, Shawn M.; Mapes, Kimberly S.; Husain, Mustafa M.; Liu, Hanli

    2012-11-01

    Repetitive transcranial magnetic stimulation (rTMS) is a technology that stimulates neurons with rapidly changing magnetic pulses with demonstrated therapeutic applications for various neuropsychiatric disorders. Functional near-infrared spectroscopy (fNIRS) is a suitable tool to assess rTMS-evoked brain responses without interference from the magnetic or electric fields generated by the TMS coil. We have previously reported a channel-wise study of combined rTMS/fNIRS on the motor and prefrontal cortices, showing a robust decrease of oxygenated hemoglobin concentration (Δ[HbO2]) at the sites of 1-Hz rTMS and the contralateral brain regions. However, the reliability of this putative clinical tool is unknown. In this study, we develop a rapid optical topography approach to spatially characterize the rTMS-evoked hemodynamic responses on a standard brain atlas. A hemispherical approximation of the brain is employed to convert the three-dimensional topography on the complex brain surface to a two-dimensional topography in the spherical coordinate system. The test-retest reliability of the combined rTMS/fNIRS is assessed using repeated measurements performed two to three days apart. The results demonstrate that the Δ[HbO2] amplitudes have moderate-to-high reliability at the group level; and the spatial patterns of the topographic images have high reproducibility in size and a moderate degree of overlap at the individual level.

  8. flexTMS--a novel repetitive transcranial magnetic stimulation device with freely programmable stimulus currents.

    PubMed

    Gattinger, Norbert; Moessnang, Georg; Gleich, Bernhard

    2012-07-01

    Transcranial magnetic stimulation (TMS) is able to noninvasively excite neuronal populations due to brief magnetic field pulses. The efficiency and the characteristics of stimulation pulse shapes influence the physiological effect of TMS. However, commercial devices allow only a minimum of control of different pulse shapes. Basically, just sinusoidal and monophasic pulse shapes with fixed pulse widths are available. Only few research groups work on TMS devices with controllable pulse parameters such as pulse shape or pulse width. We describe a novel TMS device with a full-bridge circuit topology incorporating four insulated-gate bipolar transistor (IGBT) modules and one energy storage capacitor to generate arbitrary waveforms. This flexible TMS (flexTMS ) device can generate magnetic pulses which can be adjusted with respect to pulse width, polarity, and intensity. Furthermore, the equipment allows us to set paired pulses with a variable interstimulus interval (ISI) from 0 to 20 ms with a step size of 10  μs. All user-defined pulses can be applied continually with repetition rates up to 30 pulses per second (pps) or, respectively, up to 100 pps in theta burst mode. Offering this variety of flexibility, flexTMS will allow the enhancement of existing TMS paradigms and novel research applications.

  9. Efficacy and practical issues of repetitive transcranial magnetic stimulation on chronic medically unexplained symptoms of pain.

    PubMed

    Li, Cheng-Ta; Su, Tung-Ping; Hsieh, Jen-Chuen; Ho, Shung-Tai

    2013-06-01

    Chronic pain is a common issue worldwide and remains a big challenge to physicians, particularly when the underlying causes do not meet any specific disease for settlement. Such medically unexplained somatic symptoms of pain that lack an integrated diagnosis in medicine have a high psychiatric comorbidity such as depression, and will require a multidisciplinary treatment strategy for a better outcome. Thus, most patients deserted management in spite of being inadequately treated and even presented with high resistance to analgesic drugs. Noninvasive brain stimulation, including repetitive transcranial magnetic stimulation (rTMS), has been used to treat refractory neuropathic pain and the analgesic efficacy is promising. So far, some case series and randomized rTMS studies have reported on patients with certain medically unexplained symptoms (MUSs) of pain (e.g., psychogenic pain or somatic symptoms in major depression and fibromyalgia). However, there is still no review article that is specific to the efficacy of rTMS on chronic unexplained symptoms of pain. Therefore, in the present review, we ventured to clarify the terminology and summarized the analgesic effects of rTMS on chronic MUSs of pain.

  10. Cutting edge: natural DNA repetitive extragenic sequences from gram-negative pathogens strongly stimulate TLR9.

    PubMed

    Magnusson, Mattias; Tobes, Raquel; Sancho, Jaime; Pareja, Eduardo

    2007-07-01

    Bacterial DNA exerts immunostimulatory effects on mammalian cells via the intracellular TLR9. Although broad analysis of TLR9-mediated immunostimulatory potential of synthetic oligonucleotides has been developed, which kinds of natural bacterial DNA sequences are responsible for immunostimulation are not known. This work provides evidence that the natural DNA sequences named repetitive extragenic palindromic (REPs) sequences present in Gram-negative bacteria are able to produce innate immune system stimulation via TLR9. A strong induction of IFN-alpha production by REPs from Escherichia coli, Salmonella enterica, Pseudomonas aeruginosa, and Neisseria meningitidis was detected in splenocytes from 129 mice. In addition, the involvement of TLR9 in immune stimulation by REPs was confirmed using B6.129P2-Tlr9(tm1Aki) knockout mice. Considering the involvement of TLRs in Gram-negative septic shock, it is conceivable that REPs play a role in its pathogenesis. This study highlights REPs as a potential novel target in septic shock treatment.

  11. Surface-Enhanced Femtosecond Stimulated Raman Spectroscopy at 1 MHz Repetition Rates.

    PubMed

    Buchanan, Lauren E; Gruenke, Natalie L; McAnally, Michael O; Negru, Bogdan; Mayhew, Hannah E; Apkarian, Vartkess A; Schatz, George C; Van Duyne, Richard P

    2016-11-17

    Surface-enhanced femtosecond stimulated Raman spectroscopy (SE-FSRS) is an ultrafast Raman technique that combines the sensitivity of surface-enhanced Raman scattering with the temporal resolution of femtosecond stimulated Raman spectroscopy (FSRS). Here, we present the first successful implementation of SE-FSRS using a 1 MHz amplified femtosecond laser system. We compare SE-FSRS and FSRS spectra measured at 1 MHz and 100 kHz using both equal pump average powers and equal pump energies to demonstrate that higher repetition rates allow spectra with higher signal-to-noise ratios to be obtained at lower pulse energies, a significant advance in the implementation of SE-FSRS. The ability to use lower pulse energies significantly mitigates sample damage that results from plasmonic enhancement of high-energy ultrafast pulses. As a result of the improvements to SE-FSRS developed in this Letter, we believe that SE-FSRS is now poised to become a powerful tool for studying the dynamics of plasmonic materials and adsorbates thereon.

  12. Effects of paired-pulse and repetitive stimulation on neurons in the rat medial geniculate body.

    PubMed

    Bartlett, E L; Smith, P H

    2002-01-01

    Many behaviorally relevant sounds, including language, are composed of brief, rapid, repetitive acoustic features. Recent studies suggest that abnormalities in producing and understanding spoken language are correlated with abnormal neural responsiveness to such auditory stimuli at higher auditory levels [Tallal et al., Science 271 (1996) 81-84; Wright et al., Nature 387 (1997) 176-178; Nagarajan et al., Proc. Natl. Acad. Sci. USA 96 (1999) 6483-6488] and with abnormal anatomical features in the auditory thalamus [Galaburda et al., Proc. Natl. Acad. Sci. USA 91 (1994) 8010-8013]. To begin to understand potential mechanisms for normal and abnormal transfer of sensory information to the cortex, we recorded the intracellular responses of medial geniculate body thalamocortical neurons in a rat brain slice preparation. Inferior colliculus or corticothalamic axons were excited by pairs or trains of electrical stimuli. Neurons receiving only excitatory collicular input had tufted dendritic morphology and displayed strong paired-pulse depression of their large, short-latency excitatory postsynaptic potentials. In contrast, geniculate neurons receiving excitatory and inhibitory collicular inputs could have stellate or tufted morphology and displayed much weaker depression or even paired-pulse facilitation of their smaller, longer-latency excitatory postsynaptic potentials. Depression was not blocked by ionotropic glutamate, GABA(A) or GABA(B) receptor antagonists. Facilitation was unaffected by GABA(A) receptor antagonists but was diminished by N-methyl-D-aspartate (NMDA) receptor blockade. Similar stimulation of the corticothalamic input always elicited paired-pulse facilitation. The NMDA-independent facilitation of the second cortical excitatory postsynaptic potential lasted longer and was more pronounced than that seen for the excitatory collicular inputs. Paired-pulse stimulation of isolated collicular inhibitory postsynaptic potentials generated little change in the

  13. Repetitive transcranial magnetic stimulation induces oscillatory power changes in chronic tinnitus

    PubMed Central

    Schecklmann, Martin; Lehner, Astrid; Gollmitzer, Judith; Schmidt, Eldrid; Schlee, Winfried; Langguth, Berthold

    2015-01-01

    Chronic tinnitus is associated with neuroplastic changes in auditory and non-auditory cortical areas. About 10 years ago, repetitive transcranial magnetic stimulation (rTMS) of auditory and prefrontal cortex was introduced as potential treatment for tinnitus. The resulting changes in tinnitus loudness are interpreted in the context of rTMS induced activity changes (neuroplasticity). Here, we investigate the effect of single rTMS sessions on oscillatory power to probe the capacity of rTMS to interfere with tinnitus-specific cortical plasticity. We measured 20 patients with bilateral chronic tinnitus and 20 healthy controls comparable for age, sex, handedness, and hearing level with a 63-channel electroencephalography (EEG) system. Educational level, intelligence, depressivity and hyperacusis were controlled for by analysis of covariance. Different rTMS protocols were tested: Left and right temporal and left and right prefrontal cortices were each stimulated with 200 pulses at 1 Hz and with an intensity of 60% stimulator output. Stimulation of central parietal cortex with 6-fold reduced intensity (inverted passive-cooled coil) served as sham condition. Before and after each rTMS protocol 5 min of resting state EEG were recorded. The order of rTMS protocols was randomized over two sessions with 1 week interval in between. Analyses on electrode level showed that people with and without tinnitus differed in their response to left temporal and right frontal stimulation. In tinnitus patients left temporal rTMS decreased frontal theta and delta and increased beta2 power, whereas right frontal rTMS decreased right temporal beta3 and gamma power. No changes or increases were observed in the control group. Only non-systematic changes in tinnitus loudness were induced by single sessions of rTMS. This is the first study to show tinnitus-related alterations of neuroplasticity that were specific to stimulation site and oscillatory frequency. The observed effects can be

  14. Action potential propagation through embryonic dorsal root ganglion cells in culture. II. Decrease of conduction reliability during repetitive stimulation.

    PubMed

    Lüscher, C; Streit, J; Lipp, P; Lüscher, H R

    1994-08-01

    1. The reliability of the propagation of action potentials (AP) through dorsal root ganglion (DRG) cells in embryonic slice cultures was investigated during repetitive stimulation at 1-20 Hz. Membrane potentials of DRG cells were recorded intracellularly while the axons were stimulated by an extracellular electrode. 2. In analogy to the double-pulse experiments reported previously, either one or two types of propagation failures were recorded during repetitive stimulation, depending on the cell morphology. In contrast to the double-pulse experiments, the failures appeared at longer interpulse intervals and usually only after several tens of stimuli with reliable propagation. 3. In the period with reliable propagation before the failures, a decrease in the conduction velocity and in the amplitude of the afterhyperpolarization (AHP), an increase in the total membrane conductance, and the disappearance of the action potential "shoulder" were observed. 4. The reliability of conduction during repetitive stimulation was improved by lowering the extracellular calcium concentration or by replacing the extracellular calcium by strontium. The reliability of conduction decreased by the application of cadmium, a calcium channel blocker, 4-amino pyridine, a fast potassium channel blocker, or apamin or muscarine, the blockers of calcium-dependent potassium channels. The reliability of conduction was not effected by blocking the sodium potassium pump with ouabain or by replacing extracellular sodium with lithium. 5. In the period with reliable propagation cadmium, apamin, and muscarine reduced the amplitude of the AHP. The shoulder of the action potential was more pronounced and not sensitive to repetitive stimulation when extracellular calcium was replaced by strontium. It disappeared when cadmium was applied. 6. In DRG somata changes of the intracellular Ca2+ concentration were monitored by measuring the fluorescence of the Ca2+ indicator Fluo-3 with a laser-scanning confocal

  15. Inactivation of mechano-sensitive dilatation upon repetitive mechanical stimulation of the musculo-vascular network in the rabbit.

    PubMed

    Turturici, M; Roatta, S

    2013-06-01

    Mechano-sensitivity of the vascular network is known to be implicated in the rapid dilatation at the onset of exercise, however, it is not known how this mechanism responds to repetitive mechanical stimulation. This study tests the hypothesis that the mechanically-induced hyperaemia undergoes some attenuation upon repetitive stimulation. Muscle blood flow was recorded from 9 masseteric arteries (5 right, 4 left) in 6 anesthetized rabbits. Two mechanical stimuli, masseter muscle compression (MC) and occlusion of the masseteric artery (AO), were provided in different combinations: A) repeated stimulation (0.5 Hz, for 40 s); B) single stimuli delivered at decreasing inter-stimulus interval (ISI) from 4 min to 2 s, C) single AO delivered before and immediately after a series of 20 MCs at 0.5 Hz, and vice-versa. Repetitive AO stimulation at 0.5 Hz produced a transient hyperaemia (378 ±189%) peaking at 4.5 ±1.4 s and then decaying before the end of stimulation. The hyperaemic response to individual AOs progressively decreased by 74 ±39% with decreasing ISI from 4 min to 2 s (p<0.01). Non significant differences were observed between AO and MC stimulation. Decreased response to AO was also provoked by previous repetitive MC stimulation, and vice-versa. The results provide evidence that the mechano-sensitivity of the vascular network is attenuated by previous mechanical stimulation. It is suggested that the mechano-sensitive dilatory mechanisms undergoes some inactivation whose recovery time is in the order of a few minutes.

  16. Safety of repetitive transcranial magnetic stimulation in patients with epilepsy: A systematic review.

    PubMed

    Pereira, Luisa Santos; Müller, Vanessa Teixeira; da Mota Gomes, Marleide; Rotenberg, Alexander; Fregni, Felipe

    2016-04-01

    Approximately one-third of patients with epilepsy remain with pharmacologically intractable seizures. An emerging therapeutic modality for seizure suppression is repetitive transcranial magnetic stimulation (rTMS). Despite being considered a safe technique, rTMS carries the risk of inducing seizures, among other milder adverse events, and thus, its safety in the population with epilepsy should be continuously assessed. We performed an updated systematic review on the safety and tolerability of rTMS in patients with epilepsy, similar to a previous report published in 2007 (Bae EH, Schrader LM, Machii K, Alonso-Alonso M, Riviello JJ, Pascual-Leone A, Rotenberg A. Safety and tolerability of repetitive transcranial magnetic stimulation in patients with epilepsy: a review of the literature. Epilepsy Behav. 2007; 10 (4): 521-8), and estimated the risk of seizures and other adverse events during or shortly after rTMS application. We searched the literature for reports of rTMS being applied on patients with epilepsy, with no time or language restrictions, and obtained studies published from January 1990 to August 2015. A total of 46 publications were identified, of which 16 were new studies published after the previous safety review of 2007. We noted the total number of subjects with epilepsy undergoing rTMS, medication usage, incidence of adverse events, and rTMS protocol parameters: frequency, intensity, total number of stimuli, train duration, intertrain intervals, coil type, and stimulation site. Our main data analysis included separate calculations for crude per subject risk of seizure and other adverse events, as well as risk per 1000 stimuli. We also performed an exploratory, secondary analysis on the risk of seizure and other adverse events according to the type of coil used (figure-of-8 or circular), stimulation frequency (≤ 1 Hz or > 1 Hz), pulse intensity in terms of motor threshold (<100% or ≥ 100%), and number of stimuli per session (< 500 or ≥ 500

  17. Focal hand dystonia: individualized intervention with repeated application of repetitive transcranial magnetic stimulation

    PubMed Central

    Kimberley, Teresa Jacobson; Borich, Michael R.; Schmidt, Rebekah; Carey, James R.; Gillick, Bernadette

    2016-01-01

    Objective Examine for individual factors that may predict response to inhibitory repetitive transcranial magnetic stimulation (rTMS) in focal hand dystonia (FHD); present method for determining the optimal stimulation to increase inhibition in a given patient; and examine individual responses to prolonged intervention. Design A single-subject design to determine optimal parameters to increase inhibition for a given subject and to employ the selected parameters 1/wk for 6 weeks, with 1 wk follow up, to determine response. Setting Clinical research laboratory Participants A volunteer sample of 2 subjects with FHD. One participant had TMS responses indicating impaired inhibition, the other had responses within normal limits. Interventions 1200 pulses of 1 Hz rTMS delivered using 4 different stimulation site/intensity combinations: primary motor cortex (M1) at 90% or 110% resting motor threshold (RMT); dorsal premotor cortex (PMd) at 90% or 110% of RMT. The parameters producing the greatest within-session increase in cortical silent period (CSP) duration were then used as intervention. Main outcome measures Response variables included handwriting pressure and velocity, subjective symptom rating, CSP, and short-latency intracortical inhibition and facilitation. Results The individual with baseline TMS responses indicating impaired inhibition responded favorably to the repeated intervention, with reduced handwriting force, increase in CSP and subjective report of “moderate” symptom improvement at 1-wk follow-up. The individual with normal baseline responses failed to respond to the intervention. In both subjects, 90% RMT to PMd produced greatest lengthening of CSP and was used as intervention. Conclusions An individualized understanding of neurophysiologic measures may be indicators of responsiveness to inhibitory rTMS in focal dystonia, with further work needed to determine 3 likely responders vs. non-responders. PMID:25256555

  18. Brain SPECT guided repetitive transcranial magnetic stimulation (rTMS) in treatment resistant major depressive disorder.

    PubMed

    Jha, Shailesh; Chadda, Rakesh K; Kumar, Nand; Bal, C S

    2016-06-01

    Repetitive transcranial magnetic stimulation (rTMS) has emerged as a potential treatment in treatment resistant major depressive disorder (MDD). However, there is no consensus about the exact site of stimulation for rTMS. Single-photon emission computed tomography (SPECT) offers a potential technique in deciding the site of stimulation. The present study was conducted to assess the difference in outcome of brain SPECT assisted rTMS versus standard protocol of twenty sessions of high frequency rTMS as add on treatment in 20 patients with treatment resistant MDD, given over a period of 4 weeks. Thirteen subjects (group I) received high frequency rTMS over an area of hypoperfusion in the prefrontal cortex, as identified on SPECT, whereas 7 subjects (group II) were administered rTMS in the left dorsoslateral prefrontal cortex (DLPFC) area. Improvement was monitored using standardized instruments. Patients in the group I showed a significantly better response compared to those in the group II. In group I, 46% of the subjects were responders on MADRS, 38% on BDI and 77% on CGI. The parallel figures of responders in Group II were 0% on MADRS, 14% on BDI and 43% on CGI. There were no remitters in the study. No significant untoward side effects were noticed. The study had limitations of a small sample size and non-controlled design, and all the subjects were also receiving the standard antidepressant therapy. Administration of rTMS over brain SPECT specified area of hypoperfusion may have a better clinical outcome compared to the standard protocol.

  19. Effects of Repetitive Transcranial Magnetic Stimulation in Performing Eye-Hand Integration Tasks: Four Preliminary Studies with Children Showing Low-Functioning Autism

    ERIC Educational Resources Information Center

    Panerai, Simonetta; Tasca, Domenica; Lanuzza, Bartolo; Trubia, Grazia; Ferri, Raffaele; Musso, Sabrina; Alagona, Giovanna; Di Guardo, Giuseppe; Barone, Concetta; Gaglione, Maria P.; Elia, Maurizio

    2014-01-01

    This report, based on four studies with children with low-functioning autism, aimed at evaluating the effects of repetitive transcranial magnetic stimulation delivered on the left and right premotor cortices on eye-hand integration tasks; defining the long-lasting effects of high-frequency repetitive transcranial magnetic stimulation; and…

  20. Poststroke dysphagia rehabilitation by repetitive transcranial magnetic stimulation: a noncontrolled pilot study.

    PubMed

    Verin, E; Leroi, A M

    2009-06-01

    Poststroke dysphagia is frequent and significantly increases patient mortality. In two thirds of cases there is a spontaneous improvement in a few weeks, but in the other third, oropharyngeal dysphagia persists. Repetitive transcranial magnetic stimulation (rTMS) is known to excite or inhibit cortical neurons, depending on stimulation frequency. The aim of this noncontrolled pilot study was to assess the feasibility and the effects of 1-Hz rTMS, known to have an inhibitory effect, on poststroke dysphagia. Seven patients (3 females, age = 65 +/- 10 years), with poststroke dysphagia due to hemispheric or subhemispheric stroke more than 6 months earlier (56 +/- 50 months) diagnosed by videofluoroscopy, participated in the study. rTMS at 1 Hz was applied for 20 min per day every day for 5 days to the healthy hemisphere to decrease transcallosal inhibition. The evaluation was performed using the dysphagia handicap index and videofluoroscopy. The dysphagia handicap index demonstrated that the patients had mild oropharyngeal dysphagia. Initially, the score was 43 +/- 9 of a possible 120 which decreased to 30 +/- 7 (p < 0.05) after rTMS. After rTMS, there was an improvement of swallowing coordination, with a decrease in swallow reaction time for liquids (p = 0.0506) and paste (p < 0.01), although oral transit time, pharyngeal transit time, and laryngeal closure duration were not modified. Aspiration score significantly decreased for liquids (p < 0.05) and residue score decreased for paste (p < 0.05). This pilot study demonstrated that rTMS is feasible in poststroke dysphagia and improves swallowing coordination. Our results now need to be confirmed by a randomized controlled study with a larger patient population.

  1. Repetitive magnetic stimulation improves retinal function in a rat model of retinal dystrophy

    NASA Astrophysics Data System (ADS)

    Rotenstreich, Ygal; Tzameret, Adi; Levi, Nir; Kalish, Sapir; Sher, Ifat; Zangen, Avraham; Belkin, Michael

    2014-02-01

    Vision incapacitation and blindness associated with retinal dystrophies affect millions of people worldwide. Retinal degeneration is characterized by photoreceptor cell death and concomitant remodeling of remaining retinal cells. Repetitive Magnetic Stimulation (RMS) is a non-invasive technique that creates alternating magnetic fields by brief electric currents transmitted through an insulated coil. These magnetic field generate action potentials in neurons, and modulate the expression of neurotransmitter receptors, growth factors and transcription factors which mediate plasticity. This technology has been proven effective and safe in various psychiatric disorders. Here we determined the effect of RMS on retinal function in Royal College of Surgeons (RCS) rats, a model for retinal dystrophy. Four week-old RCS and control Spargue Dawley (SD) rats received sham or RMS treatment over the right eye (12 sessions on 4 weeks). RMS treatment at intensity of at 40% of the maximal output of a Rapid2 stimulator significantly increased the electroretinogram (ERG) b-wave responses by up to 6- or 10-fold in the left and right eye respectively, 3-5 weeks following end of treatment. RMS treatment at intensity of 25% of the maximal output did not significant effect b-wave responses following end of treatment with no adverse effect on ERG response or retinal structure of SD rats. Our findings suggest that RMS treatment induces delayed improvement of retinal functions and may induce plasticity in the retinal tissue. Furthermore, this non-invasive treatment may possibly be used in the future as a primary or adjuvant treatment for retinal dystrophy.

  2. Short-term effects of repetitive transcranial magnetic stimulation on sleep bruxism – a pilot study

    PubMed Central

    Zhou, Wei-Na; Fu, Hai-Yang; Du, Yi-Fei; Sun, Jian-Hua; Zhang, Jing-Lu; Wang, Chen; Svensson, Peter; Wang, Ke-Lun

    2016-01-01

    The purpose of this study was to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) on patients with sleep bruxism (SB). Twelve patients with SB were included in an open, single-intervention pilot study. rTMS at 1 Hz and an intensity of 80% of the active motor threshold was applied to the ‘hot spot' of the masseter muscle representation at the primary motor cortex bilaterally for 20 min per side each day for 5 consecutive days. The jaw-closing muscle electromyographic (EMG) activity during sleep was recorded with a portable EMG recorder at baseline, during rTMS treatment and at follow-up for 5 days. In addition, patients scored their jaw-closing muscle soreness on a 0–10 numerical rating scale (NRS). Data were analysed with analysis of variance. The intensity of the EMG activity was suppressed during and after rTMS compared to the baseline (P = 0.04; P = 0.02, respectively). The NRS score of soreness decreased significantly during and after rTMS compared with baseline (P < 0.01). These findings indicated a significant inhibition of jaw-closing muscle activity during sleep along with a decrease of muscle soreness. This pilot study raises the possibility of therapeutic benefits from rTMS in patients with bruxism and calls for further and more controlled studies. PMID:27025267

  3. Short-term effects of repetitive transcranial magnetic stimulation on sleep bruxism - a pilot study.

    PubMed

    Zhou, Wei-Na; Fu, Hai-Yang; Du, Yi-Fei; Sun, Jian-Hua; Zhang, Jing-Lu; Wang, Chen; Svensson, Peter; Wang, Ke-Lun

    2016-03-30

    The purpose of this study was to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) on patients with sleep bruxism (SB). Twelve patients with SB were included in an open, single-intervention pilot study. rTMS at 1 Hz and an intensity of 80% of the active motor threshold was applied to the 'hot spot' of the masseter muscle representation at the primary motor cortex bilaterally for 20 min per side each day for 5 consecutive days. The jaw-closing muscle electromyographic (EMG) activity during sleep was recorded with a portable EMG recorder at baseline, during rTMS treatment and at follow-up for 5 days. In addition, patients scored their jaw-closing muscle soreness on a 0-10 numerical rating scale (NRS). Data were analysed with analysis of variance. The intensity of the EMG activity was suppressed during and after rTMS compared to the baseline (P = 0.04; P = 0.02, respectively). The NRS score of soreness decreased significantly during and after rTMS compared with baseline (P < 0.01). These findings indicated a significant inhibition of jaw-closing muscle activity during sleep along with a decrease of muscle soreness. This pilot study raises the possibility of therapeutic benefits from rTMS in patients with bruxism and calls for further and more controlled studies.

  4. Amodal semantic representations depend on both anterior temporal lobes: evidence from repetitive transcranial magnetic stimulation.

    PubMed

    Pobric, Gorana; Jefferies, Elizabeth; Ralph, Matthew A Lambon

    2010-04-01

    The key question of how the brain codes the meaning of words and pictures is the focus of vigorous debate. Is there a "semantic hub" in the temporal poles where these different inputs converge to form amodal conceptual representations? Alternatively, are there distinct neural circuits that underpin our comprehension of pictures and words? Understanding words might be primarily left-lateralised, linked to other language areas, while semantic representation of pictures may be more bilateral. To elucidate this debate, we used offline, low-frequency, repetitive transcranial magnetic stimulation (rTMS) to disrupt neural processing temporarily in the left or right temporal poles. During the induced refractory period, participants made judgements of semantic association for verbal and pictorial stimuli. The efficiency of semantic processing was reduced by rTMS, yet a perceptual task of comparable difficulty was unaffected. rTMS applied to the left or right temporal poles disrupted semantic processing for words and pictures to the same degree, while rTMS delivered at a control site had no impact. The results confirm that both temporal poles form a critical substrate within the neural network that supports conceptual knowledge, regardless of modality.

  5. Mechanisms of human motor cortex facilitation induced by subthreshold 5-Hz repetitive transcranial magnetic stimulation.

    PubMed

    Sommer, Martin; Rummel, Milena; Norden, Christoph; Rothkegel, Holger; Lang, Nicolas; Paulus, Walter

    2013-06-01

    Our knowledge about the mechanisms of human motor cortex facilitation induced by repetitive transcranial magnetic stimulation (rTMS) is still incomplete. Here we used pharmacological conditioning with carbamazepine, dextrometorphan, lorazepam, and placebo to elucidate the type of plasticity underlying this facilitation, and to probe if mechanisms reminiscent of long-term potentiation are involved. Over the primary motor cortex of 10 healthy subjects, we applied biphasic rTMS pulses of effective posterior current direction in the brain. We used six blocks of 200 pulses at 5-Hz frequency and 90% active motor threshold intensity and controlled for corticospinal excitability changes using motor-evoked potential (MEP) amplitudes and latencies elicited by suprathreshold pulses before, in between, and after rTMS. Target muscle was the dominant abductor digiti minimi muscle; we coregistered the dominant extensor carpi radialis muscle. We found a lasting facilitation induced by this type of rTMS. The GABAergic medication lorazepam and to a lesser extent the ion channel blocker carbamazepine reduced the MEP facilitation after biphasic effective posteriorly oriented rTMS, whereas the N-methyl-d-aspartate receptor-antagonist dextrometorphan had no effect. Our main conclusion is that the mechanism of the facilitation induced by biphasic effective posterior rTMS is more likely posttetanic potentiation than long-term potentiation. Additional findings were prolonged MEP latency under carbamazepine, consistent with sodium channel blockade, and larger MEP amplitudes from extensor carpi radialis under lorazepam, suggesting GABAergic involvement in the center-surround balance of excitability.

  6. Disruption of Locomotor Adaptation with Repetitive Transcranial Magnetic Stimulation Over the Motor Cortex.

    PubMed

    Choi, Julia T; Bouyer, Laurent J; Nielsen, Jens Bo

    2015-07-01

    Locomotor patterns are adapted on a trial-and-error basis to account for predictable dynamics. Once a walking pattern is adapted, the new calibration is stored and must be actively de-adapted. Here, we tested the hypothesis that storage of newly acquired ankle adaptation in walking is dependent on corticospinal mechanisms. Subjects were exposed to an elastic force that resisted ankle dorsiflexion during treadmill walking. Ankle movement was adapted in <30 strides, leading to after-effects on removal of the force. We used a crossover design to study the effects of repetitive transcranial magnetic stimulation (TMS) over the primary motor cortex (M1), compared with normal adaptation without TMS. In addition, we tested the effects of TMS over the primary sensory cortex (S1) and premotor cortex (PMC) during adaptation. We found that M1 TMS, but not S1 TMS and PMC TMS, reduced the size of ankle dorsiflexion after-effects. The results suggest that suprathreshold M1 TMS disrupted the initial processes underlying locomotor adaptation. These results are consistent with the hypothesis that corticospinal mechanisms underlie storage of ankle adaptation in walking.

  7. The effects of repetitive transcranial magnetic stimulation in an animal model of tinnitus

    PubMed Central

    Mulders, Wilhelmina H. A. M.; Vooys, Vanessa; Makowiecki, Kalina; Tang, Alex D.; Rodger, Jennifer

    2016-01-01

    Tinnitus (phantom auditory perception associated with hearing loss) can seriously affect wellbeing. Its neural substrate is unknown however it has been linked with abnormal activity in auditory pathways. Though no cure currently exists, repetitive transcranial magnetic stimulation (rTMS) has been shown to reduce tinnitus in some patients, possibly via induction of cortical plasticity involving brain derived neurotrophic factor (BDNF). We examined whether low intensity rTMS (LI-rTMS) alleviates signs of tinnitus in a guinea pig model and whether this involves changes in BDNF expression and hyperactivity in inferior colliculus. Acoustic trauma was used to evoke hearing loss, central hyperactivity and tinnitus. When animals developed tinnitus, treatment commenced (10 sessions of 10 minutes 1 Hz LI-rTMS or sham over auditory cortex over 14 days). After treatment ceased animals were tested for tinnitus, underwent single-neuron recordings in inferior colliculus to assess hyperactivity and samples from cortex and inferior colliculus were taken for BDNF ELISA. Analysis revealed a significant reduction of tinnitus after LI-rTMS compared to sham, without a statistical significant effect on BDNF levels or hyperactivity. This suggests that LI-rTMS alleviates behavioural signs of tinnitus by a mechanism independent of inferior colliculus hyperactivity and BDNF levels and opens novel therapeutic avenues for tinnitus treatment. PMID:27905540

  8. Improvements in emotion regulation following repetitive transcranial magnetic stimulation for generalized anxiety disorder.

    PubMed

    Diefenbach, Gretchen J; Assaf, Michal; Goethe, John W; Gueorguieva, Ralitza; Tolin, David F

    2016-10-01

    Generalized anxiety disorder (GAD) is characterized by emotion regulation difficulties, which are associated with abnormalities in neural circuits encompassing fronto-limbic regions including the dorsolateral prefrontal cortex (DLPFC). The aim of this study was to determine whether DLPFC neuromodulation improves emotion regulation in patients with GAD. This is a secondary analysis from a randomized-controlled trial comparing 30 sessions of low-frequency right-sided active (n=13) versus sham (n=12, sham coil) repetitive transcranial magnetic stimulation (rTMS) at the right DLPFC in patients with GAD. Results indicated statistically significant improvements in self-reported emotion regulation difficulties at posttreatment and 3-month follow-up in the active group only. Improvements were found primarily in the domains of goal-directed behaviors and impulse control and were significantly associated with a global clinician rating of improvement. These preliminary results support rTMS as a treatment for GAD and suggest improved emotion regulation as a possible mechanism of change.

  9. Effect of repetitive transcranial magnetic stimulation on mood in healthy subjects

    PubMed Central

    Moulier, Virginie; Gaudeau-Bosma, Christian; Isaac, Clémence; Allard, Anne-Camille; Bouaziz, Noomane; Sidhoumi, Djedia; Braha-Zeitoun, Sonia; Benadhira, René; Thomas, Fanny; Januel, Dominique

    2016-01-01

    Background High frequency repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) has shown significant efficiency in the treatment of resistant depression. However in healthy subjects, the effects of rTMS remain unclear. Objective Our aim was to determine the impact of 10 sessions of rTMS applied to the DLPFC on mood and emotion recognition in healthy subjects. Design In a randomised double-blind study, 20 subjects received 10 daily sessions of active (10 Hz frequency) or sham rTMS. The TMS coil was positioned on the left DLPFC through neuronavigation. Several dimensions of mood and emotion processing were assessed at baseline and after rTMS with clinical scales, visual analogue scales (VASs), and the Ekman 60 faces test. Results The 10 rTMS sessions targeting the DLPFC were well tolerated. No significant difference was found between the active group and the control group for clinical scales and the Ekman 60 faces test. Compared to the control group, the active rTMS group presented a significant improvement in their adaptation to daily life, which was assessed through VAS. Conclusion This study did not show any deleterious effect on mood and emotion recognition of 10 sessions of rTMS applied on the DLPFC in healthy subjects. This study also suggested a positive effect of rTMS on quality of life. PMID:26993786

  10. A Comprehensive Study of Repetitive Transcranial Magnetic Stimulation in Parkinson's Disease

    PubMed Central

    Kimura, Hideki; Kurimura, Masayuki; Kurokawa, Katsurou; Nagaoka, Utako; Arawaka, Shigeki; Wada, Manabu; Kawanami, Toru; Kurita, Keiji; Kato, Takeo

    2011-01-01

    The clinical benefits of repetitive transcranial magnetic stimulation (rTMS) for Parkinson's disease (PD) remain controversial. We performed a comprehensive study to examine whether rTMS is a safe and effective treatment for PD. Twelve PD patients received rTMS once a week. The crossover study design consisted of 4-week sham rTMS followed by 4-week real rTMS. The Unified Parkinson's Disease Rating Scale (UPDRS), Modified Hoehn and Yahr Stage, Schwab and England ADL Scale, Actigraph, Mini-Mental State Examination, Hamilton Depression Scale, Wechsler Adult Intelligence Scale-revised, and cerebral blood flow (CBF) and cerebrospinal fluid (CSF) examinations were used to evaluate the rTMS effects. Under both drug-on and drug-off conditions, the real rTMS improved the UPDRS scores significantly, while the sham rTMS did not. There were no significant changes in the results of the neuropsychological tests, CBF and CSF. rTMS seems to be a safe and effective therapeutic option for PD patients, especially in a wearing-off state. PMID:22389830

  11. Effects of Repetitive Transcranial Magnetic Stimulation Over Trunk Motor Spot on Balance Function in Stroke Patients

    PubMed Central

    2016-01-01

    Objective To assess the efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) on balance function in patients with chronic stroke. Methods Thirty participants with chronic stroke were enrolled in this study. High frequency (10 Hz) rTMS was delivered with butterfly-coil on trunk motor spot. Each patient received both real and sham rTMS in a random sequence. The rTMS cycles (real or sham) were composed of 10 sessions each, administered over two weeks, and separated by a 4-week washout period. Balance function was measured by Berg Balance Scale and computerized dynamic posturography to determine the effect of rTMS before and one day after the end of each treatment period, as well as at a 1-month follow-up. Results The balance function was significantly improved after high frequency rTMS as compared with that after sham rTMS (p<0.05). There was no serious adverse effect in patients during the treatment period. Conclusion In the chronic stroke patients, high frequency rTMS to the trunk motor area seems to be a helpful way to improve balance function without any specific adverse effects. Further studies are needed to identify the underlying mechanism and generate a detailed protocol. PMID:27847712

  12. Factor Analysis of Low-Frequency Repetitive Transcranial Magnetic Stimulation to the Temporoparietal Junction for Tinnitus

    PubMed Central

    Li, Bei; Wang, Meiye; Li, Ming; Yin, Shankai

    2016-01-01

    Objectives. We investigated factors that contribute to suppression of tinnitus after repetitive transcranial magnetic stimulation (rTMS). Methods. A total of 289 patients with tinnitus underwent active 1 Hz rTMS in the left temporoparietal region. A visual analog scale (VAS) was used to assess tinnitus loudness. All participants were interviewed regarding age, gender, tinnitus duration, laterality and pitch, audiometric parameters, sleep, and so forth. The resting motor thresholds (RMTs) were measured in all patients and 30 age- and gender-matched volunteers. Results. With respect to different factors that contribute to tinnitus suppression, we found improvement in the following domains: shorter duration, normal hearing (OR: 3.25, 95%CI: 2.01–5.27, p = 0.001), and without sleep disturbance (OR: 2.51, 95%CI: 1.56–4.1, p = 0.005) adjusted for age and gender. The patients with tinnitus lasting less than 1 year were more likely to show suppression of tinnitus (OR: 2.77, 95%CI: 1.48–5.19, p = 0.002) compared to those with tinnitus lasting more than 5 years. Tinnitus patients had significantly lower RMTs compared with healthy volunteers. Conclusion. Active low-frequency rTMS results in a significant reduction in the loudness of tinnitus. Significant tinnitus suppression was shown in subjects with shorter tinnitus duration, with normal hearing, and without sleep disturbance. PMID:27847647

  13. Effects of repetitive transcranial magnetic stimulation on recovery of function after spinal cord injury.

    PubMed

    Tazoe, Toshiki; Perez, Monica A

    2015-04-01

    A major goal of rehabilitation strategies after spinal cord injury (SCI) is to enhance the recovery of function. One possible avenue to achieve this goal is to strengthen the efficacy of the residual neuronal pathways. Noninvasive repetitive transcranial magnetic stimulation (rTMS) has been used in patients with motor disorders as a tool to modulate activity of corticospinal, cortical, and subcortical pathways to promote functional recovery. This article reviews a series of studies published during the last decade that used rTMS in the acute and chronic stages of paraplegia and tetraplegia in humans with complete and incomplete SCI. In the studies, rTMS has been applied over the arm and leg representations of the primary motor cortex to target 3 main consequences of SCI: sensory and motor function impairments, spasticity, and neuropathic pain. Although some studies demonstrated that consecutive sessions of rTMS improve aspects of particular functions, other studies did not show similar effects. We discuss how rTMS parameters and postinjury reorganization in the corticospinal tract, motor cortical, and spinal cord circuits might be critical factors in understanding the advantages and disadvantages of using rTMS in patients with SCI. The available data highlight the limited information on the use of rTMS after SCI and the need to further understand the pathophysiology of neuronal structures affected by rTMS to maximize the potential beneficial effects of this technique in humans with SCI.

  14. Combining near-infrared spectroscopy with electroencephalography and repetitive transcranial magnetic stimulation

    NASA Astrophysics Data System (ADS)

    Näsi, Tiina; Kotilahti, Kalle; Mäki, Hanna; Nissilä, Ilkka; Meriläinen, Pekka

    2009-07-01

    The objective of the study was to assess the usability of a near-infrared spectroscopy (NIRS) device in multimodal measurements. We combined NIRS with electroencephalography (EEG) to record hemodynamic responses and evoked potentials simultaneously, and with transcranial magnetic stimulation (TMS) to investigate hemodynamic responses to repetitive TMS (rTMS). Hemodynamic responses and visual evoked potentials (VEPs) to 3, 6, and 12 s stimuli consisting of pattern-reversing checkerboards were successfully recorded in the NIRS/EEG measurement, and ipsi- and contralateral hemodynamic responses to 0.5, 1, and 2 Hz rTMS in the NIRS/TMS measurement. In the NIRS/EEG measurements, the amplitudes of the hemodynamic responses increased from 3- to 6-s stimulus, but not from 6- to 12-s stimulus, and the VEPs showed peaks N75, P100, and N135. In the NIRS/TMS measurements, the 2-Hz stimulus produced the strongest hemodynamic responses compared to the 0.5- and 1-Hz stimuli. In two subjects oxyhemoglobin concentration decreased and in one increased as a consequence of the 2-Hz rTMS. To locate the origin of the measured NIRS responses, methods have to be developed to investigate TMS-induced scalp muscle contractions. In the future, multimodal measurements may prove useful in monitoring or treating diseases such as stroke or Alzheimer's disease.

  15. The cerebellum in emotion regulation: a repetitive transcranial magnetic stimulation study.

    PubMed

    Schutter, Dennis J L G; van Honk, Jack

    2009-03-01

    Several lines of evidence suggest that the cerebellum may play a role in the regulation of emotion. The aim of this study was to investigate the hypothesis that inhibition of cerebellar function using slow repetitive transcranial magnetic stimulation (rTMS) would lead to increased negative mood as a result of impaired emotion regulation. In a randomized counterbalanced within-subjects design, 12 healthy young right-handed volunteers received 20 min of cerebellar, occipital, or sham 1 Hz rTMS on three separate days. Mood state inventories were acquired prior to and immediately after rTMS and after an emotion regulation task (ERT). In the ERT, participants were instructed to either look at aversive and neutral scenes, or to suppress the negative feelings experienced while watching aversive scenes during which the electroencephalogram (EEG) was recorded. Results showing no changes in baseline-corrected mood were observed immediately after rTMS. However, significant increases in baseline-corrected negative mood following the ERT were reported after cerebellar rTMS exclusively. No effects on the EEG during the ERT were observed. These findings provide support for the view that the cerebellum is implicated in the regulation of emotion and mood, and concur with evidence of cerebellar abnormalities observed in disorders associated with emotion dysregulation. In order to clarify the underlying biological mechanisms involved, more research is needed.

  16. Online repetitive transcranial magnetic stimulation (TMS) to the parietal operculum disrupts haptic memory for grasping.

    PubMed

    Cattaneo, Luigi; Maule, Francesca; Tabarelli, Davide; Brochier, Thomas; Barchiesi, Guido

    2015-11-01

    The parietal operculum (OP) contains haptic memory on the geometry of objects that is readily transferrable to the motor cortex but a causal role of OP in memory-guided grasping is only speculative. We explored this issue by using online high-frequency repetitive transcranial magnetic stimulation (rTMS). The experimental task was performed by blindfolded participants acting on objects of variable size. Trials consisted in three phases: haptic exploration of an object, delay, and reach-grasp movement onto the explored object. Motor performance was evaluated by the kinematics of finger aperture. Online rTMS was applied to the left OP region separately in each of the three phases of the task. The results showed that rTMS altered grip aperture only when applied in the delay phase to the OP. In a second experiment a haptic discriminative (match-to-sample) task was carried out on objects similar to those used in the first experiment. Online rTMS was applied to the left OP. No psychophysical effects were induced by rTMS on the detection of explicit haptic object size. We conclude that neural activity in the OP region is necessary for proficient memory-guided haptic grasping. The function of OP seems to be critical while maintaining the haptic memory trace and less so while encoding it or retrieving it.

  17. Repetitive transcranial magnetic stimulator with controllable pulse parameters (cTMS).

    PubMed

    Peterchev, Angel V; Murphy, David L; Lisanby, Sarah H

    2010-01-01

    We describe a novel transcranial magnetic stimulation (TMS) device that uses a circuit topology incorporating two energy-storage capacitors and two insulated-gate bipolar transistors (IGBTs) to generate near-rectangular electric field E-field) pulses with adjustable number, polarity, duration, and amplitude of the pulse phases. This controllable-pulse-parameter TMS (cTMS) device can induce E-field pulses with phase widths of 5-200 µs and positive/negative phase amplitude ratio of 1-10. Compared to conventional monophasic and biphasic TMS, cTMS reduces energy dissipation by 78-82% and 55-57% and decreases coil heating by 15-33% and 31-41%, respectively. We demonstrate repetitive TMS (rTMS) trains of 3,000 pulses at frequencies up to 50 Hz with E-field pulse amplitude and width variability of less than 1.7% and 1%, respectively. The reduced power consumption and coil heating, and the flexible pulse parameter adjustment offered by cTMS could enhance existing TMS paradigms and could enable novel research and clinical applications with potentially enhanced potency.

  18. Noninvasive Brain Stimulation With High-Frequency and Low-Intensity Repetitive Transcranial Magnetic Stimulation Treatment for Posttraumatic Stress Disorder

    PubMed Central

    Boggio, Paulo Sergio; Rocha, Martha; Oliveira, Maira Okada; Fecteau, Shirley; Cohen, Roni B.; Campanhã, Camila; Ferreira-Santos, Eduardo; Meleiro, Alexandrina; Corchs, Felipe; Zaghi, Soroush; Pascual-Leone, Alvaro; Fregni, Felipe

    2011-01-01

    Objective We aimed to investigate the efficacy of 20 Hz repetitive transcranial magnetic stimulation (rTMS) of either right or left dorsolateral prefrontal cortex (DLPFC) as compared to sham rTMS for the relief of posttraumatic stress disorder (PTSD)–associated symptoms. Method In this double-blind, placebo-controlled phase II trial conducted between October 2005 and July 2008, 30 patients with DSM-IV–diagnosed PTSD were randomly assigned to receive 1 of the following treatments: active 20 Hz rTMS of the right DLPFC, active 20 Hz rTMS of the left DLPFC, or sham rTMS. Treatments were administered in 10 daily sessions over 2 weeks. A blinded rater assessed severity of core PTSD symptoms, depression, and anxiety before, during, and after completion of the treatment protocol. In addition, a battery of neuropsychological tests was measured before and after treatment. Results Results show that both active conditions—20 Hz rTMS of left and right DLPFC—induced a significant decrease in PTSD symptoms as indexed by the PTSD Checklist and Treatment Outcome PTSD Scale; however, right rTMS induced a larger effect as compared to left rTMS. In addition, there was a significant improvement of mood after left rTMS and a significant reduction of anxiety following right rTMS. Improvements in PTSD symptoms were long lasting; effects were still significant at the 3-month follow-up. Finally, neuropsychological evaluation showed that active 20 Hz rTMS is not associated with cognitive worsening and is safe for use in patients with PTSD. Conclusions These results support the notion that modulation of prefrontal cortex can alleviate the core symptoms of PTSD and suggest that high-frequency rTMS of right DLPFC might be the optimal treatment strategy. PMID:20051219

  19. Impact of Repetitive Transcranial Magnetic Stimulation (rTMS) on Brain Functional Marker of Auditory Hallucinations in Schizophrenia Patients

    PubMed Central

    Maïza, Olivier; Hervé, Pierre-Yve; Etard, Olivier; Razafimandimby, Annick; Montagne-Larmurier, Aurélie; Dollfus, Sonia

    2013-01-01

    Several cross-sectional functional Magnetic Resonance Imaging (fMRI) studies reported a negative correlation between auditory verbal hallucination (AVH) severity and amplitude of the activations during language tasks. The present study assessed the time course of this correlation and its possible structural underpinnings by combining structural, functional MRI and repetitive Transcranial Magnetic Stimulation (rTMS). Methods: Nine schizophrenia patients with AVH (evaluated with the Auditory Hallucination Rating scale; AHRS) and nine healthy participants underwent two sessions of an fMRI speech listening paradigm. Meanwhile, patients received high frequency (20 Hz) rTMS. Results: Before rTMS, activations were negatively correlated with AHRS in a left posterior superior temporal sulcus (pSTS) cluster, considered henceforward as a functional region of interest (fROI). After rTMS, activations in this fROI no longer correlated with AHRS. This decoupling was explained by a significant decrease of AHRS scores after rTMS that contrasted with a relative stability of cerebral activations. A voxel-based-morphometry analysis evidenced a cluster of the left pSTS where grey matter volume negatively correlated with AHRS before rTMS and positively correlated with activations in the fROI at both sessions. Conclusion: rTMS decreases the severity of AVH leading to modify the functional correlate of AVH underlain by grey matter abnormalities. PMID:24961421

  20. Effect of Repetitive Transcranial Magnetic Stimulation on fMRI Resting-State Connectivity in Multiple System Atrophy

    PubMed Central

    Chou, Ying-hui; Zhao, Yan-Ping; Hou, Bo; Feng, Feng

    2015-01-01

    Abstract Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique that has been used to treat neurological and psychiatric conditions. Although results of rTMS intervention are promising, so far, little is known about the rTMS effect on brain functional networks in clinical populations. In this study, we used a whole-brain connectivity analysis of resting-state functional magnetic resonance imaging data to uncover changes in functional connectivity following rTMS intervention and their association with motor symptoms in patients with multiple system atrophy (MSA). Patients were randomized to active rTMS or sham rTMS groups and completed a 10-session 5-Hz rTMS treatment over the left primary motor area. The results showed significant rTMS-related changes in motor symptoms and functional connectivity. Specifically, (1) significant improvement of motor symptoms was observed in the active rTMS group, but not in the sham rTMS group; and (2) several functional links involving the default mode, cerebellar, and limbic networks exhibited positive changes in functional connectivity in the active rTMS group. Moreover, the positive changes in functional connectivity were associated with improvement in motor symptoms for the active rTMS group. The present findings suggest that rTMS may improve motor symptoms by modulating functional links connecting to the default mode, cerebellar, and limbic networks, inferring a future therapeutic candidate for patients with MSA. PMID:25786196

  1. A Randomised Controlled Trial of Neuronavigated Repetitive Transcranial Magnetic Stimulation (rTMS) in Anorexia Nervosa

    PubMed Central

    McClelland, Jessica; Kekic, Maria; Bozhilova, Natali; Nestler, Steffen; Dew, Tracy; Van den Eynde, Frederique; David, Anthony S.; Rubia, Katya; Campbell, Iain C.; Schmidt, Ulrike

    2016-01-01

    Background Anorexia nervosa (AN) is associated with morbid fear of fatness, extreme food restriction and altered self-regulation. Neuroimaging data implicate fronto-striatal circuitry, including the dorsolateral prefrontal cortex (DLPFC). Methods In this double-blind parallel group study, we investigated the effects of one session of sham-controlled high-frequency repetitive transcranial magnetic stimulation (rTMS) to the left DLPFC (l-DLPFC) in 60 individuals with AN. A food exposure task was administered before and after the procedure to elicit AN-related symptoms. Outcomes The primary outcome measure was ‘core AN symptoms’, a variable which combined several subjective AN-related experiences. The effects of rTMS on other measures of psychopathology (e.g. mood), temporal discounting (TD; intertemporal choice behaviour) and on salivary cortisol concentrations were also investigated. Safety, tolerability and acceptability were assessed. Results Fourty-nine participants completed the study. Whilst there were no interaction effects of rTMS on core AN symptoms, there was a trend for group differences (p = 0.056): after controlling for pre-rTMS scores, individuals who received real rTMS had reduced symptoms post-rTMS and at 24-hour follow-up, relative to those who received sham stimulation. Other psychopathology was not altered differentially following real/sham rTMS. In relation to TD, there was an interaction trend (p = 0.060): real versus sham rTMS resulted in reduced rates of TD (more reflective choice behaviour). Salivary cortisol concentrations were unchanged by stimulation. rTMS was safe, well–tolerated and was considered an acceptable intervention. Conclusions This study provides modest evidence that rTMS to the l-DLPFC transiently reduces core symptoms of AN and encourages prudent decision making. Importantly, individuals with AN considered rTMS to be a viable treatment option. These findings require replication in multiple-session studies to evaluate

  2. Safety study of 50 Hz repetitive transcranial magnetic stimulation in patients with Parkinson’s disease

    PubMed Central

    Benninger, David H.; Lomarev, Mikhail; Wassermann, Eric; Lopez, Grisel; Houdayer, Elise; Fasano, Rebecca E.; Dang, Nguyet; Hallett, Mark

    2009-01-01

    Objective Repetitive transcranial magnetic stimulation (rTMS) has shown promising results in treating Parkinson’s disease (PD), but the best values for rTMS parameters are not established. 50 Hz rTMS may be superior to ≤ 25 Hz rTMS investigated so far. The objective of this study was to determine if 50 Hz rTMS could be delivered safely in PD patients since current safety limits are exceeded. Methods 50 Hz rTMS was applied with a circular coil on the primary motor cortex (M1). Stimulation intensity was first tested at 60% rest motor threshold [RMT] and 0.5 sec train duration and then increased in 0.5 sec steps to 2 sec, and by 10% steps to 90% RMT. Multi-channel electromyography (EMG) was recorded to control for signs of increasing time-locked EMG activity including correlates of the spread of excitation and after-discharges, or an increase of M1 excitability. Pre- and post-50 Hz rTMS assessments included EEG, Unified Parkinson Disease Rating Scale (UPDRS), Grooved Pegboard Test, Serial Reaction Time Task (SRTT), Folstein Mini-Mental Status Examination (MMSE) and Verbal Fluency to control for motor and cognitive side effects. Results Ten PD patients were investigated. Multi-channel EMG showed no signs of increased time-locked EMG activity including correlates of the spread of excitation and after-discharges, or increased M1 excitability in 9 patients. A PD patient with bi-temporal spikes in the pre-testing EEG had clinical and EMG correlates of spread of excitation at 90% RMT, but no seizure activity. Pre- and post-50 Hz assessment showed no changes. No adverse events were observed. 50 Hz rTMS was well tolerated except by one patient who wished to terminate the study due to facial muscle stimulation. Conclusion 50 Hz rTMS at an intensity of 90% RMT for 2 sec appears safe in patients with PD, but caution should be taken for patients with paroxysmal EEG activity. For this reason, comprehensive screening should include EEG before higher-frequency rTMS is applied

  3. Increased cerebellar activation after repetitive transcranial magnetic stimulation over the primary motor cortex in patients with multiple system atrophy

    PubMed Central

    Li, Linling; Wu, Tianxia; Hou, Bo; Wu, Shuang; Feng, Feng; Cui, Liying

    2016-01-01

    Background Previous review reported that the high-frequency repetitive transcranial magnetic stimulation (rTMS) over the primary motor area (M1) of Parkinson’s disease (PD) patients could alleviate their symptoms. This study aimed to investigate the effect of rTMS over the left M1 of patients with multiple system atrophy (MSA). Methods Fifteen MSA patients were randomly assigned to receive a 10-session real (EP: group of experimental patients; n=7) or sham (CP: group of control patients; n=8) rTMS stimulation over two weeks. The overall experimental procedure consisted of two functional magnetic resonance imaging (fMRI) sessions, before and after a 10-session rTMS treatment. A complex self-paced sequential tapping task was performed during fMRI scanning. In addition, 18 age and gender matched healthy controls (HC) were enrolled. Subjects from the HC group did not receive any rTMS treatment and they underwent fMRI examination only once. The primary end point was the motor score change of the Unified Multiple System Atrophy Rating Scale (UMSARS-II) measured before and after the 5th and 10th session. Task-related activation was also compared among groups. Results After active rTMS treatment, only patients of EP group significant improvement in UMSARS-II score. Compared to HC, MSA patients showed significant activation over similar brain areas except for the cerebellum. Increased activation was obtained in the bilateral cerebellum after rTMS treatment in the EP group. On the contrary, no increased activation was identified in the CP group. Conclusions Our results highlight rTMS over M1 induced motor improvement in MSA patients that may be associated with increased activation in the cerebellum. PMID:27127756

  4. Increases in frontostriatal connectivity are associated with response to dorsomedial repetitive transcranial magnetic stimulation in refractory binge/purge behaviors

    PubMed Central

    Dunlop, Katharine; Woodside, Blake; Lam, Eileen; Olmsted, Marion; Colton, Patricia; Giacobbe, Peter; Downar, Jonathan

    2015-01-01

    Background Conventional treatments for eating disorders are associated with poor response rates and frequent relapse. Novel treatments are needed, in combination with markers to characterize and predict treatment response. Here, resting-state functional magnetic resonance imaging (rs-fMRI) was used to identify predictors and correlates of response to repetitive transcranial magnetic stimulation (rTMS) of the dorsomedial prefrontal cortex (dmPFC) at 10 Hz for eating disorders with refractory binge/purge symptomatology. Methods 28 subjects with anorexia nervosa, binge−purge subtype or bulimia nervosa underwent 20–30 sessions of 10 Hz dmPFC rTMS. rs-fMRI data were collected before and after rTMS. Subjects were stratified into responder and nonresponder groups using a criterion of ≥50% reduction in weekly binge/purge frequency. Neural predictors and correlates of response were identified using seed-based functional connectivity (FC), using the dmPFC and adjacent dorsal anterior cingulate cortex (dACC) as regions of interest. Results 16 of 28 subjects met response criteria. Treatment responders had lower baseline FC from dmPFC to lateral orbitofrontal cortex and right posterior insula, and from dACC to right posterior insula and hippocampus. Responders had low baseline FC from the dACC to the ventral striatum and anterior insula; this connectivity increased over treatment. However, in nonresponders, frontostriatal FC was high at baseline, and dmPFC-rTMS suppressed FC in association with symptomatic worsening. Conclusions Enhanced frontostriatal connectivity was associated with responders to dmPFC-rTMS for binge/purge behavior. rTMS caused paradoxical suppression of frontostriatal connectivity in nonresponders. rs-fMRI could prove critical for optimizing stimulation parameters in a future sham-controlled trial of rTMS in disordered eating. PMID:26199873

  5. Effects of repetitive transcranial magnetic stimulation in performing eye-hand integration tasks: four preliminary studies with children showing low-functioning autism.

    PubMed

    Panerai, Simonetta; Tasca, Domenica; Lanuzza, Bartolo; Trubia, Grazia; Ferri, Raffaele; Musso, Sabrina; Alagona, Giovanna; Di Guardo, Giuseppe; Barone, Concetta; Gaglione, Maria P; Elia, Maurizio

    2014-08-01

    This report, based on four studies with children with low-functioning autism, aimed at evaluating the effects of repetitive transcranial magnetic stimulation delivered on the left and right premotor cortices on eye-hand integration tasks; defining the long-lasting effects of high-frequency repetitive transcranial magnetic stimulation; and investigating the real efficacy of high-frequency repetitive transcranial magnetic stimulation by comparing three kinds of treatments (high-frequency repetitive transcranial magnetic stimulation, a traditional eye-hand integration training, and both treatments combined). Results showed a significant increase in eye-hand performances only when high-frequency repetitive transcranial magnetic stimulation was delivered on the left premotor cortex; a persistent improvement up to 1 h after the end of the stimulation; better outcomes in the treatment combining high-frequency repetitive transcranial magnetic stimulation and eye-hand integration training. Based on these preliminary findings, further evaluations on the usefulness of high-frequency repetitive transcranial magnetic stimulation in rehabilitation of children with autism are strongly recommended.

  6. Preliminary guidelines for safe and effective use of repetitive transcranial magnetic stimulation in moderate to severe traumatic brain injury.

    PubMed

    Nielson, Dylan M; McKnight, Curtis A; Patel, Riddhi N; Kalnin, Andrew J; Mysiw, Walter J

    2015-04-01

    Transcranial magnetic stimulation has generated extensive interest within the traumatic brain injury (TBI) rehabilitation community, but little work has been done with repetitive protocols, which can produce prolonged changes in behavior. This is partly because of concerns about the safety of repetitive transcranial magnetic stimulation (rTMS) in subjects with TBI, particularly the risk of seizures. These risks can be minimized by careful selection of the rTMS protocol and exclusion criteria. In this article, we identify guidelines for safe use of rTMS in subjects with TBI based on a review of the literature and illustrate their application with a case study. Our subject is a 48-year-old man who sustained a severe TBI 5 years prior to beginning rTMS for the treatment of post-TBI depression. After a 4-week baseline period, we administered daily sessions of low-frequency stimulation to the right dorsolateral prefrontal cortex for 6 weeks. After stimulation, we performed monthly assessments for 3 months. The Hamilton Depression Rating Scale (HAMD) was our primary outcome measure. The stimulation was well tolerated and the patient reported no side effects. After 6 weeks of stimulation, the patient's depression was slightly improved, and these improvements continued through follow-up. At the end of follow-up, the patient's HAMD score was 49% of the average baseline score.

  7. Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression: An Economic Analysis

    PubMed Central

    Tu, Hong Anh; Palimaka, Stefan; Sehatzadeh, Shayan; Blackhouse, Gord; Yap, Belinda; Tsoi, Bernice; Bowen, Jim; O'Reilly, Daria; Holubowich, Corinne; Kaulback, Kellee; Campbell, Kaitryn

    2016-01-01

    Background Major depressive disorder (MDD, 10% over a person's lifetime) is common and costly to the health system. Unfortunately, many MDD cases are resistant to treatment with antidepressant drugs and require other treatment to reduce or eliminate depression. Electroconvulsive therapy (ECT) has long been used to treat persons with treatment-resistant depression (TRD). Despite its effectiveness, ECT has side effects that make patients intolerant to the treatment, or they refuse to use it. Repetitive transcranial magnetic stimulation (rTMS), which has fewer side effects than ECT and might be an alternative for TRD patients who are ineligible for or unwilling to undergo ECT, has been developed to treat TRD. Objectives This analysis evaluates the cost-effectiveness of rTMS for patients with TRD compared with ECT or sham rTMS and estimates the potential budgetary impact of various levels of implementation of rTMS in Ontario. Review Methods A cost-utility analysis compared the costs and health outcomes of two treatments for persons with TRD in Ontario: rTMS alone compared with ECT alone and rTMS alone compared with sham rTMS. We calculated the six-month incremental costs and quality-adjusted life-years (QALYs) for these treatments. One-way and probabilistic sensitivity analyses were performed to test the robustness of the model's results. A 1-year budget impact analysis estimated the costs of providing funding for rTMS. The base-case analysis examined the additional costs for funding six centres, where rTMS infrastructure is in place. Sensitivity and scenario analyses explored the impact of increasing diffusion of rTMS to centres with existing ECT infrastructure. All analyses were conducted from the Ontario health care payer perspective. Results ECT was cost effective compared to rTMS when the willingness to pay is greater than $37,640.66 per QALY. In the base-case analysis, which had a six-month time horizon, the cost and effectiveness for rTMS was $5,272 and 0

  8. Low-frequency repetitive transcranial magnetic stimulation for dyskinesia and motor performance in Parkinson's disease.

    PubMed

    Sayın, Sevgi; Cakmur, Raif; Yener, Görsev G; Yaka, Erdem; Uğurel, Burcu; Uzunel, Fatma

    2014-08-01

    Dyskinesias are one of the most frequent and disabling complications of the long-term treatment of Parkinson's disease (PD). Although the cause is not completely understood, it appears that an imbalance between excitatory and inhibitory inputs from the basal ganglia to the motor cortex leads to overactivation of motor and premotor areas. Overactivation of the supplementary motor area (SMA) has been observed in neuroimaging studies in dyskinetic PD patients. We investigated the effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) of the SMA on levodopa-induced dyskinesias (LID) and motor performance in PD. We tested whether longer duration (10days) and higher number of total pulses (1800 pulses) would enhance the beneficial effect. Seventeen dyskinetic PD patients were randomly assigned to real rTMS or sham (placebo) rTMS, and 1Hz rTMS or sham rTMS was applied over the SMA for 10 consecutive days. Patients were assessed at baseline and 1day after the last rTMS with a levodopa challenge test, and video recordings were taken. Dyskinesias and motor performance were rated off-line by two blinded raters using video recordings. After 10days of treatment with rTMS, we observed that 1Hz rTMS delivered over the SMA had decreased LID lasting for 24hours without a change in motor performance, whereas sham rTMS induced no significant change in dyskinesia scores. These results support a possible therapeutic effect of low-frequency rTMS in LID. However, in order to suggest rTMS as an effective treatment, long-term observations and further investigations with a larger patient population are essential.

  9. Tibialis anterior stretch reflex in early stance is suppressed by repetitive transcranial magnetic stimulation

    PubMed Central

    Zuur, Abraham T; Christensen, Mark S; Sinkjær, Thomas; Grey, Michael J; Nielsen, Jens Bo

    2009-01-01

    A rapid plantar flexion perturbation in the early stance phase of walking elicits a large stretch reflex in tibialis anterior (TA). In this study we use repetitive transcranial magnetic stimulation (rTMS) to test if this response is mediated through a transcortical pathway. TA stretch reflexes were elicited in the early stance phase of the step cycle during treadmill walking. Twenty minutes of 1 Hz rTMS at 115% resting motor threshold (MTr) significantly decreased (P < 0.05) the magnitude of the later component of the reflex at a latency of ∼100 ms up to 25 min after the rTMS. Control experiments in which stretch reflexes were elicited during sitting showed no effect on the spinally mediated short and medium latency stretch reflexes (SLR and MLR) while the long latency stretch reflex (LLR) and the motor-evoked potential (MEP) showed a significant decrease 10 min after 115% MTr rTMS. This study demonstrates that 1 Hz rTMS applied to the leg area of the motor cortex can suppress the long latency TA stretch reflex during sitting and in the stance phase of walking. These results are in line with the hypothesis that the later component of the TA stretch reflex in the stance phase of walking is mediated by a transcortical pathway. An alternative explanation for the observed results is that the reflex is mediated by subcortical structures that are affected by the rTMS. This study also shows that rTMS may be used to study the neural control of walking. PMID:19237419

  10. Topiramate and cortical excitability in humans: a study with repetitive transcranial magnetic stimulation.

    PubMed

    Inghilleri, M; Gilio, F; Conte, A; Frasca, V; Marini Bettolo, C; Iacovelli, E; Gregori, B; Prencipe, M; Berardelli, A

    2006-10-01

    Repetitive transcranial magnetic stimulation (rTMS) delivered at 5 Hz frequency and suprathreshold intensity progressively increases the size of muscle evoked potentials (MEPs) and the duration of the cortical silent period (CSP) in normal subjects. The aim of this study was to evaluate the effects of topiramate (TPM) at different doses on cortical excitability variables tested with rTMS. We tested the facilitation of the MEP size and CSP duration evoked by focal rTMS in eight patients before and after treatment with TPM at different doses for chronic neuropathic pain. In each patient, rTMS (5 Hz frequency-120% resting motor threshold) was applied at baseline and during the TPM induction phase (drug intake schedule: week I 25 mg/day, week II 50 mg/day, week III 75 mg/day, week IV 100 mg/day) and total TPM plasma concentrations were measured. The effects on the MEP size of 5 Hz-rTMS delivered over repeated sessions were tested in eight control subjects. TPM had no effect on the resting motor threshold. Antiepileptic treatment at increasing doses abolished the normal rTMS-induced MEP facilitation. ANOVA showed that this was a dose-related effect. Accordingly, in patients receiving TPM at higher doses (75 and 100 mg) rTMS failed to elicit the MEP facilitation. TPM left the progressive lengthening of the CSP during the rTMS train unchanged. In control subjects, rTMS applied over repeated sessions elicited a constant increase in MEP size. Our results suggest that TPM modulates the excitatory intracortical interneurons probably by altering rTMS-induced synaptic potentiation. These drug-induced effects are related to TPM doses and plasma concentrations. In conclusion, rTMS may be useful for quantifying the effectiveness of antiepileptic drugs and for assessing individual responses to different drugs but acting through similar mechanisms, thus combining functional neurophysiological information and laboratory data.

  11. Effects of repetitive transcranial magnetic stimulation on the somatosensory cortex during prism adaptation.

    PubMed

    Yoon, Hee-Chul; Lee, Kyung-Hyun; Huh, Dong-Chan; Lee, Ji-Hang; Lee, Dong-Hyun

    2014-04-01

    Although the behavioral characteristics and the neural correlates of prism adaptation processes have been studied extensively, the underlying mechanism is yet to be investigated. Recently, somatosensory suppression was heralded as a mechanism for the sensory re-alignment process accompanying the adaptation. Somatosensory suppression should facilitate the re-alignment process in the proprioceptive system. The shift in the proprioceptive system takes place mostly during a concurrent visual feedback (CVF) condition; during a terminal visual feedback (TVF) condition, the visual system experiences significant adaptation (visual shift), so somatosensory suppression should have minimal functional consequences under TVF. To test this hypothesis, a repetitive transcranial magnetic stimulation (rTMS) was applied to the primary somatosensory cortex as an artificial somatosensory suppression right after the reaching initiation in CVF and TVF conditions, and changes in adaptation were observed. Because somatosensory suppression is already in effect during CVF, rTMS would cause no significant changes. During TVF with rTMS, however, significantly different patterns of adaptation could be expected when compared to a sham rTMS condition. Young adults (N = 12) participated in 4 sessions (CVF/ TVF, real/sham rTMS); visual proprioceptive, and total shifts were measured. Movement time and curvature of the reaching movement were measured during the adaptation phase. Results showed that while the total shift was unchanged, the proprioceptive shift increased and the visual shift decreased in the TVF condition when rTMS was delivered. However, the total, proprioceptive, and visual shifts were not influenced by rTMS in the CVF condition. Suppression of proprioception induced by the rTMS could be one of the requisites for successful proprioceptive shift during prism adaptation.

  12. Knowledge of and Attitude Toward Repetitive Transcranial Magnetic Stimulation Among Psychiatrists in Saudi Arabia

    PubMed Central

    AlHadi, Ahmad N.; AlShiban, Abdulrahman M.; Alomar, Majed A.; Aljadoa, Othman F.; AlSayegh, Ahmed M.; Jameel, Mohammed A.

    2017-01-01

    Objectives The aims of this study were to assess psychiatrists' knowledge of and attitudes toward repetitive transcranial magnetic stimulation (rTMS) in Saudi Arabia and to determine the contributing factors. Methods A quantitative observational cross-sectional study was conducted using an online survey. The sample consisted of 96 psychiatrists in Saudi Arabia. A new valid and reliable questionnaire was developed. Results A total of 96 psychiatrists enrolled in the study, 81% of whom were men. Half of the participants were consultants. The sample mainly consisted of general psychiatrists (65%). The mean age of the participants was 37 years. The results showed that 80% of the psychiatrists had a sufficient level of knowledge about rTMS. Consultants had greater knowledge than residents. Training abroad was not significantly associated with the level of knowledge or the type of attitude. Most psychiatrists (79%) had a positive attitude toward rTMS. Only 53% of the psychiatrists said they would agree to receive rTMS if they experienced a psychotic depressive condition. A minority of psychiatrists (7%) said they would not refer their patients for rTMS. Conclusions Most of the psychiatrists surveyed had good knowledge of and a positive attitude toward rTMS. Those who had a high level of training and experience showed higher levels of knowledge. Articles were reported to be a better source for improving physician knowledge than textbooks. Having a family member or relative who was treated with rTMS positively affected psychiatrists' attitudes toward rTMS. PMID:27564426

  13. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS).

    PubMed

    Lefaucheur, Jean-Pascal; André-Obadia, Nathalie; Antal, Andrea; Ayache, Samar S; Baeken, Chris; Benninger, David H; Cantello, Roberto M; Cincotta, Massimo; de Carvalho, Mamede; De Ridder, Dirk; Devanne, Hervé; Di Lazzaro, Vincenzo; Filipović, Saša R; Hummel, Friedhelm C; Jääskeläinen, Satu K; Kimiskidis, Vasilios K; Koch, Giacomo; Langguth, Berthold; Nyffeler, Thomas; Oliviero, Antonio; Padberg, Frank; Poulet, Emmanuel; Rossi, Simone; Rossini, Paolo Maria; Rothwell, John C; Schönfeldt-Lecuona, Carlos; Siebner, Hartwig R; Slotema, Christina W; Stagg, Charlotte J; Valls-Sole, Josep; Ziemann, Ulf; Paulus, Walter; Garcia-Larrea, Luis

    2014-11-01

    A group of European experts was commissioned to establish guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS) from evidence published up until March 2014, regarding pain, movement disorders, stroke, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, consciousness disorders, tinnitus, depression, anxiety disorders, obsessive-compulsive disorder, schizophrenia, craving/addiction, and conversion. Despite unavoidable inhomogeneities, there is a sufficient body of evidence to accept with level A (definite efficacy) the analgesic effect of high-frequency (HF) rTMS of the primary motor cortex (M1) contralateral to the pain and the antidepressant effect of HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC). A Level B recommendation (probable efficacy) is proposed for the antidepressant effect of low-frequency (LF) rTMS of the right DLPFC, HF-rTMS of the left DLPFC for the negative symptoms of schizophrenia, and LF-rTMS of contralesional M1 in chronic motor stroke. The effects of rTMS in a number of indications reach level C (possible efficacy), including LF-rTMS of the left temporoparietal cortex in tinnitus and auditory hallucinations. It remains to determine how to optimize rTMS protocols and techniques to give them relevance in routine clinical practice. In addition, professionals carrying out rTMS protocols should undergo rigorous training to ensure the quality of the technical realization, guarantee the proper care of patients, and maximize the chances of success. Under these conditions, the therapeutic use of rTMS should be able to develop in the coming years.

  14. Therapeutic effects of repetitive transcranial magnetic stimulation in an animal model of Parkinson's disease.

    PubMed

    Lee, Ji Yong; Kim, Sung Hoon; Ko, Ah-Ra; Lee, Jin Suk; Yu, Ji Hea; Seo, Jung Hwa; Cho, Byung Pil; Cho, Sung-Rae

    2013-11-06

    Repetitive transcranial magnetic stimulation (rTMS) is used to treat neurological diseases such as stroke and Parkinson's disease (PD). Although rTMS has been used clinically, its underlying therapeutic mechanism remains unclear. The objective of the present study was to clarify the neuroprotective effect and therapeutic mechanism of rTMS in an animal model of PD. Adult Sprague-Dawley rats were unilaterally injected with 6-hydroxydopamine (6-OHDA) into the right striatum. Rats with PD were then treated with rTMS (circular coil, 10 Hz, 20 min/day) daily for 4 weeks. Behavioral assessments such as amphetamine-induced rotational test and treadmill locomotion test were performed, and the dopaminergic (DA) neurons of substantia nigra pas compacta (SNc) and striatum were histologically examined. Expression of neurotrophic/growth factors was also investigated by multiplex ELISA, western blotting analysis and immunohistochemistry 4 weeks after rTMS application. Among the results, the number of amphetamine-induced rotations was significantly lower in the rTMS group than in the control group at 4 weeks post-treatment. Treadmill locomotion was also significantly improved in the rTMS-treated rats. Tyrosine hydroxylase-positive DA neurons and DA fibers in rTMS group rats were greater than those in untreated group in both ipsilateral SNc and striatum, respectively. The expression levels of brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, platelet-derived growth factor, and vascular endothelial growth factor were elevated in both the 6-OHDA-injected hemisphere and the SNc of the rTMS-treated rats. In conclusion, rTMS treatment improved motor functions and survival of DA neurons, suggesting that the neuroprotective effect of rTMS treatment might be induced by upregulation of neurotrophic/growth factors in the PD animal model.

  15. Cognitive safety of dorsomedial prefrontal repetitive transcranial magnetic stimulation in major depression.

    PubMed

    Schulze, Laura; Wheeler, Sarah; McAndrews, Mary Pat; Solomon, Chloe J E; Giacobbe, Peter; Downar, Jonathan

    2016-07-01

    The most widely used target for repetitive transcranial magnetic stimulation (rTMS) in treatment-resistant depression (TRD) is the dorsolateral prefrontal cortex (DLPFC). Despite convergent evidence that the dorsomedial prefrontal cortex (DMPFC) may be a promising alternative target for rTMS in TRD, its cognitive safety profile has not previously been assessed. Here, we applied 20 sessions of rTMS to the DMPFC in 21 TRD patients. Before and after treatment, a battery of neuropsychological tasks was administered to evaluate changes in cognition across three general cognitive domains: learning and memory, attention and processing speed, and cognitive flexibility. Subjects also completed the 17-item Hamilton Rating Scale for Depression (HamD17) prior to and following treatment to measure changes in severity of depressive symptoms, and to assess the relationship between mood and cognitive performance over the course of treatment. No serious adverse effects or significant deterioration in cognitive performance were observed. Overall, subjects improved significantly on Stroop Inhibition/Switching and on Trails B, and this improvement was independent of the degree of improvement in depression symptoms. No domains or items significantly predicted clinical outcome, with the exception of baseline performance on Visual Elevator Accuracy. Clinical improvement correlated to improved performance in the overall domain of attention and processing speed, although this effect was not evident following covariate adjustment. DMPFC-rTMS did not produce any detectable cognitive adverse effects during treatment of TRD. Performance did not deteriorate significantly on any measures. Taken together, the present findings support the tolerability and cognitive safety of DMPFC-rTMS in refractory depression.

  16. Repetitive transcranial magnetic stimulation versus botulinum toxin injection in chronic migraine prophylaxis: a pilot randomized trial

    PubMed Central

    Shehata, Hatem S; Esmail, Eman H; Abdelalim, Ahmad; El-Jaafary, Shaimaa; Elmazny, Alaa; Sabbah, Asmaa; Shalaby, Nevin M

    2016-01-01

    Background Chronic migraine is a prevalent disabling disease, with major health-related burden and poor quality of life. Long-term use of preventive medications carries risk of side effects. Objectives The aim of this study was to compare repetitive transcranial magnetic stimulation (rTMS) to botulinum toxin-A (BTX-A) injection as preventive therapies for chronic migraine. Methods A pilot, randomized study was conducted on a small-scale sample of 29 Egyptian patients with chronic migraine, recruited from Kasr Al-Aini teaching hospital outpatient clinic and diagnosed according to ICHD-III (beta version). Patients were randomly assigned into two groups; 15 patients received BTX-A injection following the Phase III Research Evaluating Migraine Prophylaxis Therapy injection paradigm and 14 patients were subjected to 12 rTMS sessions delivered at high frequency (10 Hz) over the left motor cortex (MC, M1). All the patients were requested to have their 1-month headache calendar, and they were subjected to a baseline 25-item (beta version) Henry Ford Hospital Headache Disability Inventory (HDI), Headache Impact Test (HIT-6), and visual analogue scale assessment of headache intensity. The primary efficacy measures were headache frequency and severity; secondary measures were 25-item HDI, HIT-6, and number of acute medications. Follow-up visits were scheduled at weeks 4, 6, 8, 10, and 12 after baseline visit. Results A reduction in all outcome measures was achieved in both the groups. However, this improvement was more sustained in the BTX-A group, and both the therapies were well tolerated. Conclusion BTX-A injection and rTMS have favorable efficacy and safety profiles in chronic migraineurs. rTMS is of comparable efficacy to BTX-A injection in chronic migraine therapy, but with less sustained effect. PMID:27785091

  17. Cortical excitability changes after high-frequency repetitive transcranial magnetic stimulation for central poststroke pain.

    PubMed

    Hosomi, Koichi; Kishima, Haruhiko; Oshino, Satoru; Hirata, Masayuki; Tani, Naoki; Maruo, Tomoyuki; Yorifuji, Shiro; Yoshimine, Toshiki; Saitoh, Youichi

    2013-08-01

    Central poststroke pain (CPSP) is one of the most refractory chronic pain syndromes. Repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex has been demonstrated to provide moderate pain relief for CPSP. However, the mechanism underlying the pain relief remains unclear. The objective of this study was to assess changes in cortical excitability in patients with intractable CPSP before and after rTMS of the primary motor cortex. Subjects were 21 patients with CPSP of the hand who underwent rTMS. The resting motor threshold, the amplitude of the motor evoked potential, duration of the cortical silent period, short interval intracortical inhibition, and intracortical facilitation were measured as parameters of cortical excitability before and after navigation-guided 5 Hz rTMS of the primary motor cortex corresponding to the painful hand. Pain reduction from rTMS was assessed with a visual analog scale. The same parameters were measured in both hemispheres of 8 healthy controls. Eight of 21 patients experienced ≥ 30% pain reduction after rTMS (responders). The resting motor threshold in the patients was higher than those in the controls at baseline (P=.035). Intracortical facilitation in the responders was lower than in the controls and the nonresponders at baseline (P=.035 and P=.019), and significantly increased after rTMS (P=.039). There were no significant differences or changes in the other parameters. Our findings suggest that restoration of abnormal cortical excitability might be one of the mechanisms underlying pain relief as a result of rTMS in CPSP.

  18. Effect of low-frequency repetitive transcranial magnetic stimulation combined with physical therapy on L-dopa-induced painful off-period dystonia in Parkinson's disease.

    PubMed

    Kodama, Mitsuhiko; Kasahara, Takashi; Hyodo, Masaki; Aono, Koji; Sugaya, Mutsumi; Koyama, Yuji; Hanayama, Kozo; Masakado, Yoshihisa

    2011-02-01

    Previous research has shown that low-frequency repetitive transcranial magnetic stimulation over the primary motor area and supplementary motor area can reduce L-dopa-induced dyskinesias in Parkinson's disease; however, it involved only patients with peak-dose or diphasic dyskinesia. We report a case of a patient with severely painful off-period dystonia in the unilateral lower limb who underwent 0.9-Hz subthreshold repetitive transcranial magnetic stimulation over contralateral primary motor area and supplementary motor area. Repetitive transcranial magnetic stimulation over the primary motor area significantly reduced the painful dystonia and walking disturbances but repetitive transcranial magnetic stimulation over the supplementary motor area did not. The cortical silent period also prolonged after repetitive transcranial magnetic stimulation over the primary motor area. At 5 mos of approximately once a week repetitive transcranial magnetic stimulation over the primary motor area, the Unified Parkinson's Disease Rating Scale motor score also improved. This report shows that repetitive transcranial magnetic stimulation over the inhibitory primary motor area can be useful for rehabilitating patients with Parkinson's disease with off-period dystonia and suggests that this treatment should be further verified in such patients.

  19. Improved Acuity and Dexterity but Unchanged Touch and Pain Thresholds following Repetitive Sensory Stimulation of the Fingers

    PubMed Central

    Kowalewski, Rebecca; Kattenstroth, Jan-Christoph; Kalisch, Tobias; Dinse, Hubert R.

    2012-01-01

    Neuroplasticity underlies the brain's ability to alter perception and behavior through training, practice, or simply exposure to sensory stimulation. Improvement of tactile discrimination has been repeatedly demonstrated after repetitive sensory stimulation (rSS) of the fingers; however, it remains unknown if such protocols also affect hand dexterity or pain thresholds. We therefore stimulated the thumb and index finger of young adults to investigate, besides testing tactile discrimination, the impact of rSS on dexterity, pain, and touch thresholds. We observed an improvement in the pegboard task where subjects used the thumb and index finger only. Accordingly, stimulating 2 fingers simultaneously potentiates the efficacy of rSS. In fact, we observed a higher gain of discrimination performance as compared to a single-finger rSS. In contrast, pain and touch thresholds remained unaffected. Our data suggest that selecting particular fingers modulates the efficacy of rSS, thereby affecting processes controlling sensorimotor integration. PMID:22315693

  20. Kinetic changes in tetanic Ca2+ transients in enzymatically dissociated muscle fibres under repetitive stimulation

    PubMed Central

    Calderón, Juan C; Bolaños, Pura; Caputo, Carlo

    2011-01-01

    Abstract We used enzymatically dissociated flexor digitorum brevis (FDB) and soleus fibres loaded with the fast Ca2+ dye Magfluo-4 AM, and adhered to Laminin, to test whether repetitive stimulation induces progressive changes in the kinetics of Ca2+ release and reuptake in a fibre-type-dependent fashion. We applied a protocol of tetani of 350 ms, 100 Hz, every 4 s to reach a mean amplitude reduction of 25% of the first peak. Morphology type I (MT-I) and morphology type II (MT-II) fibres underwent a total of 96 and 52.8 tetani (P < 0.01 between groups), respectively. The MT-II fibres (n = 18) showed significant reductions of the amplitude (19%), an increase in rise time (8.5%) and a further reduction of the amplitude/rise time ratio (25.5%) of the first peak of the tetanic transient after 40 tetani, while MT-I fibres (n = 5) did not show any of these changes. However, both fibre types showed significant reductions in the maximum rate of rise of the first peak after 40 tetani. Two subpopulations among the MT-II fibres could be distinguished according to Ca2+ reuptake changes. Fast-fatigable MT-II fibres (fMT-II) showed an increase of 32.2% in the half-width value of the first peak, while for fatigue-resistant MT-II fibres (rMT-II), the increase amounted to 6.9%, both after 40 tetani. Significant and non-significant increases of 36.4% and 11.9% in the first time constant of decay (t1) values were seen after 40 tetani in fMT-II and rMT-II fibres, respectively. MT-I fibres did not show kinetic changes in any of the Ca2+ reuptake variables. All changes were reversed after an average recovery of 7.5 and 15.4 min for MT-I and MT-II fibres, respectively. Further experiments ruled out the possibility that the differences in the kinetic changes of the first peak of the Ca2+ transients between fibres MT-I and MT-II could be related to the inactivation of Ca2+ release mechanism. In conclusion, we established a model of enzymatically dissociated fibres, loaded with Magfluo-4 and

  1. The use of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) to relieve pain.

    PubMed

    Lefaucheur, Jean-Pascal; Antal, Andrea; Ahdab, Rechdi; Ciampi de Andrade, Daniel; Fregni, Felipe; Khedr, Eman M; Nitsche, Michael; Paulus, Walter

    2008-10-01

    Chronic pain resulting from injury of the peripheral or central nervous system may be associated with a significant dysfunction of extensive neural networks. Noninvasive stimulation techniques, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) may be suitable to treat chronic pain as they can act on these networks by modulating neural activities not only in the stimulated area, but also in remote regions that are interconnected to the site of stimulation. Motor cortex was the first cortical target that was proved to be efficacious in chronic pain treatment. At present, significant analgesic effects were also shown to occur after the stimulation of other cortical targets (including prefrontal and parietal areas) in acute provoked pain, chronic neuropathic pain, fibromyalgia, or visceral pain. Therapeutic applications of rTMS in pain syndromes are limited by the short duration of the induced effects, but prolonged pain relief can be obtained by repeating rTMS sessions every day for several weeks. Recent tDCS studies also showed some effects on various types of chronic pain. We review the evidence to date of these two techniques of noninvasive brain stimulation for the treatment of pain.

  2. Effects of different frequencies of repetitive transcranial magnetic stimulation on the recovery of upper limb motor dysfunction in patients with subacute cerebral infarction.

    PubMed

    Li, Jiang; Meng, Xiang-Min; Li, Ru-Yi; Zhang, Ru; Zhang, Zheng; Du, Yi-Feng

    2016-10-01

    Studies have confirmed that low-frequency repetitive transcranial magnetic stimulation can decrease the activity of cortical neurons, and high-frequency repetitive transcranial magnetic stimulation can increase the excitability of cortical neurons. However, there are few studies concerning the use of different frequencies of repetitive transcranial magnetic stimulation on the recovery of upper-limb motor function after cerebral infarction. We hypothesized that different frequencies of repetitive transcranial magnetic stimulation in patients with cerebral infarction would produce different effects on the recovery of upper-limb motor function. This study enrolled 127 patients with upper-limb dysfunction during the subacute phase of cerebral infarction. These patients were randomly assigned to three groups. The low-frequency group comprised 42 patients who were treated with 1 Hz repetitive transcranial magnetic stimulation on the contralateral hemisphere primary motor cortex (M1). The high-frequency group comprised 43 patients who were treated with 10 Hz repetitive transcranial magnetic stimulation on ipsilateral M1. Finally, the sham group comprised 42 patients who were treated with 10 Hz of false stimulation on ipsilateral M1. A total of 135 seconds of stimulation was applied in the sham group and high-frequency group. At 2 weeks after treatment, cortical latency of motor-evoked potentials and central motor conduction time were significantly lower compared with before treatment. Moreover, motor function scores were significantly improved. The above indices for the low- and high-frequency groups were significantly different compared with the sham group. However, there was no significant difference between the low- and high-frequency groups. The results show that low- and high-frequency repetitive transcranial magnetic stimulation can similarly improve upper-limb motor function in patients with cerebral infarction.

  3. Effects of different frequencies of repetitive transcranial magnetic stimulation on the recovery of upper limb motor dysfunction in patients with subacute cerebral infarction

    PubMed Central

    Li, Jiang; Meng, Xiang-min; Li, Ru-yi; Zhang, Ru; Zhang, Zheng; Du, Yi-feng

    2016-01-01

    Studies have confirmed that low-frequency repetitive transcranial magnetic stimulation can decrease the activity of cortical neurons, and high-frequency repetitive transcranial magnetic stimulation can increase the excitability of cortical neurons. However, there are few studies concerning the use of different frequencies of repetitive transcranial magnetic stimulation on the recovery of upper-limb motor function after cerebral infarction. We hypothesized that different frequencies of repetitive transcranial magnetic stimulation in patients with cerebral infarction would produce different effects on the recovery of upper-limb motor function. This study enrolled 127 patients with upper-limb dysfunction during the subacute phase of cerebral infarction. These patients were randomly assigned to three groups. The low-frequency group comprised 42 patients who were treated with 1 Hz repetitive transcranial magnetic stimulation on the contralateral hemisphere primary motor cortex (M1). The high-frequency group comprised 43 patients who were treated with 10 Hz repetitive transcranial magnetic stimulation on ipsilateral M1. Finally, the sham group comprised 42 patients who were treated with 10 Hz of false stimulation on ipsilateral M1. A total of 135 seconds of stimulation was applied in the sham group and high-frequency group. At 2 weeks after treatment, cortical latency of motor-evoked potentials and central motor conduction time were significantly lower compared with before treatment. Moreover, motor function scores were significantly improved. The above indices for the low- and high-frequency groups were significantly different compared with the sham group. However, there was no significant difference between the low- and high-frequency groups. The results show that low- and high-frequency repetitive transcranial magnetic stimulation can similarly improve upper-limb motor function in patients with cerebral infarction. PMID:27904488

  4. A comparison of stapedial reflex fatigue with repetitive stimulation and single-fiber EMG in myasthenia gravis.

    PubMed

    Kramer, L D; Ruth, R A; Johns, M E; Sanders, D B

    1981-06-01

    The pattern of stapedial reflex fatigue in response to pulsed acoustic stimulation was measured and compared to results of repetitive nerve stimulation and single-fiber electromyography (EMG) in 89 patients with myasthenia gravis. Studies were also made on 22 patients with other neuromuscular disorders and 40 control subjects with no evidence of neuromuscular impairment. Stapedial reflex fatigue exceeded normal control values in 84% of the patients with myasthenia gravis. Repetitive stimulation and single-fiber EMG measurements were abnormal in 56% and 91% of this same population, respectively. Stapedial reflex abnormalities were most prevalent in patients with mild forms of myasthenia (predominantly ocular or oropharyngeal weakness). Of 22 nonmyasthenic patients with neuromuscular disease tested, 6 had abnormal stapedial reflex fatigue according to our normal values, indicating that this form of testing also detects other diseases of the motor unit. The measurement of stapedial reflex fatigue is painless, is easy to perform, and requires minimal patient cooperation. Due to the relatively high occurrence of abnormal stapedial reflex fatigue in patients with myasthenia gravis, this procedure appears to have considerable potential value in screening and monitoring patients for the presence of defects in neuromuscular transmission.

  5. Low and High Frequency Repetitive Transcranial Magnetic Stimulation for the Treatment of Spasticity

    ERIC Educational Resources Information Center

    Valle, Angela C.; Dionisio, Karen; Pitskel, Naomi Bass; Pascual-Leone, Alvaro; Orsati, Fernanda; Ferreira, Merari J. L.; Boggio, Paulo S.; Lima, Moises C.; Rigonatti, Sergio P.; Fregni, Felipe

    2007-01-01

    The development of non-invasive techniques of cortical stimulation, such as transcranial magnetic stimulation (TMS), has opened new potential avenues for the treatment of neuropsychiatric diseases. We hypothesized that an increase in the activity in the motor cortex by cortical stimulation would increase its inhibitory influence on spinal…

  6. Modulation of N400 in chronic non-fluent aphasia using low frequency Repetitive Transcranial Magnetic Stimulation (rTMS).

    PubMed

    Barwood, Caroline H S; Murdoch, Bruce E; Whelan, Brooke-Mai; Lloyd, David; Riek, Stephan; O'Sullivan, John D; Coulthard, Alan; Wong, Andrew

    2011-03-01

    Low frequency Repetitive Transcranial Magnetic Stimulation (rTMS) has previously been applied to language homologues in non-fluent populations of persons with aphasia yielding significant improvements in behavioral language function up to 43 months post stimulation. The present study aimed to investigate the electrophysiological correlates associated with the application of rTMS through measurement of the semantic based N400 Event-related brain potentials (ERP) component. Low frequency (1 Hz) rTMS was applied to the anterior portion of the homologue to Broca's area (pars triangularis), for 20 min per day for 10 days, using a stereotactic neuronavigational system. Twelve non-fluent persons with aphasia, 2-6 years post stroke were stimulated. Six participants were randomly assigned to receive real stimulation and six participants were randomly assigned to receive a blind sham control condition. ERP measures were recorded at baseline, 1 week and 2 months subsequent to stimulation. The findings demonstrate treatment related changes observed in the stimulation group when compared to the placebo control group at 2 months post stimulation indicating neuromodulation of N400 as a result of rTMS. No treatment related changes were identified in the stimulation group, when compared to the sham group from baseline to 1 week post stimulation. The electrophysiological results represent the capacity of rTMS to modulate neural language networks and measures of lexical-semantic function in participants with non-fluent aphasia and suggest that time may be an important factor in brain reorganization subsequent to rTMS.

  7. Ultrafast high-repetition imaging of fuel sprays using picosecond fiber laser.

    PubMed

    Purwar, Harsh; Wang, Hongjie; Tang, Mincheng; Idlahcen, Saïd; Rozé, Claude; Blaisot, Jean-Bernard; Godin, Thomas; Hideur, Ammar

    2015-12-28

    Modern diesel injectors operate at very high injection pressures of about 2000 bar resulting in injection velocities as high as 700 m/s near the nozzle outlet. In order to better predict the behavior of the atomization process at such high pressures, high-resolution spray images at high repetition rates must be recorded. However, due to extremely high velocity in the near-nozzle region, high-speed cameras fail to avoid blurring of the structures in the spray images due to their exposure time. Ultrafast imaging featuring ultra-short laser pulses to freeze the motion of the spray appears as an well suited solution to overcome this limitation. However, most commercial high-energy ultrafast sources are limited to a few kHz repetition rates. In the present work, we report the development of a custom-designed picosecond fiber laser generating ∼ 20 ps pulses with an average power of 2.5 W at a repetition rate of 8.2 MHz, suitable for high-speed imaging of high-pressure fuel jets. This fiber source has been proof tested by obtaining backlight images of diesel sprays issued from a single-orifice injector at an injection pressure of 300 bar. We observed a consequent improvement in terms of image resolution compared to standard white-light illumination. In addition, the compactness and stability against perturbations of our fiber laser system makes it particularly suitable for harsh experimental conditions.

  8. Effects of low- and high-frequency repetitive magnetic stimulation on neuronal cell proliferation and growth factor expression: A preliminary report.

    PubMed

    Lee, Ji Yong; Park, Hyung Joong; Kim, Ji Hyun; Cho, Byung Pil; Cho, Sung-Rae; Kim, Sung Hoon

    2015-09-14

    Repetitive magnetic stimulation is a neuropsychiatric and neurorehabilitation tool that can be used to investigate the neurobiology of sensory and motor functions. Few studies have examined the effects of repetitive magnetic stimulation on the modulation of neurotrophic/growth factors and neuronal cells in vitro. Therefore, the current study examined the differential effects of repetitive magnetic stimulation on neuronal cell proliferation as well as various growth factor expression. Immortalized mouse neuroblastoma cells were used as the cell model in this study. Dishes of cultured cells were randomly divided into control, sham, low-frequency (0.5Hz, 1Tesla) and high-frequency (10Hz, 1Tesla) groups (n=4 dishes/group) and were stimulated for 3 days. Expression of neurotrophic/growth factors, Akt and Erk was investigated by Western blotting analysis 3 days after repetitive magnetic stimulation. Neuroblastoma cell proliferation was determined with a cell counting assay. There were differences in cell proliferation based on stimulus frequency. Low-frequency stimulation did not alter proliferation relative to the control, while high-frequency stimulation elevated proliferation relative to the control group. The expression levels of brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), neurotrophin-3 (NT-3) and platelet-derived growth factor (PDGF) were elevated in the high-frequency magnetic stimulation group. Akt and Erk expression was also significantly elevated in the high-frequency stimulation group, while low-frequency stimulation decreased the expression of Akt and Erk compared to the control. In conclusion, we determined that different frequency magnetic stimulation had an influence on neuronal cell proliferation via regulation of Akt and ERK signaling pathways and the expression of growth factors such as BDNF, GDNF, NT-3 and PDGF. These findings represent a promising opportunity to gain insight into how different

  9. Chemiluminometric Immuno-Analysis of Innate Immune Response against Repetitive Bacterial Stimulations for the Same Mammalian Cells

    PubMed Central

    Jeon, Jin-Woo; Cho, Il-Hoon; Ha, Un-Hwan; Seo, Sung-Kyu; Paek, Se-Hwan

    2014-01-01

    For monitoring of human cellular response to repetitive bacterial stimulations (e.g., Pseudomonas aeruginosa in a lysate form), we devised a chemiluminescent immuno-analytical system for toll-like receptor 1 (TLR1) as marker present on cell surfaces (e.g., A549). Upon stimulation, TLR1 recognizes pathogen-associated molecular patterns of the infectious agent and are then up-regulated via activation of the nuclear factor-κB (NF-κB) pathway. In this study, the receptor density was quantified by employing an antibody specific to the target receptor and by producing a chemiluminometric signal from an enzyme labeled to the binder. The activated status was then switched back to normal down-regulated stage, by changing the culture medium to one containing animal serum. The major factors affecting activation were the stimulation dose of the bacterial lysate, stimulation timing during starvation, and up- and down-regulation time intervals. Reiterative TLR regulation switching up to three times was not affected by either antibody remained after immunoassay or enzyme substrate (e.g., hydrogen peroxide) in solution. This immuno-analysis for TLRs could be unique to acquire accumulated response of the human cells to repeated stimulations and, therefore, can eventually apply to persistency testing of the cellular regulation in screening of anti-inflammatory substances. PMID:25109895

  10. High-Frequency Repetitive Sensory Stimulation as Intervention to Improve Sensory Loss in Patients with Complex Regional Pain Syndrome I.

    PubMed

    David, Marianne; Dinse, Hubert R; Mainka, Tina; Tegenthoff, Martin; Maier, Christoph

    2015-01-01

    Achieving perceptual gains in healthy individuals or facilitating rehabilitation in patients is generally considered to require intense training to engage neuronal plasticity mechanisms. Recent work, however, suggested that beneficial outcome similar to training can be effectively acquired by a complementary approach in which the learning occurs in response to mere exposure to repetitive sensory stimulation (rSS). For example, high-frequency repetitive sensory stimulation (HF-rSS) enhances tactile performance and induces cortical reorganization in healthy subjects and patients after stroke. Patients with complex regional pain syndrome (CRPS) show impaired tactile performance associated with shrinkage of cortical maps. We here investigated the feasibility and efficacy of HF-rSS, and low-frequency rSS (LF-rSS) to enhance tactile performance and reduce pain intensity in 20 patients with CRPS type I. Intermittent high- or low-frequency electrical stimuli were applied for 45 min/day to all fingertips of the affected hand for 5 days. Main outcome measures were spatial two-point-discrimination thresholds and mechanical detection thresholds measured on the tip of the index finger bilaterally. Secondary endpoint was current pain intensity. All measures were assessed before and on day 5 after the last stimulation session. HF-rSS applied in 16 patients improved tactile discrimination on the affected hand significantly without changes contralaterally. Current pain intensity remained unchanged on average, but decreased in four patients by ≥30%. This limited pain relief might be due to the short stimulation period of 5 days only. In contrast, after LF-rSS, tactile discrimination was impaired in all four patients, while detection thresholds and pain were not affected. Our data suggest that HF-rSS could be used as a novel approach in CRPS treatment to improve sensory loss. Longer treatment periods might be required to induce consistent pain relief.

  11. Repetitive Transcranial Magnetic Stimulation (rTMS) to Treat Social Anxiety Disorder: Case Reports and a Review of the Literature

    PubMed Central

    Paes, Flávia; Baczynski, Tathiana; Novaes, Felipe; Marinho, Tamires; Arias-Carrión, Oscar; Budde, Henning; Sack, Alexander T.; Huston, Joseph P.; Almada, Leonardo Ferreira; Carta, Mauro; Silva, Adriana Cardoso; Nardi, Antonio E.; Machado, Sergio

    2013-01-01

    Objectives: Social anxiety disorder (SAD) is a common and debilitating anxiety disorders. However, few studies had been dedicated to the neurobiology underlying SAD until the last decade. Rates of non-responders to standard methods of treatment remain unsatisfactorily high of approximately 25%, including SAD. Advances in our understanding of SAD could lead to new treatment strategies. A potential non invasive therapeutic option is repetitive transcranial magnetic stimulation (rTMS). Thus, we reported two cases of SAD treated with rTMS Methods: The bibliographical search used Pubmed/Medline, ISI Web of Knowledge and Scielo databases. The terms chosen for the search were: anxiety disorders, neuroimaging, repetitive transcranial magnetic stimulation. Results: In most of the studies conducted on anxiety disorders, except SAD, the right prefrontal cortex (PFC), more specifically dorsolateral PFC was stimulated, with marked results when applying high-rTMS compared with studies stimulating the opposite side. However, according to the “valence hypothesis”, anxiety disorders might be characterized by an interhemispheric imbalance associated with increased right-hemispheric activity. With regard to the two cases treated with rTMS, we found a decrease in BDI, BAI and LSAS scores from baseline to follow-up. Conclusion: We hypothesize that the application of low-rTMS over the right medial PFC (mPFC; the main structure involved in SAD circuitry) combined with high-rTMS over the left mPFC, for at least 4 weeks on consecutive weekdays, may induce a balance in brain activity, opening an attractive therapeutic option for the treatment of SAD. PMID:24278088

  12. High-Frequency Repetitive Sensory Stimulation as Intervention to Improve Sensory Loss in Patients with Complex Regional Pain Syndrome I

    PubMed Central

    David, Marianne; Dinse, Hubert R.; Mainka, Tina; Tegenthoff, Martin; Maier, Christoph

    2015-01-01

    Achieving perceptual gains in healthy individuals or facilitating rehabilitation in patients is generally considered to require intense training to engage neuronal plasticity mechanisms. Recent work, however, suggested that beneficial outcome similar to training can be effectively acquired by a complementary approach in which the learning occurs in response to mere exposure to repetitive sensory stimulation (rSS). For example, high-frequency repetitive sensory stimulation (HF-rSS) enhances tactile performance and induces cortical reorganization in healthy subjects and patients after stroke. Patients with complex regional pain syndrome (CRPS) show impaired tactile performance associated with shrinkage of cortical maps. We here investigated the feasibility and efficacy of HF-rSS, and low-frequency rSS (LF-rSS) to enhance tactile performance and reduce pain intensity in 20 patients with CRPS type I. Intermittent high- or low-frequency electrical stimuli were applied for 45 min/day to all fingertips of the affected hand for 5 days. Main outcome measures were spatial two-point-discrimination thresholds and mechanical detection thresholds measured on the tip of the index finger bilaterally. Secondary endpoint was current pain intensity. All measures were assessed before and on day 5 after the last stimulation session. HF-rSS applied in 16 patients improved tactile discrimination on the affected hand significantly without changes contralaterally. Current pain intensity remained unchanged on average, but decreased in four patients by ≥30%. This limited pain relief might be due to the short stimulation period of 5 days only. In contrast, after LF-rSS, tactile discrimination was impaired in all four patients, while detection thresholds and pain were not affected. Our data suggest that HF-rSS could be used as a novel approach in CRPS treatment to improve sensory loss. Longer treatment periods might be required to induce consistent pain relief. PMID:26635719

  13. The Effect of High-Frequency Repetitive Transcranial Magnetic Stimulation on Occupational Stress among Health Care Workers: A Pilot Study

    PubMed Central

    Kim, Young In; Kim, Hyungjin; Han, Doug Hyun

    2016-01-01

    Objective Repetitive transcranial magnetic stimulation (rTMS) was approved by the Food and Drug Administration to alleviate symptoms of treatment-resistant depression. This study aimed to evaluate the effectiveness of rTMS treatment on alleviating occupational stress by evaluating clinical symptoms and quantitative electroencephalography (QEEG). Methods Twenty-four health care workers were randomized to receive 12 sessions of active or sham rTMS delivered to the left dorsolateral prefrontal cortex (DLPFC). Each session consisted of 32 trains of 10 Hz repetitive TMS delivered in 5-second trains at 110% of the estimated prefrontal cortex threshold. Before and after the intervention, the Korean version of the occupational stress inventory (K-OSI), Beck's depression inventory (BDI), and Beck's anxiety inventory (BAI) were administered and EEG was performed using a 21-channel digital EEG system. Results After TMS, the average scores for the affective responses to stressors on the personal strain questionnaire (PSQ) subscale of K-OSI and BDI decreased significantly for the active-TMS group compared to the sham-TMS group. Also, the active-TMS group showed a significantly greater decrease in relative alpha in the F3 electrode and a significantly greater increase in the F4 electrode. Conclusion High-frequency rTMS on the left DLPFC had stress-relieving and mood-elevating effects in health care workers, likely by stimulating the left frontal lobe. PMID:27909453

  14. Within-session sensitization and between-session habituation: a robust physiological response to repetitive painful heat stimulation.

    PubMed

    May, A; Rodriguez-Raecke, R; Schulte, A; Ihle, K; Breimhorst, M; Birklein, F; Jürgens, T P

    2012-03-01

    Habituation and sensitization are important behavioural responses to repeated exposure of painful stimuli. Whereas within-session response dynamics to nociceptive stimuli is well characterized, little is known about long-term behaviour due to repetitive nociceptive stimulation. We used a standardized longitudinal heat pain paradigm in 66 healthy participants, 21 patients with chronic low back pain and 22 patients with depression who received daily sessions of 60 suprathreshold heat stimuli (48 °C each) for eight consecutive days. All three groups showed the same response: Repeated painful stimulation over several days resulted in substantially decreased pain ratings to identical painful stimuli. The decreased perception of pain over time was associated with a very robust increase in pain ratings in each single pain session, i.e., all participants sensitized within sessions and habituated between sessions. This uniform pattern was equally present in all examined groups. Chronic pain and depression do not seem to interfere with short-term sensitization and long-term habituation in this model of repetitive phasic heat pain.

  15. Ventrolateral prefrontal cortex repetitive transcranial magnetic stimulation in the treatment of depersonalization disorder: A consecutive case series.

    PubMed

    Jay, Emma-Louise; Nestler, Steffen; Sierra, Mauricio; McClelland, Jessica; Kekic, Maria; David, Anthony S

    2016-06-30

    Case reports and an open trial have reported promising responses to repetitive transcranial magnetic stimulation (rTMS) to prefrontal and temporo-parietal sites in patients with depersonalization disorder (DPD). We recently showed that a single session of rTMS to the ventrolateral prefrontal cortex (VLPFC) was associated with a reduction in symptoms and increase in physiological arousal. Seven patients with medication-resistant DSM-IV DPD received up to 20 sessions of right-sided rTMS to the VLPFC for 10 weeks. Stimulation was guided using neuronavigation software based on participants' individual structural MRIs, and delivered at 110% of resting motor threshold. A session consisted of 1Hz repetitive TMS for 15min. The primary outcome measure was reduction in depersonalization symptoms on the Cambridge Depersonalization Scale (CDS). Secondary outcomes included scores on the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). 20 sessions of rTMS treatment to right VLPFC significantly reduced scores on the CDS by on average 44% (range 2-83.5%). Two patients could be classified as "full responders", four as "partial" and one a non-responder. Response usually occurred within the first 6 sessions. There were no significant adverse events. A randomized controlled clinical trial of VLPFC rTMS for DPD is warranted.

  16. Preliminary Evidence of the Effects of High-frequency Repetitive Transcranial Magnetic Stimulation (rTMS) on Swallowing Functions in Post-Stroke Individuals with Chronic Dysphagia

    ERIC Educational Resources Information Center

    Cheng, Ivy K. Y.; Chan, Karen M. K.; Wong, C. S.; Cheung, Raymond T. F.

    2015-01-01

    Background: There is growing evidence of potential benefits of repetitive transcranial magnetic stimulation (rTMS) in the rehabilitation of dysphagia. However, the site and frequency of stimulation for optimal effects are not clear. Aims: The aim of this pilot study is to investigate the short-term effects of high-frequency 5 Hz rTMS applied to…

  17. A comparison of the effects of repetitive transcranial magnetic stimulation (rTMS) by number of stimulation sessions on hemispatial neglect in chronic stroke patients.

    PubMed

    Kim, Yong Kyun; Jung, Jae Hwan; Shin, Sung Hun

    2015-01-01

    We investigated the effect of repetitive transcranial magnetic stimulation (rTMS) applied either during one session of stimulation, or by ten sessions of low-frequency stimulation over the left parietal cortex, on hemispatial neglect in stroke patients. We enrolled 34 subjects that had experienced a stroke. All subjects received 1,200 real rTMS over the left parietal cortex at an intensity of 90% of motor thresholds with 1 Hz. Subjects were divided into two groups. One group of subjects (n = 19) received real rTMS over the left parietal cortex in a single session of stimulation, and the other group (n = 15), underwent a total of ten sessions of daily stimulations for 2 weeks. Letter cancelation test, line bisection test, and Ota's task were administered to compare the effects of different rTMS protocols, before and after rTMS. The results showed no difference in baseline value between the single session group and the ten sessions group. Total ten sessions of low-frequency rTMS over the left parietal cortex, compared with the single session of rTMS, significantly improved hemispatial neglect in letter cancelation, line bisection, and Ota's task (P < 0.01). Finally, a total of ten sessions of low-frequency rTMS can be used in treatment by rTMS for patients suffering from hemispatial neglect after stroke.

  18. Utilizing repetitive transcranial magnetic stimulation to improve language function in stroke patients with chronic non-fluent aphasia.

    PubMed

    Garcia, Gabriella; Norise, Catherine; Faseyitan, Olufunsho; Naeser, Margaret A; Hamilton, Roy H

    2013-07-02

    Transcranial magnetic stimulation (TMS) has been shown to significantly improve language function in patients with non-fluent aphasia(1). In this experiment, we demonstrate the administration of low-frequency repetitive TMS (rTMS) to an optimal stimulation site in the right hemisphere in patients with chronic non-fluent aphasia. A battery of standardized language measures is administered in order to assess baseline performance. Patients are subsequently randomized to either receive real rTMS or initial sham stimulation. Patients in the real stimulation undergo a site-finding phase, comprised of a series of six rTMS sessions administered over five days; stimulation is delivered to a different site in the right frontal lobe during each of these sessions. Each site-finding session consists of 600 pulses of 1 Hz rTMS, preceded and followed by a picture-naming task. By comparing the degree of transient change in naming ability elicited by stimulation of candidate sites, we are able to locate the area of optimal response for each individual patient. We then administer rTMS to this site during the treatment phase. During treatment, patients undergo a total of ten days of stimulation over the span of two weeks; each session is comprised of 20 min of 1 Hz rTMS delivered at 90% resting motor threshold. Stimulation is paired with an fMRI-naming task on the first and last days of treatment. After the treatment phase is complete, the language battery obtained at baseline is repeated two and six months following stimulation in order to identify rTMS-induced changes in performance. The fMRI-naming task is also repeated two and six months following treatment. Patients who are randomized to the sham arm of the study undergo sham site-finding, sham treatment, fMRI-naming studies, and repeat language testing two months after completing sham treatment. Sham patients then cross over into the real stimulation arm, completing real site-finding, real treatment, fMRI, and two- and six

  19. Blood flow and oxygenation changes due to low-frequency repetitive transcranial magnetic stimulation of the cerebral cortex

    NASA Astrophysics Data System (ADS)

    Mesquita, Rickson C.; Faseyitan, Olufunsho K.; Turkeltaub, Peter E.; Buckley, Erin M.; Thomas, Amy; Kim, Meeri N.; Durduran, Turgut; Greenberg, Joel H.; Detre, John A.; Yodh, Arjun G.; Hamilton, Roy H.

    2013-06-01

    Transcranial magnetic stimulation (TMS) modulates processing in the human brain and is therefore of interest as a treatment modality for neurologic conditions. During TMS administration, an electric current passing through a coil on the scalp creates a rapidly varying magnetic field that induces currents in the cerebral cortex. The effects of low-frequency (1 Hz), repetitive TMS (rTMS) on motor cortex cerebral blood flow (CBF) and tissue oxygenation in seven healthy adults, during/after 20 min stimulation, is reported. Noninvasive optical methods are employed: diffuse correlation spectroscopy (DCS) for blood flow and diffuse optical spectroscopy (DOS) for hemoglobin concentrations. A significant increase in median CBF (33%) on the side ipsilateral to stimulation was observed during rTMS and persisted after discontinuation. The measured hemodynamic parameter variations enabled computation of relative changes in cerebral metabolic rate of oxygen consumption during rTMS, which increased significantly (28%) in the stimulated hemisphere. By contrast, hemodynamic changes from baseline were not observed contralateral to rTMS administration (all parameters, p>0.29). In total, these findings provide new information about hemodynamic/metabolic responses to low-frequency rTMS and, importantly, demonstrate the feasibility of DCS/DOS for noninvasive monitoring of TMS-induced physiologic effects.

  20. Inhibitory repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex modulates early affective processing.

    PubMed

    Zwanzger, Peter; Steinberg, Christian; Rehbein, Maimu Alissa; Bröckelmann, Ann-Kathrin; Dobel, Christian; Zavorotnyy, Maxim; Domschke, Katharina; Junghöfer, Markus

    2014-11-01

    The dorsolateral prefrontal cortex (dlPFC) has often been suggested as a key modulator of emotional stimulus appraisal and regulation. Therefore, in clinical trials, it is one of the most frequently targeted regions for non-invasive brain stimulation such as repetitive transcranial magnetic stimulation (rTMS). In spite of various encouraging reports that demonstrate beneficial effects of rTMS in anxiety disorders, psychophysiological studies exploring the underlying neural mechanisms are sparse. Here we investigated how inhibitory rTMS influences early affective processing when applied over the right dlPFC. Before and after rTMS or sham stimulation, subjects viewed faces with fearful or neutral expressions while whole-head magnetoencephalography (MEG) was recorded. Due to the disrupted functioning of the right dlPFC, visual processing in bilateral parietal, temporal, and occipital areas was amplified starting at around 90 ms after stimulus onset. Moreover, increased fear-specific activation was found in the right TPJ area in a time-interval between 110 and 170 ms. These neurophysiological effects were reflected in slowed reaction times for fearful, but not for neutral faces in a facial expression identification task while there was no such effect on a gender discrimination control task. Our study confirms the specific and important role of the dlPFC in regulation of early emotional attention and encourages future clinical research to use minimal invasive methods such as transcranial magnetic (TMS) or direct current stimulation (tDCS).

  1. Neural correlates associated with symptom provocation in pediatric obsessive compulsive disorder after a single session of sham-controlled repetitive transcranial magnetic stimulation.

    PubMed

    Pedapati, Ernest; DiFrancesco, Mark; Wu, Steve; Giovanetti, Cathy; Nash, Tiffany; Mantovani, Antonio; Ammerman, Robert; Harris, Elana

    2015-09-30

    Treatments for pediatric obsessive-compulsive disorder (OCD) could be enhanced if the physiological changes engendered by treatment were known. This study examined neural correlates of a provocation task in youth with OCD, before and after sham-controlled repetitive transcranial magnetic stimulation (rTMS). We hypothesized that rTMS to the right dorsolateral prefrontal cortex would inhibit activity in cortico-striato-thalamic (CST) circuits associated with OCD to a greater extent than sham rTMS. After baseline (Time 1) functional magnetic resonance imaging (fMRI) during a provocation task, subjects received one session of either fMRI-guided sham (SG; n=8) or active (AG; n=10) 1-Hz rTMS over the rDLPFC for 30min. During rTMS, subjects were presented with personalized images that evoked OCD-related anxiety. Following stimulation, fMRI and the provocation task were repeated (Time 2). Contrary to our prediction for the provocation task, the AG was associated with no changes in BOLD response from Times 1 to 2. In contrast, the SG had a significant increase at Time 2 in BOLD response in the right inferior frontal gyrus and right putamen, which persisted after adjusting for age, gender, and time to scanner as covariates. This study provides an initial framework for TMS interrogation of the CST circuit in pediatric OCD.

  2. Transcranial direct current stimulation (tDCS) priming of 1Hz repetitive transcranial magnetic stimulation (rTMS) modulates experimental pain thresholds.

    PubMed

    Moloney, Tonya M; Witney, Alice G

    2013-02-08

    Transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) of primary motor cortex (M1) modulate cortical excitability. Both techniques have been demonstrated to modulate chronic pain and experimental pain thresholds, but with inconsistent effects. Preconditioning M1 with weak tDCS (1mA) standardizes the effects of subsequent stimulation via rTMS on levels of cortical excitability. Here we examine whether 1Hz rTMS, primed with tDCS, could effectively standardize the modulation of pain thresholds. Thermal pain thresholds were determined using quantitative sensory testing (QST) of the palmar thenar of both hands in 12 healthy males pre and post tDCS - 1Hz rTMS over the hand area of the left M1. Cathodal tDCS preconditioning of 1Hz rTMS successfully reversed the normal suppressive effect of low frequency rTMS and effectively modulated cold and heat pain thresholds. Conversely, anodal tDCS - 1Hz rTMS led to a decrease in cold pain thresholds. Therefore, this study supports that preconditioning M1 using cathodal tDCS before subsequent stimulation via 1Hz rTMS facilitates the production of analgesia.

  3. Stimulated Raman scattering microscopy for biomedical imaging

    NASA Astrophysics Data System (ADS)

    Min, Wei; Freudiger, Christian W.; Lu, Sijia; He, Chengwei; Kang, Jing X.; Xie, X. Sunney

    2009-02-01

    Label-free chemical contrast is highly desirable in biomedical imaging. Spontaneous Raman microscopy provides specific vibrational signatures of chemical bonds, but is often hindered by low sensitivity. Here we report a 3D multi-photon vibrational imaging technique based on stimulated Raman scattering (SRS). The sensitivity of SRS is significantly greater than that of spontaneous Raman scattering, and is further enhanced by high-frequency (MHz) phase-sensitive detection. SRS microscopy has a major advantage over previous coherent Raman techniques in that it offers background-free and easily interpretable chemical contrast. We show a variety of biomedical applications, such as differentiating distributions of omega-3 fatty acids and saturated lipids in living cells, imaging of brain and skin tissues based on intrinsic lipid contrast.

  4. Effects of shifts in the rate of repetitive stimulation on sustained attention

    NASA Technical Reports Server (NTRS)

    Krulewitz, J. E.; Warm, J. S.; Wohl, T. H.

    1975-01-01

    The effects of shifts in the rate of presentation of repetitive neutral events (background event rate) were studied in a visual vigilance task. Four groups of subjects experienced either a high (21 events/min) or a low (6 events/min) event rate for 20 min and then experienced either the same or the alternate event rate for an additional 40 min. The temporal occurrence of critical target signals was identical for all groups, irrespective of event rate. The density of critical signals was 12 signals/20 min. By the end of the session, shifts in event rate were associated with changes in performance which resembled contrast effects found in other experimental situations in which shift paradigms were used. Relative to constant event rate control conditions, a shift from a low to a high event rate depressed the probability of signal detections, while a shift in the opposite direction enhanced the probability of signal detections.

  5. Repetition suppression in transcranial magnetic stimulation-induced motor-evoked potentials is modulated by cortical inhibition.

    PubMed

    Kallioniemi, E; Pääkkönen, A; Julkunen, P

    2015-12-03

    Transcranial magnetic stimulation (TMS) can be applied to modulate cortical phenomena. The modulation effect is dependent on the applied stimulation frequency. Repetition suppression (RS) has been demonstrated in the motor system using TMS with short suprathreshold 1-Hz stimulation trains repeated at long inter-train intervals. RS has been reported to occur in the resting motor-evoked potentials (MEPs) with respect to the first pulse in a train of stimuli. Although this RS in the motor system has been described in previous studies, the neuronal origin of the phenomenon is still poorly understood. The present study evaluated RS in three TMS-induced motor responses; resting and active MEPs as well as corticospinal silent periods (SPs) in order to clarify the mechanism behind TMS-induced RS. We studied 10 healthy right-handed subjects using trains of four stimuli with stimulation intensities of 120% of the resting motor threshold (rMT) and 120% of the silent period threshold for an SP duration of 30 ms (SPT30). Inter-trial interval was 20s, with a 1-s inter-stimulus interval within the trains. We confirmed that RS appears in resting MEPs (p < 0.001), whereas active MEPs did not exhibit RS (p > 0.792). SPs, on the contrary, lengthened (p < 0.001) indicating modulation of cortical inhibition. The effects of the two stimulation intensities exhibited a similar trend; however, the SPT30 evoked a more profound inhibitory effect compared to that achieved by rMT. Moreover, the resting MEP amplitudes and SP durations correlated (rho ⩽ -0.674, p < 0.001) and the pre-TMS EMG level did not differ between stimuli in resting MEPs (F = 0.0, p ⩾ 0.999). These results imply that the attenuation of response size seen in resting MEPs might originate from increasing activity of inhibitory GABAergic interneurons which relay the characteristics of SPs.

  6. Controlled Study of 50 Hz Repetitive Transcranial Magnetic Stimulation for the Treatment of Parkinson’s Disease

    PubMed Central

    Benninger, David H.; Iseki, Kazumi; Kranick, Sarah; Luckenbaugh, David A.; Houdayer, Elise; Hallett, Mark

    2014-01-01

    Objective To investigate the safety and efficacy of 50Hz repetitive Transcranial Magnetic Stimulation(rTMS) in the treatment of motor symptoms in Parkinson’s disease(PD). Background Progression of PD is characterized by the emergence of motor deficits, which eventually respond less to dopaminergic therapy and pose a therapeutic challenge. RTMS has shown promising results in improving gait, a major cause of disability, and may provide a therapeutic alternative. Controlled studies suggest increasing stimulation frequency might enhance therapeutic efficacy. Methods In this randomized, double blind, sham-controlled study, we investigated safety and efficacy of 50Hz-rTMS of the motor cortices in 8sessions over 2weeks. Assessment of safety and clinical efficacy over a 1-month period included timed tests of gait and bradykinesia, UPDRS and additional clinical, neurophysiological and neuropsychological parameters. In addition, safety of 50Hz-rTMS was tested with EMG-EEG-monitoring during and after stimulation. Results We investigated 26 patients with mild to moderate PD: 13 received 50Hz-rTMS and 13 sham-stimulation. 50Hz-rTMS did not improve gait, bradykinesia, global and motor UPDRS, but there appeared a short-lived “on”-state improvement in activities of daily living (UPDRS II). 50Hz-rTMS lengthened the cortical silent period, but other neurophysiology and neuropsychological measures remained unchanged. EMG/EEG recorded no pathological increase of cortical excitability or epileptic activity. There were no adverse effects. Conclusion 50Hz-rTMS of the motor cortices appears safe, but fails to improve motor performance and functional status in PD. Prolonged stimulation or other techniques with rTMS might be more efficacious, but need to be established in future research. PMID:22593114

  7. Unilateral and bilateral MRI-targeted repetitive transcranial magnetic stimulation for treatment-resistant depression: a randomized controlled study

    PubMed Central

    Blumberger, Daniel M.; Maller, Jerome J.; Thomson, Lauren; Mulsant, Benoit H.; Rajji, Tarek K.; Maher, Missy; Brown, Patrick E.; Downar, Jonathan; Vila-Rodriguez, Fidel; Fitzgerald, Paul B.; Daskalakis, Zafiris J.

    2016-01-01

    Background Several factors may mitigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) over sham rTMS in patients with treatment-resistant depression (TRD). These factors include unilateral stimulation (i.e., treatment of only the left dorsolateral prefrontal cortex [DLPFC]), suboptimal methods of targeting the DLPFC and insufficient stimulation intensity (based on coil-to-cortex distance). Methods We recruited patients with TRD between the ages of 18 and 85 years from a university hospital, and participants were randomized to receive sequential bilateral rTMS (600 pulses at 1 Hz followed by 1500 pulses at 10 Hz), unilateral high-frequency left (HFL)-rTMS (2100 pulses at 10 Hz) or sham rTMS for 3 or 6 weeks depending on treatment response. Stimulation was targeted with MRI localization over the junction of the middle and anterior thirds of the middle frontal gyrus, using 120% of the coil-to-cortex adjusted motor threshold. Our primary outcome of interest was the remission rate. Results A total of 121 patients participated in this study. The remission rate was significantly higher in the bilateral group than the sham group. The remission rate in the HFL-rTMS group was intermediate and did not differ statistically from the rate in the 2 other groups. There were no significant differences in reduction of depression scores among the 3 groups. Limitations The number of pulses used per session in the unilateral group was somewhat lower in our trial than in more recent trials, and the sham condition did not involve active stimulation. Conclusion Our findings suggest that sequential bilateral rTMS is superior to sham rTMS; however, adjusting for coil-to-cortex distance did not yield enhanced efficacy rates. PMID:27269205

  8. Effects of high-frequency repetitive transcranial magnetic stimulation of primary motor cortex on laser-evoked potentials in migraine.

    PubMed

    de Tommaso, Marina; Brighina, Filippo; Fierro, Brigida; Francesco, Vito Devito; Santostasi, Roberto; Sciruicchio, Vittorio; Vecchio, Eleonora; Serpino, Claudia; Lamberti, Paolo; Livrea, Paolo

    2010-12-01

    The aim of this study was to examine the effects of high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) of the left primary motor cortex (M1) on subjective pain and evoked responses induced by laser stimulation (LEPs) of the contralateral hand and supraorbital zone in a cohort of migraine patients without aura during the inter-critical phase, and to compare the effects with those of non-migraine healthy controls. Thirteen migraine patients and 12 sex- and age-matched controls were evaluated. Each rTMS session consisted of 1,800 stimuli at a frequency of 5 Hz and 90% motor threshold intensity. Sham (control) rTMS was performed at the same stimulation position. The vertex LEP amplitude was reduced at the trigeminal and hand levels in the sham-placebo condition and after rTMS to a greater extent in the migraine patients than in healthy controls, while the laser pain rating was unaffected. These results suggest that HF rTMS of motor cortex and the sham procedure can both modulate pain-related evoked responses in migraine patients.

  9. Bilateral Repetitive Transcranial Magnetic Stimulation Combined with Intensive Swallowing Rehabilitation for Chronic Stroke Dysphagia: A Case Series Study

    PubMed Central

    Momosaki, Ryo; Abo, Masahiro; Kakuda, Wataru

    2014-01-01

    The purpose of this study was to clarify the safety and feasibility of a 6-day protocol of bilateral repetitive transcranial magnetic stimulation (rTMS) combined with intensive swallowing rehabilitation for chronic poststroke dysphagia. In-hospital treatment was provided to 4 poststroke patients (age at treatment: 56–80 years; interval between onset of stroke and treatment: 24–37 months) with dysphagia. Over 6 consecutive days, each patient received 10 sessions of rTMS at 3 Hz applied to the pharyngeal motor cortex bilaterally, followed by 20 min of intensive swallowing rehabilitation exercise. The swallowing function was evaluated by the Penetration Aspiration Scale (PAS), Modified Mann Assessment of Swallowing Ability (MMASA), Functional Oral Intake Scale (FOIS), laryngeal elevation delay time (LEDT) and Repetitive Saliva-Swallowing Test (RSST) on admission and at discharge. All patients completed the 6-day treatment protocol and none showed any adverse reactions throughout the treatment. The combination treatment improved laryngeal elevation delay time in all patients. Our proposed protocol of rTMS plus swallowing rehabilitation exercise seems to be safe and feasible for chronic stroke dysphagia, although its efficacy needs to be confirmed in a large number of patients. PMID:24803904

  10. Subgenual Cingulate Theta Activity Predicts Treatment Response of Repetitive Transcranial Magnetic Stimulation in Participants With Vascular Depression

    PubMed Central

    Narushima, Kenji; McCormick, Laurie; Yamada, Throu; Thatcher, Robert; Robinson, Robert G.

    2013-01-01

    Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for depression. Increased metabolism in the anterior cingulate cortex (ACC) is a known predictor for antidepressant response. The authors assessed whether increased theta power within the ACC predicts rTMS response in participants with vascular depression. Sixty-five participants were randomized to active or sham rTMS. Outcome was assessed using the Hamilton Depression Rating Scale. Electroencephalography was obtained, and comparisons were made among each group with a normative database using low-resolution electromagnetic tomography. Results suggest that vascular depression participants respond well to rTMS and that increased low-theta power in the subgenual ACC predicts response to rTMS. PMID:20160213

  11. Repetitive Transcranial Magnetic Stimulation (rTMS) Modulates Event-Related Potential (ERP) Indices of Attention in Autism

    PubMed Central

    Casanova, Manuel F.; Baruth, Joshua M.; El-Baz, Ayman; Tasman, Allan; Sears, Lonnie; Sokhadze, Estate

    2014-01-01

    Individuals with autism spectrum disorder (ASD) have previously been shown to have significantly augmented and prolonged event-related potentials (ERP) to irrelevant visual stimuli compared to controls at both early and later stages (e.g., N200, P300) of visual processing and evidence of an overall lack of stimulus discrimination. Abnormally large and indiscriminative cortical responses to sensory stimuli may reflect cortical inhibitory deficits and a disruption in the excitation/inhibition ratio. Low-frequency (≤1HZ) repetitive transcranial magnetic stimulation (rTMS) has been shown to increase inhibition of stimulated cortex by the activation of inhibitory circuits. It was our prediction that after 12 sessions of low-frequency rTMS applied bilaterally to the dorsolateral prefrontal cortices in individuals with ASD there would be a significant improvement in ERP indices of selective attention evoked at later (i.e., 200–600 ms) stages of attentional processing as well as an improvement in motor response error rate. We assessed 25 participants with ASD in a task of selective attention using illusory figures before and after 12 sessions of rTMS in a controlled design where a waiting-list group of 20 children with ASD performed the same task twice. We found a significant improvement in both N200 and P300 components as a result of rTMS as well as a significant reduction in response errors. We also found significant reductions in both repetitive behavior and irritability according to clinical behavioral questionnaires as a result of rTMS. We propose that rTMS has the potential to become an important therapeutic tool in ASD research and treatment. PMID:24683490

  12. Cognitive correlates of repetitive transcranial magnetic stimulation (rTMS) in treatment-resistant depression- a pilot study

    PubMed Central

    2012-01-01

    Background The aim of the current study was to investigate the cognitive correlates of repetitive transcranial magnetic stimulation (rTMS) in 10 treatment-resistant depression patients. Methods Patients received forty 20-min sessions of fast-frequency (10 Hz) rTMS of the left dorsolateral prefrontal cortex (DLPFC) over 20 days. Concept-shift ability (accuracy and duration of performance) was assessed daily with a Modified Concept-Shifting Task (mCST) in patients and in eight healthy volunteers. General cognitive functioning test (Repeatable Battery for the Assessment of Neuropsychological Status; RBANS), Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HAM-D) were applied before the first and after the last rTMS. Results Compared to before rTMS on the first 10 days, the patients performed the mCST significantly more accurately after rTMS on the last 10 days (p < .001, partial eta squared=.78) while the same comparison in healthy volunteers was not statistically significant (p = .256, partial eta squared=.18). A significant improvement in immediate memory on RBANS and reduction in BDI and HAM-D scores were also observed after the last compared to before the first rTMS. Conclusion The rTMS is associated with an improvement in selective cognitive functions that is not explained by practice effects on tasks administered repeatedly. Trial registration Name: "Repetitive Transcranial Magnetic Stimulation (rTMS) in the treatment of depression, assessed with HAM-D over a four week period." URL: www.actr.org.au Registration number: ACTRN012605000145606 PMID:23031294

  13. Low frequency repetitive transcranial magnetic stimulation targeted to PMC followed by M1 modulates excitability differently from PMC or M1 stimulation alone

    PubMed Central

    Chen, Mo; Deng, Huiqiong; Schmidt, Rebekah L.; Kimberley, Teresa J.

    2016-01-01

    Objectives The excitability of primary motor cortex (M1) can be modulated by applying low-frequency repetitive transcranial magnetic stimulation (rTMS) over M1 or premotor cortex (PMC). A comparison of inhibitory effect between the two locations has been reported with inconsistent results. This study compared the response secondary to rTMS applied over M1, PMC and a combined PMC+M1 stimulation approach which first targets stimulation over PMC then M1. Materials and Methods Ten healthy participants were recruited for a randomized, cross-over design with a 1-week wash-out between visits. Each visit consisted of a pre-test, an rTMS intervention and a post-test. Outcome measures included short interval intracortical inhibition (SICI), intracortical facilitation (ICF) and cortical silent period (CSP). Participants received one of the three interventions in random order at each visit including: 1-Hz rTMS at 90% of resting motor threshold to: M1 (1200 pulses), PMC (1200 pulses) and PMC+M1 (600 pulses each, 1200 total). Results PMC+M1 stimulation resulted in significantly greater inhibition than the other locations for ICF (P = 0.005) and CSP (P < 0.001); for SICI, increased inhibition (group effect) was not observed after any of the three interventions and there was no significant difference between the three interventions. Conclusion The results indicate that PMC+M1 stimulation may modulate brain excitability differently from PMC or M1 alone. CSP was the assessment measure most sensitive to changes in inhibition and was able to distinguish between different inhibitory protocols. This work presents a novel procedure that may have positive implications for therapeutic interventions. PMID:26307511

  14. Effects of Low Frequency Prefrontal Repetitive Transcranial Magnetic Stimulation on the N2 Amplitude in a GoNogo Task

    PubMed Central

    Grossheinrich, Nicola; Reinl, Maren; Pogarell, Oliver; Karch, Susanne; Mulert, Christoph; Brueckl, Monika; Hennig-Fast, Kristina; Rau, Anne; Epple, Maria; Hornig, Ariane; Padberg, Frank

    2013-01-01

    During the last decade, repetitive transcranial magnetic stimulation (rTMS) of the prefrontal cortex has become established as a treatment for various mental diseases. The rational of prefrontal stimulation has been adapted from the mode of action known from rTMS using motor-evoked potentials though little is known about the precise effect of rTMS at prefrontal sites. The objective of the current study is to investigate the inhibitory effect of prefrontal 1 Hz rTMS by stimulating the generators of event-related potentials (ERP) which are located in the prefrontal cortex. Thus, 1 Hz rTMS was applied offline over the left dorsolateral prefrontal cortex (DLPFC) and the medial prefrontal cortex (MPFC) in 18 healthy subjects who subsequently underwent a GoNogo task. Both active conditions were compared to sham rTMS within a randomized and counterbalanced cross-over design in one day. ERPs were recorded during task performance and the N2 and the P3 were analysed. After 1 Hz rTMS of the left DLPFC (but not of the MPFC), an inhibitory effect on the N2 amplitude was observed, which was related to inhibitory control. In contrast, after 1 Hz rTMS of the MPFC (but not at the left DLPFC) a trend towards an increased P3 amplitude was found. There was no significant modulation of latencies and behavioural data. The results argue in favour of an inhibitory effect of 1 Hz rTMS on N2 amplitudes in a GoNogo task. Our findings suggest that rTMS may mildly modulate prefrontally generated ERP immediately after stimulation, even where behavioural effects are not measurable. Thus, combined rTMS-ERP approaches need to be further established in order to serve as paradigms in experimental neuroscience and clinical research. PMID:23826214

  15. Cumulative sessions of repetitive transcranial magnetic stimulation (rTMS) build up facilitation to subsequent TMS-mediated behavioural disruptions.

    PubMed

    Valero-Cabré, Antoni; Pascual-Leone, Alvaro; Rushmore, Richard J

    2008-02-01

    A single session of repetitive transcranial magnetic stimulation (rTMS) can induce behavioural effects that outlast the duration of the stimulation train itself (off-line effects). Series of rTMS sessions on consecutive days are being used for therapeutic applications in a variety of disorders and are assumed to lead to the build-up of cumulative effects. However, no studies have carefully assessed this notion. In the present study we applied 30 daily sessions of 1 Hz rTMS (continuous train of 20 min) to repeatedly modulate activity in the posterior parietal cortex and associated neural systems in two intact cats. We assessed the effect on visuospatial orientation before and after each stimulation session. Cumulative sessions of rTMS progressively induced visuospatial neglect-like 'after-effects' of greater magnitude (from 5-10% to 40-50% error levels) and increasing spatial extent (from 90-75 degrees to 45-30 degrees eccentricity locations), affecting the visual hemifield contralateral to the stimulated hemisphere. Nonetheless, 60 min after each TMS session, visual detection-localization abilities repeatedly returned to baseline levels. Furthermore, no lasting behavioural effect could be demonstrated at any time across the study, when subjects were tested 1 or 24 h post-rTMS. We conclude that the past history of periodically cumulative rTMS sessions builds up a lasting 'memory', resulting in increased facilitation to subsequent TMS-induced disruptions. Such a phenomenon allows a behavioural effect of progressively higher magnitude, but equal duration, in response to individual TMS interventions.

  16. Abnormal plasticity of the sensorimotor cortex to slow repetitive transcranial magnetic stimulation in patients with writer's cramp.

    PubMed

    Bäumer, Tobias; Demiralay, Cüneyt; Hidding, Ute; Bikmullina, Rosalia; Helmich, Rick C; Wunderlich, Silke; Rothwell, John; Liepert, Joachim; Siebner, Hartwig R; Münchau, Alexander

    2007-01-01

    Previous studies demonstrated functional abnormalities in the somatosensory system, including a distorted functional organization of the somatosensory cortex (S1) in patients with writer's cramp. We tested the hypothesis that these functional alterations render S1 of these patients more susceptible to the "inhibitory" effects of subthreshold 1 Hz repetitive transcranial magnetic stimulation (rTMS) given to S1. Seven patients with writer's cramp and eight healthy subjects were studied. Patients also received rTMS to the motor cortex hand area (M1). As an outcome measure, short-latency afferent inhibition (SAI) was tested. SAI was studied in the relaxed first dorsal interosseous muscle using conditioning electrical stimulation of the index finger and TMS pulses over the contralateral M1. Baseline SAI did not differ between groups. S1 but not M1 rTMS reduced SAI in patients. rTMS had no effects on SAI in healthy subjects. Because SAI is mediated predominantly at a cortical level in the sensorimotor cortex, we conclude that there is an abnormal responsiveness of this area to 1 Hz rTMS in writer's cramp, which may represent a trait toward maladaptive plasticity in the sensorimotor system in these patients.

  17. Can neurophysiologic measures serve as biomarkers for the efficacy of repetitive transcranial magnetic stimulation treatment of major depressive disorder?

    PubMed

    Kobayashi, Brian; Cook, Ian A; Hunter, Aimee M; Minzenberg, Michael J; Krantz, David E; Leuchter, Andrew F

    2017-03-31

    Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for Major Depressive Disorder (MDD). There are clinical data that support the efficacy of many different approaches to rTMS treatment, and it remains unclear what combination of stimulation parameters is optimal to relieve depressive symptoms. Because of the costs and complexity of studies that would be necessary to explore and compare the large number of combinations of rTMS treatment parameters, it would be useful to establish reliable surrogate biomarkers of treatment efficacy that could be used to compare different approaches to treatment. This study reviews the evidence that neurophysiologic measures of cortical excitability could be used as biomarkers for screening different rTMS treatment paradigms. It examines evidence that: (1) changes in excitability are related to the mechanism of action of rTMS; (2) rTMS has consistent effects on measures of excitability that could constitute reliable biomarkers; and (3) changes in excitability are related to the outcomes of rTMS treatment of MDD. An increasing body of evidence indicates that these neurophysiologic measures have the potential to serve as reliable biomarkers for screening different approaches to rTMS treatment of MDD.

  18. Effects of 1-Hz repetitive transcranial magnetic stimulation on long-latency reflexes and cortical relay time.

    PubMed

    Tataroglu, Cengiz; Sair, Ahmet; Parlaz, Ahu; Deneri, Ersin

    2011-06-01

    Long-latency reflexes (LLRs) of hand muscles include a transcortical component. Cortical relay time estimated by the subtraction of motor and somatosensory evoked potentials from LLR reflects the physiology of the central neural pathway of LLR. It is believed that 1-Hz repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex can decrease cortical excitability for approximately 15 minutes at intracortical level. The aim of the study was to analyze LLR and cortical relay time before and after 1-Hz rTMS. Long-latency reflex and H reflex obtained from the thenar muscles by electrical stimulation of the median nerve of 16 healthy subjects. Additionally, motor evoked potentials and somatosensory evoked potentials were also recorded. Cortical relay time was calculated by the subtraction of motor evoked potential and somatosensory evoked potential latencies from LLR. These electrophysiologic recordings were performed before and after 15 minutes of 1-Hz rTMS over the motor area for the thenar muscles in the primary motor cortex. The amplitudes of LLR and motor evoked potential were significantly decreased after rTMS, but the H reflex of the thenar muscle and somatosensory evoked potentials were unchanged. The major finding of our study was a shortened duration of cortical relay time after rTMS. In conclusion, our findings suggest that the LLR of the thenar muscles has a transcortical pathway and cortical relay time that can give some information about the physiology of the intracortical pathway of LLR.

  19. Efficacy of repetitive transcranial magnetic stimulation with quetiapine in treating bipolar II depression: a randomized, double-blinded, control study

    PubMed Central

    Hu, Shao-hua; Lai, Jian-bo; Xu, Dong-rong; Qi, Hong-li; Peterson, Bradley S.; Bao, Ai-min; Hu, Chan-chan; Huang, Man-li; Chen, Jing-kai; Wei, Ning; Hu, Jian-bo; Li, Shu-lan; Zhou, Wei-hua; Xu, Wei-juan; Xu, Yi

    2016-01-01

    The clinical and cognitive responses to repetitive transcranial magnetic stimulation (rTMS) in bipolar II depressed patients remain unclear. In this study, thirty-eight bipolar II depressed patients were randomly assigned into three groups: (i) left high-frequency (n = 12), (ii) right low-frequency (n = 13), (iii) sham stimulation (n = 13), and underwent four-week rTMS with quetiapine concomitantly. Clinical efficacy was evaluated at baseline and weekly intervals using the 17-item Hamilton Depression Rating Scale (HDRS-17) and Montgomery-Asberg Depression Rating Scale (MADRS). Cognitive functioning was assessed before and after the study with the Wisconsin Card Sorting Test (WCST), Stroop Word-Color Interference Test (Stroop), and Trail Making Test (TMT). Thirty-five patients were included in the final analysis. Overall, the mean scores of both the HDRS-17 and the MADRS significantly decreased over the 4-week trial, which did not differ among the three groups. Exploratory analyses revealed no differences in factor scores of HDRS-17s, or in response or remission rates. Scores of WCST, Stroop, or TMT did not differ across the three groups. These findings indicated active rTMS combined with quetiapine was not superior to quetiapine monotherapy in improving depressive symptoms or cognitive performance in patients with bipolar II depression. PMID:27460201

  20. Repetitive transcranial magnetic stimulation for stroke rehabilitation-potential therapy or misplaced hope?

    PubMed

    Bates, Kristyn Alissa; Rodger, Jennifer

    2015-01-01

    Repeated sessions of transcranial magnetic stimulation (rTMS) are capable of changing and modulating neural activity beyond the period of stimulation. Because many neurological disorders are thought to involve abnormal or dysfunctional neuronal activity, it is hypothesised that the therapeutic action of rTMS may occur through modulating and reversing abnormal activity and facilitating neuroplasticity.Numerous clinical studies have investigated the safety and efficacy of rTMS treatment for a wide variety of conditions including depression, anxiety disorders including obsessive compulsive disorder, Parkinson's disease, stroke, tinnitus, affective disorders, schizophrenia and chronic pain. Despite some promising results, rTMS is not currently widely used to assist in recovery from neurotrama. In this review, we argue that the therapeutic promise of rTMS is limited because the mechanisms of action of rTMS are not completely understood and therefore it is difficult to determine which treatment protocols are appropriate for specific neurological conditions. We use the application of rTMS in motor functional recovery from cerebral ischemic stroke to illustrate the difficulties in interpreting and assessing the therapeutic potential of rTMS for neurotrauma in terms of the presumed mechanisms of action of rTMS. Future directions for research will also be discussed.

  1. Low-Frequency Repetitive Transcranial Magnetic Stimulation and Intensive Occupational Therapy for Poststroke Patients with Upper Limb Hemiparesis: Preliminary Study of a 15-Day Protocol

    ERIC Educational Resources Information Center

    Kakuda, Wataru; Abo, Masahiro; Kobayashi, Kazushige; Momosaki, Ryo; Yokoi, Aki; Fukuda, Akiko; Ishikawa, Atsushi; Ito, Hiroshi; Tominaga, Ayumi

    2010-01-01

    The purpose of the study was to determine the safety and feasibility of a 15-day protocol of low-frequency repetitive transcranial magnetic stimulation (rTMS) combined with intensive occupational therapy (OT) on motor function and spasticity in hemiparetic upper limbs in poststroke patients. Fifteen poststroke patients (age at study entry 55 [plus…

  2. Carbonic Anhydrase I, II, and VI, Blood Plasma, Erythrocyte and Saliva Zinc and Copper Increase After Repetitive Transcranial Magnetic Stimulation

    PubMed Central

    Henkin, Robert I.; Potolicchio, Samuel J.; Levy, Lucien M.; Moharram, Ramy; Velicu, Irina; Martin, Brian M.

    2010-01-01

    Introduction Repetitive transcranial magnetic stimulation (rTMS) has been used to treat symptoms from many disorders; biochemical changes occurred with this treatment. Preliminary studies with rTMS in patients with taste and smell dysfunction improved sensory function and increased salivary carbonic anhydrase (CA) VI and erythrocyte CA I, II. To obtain more information about these changes after rTMS, we measured changes in several CA enzymes, proteins, and trace metals in their blood plasma, erythrocytes, and saliva. Methods Ninety-three patients with taste and smell dysfunction were studied before and after rTMS in an open clinical trial. Before and after rTMS, we measured erythrocyte CA I, II and salivary CA VI, zinc and copper in parotid saliva, blood plasma, and erythrocytes, and appearance of novel salivary proteins by using mass spectrometry. Results After rTMS, CA I, II and CA VI activity and zinc and copper in saliva, plasma, and erythrocytes increased with significant sensory benefit. Novel salivary proteins were induced at an m/z value of 21.5K with a repetitive pattern at intervals of 5K m/z. Conclusions rTMS induced biochemical changes in specific enzymatic activities, trace metal concentrations, and induction of novel salivary proteins, with sensory improvement in patients with taste and smell dysfunction. Because patients with several neurologic disorders exhibit taste and smell dysfunction, including Parkinson disease, Alzheimer disease, and multiple sclerosis, and because rTMS improved their clinical symptoms, the biochemical changes we observed may be relevant not only in our patients with taste and smell dysfunction but also in patients with neurologic disorders with these sensory abnormalities. PMID:20090508

  3. Myoplasmic free Mg2+ concentration during repetitive stimulation of single fibres from mouse skeletal muscle.

    PubMed Central

    Westerblad, H; Allen, D G

    1992-01-01

    1. The role of the myoplasmic free Mg2+ concentration ([Mg2+]i) in fatigue was studied in intact single fibres isolated from mouse skeletal muscle. Fatigue was produced by repeated tetanic stimulation. The fluorescent Mg2+ indicator furaptra was pressure injected into fibres. In vivo calibrations were performed to convert fluorescence signals into [Mg2+]i. 2. [Mg2+]i at rest was 0.78 +/- 0.05 mM (mean +/- S.E.M., n = 14). An increase of the extracellular [Mg2+] from 0.5 to 20 mM resulted in a small elevation of [Mg2+]i (86 microM in 5 min). Removal of extracellular Na+ did not affect [Mg2+]i. An intracellular alkanization of about 0.6 pH units gave a [Mg2+]i reduction of 65 microM. 3. During fatiguing stimulation [Mg2+]i initially remained almost constant and it then suddenly started to rise towards the end of the stimulation period. The onset of the [Mg2+]i rise was always followed by a rapid tension decline. In fatigue [Mg2+]i was approximately twice as high as at rest. 4. Fibres were injected with MgCl2 to study if the rise in [Mg2+]i could explain the tension decline in fatigue. An elevation of [Mg2+]i was accompanied by a tension reduction but the [Mg2+]i for a given tension was generally much higher in rested fibres injected with MgCl2 than in fatigued fibres. Thus the rise in [Mg2+]i as such cannot explain the tension reduction in fatigue. 5. Injection of MgCl2 was also used to assess the intracellular Mg2+ buffering. The mean Mg2+ buffer power (i.e. the ratio of the change in [Mg2+]i to the amount of Mg2+ added) was 0.62. 6. ATP is the quantitatively most important binding site for Mg2+ at rest and ATP breakdown is then a likely source of the [Mg2+]i increase in fatigue. The role of ATP breakdown in the increase of [Mg2+]i was studied with metabolic inhibition: fibres were exposed to iodoacetic acid to inhibit glycolysis and cyanide to inhibit oxidative phosphorylation. The pattern during metabolic inhibition was similar to that observed during fatigue

  4. 200 ps FWHM and 100 MHz repetition rate ultrafast gated camera for optical medical functional imaging

    NASA Astrophysics Data System (ADS)

    Uhring, Wilfried; Poulet, Patrick; Hanselmann, Walter; Glazenborg, René; Zint, Virginie; Nouizi, Farouk; Dubois, Benoit; Hirschi, Werner

    2012-04-01

    The paper describes the realization of a complete optical imaging device to clinical applications like brain functional imaging by time-resolved, spectroscopic diffuse optical tomography. The entire instrument is assembled in a unique setup that includes a light source, an ultrafast time-gated intensified camera and all the electronic control units. The light source is composed of four near infrared laser diodes driven by a nanosecond electrical pulse generator working in a sequential mode at a repetition rate of 100 MHz. The resulting light pulses, at four wavelengths, are less than 80 ps FWHM. They are injected in a four-furcated optical fiber ended with a frontal light distributor to obtain a uniform illumination spot directed towards the head of the patient. Photons back-scattered by the subject are detected by the intensified CCD camera; there are resolved according to their time of flight inside the head. The very core of the intensified camera system is the image intensifier tube and its associated electrical pulse generator. The ultrafast generator produces 50 V pulses, at a repetition rate of 100 MHz and a width corresponding to the 200 ps requested gate. The photocathode and the Micro-Channel-Plate of the intensifier have been specially designed to enhance the electromagnetic wave propagation and reduce the power loss and heat that are prejudicial to the quality of the image. The whole instrumentation system is controlled by an FPGA based module. The timing of the light pulses and the photocathode gating is precisely adjustable with a step of 9 ps. All the acquisition parameters are configurable via software through an USB plug and the image data are transferred to a PC via an Ethernet link. The compactness of the device makes it a perfect device for bedside clinical applications.

  5. Motion as motivation: using repetitive flexion movements to stimulate the approach system.

    PubMed

    Haeffel, Gerald J

    2011-12-01

    Research suggests that having a healthy approach system is critical for adaptive emotional functioning. The goal of the current study (n=186 undergraduates) was to determine the efficacy of an easy-to-disseminate and cost-efficient strategy for stimulating this system. The experiment tested the effects of repeated flexion movements (rFM) on approach system activation as measured by both self-report (BAS scales) and behavior. The results showed that rFM increased approach system motivation in men but not women. Men who completed the rFM task reported significantly greater levels of fun-seeking motivation than men in the control task. Moreover, the rFM task led to changes in actual behavior. Men who completed the rFM task exhibited significantly greater persistence on a difficult laboratory task than men in the control task. In contrast, women who completed the rFM task reported significantly lower levels of fun seeking and tended to exhibit less persistence on a difficult laboratory task than women in the control task. These results provide support for embodied theories of emotion as well as additional evidence for a gender difference in approach-avoidance tendencies.

  6. Repetitive stimulation of autophagy-lysosome machinery by intermittent fasting preconditions the myocardium to ischemia-reperfusion injury.

    PubMed

    Godar, Rebecca J; Ma, Xiucui; Liu, Haiyan; Murphy, John T; Weinheimer, Carla J; Kovacs, Attila; Crosby, Seth D; Saftig, Paul; Diwan, Abhinav

    2015-01-01

    Autophagy, a lysosomal degradative pathway, is potently stimulated in the myocardium by fasting and is essential for maintaining cardiac function during prolonged starvation. We tested the hypothesis that intermittent fasting protects against myocardial ischemia-reperfusion injury via transcriptional stimulation of the autophagy-lysosome machinery. Adult C57BL/6 mice subjected to 24-h periods of fasting, every other day, for 6 wk were protected from in-vivo ischemia-reperfusion injury on a fed day, with marked reduction in infarct size in both sexes as compared with nonfasted controls. This protection was lost in mice heterozygous null for Lamp2 (coding for lysosomal-associated membrane protein 2), which demonstrate impaired autophagy in response to fasting with accumulation of autophagosomes and SQSTM1, an autophagy substrate, in the heart. In lamp2 null mice, intermittent fasting provoked progressive left ventricular dilation, systolic dysfunction and hypertrophy; worsening cardiomyocyte autophagosome accumulation and lack of protection to ischemia-reperfusion injury, suggesting that intact autophagy-lysosome machinery is essential for myocardial homeostasis during intermittent fasting and consequent ischemic cardioprotection. Fasting and refeeding cycles resulted in transcriptional induction followed by downregulation of autophagy-lysosome genes in the myocardium. This was coupled with fasting-induced nuclear translocation of TFEB (transcription factor EB), a master regulator of autophagy-lysosome machinery; followed by rapid decline in nuclear TFEB levels with refeeding. Endogenous TFEB was essential for attenuation of hypoxia-reoxygenation-induced cell death by repetitive starvation, in neonatal rat cardiomyocytes, in-vitro. Taken together, these data suggest that TFEB-mediated transcriptional priming of the autophagy-lysosome machinery mediates the beneficial effects of fasting-induced autophagy in myocardial ischemia-reperfusion injury.

  7. Repetitive Peripheral Magnetic Stimulation (15 Hz RPMS) of the Human Soleus Muscle did not Affect Spinal Excitability

    PubMed Central

    Behrens, Martin; Mau-Möller, Anett; Zschorlich, Volker; Bruhn, Sven

    2011-01-01

    The electric field induced by repetitive peripheral magnetic stimulation (RPMS) is able to activate muscles artificially due to the stimulation of deep intramuscular motor axons. RPMS applied to the muscle induces proprioceptive input to the central nervous system in different ways. Firstly, the indirect activation of mechanoreceptors and secondly, direct activation of afferent nerve fibers. The purpose of the study was to examine the effects of RPMS applied to the soleus. Thirteen male subjects received RPMS once and were investigated before and after the treatment regarding the parameters maximal M wave (Mmax), maximal H-reflex (Hmax), Hmax/Mmax-ratio, Hmax and Mmax onset latencies and plantar flexor peak twitch torque associated with Hmax (PTH). Eleven male subjects served as controls. No significant changes were observed for Hmax and PTH of the treatment group but the Hmax/Mmax-ratio increased significantly (p = 0.015) on account of a significantly decreased Mmax (p = 0.027). Hmax onset latencies were increased for the treatment group (p = 0.003) as well as for the control group (p = 0.011) while Mmax onset latencies did not change. It is concluded that the RPMS protocol did not affect spinal excitability but acted on the muscle fibres which are part of fast twitch units and mainly responsible for the generation of the maximal M wave. RPMS probably modified the integrity of neuromuscular propagation. Key points RPMS probably did not affect spinal excitability. Data suggested that RPMS likely acted on the muscle fibres which are part of fast twitch units and mainly responsible for the generation of the maximal M wave. RPMS probably modified the integrity of neuromuscular propagation. PMID:24149293

  8. Repetitive stimulation of autophagy-lysosome machinery by intermittent fasting preconditions the myocardium to ischemia-reperfusion injury

    PubMed Central

    Godar, Rebecca J; Ma, Xiucui; Liu, Haiyan; Murphy, John T; Weinheimer, Carla J; Kovacs, Attila; Crosby, Seth D; Saftig, Paul; Diwan, Abhinav

    2015-01-01

    Autophagy, a lysosomal degradative pathway, is potently stimulated in the myocardium by fasting and is essential for maintaining cardiac function during prolonged starvation. We tested the hypothesis that intermittent fasting protects against myocardial ischemia-reperfusion injury via transcriptional stimulation of the autophagy-lysosome machinery. Adult C57BL/6 mice subjected to 24-h periods of fasting, every other day, for 6 wk were protected from in-vivo ischemia-reperfusion injury on a fed day, with marked reduction in infarct size in both sexes as compared with nonfasted controls. This protection was lost in mice heterozygous null for Lamp2 (coding for lysosomal-associated membrane protein 2), which demonstrate impaired autophagy in response to fasting with accumulation of autophagosomes and SQSTM1, an autophagy substrate, in the heart. In lamp2 null mice, intermittent fasting provoked progressive left ventricular dilation, systolic dysfunction and hypertrophy; worsening cardiomyocyte autophagosome accumulation and lack of protection to ischemia-reperfusion injury, suggesting that intact autophagy-lysosome machinery is essential for myocardial homeostasis during intermittent fasting and consequent ischemic cardioprotection. Fasting and refeeding cycles resulted in transcriptional induction followed by downregulation of autophagy-lysosome genes in the myocardium. This was coupled with fasting-induced nuclear translocation of TFEB (transcription factor EB), a master regulator of autophagy-lysosome machinery; followed by rapid decline in nuclear TFEB levels with refeeding. Endogenous TFEB was essential for attenuation of hypoxia-reoxygenation-induced cell death by repetitive starvation, in neonatal rat cardiomyocytes, in-vitro. Taken together, these data suggest that TFEB-mediated transcriptional priming of the autophagy-lysosome machinery mediates the beneficial effects of fasting-induced autophagy in myocardial ischemia-reperfusion injury. PMID:26103523

  9. Longlasting antalgic effects of daily sessions of repetitive transcranial magnetic stimulation in central and peripheral neuropathic pain

    PubMed Central

    Khedr, E; Kotb, H; Kamel, N; Ahmed, M; Sadek, R; Rothwell, J

    2005-01-01

    Background and objective: A single session of repetitive transcranial magnetic stimulation (rTMS) over motor cortex had been reported to produce short term relief of some types of chronic pain. The present study investigated whether five consecutive days of rTMS would lead to longer lasting pain relief in unilateral chronic intractable neuropathic pain. Patients and methods: Forty eight patients with therapy resistant chronic unilateral pain syndromes (24 each with trigeminal neuralgia (TGN) and post-stroke pain syndrome (PSP)) participated. Fourteen from each group received 10 minutes real rTMS over the hand area of motor cortex (20 Hz, 10x10 s trains, intensity 80% of motor threshold) every day for five consecutive days. The remaining patients received sham stimulation. Pain was assessed using a visual analogue scale (VAS) and the Leeds assessment of neuropathic symptoms and signs (LANSS) scale, before, after the first, fourth, and fifth sessions, and two weeks after the last session. Results: No significant differences were found in basal pain ratings between patients receiving real- and sham-rTMS. However, a two factor ANOVA revealed a significant "± TMS" x "time" interaction indicating that real and sham rTMS had different effects on the VAS and LANSS scales. Post hoc testing showed that in both groups of patients, real-rTMS led to a greater improvement in scales than sham-rTMS, evident even two weeks after the end of the treatment. No patient experienced adverse effects. Conclusion: These results confirm that five daily sessions of rTMS over motor cortex can produce longlasting pain relief in patients with TGN or PSP. PMID:15897507

  10. Repetitive Transcranial Magnetic Stimulation as an Adjunct to Constraint-Induced Therapy: An Exploratory Randomized Controlled Trial

    PubMed Central

    Malcolm, Matthew P.; Triggs, William J.; Light, Kathye E.; Gonzalez Rothi, Leslie J.; Wu, Sam; Reid, Kimberly; Nadeau, Stephen E.

    2008-01-01

    Objective To test the potential adjuvant effect of repetitive transcranial magnetic stimulation (rTMS) on motor learning in a group of stroke survivors undergoing constraint-induced therapy (CIT) for upper-limb hemiparesis. Design This was a prospective randomized, double-blind, sham-controlled, parallel group study. Nineteen individuals, one or more years poststroke, were randomized to either a rTMS + CIT (n = 9) or a sham rTMS + CIT (n = 10) group and participated in the 2-wk intervention. Results Regardless of group assignment, participants demonstrated significant gains on the primary outcome measures: the Wolf Motor Function Test (WMFT) and the Motor Activity Log (MAL)–Amount of Use, and on secondary outcome measures including the Box and Block Test (BBT) and the MAL–How Well. Participants receiving rTMS failed to show differential improvement on either primary outcome measure. Conclusions Although this study provided further evidence that even relatively brief sessions of CIT can have a substantial effect, it provided no support for adjuvant use of rTMS. PMID:17709994

  11. Benefit of multiple sessions of perilesional repetitive transcranial magnetic stimulation for an effective rehabilitation of visuospatial function.

    PubMed

    Afifi, Linda; Jarrett Rushmore, R; Valero-Cabré, Antoni

    2013-02-01

    Noninvasive neurostimulation techniques have been used alone or in conjunction with rehabilitation therapy to treat the neurological sequelae of brain damage with rather variable therapeutic outcomes. One potential factor limiting a consistent success for such techniques may be the limited number of sessions carried out in patients, despite reports that their accrual may play a key role in alleviating neurological deficits long-term. In this study, we tested the effects of seventy consecutive sessions of perilesional high-frequency (10 Hz) repetitive transcranial magnetic stimulation (rTMS) in the treatment of chronic neglect deficits in a well-established feline model of visuospatial neglect. Under identical rTMS parameters and visuospatial testing regimes, half of the subjects improved in visuospatial orienting performance. The other half experienced either none or extremely moderate ameliorations in the neglected hemispace and displayed transient patterns of maladaptive visuospatial behavior. Detailed analyses suggest that lesion location and extent did not account for the behavioral differences observed between these two groups of animals. We conclude that multi-session perilesional rTMS regimes have the potential to induce functional ameliorations following focal chronic brain injury, and that behavioral performance prior to the onset of the rTMS treatment is the factor that best predicts positive outcomes for noninvasive neurostimulation treatments in visuospatial neglect.

  12. Benefit of Multiple Sessions of Perilesional Repetitive Transcranial Magnetic Stimulation for an Effective Rehabilitation of Visuo-Spatial Function

    PubMed Central

    Afifi, Linda; Rushmore, R. Jarrett; Valero-Cabré, Antoni

    2012-01-01

    Non-invasive neurostimulation techniques have been used alone or in conjunction with rehabilitation therapy to treat the neurological sequelae of brain damage with rather variable therapeutic outcomes. One potential factor limiting a consistent success for such techniques may be the few sessions carried out in patients, despite reports that their accrual may play a key role in alleviating neurological deficits long-term. In this study, we tested the effects of seventy consecutive sessions of perilesional high frequency (10 Hz) repetitive transcranial magnetic stimulation (rTMS) in the treatment of chronic neglect deficits in a well-established feline model of visuo-spatial neglect. Under identical rTMS parameters and visuo-spatial testing regimes, half of the subjects improved in visuo-spatial orienting performance. The other half experienced either none or extremely moderate ameliorations in the neglected hemispace and displayed transient patterns of maladaptive visuo-spatial behavior. Detailed analyses suggest that lesion location and extent did not account for the behavioral differences observed between these two groups of animals. We conclude that multi-session perilesional rTMS regimes have the potential to induce functional ameliorations following focal chronic brain injury, and that behavioral performance prior to the onset of the rTMS treatment is the factor that best predicts positive outcomes for non-invasive neurostimulation treatments in visuo-spatial neglect. PMID:23167832

  13. The effect of computer-assisted cognitive rehabilitation and repetitive transcranial magnetic stimulation on cognitive function for stroke patients

    PubMed Central

    Park, In-Seok; Yoon, Jung-Gyu

    2015-01-01

    [Purpose] This study investigated the effects of computer-assisted cognitive rehabilitation (CACR) and repetitive transcranial magnetic stimulation (rTMS) on cognitive function in patients with stroke. [Subjects and Methods] We enrolled 20 patients and divided them into CACR and rTMS groups. CACR and rTMS were performed thrice a week for 4 weeks. Cognitive function was measured with the Korean Mini-Mental State Examination (K-MMSE) and Lowenstein Occupational Therapy Cognitive Assessment-Geriatric (LOTCA-G) before and after treatment. The independent samples t-test was performed to test the homogeneity of K-MMSE and LOTCA-G before treatment and compare the differences in cognitive improvement between the CACR and rTMS groups. A paired samples t-test was used to compare cognitive function before and after treatment. [Results] Cognitive function of both the groups significantly improved after the intervention based on the K-MMSE and LOTCA-G scores. While the LOTCA-G score improved significantly more in the CACR group than in the rTMS group, no significant difference was seen in the K-MMSE scores. [Conclusion] We showed that CACR is more effective than rTMS in improving cognitive function after stroke. PMID:25931728

  14. Involvement of the superior temporal cortex and the occipital cortex in spatial hearing: evidence from repetitive transcranial magnetic stimulation.

    PubMed

    Lewald, Jörg; Meister, Ingo G; Weidemann, Jürgen; Töpper, Rudolf

    2004-06-01

    The processing of auditory spatial information in cortical areas of the human brain outside of the primary auditory cortex remains poorly understood. Here we investigated the role of the superior temporal gyrus (STG) and the occipital cortex (OC) in spatial hearing using repetitive transcranial magnetic stimulation (rTMS). The right STG is known to be of crucial importance for visual spatial awareness, and has been suggested to be involved in auditory spatial perception. We found that rTMS of the right STG induced a systematic error in the perception of interaural time differences (a primary cue for sound localization in the azimuthal plane). This is in accordance with the recent view, based on both neurophysiological data obtained in monkeys and human neuroimaging studies, that information on sound location is processed within a dorsolateral "where" stream including the caudal STG. A similar, but opposite, auditory shift was obtained after rTMS of secondary visual areas of the right OC. Processing of auditory information in the OC has previously been shown to exist only in blind persons. Thus, the latter finding provides the first evidence of an involvement of the visual cortex in spatial hearing in sighted human subjects, and suggests a close interconnection of the neural representation of auditory and visual space. Because rTMS induced systematic shifts in auditory lateralization, but not a general deterioration, we propose that rTMS of STG or OC specifically affected neuronal circuits transforming auditory spatial coordinates in order to maintain alignment with vision.

  15. The effect of computer-assisted cognitive rehabilitation and repetitive transcranial magnetic stimulation on cognitive function for stroke patients.

    PubMed

    Park, In-Seok; Yoon, Jung-Gyu

    2015-03-01

    [Purpose] This study investigated the effects of computer-assisted cognitive rehabilitation (CACR) and repetitive transcranial magnetic stimulation (rTMS) on cognitive function in patients with stroke. [Subjects and Methods] We enrolled 20 patients and divided them into CACR and rTMS groups. CACR and rTMS were performed thrice a week for 4 weeks. Cognitive function was measured with the Korean Mini-Mental State Examination (K-MMSE) and Lowenstein Occupational Therapy Cognitive Assessment-Geriatric (LOTCA-G) before and after treatment. The independent samples t-test was performed to test the homogeneity of K-MMSE and LOTCA-G before treatment and compare the differences in cognitive improvement between the CACR and rTMS groups. A paired samples t-test was used to compare cognitive function before and after treatment. [Results] Cognitive function of both the groups significantly improved after the intervention based on the K-MMSE and LOTCA-G scores. While the LOTCA-G score improved significantly more in the CACR group than in the rTMS group, no significant difference was seen in the K-MMSE scores. [Conclusion] We showed that CACR is more effective than rTMS in improving cognitive function after stroke.

  16. Repetitive transcranial magnetic stimulation induced slow wave activity modification: A possible role in disorder of consciousness differential diagnosis?

    PubMed

    Pisani, Laura Rosa; Naro, Antonino; Leo, Antonino; Aricò, Irene; Pisani, Francesco; Silvestri, Rosalia; Bramanti, Placido; Calabrò, Rocco Salvatore

    2015-12-15

    Slow wave activity (SWA) generation depends on cortico-thalamo-cortical loops that are disrupted in patients with chronic Disorders of Consciousness (DOC), including the Unresponsive Wakefulness Syndrome (UWS) and the Minimally Conscious State (MCS). We hypothesized that the modulation of SWA by means of a repetitive transcranial magnetic stimulation (rTMS) could reveal residual patterns of connectivity, thus supporting the DOC clinical differential diagnosis. We enrolled 10 DOC individuals who underwent a 24hh polysomnography followed by a real or sham 5Hz-rTMS over left primary motor area, and a second polysomnographic recording. A preserved sleep-wake cycle, a standard temporal progression of sleep stages, and a SWA perturbation were found in all of the MCS patients and in none of the UWS individuals, only following the real-rTMS. In conclusion, our combined approach may improve the differential diagnosis between MCS patients, who show a partial preservation of cortical plasticity, and UWS individuals, who lack such properties.

  17. Impact of Repetitive Transcranial Magnetic Stimulation on Post-Stroke Dysmnesia and the Role of BDNF Val66Met SNP

    PubMed Central

    Lu, Haitao; Zhang, Tong; Wen, Mei; Sun, Li

    2015-01-01

    Background Little is known about the effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) on dysmnesia and the impact of brain nucleotide neurotrophic factor (BDNF) Val66Met single-nucleotide polymorphism (SNP). This study investigated the impact of low-frequency rTMS on post-stroke dysmnesia and the impact of BDNF Val66Met SNP. Material/Methods Forty patients with post-stroke dysmnesia were prospectively randomized into the rTMS and sham groups. BDNF Val66Met SNP was determined using restriction fragment length polymorphism. Montreal Cognitive Assessment (MoCA), Loewenstein Occupational Therapy of Cognitive Assessment (LOTCA), and Rivermead Behavior Memory Test (RBMT) scores, as well as plasma BDNF concentrations, were measured at baseline and at 3 days and 2 months post-treatment. Results MoCA, LOTCA, and RBMT scores were higher after rTMS. Three days after treatment, BDNF decreased in the rTMS group but it increased in the sham group (P<0.05). Two months after treatment, RMBT scores in the rTMS group were higher than in the sham group, but not MoCA and LOTCA scores. Conclusions Low-frequency rTMS may improve after-stoke memory through various pathways, which may involve polymorphisms and several neural genes, but not through an increase in BDNF levels. PMID:25770310

  18. Analgesic effect of repetitive transcranial magnetic stimulation (rTMS) in patients with chronic low back pain.

    PubMed

    Ambriz-Tututi, Mónica; Alvarado-Reynoso, Beatriz; Drucker-Colín, René

    2016-08-22

    The objective of the present study was to assess the benefits of 1-week repetitive transcranial magnetic stimulation (rTMS) in patients with chronic low back pain (LBP). The visual analogue scale (VAS), Short Form McGill pain questionnaire (SF-MPQ), and Short Form 36 Health Survey were used to evaluate the effect of this treatment. Eighty-two patients diagnosed with LBP were divided randomly into three groups: rTMS-treated group, sham group, and physical therapy-treated group. We observed a significant reduction in VAS and SF-MPQ scores in the rTMS-treated group, but not in the sham group. Moreover, patients who received rTMS had a lower mean pain score than patients treated with physical therapy. Our study suggests that rTMS produces safe, significant, and long-term relief in patients with LBP without evident side effects. This study shows for the first time that long-term repeated sessions of rTMS decrease pain perception of LBP. Bioelectromagnetics. © 2016 Wiley Periodicals, Inc.

  19. Safety and tolerability of repetitive transcranial magnetic stimulation in patients with epilepsy: a review of the literature.

    PubMed

    Bae, Erica Hyunji; Schrader, Lara M; Machii, Katsuyuki; Alonso-Alonso, Miguel; Riviello, James J; Pascual-Leone, Alvaro; Rotenberg, Alexander

    2007-06-01

    Repetitive transcranial magnetic stimulation (rTMS) is emerging as a new therapeutic tool in epilepsy, where it can be used to suppress seizures or treat comorbid conditions such as mood disorder. However, as rTMS carries a risk of inducing seizures among other adverse events, its safety and tolerability in the population with epilepsy warrant distinct consideration, as this group is especially seizure-prone. Accordingly, we performed a review of the literature to estimate the risk of seizures and other adverse events associated with rTMS in patients with epilepsy. We performed an English-language literature search, and reviewed all studies published from January 1990 to February 2007 in which patients with epilepsy were treated with rTMS, and complemented the literature search with personal correspondence with authors when necessary. We identified 30 publications that described patients with epilepsy who underwent rTMS, and noted total number of relevant subjects, medication usage, incidence of adverse events, and rTMS parameters including stimulus frequency, number of stimuli, train duration, intertrain interval, coil type, and stimulation sites. The data were analyzed for adverse events related to rTMS. Crude per-subject risk, as well as per-subject mean risk weighted by sample size and risk per 1000 stimuli weighted by number of stimuli in each study, were computed for seizures and for other adverse events. Adverse events or lack thereof was reported in 26 studies (n=280 subjects). Adverse events attributed to rTMS were generally mild and occurred in 17.1% of subjects. Headache was most common, occurring in 9.6%. The most serious adverse event was seizure during treatment, which occurred in four patients (1.4% crude per-subject risk). All but one case were the patients' typical seizures with respect to duration and semiology, and were associated with low-frequency rTMS. A single case of an atypical seizure appearing to arise from the region of stimulation

  20. Repetitive transcranial magnetic stimulation (rTMS) influences spatial cognition and modulates hippocampal structural synaptic plasticity in aging mice.

    PubMed

    Ma, Jun; Zhang, Zhanchi; Kang, Lin; Geng, Dandan; Wang, Yanyong; Wang, Mingwei; Cui, Huixian

    2014-10-01

    Normal aging is characteristic with the gradual decline in cognitive function associated with the progressive reduction of structural and functional plasticity in the hippocampus. Repetitive transcranial magnetic stimulation (rTMS) has developed into a novel neurological and psychiatric tool that can be used to investigate the neurobiology of cognitive function. Recent studies have demonstrated that low-frequency rTMS (≤1Hz) affects synaptic plasticity in rats with vascular dementia (VaD), and it ameliorates the spatial cognitive ability in mice with Aβ1-42-mediated memory deficits, but there are little concerns about the effects of rTMS on normal aging related cognition and synaptic plasticity changes. Thus, the current study investigated the effects of rTMS on spatial memory behavior, neuron and synapse morphology in the hippocampus, and synaptic protein markers and brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) in normal aging mice, to illustrate the mechanisms of rTMS in regulating cognitive capacity. Relative to adult animals, aging caused hippocampal-dependent cognitive impairment, simultaneously inhibited the activation of the BDNF-TrkB signaling pathway, reduced the transcription and expression of synaptic protein markers: synaptophysin (SYN), growth associated protein 43 (GAP43) and post-synaptic density protein 95 (PSD95), as well as decreased synapse density and PSD (post-synaptic density) thickness. Interestingly, rTMS with low intensity (110% average resting motor threshold intensity, 1Hz, LIMS) triggered the activation of BDNF and TrkB, upregulated the level of synaptic protein markers, and increased synapse density and thickened PSD, and further reversed the spatial cognition dysfunction in aging mice. Conversely, high-intensity magnetic stimulation (150% average resting motor threshold intensity, 1Hz, HIMS) appeared to be detrimental, inducing thinning of PSDs, disordered synaptic structure, and a large number of

  1. Acoustic evaluation of short-term effects of repetitive transcranial magnetic stimulation on motor aspects of speech in Parkinson's disease.

    PubMed

    Eliasova, I; Mekyska, J; Kostalova, M; Marecek, R; Smekal, Z; Rektorova, I

    2013-04-01

    Hypokinetic dysarthria in Parkinson's disease (PD) can be characterized by monotony of pitch and loudness, reduced stress, variable rate, imprecise consonants, and a breathy and harsh voice. Using acoustic analysis, we studied the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) applied over the primary orofacial sensorimotor area (SM1) and the left dorsolateral prefrontal cortex (DLPFC) on motor aspects of voiced speech in PD. Twelve non-depressed and non-demented men with PD (mean age 64.58 ± 8.04 years, mean PD duration 10.75 ± 7.48 years) and 21 healthy age-matched men (a control group, mean age 64 ± 8.55 years) participated in the speech study. The PD patients underwent two sessions of 10 Hz rTMS over the dominant hemisphere with 2,250 stimuli/day in a random order: (1) over the SM1; (2) over the left DLPFC in the "on" motor state. Speech examination comprised the perceptual rating of global speech performance and an acoustic analysis based upon a standardized speech task. The Mann-Whitney U test was used to compare acoustic speech variables between controls and PD patients. The Wilcoxon test was used to compare data prior to and after each stimulation in the PD group. rTMS applied over the left SM1 was associated with a significant increase in harmonic-to-noise ratio and net speech rate in the sentence tasks. With respect to the vowel task results, increased median values and range of Teager-Kaiser energy operator, increased vowel space area, and significant jitter decrease were observed after the left SM1 stimulation. rTMS over the left DLPFC did not induce any significant effects. The positive results of acoustic analysis were not reflected in a subjective rating of speech performance quality as assessed by a speech therapist. Our pilot results indicate that one session of rTMS applied over the SM1 may lead to measurable improvement in voice quality and intensity and an increase in speech rate and tongue movements

  2. Fractional averaging of repetitive waveforms induced by self-imaging effects

    NASA Astrophysics Data System (ADS)

    Romero Cortés, Luis; Maram, Reza; Azaña, José

    2015-10-01

    We report the theoretical prediction and experimental observation of averaging of stochastic events with an equivalent result of calculating the arithmetic mean (or sum) of a rational number of realizations of the process under test, not necessarily limited to an integer record of realizations, as discrete statistical theory dictates. This concept is enabled by a passive amplification process, induced by self-imaging (Talbot) effects. In the specific implementation reported here, a combined spectral-temporal Talbot operation is shown to achieve undistorted, lossless repetition-rate division of a periodic train of noisy waveforms by a rational factor, leading to local amplification, and the associated averaging process, by the fractional rate-division factor.

  3. Brain imaging correlates of peripheral nerve stimulation

    PubMed Central

    Bari, Ausaf A.; Pouratian, Nader

    2012-01-01

    Direct peripheral nerve stimulation is an effective treatment for a number of disorders including epilepsy, depression, neuropathic pain, cluster headache, and urological dysfunction. The efficacy of this stimulation is ultimately due to modulation of activity in the central nervous system. However, the exact brain regions involved in each disorder and how they are modulated by peripheral nerve stimulation is not fully understood. The use of functional neuroimaging such as SPECT, PET and fMRI in patients undergoing peripheral nerve stimulation can help us to understand these mechanisms. We review the literature for functional neuroimaging performed in patients implanted with peripheral nerve stimulators for the above-mentioned disorders. These studies suggest that brain activity in response to peripheral nerve stimulation is a complex interaction between the stimulation parameters, disease type and severity, chronicity of stimulation, as well as nonspecific effects. From this information we may be able to understand which brain structures are involved in the mechanism of peripheral nerve stimulation as well as define the neural substrates underlying these disorders. PMID:23230531

  4. Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Sehatzadeh, Shayan; Tu, Hong Anh; Palimaka, Stefan; Yap, Belinda; O'Reilly, Daria; Bowen, Jim; Higgins, Caroline; Holubowich, Corinne

    2016-01-01

    Background To date, several randomized controlled trials (RCTs) have shown the efficacy of repetitive transcranial magnetic stimulation (rTMS) in the treatment of major depression. Objective This analysis examined the antidepressant efficacy of rTMS in patients with treatment-resistant unipolar depression. Methods A literature search was performed for RCTs published from January 1, 1994, to November 20, 2014. The search was updated on March 1, 2015. Two independent reviewers evaluated the abstracts for inclusion, reviewed full texts of eligible studies, and abstracted data. Meta-analyses were conducted to obtain summary estimates. The primary outcome was changes in depression scores measured by the Hamilton Rating Scale for Depression (HRSD), and we considered, a priori, the mean difference of 3.5 points to be a clinically important treatment effect. Remission and response to the treatment were secondary outcomes, and we calculated number needed to treat on the basis of these outcomes. We examined the possibility of publication bias by constructing funnel plots and by Begg's and Egger's tests. A meta-regression was undertaken to examine the effect of specific rTMS technical parameters on the treatment effects. Results Twenty-three RCTs compared rTMS with sham, and six RCTs compared rTMS with electroconvulsive therapy (ECT). Trials of rTMS versus sham showed a statistically significant improvement in depression scores with rTMS (weighted mean difference [WMD] 2.31, 95% CI 1.19–3.43; P < .001). This improvement was smaller than the pre-specified clinically important treatment effect. There was a 10% absolute difference between rTMS and sham in the rates of remission or response. This translates to a number needed to treat of 10. Risk ratios for remission and response were 2.20 (95% CI 1.44–3.38, P = .001 and 1.72 [95% CI], 1.13–2.62, P = .01), respectively, favouring rTMS. No publication bias was detected. Trials of rTMS versus ECT showed a statistically and

  5. Evaluating the Effect of Repetitive Transcranial Magnetic Stimulation on Disorders of Consciousness by Using TMS-EEG

    PubMed Central

    Bai, Yang; Xia, Xiaoyu; Kang, Jiannan; Yin, Xiaoxiao; Yang, Yi; He, Jianghong; Li, Xiaoli

    2016-01-01

    Background: The modulation efficacy of Transcranial magnetic stimulation (TMS) on consciousness improvement of patient with disorder of consciousness (DOC) has not been definitely confirmed. Objective: This study proposes TMS-EEG to assess effects of repetitive TMS (rTMS) on brain modulation of DOC. Methods: Twenty sessions of 10 Hz rTMS were applied over the dorsolateral prefrontal cortex for a patient with DOC. Measures of Coma Recovery Scale-Revised (CRS-R) score, TMS-evoked potential (TEP), perturbation complexity index (PCI), and global mean field power (GMFP) were used to evaluate the consciousness level of the patient at three intervals: before the rTMS protocol (T0), immediately after one session rTMS (T1), and immediately after 20 sessions (T2). Results: It was found that the patient was diagnosed of a minimally conscious state minus (MCS-) by means of CRS-R at the interval of T0, however the TEP and PCI indicated the patient was vegetative state (VS). At the interval of T1, there was not any clinical behavioral improvement in CRS-R, but we could find significant changes in TEP, PCI, and GMFP. At the interval of T2 there was a significant increase of consciousness level according by CRS-R score, PCI value, TEP, and GMFP after 20 sessions of 10 Hz rTMS on the patient with DOC. Conclusions: We demonstrated that TMS-EEG might be an efficient assessment tool for evaluating rTMS protocol therapeutic efficiency in DOC. PMID:27812319

  6. Cyclical changes of cortical excitability and metaplasticity in migraine: evidence from a repetitive transcranial magnetic stimulation study.

    PubMed

    Cosentino, Giuseppe; Fierro, Brigida; Vigneri, Simone; Talamanca, Simona; Paladino, Piera; Baschi, Roberta; Indovino, Serena; Maccora, Simona; Valentino, Francesca; Fileccia, Enrico; Giglia, Giuseppe; Brighina, Filippo

    2014-06-01

    The primary brain dysfunctions leading to the onset of a migraine attack remain largely unknown. Other important open questions concern the mechanisms of initiation, continuation, and termination of migraine pain, and the changes in brain function underlying migraine transformation. Brief trains of high-frequency repetitive transcranial magnetic stimulation (rTMS), when applied to the primary motor cortex at suprathreshold intensity (⩾120% of resting motor threshold [RMT]), elicit in healthy subjects a progressive, glutamate-dependent facilitation of the motor evoked potentials (MEP). Conversely, in conditions of increased cortical excitability, the rTMS trains induce inhibitory MEP responses likely mediated by cortical homeostatic mechanisms. We enrolled 66 migraine-without-aura patients, 48 migraine-with-aura patients, 14 patients affected by chronic migraine (CM), and 20 healthy controls. We assessed motor cortical response to 5-Hz rTMS trains of 10 stimuli given at 120% RMT. Patients with episodic migraine were studied in different phases of the migraine cycle: interictal, preictal, ictal, and postictal states. Results showed a facilitatory MEP response during the trains in patients evaluated in the preictal phase, whereas inhibitory responses were observed during and after a migraine attack, as well as in CM patients. In the interictal phase, different responses were observed, depending on attack frequency: facilitation in patients with low and inhibition in those with high attack recurrence. Our findings suggest that changes in cortical excitability and fluctuations in the threshold for inhibitory metaplasticity underlie the migraine attack recurrence, and could be involved in the process of migraine transformation.

  7. Therapeutic impact of repetitive transcranial magnetic stimulation (rTMS) on tinnitus: a systematic review and meta-analysis.

    PubMed

    Soleimani, Robabeh; Jalali, Mir Mohammad; Hasandokht, Tolou

    2016-07-01

    In this study, we conducted a systematic literature review and meta-analysis on the effect of repetitive transcranial magnetic stimulation (rTMS) compared with sham in chronic tinnitus patients. We searched databases, from their onset up to August 2014, for randomized controlled trials (RCT) in English that assessed the effectiveness of rTMS for chronic tinnitus. RCTs were selected according to inclusion/exclusion criteria before data were extracted. For the meta-analysis weighted mean differences (and standard deviations) of Tinnitus Questionnaire (TQ) and Tinnitus Handicap Inventory (THI) scores were determined. Therapeutic success was defined as difference of at least 7 points in the THI score between baseline and the follow-up assessment after treatment. The odds ratio (OR) for this variable was assessed. Results from 15 RCTs were analyzed. The mean difference for TQ score at 1 week after intervention was 3.42. For THI, the data of mean difference score in two groups, 1 and 6 month after intervention, was 6.71 and 12.89, respectively. The all comparisons indicated a significant medium to large effect size in follow-up which is in favor of the rTMS. The pooled OR of therapeutic success of the studies which used THI at 1 month after intervention was 15.75. These data underscore the clinical effect of rTMS in the treatment of tinnitus. However, there is high variability of studies design and reported outcomes. Replication of data in multicenter trials with a large number of patients and long-term follow-up is needed before further conclusions can be drawn.

  8. The Role of Right Inferior Parietal Cortex in Auditory Spatial Attention: A Repetitive Transcranial Magnetic Stimulation Study

    PubMed Central

    Karhson, Debra S.; Mock, Jeffrey R.; Golob, Edward J.

    2015-01-01

    Behavioral studies support the concept of an auditory spatial attention gradient by demonstrating that attentional benefits progressively diminish as distance increases from an attended location. Damage to the right inferior parietal cortex can induce a rightward attention bias, which implicates this region in the construction of attention gradients. This study used event-related potentials (ERPs) to define attention-related gradients before and after repetitive transcranial magnetic stimulation (rTMS) to the right inferior parietal cortex. Subjects (n = 16) listened to noise bursts at five azimuth locations (left to right: -90°, -45°, 0° midline, +45°, +90°) and responded to stimuli at one target location (-90°, +90°, separate blocks). ERPs as a function of non-target location were examined before (baseline) and after 0.9 Hz rTMS. Results showed that ERP attention gradients were observed in three time windows (frontal 230–340, parietal 400–460, frontal 550–750 ms). Significant transient rTMS effects were seen in the first and third windows. The first window had a voltage decrease at the farthest location when attending to either the left or right side. The third window had on overall increase in positivity, but only when attending to the left side. These findings suggest that rTMS induced a small contraction in spatial attention gradients within the first time window. The asymmetric effect of attended location on gradients in the third time window may relate to neglect of the left hemispace after right parietal injury. Together, these results highlight the role of the right inferior parietal cortex in modulating frontal lobe attention network activity. PMID:26636333

  9. Repetitive transcranial magnetic stimulation (rTMS) improves behavioral and biochemical deficits in levodopa-induced dyskinetic rats model

    PubMed Central

    Guan, Lina; Yi, Maoli; Zhang, Hongli

    2016-01-01

    Fluctuations of dopamine levels and upregulations of NR2B tyrosine phosphorylation in the striatum have been connected with levodopa (L-dopa)-induced dyskinesia (LID) in Parkinson's disease (PD). Repetitive transcranial magnetic stimulation (rTMS) is one of the noninvasive and potential method treating dyskinesia. Yet, the effect of rTMS on the above key pathological events remains unclear. In this study, we gave L-dopa treatment intraperitoneally for 22 days to 6-hydroxydopamine-lesioned PD rats to prepare LID rats model, and subsequently applied rTMS daily for 3 weeks to LID rats model. The effect of rTMS on abnormal involuntary movements (AIMs) was assessed. After ending the experiments, we further determined tyrosine hydroxylase (TH)-positive dopaminergic neurons number by immunohistochemistry, dopamine levels by HPLC, glial cell line-derived neurotrophic factor (GDNF) levels by ELISA, NR2B tyrosine phosphorylation and interactions of NR2B with Fyn by immunoblotting and immunoprecipitation. The results demonstrated that rTMS obviously attenuated AIMs scores, reduced the loss of nigral dopaminergic neurons and the fluctuations of striatal dopamine levels. Meanwhile, rTMS significantly increased the expression of GDNFwhich couldrestore the damage of dopaminergic neurons. Additionally, rTMS also reduced the levels of the NR2B tyrosine phosphorylation andits interactions with Fyn in the lesioned striatum of LID rats model. Thus, these data indicate that rTMS can provide benefit for the therapy of LID by improving the key biochemical deficits related to dyskinesia. PMID:27613848

  10. Repetitive transcranial magnetic stimulation (rTMS) improves behavioral and biochemical deficits in levodopa-induced dyskinetic rats model.

    PubMed

    Ba, Maowen; Kong, Min; Guan, Lina; Yi, Maoli; Zhang, Hongli

    2016-09-13

    Fluctuations of dopamine levels and upregulations of NR2B tyrosine phosphorylation in the striatum have been connected with levodopa (L-dopa)-induced dyskinesia (LID) in Parkinson's disease (PD). Repetitive transcranial magnetic stimulation (rTMS) is one of the noninvasive and potential method treating dyskinesia. Yet, the effect of rTMS on the above key pathological events remains unclear. In this study, we gave L-dopa treatment intraperitoneally for 22 days to 6-hydroxydopamine-lesioned PD rats to prepare LID rats model, and subsequently applied rTMS daily for 3 weeks to LID rats model. The effect of rTMS on abnormal involuntary movements (AIMs) was assessed. After ending the experiments, we further determined tyrosine hydroxylase (TH)-positive dopaminergic neurons number by immunohistochemistry, dopamine levels by HPLC, glial cell line-derived neurotrophic factor (GDNF) levels by ELISA, NR2B tyrosine phosphorylation and interactions of NR2B with Fyn by immunoblotting and immunoprecipitation. The results demonstrated that rTMS obviously attenuated AIMs scores, reduced the loss of nigral dopaminergic neurons and the fluctuations of striatal dopamine levels. Meanwhile, rTMS significantly increased the expression of GDNF, which couldrestore the damage of dopaminergic neurons. Additionally, rTMS also reduced the levels of the NR2B tyrosine phosphorylation andits interactions with Fyn in the lesioned striatum of LID rats model. Thus, these data indicate that rTMS can provide benefit for the therapy of LID by improving the key biochemical deficits related to dyskinesia.

  11. Primed low-frequency repetitive transcranial magnetic stimulation and constraint-induced movement therapy in pediatric hemiparesis: a randomized trial

    PubMed Central

    GILLICK, BERNADETTE T; KRACH, LINDA E; FEYMA, TIM; RICH, TONYA L; MOBERG, KELLI; THOMAS, WILLIAM; CASSIDY, JESSICA M; MENK, JEREMIAH; CAREY, JAMES R

    2013-01-01

    Aim The aim of this study was to determine the feasibility and efficacy of five treatments of 6Hz primed, low-frequency, repetitive transcranial magnetic stimulation (rTMS) combined with constraint-induced movement therapy (CIMT) to promote recovery of the paretic hand in children with congenital hemiparesis. Method Nineteen children with congenital hemiparesis aged between 8 and 17 years (10 males, nine females; mean age 10y 10mo, SD 2y 10mo; Manual Ability Classification Scale levels I-III) underwent five sessions of either real rTMS (n=10) or sham rTMS (n=9) alternated daily with CIMT. CIMT consisted of 13 days of continuous long-arm casting with five skin-check sessions. Each child received a total of 10 hours of one-to-one therapy. The primary outcome measure was the Assisting Hand Assessment (AHA) and the secondary outcome variables were the Canadian Occupational Performance Measure (COPM) and stereognosis. A Wilcoxon signed-rank sum test was used to analyze differences between pre- and post-test scores within the groups. Analysis of covariance was used to compute mean differences between groups adjusting for baseline. Fisher’s exact test was used to compare individual change in AHA raw scores with the smallest detectable difference (SDD) of 4 points. Results All participants receiving treatment finished the study. Improvement in AHA differed significantly between groups (p=0.007). No significant differences in the secondary outcome measures were found. Eight out of 10 participants in the rTMS/CIMT group showed improvement greater than the SDD, but only two out of nine in the sham rTMS/CIMT group showed such improvement (p=0.023). No serious adverse events occurred. Interpretation Primed, low-frequency rTMS combined with CIMT appears to be safe, feasible, and efficacious in pediatric hemiparesis. Larger clinical trials are now indicated. PMID:23962321

  12. Repetitive Transcranial Magnetic Stimulation (rTMS) in the Management of Alcohol Dependence and other Substance Abuse Disorders – Emerging Data and Clinical Relevance

    PubMed Central

    Sousa, Avinash De

    2013-01-01

    Repetitive transcranial magnetic stimulation (rTMS) has been used widely in various psychiatric disorders like depression and schizophrenia. There have been some reports of its usefulness in alcohol dependence and substance use disorders. The present paper reviews the studies done using rTMS in substance use disorders including alcohol and nicotine dependence. Various studies done have been reviewed including the proposed mechanisms of action are outlined with the future research needs and need for further clinical data PMID:25337357

  13. Imaging distributed and massed repetitions of natural scenes: Spontaneous retrieval and maintenance

    PubMed Central

    Bradley, Margaret M.; Costa, Vincent D.; Ferrari, Vera; Codispoti, Maurizio; Fitzsimmons, Jeffrey R.; Lang, Peter J.

    2015-01-01

    Repetitions that are distributed (spaced) across time prompt enhancement of a memory-related event-related potential, compared to when repetitions are massed (contiguous). Here, we employed fMRI to investigate neural enhancement and suppression effects during free viewing of natural scenes that were either novel or repeated four times with massed or distributed repetitions. Distributed repetition was uniquely associated with a repetition enhancement effect in a bilateral posterior parietal cluster that included the precuneus and posterior cingulate and which has previously been implicated in episodic memory retrieval. Unique to massed repetition, on the other hand, was enhancement in a right dorsolateral prefrontal cluster that has been implicated in short-term maintenance. Repetition suppression effects for both types of spacing were widespread in regions activated during novel picture processing. Taken together, the data are consistent with a hypothesis that distributed repetition prompts spontaneous retrieval of prior occurrences, whereas massed repetitions prompts short-term maintenance of the episodic representation, due to contiguous presentation. These processing differences may mediate the classic spacing effect in learning and memory. PMID:25504854

  14. Economic evaluation of resistant major depressive disorder treatment in Iranian population: a comparison between repetitive Transcranial Magnetic Stimulation with electroconvulsive

    PubMed Central

    Ghiasvand, Hesam; Moradi- Joo, Mohammad; Abolhassani, Nazanin; Ravaghi, Hamid; Raygani, Seyed Mansoor; Mohabbat-Bahar, Sahar

    2016-01-01

    Background: It is estimated that major depression disorders constitute 8.2% of years lived with disability (YLDs) globally. The repetitive Transcranial Magnetic Stimulation (rTMS) and Electroconvulsive Therapy (ECT) are two relative common interventions to treat major depressive disorders, especially for treatment resistant depression. In this study the cost- effectiveness and cost-utility of rTMS were compared with ECT in Iranian population suffering from major depressive disorder using a decision tree model. Methods: A decision tree model conducted to compare the cost-effectiveness ratio of rTMS with ECT in a health system prospective and 7 months’ time horizon. The outcome variables were: response rate, remission rate and quality-adjusted life-years (QALYs) of the rTMS and ECT as primary and secondary outcomes extracted from systematic reviews and randomized control trials. The costs were also calculated through a field study in one clinic and one hospital; the direct costs have only been considered. Results: The total cost for rTMS and ECTstrategieswere11015000Rials (373US$) and 11742700 Rials (397.7US$), respectively. Also the rTMS/ECT ratio of costs per improved patients was 1194410Rials (40.5 US$); the ratio for costs per QALYs utility was 21017139 Rials (711.72 US$). The incremental cost- effectiveness ratio of rTMS versus ECT was 1194410 Rials (40.44 US$) after treatment and maintenance courses. Conclusion: Given the current prevalence of depressive disorders in Iranian population, the ECT is more cost-effective than TMS. The sensitivity analysis showed that if the prevalence of major depressive disorders declines to below 5% or the costs of rTMS decrease (rTMS provided by public sector), then the rTMS becomes more cost-effective compared with ECT. However, efficacy of rTMS depends on the frequency of pulsed magnetic field, the location of rTMS on the head, the number of therapeutic sessions and the length of each session. PMID:27390700

  15. Two-photon laser-scanning microscopy for single and repetitive imaging of dorsal and lateral spinal white matter in vivo.

    PubMed

    Nadrigny, F; Le Meur, K; Steffens, H; Schomburg, E D; Safavi-Abbasi, S; Dibaj, P

    2017-02-28

    We developed appropriate surgical procedures for single and repetitive multi-photon imaging of spinal cord in vivo. By intravenous anesthesia, artificial ventilation and laminectomy, acute experiments were performed in the dorsal and lateral white matter. By volatile anesthesia and minimal-invasive surgery, chronic repetitive imaging up to 8 months were performed in the dorsal column through the window between two adjacent spines. Transgenic mouse technology enabled simultaneous imaging of labeled axons, astrocytes and microglia. Repetitive imaging showed positional shifts of microglia over time. These techniques serve for investigations of cellular dynamics and cell-cell interactions in intact and pathologically changed spinal tissue.

  16. Shaped magnetic field pulses by multi-coil repetitive transcranial magnetic stimulation (rTMS) differentially modulate anterior cingulate cortex responses and pain in volunteers and fibromyalgia patients

    PubMed Central

    2013-01-01

    Background Repetitive transcranial magnetic stimulation (rTMS) has shown promise in the alleviation of acute and chronic pain by altering the activity of cortical areas involved in pain sensation. However, current single-coil rTMS technology only allows for effects in surface cortical structures. The ability to affect activity in certain deep brain structures may however, allow for a better efficacy, safety, and tolerability. This study used PET imaging to determine whether a novel multi-coil rTMS would allow for preferential targeting of the dorsal anterior cingulate cortex (dACC), an area always activated with pain, and to provide preliminary evidence as to whether this targeted approach would allow for efficacious, safe, and tolerable analgesia both in a volunteer/acute pain model as well as in fibromyalgia chronic pain patients. Methods Part 1: Different coil configurations were tested in a placebo-controlled crossover design in volunteers (N = 16). Tonic pain was induced using a capsaicin/thermal pain model and functional brain imaging was performed by means of H215O positron emission tomography – computed tomography (PET/CT) scans. Differences in NRS pain ratings between TMS and sham treatment (NRSTMS-NRSplacebo) which were recorded each minute during the 10 minute PET scans. Part 2: 16 fibromyalgia patients were subjected to 20 multi-coil rTMS treatments over 4 weeks and effects on standard pain scales (Brief Pain Inventory, item 5, i.e. average pain NRS over the last 24 hours) were recorded. Results A single 30 minute session using one of 3 tested rTMS coil configurations operated at 1 Hz consistently produced robust reduction (mean 70% on NRS scale) in evoked pain in volunteers. In fibromyalgia patients, the 20 rTMS sessions also produced a significant pain inhibition (43% reduction in NRS pain over last 24 hours), but only when operated at 10 Hz. This degree of pain control was maintained for at least 4 weeks after the final session

  17. Effects of repetitive pulsing on multi-kHz planar laser-induced incandescence imaging in laminar and turbulent flames

    DOE PAGES

    Michael, James B.; Venkateswaran, Prabhakar; Shaddix, Christopher R.; ...

    2015-04-08

    Planar laser-induced incandescence (LII) imaging is reported at repetition rates up to 100 kHz using a burst-mode laser system to enable studies of soot formation dynamics in highly turbulent flames. Furthermore, to quantify the accuracy and uncertainty of relative soot volume fraction measurements, the temporal evolution of the LII field in laminar and turbulent flames is examined at various laser operating conditions. Under high-speed repetitive probing, it is found that LII signals are sensitive to changes in soot physical characteristics when operating at high laser fluences within the soot vaporization regime. For these laser conditions, strong planar LII signals aremore » observed at measurement rates up to 100 kHz but are primarily useful for qualitative tracking of soot structure dynamics. However, LII signals collected at lower fluences allow sequential planar measurements of the relative soot volume fraction with a sufficient signal-to-noise ratio at repetition rates of 10–50 kHz. Finally, guidelines for identifying and avoiding the onset of repetitive probe effects in the LII signals are discussed, along with other potential sources of measurement error and uncertainty.« less

  18. Effects of repetitive pulsing on multi-kHz planar laser-induced incandescence imaging in laminar and turbulent flames

    SciTech Connect

    Michael, James B.; Venkateswaran, Prabhakar; Shaddix, Christopher R.; Meyer, Terrence R.

    2015-04-08

    Planar laser-induced incandescence (LII) imaging is reported at repetition rates up to 100 kHz using a burst-mode laser system to enable studies of soot formation dynamics in highly turbulent flames. Furthermore, to quantify the accuracy and uncertainty of relative soot volume fraction measurements, the temporal evolution of the LII field in laminar and turbulent flames is examined at various laser operating conditions. Under high-speed repetitive probing, it is found that LII signals are sensitive to changes in soot physical characteristics when operating at high laser fluences within the soot vaporization regime. For these laser conditions, strong planar LII signals are observed at measurement rates up to 100 kHz but are primarily useful for qualitative tracking of soot structure dynamics. However, LII signals collected at lower fluences allow sequential planar measurements of the relative soot volume fraction with a sufficient signal-to-noise ratio at repetition rates of 10–50 kHz. Finally, guidelines for identifying and avoiding the onset of repetitive probe effects in the LII signals are discussed, along with other potential sources of measurement error and uncertainty.

  19. Effects of repetitive pulsing on multi-kHz planar laser-induced incandescence imaging in laminar and turbulent flames.

    PubMed

    Michael, James B; Venkateswaran, Prabhakar; Shaddix, Christopher R; Meyer, Terrence R

    2015-04-10

    Planar laser-induced incandescence (LII) imaging is reported at repetition rates up to 100 kHz using a burst-mode laser system to enable studies of soot formation dynamics in highly turbulent flames. To quantify the accuracy and uncertainty of relative soot volume fraction measurements, the temporal evolution of the LII field in laminar and turbulent flames is examined at various laser operating conditions. Under high-speed repetitive probing, it is found that LII signals are sensitive to changes in soot physical characteristics when operating at high laser fluences within the soot vaporization regime. For these laser conditions, strong planar LII signals are observed at measurement rates up to 100 kHz but are primarily useful for qualitative tracking of soot structure dynamics. However, LII signals collected at lower fluences allow sequential planar measurements of the relative soot volume fraction with a sufficient signal-to-noise ratio at repetition rates of 10-50 kHz. Guidelines for identifying and avoiding the onset of repetitive probe effects in the LII signals are discussed, along with other potential sources of measurement error and uncertainty.

  20. Dental caries imaging using hyperspectral stimulated Raman scattering microscopy

    NASA Astrophysics Data System (ADS)

    Wang, Zi; Zheng, Wei; Jian, Lin; Huang, Zhiwei

    2016-03-01

    We report the development of a polarization-resolved hyperspectral stimulated Raman scattering (SRS) imaging technique based on a picosecond (ps) laser-pumped optical parametric oscillator system for label-free imaging of dental caries. In our imaging system, hyperspectral SRS images (512×512 pixels) in both fingerprint region (800-1800 cm-1) and high-wavenumber region (2800-3600 cm-1) are acquired in minutes by scanning the wavelength of OPO output, which is a thousand times faster than conventional confocal micro Raman imaging. SRS spectra variations from normal enamel to caries obtained from the hyperspectral SRS images show the loss of phosphate and carbonate in the carious region. While polarization-resolved SRS images at 959 cm-1 demonstrate that the caries has higher depolarization ratio. Our results demonstrate that the polarization resolved-hyperspectral SRS imaging technique developed allows for rapid identification of the biochemical and structural changes of dental caries.

  1. Effects of low-frequency repetitive transcranial magnetic stimulation combined with intensive speech therapy on cerebral blood flow in post-stroke aphasia.

    PubMed

    Hara, Takatoshi; Abo, Masahiro; Kobayashi, Kentaro; Watanabe, Motoi; Kakuda, Wataru; Senoo, Atushi

    2015-10-01

    We provided an intervention to chronic post-stroke aphasic patients using low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) guided by a functional magnetic resonance imaging (fMRI) evaluation of language laterality, combined with intensive speech therapy (ST). We performed a single photon emission-computed tomography (SPECT) scan pre- and post-intervention and investigated the relationship between cerebral blood flow (CBF) and language function. Fifty right-handed chronic post-stroke aphasic patients were enrolled in the study. During their 11-day hospital admission, the patients received a 40-min session of 1-Hz LF-rTMS on the left or right hemisphere, according to language localization identified by the fMRI evaluation, and intensive ST daily for 10 days, except for Sunday. A SPECT scan and language evaluation by the Standard Language Test of Aphasia (SLTA) were performed at the time of admission and at 3 months following discharge. We calculated laterality indices (LIs) of regional CBF (rCBF) in 13 language-related Brodmann area (BA) regions of interest. In patients who received LF-rTMS to the intact right hemisphere (RH-LF-rTMS), the improvement in the total SLTA score was significantly correlated with the pre- and post-intervention change of LI (ΔLI) in BA44. In patients who received LF-rTMS to the lesional left hemisphere (LH-LF-rTMS), this association was not observed. Analyses of the SLTA subscales and rCBF ΔLI demonstrated that in the RH-LF-rTMS group, the SLTA Speaking subscale scores were significantly correlated with ΔLIs in BA11, 20, and 21, and the SLTA Writing subscale scores were significantly correlated with ΔLIs in BA6 and 39. Conversely, in the LH-LF-rTMS group, the SLTA Speaking subscale scores were correlated with ΔLI in BA10, and the SLTA Reading subscale scores were significantly correlated with ΔLIs in BA13, 20, 22, and 44. Our results suggest the possibility that fMRI-guided LF-rTMS combined with intensive ST may

  2. Benefits of Repetitive Transcranial Magnetic Stimulation (rTMS) for Spastic Subjects: Clinical, Functional, and Biomechanical Parameters for Lower Limb and Walking in Five Hemiparetic Patients

    PubMed Central

    Gross, Raphael; Leboeuf, Fabien; Desal, Hubert; Hamel, Olivier; Nguyen, Jean Paul; Pérot, Chantal; Buffenoir, Kévin

    2014-01-01

    Introduction. Spasticity is a disabling symptom resulting from reorganization of spinal reflexes no longer inhibited by supraspinal control. Several studies have demonstrated interest in repetitive transcranial magnetic stimulation in spastic patients. We conducted a prospective, randomized, double-blind crossover study on five spastic hemiparetic patients to determine whether this type of stimulation of the premotor cortex can provide a clinical benefit. Material and Methods. Two stimulation frequencies (1 Hz and 10 Hz) were tested versus placebo. Patients were assessed clinically, by quantitative analysis of walking and measurement of neuromechanical parameters (H and T reflexes, musculoarticular stiffness of the ankle). Results. No change was observed after placebo and 10 Hz protocols. Clinical parameters were not significantly modified after 1 Hz stimulation, apart from a tendency towards improved recruitment of antagonist muscles on the Fügl-Meyer scale. Only cadence and recurvatum were significantly modified on quantitative analysis of walking. Neuromechanical parameters were modified with significant decreases in Hmax⁡ /Mmax⁡ and T/Mmax⁡ ratios and stiffness indices 9 days or 31 days after initiation of TMS. Conclusion. This preliminary study supports the efficacy of low-frequency TMS to reduce reflex excitability and stiffness of ankle plantar flexors, while clinical signs of spasticity were not significantly modified. PMID:24883390

  3. [Functional imaging of deep brain stimulation in idiopathic Parkinson's disease].

    PubMed

    Hilker, R

    2010-10-01

    Functional brain imaging allows the effects of deep brain stimulation (DBS) on the living human brain to be investigated. In patients with advanced Parkinson's disease (PD), positron emission tomography (PET) studies were undertaken at rest as well as under motor, cognitive or behavioral activation. DBS leads to a reduction of abnormal PD-related network activity in the motor system, which partly correlates with the improvement of motor symptoms. The local increase of energy consumption within the direct target area suggests a predominant excitatory influence of the stimulation current on neuronal tissue. Remote effects of DBS of the subthalamic nucleus (STN) on frontal association cortices indicate an interference of stimulation energy with associative and limbic basal ganglia loops. Taken together, functional brain imaging provides very valuable data for advancement of the DBS technique in PD therapy.

  4. Toward proton MR spectroscopic imaging of stimulated brain function

    SciTech Connect

    Singh, M. . Dept. of Radiology)

    1992-08-01

    With the objective of complementing local cerebral metabolic studies of PET, and as a prelude to spectroscopic imaging, the authors have performed the first localized proton spectroscopic study of the stimulated human auditory cortex. Water suppressed localized spectroscopy (voxel size 3cm [times] 3cm [times] 3cm enclosing the auditory cortex, Te = 272ms, Tr = 3s) was performed on a 1.5T MRI/MRS system and spectra were acquired during stimulation with a 1kHz tone presented at 2Hz. Measurements were conducted for 30-40 min with a temporal resolution of 3.2 min (64 averages per time block). Results included in this paper from six subjects show a lactate peak which increases during stimulation compared to baseline values. These results suggest an increase in anaerobic glycolysis during stimulation and provide unique and valuable information that should complement glucose metabolism and flood flow studies of PET.

  5. Recovery of motor disability and spasticity in post-stroke after repetitive transcranial magnetic stimulation (rTMS).

    PubMed

    Málly, J; Dinya, E

    2008-07-01

    Lately it has been indicated that the stimulation of both sides of the motor cortices with different frequencies of rTMS can improve the behaviour of a paretic arm. We studied the effect of rTMS in severe cases of post-stroke after nearly 10 years. They had wide hemispheric lesion and their paresis had not changed for more than 5 years. The majority of patients could not move their fingers on the affected side. In our study we examined whether the active movement could be induced by rTMS even several years after stroke and which hemisphere (affected or unaffected) stimulated by rTMS would be the best location for attenuating the spasticity and for developing movement in the paretic arm. Sixty-four patients (more than 5 years after stroke in a stable state) were followed for 3 months. They were treated with rTMS with 1 Hz at 30% of 2.3T 100 stimuli per session twice a day for a week. The area to be stimulated was chosen according to the evoked movement by TMS in the paretic arm. That way, four groups were created and compared. In group A, where both hemispheres were stimulated (because of the single stimulation of TMS could induce movement from both sides of hemispheres) the spasticity decreased but the movement could not be influenced. A highly significant improvement in spasticity, in movement induction and in the behaviour of paresis was observed in group B, where before treatment, there was no evoked movement in the paretic arm from stimulating either hemispheres of the brain. For treatment we stimulated the unaffected hemisphere from where the intact arm is moved (ipsilateral to the paretic side). In both groups C (contralateral hemisphere to the paretic arm) and D (ipsilaterally evoked movement in the paretic arm), the spasticity decreased during the first week, but the movement of the paretic arm improved only in group C. It seems that spasticity can be modified by the stimulation either the affected or the unaffected hemisphere, but the induction of movement

  6. Intensity-dependent effects of repetitive anodal transcranial direct current stimulation on learning and memory in a rat model of Alzheimer's disease.

    PubMed

    Yu, Xuehong; Li, Yiyan; Wen, Huizhong; Zhang, Yinghui; Tian, Xuelong

    2015-09-01

    Single-session anodal transcranial direct current stimulation (tDCS) can improve the learning-memory function of patients with Alzheimer's disease (AD). After-effects of tDCS can be more significant if the stimulation is repeated regularly in a period. Here the behavioral and the histologic effects of the repetitive anodal tDCS on a rat model of AD were investigated. Sprague-Dawley rats were divided into 6 groups, the sham group, the β-amyloid (Aβ) group, the Aβ+20μA tDCS group, the Aβ+60μA tDCS group, the Aβ+100μA tDCS group and the Aβ+200μA tDCS group. Bilateral hippocampus of the rats in the Aβ group and the Aβ+tDCS groups were lesioned by Aβ1-40 to produce AD models. One day after drug injection, repetitive anodal tDCS (10 sessions in two weeks, 20min per session) was applied to the frontal cortex of the rats in the tDCS groups, while sham stimulation was applied to the Aβ group and the sham group. The spatial learning and memory capability of the rats were tested by Morris water maze. Bielschowsky's silver staining, Nissl's staining, choline acetyltransferase (ChAT) and glial-fibrillary-acidic protein (GFAP) immunohistochemistry of the hippocampus were conducted for histologic analysis. Results show in the Morris water maze task, rats in the Aβ+100μA and the Aβ+200μA tDCS groups had shorter escape latency and larger number of crossings on the platform. Significant histologic differences were observed in the Aβ+100μA and the Aβ+200μA tDCS groups compared to the Aβ group. The behavioral and the histological experiments indicate that the proposed repetitive anodal tDCS treatment can protect spatial learning and memory dysfunction of Aβ1-40-lesioned AD rats.

  7. Artistic creation as stimulated by superimposed versus separated visual images.

    PubMed

    Sobel, R S; Rothenberg, A

    1980-11-01

    An experiment was performed to examine the role of homospatial thinking in visual art. Each of 43 university-level art students produced three drawing stimulated by pairs of slides. Subjects were randomly assigned to view the pairs either superimposed on one another or separated on the screen. Drawings were independently judged by two internationally noted artists. As predicted, drawings containing an element from each component image intermingled were higher in creative potential when stimulated by the superimposed presentation; however, when sketches from either condition did not clearly contain images from both slides, the separated image presentation yielded the more creative result. Although results favor the hypothesis in part, the overall ambiguity of the data illustrates some of the difficulties in studying creative thought processes under experimental conditions.

  8. Bilateral responses of prefrontal and motor cortices to repetitive transcranial magnetic stimulation as measured by functional near infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Tian, Fenghua; Kozel, Frank Andrew; Dhamne, Sameer; McClintock, Shawn M.; Croarkin, Paul; Mapes, Kimberly; Husain, Mustafa M.; Liu, Hanli

    2009-02-01

    Simultaneously acquiring cortical functional Near Infrared Spectroscopy (fNIRS) during repeated Transcranial Magnetic Stimulation (rTMS) offers the possibility of directly investigating the effects of rTMS on brain regions without quantifiable behavioral changes. In this study, the left motor cortex and subsequently the left prefrontal cortex were stimulated at 1 Hz while fNIRS data was simultaneously acquired. Changes in hemodynamic signals were measured on both ipsilateral and contralateral sides. In each cortex, a significantly larger decrease in the concentration of oxygenated hemoglobin and a smaller increase in the concentration of deoxygenated hemoglobin during the stimulation periods were observed in both the motor and prefrontal cortices. The ipsilateral and contralateral changes showed high temporal consistency. Same experiment was repeated for each subject 2 or 3 days later. The hemodynamic responses associated with the stimulation showed good reproducibility in two sessions. To our knowledge, this is the first report of simultaneous fNIRS measurement of ipsilateral and contralateral changes of either the motor or prefrontal cortex during rTMS stimulation.

  9. Repetitive Arg-Gly-Asp peptide as a cell-stimulating agent on electrospun poly(ϵ-caprolactone) scaffold for tissue engineering.

    PubMed

    Chaisri, Pacharaporn; Chingsungnoen, Artit; Siri, Sineenat

    2013-11-01

    Electrospun scaffolds derived from poly(ϵ-caprolactone) (PCL), a well known biodegradable material, have an architecture that is suitable for hosting cells. However, their biomedical applications are restricted because these scaffolds lack the bioactivity necessary to stimulate cell responses. In this work, a repetitive Arg-Gly-Asp (rRGD) peptide was produced as a cell-stimulating agent to provide the PCL scaffold with bioactivity. DNA encoding rRGD was amplified by polymerase chain reaction using overlap primers without a DNA template, and cloned into a protein expression vector to produce a His-tag fusion peptide. In an in vitro cell adhesion assay, the purified rRGD peptide, comprising 30 RGD repeats, promoted a 1.5-fold greater cell adhesion than the commercial tripeptide RGD. The rRGD peptide was immobilized onto an electrospun PCL scaffold that had been pretreated with argon plasma and graft-polymerized with acrylic acid. Fourier transform infrared (FTIR) analysis indicated that covalently linked rRGD peptide was present on the scaffold. The PCL scaffold with immobilized rRGD showed significantly changed hydrophilic properties and an enhanced adhesion and proliferation of mouse fibroblast cells by 2.3- and 2.9-fold, respectively, compared to the PCL scaffold alone. Through its ability to promote cell adhesion and proliferation, the rRGD peptide has great potential as a stimulant for improving the suboptimal cell-matrix interaction of polymeric scaffolds for tissue engineering applications.

  10. A pilot double-blind sham-controlled trial of repetitive transcranial magnetic stimulation for patients with refractory schizophrenia treated with clozapine.

    PubMed

    de Jesus, Danilo Rocha; Gil, Alexei; Barbosa, Leonardo; Lobato, Maria Inês; Magalhães, Pedro Vieira da Silva; Favalli, Gabriela Pereira de Souza; Marcolin, Marco Antonio; Daskalakis, Zafiris Jeffrey; Belmonte-de-Abreu, Paulo da Silva

    2011-07-30

    Schizophrenia is a complex and heterogeneous psychiatric disorder. Auditory verbal hallucinations occur in 50-70% of patients with schizophrenia and are associated with significant distress, decreased quality of life and impaired social functioning. This study aimed to investigate the effects of active compared with sham 1-Hz repetitive transcranial magnetic stimulation (rTMS) applied to the left temporal-parietal cortex in patients with schizophrenia treated with clozapine. Symptom dimensions that were evaluated included general psychopathology, severity of auditory hallucinations, quality of life and functionality. Seventeen right-handed patients with refractory schizophrenia experiencing auditory verbal hallucinations and treated with clozapine were randomly allocated to receive either active rTMS or sham stimulation. A total of 384 min of rTMS was administered over 20 days using a double-masked, sham-controlled, parallel design. There was a significant reduction in Brief Psychiatric Rating Scale (BPRS) scores in the active group compared with the sham group. There was no significant difference between active and sham rTMS on Quality of Life Scale (QLS), Auditory Hallucinations Rating Scale (AHRS), Clinical Global Impressions (CGI) and functional assessment staging (FAST) scores. Compared with sham stimulation, active rTMS of the left temporoparietal cortex in clozapine-treated patients showed a positive effect on general psychopathology. However, there was no effect on refractory auditory hallucinations. Further studies with larger sample sizes are needed to confirm these findings.

  11. The efficacy of cerebellar vermal deep high frequency (theta range) repetitive transcranial magnetic stimulation (rTMS) in schizophrenia: A randomized rater blind-sham controlled study.

    PubMed

    Garg, Shobit; Sinha, Vinod Kumar; Tikka, Sai Krishna; Mishra, Preeti; Goyal, Nishant

    2016-09-30

    Repetitive transcranial magnetic stimulation (rTMS) is a promising therapeutic for schizophrenia. Treatment effects of rTMS have been variable across different symptom clusters, with negative symptoms showing better response, followed by auditory hallucinations. Cerebellum, especially vermis and its abnormalities (both structural and functional) have been implicated in cognitive, affective and positive symptoms of schizophrenia. rTMS to this alternate site has been suggested as a novel target for treating patients with this disorder. Hypothesizing cerebellar vermal magnetic stimulation as an adjunct to treat schizophrenia psychopathology, we conducted a double blind randomized sham controlled rTMS study. In this study, forty patients were randomly allocated (using block randomization method) to active high frequency (theta patterned) rTMS (n=20) and sham (n=20) groups. They received 10 sessions over 2 weeks. The Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS) scores were assessed at baseline, after last session and at 4 weeks (2 weeks post-rTMS). We found a significantly greater improvement in the group receiving active rTMS sessions, compared to the sham group on negative symptoms, and depressive symptoms. We conclude that cerebellar stimulation can be used as an effective adjunct to treat negative and affective symptoms.

  12. Application of a high-repetition-rate laser diagnostic system for single-cycle-resolved imaging in internal combustion engines.

    PubMed

    Hult, Johan; Richter, Mattias; Nygren, Jenny; Aldén, Marcus; Hultqvist, Anders; Christensen, Magnus; Johansson, Bengt

    2002-08-20

    High-repetition-rate laser-induced fluorescence measurements of fuel and OH concentrations in internal combustion engines are demonstrated. Series of as many as eight fluorescence images, with a temporal resolution ranging from 10 micros to 1 ms, are acquired within one engine cycle. A multiple-laser system in combination with a multiple-CCD camera is used for cycle-resolved imaging in spark-ignition, direct-injection stratified-charge, and homogeneous-charge compression-ignition engines. The recorded data reveal unique information on cycle-to-cycle variations in fuel transport and combustion. Moreover, the imaging system in combination with a scanning mirror is used to perform instantaneous three-dimensional fuel-concentration measurements.

  13. Repeated BOLD-fMRI Imaging of Deep Brain Stimulation Responses in Rats

    PubMed Central

    Chao, Tzu-Hao Harry; Chen, Jyh-Horng; Yen, Chen-Tung

    2014-01-01

    Functional magnetic resonance imaging (fMRI) provides a picture of the global spatial activation pattern of the brain. Interest is growing regarding the application of fMRI to rodent models to investigate adult brain plasticity. To date, most rodent studies used an electrical forepaw stimulation model to acquire fMRI data, with α-chloralose as the anesthetic. However, α-chloralose is harmful to animals, and not suitable for longitudinal studies. Moreover, peripheral stimulation models enable only a limited number of brain regions to be studied. Processing between peripheral regions and the brain is multisynaptic, and renders interpretation difficult and uncertain. In the present study, we combined the medetomidine-based fMRI protocol (a noninvasive rodent fMRI protocol) with chronic implantation of an MRI-compatible stimulation electrode in the ventroposterior (VP) thalamus to repetitively sample thalamocortical responses in the rat brain. Using this model, we scanned the forebrain responses evoked by the VP stimulation repeatedly of individual rats over 1 week. Cortical BOLD responses were compared between the 2 profiles obtained at day1 and day8. We discovered reproducible frequency- and amplitude-dependent BOLD responses in the ipsilateral somatosensory cortex (S1). The S1 BOLD responses during the 2 sessions were conserved in maximal response amplitude, area size (size ratio from 0.88 to 0.91), and location (overlap ratio from 0.61 to 0.67). The present study provides a long-term chronic brain stimulation protocol for studying the plasticity of specific neural circuits in the rodent brain by BOLD-fMRI. PMID:24825464

  14. Extracellular stimulation of mammalian neurons through repetitive activation of Na+ channels by weak capacitive currents on a silicon chip.

    PubMed

    Schoen, Ingmar; Fromherz, Peter

    2008-07-01

    Reliable extracellular stimulation of neuronal activity is the prerequisite for electrical interfacing of cultured networks and brain slices, as well as for neural implants. Safe stimulation must be achieved without damage to the cells. With respect to a future application of highly integrated semiconductor chips, we present an electrophysiological study of capacitive stimulation of mammalian cells in the geometry of adhesion on an insulated titanium dioxide/silicon electrode. We used HEK293 cells with overexpressed Na(V)1.4 channels and neurons from rat hippocampus. Weak biphasic stimuli of falling and rising voltage ramps were applied in the absence of Faradaic current and electroporation. We recorded the response of the intra- and extracellular voltage and evaluated the concomitant polarization of the attached and free cell membranes. Falling ramps efficiently depolarized the central area of the attached membrane. A transient sodium inward current was activated that gave rise to a weak depolarization of the cell on the order of 1 mV. The depolarization could be enhanced step by step by a train of biphasic stimuli until self-excitation of sodium channels set in. We applied the same protocol to cultured rat neurons and found that pulse trains of weak capacitive stimuli were able to elicit action potentials. Our results provide a basis for safe extracellular stimulation not only for cultured neurons on insulated semiconductor electrodes, but also more generally for metal electrodes in cell culture and brain tissue.

  15. Repetitive transcranial magnetic stimulation causes a short-term increase in the duration of the cortical silent period in patients with Parkinson's disease.

    PubMed

    Siebner, H R; Mentschel, C; Auer, C; Lehner, C; Conrad, B

    2000-04-28

    In ten patients with Parkinson's disease (PD) and ten age-matched healthy controls, we applied 15 30-s trains of subthreshold 5-Hz repetitive transcranial magnetic stimulation (rTMS) over the primary motor hand area. Ten minutes after rTMS, PD patients showed a significant prolongation of the transcranially evoked silent period (SP) in the contralateral first dorsal interosseus muscle, whereas the SP remained unchanged in healthy subjects. Since the duration of the transcranially evoked SP is a well-established measure of intracortical inhibition, this finding demonstrates that rTMS is capable of inducing a short-term increase in intracortical inhibition in PD. The lack of a prolongation of the SP in healthy controls suggests that PD patients may be particularly susceptible to modulatory effects of rTMS on motocortical inhibition.

  16. Hyperspectral imaging with stimulated Raman scattering by chirped femtosecond lasers.

    PubMed

    Fu, Dan; Holtom, Gary; Freudiger, Christian; Zhang, Xu; Xie, Xiaoliang Sunney

    2013-04-25

    Raman microscopy is a quantitative, label-free, and noninvasive optical imaging technique for studying inhomogeneous systems. However, the feebleness of Raman scattering significantly limits the use of Raman microscopy to low time resolutions and primarily static samples. Recent developments in narrowband stimulated Raman scattering (SRS) microscopy have significantly increased the acquisition speed of Raman based label-free imaging by a few orders of magnitude, at the expense of reduced spectroscopic information. On the basis of a spectral focusing approach, we present a fast SRS hyperspectral imaging system using chirped femtosecond lasers to achieve rapid Raman spectra acquisition while retaining the full speed and image quality of narrowband SRS imaging. We demonstrate that quantitative concentration determination of cholesterol in the presence of interfering chemical species can be achieved with sensitivity down to 4 mM. For imaging purposes, hyperspectral imaging data in the C-H stretching region is obtained within a minute. We show that mammalian cell SRS hyperspectral imaging reveals the spatially inhomogeneous distribution of saturated lipids, unsaturated lipids, cholesterol, and protein. The combination of fast spectroscopy and label-free chemical imaging will enable new applications in studying biological systems and material systems.

  17. Repetitive Transcranial Direct Current Stimulation Induced Excitability Changes of Primary Visual Cortex and Visual Learning Effects-A Pilot Study.

    PubMed

    Sczesny-Kaiser, Matthias; Beckhaus, Katharina; Dinse, Hubert R; Schwenkreis, Peter; Tegenthoff, Martin; Höffken, Oliver

    2016-01-01

    Studies on noninvasive motor cortex stimulation and motor learning demonstrated cortical excitability as a marker for a learning effect. Transcranial direct current stimulation (tDCS) is a non-invasive tool to modulate cortical excitability. It is as yet unknown how tDCS-induced excitability changes and perceptual learning in visual cortex correlate. Our study aimed to examine the influence of tDCS on visual perceptual learning in healthy humans. Additionally, we measured excitability in primary visual cortex (V1). We hypothesized that anodal tDCS would improve and cathodal tDCS would have minor or no effects on visual learning. Anodal, cathodal or sham tDCS were applied over V1 in a randomized, double-blinded design over four consecutive days (n = 30). During 20 min of tDCS, subjects had to learn a visual orientation-discrimination task (ODT). Excitability parameters were measured by analyzing paired-stimulation behavior of visual-evoked potentials (ps-VEP) and by measuring phosphene thresholds (PTs) before and after the stimulation period of 4 days. Compared with sham-tDCS, anodal tDCS led to an improvement of visual discrimination learning (p < 0.003). We found reduced PTs and increased ps-VEP ratios indicating increased cortical excitability after anodal tDCS (PT: p = 0.002, ps-VEP: p = 0.003). Correlation analysis within the anodal tDCS group revealed no significant correlation between PTs and learning effect. For cathodal tDCS, no significant effects on learning or on excitability could be seen. Our results showed that anodal tDCS over V1 resulted in improved visual perceptual learning and increased cortical excitability. tDCS is a promising tool to alter V1 excitability and, hence, perceptual visual learning.

  18. Repetitive Transcranial Direct Current Stimulation Induced Excitability Changes of Primary Visual Cortex and Visual Learning Effects—A Pilot Study

    PubMed Central

    Sczesny-Kaiser, Matthias; Beckhaus, Katharina; Dinse, Hubert R.; Schwenkreis, Peter; Tegenthoff, Martin; Höffken, Oliver

    2016-01-01

    Studies on noninvasive motor cortex stimulation and motor learning demonstrated cortical excitability as a marker for a learning effect. Transcranial direct current stimulation (tDCS) is a non-invasive tool to modulate cortical excitability. It is as yet unknown how tDCS-induced excitability changes and perceptual learning in visual cortex correlate. Our study aimed to examine the influence of tDCS on visual perceptual learning in healthy humans. Additionally, we measured excitability in primary visual cortex (V1). We hypothesized that anodal tDCS would improve and cathodal tDCS would have minor or no effects on visual learning. Anodal, cathodal or sham tDCS were applied over V1 in a randomized, double-blinded design over four consecutive days (n = 30). During 20 min of tDCS, subjects had to learn a visual orientation-discrimination task (ODT). Excitability parameters were measured by analyzing paired-stimulation behavior of visual-evoked potentials (ps-VEP) and by measuring phosphene thresholds (PTs) before and after the stimulation period of 4 days. Compared with sham-tDCS, anodal tDCS led to an improvement of visual discrimination learning (p < 0.003). We found reduced PTs and increased ps-VEP ratios indicating increased cortical excitability after anodal tDCS (PT: p = 0.002, ps-VEP: p = 0.003). Correlation analysis within the anodal tDCS group revealed no significant correlation between PTs and learning effect. For cathodal tDCS, no significant effects on learning or on excitability could be seen. Our results showed that anodal tDCS over V1 resulted in improved visual perceptual learning and increased cortical excitability. tDCS is a promising tool to alter V1 excitability and, hence, perceptual visual learning. PMID:27375452

  19. Task Type Affects Location of Language-Positive Cortical Regions by Repetitive Navigated Transcranial Magnetic Stimulation Mapping

    PubMed Central

    Hauck, Theresa; Tanigawa, Noriko; Probst, Monika; Wohlschlaeger, Afra; Ille, Sebastian; Sollmann, Nico; Maurer, Stefanie; Zimmer, Claus; Ringel, Florian; Meyer, Bernhard; Krieg, Sandro M.

    2015-01-01

    Objectives Recent repetitive TMS (rTMS) mapping protocols for language mapping revealed deficits of this method, mainly in posterior brain regions. Therefore this study analyzed the impact of different language tasks on the localization of language-positive brain regions and compared their effectiveness, especially with regard to posterior brain regions. Methods Nineteen healthy, right-handed subjects performed object naming, pseudoword reading, verb generation, and action naming during rTMS language mapping of the left hemisphere. Synchronically, 5 Hz/10 pulses were applied with a 0 ms delay Results The object naming task evoked the highest error rate (14%), followed by verb generation (13%) and action naming (11%). The latter revealed more errors in posterior than in anterior areas. Pseudoword reading barely generated errors, except for phonological paraphasias. Conclusions In general, among the evaluated language tasks, object naming is the most discriminative task to detect language-positive regions via rTMS. However, other tasks might be used for more specific questions. PMID:25928744

  20. Effect of the stimulus frequency and pulse number of repetitive transcranial magnetic stimulation on the inter-reversal time of perceptual reversal on the right superior parietal lobule

    NASA Astrophysics Data System (ADS)

    Nojima, Kazuhisa; Ge, Sheng; Katayama, Yoshinori; Ueno, Shoogo; Iramina, Keiji

    2010-05-01

    The aim of this study is to investigate the effect of the stimulus frequency and pulses number of repetitive transcranial magnetic stimulation (rTMS) on the inter-reversal time (IRT) of perceptual reversal on the right superior parietal lobule (SPL). The spinning wheel illusion was used as the ambiguous figures stimulation in this study. To investigate the rTMS effect over the right SPL during perceptual reversal, 0.25 Hz 60 pulse, 1 Hz 60 pulse, 0.5 Hz 120 pulse, 1 Hz 120 pulse, and 1 Hz 240 pulse biphasic rTMS at 90% of resting motor threshold was applied over the right SPL and the right posterior temporal lobe (PTL), respectively. As a control, a no TMS was also conducted. It was found that rTMS on 0.25 Hz 60 pulse and 1 Hz 60 pulse applied over the right SPL caused shorter IRT. In contrast, it was found that rTMS on 1 Hz 240-pulse applied over the right SPL caused longer IRT. On the other hand, there is no significant difference between IRTs when the rTMS on 0.5 Hz 120 pulse and 1 Hz 120 pulse were applied over the right SPL. Therefore, the applying of rTMS over the right SPL suggests that the IRT of perceptual reversal is effected by the rTMS conditions such as the stimulus frequency and the number of pulses.

  1. A fronto-parietal network is mediating improvement of motor function related to repetitive peripheral magnetic stimulation: A PET-H2O15 study.

    PubMed

    Struppler, Albrecht; Binkofski, Ferdinand; Angerer, Bernhard; Bernhardt, Michael; Spiegel, Sabine; Drzezga, Alexander; Bartenstein, Peter

    2007-01-01

    Repetitive peripheral magnetic stimulation (RPMS) is a focused and painless stimulation method, in which muscle contractions are elicited by depolarization of the terminal motor branches. Clinical-experimental investigations on different disorders of sensorimotor integration in the last decade have shown that RPMS can be used for the rehabilitation of motor functions after stroke. It is supposed that this therapeutic effect is based on the RPMS-induced proprioceptive inflow to the CNS. To analyze the conditioning effects of RPMS on reorganization of the motor system on cortical level positron emission tomography (PET) is used. Regional cerebral blood flow (rCBF) has been measured using H(2)O(15)-PET in eight patients with arm paresis following focal cerebral ischemic infarction before and after treatment using RPMS on upper arm flexor muscles. Behavioral measures showed a significant improvement of kinematics of finger movements and a reduction of spasticity in the affected arm following RPMS treatment. The recovery was associated with significant increase of neural activation within the superior posterior parietal lobe and the premotor cortex (PM) areas. The increase of activation of the parieto-premotor network following RPMS treatment indicates a significant conditioning effect of RPMS on the cortical level. These results emphasize the positive therapeutic effect of RPMS and describe the physiological bases of its function on the central level.

  2. Ipsilesional High Frequency Repetitive Transcranial Magnetic Stimulation Add-On Therapy Improved Diffusion Parameters of Stroke Patients with Motor Dysfunction: A Preliminary DTI Study

    PubMed Central

    Guo, Zhiwei; Jin, Yu; Peng, Haitao; Xing, Guoqiang; Liao, Xiang; Wang, Yunfeng; Chen, Huaping; He, Bin; McClure, Morgan A.

    2016-01-01

    Purpose. The aim of this study was to evaluate the effects of high frequency repetitive transcranial magnetic stimulation (HF-rTMS) on stroke patients with motor dysfunction and to investigate the underlying neural mechanism. Methods. Fifteen stroke patients were assigned to the rTMS treatment (RT) group and conventional treatment (CT) group. Patients in the RT received 10 Hz rTMS stimulation on the ipsilesional primary motor cortex for 10 days plus conventional treatment of CT, which consisted of acupuncture and antiplatelet aggregation medication. Difference in fractional anisotropy (FA) between pretreatment and posttreatment and between two groups was determined. Correlations between FA values and neurological assessments were also calculated. Results. Both groups significantly improved the neurological function after treatment. rTMS-treated patients showed better improvement in Fugl-Meyer Assessment (FMA) score and increased FA value in motor-related white matter and gray matter cortices compared with CT-treated patients and pretreatment status. Besides, the increased FA value in the ipsilesional posterior limb of the internal capsule in RT group was significantly correlated with the improved FMA score. Significance. HF-rTMS could be a supplement therapy to CT in improving motor recovery in patients with stroke. And this benefit effect may be achieved through modulating the ipsilesional corticospinal tracts and motor-related gray matter cortices. PMID:27840742

  3. In Vitro Assessment Reveals Parameters-Dependent Modulation on Excitability and Functional Connectivity of Cerebellar Slice by Repetitive Transcranial Magnetic Stimulation

    PubMed Central

    Tang, Rongyu; Zhang, Guanghao; Weng, Xiechuan; Han, Yao; Lang, Yiran; Zhao, Yuwei; Zhao, Xiaobo; Wang, Kun; Lin, Qiuxia; Wang, Changyong

    2016-01-01

    Repetitive transcranial magnetic stimulation (rTMS) is an increasingly common technique used to selectively modify neural excitability and plasticity. There is still controversy concerning the cortical response to rTMS of different frequencies. In this study, a novel in vitro paradigm utilizing the Multi-Electrodes Array (MEA) system and acute cerebellar slicing is described. In a controllable environment that comprises perfusion, incubation, recording and stimulation modules, the spontaneous single-unit spiking activity in response to rTMS of different frequencies and powers was directly measured and analyzed. Investigation using this in vitro paradigm revealed frequency-dependent modulation upon the excitability and functional connectivity of cerebellar slices. The 1-Hz rTMS sessions induced short-term inhibition or lagged inhibition, whereas 20-Hz sessions induced excitation. The level of modulation is influenced by the value of power. However the long-term response fluctuated without persistent direction. The choice of evaluation method may also interfere with the interpretation of modulation direction. Furthermore, both short-term and long-term functional connectivity was strengthened by 1-Hz rTMS and weakened by 20-Hz rTMS. PMID:27000527

  4. High-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) Improves Functional Recovery by Enhancing Neurogenesis and Activating BDNF/TrkB Signaling in Ischemic Rats.

    PubMed

    Luo, Jing; Zheng, Haiqing; Zhang, Liying; Zhang, Qingjie; Li, Lili; Pei, Zhong; Hu, Xiquan

    2017-02-20

    Repetitive transcranial magnetic stimulation (rTMS) has rapidly become an attractive therapeutic approach for stroke. However, the mechanisms underlying this remain elusive. This study aimed to investigate whether high-frequency rTMS improves functional recovery mediated by enhanced neurogenesis and activation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) pathway and to compare the effect of conventional 20 Hz rTMS and intermittent theta burst stimulation (iTBS) on ischemic rats. Rats after rTMS were sacrificed seven and 14 days after middle cerebral artery occlusion (MCAO), following evaluation of neurological function. Neurogenesis was measured using specific markers: Ki67, Nestin, doublecortin (DCX), NeuN and glial fibrillary acidic protein (GFAP), and the expression levels of BDNF were visualized by Western blotting and RT-PCR analysis. Both high-frequency rTMS methods significantly improved neurological function and reduced infarct volume. Moreover, 20 Hz rTMS and iTBS significantly promoted neurogenesis, shown by an increase of Ki67/DCX, Ki67/Nestin, and Ki67/NeuN-positive cells in the peri-infarct striatum. These beneficial effects were accompanied by elevated protein levels of BDNF and phosphorylated-TrkB. In conclusion, high-frequency rTMS improves functional recovery possibly by enhancing neurogenesis and activating BDNF/TrkB signaling pathway and conventional 20 Hz rTMS is better than iTBS at enhancing neurogenesis in ischemic rats.

  5. Meta-analysis of the effects of repetitive transcranial magnetic stimulation (rTMS) on negative and positive symptoms in schizophrenia

    PubMed Central

    Freitas, Catarina; Fregni, Felipe; Pascual-Leone, Alvaro

    2009-01-01

    Background A growing body of evidence suggests that repetitive transcranial magnetic stimulation (rTMS) can alleviate negative and positive symptoms of refractory schizophrenia. However, trials to date have been small and results are mixed. Methods We performed meta-analyses of all prospective studies of the therapeutic application of rTMS in refractory schizophrenia assessing the effects of high-frequency rTMS to the left dorsolateral prefrontal cortex (DLPFC) to treat negative symptoms, and low-frequency rTMS to the left temporo-parietal cortex (TPC) to treat auditory hallucinations (AH) and overall positive symptoms. Results When analyzing controlled (active arms) and uncontrolled studies together, the effect sizes showed significant and moderate effects of rTMS on negative and positive symptoms (based on PANSS-N or SANS, and PANSS-P or SAPS, respectively). However, the analysis for the sham-controlled studies revealed a small non-significant effect size for negative (0.27, p=0.417) and for positive symptoms (0.17, p=0.129). When specifically analyzing AH (based on AHRS, HCS or SAH), the effect size for the sham-controlled studies was large and significant (1.04; p=0.002). Conclusions These meta-analyses support the need for further controlled, larger trials to assess the clinical efficacy of rTMS on negative and positive symptoms of schizophrenia, while suggesting the need for exploration for alternative stimulation protocols. PMID:19138833

  6. High-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) Improves Functional Recovery by Enhancing Neurogenesis and Activating BDNF/TrkB Signaling in Ischemic Rats

    PubMed Central

    Luo, Jing; Zheng, Haiqing; Zhang, Liying; Zhang, Qingjie; Li, Lili; Pei, Zhong; Hu, Xiquan

    2017-01-01

    Repetitive transcranial magnetic stimulation (rTMS) has rapidly become an attractive therapeutic approach for stroke. However, the mechanisms underlying this remain elusive. This study aimed to investigate whether high-frequency rTMS improves functional recovery mediated by enhanced neurogenesis and activation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) pathway and to compare the effect of conventional 20 Hz rTMS and intermittent theta burst stimulation (iTBS) on ischemic rats. Rats after rTMS were sacrificed seven and 14 days after middle cerebral artery occlusion (MCAO), following evaluation of neurological function. Neurogenesis was measured using specific markers: Ki67, Nestin, doublecortin (DCX), NeuN and glial fibrillary acidic protein (GFAP), and the expression levels of BDNF were visualized by Western blotting and RT-PCR analysis. Both high-frequency rTMS methods significantly improved neurological function and reduced infarct volume. Moreover, 20 Hz rTMS and iTBS significantly promoted neurogenesis, shown by an increase of Ki67/DCX, Ki67/Nestin, and Ki67/NeuN-positive cells in the peri-infarct striatum. These beneficial effects were accompanied by elevated protein levels of BDNF and phosphorylated-TrkB. In conclusion, high-frequency rTMS improves functional recovery possibly by enhancing neurogenesis and activating BDNF/TrkB signaling pathway and conventional 20 Hz rTMS is better than iTBS at enhancing neurogenesis in ischemic rats. PMID:28230741

  7. Monitoring Cortical Excitability during Repetitive Transcranial Magnetic Stimulation in Children with ADHD: A Single-Blind, Sham-Controlled TMS-EEG Study

    PubMed Central

    Helfrich, Christian; Pierau, Simone S.; Freitag, Christine M.; Roeper, Jochen; Ziemann, Ulf; Bender, Stephan

    2012-01-01

    Background Repetitive transcranial magnetic stimulation (rTMS) allows non-invasive stimulation of the human brain. However, no suitable marker has yet been established to monitor the immediate rTMS effects on cortical areas in children. Objective TMS-evoked EEG potentials (TEPs) could present a well-suited marker for real-time monitoring. Monitoring is particularly important in children where only few data about rTMS effects and safety are currently available. Methods In a single-blind sham-controlled study, twenty-five school-aged children with ADHD received subthreshold 1 Hz-rTMS to the primary motor cortex. The TMS-evoked N100 was measured by 64-channel-EEG pre, during and post rTMS, and compared to sham stimulation as an intraindividual control condition. Results TMS-evoked N100 amplitude decreased during 1 Hz-rTMS and, at the group level, reached a stable plateau after approximately 500 pulses. N100 amplitude to supra-threshold single pulses post rTMS confirmed the amplitude reduction in comparison to the pre-rTMS level while sham stimulation had no influence. EEG source analysis indicated that the TMS-evoked N100 change reflected rTMS effects in the stimulated motor cortex. Amplitude changes in TMS-evoked N100 and MEPs (pre versus post 1 Hz-rTMS) correlated significantly, but this correlation was also found for pre versus post sham stimulation. Conclusion The TMS-evoked N100 represents a promising candidate marker to monitor rTMS effects on cortical excitability in children with ADHD. TMS-evoked N100 can be employed to monitor real-time effects of TMS for subthreshold intensities. Though TMS-evoked N100 was a more sensitive parameter for rTMS-specific changes than MEPs in our sample, further studies are necessary to demonstrate whether clinical rTMS effects can be predicted from rTMS-induced changes in TMS-evoked N100 amplitude and to clarify the relationship between rTMS-induced changes in TMS-evoked N100 and MEP amplitudes. The TMS-evoked N100 amplitude

  8. Recovery from Object Substitution Masking Induced by Transient Suppression of Visual Motion Processing: A Repetitive Transcranial Magnetic Stimulation Study

    ERIC Educational Resources Information Center

    Hirose, Nobuyuki; Kihara, Ken; Mima, Tatsuya; Ueki, Yoshino; Fukuyama, Hidenao; Osaka, Naoyuki

    2007-01-01

    Object substitution masking is a form of visual backward masking in which a briefly presented target is rendered invisible by a lingering mask that is too sparse to produce lower image-level interference. Recent studies suggested the importance of an updating process in a higher object-level representation, which should rely on the processing of…

  9. One hertz repetitive transcranial magnetic stimulation over dorsal premotor cortex enhances offline motor memory consolidation for sequence-specific implicit learning.

    PubMed

    Meehan, S K; Zabukovec, J R; Dao, E; Cheung, K L; Linsdell, M A; Boyd, L A

    2013-10-01

    Consolidation of motor memories associated with skilled practice can occur both online, concurrent with practice, and offline, after practice has ended. The current study investigated the role of dorsal premotor cortex (PMd) in early offline motor memory consolidation of implicit sequence-specific learning. Thirty-three participants were assigned to one of three groups of repetitive transcranial magnetic stimulation (rTMS) over left PMd (5 Hz, 1 Hz or control) immediately following practice of a novel continuous tracking task. There was no additional practice following rTMS. This procedure was repeated for 4 days. The continuous tracking task contained a repeated sequence that could be learned implicitly and random sequences that could not. On a separate fifth day, a retention test was performed to assess implicit sequence-specific motor learning of the task. Tracking error was decreased for the group who received 1 Hz rTMS over the PMd during the early consolidation period immediately following practice compared with control or 5 Hz rTMS. Enhanced sequence-specific learning with 1 Hz rTMS following practice was due to greater offline consolidation, not differences in online learning between the groups within practice days. A follow-up experiment revealed that stimulation of PMd following practice did not differentially change motor cortical excitability, suggesting that changes in offline consolidation can be largely attributed to stimulation-induced changes in PMd. These findings support a differential role for the PMd in support of online and offline sequence-specific learning of a visuomotor task and offer converging evidence for competing memory systems.

  10. Safety and efficacy of repetitive transcranial magnetic stimulation in the treatment of depression: a critical appraisal of the last 10 years.

    PubMed

    Rachid, F; Bertschy, G

    2006-01-01

    Depression is a common and debilitating illness, for which alternative treatments are urgently needed. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive and relatively painless experimental technique of altering brain physiology. The authors critically review the evidence for the efficacy, safety and tolerability of rTMS in the treatment of depression based on published data over the last decade. They also discuss studies which have examined relevant clinical, demographic, methodological, and technical parameters that might be implicated in optimizing the antidepressant efficacy of this technique. rTMS depression trials conducted through early 2006 are included in this review, which focuses mainly on the results of published sham-controlled studies, literature reviews and meta-analyses. Trials published so far have been characterized by the use of a great variety of stimulation parameters, study designs, questionable sham controls, small sample sizes and heterogeneously depressed populations, all of which have made comparisons between studies difficult. Meta-analyses of 2-week rTMS sham-controlled studies support, for the most part, the antidepressant effects of rTMS which are statistically superior to sham. However, the degree of clinical improvement remains small, although greater efficacy has been shown with longer treatment courses and predictors of response to rTMS are progressively being identified. rTMS is a promising antidepressant treatment with overall minor adverse effects. Because the clinical efficacy of rTMS as an antidepressant remains questionable, further systematic, large-scale multicenter studies comparing rTMS to a sham and/or to an antidepressant medication along with more stringent stimulation parameters are warranted in order to identify patient populations most likely to benefit and treatment parameters most likely to optimize its antidepressant efficacy.

  11. The Impact of Accelerated Right Prefrontal High-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) on Cue-Reactivity: An fMRI Study on Craving in Recently Detoxified Alcohol-Dependent Patients

    PubMed Central

    Herremans, Sarah C.; Van Schuerbeek, Peter; De Raedt, Rudi; Matthys, Frieda; Buyl, Ronald; De Mey, Johan; Baeken, Chris

    2015-01-01

    In alcohol-dependent patients craving is a difficult-to-treat phenomenon. It has been suggested that high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) may have beneficial effects. However, exactly how this application exerts its effect on the underlying craving neurocircuit is currently unclear. In an effort to induce alcohol craving and to maximize detection of HF-rTMS effects to cue-induced alcohol craving, patients were exposed to a block and event-related alcohol cue-reactivity paradigm while being scanned with fMRI. Hence, we assessed the effect of right dorsolateral prefrontal cortex (DLPFC) stimulation on cue-induced and general alcohol craving, and the related craving neurocircuit. Twenty-six recently detoxified alcohol-dependent patients were included. First, we evaluated the impact of one sham-controlled stimulation session. Second, we examined the effect of accelerated right DLPFC HF-rTMS treatment: here patients received 15 sessions in an open label accelerated design, spread over 4 consecutive days. General craving significantly decreased after 15 active HF-rTMS sessions. However, cue-induced alcohol craving was not altered. Our brain imaging results did not show that the cue-exposure affected the underlying craving neurocircuit after both one and fifteen active HF-rTMS sessions. Yet, brain activation changes after one and 15 HF-rTMS sessions, respectively, were observed in regions associated with the extended reward system and the default mode network, but only during the presentation of the event-related paradigm. Our findings indicate that accelerated HF-rTMS applied to the right DLPFC does not manifestly affect the craving neurocircuit during an alcohol-related cue-exposure, but instead it may influence the attentional network. PMID:26295336

  12. Low-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) Modulates Evoked-Gamma Frequency Oscillations in Autism Spectrum Disorder (ASD)

    PubMed Central

    Baruth, Joshua M.; Casanova, Manuel F.; El-Baz, Ayman; Horrell, Tim; Mathai, Grace; Sears, Lonnie; Sokhadze, Estate

    2010-01-01

    Introduction It has been reported that individuals with Autism Spectrum Disorder (ASD) have abnormal reactions to the sensory environment and visuo-perceptual abnormalities. Electrophysiological research has provided evidence that gamma band activity (30-80 Hz) is a physiological indicator of the co-activation of cortical cells engaged in processing visual stimuli and integrating different features of a stimulus. A number of studies have found augmented and indiscriminative gamma band power at early stages of visual processing in ASD; this may be related to decreased inhibitory processing and an increase in the ratio of cortical excitation to inhibition. Low frequency or ‘slow’ (≤1HZ) repetitive transcranial magnetic stimulation (rTMS) has been shown to increase inhibition of stimulated cortex by the activation of inhibitory circuits. Methods We wanted to test the hypothesis of gamma band abnormalities at early stages of visual processing in ASD by investigating relative evoked (i.e. ~ 100 ms) gamma power in 25 subjects with ASD and 20 age-matched controls using Kanizsa illusory figures. Additionally, we wanted to assess the effects of 12 sessions of bilateral ‘slow’ rTMS to the dorsolateral prefrontal cortex (DLPFC) on evoked gamma activity using a randomized controlled design. Results In individuals with ASD evoked gamma activity was not discriminative of stimulus type, whereas in controls early gamma power differences between target and non-target stimuli were highly significant. Following rTMS individuals with ASD showed significant improvement in discriminatory gamma activity between relevant and irrelevant visual stimuli. We also found significant improvement in the responses on behavioral questionnaires (i.e., irritability, repetitive behavior) as a result of rTMS. Conclusion We proposed that ‘slow’ rTMS may have increased cortical inhibitory tone which improved discriminatory gamma activity at early stages of visual processing. rTMS has the

  13. 100 Repetitions

    ERIC Educational Resources Information Center

    Benson, Jeffrey

    2012-01-01

    One hundred repetitions--100 "useful" repetitions. This notion has guided the author's work in alternative education programs for almost 20 years, dealing with the most challenging students, from addicts to conduct-disordered adolescents to traumatized 5th graders. There are no magic tricks. The role of educators is to align with the healthy…

  14. Microseismic reflection imaging using data from a hydraulic reservoir stimulation

    NASA Astrophysics Data System (ADS)

    Reshetnikov, A.; Kummerow, J.; Shapiro, S. A.; Asanuma, H.; Häring, M.

    2012-12-01

    In this work we present an approach which uses waveforms from induced seismicity to build a detailed high resolution image of a stimulated reservoir. The idea of Microseismic Reflection Imaging (MRI) is to treat a located microseismic event as an active seismic source and to use migration techniques adapted from reflection seismics. We apply the MRI approach to high quality microseismic data from the stimulation of Enhanced Geothermal System at Basel, Switzerland. Microseismic waveforms were recorded at 6 borehole instruments between 2 and 6 km away from the injection point. We consider precisely located microseismic cloud which consists of than 2000 events including more than 1000 multiplets. For imaging we use the Fresnel-Volume-Migration method. This is a directional migration approach which uses wavefield polarization to restrict the migration operator to a region around the actual reflection point. It helps to reduce migration artifacts caused by limited aperture. To obtain polarization of the wavefield, we use auto- and cross-variances of time samples within a time window, including several dominant periods of the P- or S-wave. We also use a hodogram linearity threshold value to exclude parts of the seismograms with unreliable polarity estimates. We migrate both PP and SS reflections data recorded at 5 different sensors. Though the image quality degrades with increasing distance between the stimulated volume and receiver, resulting images complement each other and represent a detailed high resolution reflectivity map within the reservoir. The overall shape of the reflectors is in a good agreement with the shape of the microseismic cloud. We provide a joint interpretation of obtained images and event locations. Reflectors probably are cracks with a higher permeability compared to the background rock. These first order fractures serve as pathways for fluid and elevated pressure to the medium and therefore control the shape of the cloud. The majority of

  15. Elasticity reconstructive imaging by means of stimulated echo MRI.

    PubMed

    Chenevert, T L; Skovoroda, A R; O'Donnell, M; Emelianov, S Y

    1998-03-01

    A method is introduced to measure internal mechanical displacement and strain by means of MRI. Such measurements are needed to reconstruct an image of the elastic Young's modulus. A stimulated echo acquisition sequence with additional gradient pulses encodes internal displacements in response to an externally applied differential deformation. The sequence provides an accurate measure of static displacement by limiting the mechanical transitions to the mixing period of the simulated echo. Elasticity reconstruction involves definition of a region of interest having uniform Young's modulus along its boundary and subsequent solution of the discretized elasticity equilibrium equations. Data acquisition and reconstruction were performed on a urethane rubber phantom of known elastic properties and an ex vivo canine kidney phantom using <2% differential deformation. Regional elastic properties are well represented on Young's modulus images. The long-term objective of this work is to provide a means for remote palpation and elasticity quantitation in deep tissues otherwise inaccessible to manual palpation.

  16. Challenges in comparing the acute cognitive outcomes of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) vs. electroconvulsive therapy (ECT) in major depression: A systematic review.

    PubMed

    Kedzior, Karina Karolina; Schuchinsky, Maria; Gerkensmeier, Imke; Loo, Colleen

    2017-03-02

    The present study aimed to systematically compare the cognitive outcomes of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) and electroconvulsive therapy (ECT) in head-to-head studies with major depression (MDD) patients. A systematic literature search identified six studies with 219 MDD patients that were too heterogeneous to reliably detect meaningful differences in acute cognitive outcomes after ECT vs. HF-rTMS. Cognitive effects of brain stimulation vary depending on the timeframe and methods of assessment, stimulation parameters, and maintenance treatment. Thus, acute and longer-term differences in cognitive outcomes both need to be investigated at precisely defined timeframes and with similar instruments assessing comparable functions.

  17. Synergistic effects of noradrenergic modulation with atomoxetine and 10 Hz repetitive transcranial magnetic stimulation on motor learning in healthy humans

    PubMed Central

    2014-01-01

    Background Repetitive transcranial magnetic stimulation (rTMS) is able to induce changes in neuronal activity that outlast stimulation. The underlying mechanisms are not completely understood. They might be analogous to long-term potentiation or depression, as the duration of the effects seems to implicate changes in synaptic plasticity. Norepinephrine (NE) has been shown to play a crucial role in neuronal plasticity in the healthy and injured human brain. Atomoxetine (ATX) and other NE reuptake inhibitors have been shown to increase excitability in different systems and to influence learning processes. Thus, the combination of two facilitative interventions may lead to further increase in excitability and motor learning. But in some cases homeostatic metaplasticity might protect the brain from harmful hyperexcitability. In this study, the combination of 60 mg ATX and 10 Hz rTMS over the primary motor cortex was used to examine changes in cortical excitability and motor learning and to investigate their influence on synaptic plasticity mechanisms. Results The results of this double-blind placebo-controlled study showed that ATX facilitated corticospinal and intracortical excitability in motor cortex. 10 Hertz rTMS applied during a motor task was able to further increase intracortical excitability only in combination with ATX. In addition, only the combination of 10 Hz rTMS and ATX was capable of enhancing the total number of correct responses and reaction time significantly, indicating an interaction effect between rTMS and ATX without signs of homeostatic metaplasticity. Conclusion These results suggest that pharmacologically enhanced NE transmission and 10 Hz rTMS exert a synergistic effect on motor cortex excitability and motor learning in healthy humans. PMID:24690416

  18. Repetitive transcranial magnetic stimulation of the primary motor cortex in the treatment of motor signs in Parkinson's disease: A quantitative review of the literature.

    PubMed

    Zanjani, Anosha; Zakzanis, Konstantine K; Daskalakis, Zafiris J; Chen, Robert

    2015-05-01

    Parkinson's disease (PD) is a progressive disorder characterized by the emergence of motor deficits. In light of the voluminous and conflicting findings in the literature, the aim of the present quantitative review was to examine the effects of repetitive transcranial magnetic stimulation (rTMS) targeting the primary motor cortex (M1) in the treatment of motor signs in PD. Studies meeting inclusion criteria were analyzed using meta-analytic techniques and the Unified Parkinson's Disease Rating Scale (UPDRS) sections II and III were used as outcome measures. In order to determine the treatment effects of rTMS, the UPDRS II and III scores obtained at baseline, same day, to 1 day post rTMS treatment (short-term follow-up) and 1-month post stimulation (long-term follow-up) were compared between the active and sham rTMS groups. Additionally, the placebo effect was evaluated as the changes in UPDRS III scores in the sham rTMS groups. A placebo effect was not demonstrated, because sham rTMS did not improve motor signs as measured by UPDRS III. Compared with sham rTMS, active rTMS targeting the M1 significantly improved UPDRS III scores at the short-term follow-up (Cohen's d of 0.27, UPDRS III score improvement of 3.8 points). When the long-term follow-up UPDRS III scores were compared with baseline scores, the standardized effect size between active and sham rTMS did not reach significance. However, this translated into a significant nonstandardized 6.3-point improvement on the UPDRS III. No significant improvement in the UPDRS II was found. rTMS over the M1 may improve motor signs. Further studies are needed to provide a definite conclusion.

  19. Unilateral suppression of pharyngeal motor cortex to repetitive transcranial magnetic stimulation reveals functional asymmetry in the hemispheric projections to human swallowing.

    PubMed

    Mistry, Satish; Verin, Eric; Singh, Salil; Jefferson, Samantha; Rothwell, John C; Thompson, David G; Hamdy, Shaheen

    2007-12-01

    Inhibitory patterns of repetitive transcranial magnetic stimulation (rTMS) were applied to pharyngeal motor cortex in order to establish its role in modulating swallowing activity and provide evidence for functionally relevant hemispheric asymmetry. Healthy volunteers underwent single pulse TMS before and for 60 min after differing intensities of 1 Hz rTMS (n = 9, 6 male, 3 female, mean age 34 +/- 3 years) or theta burst stimulation (TBS) (n = 9, 6 male, 3 female, mean age 37 +/- 4 years). Electromyographic responses recorded from pharynx and hand were used as a measure of cortico-motor pathway excitability. Swallowing behaviour was then examined with a reaction time protocol, before and for up to 60 min after the most effective inhibitory protocol (1 Hz) applied to each hemisphere. Interventions were conducted on separate days and compared to sham using ANOVA. Only high intensity 1 Hz rTMS consistently suppressed pharyngeal motor cortex immediately and for up to 45 min (-34 +/- 7%, P < or = 0.001). Adjacent hand and contralateral pharyngeal motor cortex showed no change in response (-15 +/- 12%, P = 0.14 and 15 +/- 12%, P = 0.45, respectively). When used to unilaterally disrupt each hemisphere, rTMS to pharyngeal motor cortex with the stronger responses altered normal (-12 +/- 3%, P < or = 0.001) and fast (-9 +/- 4%, P < or = 0.009) swallow times, not seen following rTMS to the contralateral cortex or after sham. Thus, suppression of pharyngeal motor cortex to rTMS is intensity and frequency dependent, which when applied to each hemisphere reveals functionally relevant asymmetry in the motor control of human swallowing.

  20. Repetitive transcranial magnetic stimulation improves open field locomotor recovery after low but not high thoracic spinal cord compression-injury in adult rats.

    PubMed

    Poirrier, Anne-Lise; Nyssen, Yves; Scholtes, Felix; Multon, Sylvie; Rinkin, Charline; Weber, Géraldine; Bouhy, Delphine; Brook, Gary; Franzen, Rachelle; Schoenen, Jean

    2004-01-15

    Electromagnetic fields are able to promote axonal regeneration in vitro and in vivo. Repetitive transcranial magnetic stimulation (rTMS) is used routinely in neuropsychiatric conditions and as an atraumatic method to activate descending motor pathways. After spinal cord injury, these pathways are disconnected from the spinal locomotor generator, resulting in most of the functional deficit. We have applied daily 10 Hz rTMS for 8 weeks immediately after an incomplete high (T4-5; n = 5) or low (T10-11; n = 6) thoracic closed spinal cord compression-injury in adult rats, using 6 high- and 6 low-lesioned non-stimulated animals as controls. Functional recovery of hindlimbs was assessed using the BBB locomotor rating scale. In the control group, the BBB score was significantly better from the 7th week post-injury in animals lesioned at T4-5 compared to those lesioned at T10-11. rTMS significantly improved locomotor recovery in T10-11-injured rats, but not in rats with a high thoracic injury. In rTMS-treated rats, there was significant positive correlation between final BBB score and grey matter density of serotonergic fibres in the spinal segment just caudal to the lesion. We propose that low thoracic lesions produce a greater functional deficit because they interfere with the locomotor centre and that rTMS is beneficial in such lesions because it activates this central pattern generator, presumably via descending serotonin pathways. The benefits of rTMS shown here suggest strongly that this non-invasive intervention strategy merits consideration for clinical trials in human paraplegics with low spinal cord lesions.

  1. K-alpha x-ray source using high energy and high repetition rate laser system for phase contrast imaging

    NASA Astrophysics Data System (ADS)

    Serbanescu, Cristina; Fourmaux, Sylvain; Kieffer, Jean-Claude; Kincaid, Russell; Krol, Andrzej

    2009-08-01

    K-alpha x-ray sources from laser produced plasmas provide completely new possibilities for x-ray phase-contrast imaging applications. By tightly focusing intense femtosecond laser pulses onto a solid target, K-alpha x-ray pulses are generated through the interaction of energetic electrons created in the plasma with the bulk target. In this paper, we present a continuous and efficient Mo K-alpha x-ray source produced by a femtosecond laser system operating at 100 Hz repetition rate with maximum pulse energy of 110 mJ before compression. The source has x-ray conversion efficiency greater than 10-5 into K-alpha line emission. In preparation for phase contrast imaging applications, the size of the resultant K-alpha x-ray emission spot has been also characterized. The source exhibits sufficient spatial coherence to observe phase contrast. We observe a relatively small broadening of the K-alpha source size compared to the size of the laser beam itself. Detailed characterization of the source including the x-ray spectrum and the x-ray average yield along with phase contrast images of test objects will be presented.

  2. Are neuroticism and extraversion associated with the antidepressant effects of repetitive transcranial magnetic stimulation (rTMS)? An exploratory 4-week trial.

    PubMed

    Berlim, Marcelo T; McGirr, Alexander; Beaulieu, Marie-Martine; Van den Eynde, Frederique; Turecki, Gustavo

    2013-02-08

    Several randomized, controlled trials have found high frequency repetitive transcranial magnetic stimulation (HF-rTMS) to be effective for treating major depressive disorder (MDD), but its antidepressant mechanisms have yet to be firmly understood. In this context, pre-treatment personality traits and subsequent changes in personality concomitant to treatment may be relevant for our understanding of these mechanisms. To investigate this issue we conducted a naturalistic trial in which 14 subjects with moderate to severe depression were treated with daily HF-rTMS over the left dorsolateral prefrontal cortex for 4 weeks. Objective depressive symptoms (as assessed by the HAM-D(21)) and the major personality dimensions of neuroticism and extraversion were measured pre-post HF-rTMS. Pre-rTMS levels of extraversion predicted subsequent decrease in depressive symptoms. Also, HF-rTMS treatment resulted in a decrease in neuroticism scores, and this relative decrease was associated with the relative decrease in depression. Our results suggest that HF-rTMS may positively affect the personality dimension of neuroticism. Also, pre-treatment levels of extraversion may predict the subsequent antidepressant response to HF-rTMS. However, further studies with larger samples and controlled designs are needed to better clarify these preliminary findings.

  3. Mechanism of functional recovery after repetitive transcranial magnetic stimulation (rTMS) in the subacute cerebral ischemic rat model: neural plasticity or anti-apoptosis?

    PubMed

    Yoon, Kyung Jae; Lee, Yong-Taek; Han, Tai Ryoon

    2011-10-01

    Repetitive transcranial magnetic stimulation (rTMS) has been studied increasingly in recent years to determine whether it has a therapeutic benefit on recovery after stroke. However, the underlying mechanisms of rTMS in stroke recovery remain unclear. Here, we evaluated the effect of rTMS on functional recovery and its underlying mechanism by assessing proteins associated with neural plasticity and anti-apoptosis in the peri-lesional area using a subacute cerebral ischemic rat model. Twenty cerebral ischemic rats were randomly assigned to the rTMS or the sham group at post-op day 4. A total of 3,500 impulses with 10 Hz frequency were applied to ipsilesional cortex over a 2-week period. Functional outcome was measured before (post-op day 4) and after rTMS (post-op day 18). The rTMS group showed more functional improvement on the beam balance test and had stronger Bcl-2 and weaker Bax expression on immunohistochemistry compared with the sham group. The expression of NMDA and MAP-2 showed no significant difference between the two groups. These results suggest that rTMS in subacute cerebral ischemia has a therapeutic effect on functional recovery and is associated with an anti-apoptotic mechanism in the peri-ischemic area rather than with neural plasticity.

  4. Repetitive Transcranial Magnetic Stimulation Changes Cerebral Oxygenation on the Left Dorsolateral Prefrontal Cortex in Bulimia Nervosa: A Near-Infrared Spectroscopy Pilot Study.

    PubMed

    Sutoh, Chihiro; Koga, Yasuko; Kimura, Hiroshi; Kanahara, Nobuhisa; Numata, Noriko; Hirano, Yoshiyuki; Matsuzawa, Daisuke; Iyo, Masaomi; Nakazato, Michiko; Shimizu, Eiji

    2016-01-01

    Previous studies showed that food craving in eating disorders can be weakened with high-frequency repetitive transcranial magnetic stimulation (rTMS) on the left dorsolateral prefrontal cortex (DLPFC). The aims of this study were to assess cerebral oxygenation change induced with rTMS and to assess the short-term impact of rTMS on food craving and other bulimic symptoms in patients with bulimia nervosa (BN). Eight women diagnosed with BN according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria participated in this study. We measured haemoglobin concentration changes in the DLPFC with near-infrared spectroscopy during cognitive tasks measuring self-regulatory control in response to food photo stimuli, both at baseline and after a single session of rTMS. Subjective ratings for food cravings demonstrated significant reduction. A significant decrease in cerebral oxygenation of the left DLPFC was also observed after a single session of rTMS. Measurement with NIRS after rTMS intervention may be applicable for discussing the mechanisms underlying rTMS modulation in patients with BN.

  5. Bilateral repetitive transcranial magnetic stimulation for treatment-resistant depression: a systematic review and meta-analysis of randomized controlled trials

    PubMed Central

    Zhang, Y.Q.; Zhu, D.; Zhou, X.Y.; Liu, Y.Y.; Qin, B.; Ren, G.P.; Xie, P.

    2015-01-01

    There has been concern regarding the use of controversial paradigms for repetitive transcranial magnetic stimulation (rTMS) to manage treatment-resistant depression (TRD). This meta-analysis assessed the efficacy of bilateral rTMS compared with unilateral and sham rTMS in patients with TRD. PubMed, Embase, CENTRAL, PsycINFO, Web of Science, EAGLE and NTIS databases were searched to identify relevant studies, and randomized controlled trials (RCTs) on bilateral rTMS for TRD patients were included. The response was defined as the primary outcome, and remission was the secondary outcome. Ten RCTs that included 634 patients met the eligibility criteria. The risk ratio (RRs) of both the primary and secondary outcomes of bilateral rTMS showed non-significant increases compared to unilateral rTMS (RR=1.01, P=0.93; odds ratio [OR]=0.77, P=0.22). Notably, the RR of the primary bilateral rTMS outcome was significantly increased compared to that for sham rTMS (RR=3.43, P=0.0004). The results of our analysis demonstrated that bilateral rTMS was significantly more effective than sham rTMS but not unilateral rTMS in patients with TRD. Thus, bilateral rTMS may not be a useful paradigm for patients with TRD. PMID:25590350

  6. Bilateral repetitive transcranial magnetic stimulation for treatment-resistant depression: a systematic review and meta-analysis of randomized controlled trials.

    PubMed

    Zhang, Y Q; Zhu, D; Zhou, X Y; Liu, Y Y; Qin, B; Ren, G P; Xie, P

    2015-03-01

    There has been concern regarding the use of controversial paradigms for repetitive transcranial magnetic stimulation (rTMS) to manage treatment-resistant depression (TRD). This meta-analysis assessed the efficacy of bilateral rTMS compared with unilateral and sham rTMS in patients with TRD. PubMed, Embase, CENTRAL, PsycINFO, Web of Science, EAGLE and NTIS databases were searched to identify relevant studies, and randomized controlled trials (RCTs) on bilateral rTMS for TRD patients were included. The response was defined as the primary outcome, and remission was the secondary outcome. Ten RCTs that included 634 patients met the eligibility criteria. The risk ratio (RRs) of both the primary and secondary outcomes of bilateral rTMS showed non-significant increases compared to unilateral rTMS (RR=1.01, P=0.93; odds ratio [OR]=0.77, P=0.22). Notably, the RR of the primary bilateral rTMS outcome was significantly increased compared to that for sham rTMS (RR=3.43, P=0.0004). The results of our analysis demonstrated that bilateral rTMS was significantly more effective than sham rTMS but not unilateral rTMS in patients with TRD. Thus, bilateral rTMS may not be a useful paradigm for patients with TRD.

  7. Functional inhibition of the human middle temporal cortex affects non-visual motion perception: a repetitive transcranial magnetic stimulation study during tactile speed discrimination.

    PubMed

    Ricciardi, Emiliano; Basso, Demis; Sani, Lorenzo; Bonino, Daniela; Vecchi, Tomaso; Pietrini, Pietro; Miniussi, Carlo

    2011-02-01

    The visual motion-responsive middle temporal complex (hMT+) is activated during tactile and aural motion discrimination in both sighted and congenitally blind individuals, suggesting a supramodal organization of this area. Specifically, non-visual motion processing has been found to activate the more anterior portion of the hMT+. In the present study, repetitive transcranial magnetic stimulation (rTMS) was used to determine whether this more anterior portion of hMT+ truly plays a functional role in tactile motion processing. Sixteen blindfolded, young, healthy volunteers were asked to detect changes in the rotation velocity of a random Braille-like dot pattern by using the index or middle finger of their right hand. rTMS was applied for 600 ms (10 Hz, 110% motor threshold), 200 ms after the stimulus onset with a figure-of-eight coil over either the anterior portion of hMT+ or a midline parieto-occipital site (as a control). Accuracy and reaction times were significantly impaired only when TMS was applied on hMT+, but not on the control area. These results indicate that the recruitment of hMT+ is necessary for tactile motion processing, and thus corroborate the hypothesis of a 'supramodal' functional organization for this sensory motion processing area.

  8. QEEG Theta Cordance in the Prediction of Treatment Outcome to Prefrontal Repetitive Transcranial Magnetic Stimulation or Venlafaxine ER in Patients With Major Depressive Disorder.

    PubMed

    Bares, Martin; Brunovsky, Martin; Novak, Tomas; Kopecek, Miloslav; Stopkova, Pavla; Sos, Peter; Höschl, Cyril

    2015-04-01

    The aims of this double-blind study were to assess and compare the efficacy of quantitative electroencephalographic (QEEG) prefrontal theta band cordance in the prediction of response to 4-week, right, prefrontal, 1-Hz repetitive transcranial magnetic stimulation (rTMS) or venlafaxine ER in patients with major depressive disorder (MDD). Prefrontal QEEG cordance values of 50 inpatients (25 subjects in each group) completing 4 weeks of the study were obtained at baseline and after 1 week of treatment. Depressive symptoms were assessed using Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline and at week 1 and 4. Treatment response was defined as a ≥50% reduction in baseline MADRS total score. All responders (n = 9) and 6 of 16 nonresponders in the rTMS group had reduced cordance at week 1 (P < .01). Reduction of theta cordance value at week 1 was detected in all responders (n = 10) to venlafaxine ER, but only in 4 of 15 nonresponders (P = .005). The comparison of the areas under the curve of cordance change for prediction of response between rTMS (0.75) and venlafaxine ER (0.89) treated groups yielded no significant difference (P = .27). Our study indicates that prefrontal QEEG cordance is a promising tool not only for predicting the response to certain antidepressants but also to rTMS treatment, with comparable predictive efficacy for both therapeutic interventions.

  9. Does a combined intervention program of repetitive transcranial magnetic stimulation and intensive occupational therapy affect cognitive function in patients with post-stroke upper limb hemiparesis?

    PubMed Central

    Hara, Takatoshi; Abo, Masahiro; Kakita, Kiyohito; Masuda, Takeshi; Yamazaki, Ryunosuke

    2016-01-01

    Low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) to the contralesional hemisphere and intensive occupational therapy (iOT) have been shown to contribute to a significant improvement in upper limb hemiparesis in patients with chronic stroke. However, the effect of the combined intervention program of LF-rTMS and iOT on cognitive function is unknown. We retrospectively investigated whether the combined treatment influence patient's Trail-Making Test part B (TMT-B) performance, which is a group of easy and inexpensive neuropsychological tests that evaluate several cognitive functions. Twenty-five patients received 11 sessions of LF-rTMS to the contralesional hemisphere and 2 sessions of iOT per day over 15 successive days. Patients with right- and left-sided hemiparesis demonstrated significant improvements in upper limb motor function following the combined intervention program. Only patients with right-sided hemiparesis exhibited improved TMT-B performance following the combined intervention program, and there was a significant negative correlation between Fugl-Meyer Assessment scale total score change and TMT-B performance. The results indicate the possibility that LF-rTMS to the contralesional hemisphere combined with iOT improves the upper limb motor function and cognitive function of patients with right-sided hemiparesis. However, further studies are necessary to elucidate the mechanism of improved cognitive function. PMID:28197189

  10. Does a combined intervention program of repetitive transcranial magnetic stimulation and intensive occupational therapy affect cognitive function in patients with post-stroke upper limb hemiparesis?

    PubMed

    Hara, Takatoshi; Abo, Masahiro; Kakita, Kiyohito; Masuda, Takeshi; Yamazaki, Ryunosuke

    2016-12-01

    Low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) to the contralesional hemisphere and intensive occupational therapy (iOT) have been shown to contribute to a significant improvement in upper limb hemiparesis in patients with chronic stroke. However, the effect of the combined intervention program of LF-rTMS and iOT on cognitive function is unknown. We retrospectively investigated whether the combined treatment influence patient's Trail-Making Test part B (TMT-B) performance, which is a group of easy and inexpensive neuropsychological tests that evaluate several cognitive functions. Twenty-five patients received 11 sessions of LF-rTMS to the contralesional hemisphere and 2 sessions of iOT per day over 15 successive days. Patients with right- and left-sided hemiparesis demonstrated significant improvements in upper limb motor function following the combined intervention program. Only patients with right-sided hemiparesis exhibited improved TMT-B performance following the combined intervention program, and there was a significant negative correlation between Fugl-Meyer Assessment scale total score change and TMT-B performance. The results indicate the possibility that LF-rTMS to the contralesional hemisphere combined with iOT improves the upper limb motor function and cognitive function of patients with right-sided hemiparesis. However, further studies are necessary to elucidate the mechanism of improved cognitive function.

  11. Does Therapeutic Repetitive Transcranial Magnetic Stimulation Cause Cognitive Enhancing Effects in Patients with Neuropsychiatric Conditions? A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

    PubMed

    Martin, Donel M; McClintock, Shawn M; Forster, Jane; Loo, Colleen K

    2016-09-01

    Repetitive transcranial magnetic stimulation (rTMS) is increasingly used as a therapeutic intervention for neuropsychiatric illnesses and has demonstrated efficacy for treatment of major depression. However, an unresolved question is whether a course of rTMS treatment results in effects on cognitive functioning. In this systematic review and meta-analysis we aimed to quantitatively determine whether a course of rTMS has cognitive enhancing effects. We examined cognitive outcomes from randomised, sham-controlled studies conducted in patients with neuropsychiatric conditions where rTMS was administered to the dorsolateral prefrontal cortex (DLPFC) across repeated sessions, searched from PubMed/MEDLINE and other databases up until October 2015. Thirty studies met our inclusion criteria. Cognitive outcomes were pooled and examined across the following domains: Global cognitive function, executive function, attention, working memory, processing speed, visual memory, verbal memory and visuospatial ability. Active rTMS treatment was unassociated with generalised gains across the majority of domains of cognitive functioning examined. Secondary analyses revealed a moderate sized positive effect for improved working memory in a small number of studies in patients with schizophrenia (k = 3, g = 0.507, 95 % CI = [0.183-0.831], p < .01). Therapeutic rTMS when administered to the DLPFC in patients with neuropsychiatric conditions does not result in robust cognitive enhancing effects.

  12. Self-harm and suicidal acts: a suitable case for treatment of impulsivity-driven behaviour with repetitive transcranial magnetic stimulation (rTMS)

    PubMed Central

    Shergill, Sukhwinder S.; David, Anthony S.; Fonagy, Peter; Zaman, Rashid; Downar, Jonathan; Eliott, Emma; Bhui, Kamaldeep

    2015-01-01

    Summary Suicidal thinking, self-harm and suicidal acts are common, although determining their precise prevalence is complex. Epidemiological work has identified a number of associated demographic and clinical factors, though, with the exception of past acts of self-harm, these are non-specific and weak future predictors. There is a critical need shift focus from managing ‘suicidality-by-proxy’ through general mental health treatments, to better understand the neuropsychology and neurophysiology of such behaviour to guide targeted interventions. The model of the cognitive control of emotion (MCCE) offers such a paradigm, with an underlying pan-diagnostic pathophysiology of a hypoactive prefrontal cortex failing to suitably inhibit an overactive threat-responding limbic system. The result is a phenotype – from any number of causative gene–environment interactions – primed to impulsively self-harm. We argue that such neural dysconnectivity is open to potential therapeutic modification from repetitive transcranial magnetic stimulation (rTMS). The current evidence base for this is undoubtedly extremely limited, but the societal and clinical burden self-harm and suicide pose warrants such investigation. Declaration of interest K.B. is the Editor of BJPsych Open, but had no editorial involvement in the review or decision process regarding this paper. Copyright and usage © The Royal College of Psychiatrists 2015. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence. PMID:27703728

  13. Denoising Stimulated Raman Spectroscopic Images by Total Variation Minimization

    PubMed Central

    Liao, Chien-Sheng; Choi, Joon Hee; Zhang, Delong; Chan, Stanley H.; Cheng, Ji-Xin

    2016-01-01

    High-speed coherent Raman scattering imaging is opening a new avenue to unveiling the cellular machinery by visualizing the spatio-temporal dynamics of target molecules or intracellular organelles. By extracting signals from the laser at MHz modulation frequency, current stimulated Raman scattering (SRS) microscopy has reached shot noise limited detection sensitivity. The laser-based local oscillator in SRS microscopy not only generates high levels of signal, but also delivers a large shot noise which degrades image quality and spectral fidelity. Here, we demonstrate a denoising algorithm that removes the noise in both spatial and spectral domains by total variation minimization. The signal-to-noise ratio of SRS spectroscopic images was improved by up to 57 times for diluted dimethyl sulfoxide solutions and by 15 times for biological tissues. Weak Raman peaks of target molecules originally buried in the noise were unraveled. Coupling the denoising algorithm with multivariate curve resolution allowed discrimination of fat stores from protein-rich organelles in C. elegans. Together, our method significantly improved detection sensitivity without frame averaging, which can be useful for in vivo spectroscopic imaging. PMID:26955400

  14. Two-photon imaging with 80 MHz and 1-GHz repetition rate Ti:sapphire oscillators

    NASA Astrophysics Data System (ADS)

    Studier, Hauke; Breunig, Hans Georg; König, Karsten

    2010-02-01

    We report on multiphoton optical imaging with a laser scanning microscope (TauMapTM, Jenlab GmbH) in combination with two different excitation fs-lasers: a 80 MHz Ti:sapphire oscillator generating spectrally tunable 100 fs pulses and a 1 GHz Ti:sapphire oscillator producing ultra broadband 6 fs pulses. While the ultra-broadband pulses enable simultaneous excitation of several different types of fluorophores due their large spectral width, the 100 fs pulses are spectrally more selective and require tuning the center wavelength to cover the same excitation range. The wavelength selectivity was confirmed in measurements with microspheres with absorption maxima in the green and blue spectral region. Furthermore, the potential of both lasers for imaging of human skin is evaluated.

  15. Continuous-Wave Stimulated Emission Depletion Microscope for Imaging Actin Cytoskeleton in Fixed and Live Cells

    PubMed Central

    Neupane, Bhanu; Jin, Tao; Mellor, Liliana F.; Loboa, Elizabeth G.; Ligler, Frances S.; Wang, Gufeng

    2015-01-01

    Stimulated emission depletion (STED) microscopy provides a new opportunity to study fine sub-cellular structures and highly dynamic cellular processes, which are challenging to observe using conventional optical microscopy. Using actin as an example, we explored the feasibility of using a continuous wave (CW)-STED microscope to study the fine structure and dynamics in fixed and live cells. Actin plays an important role in cellular processes, whose functioning involves dynamic formation and reorganization of fine structures of actin filaments. Frequently used confocal fluorescence and STED microscopy dyes were employed to image fixed PC-12 cells (dyed with phalloidin- fluorescein isothiocyante) and live rat chondrosarcoma cells (RCS) transfected with actin-green fluorescent protein (GFP). Compared to conventional confocal fluorescence microscopy, CW-STED microscopy shows improved spatial resolution in both fixed and live cells. We were able to monitor cell morphology changes continuously; however, the number of repetitive analyses were limited primarily by the dyes used in these experiments and could be improved with the use of dyes less susceptible to photobleaching. In conclusion, CW-STED may disclose new information for biological systems with a proper characteristic length scale. The challenges of using CW-STED microscopy to study cell structures are discussed. PMID:26393614

  16. Laboratory imaging of stimulation fluid displacement from hydraulic fractures

    SciTech Connect

    Tidwell, V.; Parker, M.

    1996-11-01

    Laboratory experiments were conducted to physically investigate the processes governing stimulation fluid displacement from hydraulic fractures. Experiments were performed on two scales: meter-scale in a 1500 cm{sup 2} sand pack and core-scale in a 65 cm{sup 2} API linear conductivity cell. High-resolution light transmission imaging was employed at the meter-scale to visualize and quantify processes governing fluid displacement. For comparison, complimentary tests were performed using an API conductivity cell under ambient test conditions and at elevated closure stress. In these experiments viscous fingering and gravity drainage were identified as the dominant processes governing fluid displacement. Fluid viscosity was found to dictate the relative importance of the competing displacement processes and ultimately determine the residual liquid saturation of the sand pack. The process by which fluid displacement occurs was seen to effect the shape of both the gas and liquid phase relative permeability functions. Knowledge of such viscosity/relative permeability relationships may prove useful in bounding predictions of post-stimulation recovery of gels from the fracture pack.

  17. Concordance Between BeamF3 and MRI-neuronavigated Target Sites for Repetitive Transcranial Magnetic Stimulation of the Left Dorsolateral Prefrontal Cortex

    PubMed Central

    Mir-Moghtadaei, Arsalan; Caballero, Ruth; Fried, Peter; Fox, Michael D.; Lee, Katherine; Giacobbe, Peter; Daskalakis, Zafiris J.; Blumberger, Daniel M.; Downar, Jonathan

    2016-01-01

    Background The dorsolateral prefrontal cortex (DLPFC) is a common target for repetitive transcranial magnetic stimulation (rTMS) in major depression, but the conventional “5 cm rule” misses DLPFC in > 1/3 cases. Another heuristic, BeamF3, locates the F3 EEG site from scalp measurements. MRI-guided neuronavigation is more onerous, but can target a specific DLPFC stereotaxic coordinate directly. The concordance between these two approaches has not previously been assessed. Objective To quantify the discrepancy in scalp site between BeamF3 versus MRI-guided neuronavigation for left DLPFC. Methods Using 100 pre-treatment MRIs from subjects undergoing left DLPFC-rTMS, we localized the scalp site at minimum Euclidean distance from a target MNI coordinate (X − 38 Y + 44 Z + 26) derived from our previous work. We performed nasion-inion, tragus–tragus, and head-circumference measurements on the same subjects’ MRIs, and applied the BeamF3 heuristic. We then compared the distance between BeamF3 and MRI-guided scalp sites. Results BeamF3-to-MRI-guided discrepancies were <0.65 cm in 50% of subjects, <0.99 cm in 75% of subjects, and <1.36 cm in 95% of subjects. The angle from midline to the scalp site did not differ significantly using MRI-guided versus BeamF3 methods. However, the length of the radial arc from vertex to target site was slightly but significantly longer (mean 0.35 cm) with MRI-guidance versus BeamF3. Conclusions The BeamF3 heuristic may provide a reasonable approximation to MRI-guided neuronavigation for locating left DLPFC in a majority of subjects. A minor optimization of the heuristic may yield additional concordance. PMID:26115776

  18. Effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) on spontaneously hypertensive rats, an animal model of attention-deficit/hyperactivity disorder.

    PubMed

    Kim, Jungyun; Park, Heamen; Yu, Seong-Lan; Jee, Sungju; Cheon, Keun-Ah; Song, Dong Ho; Kim, Seung Jun; Im, Woo-Young; Kang, Jaeku

    2016-10-01

    The current treatment of choice for attention deficit hyperactivity disorder (ADHD) is pharmacotherapy. A search for new treatment options is underway, however, as the wide application of drugs to the general population of patients with ADHD is limited by side effects and the variance of pharmacokinetic effects of the drugs in each patient. In the present study, we applied repetitive transcranial magnetic stimulation (rTMS), a non-invasive treatment used in a number of other psychiatric disorders, to spontaneously hypertensive rats (SHRs), an animal model of ADHD, in order to assess the efficacy of the treatment in modifying behavioural symptoms as well as levels of dopamine, noradrenaline, serotonin, and brain-derived neurotrophic factor (BDNF). A total of fifteen sessions of high-frequency rTMS treatment were administered. Behavioural symptoms were observed using open field, Y-maze, and elevated plus-maze tests. Upon completion of the experiments, rats were sacrificed, and the neurochemical changes in brain tissue were analysed using high performance liquid chromatography and Western blotting. The SHRs treated with rTMS tended to exhibit less locomotor activity in the open field test over the course of treatment, but there was no improvement in inattention as measured by the Y-maze test. Furthermore, BDNF concentration increased and noradrenaline concentration decreased in the prefrontal cortex of SHRs treated with rTMS. The results of the present preclinical study indicate that rTMS may constitute a new modality of treatment for patients with ADHD, through further evaluation of specific treatment parameters as well as safety and efficacy in humans are required.

  19. Effect of combined low-frequency repetitive transcranial magnetic stimulation and virtual reality training on upper limb function in subacute stroke: a double-blind randomized controlled trail.

    PubMed

    Zheng, Chan-juan; Liao, Wei-jing; Xia, Wen-guang

    2015-04-01

    The effect of combined low-frequency repetitive transcranial magnetic stimulation (LF rTMS) and virtual reality (VR) training in patients after stroke was assessed. In a double-blind randomized controlled trial, 112 patients with hemiplegia after stroke were randomly divided into two groups: experimental and control. In experimental group, the patients received LF rTMS and VR training treatment, and those in control group received sham rTMS and VR training treatment. Participants in both groups received therapy of 6 days per week for 4 weeks. The primary endpoint including the upper limb motor function test of Fugl-meyer assessment (U-FMA) and wolf motor function test (WMFT), and the secondary endpoint including modified Barthel index (MBI) and 36-item Short Form Health Survey Questionnaire (SF-36) were assessed before and 4 weeks after treatment. Totally, 108 subjects completed the study (55 in experimental group and 53 in control group respectively). After 4-week treatment, the U-FMA scores [mean difference of 13.2, 95% confidence interval (CI) 3.6 to 22.7, P<0.01], WMFT scores (mean difference of 2.9, 95% CI 2.7 to 12.3, P<0.01), and MBI scores (mean difference 16.1, 95% CI 3.8 to 9.4, P<0.05) were significantly increased in the experimental group as compared with the control group. The results suggested the combined use of LF rTMS with VR training could effectively improve the upper limb function, the living activity, and the quality of life in patients with hemiplegia following subacute stroke, which may provide a better rehabilitation treatment for subacute stroke.

  20. Repetitive transcranial magnetic stimulation (rTMS) for the treatment of depression in Parkinson disease: a meta-analysis of randomized controlled clinical trials.

    PubMed

    Xie, Cheng-Long; Chen, Jie; Wang, Xiao-Dan; Pan, Jia-Lin; Zhou, Yi; Lin, Shi-Yi; Xue, Xiao-Dong; Wang, Wen-Wen

    2015-10-01

    The objective of this meta-analysis was to evaluate the effects of repetitive transcranial magnetic stimulation (rTMS) for the treatment of depression in patients with Parkinson disease in order to arrive at qualitative and quantitative conclusions about the efficacy of rTMS. We included randomized controlled trials examining the effects of rTMS compared with sham-rTMS or selective serotonin re-uptake inhibitors (SSRIs). The quality of included studies was strictly evaluated. Data analyses were performed using the RevMan5.1 software. Eight studies including 312 patients met all inclusion criteria. The results showed that rTMS could evidently improve the HRSD score compared with sham-rTMS (p < 0.00001). However, we found similar antidepressant efficacy between rTMS and SSRIs groups in terms of HRSD and BDI score (p = 0.65; p = 0.75, respectively). Furthermore, patients who received rTMS could evidently show improvement on the unified Parkinson's disease rating scale (UPDRS), ADL score, and UPDRS motor score compared with sham-rTMS or SSRIs (p < 0.05, p = 0.05, respectively). The subgroup analysis by frequency of rTMS evidenced that the efficacy of low-frequency rTMS was superior to sham-rTMS (p < 0.0001) in terms of the outcome measure according to HAMD scale. Meanwhile, the high-frequency rTMS has the same antidepressant efficacy as SSRIs (p = 0.94). The current meta-analysis provided evidence that rTMS was superior to sham-rTMS and had similar antidepressant efficacy as SSRIs, and may have the additional advantage of some improvement in motor function.

  1. Different frequency repetitive transcranial magnetic stimulation (rTMS) for posttraumatic stress disorder (PTSD): A systematic review and meta-analysis.

    PubMed

    Yan, Tingting; Xie, Qinglian; Zheng, Zhong; Zou, Ke; Wang, Lijuan

    2017-06-01

    Posttraumatic stress disorder (PTSD) is a psychiatric disorder. Repetitive transcranial magnetic stimulation (rTMS) has been found to be effective for treating PTSD, but whether different frequencies have different effects remains controversial. We conducted this systematic review and meta-analysis to address this question. We searched the literature for studies written in English or Chinese in 9 electronic databases from the databases' inception to August 1, 2016. Additional articles were identified from the reference lists of identified studies and from personal reference collections. Eighteen articles were included, and 11 were suitable for the meta-analysis (Combined sample size was 377 (217 in active rTMS groups, 160 in sham-controlled groups)). Low-frequency (LF) rTMS resulted in a significant reduction in the PTSD total score and the depression score (1. PTSD total score: pooled SMD, 0.92; CI, 0.11-1.72; 2. Depression: pooled SMD, 0.54; CI, 0.08-1.00). High-frequency (HF) rTMS showed the following results: 1. PTSD total score: pooled SMD, 3.24; CI, 2.24-4.25; 2. re-experiencing: pooled SMD, -1.77; CI, -2.49-(-1.04); 3. Avoidance: pooled SMD, -1.57; CI, -2.50-(-0.84); 4. hyperarousal: pooled SMD, -1.32; CI, -2.17-(-0.47); 5. depression: pooled SMD, 1.92; CI, 0.80-3.03; and 6. Anxiety: pooled SMD, 2.67; CI, 1.82-3.52. Therefore, both HF and LF rTMS can alleviate PTSD symptoms. Although the evidence is extremely limited, LF rTMS can reduce overall PTSD and depression symptoms. HF rTMS can improve the main and related symptoms of PTSD. However, additional research is needed to substantiate these findings.

  2. Role of Brain-Derived Neurotrophic Factor in Beneficial Effects of Repetitive Transcranial Magnetic Stimulation for Upper Limb Hemiparesis after Stroke

    PubMed Central

    Kakuda, Wataru; Miyano, Satoshi; Momosaki, Ryo; Abo, Masahiro

    2016-01-01

    Background Repetitive transcranial magnetic stimulation (rTMS) can improve upper limb hemiparesis after stroke but the mechanism underlying its efficacy remains elusive. rTMS seems to alter brain-derived neurotrophic factor (BDNF) and such effect is influenced by BDNF gene polymorphism. Objectives To investigate the molecular effects of rTMS on serum levels of BDNF, its precursor proBDNF and matrix metalloproteinase-9 (MMP-9) in poststroke patients with upper limb hemiparesis. Methods Poststroke patients with upper limb hemiparesis were studied. Sixty-two patients underwent rehabilitation plus rTMS combination therapy and 33 patients underwent rehabilitation monotherapy without rTMS for 14 days at our hospital. One Hz rTMS was applied over the motor representation of the first dorsal interosseous muscle on the non-lesional hemisphere. Fugl-Meyer Assessment and Wolf Motor Function (WMFT) were used to evaluate motor function on the affected upper limb before and after intervention. Blood samples were collected for analysis of BDNF polymorphism and measurement of BDNF, proBDNF and MMP-9 levels. Results Two-week combination therapy increased BDNF and MMP-9 serum levels, but not serum proBDNF. Serum BDNF and MMP-9 levels did not correlate with motor function improvement, though baseline serum proBDNF levels correlated negatively and significantly with improvement in WMFT (ρ = -0.422, p = 0.002). The outcome of rTMS therapy was not altered by BDNF gene polymorphism. Conclusions The combination therapy of rehabilitation plus low-frequency rTMS seems to improve motor function in the affected limb, by activating BDNF processing. BDNF and its precursor proBDNF could be potentially suitable biomarkers for poststroke motor recovery. PMID:27007747

  3. Repetitive transcranial magnetic stimulation enhances spatial learning and synaptic plasticity via the VEGF and BDNF-NMDAR pathways in a rat model of vascular dementia.

    PubMed

    Zhang, N; Xing, M; Wang, Y; Tao, H; Cheng, Y

    2015-12-17

    This study aimed to evaluate the effects of repetitive transcranial magnetic stimulation (rTMS) on learning and memory in a rat model of vascular dementia (VaD) and to analyze the associated mechanisms. Bilateral carotid artery occlusion (2-VO) was used to establish a rat model of VaD. High-frequency (5Hz) rTMS was performed on rats for four weeks. Spatial learning and memory abilities were evaluated using the Morris water maze (MWM), and synaptic plasticity in the hippocampus was assessed via long-term potentiation (LTP). Hippocampal expression of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF) and three subunits of the N-methyl-D-aspartic acid receptor (NMDAR), NR1, NR2A and NR2B, was analyzed by Western blotting. Compared with the VaD group, escape latency was decreased (P<0.05) and the time spent in the target quadrant and the percentage of swimming distance within that quadrant were increased (P<0.05) in the rTMS group. LTP at hippocampal CA3-CA1 synapses was enhanced by rTMS (P<0.05). VEGF expression was up-regulated following 2-VO and was further increased by rTMS (P<0.05). BDNF, NR1 and NR2B expression was decreased in the VaD group and increased by rTMS (P<0.05). There were no significant differences in NR2A expression among the three groups. These results suggest that rTMS improved learning and memory in the VaD model rats via the up-regulation of VEGF, BDNF and NMDARs. In addition, NR2B may be more important than NR2A for LTP induction in the hippocampus during rTMS treatment of VaD.

  4. The Effects of Different Repetitive Transcranial Magnetic Stimulation (rTMS) Protocols on Cortical Gene Expression in a Rat Model of Cerebral Ischemic-Reperfusion Injury

    PubMed Central

    Ljubisavljevic, Milos R.; Javid, Asma; Oommen, Joji; Parekh, Khatija; Nagelkerke, Nico; Shehab, Safa; Adrian, Thomas E.

    2015-01-01

    Although repetitive Transcranial Magnetic Stimulation (rTMS) in treatment of stroke in humans has been explored over the past decade the data remain controversial in terms of optimal stimulation parameters and the mechanisms of rTMS long-term effects. This study aimed to explore the potential of different rTMS protocols to induce changes in gene expression in rat cortices after acute ischemic-reperfusion brain injury. The stroke was induced by middle cerebral artery occlusion (MCAO) with subsequent reperfusion. Changes in the expression of 96 genes were examined using low-density expression arrays after MCAO alone and after MCAO combined with 1Hz, 5Hz, continuous (cTBS) and intermittent (iTBS) theta-burst rTMS. rTMS over the lesioned hemisphere was given for two weeks (with a 2-day pause) in a single daily session and a total of 2400 pulses. MCAO alone induced significant upregulation in the expression of 44 genes and downregulation in 10. Two weeks of iTBS induced significant increase in the expression of 52 genes. There were no downregulated genes. 1Hz and 5Hz had no significant effects on gene expression, while cTBS effects were negligible. Upregulated genes included those involved in angiogenesis, inflammation, injury response and cellular repair, structural remodeling, neuroprotection, neurotransmission and neuronal plasticity. The results show that long-term rTMS in acute ischemic-reperfusion brain injury induces complex changes in gene expression that span multiple pathways, which generally promote the recovery. They also demonstrate that induced changes primarily depend on the rTMS frequency (1Hz and 5Hz vs. iTBS) and pattern (cTBS vs. iTBS). The results further underlines the premise that one of the benefits of rTMS application in stroke may be to prime the brain, enhancing its potential to cope with the injury and to rewire. This could further augment its potential to favorably respond to rehabilitation, and to restore some of the loss functions. PMID

  5. The Effects of Different Repetitive Transcranial Magnetic Stimulation (rTMS) Protocols on Cortical Gene Expression in a Rat Model of Cerebral Ischemic-Reperfusion Injury.

    PubMed

    Ljubisavljevic, Milos R; Javid, Asma; Oommen, Joji; Parekh, Khatija; Nagelkerke, Nico; Shehab, Safa; Adrian, Thomas E

    2015-01-01

    Although repetitive Transcranial Magnetic Stimulation (rTMS) in treatment of stroke in humans has been explored over the past decade the data remain controversial in terms of optimal stimulation parameters and the mechanisms of rTMS long-term effects. This study aimed to explore the potential of different rTMS protocols to induce changes in gene expression in rat cortices after acute ischemic-reperfusion brain injury. The stroke was induced by middle cerebral artery occlusion (MCAO) with subsequent reperfusion. Changes in the expression of 96 genes were examined using low-density expression arrays after MCAO alone and after MCAO combined with 1Hz, 5Hz, continuous (cTBS) and intermittent (iTBS) theta-burst rTMS. rTMS over the lesioned hemisphere was given for two weeks (with a 2-day pause) in a single daily session and a total of 2400 pulses. MCAO alone induced significant upregulation in the expression of 44 genes and downregulation in 10. Two weeks of iTBS induced significant increase in the expression of 52 genes. There were no downregulated genes. 1Hz and 5Hz had no significant effects on gene expression, while cTBS effects were negligible. Upregulated genes included those involved in angiogenesis, inflammation, injury response and cellular repair, structural remodeling, neuroprotection, neurotransmission and neuronal plasticity. The results show that long-term rTMS in acute ischemic-reperfusion brain injury induces complex changes in gene expression that span multiple pathways, which generally promote the recovery. They also demonstrate that induced changes primarily depend on the rTMS frequency (1Hz and 5Hz vs. iTBS) and pattern (cTBS vs. iTBS). The results further underlines the premise that one of the benefits of rTMS application in stroke may be to prime the brain, enhancing its potential to cope with the injury and to rewire. This could further augment its potential to favorably respond to rehabilitation, and to restore some of the loss functions.

  6. Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression in Adult and Youth Populations: A Systematic Literature Review and Meta-Analysis

    PubMed Central

    Leggett, Laura E.; Soril, Lesley J. J.; Coward, Stephanie; Lorenzetti, Diane L.; MacKean, Gail; Clement, Fiona M.

    2015-01-01

    Background: Between 30% and 60% of individuals with major depressive disorder will have treatment-resistant depression (TRD): depression that does not subside with pharmaceutical treatment. Repetitive transcranial magnetic stimulation (rTMS) is an emerging treatment for TRD. Objective: To establish the efficacy and optimal protocol for rTMS among adults and youth with TRD. Data Sources: Two systematic reviews were conducted: one to determine the efficacy of rTMS for adults with TRD and another to determine the effectiveness of rTMS for youth with TRD. For adults, MEDLINE, Cochrane Central Register of Controlled Trials, PubMed, EMBASE, PsycINFO, Cochrane Database of Systematic Reviews, and Health Technology Assessment Database were searched from inception until January 10, 2014 with no language restrictions. Terms aimed at capturing the target diagnosis, such as depression and depressive disorder, were combined with terms describing the technology, such as transcranial magnetic stimulation and rTMS. Results were limited to studies involving human participants and designed as a randomized controlled trial. For youth, the search was altered to include youth only (aged 13–25 years) and all study designs. When possible, meta-analysis of response and remission rates was conducted. Study Selection: Seventy-three articles were included in this review: 70 on adult and 3 on youth populations. Results: Meta-analysis comparing rTMS and sham in adults found statistically significant results favoring rTMS for response (RR: 2.35 [95% CI, 1.70–3.25]) and remission (RR: 2.24 [95% CI, 1.53–3.27]). No statistically significant differences were found when comparing high- and low-frequency, unilateral and bilateral, low- and high-intensity rTMS or rTMS and electroconvulsive therapy (ECT). While meta-analysis of results from the youth literature was not possible, the limited evidence base suggests that rTMS may be effective for treating TRD in youth. Conclusions: The evidence

  7. Calcium imaging of infrared-stimulated activity in rodent brain.

    PubMed

    Cayce, Jonathan Matthew; Bouchard, Matthew B; Chernov, Mykyta M; Chen, Brenda R; Grosberg, Lauren E; Jansen, E Duco; Hillman, Elizabeth M C; Mahadevan-Jansen, Anita

    2014-04-01

    Infrared neural stimulation (INS) is a promising neurostimulation technique that can activate neural tissue with high spatial precision and without the need for exogenous agents. However, little is understood about how infrared light interacts with neural tissue on a cellular level, particularly within the living brain. In this study, we use calcium sensitive dye imaging on macroscopic and microscopic scales to explore the spatiotemporal effects of INS on cortical calcium dynamics. The INS-evoked calcium signal that was observed exhibited a fast and slow component suggesting activation of multiple cellular mechanisms. The slow component of the evoked signal exhibited wave-like properties suggesting network activation, and was verified to originate from astrocytes through pharmacology and 2-photon imaging. We also provide evidence that the fast calcium signal may have been evoked through modulation of glutamate transients. This study demonstrates that pulsed infrared light can induce intracellular calcium modulations in both astrocytes and neurons, providing new insights into the mechanisms of action of INS in the brain.

  8. Low-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) Affects Event-Related Potential Measures of Novelty Processing in Autism

    PubMed Central

    Baruth, Joshua; Tasman, Allan; Mansoor, Mehreen; Ramaswamy, Rajesh; Sears, Lonnie; Mathai, Grace; El-Baz, Ayman; Casanova, Manuel F.

    2009-01-01

    In our previous study on individuals with autism spectrum disorder (ASD) (Sokhadze et al., Appl Psychophysiol Biofeedback 34:37–51, 2009a) we reported abnormalities in the attention-orienting frontal event-related potentials (ERP) and the sustained-attention centro-parietal ERPs in a visual oddball experiment. These results suggest that individuals with autism over-process information needed for the successful differentiation of target and novel stimuli. In the present study we examine the effects of low-frequency, repetitive Transcranial Magnetic Stimulation (rTMS) on novelty processing as well as behavior and social functioning in 13 individuals with ASD. Our hypothesis was that low-frequency rTMS application to dorsolateral prefrontal cortex (DLFPC) would result in an alteration of the cortical excitatory/inhibitory balance through the activation of inhibitory GABAergic double bouquet interneurons. We expected to find post-TMS differences in amplitude and latency of early and late ERP components. The results of our current study validate the use of low-frequency rTMS as a modulatory tool that altered the disrupted ratio of cortical excitation to inhibition in autism. After rTMS the parieto-occipital P50 amplitude decreased to novel distracters but not to targets; also the amplitude and latency to targets increased for the frontal P50 while decreasing to non-target stimuli. Low-frequency rTMS minimized early cortical responses to irrelevant stimuli and increased responses to relevant stimuli. Improved selectivity in early cortical responses lead to better stimulus differentiation at later-stage responses as was made evident by our P3b and P3a component findings. These results indicate a significant change in early, middle-latency and late ERP components at the frontal, centro-parietal, and parieto-occipital regions of interest in response to target and distracter stimuli as a result of rTMS treatment. Overall, our preliminary results show that rTMS may prove to

  9. Efficacy and safety of the Chinese herbal medicine shuganjieyu with and without adjunctive repetitive transcranial magnetic stimulation (rTMS) for geriatric depression: a randomized controlled trial

    PubMed Central

    XIE, Minmin; JIANG, Wenhai; YANG, Haibo

    2015-01-01

    Background Pharmacological treatment of geriatric depression is often ineffective because patients cannot tolerate adequate doses of antidepressant medications. Aim Examine the efficacy and safety of shuganjieyu – the first Chinese herbal medicine approved for the treatment of depression by China’s drug regulatory agency -- with and without adjunctive treatment with repetitive transcranial magnetic stimulation (rTMS) in the treatment of geriatric depression. Methods Sixty-five inpatients 60 or older who met ICD-10 criteria for depression were randomly assigned to an experimental group (shuganjieyu + rTMS) (n=36) or a control group (shuganjieyu + sham rTMS)(n=29). All participants received 4 capsules of shuganjieyu daily for 6 weeks. rTMS (or sham rTMS) was administered 20 minutes daily, five days a week for 4 weeks. Blinded raters used the Hamilton Rating Scale for Depression (HAMD-17) and the Treatment Emergent Symptom Scale to assess clinical efficacy and safety at baseline and 1, 2, 4, and 6 weeks after starting treatment. Over the six-week trial, there was only one dropout from the experimental group and two dropouts from the control group. Results None of the patients had serious side effects, but 40% in the experimental group and 50% in the control group experienced minor side effects that all resolved spontaneously. Both groups showed substantial stepwise improvement in depressive symptoms over the 6 weeks. Repeated measures ANOVA found no differences between the two groups. After 6 weeks, 97% of the experimental group had experienced a 25% or greater drop in the level of depression, but only 20% had experience a 50% or greater drop in the level of depression; the corresponding values in the control group were 96% and 19%. There were some minor, non-significant differences in the onset of the treatment effect between the different types of depressive symptoms, but by the second week of treatment all five HAMD-17 subscale scores had improved significantly

  10. Subcellular chemical and morphological analysis by stimulated Raman scattering microscopy and image analysis techniques

    PubMed Central

    D’Arco, Annalisa; Brancati, Nadia; Ferrara, Maria Antonietta; Indolfi, Maurizio; Frucci, Maria; Sirleto, Luigi

    2016-01-01

    The visualization of heterogeneous morphology, segmentation and quantification of image features is a crucial point for nonlinear optics microscopy applications, spanning from imaging of living cells or tissues to biomedical diagnostic. In this paper, a methodology combining stimulated Raman scattering microscopy and image analysis technique is presented. The basic idea is to join the potential of vibrational contrast of stimulated Raman scattering and the strength of imaging analysis technique in order to delineate subcellular morphology with chemical specificity. Validation tests on label free imaging of polystyrene-beads and of adipocyte cells are reported and discussed. PMID:27231626

  11. Autonomic neurosurgery: from microvascular decompression to image guided stimulation

    PubMed Central

    Pereira, EAC; Green, AL

    2007-01-01

    The paper reviews mechanisms underlying autonomic disorders, with a focus on cardiovascular dysfunction. Neurosurgical approaches are described for medically refractory hypertension and orthostatic hypotension. After review of microvascular decompression of the rostral ventrolateral medulla, stereotactic CT and MRI guided deep brain stimulation of the periaqueductal grey matter (PAG) is evaluated. Results are presented from patient studies showing reductions in blood pressure with ventral PAG stimulation and increases in blood pressure with dorsal PAG stimulation. A rationale for the treatment of autonomic disorders by neurosurgical intervention is discussed. PMID:21614256

  12. Repetitive Model of Mild Traumatic Brain Injury Produces Cortical Abnormalities Detectable by Magnetic Resonance Diffusion Imaging (DTI/DKI), Histopathology, and Behavior.

    PubMed

    Yu, Fengshan; Shukla, Dinesh K; Armstrong, Regina C; Marion, Christina M; Radomski, Kryslaine L; Selwyn, Reed G; Dardzinski, Bernard J

    2016-12-20

    Noninvasive detection of mild traumatic brain injury (mTBI) is important for evaluating acute through chronic effects of head injuries, particularly after repetitive impacts. To better detect abnormalities from mTBI, we performed longitudinal studies (baseline, 3, 6, and 42 days) using magnetic resonance diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) in adult mice after repetitive mTBI (r-mTBI; daily × 5) or sham procedure. This r-mTBI produced righting reflex delay and was first characterized in the corpus callosum to demonstrate low levels of axon damage, astrogliosis, and microglial activation, without microhemorrhages. High-resolution DTI-DKI was then combined with post-imaging pathological validation along with behavioral assessments targeted for the impact regions. In the corpus callosum, only DTI fractional anisotropy at 42 days showed significant change post-injury. Conversely, cortical regions under the impact site (M1-M2, anterior cingulate) had reduced axial diffusivity (AD) at all time points with a corresponding increase in axial kurtosis (Ka) at 6 days. Post-imaging neuropathology showed microglial activation in both the corpus callosum and cortex at 42 days after r-mTBI. Increased cortical microglial activation correlated with decreased cortical AD after r-mTBI (r = -0.853; n = 5). Using Thy1-YFP-16 mice to fluorescently label neuronal cell bodies and processes revealed low levels of axon damage in the cortex after r-mTBI. Finally, r-mTBI produced social deficits consistent with the function of this anterior cingulate region of cortex. Overall, vulnerability of cortical regions is demonstrated after mild repetitive injury, with underlying differences of DTI and DKI, microglial activation, and behavioral deficits.

  13. Alteration of default mode network in high school football athletes due to repetitive subconcussive mild traumatic brain injury: a resting-state functional magnetic resonance imaging study.

    PubMed

    Abbas, Kausar; Shenk, Trey E; Poole, Victoria N; Breedlove, Evan L; Leverenz, Larry J; Nauman, Eric A; Talavage, Thomas M; Robinson, Meghan E

    2015-03-01

    Long-term neurological damage as a result of head trauma while playing sports is a major concern for football athletes today. Repetitive concussions have been linked to many neurological disorders. Recently, it has been reported that repetitive subconcussive events can be a significant source of accrued damage. Since football athletes can experience hundreds of subconcussive hits during a single season, it is of utmost importance to understand their effect on brain health in the short and long term. In this study, resting-state functional magnetic resonance imaging (rs-fMRI) was used to study changes in the default mode network (DMN) after repetitive subconcussive mild traumatic brain injury. Twenty-two high school American football athletes, clinically asymptomatic, were scanned using the rs-fMRI for a single season. Baseline scans were acquired before the start of the season, and follow-up scans were obtained during and after the season to track the potential changes in the DMN as a result of experienced trauma. Ten noncollision-sport athletes were scanned over two sessions as controls. Overall, football athletes had significantly different functional connectivity measures than controls for most of the year. The presence of this deviation of football athletes from their healthy peers even before the start of the season suggests a neurological change that has accumulated over the years of playing the sport. Football athletes also demonstrate short-term changes relative to their own baseline at the start of the season. Football athletes exhibited hyperconnectivity in the DMN compared to controls for most of the sessions, which indicates that, despite the absence of symptoms typically associated with concussion, the repetitive trauma accrued produced long-term brain changes compared to their healthy peers.

  14. CMOS Image Sensor and System for Imaging Hemodynamic Changes in Response to Deep Brain Stimulation.

    PubMed

    Zhang, Xiao; Noor, Muhammad S; McCracken, Clinton B; Kiss, Zelma H T; Yadid-Pecht, Orly; Murari, Kartikeya

    2016-06-01

    Deep brain stimulation (DBS) is a therapeutic intervention used for a variety of neurological and psychiatric disorders, but its mechanism of action is not well understood. It is known that DBS modulates neural activity which changes metabolic demands and thus the cerebral circulation state. However, it is unclear whether there are correlations between electrophysiological, hemodynamic and behavioral changes and whether they have any implications for clinical benefits. In order to investigate these questions, we present a miniaturized system for spectroscopic imaging of brain hemodynamics. The system consists of a 144 ×144, [Formula: see text] pixel pitch, high-sensitivity, analog-output CMOS imager fabricated in a standard 0.35 μm CMOS process, along with a miniaturized imaging system comprising illumination, focusing, analog-to-digital conversion and μSD card based data storage. This enables stand alone operation without a computer, nor electrical or fiberoptic tethers. To achieve high sensitivity, the pixel uses a capacitive transimpedance amplifier (CTIA). The nMOS transistors are in the pixel while pMOS transistors are column-parallel, resulting in a fill factor (FF) of 26%. Running at 60 fps and exposed to 470 nm light, the CMOS imager has a minimum detectable intensity of 2.3 nW/cm(2) , a maximum signal-to-noise ratio (SNR) of 49 dB at 2.45 μW/cm(2) leading to a dynamic range (DR) of 61 dB while consuming 167 μA from a 3.3 V supply. In anesthetized rats, the system was able to detect temporal, spatial and spectral hemodynamic changes in response to DBS.

  15. Handheld nonlinear microscope system comprising a 2 MHz repetition rate, mode-locked Yb-fiber laser for in vivo biomedical imaging.

    PubMed

    Krolopp, Ádám; Csákányi, Attila; Haluszka, Dóra; Csáti, Dániel; Vass, Lajos; Kolonics, Attila; Wikonkál, Norbert; Szipőcs, Róbert

    2016-09-01

    A novel, Yb-fiber laser based, handheld 2PEF/SHG microscope imaging system is introduced. It is suitable for in vivo imaging of murine skin at an average power level as low as 5 mW at 200 kHz sampling rate. Amplified and compressed laser pulses having a spectral bandwidth of 8 to 12 nm at around 1030 nm excite the biological samples at a ~1.89 MHz repetition rate, which explains how the high quality two-photon excitation fluorescence (2PEF) and second harmonic generation (SHG) images are obtained at the average power level of a laser pointer. The scanning, imaging and detection head, which comprises a conventional microscope objective for beam focusing, has a physical length of ~180 mm owing to the custom designed imaging telescope system between the laser scanner mirrors and the entrance aperture of the microscope objective. Operation of the all-fiber, all-normal dispersion Yb-fiber ring laser oscillator is electronically controlled by a two-channel polarization controller for Q-switching free mode-locked operation. The whole nonlinear microscope imaging system has the main advantages of the low price of the fs laser applied, fiber optics flexibility, a relatively small, light-weight scanning and detection head, and a very low risk of thermal or photochemical damage of the skin samples.

  16. Handheld nonlinear microscope system comprising a 2 MHz repetition rate, mode-locked Yb-fiber laser for in vivo biomedical imaging

    PubMed Central

    Krolopp, Ádám; Csákányi, Attila; Haluszka, Dóra; Csáti, Dániel; Vass, Lajos; Kolonics, Attila; Wikonkál, Norbert; Szipőcs, Róbert

    2016-01-01

    A novel, Yb-fiber laser based, handheld 2PEF/SHG microscope imaging system is introduced. It is suitable for in vivo imaging of murine skin at an average power level as low as 5 mW at 200 kHz sampling rate. Amplified and compressed laser pulses having a spectral bandwidth of 8 to 12 nm at around 1030 nm excite the biological samples at a ~1.89 MHz repetition rate, which explains how the high quality two-photon excitation fluorescence (2PEF) and second harmonic generation (SHG) images are obtained at the average power level of a laser pointer. The scanning, imaging and detection head, which comprises a conventional microscope objective for beam focusing, has a physical length of ~180 mm owing to the custom designed imaging telescope system between the laser scanner mirrors and the entrance aperture of the microscope objective. Operation of the all-fiber, all-normal dispersion Yb-fiber ring laser oscillator is electronically controlled by a two-channel polarization controller for Q-switching free mode-locked operation. The whole nonlinear microscope imaging system has the main advantages of the low price of the fs laser applied, fiber optics flexibility, a relatively small, light-weight scanning and detection head, and a very low risk of thermal or photochemical damage of the skin samples. PMID:27699118

  17. Hemisphere-Specific Effects of Subthalamic Nucleus Deep Brain Stimulation on Speaking Rate and Articulatory Accuracy of Syllable Repetitions in Parkinson's Disease.

    PubMed

    Wang, Emily Q; Metman, Leo Verhagen; Bakay, Roy A E; Arzbaecher, Jean; Bernard, Bryan; Corcos, Daniel M

    2006-01-01

    This study tested the hypothesis that left versus right deep brain stimulation (DBS) of the subthalamic nucleus (STN) would have differential effects on speech. Twenty right-handed individuals with advanced Parkinson's disease (PD) underwent unilateral STN DBS. Ten were operated on the right and 10 on the left hemisphere as indicated by severity of nonspeech motor function. Speech was evaluated before surgery and 3 to 6 months after surgery with stimulator-off and with stimulator-on, with all participants off anti-parkinsonian medication for 12 hours before evaluation. Evaluators and patient speakers were blinded to the stimulator status at the postsurgery evaluations. Motor performance was assessed with UPDRS-III. Each participant produced three samples of diadochokinetic syllables. Syllable rate, syllable and vowel duration, VOT, and F0 were obtained. The diadochokinetic syllables were rated for articulatory accuracy and speaking rate. Twenty graduate clinicians served as judges. The samples were randomly presented via headphones. A mixed ANOVA with repeated measures was used to assess the significance of the changes in UPRS-III scores and speech measures. The results indicated that unilateral STN DBS produced improvement in nonspeech motor function regardless of the side of stimulation. In contrast, the changes in articulatory accuracy and syllable rate associated with the STN DBS were hemisphere specific.

  18. Live-cell stimulated Raman scattering imaging of alkyne-tagged biomolecules.

    PubMed

    Hong, Senlian; Chen, Tao; Zhu, Yuntao; Li, Ang; Huang, Yanyi; Chen, Xing

    2014-06-02

    Alkynes can be metabolically incorporated into biomolecules including nucleic acids, proteins, lipids, and glycans. In addition to the clickable chemical reactivity, alkynes possess a unique Raman scattering within the Raman-silent region of a cell. Coupling this spectroscopic signature with Raman microscopy yields a new imaging modality beyond fluorescence and label-free microscopies. The bioorthogonal Raman imaging of various biomolecules tagged with an alkyne by a state-of-the-art Raman imaging technique, stimulated Raman scattering (SRS) microscopy, is reported. This imaging method affords non-invasiveness, high sensitivity, and molecular specificity and therefore should find broad applications in live-cell imaging.

  19. Intense high repetition rate Mo Kα x-ray source generated from laser solid interaction for imaging application.

    PubMed

    Huang, K; Li, M H; Yan, W C; Guo, X; Li, D Z; Chen, Y P; Ma, Y; Zhao, J R; Li, Y F; Zhang, J; Chen, L M

    2014-11-01

    We report an efficient Mo Kα x-ray source produced by interaction of femtosecond Ti: sapphire laser pulses with a solid Molybdenum target working at 1 kHz repetition rate. The generated Mo Kα x-ray intensity reaches to 4.7 × 10(10) photons sr(-1) s(-1), corresponding to an average power of 0.8 mW into 2π solid angle. The spatial resolution of this x-ray source is measured to be 26 lp/mm. With the high flux and high spatial resolution characteristics, high resolving in-line x-ray radiography was realized on test objects and large size biological samples within merely half a minute. This experiment shows the possibility of laser plasma hard x-ray source as a new low cost and high resolution system for radiography and its ability of ultrafast x-ray pump-probe study of matter.

  20. Functional tissue pulsatility imaging of the brain during visual stimulation.

    PubMed

    Kucewicz, John C; Dunmire, Barbrina; Leotta, Daniel F; Panagiotides, Heracles; Paun, Marla; Beach, Kirk W

    2007-05-01

    Functional tissue pulsatility imaging is a new ultrasonic technique being developed to map brain function by measuring changes in tissue pulsatility as a result of changes in blood flow with neuronal activation. The technique is based in principle on plethysmography, an older, nonultrasound technology for measuring expansion of a whole limb or body part as a result of perfusion. Perfused tissue expands by a fraction of a percent early in each cardiac cycle when arterial inflow exceeds venous outflow, and it relaxes later in the cardiac cycle when venous drainage dominates. Tissue pulsatility imaging (TPI) uses tissue Doppler signal processing methods to measure this pulsatile "plethysmographic" signal from hundreds or thousands of sample volumes in an ultrasound image plane. A feasibility study was conducted to determine if TPI could be used to detect regional brain activation during a visual contrast-reversing checkerboard block paradigm study. During a study, ultrasound data were collected transcranially from the occipital lobe as a subject viewed alternating blocks of a reversing checkerboard (stimulus condition) and a static, gray screen (control condition). Multivariate analysis of variance was used to identify sample volumes with significantly different pulsatility waveforms during the control and stimulus blocks. In 7 of 14 studies, consistent regions of activation were detected from tissue around the major vessels perfusing the visual cortex.

  1. Repetition Reduction: Lexical Repetition in the Absence of Referent Repetition

    ERIC Educational Resources Information Center

    Lam, Tuan Q.; Watson, Duane G.

    2014-01-01

    Compared to words that are new to a discourse, repeated words are produced with reduced acoustic prominence. Although these effects are often attributed to priming in the production system, the locus of the effect within the production system remains unresolved because, in natural speech, repetition often involves repetition of referents and…

  2. Kaposi's sarcoma-associated herpesvirus Rta tetramers make high-affinity interactions with repetitive DNA elements in the Mta promoter to stimulate DNA binding of RBP-Jk/CSL.

    PubMed

    Palmeri, Diana; Carroll, Kyla Driscoll; Gonzalez-Lopez, Olga; Lukac, David M

    2011-11-01

    Kaposi's sarcoma-associated herpesvirus (KSHV; also known as human herpesvirus 8 [HHV-8]) is the etiologic agent of Kaposi's sarcoma (KS) and lymphoproliferative diseases. We previously demonstrated that the KSHV lytic switch protein Rta stimulates DNA binding of the cellular RBP-Jk/CSL protein, the nuclear component of the Notch pathway, on Rta target promoters. In the current study, we define the promoter requirements for formation of transcriptionally productive Rta/RBP-Jk/DNA complexes. We show that highly pure Rta footprints 7 copies of a previously undescribed repetitive element in the promoter of the essential KSHV Mta gene. We have termed this element the "CANT repeat." CANT repeats are found on both strands of DNA and have a consensus sequence of ANTGTAACANT(A/T)(A/T)T. We demonstrate that Rta tetramers make high-affinity interactions (i.e., nM) with 64 bp of the Mta promoter but not single CANT units. The number of CANT repeats, their presence in palindromes, and their positions relative to the RBP-Jk binding site determine the optimal target for Rta stimulation of RBP-Jk DNA binding and formation of ternary Rta/RBP-Jk/DNA complexes. DNA binding and tetramerization mutants of Rta fail to stimulate RBP-Jk DNA binding. Our chromatin immunoprecipitation assays show that RBP-Jk DNA binding is broadly, but selectively, stimulated across the entire KSHV genome during reactivation. We propose a model in which tetramerization of Rta allows it to straddle RBP-Jk and contact repeat units on both sides of RBP-Jk. Our study integrates high-affinity Rta DNA binding with the requirement for a cellular transcription factor in Rta transactivation.

  3. Repetitive strain injury.

    PubMed

    van Tulder, Maurits; Malmivaara, Antti; Koes, Bart

    2007-05-26

    Repetitive strain injury remains a controversial topic. The term repetitive strain injury includes specific disorders such as carpal tunnel syndrome, cubital tunnel syndrome, Guyon canal syndrome, lateral epicondylitis, and tendonitis of the wrist or hand. The diagnosis is usually made on the basis of history and clinical examination. Large high-quality studies using newer imaging techniques, such as MRI and ultrasonography are few. Consequently, the role of such imaging in diagnosis of upper limb disorders remains unclear. In many cases, no specific diagnosis can be established and complaints are labelled as non-specific. Little is known about the effectiveness of treatment options for upper limb disorders. Strong evidence for any intervention is scarce and the effect, if any, is mainly short-term pain relief. Exercise is beneficial for non-specific upper limb disorders. Immobilising hand braces and open carpal tunnel surgery release are beneficial for carpal tunnel syndrome, and topical and oral non-steroidal anti-inflammatory drugs, and corticosteroid injections are helpful for lateral epicondylitis. Exercise is probably beneficial for neck pain, as are corticosteroid injections and exercise for shoulder pain. Although upper limb disorders occur frequently in the working population, most trials have not exclusively included a working population or assessed effects on work-related outcomes. Further high-quality trials should aim to include sufficient sample sizes, working populations, and work-related outcomes.

  4. Intense high repetition rate Mo Kα x-ray source generated from laser solid interaction for imaging application

    SciTech Connect

    Huang, K.; Li, M. H.; Yan, W. C.; Ma, Y.; Zhao, J. R.; Li, Y. F.; Chen, L. M.; Guo, X.; Li, D. Z.; Chen, Y. P.; Zhang, J.

    2014-11-15

    We report an efficient Mo Kα x-ray source produced by interaction of femtosecond Ti: sapphire laser pulses with a solid Molybdenum target working at 1 kHz repetition rate. The generated Mo Kα x-ray intensity reaches to 4.7 × 10{sup 10} photons sr{sup −1} s{sup −1}, corresponding to an average power of 0.8 mW into 2π solid angle. The spatial resolution of this x-ray source is measured to be 26 lp/mm. With the high flux and high spatial resolution characteristics, high resolving in-line x-ray radiography was realized on test objects and large size biological samples within merely half a minute. This experiment shows the possibility of laser plasma hard x-ray source as a new low cost and high resolution system for radiography and its ability of ultrafast x-ray pump-probe study of matter.

  5. Imaging artifacts induced by electrical stimulation during conventional fMRI of the brain.

    PubMed

    Antal, Andrea; Bikson, Marom; Datta, Abhishek; Lafon, Belen; Dechent, Peter; Parra, Lucas C; Paulus, Walter

    2014-01-15

    Functional magnetic resonance imaging (fMRI) of brain activation during transcranial electrical stimulation is used to provide insight into the mechanisms of neuromodulation and targeting of particular brain structures. However, the passage of current through the body may interfere with the concurrent detection of blood oxygen level-dependent (BOLD) signal, which is sensitive to local magnetic fields. To test whether these currents can affect concurrent fMRI recordings we performed conventional gradient echo-planar imaging (EPI) during transcranial direct current (tDCS) and alternating current stimulation (tACS) on two post-mortem subjects. tDCS induced signals in both superficial and deep structures. The signal was specific to the electrode montage, with the strongest signal near cerebrospinal fluid (CSF) and scalp. The direction of change relative to non-stimulation reversed with tDCS stimulation polarity. For tACS there was no net effect of the MRI signal. High-resolution individualized modeling of current flow and induced static magnetic fields suggested a strong coincidence of the change EPI signal with regions of large current density and magnetic fields. These initial results indicate that (1) fMRI studies of tDCS must consider this potentially confounding interference from current flow and (2) conventional MRI imaging protocols can be potentially used to measure current flow during transcranial electrical stimulation. The optimization of current measurement and artifact correction techniques, including consideration of the underlying physics, remains to be addressed.

  6. Chronic occupational repetitive strain injury.

    PubMed Central

    O'Neil, B. A.; Forsythe, M. E.; Stanish, W. D.

    2001-01-01

    OBJECTIVE: To review common repetitive strain injuries (RSIs) that occur in the workplace, emphasizing diagnosis, treatment, and etiology of these conditions. QUALITY OF EVIDENCE: A MEDLINE search from January 1966 to June 1999 focused on articles published since 1990 because RSIs are relatively new diagnoses. MeSH headings that were explored using the thesaurus included "cumulative trauma disorder," "overuse injury," and "repetitive strain injury." The search was limited to English articles only, and preference was given to randomized controlled trials. MAIN MESSAGE: Repetitive strain injuries result from repeated stress to the body's soft tissue structures including muscles, tendons, and nerves. They often occur in patients who perform repetitive movements either in their jobs or in extracurricular activities. Common RSIs include tendon-related disorders, such as rotator cuff tendonitis, and peripheral nerve entrapment disorders, such as carpal tunnel syndrome. A careful history and physical examination often lead to the diagnosis, but newer imaging techniques, such as magnetic resonance imaging and ultrasound, can help in refractory cases. Conservative management with medication, physiotherapy, or bracing is the mainstay of treatment. Surgery is reserved for cases that do not respond to treatment. CONCLUSION: Repetitive strain injury is common; primary care physicians must establish a diagnosis and, more importantly, its relationship to occupation. Treatment can be offered by family physicians who refer to specialists for cases refractory to conservative management. PMID:11228032

  7. In vivo functional photoacoustic micro-imaging of the electrically stimulated rat brain with multiwavelengths

    NASA Astrophysics Data System (ADS)

    Liao, Lun-De; Li, Meng-Lin; Lai, Hsin-Yi; Chen, You-Yin; Chao, Paul C.-P.; Wang, Po-Hsun

    2010-02-01

    In this study, we report on using multi-wavelength photoacoustic microscopy to image hemodynamic changes of total hemoglobin concentration (HbT) (i.e., blood volume) and oxygenation (SO2) in rat brain cortex vessels with electrical stimulation. Electrical stimulation of the rat left forelimb was applied to evoke changes in vascular dynamics of the rat somatosensory cortex. The applied current pulses were with a pulse frequency of 3 Hz, pulse duration of 0.2 ms, and pulse amplitude of 5 mA, respectively. The imaging target of rat brains was demarcated at AP 0 - -2.5 mm and ML +/- 6 mm with respect to bregma. HbT changes were probed by images acquired at 570 nm, a hemoglobin isosbestic point while SO2 changes were imaged by those acquired at 560 nm or 600 nm and their derivatives, which were normalized to those with 570 nm wavelengths. Correlation between the electrical stimulation paradigm and images acquired at 570, 560, and 600 nm in contralateral and ipsilateral vasculature was statistically analyzed, showing that the HbT and SO2 changes revealed by multi-wavelength photoacoustic images spatially correlated with contralateral vasculature.

  8. A Noninvasive Imaging Approach to Understanding Speech Changes following Deep Brain Stimulation in Parkinson's Disease

    ERIC Educational Resources Information Center

    Narayana, Shalini; Jacks, Adam; Robin, Donald A.; Poizner, Howard; Zhang, Wei; Franklin, Crystal; Liotti, Mario; Vogel, Deanie; Fox, Peter T.

    2009-01-01

    Purpose: To explore the use of noninvasive functional imaging and "virtual" lesion techniques to study the neural mechanisms underlying motor speech disorders in Parkinson's disease. Here, we report the use of positron emission tomography (PET) and transcranial magnetic stimulation (TMS) to explain exacerbated speech impairment following…

  9. A K-alpha x-ray source using high energy and high repetition rate laser system for phase contrast imaging.

    PubMed

    Serbanescu, Cristina; Fourmaux, Sylvain; Kieffer, Jean-Claude; Kincaid, Russell; Krol, Andrzej

    2009-01-01

    K-alpha x-ray sources from laser produced plasmas provide completely new possibilities for x-ray phase-contrast imaging applications. By tightly focusing intense femtosecond laser pulses onto a solid target K-alpha x-ray pulses are generated through the interaction of energetic electrons created in the plasma with the bulk target. In this paper, we present a continuous and efficient Mo K-alpha x-ray source produced by a femtosecond laser system operating at 100 Hz repetition rate with maximum pulse energy of 110 mJ before compression. The source has an x-ray conversion efficiency of greater than 10(-5) into K-alpha line emission. In preparation for phase contrast imaging applications, the size of the resultant K-alpha x-ray emission spot has been also characterized. The source exhibits sufficient spatial coherence to observe phase contrast. We observe a relatively small broadening of the K-alpha source size compared to the size of the laser beam itself. Detailed characterization of the source including the x-ray spectrum and the x-ray average yield along with phase contrast images of test objects will be presented.

  10. Development of in situ Imaging Probe for Surgical Operation of Deep Brain Stimulation

    NASA Astrophysics Data System (ADS)

    Noda, Toshihiko; Yi-Li, Pan; Tagawa, Ayato; Kobayashi, Takuma; Sasagawa, Kiyotaka; Tokuda, Takashi; Hatanaka, Yumiko; Nakano, Naoki; Kato, Amami; Shiosaka, Sadao; Ohta, Jun

    A novel clinical medical tool for surgical operation of deep brain stimulation was fabricated and evaluated. Dedicated micro-CMOS image sensor was mounted on the tip of quite fine probe tube. The probe has the same diameter as a probe that is utilized in surgical operation. A light source LED was also mounted on the tip of probe. Imaging trial using a postmortem brain was performed with the fabricated probe. The probe can be inserted into a brain easily and take still images of the brain.

  11. Characterization of cerebral blood flow response to sciatic nerve stimulation using laser speckle imaging

    NASA Astrophysics Data System (ADS)

    Wang, Zheng; Luo, Qingming; Cheng, Haiying; Lu, Qiang

    2003-12-01

    Laser speckle imaging (LSI) through a thinned skull over the somatosensory cortex was utilized to map the spatiotemporal characteristics of local cerebral flood flow (CBF) in anesthetized rats during sciatic nerve stimulation. Region-of-interest selection and Temporal clustering analysis (TCA) method was illustrated on the dataset from high-resolution optical imaging to detect the timing and location of CBF activation. Contralateral hindlimb sensory cortical microflow was activated to increase promptly in less than 1 s after the onset of 2 s electrical stimulation then evolved in different discrete regions. Individual arteries, veins and capillaries in different diameters were activated with the time going. This pattern is similar but slightly elaborated to the results obtained from laser Doppler flowmetry (LDF), functional magnetic resonance imaging (fMRI). We presented this combination to characterize the behaviors of CBF response to neuronal activity, which might possibly lead to a better understanding of neurovascular coupling and fMRI signals.

  12. Assessment of an optically stimulated infrared emission from image intensifier tube photocathodes

    NASA Astrophysics Data System (ADS)

    Wales, Jesse G.; Marasco, Peter L.

    2005-05-01

    Anecdotal evidence suggested that bright, night-vision imaging system (NVIS) compatible, green cockpit displays could cause a veiling luminance in night-vision goggles (NVGs) and degrade visual performance. The mechanism suspected of causing this veiling luminance was an infrared emission from the image intensifier tube photocathode stimulated by visible, NVIS compatible light. This paper describes an effort to measure this stimulated infrared emission from three different image intensifier tubes. Measurements of the emission were analyzed with respect to tube age, the wavelength of incident illumination, and illumination angle of incidence. The emission was found during certain combinations of light wavelengths, angles, and intensities. However, results suggest that this phenomenon is not sufficiently strong to cause observable veiling luminance in NVGs.

  13. Optical imaging of the retina in response to the electrical stimulation

    NASA Astrophysics Data System (ADS)

    Fujikado, Takashi; Okawa, Yoshitaka; Miyoshi, Tomomitsu; Hirohara, Yoko; Mihashi, Toshifumi; Tano, Yasuo

    2008-02-01

    Purposes: To determine if reflectance changes of the retina can be detected following electrical stimulation to the retina using a newly developed optical-imaging fundus camera. Methods: Eyes of cats were examined after pupil dilation. Retina was stimulated either focally by a ball-type electrode (BE) placed on the fenestrated sclera or diffusely using a ring-type electrode (RE) placed on the corneoscleral limbus. Electrical stimulation by biphasic pulse trains was applied for 4 seconds. Fundus images with near-infrared (800-880 nm) light were obtained between 2 seconds before and 20 seconds after the electrical stimulation (ES). A two-dimensional map of the reflectance changes (RCs) was constructed. The effect of Tetrodotoxin (TTX) was also investigated on RCs by ES using RE. Results: RCs were observed around the retinal locus where the stimulating electrodes were positioned (BE) or in the retina of the posterior pole (RE), in which the latency was about 0.5 to 1.0 sec and the peak time about 2 to 5 sec after the onset of ES. The intensity of the RCs increased with the increase of the stimulus current in both cases. RCs were completely suppressed after the injection of TTX. Conclusions: The functional changes of the retina either by focal or diffuse electrical stimulation were successfully detected by optical imaging of the retina. The contribution of retinal ganglion cells on RCs by ES was confirmed by TTX experiment. This method may be applied to the objective evaluation of the artificial retina.

  14. Comparison between neurostimulation techniques repetitive transcranial magnetic stimulation vs electroconvulsive therapy for the treatment of resistant depression: patient preference and cost-effectiveness

    PubMed Central

    Magnezi, Racheli; Aminov, Emanuel; Shmuel, Dikla; Dreifuss, Merav; Dannon, Pinhas

    2016-01-01

    Objectives Major depressive disorder (MDD) is a common disorder, widely distributed in the population, and is often associated with severe symptoms and functional impairment. It has been estimated that 30% of MDD patients do not benefit adequately from therapeutic interventions, including pharmacotherapy and psychotherapy. Treatment-resistant depression (TRD) is generally defined as a failure to achieve remission, despite therapeutic interventions. Aim The most effective treatment alternatives for TRD are hospitalization, electroconvulsive therapy (ECT), and transcranial magnetic stimulation (TMS). Here we compared the clinical effectiveness of ECT and TMS, including success rates, patient responses, side-effect profiles, and financial worthiness. Results We found that ECT (P<0.0001) was more effective than TMS (P<0.012) (not statistically significant in group effect) in TRD patients. However, ECT patients reported a higher percentage of side effects (P<0.01) and the TMS treatment scored better in terms of patient preference. The cost benefit of ECT was higher than that of TMS (US$2075 vs US$814). Patient’s preferences for treatment could be more intense in the TMS, if the TMS is included in the Health Maintenance Organization’s service list. Conclusion We propose that both of these treatment options should be available in psychiatric wards, thus expanding the therapeutic toolkit for TRD. PMID:27536079

  15. Hyperspectral imaging with in-line interferometric femtosecond stimulated Raman scattering spectroscopy.

    PubMed

    Dobner, Sven; Fallnich, Carsten

    2014-02-28

    We present the hyperspectral imaging capabilities of in-line interferometric femtosecond stimulated Raman scattering. The beneficial features of this method, namely, the improved signal-to-background ratio compared to other applicable broadband stimulated Raman scattering methods and the simple experimental implementation, allow for a rather fast acquisition of three-dimensional raster-scanned hyperspectral data-sets, which is shown for PMMA beads and a lipid droplet in water as a demonstration. A subsequent application of a principle component analysis displays the chemical selectivity of the method.

  16. Evaluation of the dependence of CEST-EPI measurement on repetition time, RF irradiation duty cycle and imaging flip angle for enhanced pH sensitivity.

    PubMed

    Sun, Phillip Zhe; Lu, Jie; Wu, Yin; Xiao, Gang; Wu, Renhua

    2013-09-07

    Chemical exchange saturation transfer (CEST) is a magnetic resonance imaging (MRI) contrast mechanism that can detect dilute CEST agents and microenvironmental properties, with a host of promising applications. Experimental measurement of the CEST effect is complex, and depends on not only CEST agent concentration and exchange rate, but also experimental parameters such as RF irradiation amplitude and scheme. Although echo planar imaging (EPI) has been increasingly used for CEST MRI, the relationship between CEST effect and repetition time (TR), RF irradiation duty cycle (DC) and EPI flip angle (α) has not been fully evaluated and optimized to enhance CEST MRI sensitivity. In addition, our study evaluated gradient echo CEST-EPI by quantifying the CEST effect and its signal-to-noise ratio per unit time (SNRput) as functions of TR, DC and α. We found that CEST effect increased with TR and DC but decreased with α. Importantly, we found that SNRput peaked at intermediate TRs of about twice the T1 and α, at approximately 75°, and increased with RF DC. The simulation results were validated using a dual-pH creatine-gel CEST phantom. In summary, our study provides a useful framework for optimizing CEST MRI experiments.

  17. Evaluation of the dependence of CEST-EPI measurement on repetition time, RF irradiation duty cycle and imaging flip angle for enhanced pH sensitivity

    NASA Astrophysics Data System (ADS)

    Zhe Sun, Phillip; Lu, Jie; Wu, Yin; Xiao, Gang; Wu, Renhua

    2013-09-01

    Chemical exchange saturation transfer (CEST) is a magnetic resonance imaging (MRI) contrast mechanism that can detect dilute CEST agents and microenvironmental properties, with a host of promising applications. Experimental measurement of the CEST effect is complex, and depends on not only CEST agent concentration and exchange rate, but also experimental parameters such as RF irradiation amplitude and scheme. Although echo planar imaging (EPI) has been increasingly used for CEST MRI, the relationship between CEST effect and repetition time (TR), RF irradiation duty cycle (DC) and EPI flip angle (α) has not been fully evaluated and optimized to enhance CEST MRI sensitivity. In addition, our study evaluated gradient echo CEST-EPI by quantifying the CEST effect and its signal-to-noise ratio per unit time (SNRput) as functions of TR, DC and α. We found that CEST effect increased with TR and DC but decreased with α. Importantly, we found that SNRput peaked at intermediate TRs of about twice the T1 and α, at approximately 75°, and increased with RF DC. The simulation results were validated using a dual-pH creatine-gel CEST phantom. In summary, our study provides a useful framework for optimizing CEST MRI experiments.

  18. Nonconventional interventions for chronic post-traumatic stress disorder: Ketamine, repetitive trans-cranial magnetic stimulation (rTMS), and alternative approaches.

    PubMed

    Pradhan, Basant; Kluewer D'Amico, Jessica; Makani, Ramkrishna; Parikh, Tapan

    2016-01-01

    It is alarming that only 59% of those who have post-traumatic stress disorder (PTSD) respond to selective serotonin reuptake inhibitors. Many existing treatments, both pharmacological and nonpharmacological, do not directly target trauma memories that lay at the core of the PTSD pathogenesis. Notable exceptions are medications like ketamine and propranolol and trauma-focused psychotherapies like eye-movement desensitization and reprocessing therapy (developed by Shapiro) and Trauma Interventions using Mindfulness Based Extinction and Reconsolidation (TIMBER) for trauma memories (developed by Pradhan). Although the antidepressant effects of ketamine are no longer news, ketamine's effects on treatment refractory PTSD (TR-PTSD) is a recent concept. As TR-PTSD has a marked public health burden and significant limitations in terms of treatment interventions, a thorough assessment of current strategies is required. Research to bring clarity to the underlying pathophysiology and neurobiology of TR-PTSD delineating the chemical, structural, and circuitry abnormalities will take time. In the interim, in the absence of a 1-size-fits-all therapeutic approach, pragmatically parallel lines of research can be pursued using the pharmacological and nonpharmacological treatments that have a strong theoretical rationale for efficacy. This article aims to review the current literature on interventions for PTSD, most notably ketamine, trans-cranial magnetic stimulation treatment, yoga and mindfulness interventions, and TIMBER. We present an outline for their future use, alone as well as in combination, with a hope of providing additional insights as well as advocating for developing more effective therapeutic intervention for this treatment-resistant and debilitating condition.

  19. Repetitive transcranial magnetic stimulation (rTMS) combined with cognitive training is a safe and effective modality for the treatment of Alzheimer's disease: clinical experience.

    PubMed

    Rabey, Jose Martin; Dobronevsky, Evgenia

    2016-12-01

    Alzheimer's disease (AD) is the most common type of dementia among the elderly. Common treatments available and non-pharmacological interventions have their limitations, and new therapeutic approaches are critically needed. Transcranial magnetic stimulation (TMS) is a non-invasive technique that generates an electric current-inducing modulation in cortical excitability. The previous clinical trials showed that combinations of rTMS and cognitive training (rTMS-COG), as provided by the NeuroAD medical device system, offer a novel, safe, and effective method improving mild-to-moderate AD patients. In this article, we present our experience with rTMS-COG treatment, in clinical settings, of 30 mild-to-moderate AD patients that received rTMS-COG commercial treatments in two clinics for 1-h daily sessions, 5 days per week, for 6 weeks (30 sessions). Five patients returned for a second treatment. ADAS-Cog and MMSE scores were measured pre- and post-treatments. The main analyses were conducted on patients who received 1 treatment (n = 30). Data received from the five returning patients were analyzed separately. The effect of rTMS-COG treatment was statistically significant regarding both ADAS-Cog (-2.4 point improvement, PV <0.001) and MMSE (+1.7 points improvement, PV <0.001) scores. About 80 % of patients gained some cognitive improvement following NeuroAD treatment, with more than 60 % improving by more than two points, for a minimum of 9 months. The Neuronix NeuroAD System was shown to be a safe and effective non-invasive modality for cognitive improvement of Alzheimer patients, with measurable outcomes lasting, in some of them, for up to 1 year, following completion of the 6-week daily intervention course (a carryover effect).

  20. A Study on Analysis of EEG Caused by Grating Stimulation Imaging

    NASA Astrophysics Data System (ADS)

    Urakawa, Hiroshi; Nishimura, Toshihiro; Tsubai, Masayoshi; Itoh, Kenji

    Recently, many researchers have studied a visual perception. Focus is attended to studies of the visual perception phenomenon by using the grating stimulation images. The previous researches have suggested that a subset of retinal ganglion cells responds to motion in the receptive field center, but only if the wider surround moves with a different trajectory. We discuss the function of human retina, and measure and analysis EEG(electroencephalography) of a normal subject who looks on grating stimulation images. We confirmed the visual perception of human by EEG signal analysis. We also have obtained that a sinusoidal grating stimulation was given, asymmetry was observed the α wave element in EEG of the symmetric part in a left hemisphere and a right hemisphere of the brain. Therefore, it is presumed that projected image is even when the still picture is seen and the image projected onto retinas of right and left eyes is not even for the dynamic scene. It evaluated it by taking the envelope curve for the detected α wave, and using the average and standard deviation.

  1. Stochastic optical reconstruction microscopy (STORM) in comparison with stimulated emission depletion (STED) and other imaging methods.

    PubMed

    Tam, Johnny; Merino, David

    2015-11-01

    Stochastic optical reconstruction microscopy (STORM) and stimulated emission depletion (STED) microscopy are two super-resolution optical microscopy approaches that have rapidly gained popularity in recent years. Both modalities offer super-resolution imaging capabilities with the potential for imaging in multiple colors, three-dimensions, and the possibility to image in live cells. In this review, we focus on the specific advantages and disadvantages of each technique in the context of each other. STORM has been reported to achieve higher spatial resolution when compared to STED, but a lengthy acquisition may be required. STED utilizes relatively higher laser intensities, but is able to generate a super-resolution image immediately after acquisition without the need for any additional data processing. Ultimately, the choice between STORM and STED will depend not only on the specific application, but also on the users' ability to understand and optimize the various parameters ranging from sample preparation to image acquisition, which determine the quality of the final image. Stochastic optical reconstruction microscopy (STORM) and stimulated emission depletion (STED) are two super-resolution microscopy approaches that have rapidly gained popularity in recent years. STORM is based on the precise localization of a large number of individual molecules that together form a super-resolved image (bottom), whereas STED is based on the scanning of two super-imposed light sources which together allow for a super-resolved spot on the sample to be imaged (top). We discuss the specific advantages and disadvantages of each technique and explain the various parameters that affect image quality, which should be taken into consideration when planning experiments.

  2. The positive effects of high-frequency right dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation on memory, correlated with increases in brain metabolites detected by proton magnetic resonance spectroscopy in recently detoxified alcohol-dependent patients

    PubMed Central

    Qiao, Jun; Jin, Guixing; Lei, Licun; Wang, Lan; Du, Yaqiang; Wang, Xueyi

    2016-01-01

    Objective To explore the effect of right dorsolateral prefrontal cortex (DLPFC) repetitive transcranial magnetic stimulation (rTMS) on memory, and its correlation with levels of hippocampal brain metabolites detected by proton magnetic resonance spectroscopy (1H-MRS) in recently detoxified alcohol-dependent patients. Materials and methods In this randomized, double-blind sham-controlled trial, alcohol-dependent patients were enrolled and randomized into two groups: the experimental group (rTMS, 10 Hz, on right DLPFC, 20 sessions) and the control group (sham stimulation). Memory function was assessed using Hopkins Verbal Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R) before and after treatment. 1H-MRS was used to detect the levels of N-acetyl aspartic acid (NAA), choline (Cho), and creatine (Cr) in bilateral hippocampi before and after treatment. Results Thirty-eight patients (18 in the experimental group and 20 in the control group) were included in the analyses. The experimental group showed significantly greater changes in HVLT-R, BVMT-R, NAA/Cr, and Cho/Cr after rTMS from baseline than the control group. The percentage change in BVMT-R and HVLT-R correlated with the percentage change in NAA/Cr and Cho/Cr in the right brain. Conclusion High-frequency right DLPFC rTMS was associated with improvement in memory dysfunction, which is correlated with levels of hippocampal brain metabolites detected by 1H-MRS in recently detoxified alcohol-dependent patients. PMID:27695332

  3. A femtosecond stimulated Raman loss (fSRL) microscope for highly sensitive bond-selective imaging

    NASA Astrophysics Data System (ADS)

    Zhang, Delong; Slipchenko, Mikhail N.; Yue, Shuhua; Li, Junjie; Cheng, Ji-Xin

    2011-03-01

    We demonstrate nonlinear vibrational imaging of isolated Raman bands by detecting femtosecond pulse stimulated Raman loss. Femtosecond pulse excitation produces a stimulated Raman loss signal that is 12 times larger than what picosecond pulse excitation produces. The strong signal allowed real-time, bond-selective imaging of deuterated palmitic acid-d31 inside live cells, and 3D sectioning of fat storage in live C. elegans. With the high peak power provided by femtosecond pulses, this system is highly compatible with other nonlinear optical modalities such as two-photon excited fluorescence. With most of the excitation power contributed by the Stokes beam in the 1.0 - 1.2 μm wavelength range, photodamage of biological samples was not observed.

  4. A CMOS image sensor using high-speed lock-in pixels for stimulated Raman scattering

    NASA Astrophysics Data System (ADS)

    Lioe, DeXing; Mars, Kamel; Takasawa, Taishi; Yasutomi, Keita; Kagawa, Keiichiro; Hashimoto, Mamoru; Kawahito, Shoji

    2016-03-01

    A CMOS image sensor using high-speed lock-in pixels for stimulated Raman scattering (SRS) spectroscopy is presented in this paper. The effective SRS signal from the stimulated emission of SRS mechanism is very small in contrast to the offset of a probing laser source, which is in the ratio of 10-4 to 10-5. In order to extract this signal, the common offset component is removed, and the small difference component is sampled using switched-capacitor integrator with a fully differential amplifier. The sampling is performed over many integration cycles to achieve appropriate amplification. The lock-in pixels utilizes high-speed lateral electric field charge modulator (LEFM) to demodulate the SRS signal which is modulated at high-frequency of 20MHz. A prototype chip is implemented using 0.11μm CMOS image sensor technology.

  5. Contrast Enhancement for Thermal Acoustic Breast Cancer Imaging via Resonant Stimulation

    DTIC Science & Technology

    2008-03-01

    Wang, “Time-domain reconstruction for thermoa- coustic tomography in a speherical geometry,” IEEE Trans. Med. Imag., vol. 21, no. 7, pp. 814–822, Jul...comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS...excited into resonance via EM stimulation, the effective acoustic scattering cross-section may increase by a factor in excess of 100 based on

  6. Stimulated Raman hyperspectral imaging based on spectral filtering of broadband fiber laser pulses.

    PubMed

    Ozeki, Yasuyuki; Umemura, Wataru; Sumimura, Kazuhiko; Nishizawa, Norihiko; Fukui, Kiichi; Itoh, Kazuyoshi

    2012-02-01

    We demonstrate a technique of hyperspectral imaging in stimulated Raman scattering (SRS) microscopy using a tunable optical filter, whose transmission wavelength can be varied quickly by a galvanometer mirror. Experimentally, broadband Yb fiber laser pulses are synchronized with picosecond Ti:sapphire pulses, and then spectrally filtered out by the filter. After amplification by fiber amplifiers, we obtain narrowband pulses with a spectral width of <3.3 cm(-1) and a wavelength tunability of >225 cm(-1). By using these pulses, we accomplish SRS imaging of polymer beads with spectral information.

  7. Label-free biomedical imaging of lipids by stimulated Raman scattering microscopy.

    PubMed

    Ramachandran, Prasanna V; Mutlu, Ayse Sena; Wang, Meng C

    2015-01-05

    Advances in modern optical microscopy have provided unparalleled tools to study intracellular structure and function, yet visualizing lipid molecules within a cell remains challenging. Stimulated Raman Scattering (SRS) microscopy is a recently developed imaging modality that addresses this challenge. By selectively imaging the vibration of chemical moieties enriched in lipids, this technique allows for rapid imaging of lipid molecules in vivo without the need for perturbative extrinsic labels. SRS microscopy has been effectively employed in the study of fat metabolism, helping uncover novel regulators of lipid storage. This unit provides a brief introduction to the principle of SRS microscopy, and describes methods for its use in imaging lipids in cells, tissues, and whole organisms.

  8. Imaging brain hemodynamic changes during rat forepaw electrical stimulation using functional photoacoustic microscopy.

    PubMed

    Liao, Lun-De; Li, Meng-Lin; Lai, Hsin-Yi; Shih, Yen-Yu I; Lo, Yu-Chun; Tsang, Siny; Chao, Paul Chang-Po; Lin, Chin-Teng; Jaw, Fu-Shan; Chen, You-Yin

    2010-08-15

    The present study reported the development of a novel functional photoacoustic microscopy (fPAM) system for investigating hemodynamic changes in rat cortical vessels associated with electrical forepaw stimulation. Imaging of blood optical absorption by fPAM at multiple appropriately-selected and distinct wavelengths can be used to probe changes in total hemoglobin concentration (HbT, i.e., cerebral blood volume [CBV]) and hemoglobin oxygen saturation (SO(2)). Changes in CBV were measured by images acquired at a wavelength of 570nm (lambda(570)), an isosbestic point of the molar extinction spectra of oxy- and deoxy-hemoglobin, whereas SO(2) changes were sensed by pixel-wise normalization of images acquired at lambda(560) or lambda(600) to those at lambda(570). We demonstrated the capacity of the fPAM system to image and quantify significant contralateral changes in both SO(2) and CBV driven by electrical forepaw stimulation. The fPAM system complements existing imaging techniques, with the potential to serve as a favorable tool for explicitly studying brain hemodynamics in animal models.

  9. Spectrometer-free vibrational imaging by retrieving stimulated Raman signal from highly scattered photons

    PubMed Central

    Liao, Chien-Sheng; Wang, Pu; Wang, Ping; Li, Junjie; Lee, Hyeon Jeong; Eakins, Gregory; Cheng, Ji-Xin

    2015-01-01

    In vivo vibrational spectroscopic imaging is inhibited by relatively slow spectral acquisition on the second scale and low photon collection efficiency for a highly scattering system. Recently developed multiplex coherent anti-Stokes Raman scattering and stimulated Raman scattering techniques have improved the spectral acquisition time down to microsecond scale. These methods using a spectrometer setting are not suitable for turbid systems in which nearly all photons are scattered. We demonstrate vibrational imaging by spatial frequency multiplexing of incident photons and single photodiode detection of a stimulated Raman spectrum within 60 μs. Compared to the spectrometer setting, our method improved the photon collection efficiency by two orders of magnitude for highly scattering specimens. We demonstrated in vivo imaging of vitamin E distribution on mouse skin and in situ imaging of human breast cancerous tissues. The reported work opens new opportunities for spectroscopic imaging in a surgical room and for development of deep-tissue Raman spectroscopy toward molecular level diagnosis. PMID:26601311

  10. Spatially controlled optogenetic light stimulation and recording platform via imaging fiber bundles (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Suárez, Javier I.; Sengupta, Parijat; Mun, Jonathan; Iyer, Rajashekar; Rhodes, Justin; Gillette, Martha U.; Boppart, Stephen A.

    2016-03-01

    Current methods for light delivery in in vivo optogenetic applications are typically accomplished via a single multimode fiber that diffuses light over a large area of the brain, and relies on the spatial distribution of transfected light-sensitive neurons for targeted control. In our investigations, an imaging fiber bundle (Schott) containing 4,500 individual fibers, each with a diameter of 7.5 µm, and an overall outer bundle diameter of 530 µm, served as a conduit for light delivery and optical recording/imaging. The use of this fiber bundle, in contrast to a single multimode fiber, allows for individually-addressable fibers, spatial selectivity at the stimulus site, more precise control of light delivery, and full field-of-view imaging and/or optical recordings of individual neurons in local neural circuits. An objective coupled the two continuous wave diode laser sources (561nm/488nm) (Coherent) for stimulation and imaging into the fiber bundle while a set of galvanometer-scanning mirrors was used to couple the light stimulus to distinct fibers within the proximal end of the imaging fiber bundle. In our study, C1V1(E122T/E162T)-TS-p2A-mCherry (Karl Deisseroth, Stanford) and GCaMP6s transgenic mice (Jackson Labs) were utilized for this all-optical approach. The results of our investigation demonstrate that imaging fiber bundles provide a new level of spatial selectivity and control of light delivery to specific neurons, as well as function as a conduit for optical imaging and recording at the in vivo site of stimulation, in contrast to the use of single multimode fibers that diffusely illuminate neural tissue and lack in vivo imaging capabilities.

  11. Evaluation of the dependence of CEST-EPI measurement on repetition time, RF irradiation duty cycle and imaging flip angle for enhanced pH sensitivity

    PubMed Central

    Sun, Phillip Zhe; Lu, Jie; Wu, Yin; Xiao, Gang; Wu, Renhua

    2013-01-01

    Chemical exchange saturation transfer (CEST) is an MRI contrast mechanism that can detect dilute CEST agents and microenvironmental properties, with a host of promising applications. Experimental measurement of the CEST effect is complex, and depends on not only CEST agent concentration and exchange rate, but also experimental parameters such as RF irradiation amplitude and scheme. Although echo planar imaging (EPI) has been increasingly used for CEST MRI, the relationship between CEST effect and repetition time (TR), RF irradiation duty cycle (DC) and EPI flip angle (α) has not been fully evaluated and optimized to enhance CEST MRI sensitivity. In addition, our study evaluated gradient echo CEST-EPI by quantifying the CEST effect and its signal-to-noise ratio per unit time (SNRput) as functions of TR, duty cycle and α. We found that CEST effect increased with TR and duty cycle but decreased with α. Importantly, we found that SNRput peaked at intermediate TRs of about twice the T1 and α, at approximately 75°, and increased with RF duty cycle. The simulation results were validated using a dual-pH creatine-gel CEST phantom. In summary, our study provides a useful framework for optimizing CEST MRI experiments. PMID:23939228

  12. Time-lens Based Hyperspectral Stimulated Raman Scattering Imaging and Quantitative Spectral Analysis

    PubMed Central

    Wang, Ke; Zhang, Delong; Charan, Kriti; Slipchenko, Mikhail N.; Wang, Ping; Xu, Chris; Cheng, Ji-Xin

    2014-01-01

    We demonstrate a hyperspectral stimulated Raman scattering (SRS) microscope through spectral-transformed excitation. The 1064-nm Stokes pulse was from a synchronized time-lens source, generated through time-domain phase modulation of a continuous wave (CW) laser. The tunable pump pulse was from linear spectral filtering of a femtosecond laser output with an intra-pulse spectral scanning pulse shaper. By electronically modulating the time-lens source at 2.29 MHz, hyperspectral stimulated Raman loss (SRL) images were obtained on a laser-scanning microscope. Using this microscope, DMSO in aqueous solution with a concentration down to 28 mM could be detected at 2 μs time constant. Hyper-spectral SRL images of prostate cancer cells were obtained. Multivariate curve resolution analysis was further applied to decompose the SRL images into concentration maps of CH2 and CH3 bonds. This method offers exciting potential in label-free imaging of live cells using fingerprint Raman bands. Hyperspectral SRS microscopy using a synchronized time-lens source allows mapping of different cellular contents. PMID:23840041

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

    SciTech Connect

    Castello, Marco; Diaspro, Alberto; Vicidomini, Giuseppe

    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 and experimental data, show that the SNR of the restored image improves relative to the gated image, thereby improving the effective resolution.

  14. Neutron Stimulated Emission Computed Tomography: A New Technique for Spectroscopic Medical Imaging

    NASA Astrophysics Data System (ADS)

    Kapadia, A. J.

    Neutron stimulated emission computed tomography (NSECT) is being developed as a new medical-imaging technique to quantify spatial distributions of elements in a sample through inelastic scattering of fast neutrons and detection of the resulting gamma rays. It has the potential to diagnose several disorders in the human body that are characterized by changes in element concentration in the diseased tissue. NSECT is sensitive to several naturally occurring elements in the human body that demonstrate concentration changes in the presence of diseases. NSECT, therefore, has the potential to noninvasively diagnose such disorders with radiation dose that is comparable to other ionizing imaging modalities. This chapter discusses the development and progress of NSECT and presents an overview of the current status of the imaging technique.

  15. Monitoring peripheral nerve degeneration in ALS by label-free stimulated Raman scattering imaging

    NASA Astrophysics Data System (ADS)

    Tian, Feng; Yang, Wenlong; Mordes, Daniel A.; Wang, Jin-Yuan; Salameh, Johnny S.; Mok, Joanie; Chew, Jeannie; Sharma, Aarti; Leno-Duran, Ester; Suzuki-Uematsu, Satomi; Suzuki, Naoki; Han, Steve S.; Lu, Fa-Ke; Ji, Minbiao; Zhang, Rosanna; Liu, Yue; Strominger, Jack; Shneider, Neil A.; Petrucelli, Leonard; Xie, X. Sunney; Eggan, Kevin

    2016-10-01

    The study of amyotrophic lateral sclerosis (ALS) and potential interventions would be facilitated if motor axon degeneration could be more readily visualized. Here we demonstrate that stimulated Raman scattering (SRS) microscopy could be used to sensitively monitor peripheral nerve degeneration in ALS mouse models and ALS autopsy materials. Three-dimensional imaging of pre-symptomatic SOD1 mouse models and data processing by a correlation-based algorithm revealed that significant degeneration of peripheral nerves could be detected coincidentally with the earliest detectable signs of muscle denervation and preceded physiologically measurable motor function decline. We also found that peripheral degeneration was an early event in FUS as well as C9ORF72 repeat expansion models of ALS, and that serial imaging allowed long-term observation of disease progression and drug effects in living animals. Our study demonstrates that SRS imaging is a sensitive and quantitative means of measuring disease progression, greatly facilitating future studies of disease mechanisms and candidate therapeutics.

  16. Post-operative assessment in Deep Brain Stimulation based on multimodal images: registration workflow and validation

    NASA Astrophysics Data System (ADS)

    Lalys, Florent; Haegelen, Claire; Abadie, Alexandre; Jannin, Pierre

    2009-02-01

    Object Movement disorders in Parkinson disease patients may require functional surgery, when medical therapy isn't effective. In Deep Brain Stimulation (DBS) electrodes are implanted within the brain to stimulate deep structures such as SubThalamic Nucleus (STN). This paper describes successive steps for constructing a digital Atlas gathering patient's location of electrodes and contacts for post operative assessment. Materials and Method 12 patients who had undergone bilateral STN DBS have participated to the study. Contacts on post-operative CT scans were automatically localized, based on black artefacts. For each patient, post operative CT images were rigidly registered to pre operative MR images. Then, pre operative MR images were registered to a MR template (super-resolution Collin27 average MRI template). This last registration was the combination of global affine, local affine and local non linear registrations, respectively. Four different studies were performed in order to validate the MR patient to template registration process, based on anatomical landmarks and clinical scores (i.e., Unified Parkinson's disease rating Scale). Visualisation software was developed for displaying into the template images the stimulated contacts represented as cylinders with a colour code related to the improvement of the UPDRS. Results The automatic contact localization algorithm was successful for all the patients. Validation studies for the registration process gave a placement error of 1.4 +/- 0.2 mm and coherence with UPDRS scores. Conclusion The developed visualization tool allows post-operative assessment for previous interventions. Correlation with additional clinical scores will certainly permit to learn more about DBS and to better understand clinical side-effects.

  17. Biocompatible Optically Transparent MEMS for Micromechanical Stimulation and Multimodal Imaging of Living Cells.

    PubMed

    Fior, Raffaella; Kwok, Jeanie; Malfatti, Francesca; Sbaizero, Orfeo; Lal, Ratnesh

    2015-08-01

    Cells and tissues in our body are continuously subjected to mechanical stress. Mechanical stimuli, such as tensile and contractile forces, and shear stress, elicit cellular responses, including gene and protein alterations that determine key behaviors, including proliferation, differentiation, migration, and adhesion. Several tools and techniques have been developed to study these mechanobiological phenomena, including micro-electro-mechanical systems (MEMS). MEMS provide a platform for nano-to-microscale mechanical stimulation of biological samples and quantitative analysis of their biomechanical responses. However, current devices are limited in their capability to perform single cell micromechanical stimulations as well as correlating their structural phenotype by imaging techniques simultaneously. In this study, a biocompatible and optically transparent MEMS for single cell mechanobiological studies is reported. A silicon nitride microfabricated device is designed to perform uniaxial tensile deformation of single cells and tissue. Optical transparency and open architecture of the device allows coupling of the MEMS to structural and biophysical assays, including optical microscopy techniques and atomic force microscopy (AFM). We demonstrate the design, fabrication, testing, biocompatibility and multimodal imaging with optical and AFM techniques, providing a proof-of-concept for a multimodal MEMS. The integrated multimodal system would allow simultaneous controlled mechanical stimulation of single cells and correlate cellular response.

  18. Biocompatible optically transparent MEMS for micromechanical stimulation and multimodal imaging of living cells

    PubMed Central

    Fior, Raffaella; Kwok, Jeanie; Malfatti, Francesca; Sbaizero, Orfeo; Lal, Ratnesh

    2015-01-01

    Cells and tissues in our body are continuously subjected to mechanical stress. Mechanical stimuli, such as tensile and contractile forces, and shear stress, elicit cellular responses, including gene and protein alterations that determine key behaviors, including proliferation, differentiation, migration, and adhesion. Several tools and techniques have been developed to study these mechanobiological phenomena, including micro-electro-mechanical systems (MEMS). MEMS provide a platform for nano-to-microscale mechanical stimulation of biological samples and quantitative analysis of their biomechanical responses. However, current devices are limited in their capability to perform single cell micromechanical stimulations as well as correlating their structural phenotype by imaging techniques simultaneously. In this study, a biocompatible and optically transparent MEMS for single cell mechanobiological studies is reported. A silicon nitride microfabricated device is designed to perform uniaxial tensile deformation of single cells and tissue. Optical transparency and open architecture of the device allows coupling of the MEMS to structural and biophysical assays, including optical microscopy techniques and atomic force microscopy (AFM). We demonstrate the design, fabrication, testing, biocompatibility and multimodal imaging with optical and AFM techniques, providing a proof-of-concept for a multimodal MEMS. The integrated multimodal system would allow simultaneous controlled mechanical stimulation of single cells and correlate cellular response. PMID:25549773

  19. Image-Guided Transcranial Focused Ultrasound Stimulates Human Primary Somatosensory Cortex

    PubMed Central

    Lee, Wonhye; Kim, Hyungmin; Jung, Yujin; Song, In-Uk; Chung, Yong An; Yoo, Seung-Schik

    2015-01-01

    Focused ultrasound (FUS) has recently been investigated as a new mode of non-invasive brain stimulation, which offers exquisite spatial resolution and depth control. We report on the elicitation of explicit somatosensory sensations as well as accompanying evoked electroencephalographic (EEG) potentials induced by FUS stimulation of the human somatosensory cortex. As guided by individual-specific neuroimage data, FUS was transcranially delivered to the hand somatosensory cortex among healthy volunteers. The sonication elicited transient tactile sensations on the hand area contralateral to the sonicated hemisphere, with anatomical specificity of up to a finger, while EEG recordings revealed the elicitation of sonication-specific evoked potentials. Retrospective numerical simulation of the acoustic propagation through the skull showed that a threshold of acoustic intensity may exist for successful cortical stimulation. The neurological and neuroradiological assessment before and after the sonication, along with strict safety considerations through the individual-specific estimation of effective acoustic intensity in situ and thermal effects, showed promising initial safety profile; however, equal/more rigorous precautionary procedures are advised for future studies. The transient and localized stimulation of the brain using image-guided transcranial FUS may serve as a novel tool for the non-invasive assessment and modification of region-specific brain function. PMID:25735418

  20. Image-guided transcranial focused ultrasound stimulates human primary somatosensory cortex.

    PubMed

    Lee, Wonhye; Kim, Hyungmin; Jung, Yujin; Song, In-Uk; Chung, Yong An; Yoo, Seung-Schik

    2015-03-04

    Focused ultrasound (FUS) has recently been investigated as a new mode of non-invasive brain stimulation, which offers exquisite spatial resolution and depth control. We report on the elicitation of explicit somatosensory sensations as well as accompanying evoked electroencephalographic (EEG) potentials induced by FUS stimulation of the human somatosensory cortex. As guided by individual-specific neuroimage data, FUS was transcranially delivered to the hand somatosensory cortex among healthy volunteers. The sonication elicited transient tactile sensations on the hand area contralateral to the sonicated hemisphere, with anatomical specificity of up to a finger, while EEG recordings revealed the elicitation of sonication-specific evoked potentials. Retrospective numerical simulation of the acoustic propagation through the skull showed that a threshold of acoustic intensity may exist for successful cortical stimulation. The neurological and neuroradiological assessment before and after the sonication, along with strict safety considerations through the individual-specific estimation of effective acoustic intensity in situ and thermal effects, showed promising initial safety profile; however, equal/more rigorous precautionary procedures are advised for future studies. The transient and localized stimulation of the brain using image-guided transcranial FUS may serve as a novel tool for the non-invasive assessment and modification of region-specific brain function.

  1. Image-Guided Transcranial Focused Ultrasound Stimulates Human Primary Somatosensory Cortex

    NASA Astrophysics Data System (ADS)

    Lee, Wonhye; Kim, Hyungmin; Jung, Yujin; Song, In-Uk; Chung, Yong An; Yoo, Seung-Schik

    2015-03-01

    Focused ultrasound (FUS) has recently been investigated as a new mode of non-invasive brain stimulation, which offers exquisite spatial resolution and depth control. We report on the elicitation of explicit somatosensory sensations as well as accompanying evoked electroencephalographic (EEG) potentials induced by FUS stimulation of the human somatosensory cortex. As guided by individual-specific neuroimage data, FUS was transcranially delivered to the hand somatosensory cortex among healthy volunteers. The sonication elicited transient tactile sensations on the hand area contralateral to the sonicated hemisphere, with anatomical specificity of up to a finger, while EEG recordings revealed the elicitation of sonication-specific evoked potentials. Retrospective numerical simulation of the acoustic propagation through the skull showed that a threshold of acoustic intensity may exist for successful cortical stimulation. The neurological and neuroradiological assessment before and after the sonication, along with strict safety considerations through the individual-specific estimation of effective acoustic intensity in situ and thermal effects, showed promising initial safety profile; however, equal/more rigorous precautionary procedures are advised for future studies. The transient and localized stimulation of the brain using image-guided transcranial FUS may serve as a novel tool for the non-invasive assessment and modification of region-specific brain function.

  2. Label-free DNA imaging in vivo with stimulated Raman scattering microscopy

    PubMed Central

    Lu, Fa-Ke; Basu, Srinjan; Igras, Vivien; Hoang, Mai P.; Ji, Minbiao; Fu, Dan; Holtom, Gary R.; Neel, Victor A.; Freudiger, Christian W.; Fisher, David E.; Xie, X. Sunney

    2015-01-01

    Label-free DNA imaging is highly desirable in biology and medicine to perform live imaging without affecting cell function and to obtain instant histological tissue examination during surgical procedures. Here we show a label-free DNA imaging method with stimulated Raman scattering (SRS) microscopy for visualization of the cell nuclei in live animals and intact fresh human tissues with subcellular resolution. Relying on the distinct Raman spectral features of the carbon-hydrogen bonds in DNA, the distribution of DNA is retrieved from the strong background of proteins and lipids by linear decomposition of SRS images at three optimally selected Raman shifts. Based on changes on DNA condensation in the nucleus, we were able to capture chromosome dynamics during cell division both in vitro and in vivo. We tracked mouse skin cell proliferation, induced by drug treatment, through in vivo counting of the mitotic rate. Furthermore, we demonstrated a label-free histology method for human skin cancer diagnosis that provides comparable results to other conventional tissue staining methods such as H&E. Our approach exhibits higher sensitivity than SRS imaging of DNA in the fingerprint spectral region. Compared with spontaneous Raman imaging of DNA, our approach is three orders of magnitude faster, allowing both chromatin dynamic studies and label-free optical histology in real time. PMID:26324899

  3. Posture-cognitive dual-tasking: A relevant marker of depression-related psychomotor retardation. An illustration of the positive impact of repetitive transcranial magnetic stimulation in patients with major depressive disorder.

    PubMed

    Deschamps, Thibault; Sauvaget, Anne; Pichot, Anne; Valrivière, Pierre; Maroulidès, Maxime; Bois, Aurore; Bulteau, Samuel; Thomas-Ollivier, Véronique

    2016-12-01

    This study examined whether postural control variables, particularly the center-of-pressure (COP) velocity-based parameters, could be a relevant hallmark of depression-related psychomotor retardation (PMR). We first aimed at investigating the interplay between the PMR scores and the COP performance in patients with major depressive disorder (MDD), as compared to age-matched healthy controls; secondly, we focused on the impact of a repetitive transcranial magnetic stimulation (rTMS) treatment on depression, PMR scores and postural performance. 16 MDD patients, and a control group of 16 healthy adults, were asked to maintain quiet standing balance during two trials with or without vision, and while backward counting (dual task). All the position and velocity-based COP variables were computed. Before and after the rTMS session (n eligible MDD = 10), we assessed the depression level with the Montgomery-Asberg Depression Rating Scale (MADRS), the PMR scores with the French Retardation Rating Scale for Depression (ERD), and postural performance. Before the treatment, significant positive partial correlations were found between the pre-ERD scores and the velocity-based COP variables, especially in the dual-task conditions (p < 0.05). In contrast, there was no significant correlation between the post-ERD scores and any postural parameter after the treatment. The MADRS and ERD scores showed a significant decrease between before and after the rTMS intervention. For the first time, the findings clearly validated the view that the assessment of postural performance - easy to envisage in clinical settings-constitutes a reliable and objective marker of PMR in MDD patients.

  4. Repetitive transcranial magnetic stimulation (rTMS) augmentation of selective serotonin reuptake inhibitors (SSRIs) for SSRI-resistant obsessive-compulsive disorder (OCD): a meta-analysis of randomized controlled trials

    PubMed Central

    Ma, Zhong-Rui; Shi, Li-Jun

    2014-01-01

    Background and objective: Randomized controlled trials (RCTs) on repetitive transcranial magnetic stimulation (rTMS) as augmentation of selective serotonin reuptake inhibitors (SSRIs) for SSRI-resistant obsessive-compulsive disorder (OCD) have yielded conflicting results. Therefore, this meta-analysis was conducted to assess the efficacy of this strategy for SSRI-resistant OCD. Methods: Scientific and medical databases, including international databases (PubMed, MEDLINE, EMBASE, CCTR, Web of Science, PsycINFO), two Chinese databases (CBM-disc, CNKI), and relevant websites dated up to July 2014, were searched for RCTs on this strategy for treating OCD. Mantel-Haenszel random-effects model was used. Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score, response rates and drop-out rates were evaluated. Results: Data were obtained from nine RCTs consisting of 290 subjects. Active rTMS was an effective augmentation strategy in treating SSRI-resistant OCD with a pooled WMD of 3.89 (95% CI = [1.27, 6.50]) for reducing Y-BOCS score and a pooled odds ratio (OR) of 2.65 (95% CI = [1.36, 5.17] for response rates. No significant differences in drop-out rates were found. No publication bias was detected. Conclusion: The pooled examination demonstrated that this strategy seems to be efficacious and acceptable for treating SSRI-resistant OCD. As the number of RCTs included here was limited, further large-scale multi-center RCTs are required to validate our conclusions. PMID:25663986

  5. IMAGE Observations of Sounder Stimulated and Naturally Occurring Fast Z mode Cavity Noise

    NASA Astrophysics Data System (ADS)

    Sonwalkar, V. S.; Taylor, C.; Reddy, A.

    2015-12-01

    We report first observations of sounder stimulated and naturally occurring fast Z mode (ZM) cavity noise detected by the Radio Plasma Imager (RPI) on the IMAGE satellite. The fast Z mode cavity noise is a banded, structure-less radio emission trapped inside fast Z mode cavities, which are characterized by a minimum (fz,min) in fast Z mode cut-off frequency (fz) along a geomagnetic field line [Gurnett et al., JGR, 1983]. Fast Z mode waves reflect at fz ~ f, where f is the wave frequency. Waves in the frequency range fz,min < f < fz,max, where fz,max is the maximum fz above fz,min altitude, are trapped within the cavity as they bounce back and forth between reflection altitudes (fz ~ f) above and below the fz,min altitude. These trapped waves will be observed by a satellite passing through the cavity. The observed cavity noise lower cutoff is at the local Z mode cut-off frequency (fz,Sat) and the upper cut-off is presumably close to fz,max. The cavity noise is observed typically inside the plasmasphere. Comparison of cavity noise as observed on the plasmagram obtained during active sounding with that observed on the dynamic spectra obtained from the interspersed passive wave measurements indicate that the cavity noise is either stimulated by transmissions from the sounder (RPI) or is of natural origin. The sounder stimulated noise is often accompanied by fast Z mode echoes. The naturally occurring cavity noise is observed on both the plasmagram and the dynamic spectra. We believe the stimulated cavity noise is generated due to scattering from small-scale irregularities of waves transmitted by RPI. One potential candidate for the source of naturally occurring Z mode cavity noise is the ring current electrons that can generate fast ZM waves via higher order cyclotron resonance [Nishimura et al., Earth Planets Space, 2007].

  6. Imaging the response of the retina to electrical stimulation with genetically encoded calcium indicators.

    PubMed

    Weitz, Andrew C; Behrend, Matthew R; Lee, Nan Sook; Klein, Ronald L; Chiodo, Vince A; Hauswirth, William W; Humayun, Mark S; Weiland, James D; Chow, Robert H

    2013-04-01

    Epiretinal implants for the blind are designed to stimulate surviving retinal neurons, thus bypassing the diseased photoreceptor layer. Single-unit or multielectrode recordings from isolated animal retina are commonly used to inform the design of these implants. However, such electrical recordings provide limited information about the spatial patterns of retinal activation. Calcium imaging overcomes this limitation, as imaging enables high spatial resolution mapping of retinal ganglion cell (RGC) activity as well as simultaneous recording from hundreds of RGCs. Prior experiments in amphibian retina have demonstrated proof of principle, yet experiments in mammalian retina have been hindered by the inability to load calcium indicators into mature mammalian RGCs. Here, we report a method for labeling the majority of ganglion cells in adult rat retina with genetically encoded calcium indicators, specifically GCaMP3 and GCaMP5G. Intravitreal injection of an adeno-associated viral vector targets ∼85% of ganglion cells with high specificity. Because of the large fluorescence signals provided by the GCaMP sensors, we can now for the first time visualize the response of the retina to electrical stimulation in real-time. Imaging transduced retinas mounted on multielectrode arrays reveals how stimulus pulse shape can dramatically affect the spatial extent of RGC activation, which has clear implications in prosthetic applications. Our method can be easily adapted to work with other fluorescent indicator proteins in both wild-type and transgenic mammals.

  7. Multimodal 7T Imaging of Thalamic Nuclei for Preclinical Deep Brain Stimulation Applications

    PubMed Central

    Xiao, YiZi; Zitella, Laura M.; Duchin, Yuval; Teplitzky, Benjamin A.; Kastl, Daniel; Adriany, Gregor; Yacoub, Essa; Harel, Noam; Johnson, Matthew D.

    2016-01-01

    Precise neurosurgical targeting of electrode arrays within the brain is essential to the successful treatment of a range of brain disorders with deep brain stimulation (DBS) therapy. Here, we describe a set of computational tools to generate in vivo, subject-specific atlases of individual thalamic nuclei thus improving the ability to visualize thalamic targets for preclinical DBS applications on a subject-specific basis. A sequential nonlinear atlas warping technique and a Bayesian estimation technique for probabilistic crossing fiber tractography were applied to high field (7T) susceptibility-weighted and diffusion-weighted imaging, respectively, in seven rhesus macaques. Image contrast, including contrast within thalamus from the susceptibility-weighted images, informed the atlas warping process and guided the seed point placement for fiber tractography. The susceptibility-weighted imaging resulted in relative hyperintensity of the intralaminar nuclei and relative hypointensity in the medial dorsal nucleus, pulvinar, and the medial/ventral border of the ventral posterior nuclei, providing context to demarcate borders of the ventral nuclei of thalamus, which are often targeted for DBS applications. Additionally, ascending fiber tractography of the medial lemniscus, superior cerebellar peduncle, and pallidofugal pathways into thalamus provided structural demarcation of the ventral nuclei of thalamus. The thalamic substructure boundaries were validated through in vivo electrophysiological recordings and post-mortem blockface tissue sectioning. Together, these imaging tools for visualizing and segmenting thalamus have the potential to improve the neurosurgical targeting of DBS implants and enhance the selection of stimulation settings through more accurate computational models of DBS. PMID:27375422

  8. The Negative Repetition Effect

    ERIC Educational Resources Information Center

    Mulligan, Neil W.; Peterson, Daniel J.

    2013-01-01

    A fundamental property of human memory is that repetition enhances memory. Peterson and Mulligan (2012) recently documented a surprising "negative repetition effect," in which participants who studied a list of cue-target pairs twice recalled fewer targets than a group who studied the pairs only once. Words within a pair rhymed, and…

  9. Repetitive Stress Injuries

    MedlinePlus

    ... any problems since. What Are Repetitive Stress Injuries? Repetitive stress injuries (RSIs) are injuries that happen when too much stress is placed on a part of the body, resulting in inflammation (pain and swelling), muscle strain, or tissue damage. This stress generally occurs from ...

  10. An optically stimulated luminescence dosimeter for measuring patient exposure from imaging guidance procedures.

    PubMed

    Ding, George X; Malcolm, Arnold W

    2013-09-07

    There is a growing interest in patient exposure resulting from an x-ray imaging procedure used in image-guided radiation therapy. This study explores a feasibility to use a commercially available optically stimulated luminescence (OSL) dosimeter, nanoDot, for estimating imaging radiation exposure to patients. The kilovoltage x-ray sources used for kV-cone-beam CT (CBCT) imaging acquisition procedures were from a Varian on-board imager (OBI) image system. An ionization chamber was used to determine the energy response of nanoDot dosimeters. The chamber calibration factors for x-ray beam quality specified by half-value layer were obtained from an Accredited Dosimetry Calibration Laboratory. The Monte Carlo calculated dose distributions were used to validate the dose distributions measured by using the nanoDot dosimeters in phantom and in vivo. The range of the energy correction factors for the nanoDot as a function of photon energy and bow-tie filters was found to be 0.88-1.13 for different kVp and bow-tie filters. Measurement uncertainties of nanoDot were approximately 2-4% after applying the energy correction factors. The tests of nanoDot placed on a RANDO phantom and on patient's skin showed consistent results. The nanoDot is suitable dosimeter for in vivo dosimetry due to its small size and manageable energy dependence. The dosimeter placed on a patient's skin has potential to serve as an experimental method to monitor and to estimate patient exposure resulting from a kilovoltage x-ray imaging procedure. Due to its large variation in energy response, nanoDot is not suitable to measure radiation doses resulting from mixed beams of megavoltage therapeutic and kilovoltage imaging radiations.

  11. Roles of repetitive sequences

    SciTech Connect

    Bell, G.I.

    1991-12-31

    The DNA of higher eukaryotes contains many repetitive sequences. The study of repetitive sequences is important, not only because many have important biological function, but also because they provide information on genome organization, evolution and dynamics. In this paper, I will first discuss some generic effects that repetitive sequences will have upon genome dynamics and evolution. In particular, it will be shown that repetitive sequences foster recombination among, and turnover of, the elements of a genome. I will then consider some examples of repetitive sequences, notably minisatellite sequences and telomere sequences as examples of tandem repeats, without and with respectively known function, and Alu sequences as an example of interspersed repeats. Some other examples will also be considered in less detail.

  12. Real-time CARS imaging reveals a calpain-dependent pathway for paranodal myelin retraction during high-frequency stimulation.

    PubMed

    Huff, Terry B; Shi, Yunzhou; Sun, Wenjing; Wu, Wei; Shi, Riyi; Cheng, Ji-Xin

    2011-03-03

    High-frequency electrical stimulation is becoming a promising therapy for neurological disorders, however the response of the central nervous system to stimulation remains poorly understood. The current work investigates the response of myelin to electrical stimulation by laser-scanning coherent anti-Stokes Raman scattering (CARS) imaging of myelin in live spinal tissues in real time. Paranodal myelin retraction at the nodes of Ranvier was observed during 200 Hz electrical stimulation. Retraction was seen to begin minutes after the onset of stimulation and continue for up to 10 min after stimulation was ceased, but was found to reverse after a 2 h recovery period. The myelin retraction resulted in exposure of Kv 1.2 potassium channels visualized by immunofluorescence. Accordingly, treating the stimulated tissue with a potassium channel blocker, 4-aminopyridine, led to the appearance of a shoulder peak in the compound action potential curve. Label-free CARS imaging of myelin coupled with multiphoton fluorescence imaging of immuno-labeled proteins at the nodes of Ranvier revealed that high-frequency stimulation induced paranodal myelin retraction via pathologic calcium influx into axons, calpain activation, and cytoskeleton degradation through spectrin break-down.

  13. The Number of Accumulated Photons and the Quality of Stimulated Emission Depletion Lifetime Images

    SciTech Connect

    Syed, Aleem; Lesoine, Michael D; Bhattacharjee, Ujjal; Petrich, Jacob W; Smith, Emily A

    2014-03-03

    Time binning is used to increase the number of photon counts in the peak channel of stimulated emission depletion (STED) fluorescence lifetime decay curves to determine how it affects the resulting lifetime image. The fluorescence lifetime of the fluorophore, Alexa Fluor 594 phalloidin, bound to F-actin is probed in cultured S2 cells at a spatial resolution of ~40 nm. This corresponds to a tenfold smaller probe volume compared to confocal imaging, and a reduced number of photons contributing to the signal. Pixel-by-pixel fluorescence lifetime measurements and error analysis show that an average of 40 ± 30 photon counts in the peak channel with a signal-to-noise ratio of 20 is enough to calculate a reliable fluorescence lifetime from a single exponential fluorescence decay. No heterogeneity in the actin cytoskeleton in different regions of the cultured cells was measured in the 40- to 400-nm spatial regime.

  14. Are you real? Visual simulation of social housing by mirror image stimulation in single housed mice.

    PubMed

    Fuss, Johannes; Richter, S Helene; Steinle, Jörg; Deubert, Gerald; Hellweg, Rainer; Gass, Peter

    2013-04-15

    Individual housing of social species is a common phenomenon in laboratory animal facilities. Single housing, however, is known to inflict social deprivation with a number of detrimental consequences. Aiming to improve housing conditions of single housed rodents, we investigated the simulation of social housing by mirrors in a series of behavioural experiments and biochemical parameters in mice. We found that chronic mirror-image stimulation increased exploratory behaviours in the holeboard and novel cage tests, but did not alter anxiety, locomotor, or depression-like behaviours. Moreover, no influence on visual recognition memory was observed. Hippocampal brain-derived neurotrophic factor (BDNF) levels, a biomarker for enrichment effects, were unaltered. In line, mirror-image stimulation did not alter home cage behaviour in mice housed with and without mirrors when left undisturbed. Thus, though we found subtle behavioural effects after long-term mirror exposure, we conclude that the simulation of social housing by mirrors is not sufficient to gain the presumably beneficial outcomes induced by social housing.

  15. High-speed stimulated Raman spectral imaging for digital staining of mouse cancer tissues

    NASA Astrophysics Data System (ADS)

    Otsuka, Yoichi; Satoh, Shuya; Kyogaku, Masafumi; Hashimoto, Hiroyuki; Itoh, Kazuyoshi; Ozeki, Yasuyuki

    2014-03-01

    We previously reported the combination of the high-speed stimulated Raman scattering (SRS) microscope and the multivariate analysis (principal component analysis and independent component analysis) for the tissue imaging. The results indicated the visualization of tissue components without chemical staining. Here, we report the multi-area observation of the tumor-grafted mouse tissue based on the same approach. The tumor-grafted mouse (balb/cAcJ nu/nu) was prepared by injection of human pancreatic carcinoma cell line (SUIT-2) into the tail of pancreas. Both of the pancreas cancer and the liver metastasis were harvested and fixed in formalin. Tissues were cryo-sectioned with a thickness of 100 μm and observed. The multispectral images (130 μm square, 500 x 500 pixels) of C-H vibration range from 2800 to 3100cm-1 (91 different Raman shift images) were obtained at a frame rate of 30 frames/sec. The data acquisition both of pancreas and liver were continued for the 48 adjacent areas for the observation both of cancerous and non-cancerous region, respectively. All the datasets were combined to analyze for multivariate analysis. We propose a protocol for drastic data reduction, which we found to give reproducible results and allows fast calculation of ICA. The independent component images indicated the different shapes and compositions between the cancerous region and the non-cancerous region.

  16. 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

  17. Imaging Complex Protein Metabolism in Live Organisms by Stimulated Raman Scattering Microscopy with Isotope Labeling

    PubMed Central

    2016-01-01

    Protein metabolism, consisting of both synthesis and degradation, is highly complex, playing an indispensable regulatory role throughout physiological and pathological processes. Over recent decades, extensive efforts, using approaches such as autoradiography, mass spectrometry, and fluorescence microscopy, have been devoted to the study of protein metabolism. However, noninvasive and global visualization of protein metabolism has proven to be highly challenging, especially in live systems. Recently, stimulated Raman scattering (SRS) microscopy coupled with metabolic labeling of deuterated amino acids (D-AAs) was demonstrated for use in imaging newly synthesized proteins in cultured cell lines. Herein, we significantly generalize this notion to develop a comprehensive labeling and imaging platform for live visualization of complex protein metabolism, including synthesis, degradation, and pulse–chase analysis of two temporally defined populations. First, the deuterium labeling efficiency was optimized, allowing time-lapse imaging of protein synthesis dynamics within individual live cells with high spatial–temporal resolution. Second, by tracking the methyl group (CH3) distribution attributed to pre-existing proteins, this platform also enables us to map protein degradation inside live cells. Third, using two subsets of structurally and spectroscopically distinct D-AAs, we achieved two-color pulse–chase imaging, as demonstrated by observing aggregate formation of mutant hungtingtin proteins. Finally, going beyond simple cell lines, we demonstrated the imaging ability of protein synthesis in brain tissues, zebrafish, and mice in vivo. Hence, the presented labeling and imaging platform would be a valuable tool to study complex protein metabolism with high sensitivity, resolution, and biocompatibility for a broad spectrum of systems ranging from cells to model animals and possibly to humans. PMID:25560305

  18. Clinically Meaningful Efficacy and Acceptability of Low-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) for Treating Primary Major Depression: A Meta-Analysis of Randomized, Double-Blind and Sham-Controlled Trials

    PubMed Central

    Berlim, Marcelo T; Van den Eynde, Frederique; Jeff Daskalakis, Z

    2013-01-01

    Clinical trials on low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) over the right dorsolateral prefrontal cortex have yielded conflicting evidence concerning its overall efficacy for treating major depression (MD). As this may have been the result of limited statistical power of individual trials, we have carried the present systematic review and meta-analysis to examine this issue. We searched the literature for English language randomized, double-blind and sham-controlled trials (RCTs) on LF-rTMS for treating MD from 1995 through July 2012 using EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, SCOPUS, and ProQuest Dissertations & Theses, and from October 2008 until July 2012 using MEDLINE. The main outcome measures were response and remission rates as well as overall dropout rates at study end. We used a random-effects model, odds ratios (ORs) and number needed to treat (NNT). Data were obtained from eight RCTs, totaling 263 subjects with MD. After an average of 12.6±3.9 rTMS sessions, 38.2% (50/131) and 15.1% (20/132) of subjects receiving active LF-rTMS and sham rTMS were classified as responders (OR=3.35; 95% CI=1.4–8.02; p=0.007). Also, 34.6% (35/101) and 9.7% (10/103) of subjects receiving active LF-rTMS and sham rTMS were classified as remitters (OR=4.76; 95% CI=2.13–10.64; p<0.0001). The associated NNT for both response and remission rates was 5. Sensitivity analyses have shown that protocols delivering >1200 magnetic pulses in total as well as those offering rTMS as a monotherapy for MD were associated with higher rates of response to treatment. No differences on mean baseline depression scores and dropout rates for active and sham rTMS groups were found. Finally, the risk of publication bias was low. In conclusion, LF-rTMS is a promising treatment for MD, as it provides clinically meaningful benefits that are comparable to those of standard antidepressants and high-frequency rTMS. Furthermore, LF-rTMS seems to

  19. More female patients and fewer stimuli per session are associated with the short-term antidepressant properties of repetitive transcranial magnetic stimulation (rTMS): a meta-analysis of 54 sham-controlled studies published between 1997–2013

    PubMed Central

    Kedzior, Karina Karolina; Azorina, Valeriya; Reitz, Sarah Kim

    2014-01-01

    Background Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) appears to have short-term antidepressant properties. The aim of the current study was to update our previous meta-analysis and to investigate factors associated with the antidepressant properties of rTMS. Method Following a systematic literature search conducted in Medline and PsycInfo, N=14 sham-controlled, parallel design studies (published after 2008 to August 2013) that had utilized rTMS of the DLPFC in major depression were included in the current meta-analysis. The sensitivity and moderator analyses also included data from N=40 studies (published in 1997–2008) from our previous meta-analysis. The effect size (Cohen’s d) in each study was the standardized difference in mean depression scores (on Hamilton Depression Rating Scale, Beck Depression Inventory, Montgomery Åsberg Depression Rating Scale) from baseline to final (after last session) in rTMS compared to sham groups. Results According to a random-effects model with inverse-variance weights, depression scores were significantly reduced after rTMS compared to sham in studies published from 2008–2013 based on N=659 patients (overall mean weighted d=−0.42, 95% confidence interval: −0.66, −0.18, P=0.001). Combining studies from our past and current meta-analyses (published in 1997–2013; N=54) revealed that depression was significantly reduced after left-fast (>1 Hz), right-slow (≤1 Hz), and bilateral (or sequential) rTMS of DLPFC compared to sham. Significant antidepressant properties of rTMS were observed in studies with patients who were treatment resistant, unipolar (or bipolar), non-psychotic, medication-free (or started on antidepressants concurrently with rTMS). According to univariate meta-regressions, depression scores were significantly lower in studies with more female patients and fewer stimuli per session. There was little evidence that publication bias occurred in the

  20. Trialogue: Preparation, Repetition and...

    ERIC Educational Resources Information Center

    Oberg, Antoinette; And Others

    1996-01-01

    This paper interrogates both curriculum theory and the limits and potentials of textual forms. A set of overlapping discourses (a trialogue) focuses on inquiring into the roles of obsession and repetition in creating deeply interpretive locations for understanding. (SM)

  1. Laser stimulation for pain research

    NASA Astrophysics Data System (ADS)

    Clark, Stuart; Dickinson, Mark R.; King, Terence A.; Jones, Anthony; Chen, Andrew; Derbyshire, Stuart; Townsend, D. W.; Kinahan, Paul E.; Mintun, M. A.; Nichols, T.

    1996-01-01

    Pain is a serious medical problem; it inflicts huge economic loss and personal suffering. Pain signals are conducted via small, non- and partially myelinated A-delta and C nerve fibers and lasers are particularly well suited to stimulating these fibers. Large myelinated fibers convey touch and vibration information and these fibers are also discharged when contact thermodes and other touch pain stimuli are used and this would give a more muddled signal for functional imaging experiments. The advantages of lasers over conventional methods of pain stimulation are good temporal resolution, no variable parameters are involved such as contact area and they give very reproducible results. Accurate inter-stimulus changes can be achieved by computer control of the laser pulse duration, pulse height and repetition rate and this flexibility enables complex stimulation paradigms to be realized. We present a flexible carbon dioxide laser system designed to generate these stimuli for the study of human cerebral pain responses. We discuss the advantages within research of this system over other methods of pain stimulation such as thermal, electrical and magnetic. The stimulator is used in conjunction with functional magnetic resonance imaging, positron emission tomography and electrophysiological methods of imaging the brain's activity. This combination is a powerful tool for the study of pain-induced activity in different areas of the brain. An accurate understanding of the brain's response to pain will help in research into the areas of rheumatoid arthritis and chronic back pain.

  2. Characterizing temporal repetition

    SciTech Connect

    Cukierman, D.; Delgrande, J.

    1996-12-31

    We are investigating the representation and reasoning about schedulable, repeated activities, specified using calendars. Examples of such activities include meeting every Tuesday and Thursday during a semester and attending a seminar every first day of a month. This research provides for a valuable framework for scheduling systems, financial systems and, in general, date-based systems. Very recently work has been done related to reasoning about repetition in the Artificial Intelligence community and others. A partial reference list is provided here. However, to our knowledge no extensive taxonomy of repetition has been proposed in the literature. We believe that reasoning about repeated activities calls for a study and precise definition of the topological characteristics in a repetitive series. In this abstract we summarize a proposal to classify types of repetition according to parameters. The combination of all possible values of these parameters provides a complete taxonomy of repetitive classes with respect to the proposed parameters. Several notions of repetition are considered, some are extremely general, some are very specific.

  3. Use of Optically Stimulated Luminescence Imaging Plates and Reader for Arms Control Applications

    SciTech Connect

    Miller, Steven D.; Tomeraasen, Paul L.; Burghard, Brion J.; Traub, Richard J.

    2001-07-05

    Optically Stimulated Luminescence (OSL) technology has been pioneered at the Pacific Northwest National Laboratory (PNNL) for applications in personnel radiation dosimetry and commercially has become highly successful in replacing older technologies such as Thermoluminescence Dosimeters (TLDs) and film. OSL phosphors are used to measure radiation exposure by illuminating them with light after ionizing radiation exposure and measuring the amount of light emitted by the OSL phosphor. By using a two-dimensional plate of OSL material and raster scanning a light beam across the OSL plate a radiation pattern or image can be measured. The Arms Control community requires an electrons-free medium to measure the attributes of extent and symmetry on Pu pits in storage containers. OSL technology, used in the two-dimensional imaging mode, provides a means to measure these attributes with exposure times on the order of an hour. A special OSL reader has been built by PNNL to measure OSL imaging plates with a size of 20 cm by 30 cm. The reader uses 10 light emitting diode clusters with 10 corresponding photomultiplier tubes to measure an OSL imaging plate in less than 5 minutes. The resolution of each of the 10 measurement assemblies is 1 square-centimeter. A collimator assembly employing a Venetian-blind type collimator is used in conjunction with the OSL film to image the Pu pit within the storage container. The output of the OSL reader is a two dimensional array of intensities that will be used with the appropriate information barriers to measure extent and symmetry. This device also clearly distinguishes the difference between a point source and a distributed source. Details of the OSL technology, OSL reader system, collimator design, and system performance will be presented.

  4. Monitoring peripheral nerve degeneration in ALS by label-free stimulated Raman scattering imaging

    PubMed Central

    Tian, Feng; Yang, Wenlong; Mordes, Daniel A.; Wang, Jin-Yuan; Salameh, Johnny S.; Mok, Joanie; Chew, Jeannie; Sharma, Aarti; Leno-Duran, Ester; Suzuki-Uematsu, Satomi; Suzuki, Naoki; Han, Steve S.; Lu, Fa-Ke; Ji, Minbiao; Zhang, Rosanna; Liu, Yue; Strominger, Jack; Shneider, Neil A.; Petrucelli, Leonard; Xie, X. Sunney; Eggan, Kevin

    2016-01-01

    The study of amyotrophic lateral sclerosis (ALS) and potential interventions would be facilitated if motor axon degeneration could be more readily visualized. Here we demonstrate that stimulated Raman scattering (SRS) microscopy could be used to sensitively monitor peripheral nerve degeneration in ALS mouse models and ALS autopsy materials. Three-dimensional imaging of pre-symptomatic SOD1 mouse models and data processing by a correlation-based algorithm revealed that significant degeneration of peripheral nerves could be detected coincidentally with the earliest detectable signs of muscle denervation and preceded physiologically measurable motor function decline. We also found that peripheral degeneration was an early event in FUS as well as C9ORF72 repeat expansion models of ALS, and that serial imaging allowed long-term observation of disease progression and drug effects in living animals. Our study demonstrates that SRS imaging is a sensitive and quantitative means of measuring disease progression, greatly facilitating future studies of disease mechanisms and candidate therapeutics. PMID:27796305

  5. Microsecond Scale Vibrational Spectroscopic Imaging by Multiplex Stimulated Raman Scattering Microscopy

    PubMed Central

    Liao, Chien-Sheng; Slipchenko, Mikhail N.; Wang, Ping; Li, Junjie; Lee, Seung-Young; Oglesbee, Robert A.; Cheng, Ji-Xin

    2015-01-01

    Real-time vibrational spectroscopic imaging is desired for monitoring cellular states and cellular processes in a label-free manner. Raman spectroscopic imaging of highly dynamic systems is inhibited by relatively slow spectral acquisition on millisecond to second scale. Here, we report microsecond scale vibrational spectroscopic imaging by lock-in free parallel detection of spectrally dispersed stimulated Raman scattering signal. Using a homebuilt tuned amplifier array, our method enables Raman spectral acquisition, within the window defined by the broadband pulse, at the speed of 32 microseconds and with close to shot-noise limited detection sensitivity. Incorporated with multivariate curve resolution analysis, our platform allows compositional mapping of lipid droplets in single live cells, observation of intracellular retinoid metabolism, discrimination of fat droplets from protein-rich organelles in Caenorhabditis elegans, spectral detection of fast flowing tumor cells, and monitoring drug diffusion through skin tissue in vivo. The reported technique opens new opportunities for compositional analysis of cellular compartment in a microscope setting and high-throughput spectral profiling of single cells in a flow cytometer setting. PMID:26167336

  6. Antidepressant effects of magnetic resonance imaging--based stimulation on major depressive disorder: a double-blind randomized clinical trial.

    PubMed

    Vaziri-Bozorg, Seyed Mehran; Ghasemi-Esfe, Ahmad Reza; Khalilzadeh, Omid; Sotoudeh, Houman; Rokni-Yazdi, Hadi; Ghanaati, Hossein; Firouznia, Kavous; Sharifi, Vandad; Tabatabayee, Maryam; Kooraki, Soheil; Shakiba, Madjid

    2012-03-01

    Antidepressant effects of magnetic resonance imaging (MRI) based stimulation have been reported in animal studies, but no human studies are available on subjects with major depressive disorder. Here, the efficacy of two diagnostic MRI protocols (echo-planar diffusion-weighted imaging (DWI) and T1-weighted imaging) was assessed in patients with major depressive disorder. In this double-blind randomized clinical trial, 51 patients with clinically proven major depressive disorder were randomly enrolled into three equal groups. All patients were receiving a selective serotonin reuptake inhibitor as the only antidepressant treatment. The first group received echo-planar DW stimulation (DWI group), the second group received T1-weighted stimulation (T1 group), and the third group experienced a similar condition without receiving any magnetic stimulation (sham group). The Hamilton rating scale for depression (HAMD24) and Beck depression inventory (BDI) were used to assess the effect of MR stimulation on depressive symptoms. In comparison to baseline, mean HAMD24 and BDI scores significantly (p < 0.001) decreased in the DWI (by 35% and 39%) and T1 (by 38% and 39%) groups 2 weeks after MR stimulation. In the sham group, reduction in HAMD24 (19%, p = 0.04) and BDI score (15%, p = 0.07) were lower than the MR stimulation groups. Two weeks after the MR experiments, changes in mean HAMD24 score and BDI score were significantly (p < 0.05) higher in subjects treated with MR stimulation (DWI or T1) vs. sham group. In conclusion, this study demonstrated the antidepressant effects of DWI and T1 MRI protocols. Our results may point to usefulness of MR stimulation for clinical use in patients with major depressive disorder.

  7. Neuroimaging in repetitive brain trauma

    PubMed Central

    2014-01-01

    Sports-related concussions are one of the major causes of mild traumatic brain injury. Although most patients recover completely within days to weeks, those who experience repetitive brain trauma (RBT) may be at risk for developing a condition known as chronic traumatic encephalopathy (CTE). While this condition is most commonly observed in athletes who experience repetitive concussive and/or subconcussive blows to the head, such as boxers, football players, or hockey players, CTE may also affect soldiers on active duty. Currently, the only means by which to diagnose CTE is by the presence of phosphorylated tau aggregations post-mortem. Non-invasive neuroimaging, however, may allow early diagnosis as well as improve our understanding of the underlying pathophysiology of RBT. The purpose of this article is to review advanced neuroimaging methods used to investigate RBT, including diffusion tensor imaging, magnetic resonance spectroscopy, functional magnetic resonance imaging, susceptibility weighted imaging, and positron emission tomography. While there is a considerable literature using these methods in brain injury in general, the focus of this review is on RBT and those subject populations currently known to be susceptible to RBT, namely athletes and soldiers. Further, while direct detection of CTE in vivo has not yet been achieved, all of the methods described in this review provide insight into RBT and will likely lead to a better characterization (diagnosis), in vivo, of CTE than measures of self-report. PMID:25031630

  8. Neuroimaging in repetitive brain trauma.

    PubMed

    Ng, Thomas Sc; Lin, Alexander P; Koerte, Inga K; Pasternak, Ofer; Liao, Huijun; Merugumala, Sai; Bouix, Sylvain; Shenton, Martha E

    2014-01-01

    Sports-related concussions are one of the major causes of mild traumatic brain injury. Although most patients recover completely within days to weeks, those who experience repetitive brain trauma (RBT) may be at risk for developing a condition known as chronic traumatic encephalopathy (CTE). While this condition is most commonly observed in athletes who experience repetitive concussive and/or subconcussive blows to the head, such as boxers, football players, or hockey players, CTE may also affect soldiers on active duty. Currently, the only means by which to diagnose CTE is by the presence of phosphorylated tau aggregations post-mortem. Non-invasive neuroimaging, however, may allow early diagnosis as well as improve our understanding of the underlying pathophysiology of RBT. The purpose of this article is to review advanced neuroimaging methods used to investigate RBT, including diffusion tensor imaging, magnetic resonance spectroscopy, functional magnetic resonance imaging, susceptibility weighted imaging, and positron emission tomography. While there is a considerable literature using these methods in brain injury in general, the focus of this review is on RBT and those subject populations currently known to be susceptible to RBT, namely athletes and soldiers. Further, while direct detection of CTE in vivo has not yet been achieved, all of the methods described in this review provide insight into RBT and will likely lead to a better characterization (diagnosis), in vivo, of CTE than measures of self-report.

  9. [Repetitive strain injuries. Forearm pain caused by tissue responses to repetitive strain].

    PubMed

    Sorgatz, H

    2002-10-01

    According to the National Research Council, painful work-related upper limb disorders are caused by different pathophysiological mechanisms, one of which is repetitive strain injury (RSI). Forearm pain, tenderness, and paresthesias are thought to result from a continual risk of exceeding limits of "cumulative trauma load tolerance" (CTLT, cf. NRC 2001) in soft tissue by thousands of high-frequency, repetitive movements. On the other hand, repetitive painful stimulations also produce neuroplastic changes in the spinal and supraspinal nociceptive systems. Thus, repetitive motor and nociceptive impulses become part of the same motor programs, which are also responsible for high-frequency movements and tissue damage. In this way RSI pain may be felt as a task-related response, even after all injuries are completely healed. Consequences of this neuroplastic CTLT model for RSI prevention and therapy are discussed.

  10. Diffusion tensor imaging and neuromodulation: DTI as key technology for deep brain stimulation.

    PubMed

    Coenen, Volker Arnd; Schlaepfer, Thomas E; Allert, Niels; Mädler, Burkhard

    2012-01-01

    Diffusion tensor imaging (DTI) is more than just a useful adjunct to invasive techniques like optogenetics which recently have tremendously influenced our understanding of the mechanisms of deep brain stimulation (DBS). In combination with other technologies, DTI helps us to understand which parts of the brain tissue are connected to others and which ones are truly influenced with neuromodulation. The complex interaction of DBS with the surrounding tissues-scrutinized with DTI-allows to create testable hypotheses that can explain network interactions. Those interactions are vital for our understanding of the net effects of neuromodulation. This work naturally was first done in the field of movement disorder surgery, where a lot of experience regarding therapeutic effects and only a short latency between initiation of neuromodulation and alleviation of symptoms exist. This chapter shows the journey over the past 10 years with first applications in DBS toward current research in affect regulating network balances and their therapeutic alterations with the neuromodulation technology.

  11. Analysis of electrodes' placement and deformation in deep brain stimulation from medical images

    NASA Astrophysics Data System (ADS)

    Mehri, Maroua; Lalys, Florent; Maumet, Camille; Haegelen, Claire; Jannin, Pierre

    2012-02-01

    Deep brain stimulation (DBS) is used to reduce the motor symptoms such as rigidity or bradykinesia, in patients with Parkinson's disease (PD). The Subthalamic Nucleus (STN) has emerged as prime target of DBS in idiopathic PD. However, DBS surgery is a difficult procedure requiring the exact positioning of electrodes in the pre-operative selected targets. This positioning is usually planned using patients' pre-operative images, along with digital atlases, assuming that electrode's trajectory is linear. However, it has been demonstrated that anatomical brain deformations induce electrode's deformations resulting in errors in the intra-operative targeting stage. In order to meet the need of a higher degree of placement accuracy and to help constructing a computer-aided-placement tool, we studied the electrodes' deformation in regards to patients' clinical data (i.e., sex, mean PD duration and brain atrophy index). Firstly, we presented an automatic algorithm for the segmentation of electrode's axis from post-operative CT images, which aims to localize the electrodes' stimulated contacts. To assess our method, we applied our algorithm on 25 patients who had undergone bilateral STNDBS. We found a placement error of 0.91+/-0.38 mm. Then, from the segmented axis, we quantitatively analyzed the electrodes' curvature and correlated it with patients' clinical data. We found a positive significant correlation between mean curvature index of the electrode and brain atrophy index for male patients and between mean curvature index of the electrode and mean PD duration for female patients. These results help understanding DBS electrode' deformations and would help ensuring better anticipation of electrodes' placement.

  12. Direct Imaging of Natural Fractures and Stress Compartments Stimulated by Hydraulic Fracturing

    NASA Astrophysics Data System (ADS)

    Lacazette, A.; Vermilye, J. M.

    2014-12-01

    This contribution will present results from passive seismic studies of hydraulic fracture treatments in North American and Asian basins. One of the key data types is a comparatively new surface-based seismic imaging product - "Tomographic Fracture Images®" (TFI®). The procedure is an extension of Seismic Emission Tomography (SET), which is well-established and widely used. Conventional microseismic results - microearthquake hypocenter locations, magnitudes, and focal mechanism solutions - are also obtained from the data via a branch of the processing workflow. TFI is accomplished by summing the individual time steps in a multidimensional SET hypervolume over extended periods of time, such as an entire frac stage. The dimensions of a SET hypervolume are the X, Y, and Z coordinates of the voxels, the time step (typically on the order of 100 milliseconds), and the seismic activity value. The resulting summed volume is skeletonized to produce images of the main fracture surfaces, which are known to occupy the maximum activity surfaces of the high activity clouds from theory, field studies, and experiments. The orientation vs. area of the resulting TFIs can be analyzed in detail and compared with independent data sets such as volumetric structural attributes from reflection seismic data and borehole fracture data. We find that the primary effect of hydraulic fracturing is to stimulate preexisting natural fracture networks and faults. The combination of TFIs with hypocenter distributions and microearthquake focal mechanisms provides detailed information on subsurface stress compartmentalization. Faults are directly imaged which allows discrimination of fault planes from auxiliary planes of focal mechanism solutions. Examples that will be shown include simultaneous movement on a thrust fault and tear fault and examples of radically different stress compartments (e.g. extensional vs. wrench faulting) stimulated during a single hydraulic fracture treatment. The figure

  13. Targeted Melanoma Imaging and Therapy with Radiolabeled Alpha-Melanocyte Stimulating Hormone Peptide Analogues

    PubMed Central

    Quinn, Thomas; Zhang, Xiuli; Miao, Yubin

    2010-01-01

    Radiolabeled alpha-melanocyte stimulating hormone (α-MSH) analogues have been used to define the expression, affinity and function of the melanocortin-1 receptor (MC1-R). The MC1-R is one of a family of five G-protein linker receptors, which is primarily involved in regulation of skin pigmentation. Over-expression of the MC1-R on melanoma tumor cells has made it an attractive target for the development of α-MSH peptide based imaging and therapeutic agents. Initially, the native α-MSH peptide was radiolabeled directly, but it suffered from low specific activity and poor stability. The addition of non-natural amino acids yielded α-MSH analogues with greater MC-1R affinity and stability. Furthermore, peptide cyclization via disulfide and lactam bond formation as well as site-specific metal coordination resulted in additional gains in receptor affinity and peptide stability in vitro and in vivo. Radiochemical stability of the α-MSH analogues was improved through the conjugation of metal chelators to the peptide’s N-terminus or lysine residues for radionuclide coordination. In vitro cell binding studies demonstrated that the radiolabeled α-MSH analogues had low to subnanomolar affinities for the MC1-R. Biodistribution and imaging studies in the B16 mouse melanoma modeled showed rapid tumor uptake of the radiolabeled peptides, with the cyclic peptides demonstrating prolonged tumor retention. Cyclic α-MSH analogues labeled with beta and alpha emitting radionuclides demonstrated melanoma therapeutic efficacy in the B16 melanoma mouse model. Strong pre-clinical imaging and therapy data highlight the clinical potential use of radiolabeled α-MSH peptides for melanoma imaging and treatment of disseminated disease. PMID:20467398

  14. fMRI repetition suppression: neuronal adaptation or stimulus expectation?

    PubMed

    Larsson, Jonas; Smith, Andrew T

    2012-03-01

    Measurements of repetition suppression with functional magnetic resonance imaging (fMRI adaptation) have been used widely to probe neuronal population response properties in human cerebral cortex. fMRI adaptation techniques assume that fMRI repetition suppression reflects neuronal adaptation, an assumption that has been challenged on the basis of evidence that repetition-related response changes may reflect unrelated factors, such as attention and stimulus expectation. Specifically, Summerfield et al. (Summerfield C, Trittschuh EH, Monti JM, Mesulam MM, Egner T. 2008. Neural repetition suppression reflects fulfilled perceptual expectations. Nat Neurosci. 11:1004-1006) reported that the relative frequency of stimulus repetitions and non-repetitions influenced the magnitude of repetition suppression in the fusiform face area, suggesting that stimulus expectation accounted for most of the effect of repetition. We confirm that stimulus expectation can significantly influence fMRI repetition suppression throughout visual cortex and show that it occurs with long as well as short adaptation durations. However, the effect was attention dependent: When attention was diverted away from the stimuli, the effects of stimulus expectation completely disappeared. Nonetheless, robust and significant repetition suppression was still evident. These results suggest that fMRI repetition suppression reflects a combination of neuronal adaptation and attention-dependent expectation effects that can be experimentally dissociated. This implies that with an appropriate experimental design, fMRI adaptation can provide valid measures of neuronal adaptation and hence response specificity.

  15. Bioorthogonal chemical imaging of metabolic activities in live mammalian hippocampal tissues with stimulated Raman scattering

    PubMed Central

    Hu, Fanghao; Lamprecht, Michael R.; Wei, Lu; Morrison, Barclay; Min, Wei

    2016-01-01

    Brain is an immensely complex system displaying dynamic and heterogeneous metabolic activities. Visualizing cellular metabolism of nucleic acids, proteins, and lipids in brain with chemical specificity has been a long-standing challenge. Recent development in metabolic labeling of small biomolecules allows the study of these metabolisms at the global level. However, these techniques generally require nonphysiological sample preparation for either destructive mass spectrometry imaging or secondary labeling with relatively bulky fluorescent labels. In this study, we have demonstrated bioorthogonal chemical imaging of DNA, RNA, protein and lipid metabolism in live rat brain hippocampal tissues by coupling stimulated Raman scattering microscopy with integrated deuterium and alkyne labeling. Heterogeneous metabolic incorporations for different molecular species and neurogenesis with newly-incorporated DNA were observed in the dentate gyrus of hippocampus at the single cell level. We further applied this platform to study metabolic responses to traumatic brain injury in hippocampal slice cultures, and observed marked upregulation of protein and lipid metabolism particularly in the hilus region of the hippocampus within days of mechanical injury. Thus, our method paves the way for the study of complex metabolic profiles in live brain tissue under both physiological and pathological conditions with single-cell resolution and minimal perturbation. PMID:28000773

  16. Registration and real-time visualization of transcranial magnetic stimulation with 3-D MR images.

    PubMed

    Noirhomme, Quentin; Ferrant, Matthieu; Vandermeeren, Yves; Olivier, Etienne; Macq, Benoît; Cuisenaire, Olivier

    2004-11-01

    This paper describes a method for registering and visualizing in real-time the results of transcranial magnetic stimulations (TMS) in physical space on the corresponding anatomical locations in MR images of the brain. The method proceeds in three main steps. First, the patient scalp is digitized in physical space with a magnetic-field digitizer, following a specific digitization pattern. Second, a registration process minimizes the mean square distance between those points and a segmented scalp surface extracted from the magnetic resonance image. Following this registration, the physician can follow the change in coil position in real-time through the visualization interface and adjust the coil position to the desired anatomical location. Third, amplitude of motor evoked potentials can be projected onto the segmented brain in order to create functional brain maps. The registration has subpixel accuracy in a study with simulated data, while we obtain a point to surface root-mean-square error of 1.17+/-0.38 mm in a 24 subject study.

  17. Bioorthogonal chemical imaging of metabolic activities in live mammalian hippocampal tissues with stimulated Raman scattering

    NASA Astrophysics Data System (ADS)

    Hu, Fanghao; Lamprecht, Michael R.; Wei, Lu; Morrison, Barclay; Min, Wei

    2016-12-01

    Brain is an immensely complex system displaying dynamic and heterogeneous metabolic activities. Visualizing cellular metabolism of nucleic acids, proteins, and lipids in brain with chemical specificity has been a long-standing challenge. Recent development in metabolic labeling of small biomolecules allows the study of these metabolisms at the global level. However, these techniques generally require nonphysiological sample preparation for either destructive mass spectrometry imaging or secondary labeling with relatively bulky fluorescent labels. In this study, we have demonstrated bioorthogonal chemical imaging of DNA, RNA, protein and lipid metabolism in live rat brain hippocampal tissues by coupling stimulated Raman scattering microscopy with integrated deuterium and alkyne labeling. Heterogeneous metabolic incorporations for different molecular species and neurogenesis with newly-incorporated DNA were observed in the dentate gyrus of hippocampus at the single cell level. We further applied this platform to study metabolic responses to traumatic brain injury in hippocampal slice cultures, and observed marked upregulation of protein and lipid metabolism particularly in the hilus region of the hippocampus within days of mechanical injury. Thus, our method paves the way for the study of complex metabolic profiles in live brain tissue under both physiological and pathological conditions with single-cell resolution and minimal perturbation.

  18. Can We Use Neurocognition to Predict Repetition of Self-Harm, and Why Might This Be Clinically Useful? A Perspective

    PubMed Central

    de Cates, Angharad N.; Broome, Matthew R.

    2016-01-01

    Over 800,000 people die by suicide each year globally, with non-fatal self-harm 20 times more common. With each episode of self-harm, the risks of future self-harm and suicide increase, as well as personal and healthcare costs. Therefore, early delineation of those at high risk of future self-harm is important. Historically, research has focused on clinical and demographic factors, but risk assessments based on these have low sensitivity to predict repetition. Various neurocognitive factors have been associated with self-harming behavior, but it is less certain if we can use these factors clinically (i) as risk markers to predict future self-harm and (ii) to become therapeutic targets for interventions. Recent systematic reviews and meta-analyses of behavioral tasks and fMRI studies point to an emerging hypothesis for neurocognition in self-harm: an underactive pre-frontal cortex is unable to respond appropriately to non-emotional stimuli, or inhibit a hyperactive emotionally-/threat-driven limbic system. However, there is almost no imaging data examining repetition of self-harm. Extrapolating from the non-repetition data, there may be several potential neurocognitive targets for interventions to prevent repeat self-harm: cognitive training; pharmacological regimes to promote non-emotional neurocognition; or other techniques, such as repetitive transcranial magnetic stimulation. Hence, there is an urgent need for imaging studies examining repetition and to test specific hypotheses. Until we investigate the functional neurocognitive basis underlying repetition of self-harm in a systematic manner using second-generational imaging techniques, we will be unable to inform third-generational imaging and potential future clinical applications. PMID:26858659

  19. Label-free chemically specific imaging in planta with stimulated Raman scattering microscopy.

    PubMed

    Mansfield, Jessica C; Littlejohn, George R; Seymour, Mark P; Lind, Rob J; Perfect, Sarah; Moger, Julian

    2013-05-21

    The growing world population puts ever-increasing demands on the agricultural and agrochemical industries to increase agricultural yields. This can only be achieved by investing in fundamental plant and agrochemical research and in the development of improved analytical tools to support research in these areas. There is currently a lack of analytical tools that provide noninvasive structural and chemical analysis of plant tissues at the cellular scale. Imaging techniques such as coherent anti-Stokes Raman scattering (CARS) and stimulated Raman scattering (SRS) microscopy provide label-free chemically specific image contrast based on vibrational spectroscopy. Over the past decade, these techniques have been shown to offer clear advantages for a vast range of biomedical research applications. The intrinsic vibrational contrast provides label-free quantitative functional analysis, it does not suffer from photobleaching, and it allows near real-time imaging in 3D with submicrometer spatial resolution. However, due to the susceptibility of current detection schemes to optical absorption and fluorescence from pigments (such as chlorophyll), the plant science and agrochemical research communities have not been able to benefit from these techniques and their application in plant research has remained virtually unexplored. In this paper, we explore the effect of chlorophyll fluorescence and absorption in CARS and SRS microscopy. We show that with the latter it is possible to use phase-sensitive detection to separate the vibrational signal from the (electronic) absorption processes. Finally, we demonstrate the potential of SRS for a range of in planta applications by presenting in situ chemical analysis of plant cell wall components, epicuticular waxes, and the deposition of agrochemical formulations onto the leaf surface.

  20. Accurate CT-MR image registration for deep brain stimulation: a multi-observer evaluation study

    NASA Astrophysics Data System (ADS)

    Rühaak, Jan; Derksen, Alexander; Heldmann, Stefan; Hallmann, Marc; Meine, Hans

    2015-03-01

    Since the first clinical interventions in the late 1980s, Deep Brain Stimulation (DBS) of the subthalamic nucleus has evolved into a very effective treatment option for patients with severe Parkinson's disease. DBS entails the implantation of an electrode that performs high frequency stimulations to a target area deep inside the brain. A very accurate placement of the electrode is a prerequisite for positive therapy outcome. The assessment of the intervention result is of central importance in DBS treatment and involves the registration of pre- and postinterventional scans. In this paper, we present an image processing pipeline for highly accurate registration of postoperative CT to preoperative MR. Our method consists of two steps: a fully automatic pre-alignment using a detection of the skull tip in the CT based on fuzzy connectedness, and an intensity-based rigid registration. The registration uses the Normalized Gradient Fields distance measure in a multilevel Gauss-Newton optimization framework and focuses on a region around the subthalamic nucleus in the MR. The accuracy of our method was extensively evaluated on 20 DBS datasets from clinical routine and compared with manual expert registrations. For each dataset, three independent registrations were available, thus allowing to relate algorithmic with expert performance. Our method achieved an average registration error of 0.95mm in the target region around the subthalamic nucleus as compared to an inter-observer variability of 1.12 mm. Together with the short registration time of about five seconds on average, our method forms a very attractive package that can be considered ready for clinical use.

  1. Longitudinal magnetic resonance imaging reveals striatal hypertrophy in a rat model of long-term stimulant treatment

    PubMed Central

    Biezonski, D; Shah, R; Krivko, A; Cha, J; Guilfoyle, D N; Hrabe, J; Gerum, S; Xie, S; Duan, Y; Bansal, R; Leventhal, B L; Peterson, B S; Kellendonk, C; Posner, J

    2016-01-01

    Stimulant treatment is highly effective in mitigating symptoms associated with attention-deficit/hyperactivity disorder (ADHD), though the neurobiological underpinnings of this effect have not been established. Studies using anatomical magnetic resonance imaging (MRI) in children with ADHD have suggested that long-term stimulant treatment may improve symptoms of ADHD in part by stimulating striatal hypertrophy. This conclusion is limited, however, as these studies have either used cross-sectional sampling or did not assess the impact of treatment length on their dependent measures. We therefore used longitudinal anatomical MRI in a vehicle-controlled study design to confirm causality regarding stimulant effects on striatal morphology in a rodent model of clinically relevant long-term stimulant treatment. Sprague Dawley rats were orally administered either lisdexamfetamine (LDX, ‘Vyvanse') or vehicle (N=12 per group) from postnatal day 25 (PD25, young juvenile) until PD95 (young adult), and imaged one day before and one day after the 70-day course of treatment. Our LDX dosing regimen yielded blood levels of dextroamphetamine comparable to those documented in patients. Longitudinal analysis of striatal volume revealed significant hypertrophy in LDX-treated animals when compared to vehicle-treated controls, with a significant treatment by time point interaction. These findings confirm a causal link between long-term stimulant treatment and striatal hypertrophy, and support utility of longitudinal MRI in rodents as a translational approach for bridging preclinical and clinical research. Having demonstrated comparable morphological effects in both humans and rodents using the same imaging technology, future studies may now use this rodent model to identify the underlying cellular mechanisms and behavioral consequences of stimulant-induced striatal hypertrophy. PMID:27598968

  2. Longitudinal magnetic resonance imaging reveals striatal hypertrophy in a rat model of long-term stimulant treatment.

    PubMed

    Biezonski, D; Shah, R; Krivko, A; Cha, J; Guilfoyle, D N; Hrabe, J; Gerum, S; Xie, S; Duan, Y; Bansal, R; Leventhal, B L; Peterson, B S; Kellendonk, C; Posner, J

    2016-09-06

    Stimulant treatment is highly effective in mitigating symptoms associated with attention-deficit/hyperactivity disorder (ADHD), though the neurobiological underpinnings of this effect have not been established. Studies using anatomical magnetic resonance imaging (MRI) in children with ADHD have suggested that long-term stimulant treatment may improve symptoms of ADHD in part by stimulating striatal hypertrophy. This conclusion is limited, however, as these studies have either used cross-sectional sampling or did not assess the impact of treatment length on their dependent measures. We therefore used longitudinal anatomical MRI in a vehicle-controlled study design to confirm causality regarding stimulant effects on striatal morphology in a rodent model of clinically relevant long-term stimulant treatment. Sprague Dawley rats were orally administered either lisdexamfetamine (LDX, 'Vyvanse') or vehicle (N=12 per group) from postnatal day 25 (PD25, young juvenile) until PD95 (young adult), and imaged one day before and one day after the 70-day course of treatment. Our LDX dosing regimen yielded blood levels of dextroamphetamine comparable to those documented in patients. Longitudinal analysis of striatal volume revealed significant hypertrophy in LDX-treated animals when compared to vehicle-treated controls, with a significant treatment by time point interaction. These findings confirm a causal link between long-term stimulant treatment and striatal hypertrophy, and support utility of longitudinal MRI in rodents as a translational approach for bridging preclinical and clinical research. Having demonstrated comparable morphological effects in both humans and rodents using the same imaging technology, future studies may now use this rodent model to identify the underlying cellular mechanisms and behavioral consequences of stimulant-induced striatal hypertrophy.

  3. An integrated optical coherence microscopy imaging and optical stimulation system for optogenetic pacing in Drosophila melanogaster (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Alex, Aneesh; Li, Airong; Men, Jing; Jerwick, Jason; Tanzi, Rudolph E.; Zhou, Chao

    2016-03-01

    Electrical stimulation is the clinical standard for cardiac pacing. Although highly effective in controlling cardiac rhythm, the invasive nature, non-specificity to cardiac tissues and possible tissue damage limits its applications. Optogenetic pacing of the heart is a promising alternative, which is non-invasive and more specific, has high spatial and temporal precision, and avoids the shortcomings in electrical stimulation. Drosophila melanogaster, which is a powerful model organism with orthologs of nearly 75% of human disease genes, has not been studied for optogenetic pacing in the heart. Here, we developed a non-invasive integrated optical pacing and optical coherence microscopy (OCM) imaging system to control the heart rhythm of Drosophila at different developmental stages using light. The OCM system is capable of providing high imaging speed (130 frames/s) and ultrahigh imaging resolutions (1.5 μm and 3.9 μm for axial and transverse resolutions, respectively). A light-sensitive pacemaker was developed in Drosophila by specifically expressing the light-gated cation channel, channelrhodopsin-2 (ChR2) in transgenic Drosophila heart. We achieved non-invasive and specific optical control of the Drosophila heart rhythm throughout the fly's life cycle (larva, pupa, and adult) by stimulating the heart with 475 nm pulsed laser light. Heart response to stimulation pulses was monitored non-invasively with OCM. This integrated non-invasive optogenetic control and in vivo imaging technique provides a novel platform for performing research studies in developmental cardiology.

  4. Repetitive strain injury.

    PubMed

    Al-Otaibi, S T

    2001-05-01

    Repetitive strain injury is a group of musculoskeletal disorders affecting muscles, tendons, nerves and blood vessels. These disorders could be attributed to occupational causes; however non-occupational causes should be excluded. The management of these cases required a multidisciplinary team approach.

  5. Repetition through Successive Approximations.

    ERIC Educational Resources Information Center

    Littell, Katherine M.

    This study was conducted in an attempt to provide an alternative to the long-established method of tape listening and repetition drills, a method that has had disappointing results. It is suggested that the rate of speed of phonic presentation is not commensurate with the rate of comprehension. The proposed method seeks to prevent cognitive…

  6. Neural Correlates of Restricted, Repetitive Behaviors in Autism Spectrum Disorders

    DTIC Science & Technology

    2013-10-01

    Restricted , Repetitive Behaviors in Autism Spectrum Disorders 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-1-0774 5c... Repetitive Behaviors in Autism Spectrum Disorders PRINCIPAL INVESTIGATOR: Associate Professor of Psychiatry Manoach, Dara CONTRACTING...speech network of individuals with autism spectrum disorder NeuroImage: Clinical. in press. CONCLUSION

  7. Shifts in connectivity during procedural learning after motor cortex stimulation: A combined transcranial magnetic stimulation/functional magnetic resonance imaging study.

    PubMed

    Steel, Adam; Song, Sunbin; Bageac, Devin; Knutson, Kristine M; Keisler, Aysha; Saad, Ziad S; Gotts, Stephen J; Wassermann, Eric M; Wilkinson, Leonora

    2016-01-01

    Inhibitory transcranial magnetic stimulation (TMS), of which continuous theta burst stimulation (cTBS) is a common form, has been used to inhibit cortical areas during investigations of their function. cTBS applied to the primary motor area (M1) depresses motor output excitability via a local effect and impairs procedural motor learning. This could be due to an effect on M1 itself and/or to changes in its connectivity with other nodes in the learning network. To investigate this issue, we used functional magnetic resonance imaging to measure changes in brain activation and connectivity during implicit procedural learning after real and sham cTBS of M1. Compared to sham, real cTBS impaired motor sequence learning, but caused no local or distant changes in brain activation. Rather, it reduced functional connectivity between motor (M1, dorsal premotor & supplementary motor areas) and visual (superior & inferior occipital gyri) areas. It also increased connectivity between frontal associative (superior & inferior frontal gyri), cingulate (dorsal & middle cingulate), and temporal areas. This potentially compensatory shift in coupling, from a motor-based learning network to an associative learning network accounts for the behavioral effects of cTBS of M1. The findings suggest that the inhibitory TMS affects behavior via relatively subtle and distributed effects on connectivity within networks, rather than by taking the stimulated area "offline".

  8. Preclinical Melanoma Imaging with 68Ga-Labeled α-Melanocyte-Stimulating Hormone Derivatives Using PET

    PubMed Central

    Zhang, Chengcheng; Zhang, Zhengxing; Lin, Kuo-Shyan; Pan, Jinhe; Dude, Iulia; Hundal-Jabal, Navjit; Colpo, Nadine; Bénard, François

    2017-01-01

    It is estimated that melanoma accounted for 76,380 new cases and 10,130 deaths in the United States in 2016. The melanocortin 1 receptor (MC1R) is highly expressed in the vast majority of melanomas, which makes it an attractive target for molecular imaging and radionuclide therapy. Lactam bridge-cyclized α-melanocyte-stimulating hormone (Ac-Nle4-cyclo[Asp5-His-D-Phe7-Arg-Trp-Lys10]-NH2, or Nle-CycMSHhex) analogues have been successfully developed and studied for MC1R-targeted imaging, predominantly with single-photon emission computed tomography (SPECT). The goal of this study was to design and evaluate novel peptides for melanoma imaging with positron emission tomography (PET). We designed and synthesized three peptides, DOTA-PEG2-Nle-CycMSHhex (CCZ01047), DOTA-4-amino-(1-carboxymethyl) piperidine (Pip)-Nle-CycMSHhex (CCZ01048), and DOTA-Pip-Pip-Nle-CycMSHhex (CCZ01056). All three peptides exhibited high binding affinity to MC1R with sub-nanomolar Ki values, rapid internalization into B16F10 melanoma cells and high in vivo stability with more than 93% remaining intact at 15 min post-injection (p.i.) in blood plasma. All three 68Ga-labeled tracers produced high contrast PET images in C57BL/6J mice bearing B16F10 tumors, and their respective tumor uptakes were 8.0 ± 3.0, 12.3 ± 3.3, and 6.5 ± 1.4 %ID/g at 1 h p.i. Minimal normal organ activity was observed at 1 h p.i., except for kidneys (5.1 ± 1.4, 4.7 ± 0.5, and 6.2 ± 2.0 %ID/g, respectively), and thyroid (4.1 ± 0.6 %ID/g for CCZ01047 and 2.4 ± 0.6 %ID/g for CCZ01048). Due to high accumulation at tumor sites and rapid background clearance of 68Ga-CCZ01048, we further evaluated it at 2 h p.i., and a tumor uptake of 21.9 ± 4.6 %ID/g was observed, with background activity further decreased. Exceptional image contrast was also achieved, i.e. tumor-to-blood, tumor-to-muscle, tumor-to-bone and tumor-to-kidney ratios were 96.4 ± 13.9, 210.9 ± 20.9, 39.6 ± 11.9 and 4.0 ± 0.9, respectively. A blocking study

  9. Topographic mapping of trans-cranial magnetic stimulation data on surface rendered MR images of the brain.

    PubMed

    Singh, K D; Hamdy, S; Aziz, Q; Thompson, D G

    1997-10-01

    We present a method for the coregistration and topographic mapping of trans-cranial magnetic stimulation (TCMS) data on surface rendered images of the cortex, derived from Magnetic Resonance Images (MRI). We describe the TCMS procedure and the methods used to locate the TCM stimulation sites in the MRI coordinate system, and the algorithms needed to depict the TCMS distribution as a pseudocolour contour map on the cortical surface. The methods are validated using TCMS data from the hand (thenar) and leg (tibialis muscle). The methods used correctly depict the expected motor representations of each of these areas and we therefore propose that this technique may be used as a functional imaging tool in the investigation of cortical function in both normals and patients.

  10. A review of neuroimaging findings in repetitive brain trauma.

    PubMed

    Koerte, Inga K; Lin, Alexander P; Willems, Anna; Muehlmann, Marc; Hufschmidt, Jakob; Coleman, Michael J; Green, Isobel; Liao, Huijun; Tate, David F; Wilde, Elisabeth A; Pasternak, Ofer; Bouix, Sylvain; Rathi, Yogesh; Bigler, Erin D; Stern, Robert A; Shenton, Martha E

    2015-05-01

    Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease confirmed at postmortem. Those at highest risk are professional athletes who participate in contact sports and military personnel who are exposed to repetitive blast events. All neuropathologically confirmed CTE cases, to date, have had a history of repetitive head impacts. This suggests that repetitive head impacts may be necessary for the initiation of the pathogenetic cascade that, in some cases, leads to CTE. Importantly, while all CTE appears to result from repetitive brain trauma, not all repetitive brain trauma results in CTE. Magnetic resonance imaging has great potential for understanding better the underlying mechanisms of repetitive brain trauma. In this review, we provide an overview of advanced imaging techniques currently used to investigate brain anomalies. We also provide an overview of neuroimaging findings in those exposed to repetitive head impacts in the acute/subacute and chronic phase of injury and in more neurodegenerative phases of injury, as well as in military personnel exposed to repetitive head impacts. Finally, we discuss future directions for research that will likely lead to a better understanding of the underlying mechanisms separating those who recover from repetitive brain trauma vs. those who go on to develop CTE.

  11. Hyperspectral stimulated Raman scattering and multiphoton imaging for digital pathology of colonic disease

    NASA Astrophysics Data System (ADS)

    Wang, Zi; Zheng, Wei; Lin, Jian; Huang, Zhiwei

    2016-03-01

    Histopathology examinations of H&E stained biopsied tissues is the golden standard for colonic diseases (e.g., polyps, adenoma, and adenocarcinoma) diagnosis. However, staining effect of sample and doctor's expertise degree may greatly influence the diagnosis results. The information provided by the H&E stained sample is also limited to the morphological and PH information and no quantative information is available. In this paper, we report the development of a unique multimodal nonlinear optical microscopy (i.e., hyperspectral stimulated Raman scattering (hsSRS), second-harmonic generation (SHG), third-harmonic generation (THG), two-photon excitation fluorescence (TPEF)) platform for the diagnosis and characterization of colonic diseases. HsSRS in both fingerprint (800-1800 cm-1) and high-wavenumber (2800-3600 cm-1) regions allows us to discriminate different constituents with tiny difference in the Raman spectra. The increase of proteins and reduction of lipids could be observed with the progress of colonic cancer. SHG shows the distribution of collagen, which is found to aggregate for adenocarcinoma. TPEF provides the cell morphological and can reflect the damage inside glands caused by the diseases. THG shows the increase of optical heterogeneity related to cancer process. This work shows that the integrated hsSRS and TPEF/SHG/THG imaging technique can be an effective method for digital pathology of colonic diseases at the molecular and sub-cellular levels.

  12. Computer-controlled stimulation for functional magnetic resonance imaging studies of the neonatal olfactory system

    PubMed Central

    Arichi, T; Gordon-Williams, R; Allievi, A; Groves, AM; Burdet, E; Edwards, AD

    2013-01-01

    Aim Olfactory sensation is highly functional early in human neonatal life, with studies suggesting that odours can influence behaviour and infant–mother bonding. Due to its good spatial properties, blood oxygen level–dependent (BOLD) contrast functional magnetic resonance imaging (fMRI) has the potential to rapidly advance our understanding of the neural activity which underlies the development of olfactory perception in this key period. We aimed to design an ‘olfactometer’ specifically for use with neonatal subjects for fMRI studies of odour perception. Methods We describe a fully automated and programmable, fMRI compatible system capable of presenting odorant liquids. To prevent contamination of the system and minimize between-subject infective risk, the majority of the olfactometer is constructed from single-use, readily available clinical equipment. The system was used to present the odour of infant formula milk in a validation group of seven neonatal subjects at term equivalent postmenstrual age (median age 40 weeks). Results A safe, reliable and reproducible pattern of stimulation was delivered leading to well-localized positive BOLD functional responses in the piriform cortex, amygdala, thalamus, insular cortex and cerebellum. Conclusions The described system is therefore suitable for detailed studies of the ontology of olfactory sensation and perception during early human brain development. PMID:23789919

  13. Single-shot T1 mapping using simultaneous acquisitions of spin- and stimulated-echo-planar imaging (2D ss-SESTEPI).

    PubMed

    Shi, Xianfeng; Kim, Seong-Eun; Jeong, Eun-Kee

    2010-09-01

    The conventional stimulated-echo NMR sequence only measures the longitudinal component while discarding the transverse component, after tipping up the prepared magnetization. This transverse magnetization can be used to measure a spin echo, in addition to the stimulated echo. Two-dimensional single-shot spin- and stimulated-echo-planar imaging (ss-SESTEPI) is an echo-planar-imaging-based single-shot imaging technique that simultaneously acquires a spin-echo-planar image and a stimulated-echo-planar image after a single radiofrequency excitation. The magnitudes of the spin-echo-planar image and stimulated-echo-planar image differ by T(1) decay and diffusion weighting for perfect 90 degrees radiofrequency and thus can be used to rapidly measure T(1). However, the spatial variation of amplitude of radiofrequency field induces uneven splitting of the transverse magnetization for the spin-echo-planar image and stimulated-echo-planar image within the imaging field of view. Correction for amplitude of radiofrequency field inhomogeneity is therefore critical for two-dimensional ss-SESTEPI to be used for T(1) measurement. We developed a method for amplitude of radiofrequency field inhomogeneity correction by acquiring an additional stimulated-echo-planar image with minimal mixing time, calculating the difference between the spin echo and the stimulated echo and multiplying the stimulated-echo-planar image by the inverse functional map. Diffusion-induced decay is corrected by measuring the average diffusivity during the prescanning. Rapid single-shot T(1) mapping may be useful for various applications, such as dynamic T(1) mapping for real-time estimation of the concentration of contrast agent in dynamic contrast enhancement MRI.

  14. Single-wavelength two-photon excitation–stimulated emission depletion (SW2PE-STED) superresolution imaging

    PubMed Central

    Bianchini, Paolo; Harke, Benjamin; Galiani, Silvia; Vicidomini, Giuseppe; Diaspro, Alberto

    2012-01-01

    We developed a new class of two-photon excitation–stimulated emission depletion (2PE-STED) optical microscope. In this work, we show the opportunity to perform superresolved fluorescence imaging, exciting and stimulating the emission of a fluorophore by means of a single wavelength. We show that a widely used red-emitting fluorophore, ATTO647N, can be two-photon excited at a wavelength allowing both 2PE and STED using the very same laser source. This fact opens the possibility to perform 2PE microscopy at four to five times STED-improved resolution, while exploiting the intrinsic advantages of nonlinear excitation. PMID:22493221

  15. A methodology for on-board CBCT imaging dose using optically stimulated luminescence detectors.

    PubMed

    Mail, Noor; Yusuf, Muhammad; Alothmany, Nazeeh; Kinsara, A Abdulrahman; Abdulkhaliq, Fahad; Ghamdi, Suliman M; Saoudi, Abdelhamid

    2016-09-08

    Cone-beam computed tomography CBCT systems are used in radiation therapy for patient alignment and positioning. The CBCT imaging procedure for patient setup adds substantial radiation dose to patient's normal tissue. This study pre-sents a complete procedure for the CBCT dosimetry using the InLight optically-stimulated-luminescence (OSL) nanoDots. We report five dose parameters: the mean slice dose (DMSD); the cone beam dose index (CBDIW); the mean volume dose (DMVD); point-dose profile, D(FOV); and the off-field Dose. In addition, CBCT skin doses for seven pelvic tumor patients are reported. CBCT-dose mea-surement was performed on a custom-made cylindrical acrylic body phantom (50cm length, 32cm diameter). We machined 25 circular disks (2 cm thick) with grooves and holes to hold OSL-nanoDots. OSLs that showed similar sensitivities were selected and calibrated against a Farmer-type ionization-chamber (0.6 CT) before being inserted into the grooves and holes. For the phantom scan, a standard CBCT-imaging protocol (pelvic sites: 125 kVp, 80 mA and 25 ms) was used. Five dose parameters were quantified: DMSD, CBDIW, DMVD, D(FOV), and the off-field dose. The DMSD for the central slice was 31.1 ± 0.85 mGy, and CBDIW was 34.5± 0.6 mGy at 16cm FOV. The DMVD was 25.6 ± 1.1 mGy. The off-field dose was 10.5 mGy. For patients, the anterior and lateral skin doses attributable to CBCT imaging were 39.04 ± 4.4 and 27.1 ± 1.3 mGy, respectively.OSL nanoDots were convenient to use in measuring CBCT dose. The method of selecting the nanoDots greatly reduced uncertainty in the OSL measurements. Our detailed calibration procedure and CBCT dose measurements and calculations could prove useful in developing OSL routines for CBCT quality assessment, which in turn gives them the property of high spatial resolution, meaning that they have the potential for measurement of dose in regions of severe dose-gradients.

  16. Functional transcranial photoacoustic micro-imaging of mouse cerebrovascular cross-section and hemoglobin oxygenation changes during forepaw electrical stimulation

    NASA Astrophysics Data System (ADS)

    Liao, Lun-De; Chen, You-Yin; Lin, Chin-Teng; Chang, Jyh-Yeong; Li, Meng-Lin

    2011-03-01

    In this study, we report on using a 50-MHz functional photoacoustic microscopy (PAM) to transcranially image the cross-section and hemoglobin oxygenation (SO2) changes of single mouse cortical vessels in response to left forepaw electrical stimulation. Three difference levels of the cortical vessels (i.e., with different-sized diameters of 350, 100 and 55 μm) on activated regions were marked to measure their functional cross-section and SO2 changes as a function of time. Electrical stimulation of the mouse left forelimb was applied to evoke functional changes in vascular dynamics of the mouse somatosensory cortex. The applied current pulses were with a pulse frequency of 3 Hz, pulse duration of 0.2 ms, and pulse amplitude of 2 mA. The cerebrovascular cross-section changes, which indicate changes in cerebral blood volume (CBV), were probed by images acquired at 570 nm, a hemoglobin isosbestic point, while SO2 changes were monitored by the derivatives of 560-nm images normalized to 570-nm ones. The results show that vessel diameter and SO2 were significantly dilated and increased when compared with those of the controlled ones. In summary, the PAM shows its promise as a new imaging modality for transcranially functional quantification of single vessel diameter (i.e., CBV) and SO2 changes without any contrast agents applied during stimulation.

  17. Pedunculopontine Nucleus Region Deep Brain Stimulation in Parkinson Disease: Surgical Techniques, Side Effects, and Postoperative Imaging

    PubMed Central

    Hamani, Clement; Lozano, Andres M.; Mazzone, Paolo A.M.; Moro, Elena; Hutchison, William; Silburn, Peter A.; Zrinzo, Ludvic; Alam, Mesbah; Goetz, Laurent; Pereira, Erlick; Rughani, Anand; Thevathasan, Wesley; Aziz, Tipu; Bloem, Bastiaan R.; Brown, Peter; Chabardes, Stephan; Coyne, Terry; Foote, Kelly; Garcia-Rill, Edgar; Hirsch, Etienne C.; Okun, Michael S.; Krauss, Joachim K.

    2017-01-01

    The pedunculopontine nucleus (PPN) region has received considerable attention in clinical studies as a target for deep brain stimulation (DBS) in Parkinson disease. These studies have yielded variable results with an overall impression of improvement in falls and freezing in many but not all patients treated. We evaluated the available data on the surgical anatomy and terminology of the PPN region in a companion paper. Here we focus on issues concerning surgical technique, imaging, and early side effects of surgery. The aim of this paper was to gain more insight into the reasoning for choosing specific techniques and to discuss short-comings of available studies. Our data demonstrate the wide range in almost all fields which were investigated. There are a number of important challenges to be resolved, such as identification of the optimal target, the choice of the surgical approach to optimize electrode placement, the impact on the outcome of specific surgical techniques, the reliability of intraoperative confirmation of the target, and methodological differences in postoperative validation of the electrode position. There is considerable variability both within and across groups, the overall experience with PPN DBS is still limited, and there is a lack of controlled trials. Despite these challenges, the procedure seems to provide benefit to selected patients and appears to be relatively safe. One important limitation in comparing studies from different centers and analyzing outcomes is the great variability in targeting and surgical techniques, as shown in our paper. The challenges we identified will be of relevance when designing future studies to better address several controversial issues. We hope that the data we accumulated may facilitate the development of surgical protocols for PPN DBS. PMID:27728909

  18. A Non-Invasive Imaging Approach to Understanding Speech Changes following Deep Brain Stimulation in Parkinson’s Disease

    PubMed Central

    Narayana, Shalini; Jacks, Adam; Robin, Donald A.; Poizner, Howard; Zhang, Wei; Franklin, Crystal; Liotti, Mario; Vogel, Deanie; Fox, Peter T.

    2009-01-01

    Purpose To explore the use of non-invasive functional imaging and “virtual” lesion techniques to study the neural mechanisms underlying motor speech disorders in Parkinson’s disease. Here, we report the use of Positron Emission Tomography (PET) and transcranial magnetic stimulation (TMS) to explain exacerbated speech impairment following subthalamic nucleus deep brain stimulation (STN-DBS) in a patient with Parkinson’s disease. Method Perceptual and acoustic speech measures as well as cerebral blood flow (CBF) during speech as measured by PET were obtained with STN-DBS on and off. TMS was applied to a region in the speech motor network found to be abnormally active during DBS. Speech disruption by TMS was compared both perceptually and acoustically with that resulting from DBS on. Results Speech production was perceptually inferior and acoustically less contrastive during left STN stimulation compared to no stimulation. Increased neural activity in left dorsal premotor cortex (PMd) was observed during DBS on. “Virtual” lesioning of this region resulted in speech characterized by decreased speech segment duration, increased pause duration, and decreased intelligibility. Conclusions This case report provides evidence that impaired speech production accompanying STN-DBS may be resulting from unintended activation of PMd. Clinical application of functional imaging and TMS may lead to optimizing the delivery of STN-DBS to improve outcomes for speech production as well as general motor abilities. PMID:19029533

  19. Mechanistic study of macrophage activation by LPS stimulation using fluorescence imaging techinques

    NASA Astrophysics Data System (ADS)

    Lu, Cuixia; Zhou, Feifan; Chen, Wei R.; Xing, Da

    2012-03-01

    Lipopolysaccharide (LPS), a structural component of the outer membrane of gram negative bacteria, has been suggested that stimulates macrophages secrete a wide variety of inflammatory mediators, such as nitric oxide (NO). However, the cellular mechanisms of NO generation in macrophage by LPS stimulation are not well known. In this study, LPS stimulated NO generation in macrophage was determined by measuring fluorescence changes with a NO specific probe DAF-FM DA. Using the fluorescence resonance energy transfer (FRET) techniques, we found an increase of protein kinase C (PKC) activation was dynamically monitored in macrophages treated with LPS. Nuclear factor kappa B (NF-κB) translocated from the cytoplasm to the nucleus in macrophage was measured by confocal laser scanning microscopy. Moreover, the PKC inhibitor GÖ6983 inhibited LPS-stimulated NF-κB activation and NO production. These results indicated that LPS stimulated NF-κB mediated NO production by activating PKC.

  20. Mechanistic study of macrophage activation by LPS stimulation using fluorescence imaging techinques

    NASA Astrophysics Data System (ADS)

    Lu, Cuixia; Zhou, Feifan; Chen, Wei R.; Xing, Da

    2011-11-01

    Lipopolysaccharide (LPS), a structural component of the outer membrane of gram negative bacteria, has been suggested that stimulates macrophages secrete a wide variety of inflammatory mediators, such as nitric oxide (NO). However, the cellular mechanisms of NO generation in macrophage by LPS stimulation are not well known. In this study, LPS stimulated NO generation in macrophage was determined by measuring fluorescence changes with a NO specific probe DAF-FM DA. Using the fluorescence resonance energy transfer (FRET) techniques, we found an increase of protein kinase C (PKC) activation was dynamically monitored in macrophages treated with LPS. Nuclear factor kappa B (NF-κB) translocated from the cytoplasm to the nucleus in macrophage was measured by confocal laser scanning microscopy. Moreover, the PKC inhibitor GÖ6983 inhibited LPS-stimulated NF-κB activation and NO production. These results indicated that LPS stimulated NF-κB mediated NO production by activating PKC.

  1. Brain activation related to affective dimension during thermal stimulation in humans: a functional magnetic resonance imaging study.

    PubMed

    Sung, Eun-Jung; Yoo, Seung-Schik; Yoon, Hyo Woon; Oh, Sung-Suk; Han, Yeji; Park, Hyun Wook

    2007-07-01

    The aim of this study was to identify the activated brain region that is involved with the affective dimension of thermal stimulation (not pain, but innocuous warming) using functional MR imaging. Twelve healthy, right-handed male subjects participated in the study. Thermal stimulation with two different temperatures of 41 degrees C and 34 degrees C was applied to the subjects using a fomentation pack, wrapped around the right lower leg of each subject. On the basis of the subjects' responses after the scanning sessions, the authors were able to observe that the subjects felt "warm" and "slightly pleasant and comfortable" under the 41 degrees C condition. The experimental results indicated that warm stimulation produced a significant increase of activation compared to thermal neutral stimulation in various regions such as contralateral insular, ipsilateral cerebellum, ipsilateral putamen, contralateral middle frontal gyrus, ipsilateral inferior frontal gyrus, contralateral postcentral gyrus, and contralateral paracentral lobule. The activated regions are known to be related to thermal sensory, affective/emotional awareness, cognitive functions, sensory-discrimination, and emotion/affective processing, and so on. These results suggest that an appropriate thermal stimulation can produce a positive emotion and activate emotion/affect related regions of the brain.

  2. IMAGING SIGNAL TRANSDUCTION VIA ARACHIDONIC ACID IN THE HUMAN BRAIN DURING VISUAL STIMULATION, BY MEANS OF POSITRON EMISSION TOMOGRAPHY

    PubMed Central

    Esposito, Giuseppe; Giovacchini, Giampiero; Der, Margaret; Liow, Jeih-San; Bhattacharjee, Abesh K.; Ma, Kaizong; Herscovitch, Peter; Channing, Michael; Eckelman, William C.; Hallett, Mark; Carson, Richard E.; Rapoport, Stanley I.

    2007-01-01

    Background Arachidonic acid (AA, 20:4n-6), an important second messenger, is released from membrane phospholipid following receptor mediated activation of phospholipase A2 (PLA2). This signaling process can be imaged in brain as a regional brain AA incorporation coefficient K*. Hypothesis K* will be increased in brain visual areas of subjects submitted to visual stimulation. Subjects and methods Regional values of K* were measured with positron emission tomography (PET), following the intravenous injection of [1-11C]AA, in 16 healthy volunteers subjected to visual stimulation at flash frequencies 2.9 Hz (8 subjects) or 7.8 Hz (8 subjects), compared with the dark (0 Hz) condition. Regional cerebral blood flow (rCBF) was measured with intravenous [15O]water under comparable conditions. Results During flash stimulation at 2.9 Hz or 7.8 Hz vs. 0 Hz, K* was increased significantly by 2.3–8.9% in Brodmann areas 17, 18 and 19, and in additional frontal, parietal and temporal cortical regions. rCBF was increased significantly by 3.1% – 22%, often in comparable regions. Increments at 7.8 Hz often exceeded those at 2.9 Hz for both K* and rCBF. Decrements in both parameters also were produced, particularly in frontal brain regions. Conclusions AA plays a role in signaling processes provoked by visual stimulation, since visual stimulation at flash frequencies of 2.9 and 7.8 Hz compared to 0 Hz modifies both K* for AA and rCBF in visual and related areas of the human brain. The two-stimulus condition paradigm of this study might be used with PET to image effects of other functional activations and of drugs on brain signaling via AA. PMID:17196833

  3. Polarization-resolved hyperspectral stimulated Raman scattering microscopy for label-free biomolecular imaging of the tooth

    NASA Astrophysics Data System (ADS)

    Wang, Zi; Zheng, Wei; Hsu, Chin-Ying Stephen; Huang, Zhiwei

    2016-01-01

    We report the development and implementation of a rapid polarization-resolved hyperspectral stimulated Raman scattering (SRS) microscopy technique for label-free biomolecular imaging of the tooth. The hyperspectral SRS imaging technique developed covers both fingerprint (800-1800 cm-1) and high-wavenumber (2800-3600 cm-1) regions for tooth Raman imaging without fluorescence background interference with an imaging speed of <0.3 s per frame of 512 × 512 pixels (˜1 μs per pixel), that is, >106 faster than confocal Raman imaging. Significant differences of hyperspectral SRS spectra among different tooth locations (e.g., dentin, enamel, and dentin-enamel junction) are observed, revealing the biochemical distribution differences across the tooth. Further polarization-resolved SRS imaging shows different polarization dependences related to the molecular orientation differences of various tooth locations. This work demonstrates the potential of polarization-resolved hyperspectral SRS imaging technique developed in rapidly characterizing biochemical structures and compositions as well as biomolecule organizations/orientations of the tooth without labeling.

  4. Application of the optically stimulated luminescence (OSL) technique for mouse dosimetry in micro-CT imaging

    SciTech Connect

    Vrigneaud, Jean-Marc; Courteau, Alan; Oudot, Alexandra; Collin, Bertrand; Ranouil, Julien; Morgand, Loïc; Raguin, Olivier; Walker, Paul; Brunotte, François

    2013-12-15

    Purpose: Micro-CT is considered to be a powerful tool to investigate various models of disease on anesthetized animals. In longitudinal studies, the radiation dose delivered by the micro-CT to the same animal is a major concern as it could potentially induce spurious effects in experimental results. Optically stimulated luminescence dosimeters (OSLDs) are a relatively new kind of detector used in radiation dosimetry for medical applications. The aim of this work was to assess the dose delivered by the CT component of a micro-SPECT (single-photon emission computed tomography)/CT camera during a typical whole-body mouse study, using commercially available OSLDs based on Al{sub 2}O{sub 3}:C crystals.Methods: CTDI (computed tomography dose index) was measured in micro-CT with a properly calibrated pencil ionization chamber using a rat-like phantom (60 mm in diameter) and a mouse-like phantom (30 mm in diameter). OSLDs were checked for reproducibility and linearity in the range of doses delivered by the micro-CT. Dose measurements obtained with OSLDs were compared to those of the ionization chamber to correct for the radiation quality dependence of OSLDs in the low-kV range. Doses to tissue were then investigated in phantoms and cadavers. A 30 mm diameter phantom, specifically designed to insert OSLDs, was used to assess radiation dose over a typical whole-body mouse imaging study. Eighteen healthy female BALB/c mice weighing 27.1 ± 0.8 g (1 SD) were euthanized for small animal measurements. OLSDs were placed externally or implanted internally in nine different locations by an experienced animal technician. Five commonly used micro-CT protocols were investigated.Results: CTDI measurements were between 78.0 ± 2.1 and 110.7 ± 3.0 mGy for the rat-like phantom and between 169.3 ± 4.6 and 203.6 ± 5.5 mGy for the mouse-like phantom. On average, the displayed CTDI at the operator console was underestimated by 1.19 for the rat-like phantom and 2.36 for the mouse

  5. Functional magnetic resonance imaging of the rat cerebellum during electrical stimulation of the fore- and hindpaw at 7 T

    NASA Astrophysics Data System (ADS)

    Peeters, Ronald; Verhoye, Marleen; Vos, Bart; De Schutter, Erik; Van der Linden, Anne-Marie

    1999-05-01

    Blood oxygenation level dependent contrast (BOLD) functional MRI responses at 7T were observed in the cerebellum of alpha- chloralose anesthetized rats in response to innocuous electrical stimulation of a forepaw or hindpaw. The responses were imaged in both coronal and sagittal slices which allowed for a clear delineation and localization of the observed activations. We demonstrate the validity of our fMRI protocol by imaging the responses in somatosensory cortex to the same stimuli and by showing a high level of reproducibility of the cerebellar responses. Widespread bilateral activations were found with mainly a patchy and medio-lateral band organization, more pronounced ipsilaterally. There was no overlap between the cerebellar activations caused by forepaw or hindpaw stimulation. Most remarkable was the overall horizontal organization of these responses: for both stimulation paradigms the patches and bands of activation were roughly positioned in either a cranial or caudal plane running antero-posteriorly through the whole cerebellum. This is the first fMRI study in the cerebellum of the rat. We relate our findings to the known projection patterns found with other techniques and to human fMRI studies. The horizontal organization found wasn't observed before in other studies using other techniques.

  6. Functional Magnetic Resonance Imaging of Electrical and Optogenetic Deep Brain Stimulation at the Rat Nucleus Accumbens

    PubMed Central

    Albaugh, Daniel L.; Salzwedel, Andrew; Van Den Berge, Nathalie; Gao, Wei; Stuber, Garret D.; Shih, Yen-Yu Ian

    2016-01-01

    Deep brain stimulation of the nucleus accumbens (NAc-DBS) is an emerging therapy for diverse, refractory neuropsychiatric diseases. Although DBS therapy is broadly hypothesized to work through large-scale neural modulation, little is known regarding the neural circuits and networks affected by NAc-DBS. Using a healthy, sedated rat model of NAc-DBS, we employed both evoked- and functional connectivity (fc) MRI to examine the functional circuit and network changes achieved by electrical NAc stimulation. Optogenetic-fMRI experiments were also undertaken to evaluate the circuit modulation profile achieved by selective stimulation of NAc neurons. NAc-DBS directly modulated neural activity within prefrontal cortex and a large number of subcortical limbic areas (e.g., amygdala, lateral hypothalamus), and influenced functional connectivity among sensorimotor, executive, and limbic networks. The pattern and extent of circuit modulation measured by evoked-fMRI was relatively insensitive to DBS frequency. Optogenetic stimulation of NAc cell bodies induced a positive fMRI signal in the NAc, but no other detectable downstream responses, indicating that therapeutic NAc-DBS might exert its effect through antidromic stimulation. Our study provides a comprehensive mapping of circuit and network-level neuromodulation by NAc-DBS, which should facilitate our developing understanding of its therapeutic mechanisms of action. PMID:27601003

  7. Repetitive behaviour in kennelled domestic dog: stereotypical or not?

    PubMed

    Denham, Hamish D C; Bradshaw, John W S; Rooney, Nicola J

    2014-04-10

    Repetitive behaviour is common in kennelled dogs, yet its motivational basis remains relatively unexplored. We examine the repetitive behaviour of 30 kennelled working dogs in ten contexts both coinciding with, and in the absence of, commonly occurring arousing stimuli, such as care staff, other dogs and food preparation. A large proportion (93%) of subjects performed some repetitive behaviour, most commonly bouncing, but only 17% in the absence of the arousing stimuli. Subjects could be divided into four groups according to the stimuli eliciting, and the duration, of their repetitive behaviour, and these groups were compared on the basis of their cortisol response to an acute psychogenic stressor--a veterinary examination. Urinary cortisol/creatinine response curves differed significantly between the groups. In particular, those dogs which performed repetitive behaviour at times of minimal stimulation, showed a distinctly different pattern of response, with cortisol levels decreasing, as compared to increasing, after the veterinary examination. We conclude that dogs showing repetitive behaviours at times of high arousal are motivationally distinct from those "stereotyping" in the absence of stimulation. We suggest that those dogs showing spontaneous repetitive behaviours may have past experiences and/or temperaments that affect both their reactions to a veterinary examination and to long-term kennelling. For example, some dogs may find isolation from humans particularly aversive, hence affecting their reactions both to being left in a kennel and to being taken to the veterinary surgeon. Alternatively, such dogs may have atypical responsiveness of their hypothalamic-pituitary-adrenal (HPA) axis, possibly brought about through chronic stress. High levels of repetitive behaviours in response to inaccessible husbandry events may be explained if such behaviour has inadvertently been reinforced by attention from staff, and therefore may not always be indicative of

  8. Studies on magnetism and bioelectromagnetics for 45 years: from magnetic analog memory to human brain stimulation and imaging.

    PubMed

    Ueno, Shoogo

    2012-01-01

    Forty-five years of studies on magnetism and bioelectromagnetics, in our laboratory, are presented. This article is prepared for the d'Arsonval Award Lecture. After a short introduction of our early work on magnetic analog memory, we review and discuss the following topics: (1) Magnetic nerve stimulation and localized transcranial magnetic stimulation (TMS) of the human brain by figure-eight coils; (2) Measurements of weak magnetic fields generated from the brain by superconducting quantum interference device (SQUID) systems, called magnetoencephalography (MEG), and its application in functional brain studies; (3) New methods of magnetic resonance imaging (MRI) for the imaging of impedance of the brain, called impedance MRI, and the imaging of neuronal current activities in the brain, called current MRI; (4) Cancer therapy and other medical treatments by pulsed magnetic fields; (5) Effects of static magnetic fields and magnetic control of cell orientation and cell growth; and (6) Effects of radio frequency magnetic fields and control of iron ion release and uptake from and into ferritins, iron cage proteins. These bioelectromagnetic studies have opened new horizons in magnetism and medicine, in particular for brain research and treatment of ailments such as depression, Parkinson's, and Alzheimer's diseases.

  9. rTMS of the occipital cortex abolishes Braille reading and repetition priming in blind subjects.

    PubMed

    Kupers, R; Pappens, M; de Noordhout, A Maertens; Schoenen, J; Ptito, M; Fumal, A

    2007-02-27

    To study the functional involvement of the visual cortex in Braille reading, we applied repetitive transcranial magnetic stimulation (rTMS) over midoccipital (MOC) and primary somatosensory (SI) cortex in blind subjects. After rTMS of MOC, but not SI, subjects made significantly more errors and showed an abolishment of the improvement in reading speed following repetitive presentation of the same word list, suggesting a role of the visual cortex in repetition priming in the blind.

  10. Image-guided preoperative prediction of pyramidal tract side effect in deep brain stimulation

    NASA Astrophysics Data System (ADS)

    Baumgarten, C.; Zhao, Y.; Sauleau, P.; Malrain, C.; Jannin, P.; Haegelen, C.

    2016-03-01

    Deep brain stimulation of the medial globus pallidus is a surgical procedure for treating patients suffering from Parkinson's disease. Its therapeutic effect may be limited by the presence of pyramidal tract side effect (PTSE). PTSE is a contraction time-locked to the stimulation when the current spreading reaches the motor fibers of the pyramidal tract within the internal capsule. The lack of side-effect predictive model leads the neurologist to secure an optimal electrode placement by iterating clinical testing on an awake patient during the surgical procedure. The objective of the study was to propose a preoperative predictive model of PTSE. A machine learning based method called PyMAN (for Pyramidal tract side effect Model based on Artificial Neural network) that accounted for the current of the stimulation, the 3D electrode coordinates and the angle of the trajectory, was designed to predict the occurrence of PTSE. Ten patients implanted in the medial globus pallidus have been tested by a clinician to create a labeled dataset of the stimulation parameters that trigger PTSE. The kappa index value between the data predicted by PyMAN and the labeled data was .78. Further evaluation studies are desirable to confirm whether PyMAN could be a reliable tool for assisting the surgeon to prevent PTSE during the preoperative planning.

  11. Repetition Blindness for Rotated Objects

    ERIC Educational Resources Information Center

    Hayward, William G.; Zhou, Guomei; Man, Wai-Fung; Harris, Irina M.

    2010-01-01

    Repetition blindness (RB) is the finding that observers often miss the repetition of an item within a rapid stream of words or objects. Recent studies have shown that RB for objects is largely unaffected by variations in viewpoint between the repeated items. In 5 experiments, we tested RB under different axes of rotation, with different types of…

  12. Functional Circuitry Effect of Ventral Tegmental Area Deep Brain Stimulation: Imaging and Neurochemical Evidence of Mesocortical and Mesolimbic Pathway Modulation

    PubMed Central

    Settell, Megan L.; Testini, Paola; Cho, Shinho; Lee, Jannifer H.; Blaha, Charles D.; Jo, Hang J.; Lee, Kendall H.; Min, Hoon-Ki

    2017-01-01

    Background: The ventral tegmental area (VTA), containing mesolimbic and mesocortical dopaminergic neurons, is implicated in processes involving reward, addiction, reinforcement, and learning, which are associated with a variety of neuropsychiatric disorders. Electrical stimulation of the VTA or the medial forebrain bundle and its projection target the nucleus accumbens (NAc) is reported to improve depressive symptoms in patients affected by severe, treatment-resistant major depressive disorder (MDD) and depressive-like symptoms in animal models of depression. Here we sought to determine the neuromodulatory effects of VTA deep brain stimulation (DBS) in a normal large animal model (swine) by combining neurochemical measurements with functional magnetic resonance imaging (fMRI). Methods: Animals (n = 8 swine) were implanted with a unilateral DBS electrode targeting the VTA. During stimulation (130 Hz frequency, 0.25 ms pulse width, and 3 V amplitude), fMRI was performed. Following fMRI, fast-scan cyclic voltammetry in combination with carbon fiber microelectrodes was performed to quantify VTA-DBS-evoked dopamine release in the ipsilateral NAc. In a subset of swine, the blood oxygen level-dependent (BOLD) percent change evoked by stimulation was performed at increasing voltages (1, 2, and 3 V). Results: A significant increase in VTA-DBS-evoked BOLD signal was found in the following regions: the ipsilateral dorsolateral prefrontal cortex, anterior and posterior cingulate, insula, premotor cortex, primary somatosensory cortex, and striatum. A decrease in the BOLD signal was also observed in the contralateral parahippocampal cortex, dorsolateral and anterior prefrontal cortex, insula, inferior temporal gyrus, and primary somatosensory cortex (Bonferroni-corrected < 0.001). During neurochemical measurements, stimulation time-locked changes in dopamine release were recorded in the NAc, confirming that mesolimbic dopaminergic neurons were stimulated by DBS. In the

  13. Integrated femtosecond stimulated Raman scattering and two-photon fluorescence imaging of subcellular lipid and vesicular structures

    NASA Astrophysics Data System (ADS)

    Li, Xuesong; Lam, Wen Jiun; Cao, Zhe; Hao, Yan; Sun, Qiqi; He, Sicong; Mak, Ho Yi; Qu, Jianan Y.

    2015-11-01

    The primary goal of this study is to demonstrate that stimulated Raman scattering (SRS) as a new imaging modality can be integrated into a femtosecond (fs) nonlinear optical (NLO) microscope system. The fs sources of high pulse peak power are routinely used in multimodal nonlinear microscopy to enable efficient excitation of multiple NLO signals. However, with fs excitations, the SRS imaging of subcellular lipid and vesicular structures encounters significant interference from proteins due to poor spectral resolution and a lack of chemical specificity, respectively. We developed a unique NLO microscope of fs excitation that enables rapid acquisition of SRS and multiple two-photon excited fluorescence (TPEF) signals. In the in vivo imaging of transgenic C. elegans animals, we discovered that by cross-filtering false positive lipid signals based on the TPEF signals from tryptophan-bearing endogenous proteins and lysosome-related organelles, the imaging system produced highly accurate assignment of SRS signals to lipid. Furthermore, we demonstrated that the multimodal NLO microscope system could sequentially image lipid structure/content and organelles, such as mitochondria, lysosomes, and the endoplasmic reticulum, which are intricately linked to lipid metabolism.

  14. Lock-in-detection-free line-scan stimulated Raman scattering microscopy for near video-rate Raman imaging.

    PubMed

    Wang, Zi; Zheng, Wei; Huang, Zhiwei

    2016-09-01

    We report on the development of a unique lock-in-detection-free line-scan stimulated Raman scattering microscopy technique based on a linear detector with a large full well capacity controlled by a field-programmable gate array (FPGA) for near video-rate Raman imaging. With the use of parallel excitation and detection scheme, the line-scan SRS imaging at 20 frames per second can be acquired with a ∼5-fold lower excitation power density, compared to conventional point-scan SRS imaging. The rapid data communication between the FPGA and the linear detector allows a high line-scanning rate to boost the SRS imaging speed without the need for lock-in detection. We demonstrate this lock-in-detection-free line-scan SRS imaging technique using the 0.5 μm polystyrene and 1.0 μm poly(methyl methacrylate) beads mixed in water, as well as living gastric cancer cells.

  15. Integrated femtosecond stimulated Raman scattering and two-photon fluorescence imaging of subcellular lipid and vesicular structures.

    PubMed

    Li, Xuesong; Lam, Wen Jiun; Cao, Zhe; Hao, Yan; Sun, Qiqi; He, Sicong; Mak, Ho Yi; Qu, Jianan Y

    2015-11-01

    The primary goal of this study is to demonstrate that stimulated Raman scattering (SRS) as a new imaging modality can be integrated into a femtosecond (fs) nonlinear optical (NLO) microscope system. The fs sources of high pulse peak power are routinely used in multimodal nonlinear microscopy to enable efficient excitation of multiple NLO signals. However, with fs excitations, the SRS imaging of subcellular lipid and vesicular structures encounters significant interference from proteins due to poor spectral resolution and a lack of chemical specificity, respectively. We developed a unique NLO microscope of fs excitation that enables rapid acquisition of SRS and multiple two-photon excited fluorescence (TPEF) signals. In the in vivo imaging of transgenic C. elegans animals, we discovered that by cross-filtering false positive lipid signals based on the TPEF signals from tryptophan-bearing endogenous proteins and lysosome-related organelles, the imaging system produced highly accurate assignment of SRS signals to lipid. Furthermore, we demonstrated that the multimodal NLO microscope system could sequentially image lipid structure/content and organelles, such as mitochondria, lysosomes, and the endoplasmic reticulum, which are intricately linked to lipid metabolism.

  16. Contrast Enhancement for Thermal Acoustic Breast Cancer Imaging via Resonant Stimulation

    DTIC Science & Technology

    2009-03-01

    Olsen and J. C. Lin, “Acoustic imaging of a model of a human hand using pulsed microwave irradiation,” Bioelectromagnetics, vol. 4, pp. 397–400, 1983. [2...E. Steen and B. Olstad, “Volume rendering of 3-D medical ultrasound data using direct feature mapping,” IEEE Trans. Med. Imag., vol. 13, no. 6, pp

  17. Perceptual Repetition Blindness Effects

    NASA Technical Reports Server (NTRS)

    Hochhaus, Larry; Johnston, James C.; Null, Cynthia H. (Technical Monitor)

    1994-01-01

    The phenomenon of repetition blindness (RB) may reveal a new limitation on human perceptual processing. Recently, however, researchers have attributed RB to post-perceptual processes such as memory retrieval and/or reporting biases. The standard rapid serial visual presentation (RSVP) paradigm used in most RB studies is, indeed, open to such objections. Here we investigate RB using a "single-frame" paradigm introduced by Johnston and Hale (1984) in which memory demands are minimal. Subjects made only a single judgement about whether one masked target word was the same or different than a post-target probe. Confidence ratings permitted use of signal detection methods to assess sensitivity and bias effects. In the critical condition for RB a precue of the post-target word was provided prior to the target stimulus (identity precue), so that the required judgement amounted to whether the target did or did not repeat the precue word. In control treatments, the precue was either an unrelated word or a dummy.

  18. Orthographic repetition blindness.

    PubMed

    Harris, C L; Morris, A L

    2000-11-01

    Repetition blindness (RB) is the failure to report the second occurrence of a repeated word, when words are sequentially and briefly displayed (Kanwisher, 1987). RB is also observed for non-identical words, such as home, dome. Explanations for non-identity RB assume that similarity at the level of the whole word causes the second word to be suppressed ("similarity inhibition"). Three experiments demonstrate that RB is robust for diverse types of orthographic relatedness, including critical words that share only their first initial letter, their last two letters, first three letters, middle three letters, beginning and final letters, three alternating letters, and three non-aligned letters (as in chance hand). The theoretical construct of similarity inhibition may be able to account for these data, although one mechanism previously proposed in the literature, neighbourhood inhibition, is probably not a useful way to explain the data on RB for words sharing only one or two letters. We introduce an alternative explanation for orthographic RB: Only the repeated letters are suppressed, and amount of RB depends on how easily the perceiver can reconstruct the target word from the non-suppressed letters.

  19. Repetitive strain injury.

    PubMed

    Helliwell, P S; Taylor, W J

    2004-08-01

    Pain in the forearm is relatively common in the community. In the workplace forearm pain is associated with work involving frequent repetition, high forces, and prolonged abnormal postures. Nevertheless, other factors are involved in the presentation and the continuation of the pain. Notable among these factors are psychosocial issues and the workplace environment-the attitude to workers and their welfare, the physical conditions, and design of the job. Primary prevention may be effective but active surveillance is important with early intervention and an active management approach. Physical treatments have not been extensively evaluated. In the established case, management should be multidisciplinary, addressing physical aspects of the job but also addressing the "yellow, blue, and black flags" which should be viewed as obstacles to recovery. For the worker "on sick" a dialogue should be established between the worker, the primary care physician, and the workplace. Return to work should be encouraged and facilitated by medical interventions and light duty options. Rehabilitation programmes may be of use in chronic cases.

  20. Perceptual repetition blindness effects.

    PubMed

    Hochhaus, L; Johnston, J C

    1996-04-01

    Repetition blindness (RB) may reveal a new limitation on human perceptual processing. Recently, however, researchers have attributed RB to postperceptual processes. The standard rapid serial visual presentation (RSVP) paradigm used in most RB studies is open to such objections. The "single-frame" paradigm introduced by J. C. Johnston and B. L. Hale (1984) allowed investigation of RB with minimal memory demands. Participants made a judgment about whether 1 masked target word was the same or different than a posttarget probe. Confidence ratings permitted use of signal detection methods. In the critical condition for RB, a precue of the posttarget word was provided prior to the target stimulus so that the required judgment amounted to whether the target did or did not repeat the precue word. In control treatments, the precue was an unrelated word or a dummy. Results showed that perceptual sensitivity was significantly reduced in the RB condition relative to baseline control conditions. The data showed that RB can be obtained under conditions in which memory problems are minimal and perceptual sensitivity is assessed independently of biases. RB therefore can be a perceptual phenomenon.

  1. Study of complex hemodynamic fluctuations in the human brain by simultaneous near-infrared spectro-imaging and functional magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Toronov, Vladislav Y.; Franceschini, Maria-Angela; Fantini, Sergio; Webb, Andrew G.; Gratton, Enrico

    2004-05-01

    In this paper we discuss temporal and spatial patterns of brain hemodynamics under rest and motor stimulation conditions obtained by functional magnetic resonance imaging and simultaneous fast multi-channel near-infrared spectro-imaging in the human motor cortex. Our data indicate that the main difference between the brain hemodynamics under the repetitive stimulation and the rest conditions is not in the appearance of hemoglobin concentration changes during the stimulations (since fluctuations occur at rest as well), but in their more regular, i.e. phase-synchronous with the stimulation behavior.

  2. Multi-purpose two- and three-dimensional momentum imaging of charged particles for attosecond experiments at 1 kHz repetition rate

    SciTech Connect

    Månsson, Erik P. Sorensen, Stacey L.; Gisselbrecht, Mathieu; Arnold, Cord L.; Kroon, David; Guénot, Diego; Fordell, Thomas; Johnsson, Per; L’Huillier, Anne; Lépine, Franck

    2014-12-15

    We report on the versatile design and operation of a two-sided spectrometer for the imaging of charged-particle momenta in two dimensions (2D) and three dimensions (3D). The benefits of 3D detection are to discern particles of different mass and to study correlations between fragments from multi-ionization processes, while 2D detectors are more efficient for single-ionization applications. Combining these detector types in one instrument allows us to detect positive and negative particles simultaneously and to reduce acquisition times by using the 2D detector at a higher ionization rate when the third dimension is not required. The combined access to electronic and nuclear dynamics available when both sides are used together is important for studying photoreactions in samples of increasing complexity. The possibilities and limitations of 3D momentum imaging of electrons or ions in the same spectrometer geometry are investigated analytically and three different modes of operation demonstrated experimentally, with infrared or extreme ultraviolet light and an atomic/molecular beam.

  3. MULTI-CHANNEL TRANSDERMAL STIMULATION OF THE BRAIN

    DTIC Science & Technology

    channels are available and in each, repetition rate, pulse durations, and intensity are remotely controlled, allowing the adjustment of parameters of brain stimulation in completely unrestricted subjects.

  4. Neural Basis of Repetition Priming during Mathematical Cognition: Repetition Suppression or Repetition Enhancement?

    ERIC Educational Resources Information Center

    Salimpoor, Valorie N.; Chang, Catie; Menon, Vinod

    2010-01-01

    We investigated the neural basis of repetition priming (RP) during mathematical cognition. Previous studies of RP have focused on repetition suppression as the basis of behavioral facilitation, primarily using word and object identification and classification tasks. More recently, researchers have suggested associative stimulus-response learning…

  5. Multiple single-point imaging (mSPI) as a tool for capturing and characterizing MR signals and repetitive signal disturbances with high temporal resolution: the MRI scanner as a high-speed camera.

    PubMed

    Bakker, Chris J G; van Gorp, Jetse S; Verwoerd, Jan L; Westra, Albert H; Bouwman, Job G; Zijlstra, Frank; Seevinck, Peter R

    2013-09-01

    In this paper we aim to lay down and demonstrate the use of multiple single-point imaging (mSPI) as a tool for capturing and characterizing steady-state MR signals and repetitive disturbances thereof with high temporal resolution. To achieve this goal, various 2D mSPI sequences were derived from the nearest standard 3D imaging sequences by (i) replacing the excitation of a 3D slab by the excitation of a 2D slice orthogonal to the read axis, (ii) setting the readout gradient to zero, and (iii) leaving out the inverse Fourier transform in the read direction. The thus created mSPI sequences, albeit slow with regard to the spatial encoding part, were shown to result into a series of densely spaced 2D single-point images in the time domain enabling monitoring of the evolution of the magnetization with a high temporal resolution and without interference from any encoding gradients. The high-speed capabilities of mSPI were demonstrated by capturing and characterizing the free induction decays and spin echoes of substances with long T2s (>30 ms) and long and short T2*s (4 - >30 ms) and by monitoring the perturbation of the transverse magnetization by, respectively, a titanium cylinder, representing a static disturbance; a pulsed magnetic field gradient, representing a stimulus inherent to a conventional MRI experiment; and a pulsed electric current, representing an external stimulus. The results of the study indicate the potential of mSPI for assessing the evolution of the magnetization and, when properly synchronized with the acquisition, repeatable disturbances thereof with a temporal resolution that is ultimately limited by the bandwidth of the receiver, but in practice governed by the SNR of the experiment and the magnitude of the disturbance. Potential applications of mSPI can be envisaged in research areas that are concerned with MR signal behavior, MR system performance and MR evaluation of magnetically evoked responses.

  6. Temporal comparison of functional brain imaging with diffuse optical tomography and fMRI during rat forepaw stimulation

    NASA Astrophysics Data System (ADS)

    Siegel, Andrew M.; Culver, Joseph P.; Mandeville, Joseph B.; Boas, David A.

    2003-05-01

    The time courses of oxyhaemoglobin ([HbO2]), deoxyhaemoglobin ([HbR]) and total haemoglobin ([HbT]) concentration changes following cortical activation in rats by electrical forepaw stimulation were measured using diffuse optical tomography (DOT) and compared to similar measurements performed previously with fMRI at 2.0 T and 4.7 T. We also explored the qualitative effects of varying stimulus parameters on the temporal evolution of the hemodynamic response. DOT images were reconstructed at a depth of 1.5 mm over a 1 cm square area from 2 mm anterior to bregma to 8 mm posterior to bregma. The measurement set included 9 sources and 16 detectors with an imaging frame rate of 10 Hz. Both DOT [HbR] and [HbO2] time courses were compared to the fMRI BOLD time course during stimulation, and the DOT [HbT] time course was compared to the fMRI cerebral plasma volume (CPV) time course. We believe that DOT and fMRI can provide similar temporal information for both blood volume and deoxyhaemoglobin changes, which helps to cross-validate these two techniques and to demonstrate that DOT can be useful as a complementary modality to fMRI for investigating the hemodynamic response to neuronal activity.

  7. Functional magnetic resonance imaging of cerebral activation during spinal cord stimulation in failed back surgery syndrome patients.

    PubMed

    Stancák, Andrej; Kozák, Jirí; Vrba, Ivan; Tintera, Jaroslav; Vrána, Jirí; Polácek, Hubert; Stancák, Marián

    2008-02-01

    Spinal cord stimulation (SCS) consisting of electrical stimulation of the dorsal spinal cord using epidural electrodes has been shown to relieve chronic neuropathic pain. To analyze the cerebral activation patterns related to SCS, and to evaluate the effects of SCS on the processing of acute experimental pain, we performed functional magnetic resonance imaging (fMRI) on eight patients suffering from failed back surgery syndrome who were also being treated with SCS for severe pain in their legs and lower back. Three types of stimulation were used, each lasting 36s: (i) SCS, (ii) heat pain (HP) applied to the leg affected by neuropathic pain, and (iii) simultaneous HP and SCS. During SCS, we found increased activation of the medial primary sensorimotor cortex somatotopically corresponding to the foot and/or perineal region, contralateral posterior insula, and the ipsilateral secondary somatosensory cortex (S2). Decreased activation was seen in the bilateral primary motor cortices and the ipsilateral primary somatosensory cortex corresponding to the shoulder, elbow and hand. Compared to separately presented HP and SCS, simultaneous HP and SCS showed statistically significant activation of the bilateral inferior temporal cortex and the ipsilateral cerebellar cortex. The activation of the primary motor cortex, insula and S2 during SCS may directly interfere with the processing of neuropathic pain. When SCS is associated with heat pain, the paralimbic association cortex and cerebellum show activation exceeding the sum of activations resulting from separate SCS and heat pain stimulation. The explanation of this could possibly rest with the continuous comparisons of simultaneous pain and somatosensory sensations occurring in a single dermatome.

  8. Second-Impact Syndrome and a Small Subdural Hematoma: An Uncommon Catastrophic Result of Repetitive Head Injury with a Characteristic Imaging Appearance

    PubMed Central

    Gean, Alisa D.

    2010-01-01

    Abstract There have been a handful of previously published cases of athletes who were still symptomatic from a prior head injury, and then suffered a second injury in which a thin, acute subdural hematoma (SDH) with unilateral hemisphere vascular engorgement was demonstrated on CT scan. In those cases, the cause of the brain swelling/dysautoregulation was ascribed to the presence of the acute SDH rather than to the acceleration/deceleration forces that caused the SDH. We believe that the brain swelling is due to “second-impact dysautoregulation,” rather than due to the effect of the SDH on the underlying hemisphere. To support our hypothesis, we present 10 additional cases of acute hemispheric swelling in association with small SDHs in athletes who received a second head injury while still symptomatic from a previous head injury. The clinical history and the unique neuroimaging features of this entity on CT are described and illustrated in detail. The CT findings included an engorged cerebral hemisphere with initial preservation of grey-white matter differentiation, and abnormal mass effect and midline shift that appeared disproportionately greater than the size of the SDH. In addition, the imaging similarities between our patients and those with non-accidental head trauma (shaken-baby syndrome) will be discussed. PMID:20536318

  9. STED microscopy--super-resolution bio-imaging utilizing a stimulated emission depletion.

    PubMed

    Otomo, Kohei; Hibi, Terumasa; Kozawa, Yuichi; Nemoto, Tomomi

    2015-08-01

    One of the most popular super-resolution microscopies that breaks the diffraction barrier is stimulated emission depletion (STED) microscopy. As the optical set-up of STED microscopy is based on a laser scanning microscopy (LSM) system, it potentially has several merits of LSM like confocal or two-photon excitation LSM. In this article, we first describe the principles of STED microscopy and then describe the features of our newly developed two-photon excitation STED microscopy. On the basis of our recent results and those of other researchers, we conclude by discussing future research and new technologies in this field.

  10. Perceptual distortions of the human body image produced by local anaesthesia, pain and cutaneous stimulation

    PubMed Central

    Gandevia, S C; Phegan, C M L

    1999-01-01

    Knowledge of the size and orientation of the hand is essential if it is to be moved accurately in space. We used two psychophysical methods to determine whether the perceived size of a body part changes when its sensory input is changed: first, the selection of scaled drawings which matched the apparent size of a body part, and second, a motor task in which the subject drew the body part to depict its perceived size.Complete anaesthesia of the thumb (with a digital nerve block) significantly increased its perceived size by 60–70% when assessed with both psychophysical methods. During this anaesthesia, the perceived size of the adjacent index finger or digits on the contralateral side was unaltered. However, the size of the unanaesthetized lips increased (by ∼50%).Marked sensory loss for the lips (produced by topical anaesthetics) significantly increased their perceived size when assessed with both methods of measurement. There was a small increase in apparent size of the thumb.To determine whether changes in perceived size could also be produced by an elevation of peripheral inputs, innocuous electrical stimulation of the digital nerves and also painful cooling of the digit were used. Both procedures produced small but significant increases in perceived size of the stimulated part.The results highlight lability in the perceived size of parts of the body and how this affects motor output. The data may reveal perceptual consequences of acute changes in central somatosensory maps, changes which are known to occur with deafferentation. PMID:9852339

  11. Perceptual distortions of the human body image produced by local anaesthesia, pain and cutaneous stimulation.

    PubMed

    Gandevia, S C; Phegan, C M

    1999-01-15

    1. Knowledge of the size and orientation of the hand is essential if it is to be moved accurately in space. We used two psychophysical methods to determine whether the perceived size of a body part changes when its sensory input is changed: first, the selection of scaled drawings which matched the apparent size of a body part, and second, a motor task in which the subject drew the body part to depict its perceived size. 2. Complete anaesthesia of the thumb (with a digital nerve block) significantly increased its perceived size by 60-70% when assessed with both psychophysical methods. During this anaesthesia, the perceived size of the adjacent index finger or digits on the contralateral side was unaltered. However, the size of the unanaesthetized lips increased (by approximately 50%). 3. Marked sensory loss for the lips (produced by topical anaesthetics) significantly increased their perceived size when assessed with both methods of measurement. There was a small increase in apparent size of the thumb. 4. To determine whether changes in perceived size could also be produced by an elevation of peripheral inputs, innocuous electrical stimulation of the digital nerves and also painful cooling of the digit were used. Both procedures produced small but significant increases in perceived size of the stimulated part. 5. The results highlight lability in the perceived size of parts of the body and how this affects motor output. The data may reveal perceptual consequences of acute changes in central somatosensory maps, changes which are known to occur with deafferentation.

  12. Simultaneous stimulated Raman scattering and higher harmonic generation imaging for liver disease diagnosis without labeling

    NASA Astrophysics Data System (ADS)

    Lin, Jian; Wang, Zi; Zheng, Wei; Huang, Zhiwei

    2014-02-01

    Nonlinear optical microscopy (e.g., higher harmonic (second-/third- harmonic) generation (HHG), simulated Raman scattering (SRS)) has high diagnostic sensitivity and chemical specificity, making it a promising tool for label-free tissue and cell imaging. In this work, we report a development of a simultaneous SRS and HHG imaging technique for characterization of liver disease in a bile-duct-ligation rat-modal. HHG visualizes collagens formation and reveals the cell morphologic changes associated with liver fibrosis; whereas SRS identifies the distributions of hepatic fat cells formed in steatosis liver tissue. This work shows that the co-registration of SRS and HHG images can be an effective means for label-free diagnosis and characterization of liver steatosis/fibrosis at the cellular and molecular levels.

  13. Microscopy imaging system and method employing stimulated raman spectroscopy as a contrast mechanism

    DOEpatents

    Xie, Xiaoliang Sunney; Freudiger, Christian; Min, Wei

    2011-09-27

    A microscopy imaging system includes a first light source for providing a first train of pulses at a first center optical frequency .omega..sub.1, a second light source for providing a second train of pulses at a second center optical frequency .omega..sub.2, a modulator system, an optical detector, and a processor. The modulator system is for modulating a beam property of the second train of pulses at a modulation frequency f of at least 100 kHz. The optical detector is for detecting an integrated intensity of substantially all optical frequency components of the first train of pulses from the common focal volume by blocking the second train of pulses being modulated. The processor is for detecting, a modulation at the modulation frequency f, of the integrated intensity of the optical frequency components of the first train of pulses to provide a pixel of an image for the microscopy imaging system.

  14. Paucity of moderately repetitive sequences

    SciTech Connect

    Schmid, C.W.

    1991-01-01

    We examined clones of renatured repetitive human DNA to find novel repetitive DNAs. After eliminating known repeats, the remaining clones were subjected to sequence analysis. These clones also corresponded to known repeats, but with greater sequence diversity. This indicates that either these libraries were depleted of short interspersed repeats in construction, or these repeats are much less prevalent in the human genome than is indicated by data from {und Xenopus} or sea urchin studies. We directly investigated the sequence composition of human DNA through traditional renaturation techniques with the goal of estimating the limits of abundance of repetitive sequence classes in human DNA. Our results sharply limit the maximum possible abundance to 1--2% of the human genome. Our estimate, minus the known repeats in this fraction, leaves about 1% (3 {times} 10{sup 7} nucleotides) of the human genome for novel repetitive elements. 2 refs. (MHB)

  15. Repetitively pumped electron beam device

    DOEpatents

    Schlitt, L.G.

    1979-07-24

    Disclosed is an apparatus for producing fast, repetitive pulses of controllable length of an electron beam by phased energy storage in a transmission line of length matched to the number of pulses and specific pulse lengths desired. 12 figs.

  16. Modeling repetitive motions using structured light.

    PubMed

    Xu, Yi; Aliaga, Daniel G

    2010-01-01

    Obtaining models of dynamic 3D objects is an important part of content generation for computer graphics. Numerous methods have been extended from static scenarios to model dynamic scenes. If the states or poses of the dynamic object repeat often during a sequence (but not necessarily periodically), we call such a repetitive motion. There are many objects, such as toys, machines, and humans, undergoing repetitive motions. Our key observation is that when a motion-state repeats, we can sample the scene under the same motion state again but using a different set of parameters; thus, providing more information of each motion state. This enables robustly acquiring dense 3D information difficult for objects with repetitive motions using only simple hardware. After the motion sequence, we group temporally disjoint observations of the same motion state together and produce a smooth space-time reconstruction of the scene. Effectively, the dynamic scene modeling problem is converted to a series of static scene reconstructions, which are easier to tackle. The varying sampling parameters can be, for example, structured-light patterns, illumination directions, and viewpoints resulting in different modeling techniques. Based on this observation, we present an image-based motion-state framework and demonstrate our paradigm using either a synchronized or an unsynchronized structured-light acquisition method.

  17. A Perceptual Repetition Blindness Effect

    NASA Technical Reports Server (NTRS)

    Hochhaus, Larry; Johnston, James C.; Null, Cynthia H. (Technical Monitor)

    1994-01-01

    Before concluding Repetition Blindness is a perceptual phenomenon, alternative explanations based on memory retrieval problems and report bias must be rejected. Memory problems were minimized by requiring a judgment about only a single briefly displayed field. Bias and sensitivity effects were empirically measured with an ROC-curve analysis method based on confidence ratings. Results from five experiments support the hypothesis that Repetition Blindness can be a perceptual phenomenon.

  18. Imaging the Spatio-Temporal Dynamics of Supragranular Activity in the Rat Somatosensory Cortex in Response to Stimulation of the Paws

    PubMed Central

    Morales-Botello, M. L.; Aguilar, J.; Foffani, G.

    2012-01-01

    We employed voltage-sensitive dye (VSD) imaging to investigate the spatio-temporal dynamics of the responses of the supragranular somatosensory cortex to stimulation of the four paws in urethane-anesthetized rats. We obtained the following main results. (1) Stimulation of the contralateral forepaw evoked VSD responses with greater amplitude and smaller latency than stimulation of the contralateral hindpaw, and ipsilateral VSD responses had a lower amplitude and greater latency than contralateral responses. (2) While the contralateral stimulation initially activated only one focus, the ipsilateral stimulation initially activated two foci: one focus was typically medial to the focus activated by contralateral stimulation and was stereotaxically localized in the motor cortex; the other focus was typically posterior to the focus activated by contralateral stimulation and was stereotaxically localized in the somatosensory cortex. (3) Forepaw and hindpaw somatosensory stimuli activated large areas of the sensorimotor cortex, well beyond the forepaw and hindpaw somatosensory areas of classical somatotopic maps, and forepaw stimuli activated larger cortical areas with greater activation velocity than hindpaw stimuli. (4) Stimulation of the forepaw and hindpaw evoked different cortical activation dynamics: forepaw responses displayed a clear medial directionality, whereas hindpaw responses were much more uniform in all directions. In conclusion, this work offers a complete spatio-temporal map of the supragranular VSD cortical activation in response to stimulation of the paws, showing important somatotopic differences between contralateral and ipsilateral maps as well as differences in the spatio-temporal activation dynamics in response to forepaw and hindpaw stimuli. PMID:22829873

  19. Vibrational imaging of glucose uptake activity in live cells and tissues by stimulated Raman scattering microscopy (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Hu, Fanghao; Chen, Zhixing; Zhang, Luyuan; Shen, Yihui; Wei, Lu; Min, Wei

    2016-03-01

    Glucose is consumed as an energy source by virtually all living organisms, from bacteria to humans. Its uptake activity closely reflects the cellular metabolic status in various pathophysiological transformations, such as diabetes and cancer. Extensive efforts such as positron emission tomography, magnetic resonance imaging and fluorescence microscopy have been made to specifically image glucose uptake activity but all with technical limitations. Here, we report a new platform to visualize glucose uptake activity in live cells and tissues with subcellular resolution and minimal perturbation. A novel glucose analogue with a small alkyne tag (carbon-carbon triple bond) is developed to mimic natural glucose for cellular uptake, which can be imaged with high sensitivity and specificity by targeting the strong and characteristic alkyne vibration on stimulated Raman scattering (SRS) microscope to generate a quantitative three dimensional concentration map. Cancer cells with differing metabolic characteristics can be distinguished. Heterogeneous uptake patterns are observed in tumor xenograft tissues, neuronal culture and mouse brain tissues with clear cell-cell variations. Therefore, by offering the distinct advantage of optical resolution but without the undesirable influence of bulky fluorophores, our method of coupling SRS with alkyne labeled glucose will be an attractive tool to study energy demands of living systems at the single cell level.

  20. Radiation dose measurements of an on-board imager X-ray unit using optically-stimulated luminescence dosimeters.

    PubMed

    Smith, Leon; Haque, Mamoon; Morales, Johnny; Hill, Robin

    2015-12-01

    Cone beam computed tomography (CBCT) is now widely used to image radiotherapy patients prior to treatment for the purpose of accurate patient setup. However each CBCT image delivered to a patient increases the total radiation dose that they receive. The measurement of the dose delivered from the CBCT images is not readily performed in the clinic. In this study, we have used commercially available optically stimulated luminescence (OSLD) dosimeters to measure the dose delivered by the Varian OBI on a radiotherapy linear accelerator. Calibration of the OSLDs was achieved by using a therapeutic X-ray unit. The dose delivered by a head CBCT scan was found to be 3.2 ± 0.3 mGy which is similar in magnitude to the dose of a head computed tomography (CT) scan. The results of this study suggest that the radiation hazard associated with CBCT is of a similar nature to that of conventional CT scans. We have also demonstrated that the OSLDs are suitable for these low X-ray dose measurements.

  1. Heating induced near deep brain stimulation lead electrodes during magnetic resonance imaging with a 3 T transceive volume head coil

    NASA Astrophysics Data System (ADS)

    Shrivastava, Devashish; Abosch, Aviva; Hughes, John; Goerke, Ute; DelaBarre, Lance; Visaria, Rachana; Harel, Noam; Vaughan, J. Thomas

    2012-09-01

    Heating induced near deep brain stimulation (DBS) lead electrodes during magnetic resonance imaging with a 3 T transceive head coil was measured, modeled, and imaged in three cadaveric porcine heads (mean body weight = 85.47 ± 3.19 kg, mean head weight = 5.78 ± 0.32 kg). The effect of the placement of the extra-cranial portion of the DBS lead on the heating was investigated by looping the extra-cranial lead on the top, side, and back of the head, and placing it parallel to the coil's longitudinal axial direction. The heating was induced using a 641 s long turbo spin echo sequence with the mean whole head average specific absorption rate of 3.16 W kg-1. Temperatures were measured using fluoroptic probes at the scalp, first and second electrodes from the distal lead tip, and 6 mm distal from electrode 1 (T6 mm). The heating was modeled using the maximum T6 mm and imaged using a proton resonance frequency shift-based MR thermometry method. Results showed that the heating was significantly reduced when the extra-cranial lead was placed in the longitudinal direction compared to the other placements (peak temperature change = 1.5-3.2 °C versus 5.1-24.7 °C). Thermal modeling and MR thermometry may be used together to determine the heating and improve patient safety online.

  2. Current distribution in skeletal muscle activated by functional electrical stimulation: image-series formulation and isometric recruitment curve.

    PubMed

    Livshitz, L M; Einziger, P D; Mizrahi, J

    2000-01-01

    The present work develops an analytical model that allows one to estimate the current distribution within the whole muscle and the resulting isometric recruitment curve (IRC). The quasistatic current distribution, expressed as an image series, i.e., a collection of properly weighted and shifted point-source responses, outlines an extension for more than three layers of the classical image theory in conductive plane-stratified media. Evaluation of the current distribution via the image series expansions requires substantially less computational time than the standard integral representation. The expansions use a unique recursive representation for Green's function, that is a generic characteristic of the stratification. This approach permits one to verify which of the tissue electrical properties are responsible for the current density distribution within the muscle, and how significant their combinations are. In addition, the model permits one to study the effect of different electrode placement on the shape and the magnitude of the potential distribution. A simple IRC model was used for parameter estimation and model verification by comparison with experimentally obtained isometric recruitment curves. Sensitivity of the model to different parameters such as conductivity of the tissues and activation threshold was verified. The resulting model demonstrated characteristic features that were similar to those of experimentally obtained data. The model also quantitatively confirmed the differences existing between surface (transcutaneous) and implanted (percutaneous) electrode stimulation.

  3. Heating induced near deep brain stimulation lead electrodes during magnetic resonance imaging with a 3 T transceive volume head coil.

    PubMed

    Shrivastava, Devashish; Abosch, Aviva; Hughes, John; Goerke, Ute; DelaBarre, Lance; Visaria, Rachana; Harel, Noam; Vaughan, J Thomas

    2012-09-07

    Heating induced near deep brain stimulation (DBS) lead electrodes during magnetic resonance imaging with a 3 T transceive head coil was measured, modeled, and imaged in three cadaveric porcine heads (mean body weight = 85.47 ± 3.19 kg, mean head weight = 5.78 ± 0.32 kg). The effect of the placement of the extra-cranial portion of the DBS lead on the heating was investigated by looping the extra-cranial lead on the top, side, and back of the head, and placing it parallel to the coil's longitudinal axial direction. The heating was induced using a 641 s long turbo spin echo sequence with the mean whole head average specific absorption rate of 3.16 W kg(-1). Temperatures were measured using fluoroptic probes at the scalp, first and second electrodes from the distal lead tip, and 6 mm distal from electrode 1 (T(6 mm)). The heating was modeled using the maximum T(6 mm) and imaged using a proton resonance frequency shift-based MR thermometry method. Results showed that the heating was significantly reduced when the extra-cranial lead was placed in the longitudinal direction compared to the other placements (peak temperature change = 1.5-3.2 °C versus 5.1-24.7 °C). Thermal modeling and MR thermometry may be used together to determine the heating and improve patient safety online.

  4. Three-dimensional distribution of sensory stimulation-evoked neuronal activity of spinal dorsal horn neurons analyzed by in vivo calcium imaging.

    PubMed

    Nishida, Kazuhiko; Matsumura, Shinji; Taniguchi, Wataru; Uta, Daisuke; Furue, Hidemasa; Ito, Seiji

    2014-01-01

    The spinal dorsal horn comprises heterogeneous populations of interneurons and projection neurons, which form neuronal circuits crucial for processing of primary sensory information. Although electrophysiological analyses have uncovered sensory stimulation-evoked neuronal activity of various spinal dorsal horn neurons, monitoring these activities from large ensembles of neurons is needed to obtain a comprehensive view of the spinal dorsal horn circuitry. In the present study, we established in vivo calcium imaging of multiple spinal dorsal horn neurons by using a two-photon microscope and extracted three-dimensional neuronal activity maps of these neurons in response to cutaneous sensory stimulation. For calcium imaging, a fluorescence resonance energy transfer (FRET)-based calcium indicator protein, Yellow Cameleon, which is insensitive to motion artifacts of living animals was introduced into spinal dorsal horn neurons by in utero electroporation. In vivo calcium imaging following pinch, brush, and heat stimulation suggests that laminar distribution of sensory stimulation-evoked neuronal activity in the spinal dorsal horn largely corresponds to that of primary afferent inputs. In addition, cutaneous pinch stimulation elicited activities of neurons in the spinal cord at least until 2 spinal segments away from the central projection field of primary sensory neurons responsible for the stimulated skin point. These results provide a clue to understand neuronal processing of sensory information in the spinal dorsal horn.

  5. Pre- and post-stimulation characterization of geothermal well GRT-1, Rittershoffen, France: insights from acoustic image logs of hard fractured rock

    NASA Astrophysics Data System (ADS)

    Vidal, Jeanne; Genter, Albert; Schmittbuhl, Jean

    2016-08-01

    Geothermal well GRT-1 (Rittershoffen, Alsace) was drilled in 2012. Its open-hole section (extending down to a depth of 2.6 km) penetrated fractured sandstones and granite. In 2013, the well was subjected to Thermal, Chemical and Hydraulic (TCH) stimulation, which improved the injectivity index fivefold. The goal of the study was to assess the impact of the stimulation by comparing pre- and post-stimulation well-logging (acoustic and temperature [T] logs) and mud-logging data. This comparison revealed modifications of almost all the natural fractures. However, not all of these fractures are associated with permeability enhancement, and the post-stimulation T logs are important for characterizing this enhancement. Chemical alteration due to mechanical erosion at the tops and bottoms of the fractures was observed in the sandstones. These zones display indications of very small new permeability after the TCH stimulation. Because a major fault zone caved extensively where it crosses the borehole, it was not imaged in the acoustic logs. However, this originally permeable zone was enhanced as demonstrated by the T logs. Based on the natural injectivity of this fault zone, hydraulic erosion and thermal microcracking of its internal quartz veins are associated with this permeability enhancement. Although local changes in the borehole wall observed in the acoustic images cannot be directly linked to the improved injectivity index, the comparison of the acoustic image logs allows for identification of fracture zones impacted by the TCH stimulation.

  6. Listening to speech recruits specific tongue motor synergies as revealed by transcranial magnetic stimulation and tissue-Doppler ultrasound imaging.

    PubMed

    D'Ausilio, A; Maffongelli, L; Bartoli, E; Campanella, M; Ferrari, E; Berry, J; Fadiga, L

    2014-01-01

    The activation of listener's motor system during speech processing was first demonstrated by the enhancement of electromyographic tongue potentials as evoked by single-pulse transcranial magnetic stimulation (TMS) over tongue motor cortex. This technique is, however, technically challenging and enables only a rather coarse measurement of this motor mirroring. Here, we applied TMS to listeners' tongue motor area in association with ultrasound tissue Doppler imaging to describe fine-grained tongue kinematic synergies evoked by passive listening to speech. Subjects listened to syllables requiring different patterns of dorso-ventral and antero-posterior movements (/ki/, /ko/, /ti/, /to/). Results show that passive listening to speech sounds evokes a pattern of motor synergies mirroring those occurring during speech production. Moreover, mirror motor synergies were more evident in those subjects showing good performances in discriminating speech in noise demonstrating a role of the speech-related mirror system in feed-forward processing the speaker's ongoing motor plan.

  7. A stimulated Raman scattering imager using high-speed lateral electric field modulator and lock-in pixels amplifiers

    NASA Astrophysics Data System (ADS)

    Mars, Kamel; Guseul, Beak; Han, Sang Man; Takasawa, Taishi; Yasutomi, Keita; Kagawa, Keiichiro; Hashimoto, Mamoru; Kawahito, Shoji

    2014-03-01

    A high speed Lateral Electric Field Modulator (LEFM) and lock-in pixels amplifiers for stimulated Raman scattering (SRS)imager is presented. Since the generated signal from the SRS process is very small compared to the offset signal, a technique suitable for extracting and amplifying the SRS signal is needed. The offset can be canceled by tuning the phase delay between the demodulated pixel output signal and the sampling clock. The small SRS signal in large offset is amplified by the differential integration. The proposed technique has been investigated with an implementation of 64x8 pixels array using a pinned photodiode LEFM an lock-in pixels amplifiers. Very small signal can be extracted from large offset signal. A ratio of the detected small SRS to offset signal of less 10-5 is achieved.

  8. Water Flow Investigation on Quartz Sand with 13-interval Stimulated Echo Multi Slice Imaging

    NASA Astrophysics Data System (ADS)

    Spindler, Natascha; Pohlmeier, Andreas; Galvosas, Petrik

    2011-03-01

    Understanding root water uptake in soils is of high importance for securing nutrition in the context of climate change and linked phenomena like stronger varying weather conditions (draught, strong rain). One step to understand how root water uptake occurs is the knowledge of the water flow in soil towards plant roots. Magnetic Resonance Imaging (MRI) in combination with q-space imaging is potentially the most powerful analytical tool for non-invasive three dimensional visualization of flow and transport in porous media. Numerous attempts have been made to measure local velocity in porous media by combining velocity phase encoding with fast imaging methods, where flow velocities in the vascular bundles of plant stems were investigated. In contrast to water situated in the cellular structure of plants, NMR signal arising from water in the pore space in soil may be much more affected by the presence of internal magnetic field gradients. In this work we account for the existence of these gradients by employing bipolar pulsed field magnetic gradients for velocity encoding. This enables one to study flow through sand (as a model system for soil) at flow rates relevant for the water uptake of plant roots.

  9. Imaging transcranial direct current stimulation (tDCS) of the prefrontal cortex-correlation or causality in stimulation-mediated effects?

    PubMed

    Wörsching, Jana; Padberg, Frank; Ertl-Wagner, Birgit; Kumpf, Ulrike; Kirsch, Beatrice; Keeser, Daniel

    2016-10-01

    Transcranial current stimulation approaches include neurophysiologically distinct non-invasive brain stimulation techniques widely applied in basic, translational and clinical research: transcranial direct current stimulation (tDCS), oscillating transcranial direct current stimulation (otDCS), transcranial alternating current stimulation (tACS) and transcranial random noise stimulation (tRNS). Prefrontal tDCS seems to be an especially promising tool for clinical practice. In order to effectively modulate relevant neural circuits, systematic research on prefrontal tDCS is needed that uses neuroimaging and neurophysiology measures to specifically target and adjust this method to physiological requirements. This review therefore analyses the various neuroimaging methods used in combination with prefrontal tDCS in healthy and psychiatric populations. First, we provide a systematic overview on applications, computational models and studies combining neuroimaging or neurophysiological measures with tDCS. Second, we categorise these studies in terms of their experimental designs and show that many studies do not vary the experimental conditions to the extent required to demonstrate specific relations between tDCS and its behavioural or neurophysiological effects. Finally, to support best-practice tDCS research we provide a methodological framework for orientation among experimental designs.

  10. In situ label-free imaging of hemicellulose in plant cell walls using stimulated Raman scattering microscopy

    DOE PAGES

    Zeng, Yining; Yarbrough, John M.; Mittal, Ashutosh; ...

    2016-11-22

    Plant hemicellulose (largely xylan) is an excellent feedstock for renewable energy production and second only to cellulose in abundance. Beyond a source of fermentable sugars, xylan constitutes a critical polymer in the plant cell wall, where its precise role in wall assembly, maturation, and deconstruction remains primarily hypothetical. Effective detection of xylan, particularly by in situ imaging of xylan in the presence of other biopolymers, would provide critical information for tackling the challenges of understanding the assembly and enhancing the liberation of xylan from plant materials. Raman-based imaging techniques, especially the highly sensitive stimulated Raman scattering (SRS) microscopy, have provenmore » to be valuable tools for label-free imaging. However, due to the complex nature of plant materials, especially those same chemical groups shared between xylan and cellulose, the utility of specific Raman vibrational modes that are unique to xylan have been debated. Here, we report a novel approach based on combining spectroscopic analysis and chemical/enzymatic xylan removal from corn stover cell walls, to make progress in meeting this analytical challenge. We have identified several Raman peaks associated with xylan content in cell walls for label-free in situ imaging xylan in plant cell wall. We demonstrated that xylan can be resolved from cellulose and lignin in situ using enzymatic digestion and label-free SRS microscopy in both 2D and 3D. As a result, we believe that this novel approach can be used to map xylan in plant cell walls and that this ability will enhance our understanding of the role played by xylan in cell wall biosynthesis and deconstruction.« less

  11. In situ label-free imaging of hemicellulose in plant cell walls using stimulated Raman scattering microscopy

    SciTech Connect

    Zeng, Yining; Yarbrough, John M.; Mittal, Ashutosh; Tucker, Melvin P.; Vinzant, Todd B.; Decker, Stephen R.; Himmel, Michael E.

    2016-11-22

    Plant hemicellulose (largely xylan) is an excellent feedstock for renewable energy production and second only to cellulose in abundance. Beyond a source of fermentable sugars, xylan constitutes a critical polymer in the plant cell wall, where its precise role in wall assembly, maturation, and deconstruction remains primarily hypothetical. Effective detection of xylan, particularly by in situ imaging of xylan in the presence of other biopolymers, would provide critical information for tackling the challenges of understanding the assembly and enhancing the liberation of xylan from plant materials. Raman-based imaging techniques, especially the highly sensitive stimulated Raman scattering (SRS) microscopy, have proven to be valuable tools for label-free imaging. However, due to the complex nature of plant materials, especially those same chemical groups shared between xylan and cellulose, the utility of specific Raman vibrational modes that are unique to xylan have been debated. Here, we report a novel approach based on combining spectroscopic analysis and chemical/enzymatic xylan removal from corn stover cell walls, to make progress in meeting this analytical challenge. We have identified several Raman peaks associated with xylan content in cell walls for label-free in situ imaging xylan in plant cell wall. We demonstrated that xylan can be resolved from cellulose and lignin in situ using enzymatic digestion and label-free SRS microscopy in both 2D and 3D. As a result, we believe that this novel approach can be used to map xylan in plant cell walls and that this ability will enhance our understanding of the role played by xylan in cell wall biosynthesis and deconstruction.

  12. Hyperspectral-stimulated Raman scattering imaging of cholesteryl ester accumulation: new avenue to diagnosis of human prostate cancer

    NASA Astrophysics Data System (ADS)

    Du, Jun; Wang, Ping; Yue, Shuhua

    2016-10-01

    Most prostate cancers (PCa) are slowly growing, and only the aggressive ones require early diagnosis and effective treatment. The current standard for PCa diagnosis remains histopathology. Nonetheless, for the differentiation between Gleason score 6 (low-risk PCa), which can be left without treatment, and Gleason score 7 (high-risk PCa), which requires active treatment, the inter-observer discordance can be up to 40%. Our previous study reveals that cholesteryl ester (CE) accumulation induced by PI3K/AKT activation underlies human PCa aggressiveness. However, Raman spectromicroscopy used in this study could only provide compositional information of certain lipid droplets (LDs) selected by the observer, which overlooked cell-to-cell variation and hindered translation to accurate automated diagnosis. Here, we demonstrated quantitative mapping of CE level in human prostate tissues using hyperspectral stimulated Raman scattering (SRS) microscopy that renders compositional information for every pixel in the image. Specifically, hundreds of SRS images at Raman shift between 1620-1800 cm-1 were taken, and multivariate curve resolution algorism was used to retrieve concentration images of acyl C=C bond, sterol C=C bond, and ester C=O bond. Given that the ratio between images of sterol C=C and ester C=O (sterol C=C/C=O) is nonlinearly proportional to CE percentage out of total lipid, we were able to quantitatively map CE level. Our data showed that CE level was significantly greater in high Gleason grade compared to low Gleason grade, and could be a factor that significantly contributed to cancer recurrence. Our study provides an opportunity towards more accurate PCa diagnosis and prediction of aggressiveness.

  13. How Does Brain Activation Differ in Children with Unilateral Cerebral Palsy Compared to Typically Developing Children, during Active and Passive Movements, and Tactile Stimulation? An fMRI Study

    ERIC Educational Resources Information Center

    Van de Winckel, Ann; Klingels, Katrijn; Bruyninckx, Frans; Wenderoth, Nici; Peeters, Ron; Sunaert, Stefan; Van Hecke, Wim; De Cock, Paul; Eyssen, Maria; De Weerdt, Willy; Feys, Hilde

    2013-01-01

    The aim of the functional magnetic resonance imaging (fMRI) study was to investigate brain activation associated with active and passive movements, and tactile stimulation in 17 children with right-sided unilateral cerebral palsy (CP), compared to 19 typically developing children (TD). The active movements consisted of repetitive opening and…

  14. Intranuclear Anchoring of Repetitive DNA Sequences

    PubMed Central

    Weipoltshammer, Klara; Schöfer, Christian; Almeder, Marlene; Philimonenko, Vlada V.; Frei, Klemens; Wachtler, Franz; Hozák, Pavel

    1999-01-01

    Centromeres, telomeres, and ribosomal gene clusters consist of repetitive DNA sequences. To assess their contributions to the spatial organization of the interphase genome, their interactions with the nucleoskeleton were examined in quiescent and activated human lymphocytes. The nucleoskeletons were prepared using “physiological” conditions. The resulting structures were probed for specific DNA sequences of centromeres, telomeres, and ribosomal genes by in situ hybridization; the electroeluted DNA fractions were examined by blot hybridization. In both nonstimulated and stimulated lymphocytes, centromeric alpha-satellite repeats were almost exclusively found in the eluted fraction, while telomeric sequences remained attached to the nucleoskeleton. Ribosomal genes showed a transcription-dependent attachment pattern: in unstimulated lymphocytes, transcriptionally inactive ribosomal genes located outside the nucleolus were eluted completely. When comparing transcription unit and intergenic spacer, significantly more of the intergenic spacer was removed. In activated lymphocytes, considerable but similar amounts of both rDNA fragments were eluted. The results demonstrate that: (a) the various repetitive DNA sequences differ significantly in their intranuclear anchoring, (b) telomeric rather than centromeric DNA sequences form stable attachments to the nucleoskeleton, and (c) different attachment mechanisms might be responsible for the interaction of ribosomal genes with the nucleoskeleton. PMID:10613900

  15. Super-resolution stimulated emission depletion imaging of slit diaphragm proteins in optically cleared kidney tissue.

    PubMed

    Unnersjö-Jess, David; Scott, Lena; Blom, Hans; Brismar, Hjalmar

    2016-01-01

    The glomerular filtration barrier, consisting of podocyte foot processes with bridging slit diaphragm, glomerular basement membrane, and endothelium, is a key component for renal function. Previously, the subtlest elements of the filtration barrier have only been visualized using electron microscopy. However, electron microscopy is mostly restricted to ultrathin two-dimensional samples, and the possibility to simultaneously visualize multiple different proteins is limited. Therefore, we sought to implement a super-resolution immunofluorescence microscopy protocol for the study of the filtration barrier in the kidney. Recently, several optical clearing methods have been developed making it possible to image through large volumes of tissue and even whole organs using light microscopy. Here we found that hydrogel-based optical clearing is a beneficial tool to study intact renal tissue at the nanometer scale. When imaging samples using super-resolution STED microscopy, the staining quality was critical in order to assess correct nanoscale information. The signal-to-noise ratio and immunosignal homogeneity were both improved in optically cleared tissue. Thus, STED of slit diaphragms in fluorescently labeled, optically cleared, intact kidney samples is a new tool for studying the glomerular filtration barrier in health and disease.

  16. A novel combinational approach of microstimulation and bioluminescence imaging to study the mechanisms of action of cerebral electrical stimulation in mice

    PubMed Central

    Arsenault, Dany; Drouin-Ouellet, Janelle; Saint-Pierre, Martine; Petrou, Petros; Dubois, Marilyn; Kriz, Jasna; Barker, Roger A; Cicchetti, Antonio; Cicchetti, Francesca

    2015-01-01

    Key points We have developed a unique prototype to perform brain stimulation in mice. This system presents a number of advantages and new developments: 1) all stimulation parameters can be adjusted, 2) both positive and negative current pulses can be generated, guaranteeing electrically balanced stimulation regimen, 3) which can be produced with both low and high impedance electrodes, 4) the developed electrodes ensure localized stimulation and 5) can be used to stimulate and/or record brain potential and 6) in vivo recording of electric pulses allows the detection of defective electrodes (wire breakage or short circuits). This new micro-stimulator device further allows simultaneous live bioluminescence imaging of the mouse brain, enabling real time assessment of the impact of stimulation on cerebral tissue. The use of this novel tool in various transgenic mouse models of disease opens up a whole new range of possibilities in better understanding brain stimulation. Abstract Deep brain stimulation (DBS) is used to treat a number of neurological conditions and is currently being tested to intervene in neuropsychiatric conditions. However, a better understanding of how it works would ensure that side effects could be minimized and benefits optimized. We have thus developed a unique device to perform brain stimulation (BS) in mice and to address fundamental issues related to this methodology in the pre-clinical setting. This new microstimulator prototype was specifically designed to allow simultaneous live bioluminescence imaging of the mouse brain, allowing real time assessment of the impact of stimulation on cerebral tissue. We validated the authenticity of this tool in vivo by analysing the expression of toll-like receptor 2 (TLR2), corresponding to the microglial response, in the stimulated brain regions of TLR2-fluc-GFP transgenic mice, which we further corroborated with post-mortem analyses in these animals as well as in human brains of patients who underwent DBS

  17. Assessing Cholesterol Storage in Live Cells and C. elegans by Stimulated Raman Scattering Imaging of Phenyl-Diyne Cholesterol

    NASA Astrophysics Data System (ADS)

    Lee, Hyeon Jeong; Zhang, Wandi; Zhang, Delong; Yang, Yang; Liu, Bin; Barker, Eric L.; Buhman, Kimberly K.; Slipchenko, Lyudmila V.; Dai, Mingji; Cheng, Ji-Xin

    2015-01-01

    We report a cholesterol imaging method using rationally synthesized phenyl-diyne cholesterol (PhDY-Chol) and stimulated Raman scattering (SRS) microscope. The phenyl-diyne group is biologically inert and provides a Raman scattering cross section that is 88 times larger than the endogenous C = O stretching mode. SRS microscopy offers an imaging speed that is faster than spontaneous Raman microscopy by three orders of magnitude, and a detection sensitivity of 31 μM PhDY-Chol (~1,800 molecules in the excitation volume). Inside living CHO cells, PhDY-Chol mimics the behavior of cholesterol, including membrane incorporation and esterification. In a cellular model of Niemann-Pick type C disease, PhDY-Chol reflects the lysosomal accumulation of cholesterol, and shows relocation to lipid droplets after HPβCD treatment. In live C. elegans, PhDY-Chol mimics cholesterol uptake by intestinal cells and reflects cholesterol storage. Together, our work demonstrates an enabling platform for study of cholesterol storage and trafficking in living cells and vital organisms.

  18. Repetitively Q-switched Nd:BeL lasers

    NASA Technical Reports Server (NTRS)

    Degnan, J.; Birnbaum, M.; Deshazer, L. G.

    1979-01-01

    The thermal and mechanical characteristics which will ultimately limit the performance of Nd:BeL at high average power levels were investigated. The output beam characteristics (pulse width, peak power, beam dimensions and collimation) were determined at high repetition rates for both Nd:BeL and Nd:YAG. The output of Nd:BeL was shown to exceed that of Nd:YAG by a factor of 2.7 at low Q-switched repetition rates (1 Hz). This result follows from the smaller stimulated emission cross section of x-axis Nb:BeL compared to that of NdYAG by the same factor. At high repetition rates (10 Hz) the output of Nd:Bel falls to a level of three-fifths of its low repetition rate value while under similar tests the output of Nd:YAG remains essentially constant. A comparison of the measured values of the elasto-optic coefficients, the dn/dT values and the linear expansion coefficients for BeL and YAG failed to provide an explanation for the performance of BeL; however, thermal lensing was observed in Nd:BeL. Results imply that the output of a high repetition rate Q-switched Nd:BeL laser (high thermal loading) could be dramatically increased by utilization of a resonator design to compensate for the thermal lensing effects.

  19. Adaptation to sensory stimulation in the Rat Barrel Cortex

    NASA Astrophysics Data System (ADS)

    Heiss, Jaime

    Sustained stimulation of sensory organs results in adaptation of the neuronal response along the sensory pathway. Whether or not cortical adaptation affects equally excitatory and inhibitory inputs is poorly understood. This question was examined using patch recordings of neurons in the barrel cortex of anesthetized rats while repetitively stimulating the principal whisker. After characterizing the excitation and inhibition evoked either by single or double whisker deflection or by different stimulation strengths, it was found that inhibition, unlike excitation, sums linearly and adapts more, causing the balance between these inputs to shift towards excitation. A comparison of the latency of thalamic firing and evoked synaptic inputs in the cortex strongly suggests that adaptation of inhibition results mostly from depression of inhibitory synapses rather than reduction in the firing of inhibitory cells. A similar change in the balance was reproduced by a simple feedforward model. The differential adaptation of the synaptic inputs that shifts the balance toward excitation may act as a gain mechanism which enhances the subthreshold response during sustained stimulation, despite a reduction in excitation. Natural sensory stimulation rarely arrives in an isolated manner, but in a context of several stimulations, like when a rat sweeps its whisker along a surface with a given texture. It was shown that individual single cells sporadically fail to respond, in a very variable fashion from trial to trial. Whether or not adaptation is correlated among neighboring neurons or is it a private, independent phenomenon was investigated by performing simultaneous recordings. Neighboring neurons presented a highly correlated responsiveness to repetitive stimulation, which strongly varied from trial to trial in a synchronized way. Population averages of a single trial obtained by LFP recordings and VSD imaging differed considerably from the time average but was highly correlated to

  20. Sensitivity of measurements of regional brain activation with oxygen-15-water and PET to time of stimulation and period of image reconstruction

    SciTech Connect

    Volkow, N.D.; Mullani, N.; Gould, L.K.; Adler, S.S.; Gatley, S.J. )

    1991-01-01

    Measurement of oxygen-15- (15O) water uptake with positron emission tomography (PET) is a sensitive technique to monitor regional brain activation secondary to stimulation paradigms. In order to investigate data acquisition times that show maximal changes in regional activation and to assess the optimal time for stimulus presentation, we investigated 10 controls with 15O-water and PET during baseline and stroboscopic light stimulation. Sequential scans were done varying the time of stimulus presentation. The images were reconstructed using three different periods of data acquisition: uptake phase (initial 30-35 sec), washout phase (40 sec following peak activity in brain), and total activity (3 min). The images reconstructed during the uptake phase showed the largest changes in occipital cortex from stimulation. Maximal changes in occipital cortex were obtained when the visual stimulus was maintained during the uptake phase only.

  1. Comparison of navigated transcranial magnetic stimulation and functional magnetic resonance imaging for preoperative mapping in rolandic tumor surgery.

    PubMed

    Coburger, Jan; Musahl, Christian; Henkes, Hans; Horvath-Rizea, Diana; Bittl, Markus; Weissbach, Claudia; Hopf, Nikolai

    2013-01-01

    Navigated transcranial magnetic stimulation (nTMS) is a novel tool for preoperative functional mapping. It detects eloquent cortical areas directly, comparable to intraoperative direct cortical stimulation (DCS). The aim of this study was to evaluate the advantage of nTMS in comparison with functional magnetic resonance imaging (fMRI) in the clinical setting. Special focus was placed on accuracy of motor cortex localization in patients with rolandic lesions. Thirty consecutive patients were enrolled in the study. All patients received an fMRI and nTMS examination preoperatively. Feasibility of the technique and spatial resolution of upper and lower extremity cortical mapping were compared with fMRI. Consistency of preoperative mapping with intraoperative DCS was assessed via the neuronavigation system. nTMS was feasible in all 30 patients. fMRI was impossible in 7 out of 30 patients with special clinical conditions, pediatric patients, central vascular lesions, or compliance issues. The mean accuracy to localize motor cortex of nTMS was higher than in fMRI. In the subgroup of intrinsic tumors, nTMS produced statistically significant higher accuracy scores of the lower extremity localization than fMRI. fMRI failed to localize hand or leg areas in 6 out of 23 cases. Using nTMS, a preoperative localization of the central sulcus was possible in all patients. Verification of nTMS motor cortex localization with DCS was achieved in all cases. The fMRI localization of the hand area proved to be postcentral in one case. nTMS has fewer restrictions for preoperative functional mapping than fMRI and requires only a limited level of compliance. nTMS scores higher on the accuracy scale than fMRI. nTMS represents a highly valuable supplement for the preoperative functional planning in the clinical routine.

  2. Neural Correlates of Restricted, Repetitive Behaviors in Autism Spectrum Disorders

    DTIC Science & Technology

    2013-10-01

    Repetitive Behaviors in Autism Spectrum Disorders PRINCIPAL INVESTIGATOR: Manoach, Dara CONTRACTING ORGANIZATION: Massachusetts General... Behaviors in Autism Spectrum Disorders 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-1-0773 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Dara...with autism spectrum disorder NeuroImage: Clinical. in press. CONCLUSION We have completed data

  3. Repetition Blindness Occurs in Nonwords

    ERIC Educational Resources Information Center

    Harris, Catherine L.; Morris, Alison L.

    2004-01-01

    Theorists have predicted that repetition blindness (RB) should be absent for nonwords because they do not activate preexisting mental types. The authors hypothesized that RB would be observed for nonwords because RB can occur at a sublexical level. Four experiments showed that RB is observed for word-nonword pairs (noon noof), orthographically…

  4. Precautions regarding Nonword Repetition Tasks

    ERIC Educational Resources Information Center

    Smith, Bruce

    2006-01-01

    Using nonword repetition tasks as an experimental approach with both adults and children has become quite common in the past 10 to 15 years for studying lexical learning and phonological processing (e.g., Bailey & Hahn, 2001; Gathercole, Frankish, Pickering & Peaker, 1998; Munson, Edwards, & Beckman, 2005; Storkel, 2001; Vitevich & Luce, 2005). In…

  5. Constructive and Unconstructive Repetitive Thought

    ERIC Educational Resources Information Center

    Watkins, Edward R.

    2008-01-01

    The author reviews research showing that repetitive thought (RT) can have constructive or unconstructive consequences. The main unconstructive consequences of RT are (a) depression, (b) anxiety, and (c) difficulties in physical health. The main constructive consequences of RT are (a) recovery from upsetting and traumatic events, (b) adaptive…

  6. 203Pb-Labeled Alpha-Melanocyte-Stimulating Hormone Peptide as an Imaging Probe for Melanoma Detection

    SciTech Connect

    Yubin, Miao; Figueroa, Said D.; Fisher, Darrell R.; Moore, Herbert A.; Testa, Richard F.; Hoffman, Timothy J.; Quinn, Thomas P.

    2008-05-01

    Abbreviations: a-MSH; alpha melanocyte stimulating hormone, DOTA; 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, Re(Arg11)CCMSH; DOTA-[Cys3,4,10, D-Phe7, Arg11]a-MSH3-13, NDP; [Nle4,d-Phe7] a-MSH3-13. Abstract Peptide-targeted alpha therapy with 200 mCi of 212Pb-DOTA-Re(Arg11)CCMSH cured 45% of B16/F1 murine melanoma-bearing C57 mice in a 120-day study, highlighting its melanoma treatment potential. However, there is a need to develop an imaging surrogate for patient specific dosimetry and to monitor the tumor response to 212Pb-DOTA-Re(Arg11)CCMSH therapy. The purpose of this study was to evaluate the potential of 203Pb-DOTA-Re(Arg11)CCMSH as a matched-pair SPECT imaging agent for 212Pb-DOTA-Re(Arg11)CCMSH. Method: DOTA-Re(Arg11)CCMSH was labeled with 203Pb in 0.5 M NH4OAc buffer at pH 5.4. The internalization and efflux of 203Pb-DOTA-Re(Arg11)CCMSH were determined in B16/F1 melanoma cells. The pharmacokinetics of 203Pb-DOTA-Re(Arg11)CCMSH were examined in B16/F1 melanoma-bearing C57 mice. A micro-SPECT/CT imaging study was performed with 203Pb-DOTA-Re(Arg11)CCMSH in a B16/F1 melanoma-bearing C57 mouse at 2 h post-injection. Results: 203Pb-DOTA-Re(Arg11)CCMSH was easily prepared in NH4OAc buffer and completely separated from the excess non-radiolabeled peptide by RP-HPLC. 203Pb-DOTA-Re(Arg11)CCMSH displayed fast internalization and extended retention in B16/F1 cells. Approximately 73% of 203Pb-DOTA-Re(Arg11)CCMSH activity internalized after a 20-min incubation at 25C. After incubating the cells in culture media for 20 min, 78% of internalized activity remained in the cells. 203Pb-DOTA-Re(Arg11)CCMSH exhibited similar biodistribution pattern with 212Pb-DOTA-Re(Arg11)CCMSH in B16/F1 melanoma-bearing mice. 203Pb-DOTA-Re(Arg11)CCMSH exhibited the peak tumor uptake of 12.00 +/- 3.20 %ID/g at 1 h post-injection. The tumor uptake gradually decreased to 3.43 +/- 1.12 %ID/g at 48 h post-injection. 203Pb-DOTA-Re(Arg11)CCMSH exhibited the peak tumor to kidney

  7. Repetitive Visual Stimulation Enhances Recovery from Severe Amblyopia

    ERIC Educational Resources Information Center

    Montey, Karen L.; Eaton, Nicolette C.; Quinlan, Elizabeth M.

    2013-01-01

    Severe amblyopia, characterized by a significant reduction in visual acuity through the affected eye, is highly resistant to reversal in adulthood. We have previously shown that synaptic plasticity can be reactivated in the adult rat visual cortex by dark exposure, and the reactivated plasticity can be harnessed to promote the recovery from severe…

  8. The Length of the Terminal Repetition in Adenovirus-2 DNA

    PubMed Central

    Roberts, Richard J.; Arrand, John R.; Keller, Walter

    1974-01-01

    Adenovirus-2 DNA was end-labeled by partial digestion with Escherichia coli exonuclease III and resynthesis with the DNA polymerase from avian myeloblastosis virus and α-32P-labeled deoxyribonucleoside triphosphates. This end-labeled DNA was cleaved with several specific endonucleases and the terminal fragments were characterized by gel electrophoresis and pyrimidine tract analysis. Two endonucleases gave identical fragments from both ends, presumably from cleavage within the inverted terminal repetition, while all other endonucleases gave dissimilar fragments from the two ends. From the sizes of these fragments it is estimated that the inverted terminal repetition is between 100 and 140 nucleotide pairs long. Images PMID:4139703

  9. Examining Cortical Dynamics and Connectivity with Simultaneous Single-Pulse Transcranial Magnetic Stimulation and Fast Optical Imaging

    PubMed Central

    Parks, Nathan A.; Maclin, Edward L.; Low, Kathy A.; Beck, Diane M.; Fabiani, Monica; Gratton, Gabriele

    2011-01-01

    Transcranial magnetic stimulation (TMS) is a widely used experimental and clinical technique that directly induces activity in human cortex using magnetic fields. However, the neural mechanisms of TMS-induced activity are not well understood. Here, we introduce a novel method of imaging TMS-evoked activity using a non-invasive fast optical imaging tool, the event-related optical signal (EROS). EROS measures changes in the scattering of near-infrared light that occur synchronously with electrical activity in cortical tissue. EROS has good temporal and spatial resolution, allowing the dynamics and spatial spread of a TMS pulse to be measured. We used EROS to monitor activity induced in primary motor cortex (M1) by a TMS pulse. Left- and right-hand representations were mapped using standard TMS procedures. Optical sources and detectors mounted on thin rubber patches were then centered on M1 hand representations. EROS was recorded bilaterally from motor cortex while unilateral TMS was simultaneously delivered. Robust ipsilateral EROS activations were apparent within 16 ms of a pulse for TMS delivered to both left and right hemispheres. Clear motor evoked potentials (MEPs) were also elicited by these TMS pulses. Movement artifacts could be excluded as a source of EROS, as no activation was present on short-distance optical channels. For left hemisphere TMS subsequent (40 ms) contralateral activity was also present, presumably due to trans-synaptic propagation of TMS-evoked activity. Results demonstrate that concurrent TMS/EROS is a viable and potentially powerful method for studying TMS-induced activity in the human brain. With further development, this technique may be applied more broadly in the study of the dynamics of causal cortico-cortical connectivity. PMID:21925608

  10. Understanding communicative actions: a repetitive TMS study.

    PubMed

    Stolk, Arjen; Noordzij, Matthijs L; Volman, Inge; Verhagen, Lennart; Overeem, Sebastiaan; van Elswijk, Gijs; Bloem, Bas; Hagoort, Peter; Toni, Ivan

    2014-02-01

    Despite the ambiguity inherent in human communication, people are remarkably efficient in establishing mutual understanding. Studying how people communicate in novel settings provides a window into the mechanisms supporting the human competence to rapidly generate and understand novel shared symbols, a fundamental property of human communication. Previous work indicates that the right posterior superior temporal sulcus (pSTS) is involved when people understand the intended meaning of novel communicative actions. Here, we set out to test whether normal functioning of this cerebral structure is required for understanding novel communicative actions using inhibitory low-frequency repetitive transcranial magnetic stimulation (rTMS). A factorial experimental design contrasted two tightly matched stimulation sites (right pSTS vs left MT+, i.e., a contiguous homotopic task-relevant region) and tasks (a communicative task vs a visual tracking task that used the same sequences of stimuli). Overall task performance was not affected by rTMS, whereas changes in task performance over time were disrupted according to TMS site and task combinations. Namely, rTMS over pSTS led to a diminished ability to improve action understanding on the basis of recent communicative history, while rTMS over MT+ perturbed improvement in visual tracking over trials. These findings qualify the contributions of the right pSTS to human communicative abilities, showing that this region might be necessary for incorporating previous knowledge, accumulated during interactions with a communicative partner, to constrain the inferential process that leads to action understanding.

  11. Imaging the intracellular distribution of tyrosine kinase inhibitors in living cells with quantitative hyperspectral stimulated Raman scattering

    NASA Astrophysics Data System (ADS)

    Fu, Dan; Zhou, Jing; Zhu, Wenjing Suzanne; Manley, Paul W.; Wang, Y. Karen; Hood, Tami; Wylie, Andrew; Xie, X. Sunney

    2014-07-01

    ABL1 tyrosine-kinase inhibitors (TKI) are front-line therapy for chronic myelogenous leukaemia and are among the best-known examples of targeted cancer therapeutics. However, the dynamic uptake into cells of TKIs of low molecular weight and their intracellular behaviour is unknown because of the difficulty of observing non-fluorescent small molecules at subcellular resolution. Here we report the direct label-free visualization and quantification of two TKI drugs (imatinib and nilotinib) inside living cells using hyperspectral stimulated Raman scattering imaging. Concentrations of both drugs were enriched over 1,000-fold in lysosomes as a result of their lysosomotropic properties. In addition, low solubility appeared to contribute significantly to the surprisingly large accumulation of nilotinib. We further show that the lysosomal trapping of imatinib was reduced more than tenfold when chloroquine is used simultaneously, which suggests that chloroquine may increase the efficacy of TKIs through lysosome-mediated drug-drug interaction in addition to the commonly proposed autophagy-inhibition mechanism.

  12. A microfluidic platform with pH imaging for chemical and hydrodynamic stimulation of intact oral biofilms.

    PubMed

    Gashti, M Parvinzadeh; Asselin, J; Barbeau, J; Boudreau, D; Greener, J

    2016-04-21

    A microfluidic platform with a fluorescent nanoparticle-based sensor is demonstrated for real-time, ratiometric pH imaging of biofilms. Sensing is accomplished by a thin patterned layer of covalently bonded Ag@SiO2+FiTC nanoparticles on an embedded planar glass substrate. The system is designed to be sensitive, responsive and give sufficient spatial resolution to enable new micro-scale studies of the dynamic response of oral biofilms to well-controlled chemical and hydrodynamic stimulation. Performance under challenging operational conditions is demonstrated, which include long-duration exposure to sheer stresses, photoexcitation and pH sensor biofouling. After comprehensive validation, the device was used to monitor pH changes at the attachment surface of a biofilm of the oral bacteria, Streptococcus salivarius. By controlling flow and chemical concentration conditions in the microchannel, biochemical and mass transport contributions to the Stephan curve could be probed individually. This opens the way for the analysis of separate contributions to dental caries due to localized acidification directly at the biofilm tooth interface.

  13. Contributions of structural connectivity and cerebrovascular parameters to functional magnetic resonance imaging signals in mice at rest and during sensory paw stimulation.

    PubMed

    Schroeter, Aileen; Grandjean, Joanes; Schlegel, Felix; Saab, Bechara J; Rudin, Markus

    2016-01-01

    Previously, we reported widespread bilateral increases in stimulus-evoked functional magnetic resonance imaging signals in mouse brain to unilateral sensory paw stimulation. We attributed the pattern to arousal-related cardiovascular changes overruling cerebral autoregulation thereby masking specific signal changes elicited by local neuronal activity. To rule out the possibility that interhemispheric neuronal communication might contribute to bilateral functional magnetic resonance imaging responses, we compared stimulus-evoked functional magnetic resonance imaging responses to unilateral hindpaw stimulation in acallosal I/LnJ, C57BL/6, and BALB/c mice. We found bilateral blood-oxygenation-level dependent signal changes in all three strains, ruling out a dominant contribution of transcallosal communication as reason for bilaterality. Analysis of functional connectivity derived from resting-state functional magnetic resonance imaging, revealed that bilateral cortical functional connectivity is largely abolished in I/LnJ animals. Cortical functional connectivity in all strains correlated with structural connectivity in corpus callosum as revealed by diffusion tensor imaging. Given the profound influence of systemic hemodynamics on stimulus-evoked functional magnetic resonance imaging outcomes, we evaluated whether functional connectivity data might be affected by cerebrovascular parameters, i.e. baseline cerebral blood volume, vascular reactivity, and reserve. We found that effects of cerebral hemodynamics on functional connectivity are largely outweighed by dominating contributions of structural connectivity. In contrast, contributions of transcallosal interhemispheric communication to the occurrence of ipsilateral functional magnetic resonance imaging response of equal amplitude to unilateral stimuli seem negligible.

  14. Light-controlled biphasic current stimulator IC using CMOS image sensors for high-resolution retinal prosthesis and in vitro experimental results with rd1 mouse.

    PubMed

    Oh, Sungjin; Ahn, Jae-Hyun; Lee, Sangmin; Ko, Hyoungho; Seo, Jong Mo; Goo, Yong-Sook; Cho, Dong-il Dan

    2015-01-01

    Retinal prosthetic devices stimulate retinal nerve cells with electrical signals proportional to the incident light intensities. For a high-resolution retinal prosthesis, it is necessary to reduce the size of the stimulator pixels as much as possible, because the retinal nerve cells are concentrated in a small area of approximately 5 mm × 5 mm. In this paper, a miniaturized biphasic current stimulator integrated circuit is developed for subretinal stimulation and tested in vitro. The stimulator pixel is miniaturized by using a complementary metal-oxide-semiconductor (CMOS) image sensor composed of three transistors. Compared to a pixel that uses a four-transistor CMOS image sensor, this new design reduces the pixel size by 8.3%. The pixel size is further reduced by simplifying the stimulation-current generating circuit, which provides a 43.9% size reduction when compared to the design reported to be the most advanced version to date for subretinal stimulation. The proposed design is fabricated using a 0.35 μm bipolar-CMOS-DMOS process. Each pixel is designed to fit in a 50 μ m × 55 μm area, which theoretically allows implementing more than 5000 pixels in the 5 mm × 5 mm area. Experimental results show that a biphasic current in the range of 0 to 300 μA at 12 V can be generated as a function of incident light intensities. Results from in vitro experiments with rd1 mice indicate that the proposed method can be effectively used for retinal prosthesis with a high resolution.

  15. Computer-Related Repetitive Stress Injuries

    MedlinePlus

    ... RSIs are linked to the stress of repetitive motions at the computer or overuse injuries in sports. ... use, texting, playing musical instruments, or the repetitive motion of sports like tennis. An RSI occurs when ...

  16. Repetitively pulsed vacuum insulator flashover

    SciTech Connect

    Ginn, J.W.; Buttram, M.T.

    1987-01-01

    Experiments were performed to determine the flashover strength of various vacuum insulators under conditions of repetitive pulsing. The pulse duration was 30 ns, and the thickness of a typical insulator sample was 1.8 cm. Data were taken for 45 insulators from five different materials. An insulator was subjected to an extended series of pulses at a given repetition rate and field. If flashover was not detected, the field level was increased and the sequence repeated. At rates up to 50 pulses per second, there was no apparent dependence of flashover field on rate. In addition, some ''single shot'' data were taken, including various modifications of the geometries and surface textures of the insulators. Only two to the modifications increased the flashover strength significantly over that of a 45 sample: (1) annealing some plastics (roughly a 35% increase), and (2) extending the insulator to cover the surfaces of both electrodes (an increase of nearly a factor of two).

  17. Expectancy and Repetition in Task Preparation

    NASA Technical Reports Server (NTRS)

    Ruthruff, E.; Remington, R. W.; Johnston, James C.; Null, Cynthia H. (Technical Monitor)

    1996-01-01

    We studied the mechanisms of task preparation using a design that pitted task expectancy against task repetition. In one experiment, two simple cognitive tasks were presented in a predictable sequence containing both repetitions and non-repetitions. The typical task sequence was AABBAABB. Occasional violations of this sequence allowed us to measure the effects of valid versus invalid expectancy. With this design, we were able to study the effects of task expectancy, task repetition, and interaction.

  18. Chromosome specific repetitive DNA sequences

    DOEpatents

    Moyzis, Robert K.; Meyne, Julianne

    1991-01-01

    A method is provided for determining specific nucleotide sequences useful in forming a probe which can identify specific chromosomes, preferably through in situ hybridization within the cell itself. In one embodiment, chromosome preferential nucleotide sequences are first determined from a library of recombinant DNA clones having families of repetitive sequences. Library clones are identified with a low homology with a sequence of repetitive DNA families to which the first clones respectively belong and variant sequences are then identified by selecting clones having a pattern of hybridization with genomic DNA dissimilar to the hybridization pattern shown by the respective families. In another embodiment, variant sequences are selected from a sequence of a known repetitive DNA family. The selected variant sequence is classified as chromosome specific, chromosome preferential, or chromosome nonspecific. Sequences which are classified as chromosome preferential are further sequenced and regions are identified having a low homology with other regions of the chromosome preferential sequence or with known sequences of other family me This invention is the result of a contract with the Department of Energy (Contract No. W-7405-ENG-36).

  19. Non-invasive brain stimulation in early rehabilitation after stroke.

    PubMed

    Blesneag, A V; Popa, L; Stan, A D

    2015-01-01

    The new tendency in rehabilitation involves non-invasive tools that, if applied early after stroke, promote neurorecovery. Repetitive transcranial magnetic stimulation and transcranial direct current stimulation may correct the disruption of cortical excitability and effectively contribute to the restoration of movement and speech. The present paper analyses the results of non-invasive brain stimulation (NIBS) trials, highlighting different aspects related to the repetitive transcranial magnetic stimulation frequency, transcranial direct current stimulation polarity, the period and stimulation places in acute and subacute ischemic strokes. The risk of adverse events, the association with motor or language recovery specific training, and the cumulative positive effect evaluation are also discussed.

  20. Repetitive DNA sequences in Mycoplasma pneumoniae.

    PubMed Central

    Wenzel, R; Herrmann, R

    1988-01-01

    Two types of different repetitive DNA sequences called RepMP1 and RepMP2 were identified in the genome of Mycoplasma pneumoniae. The number of these repeated elements, their nucleotide sequence and their localization on a physical map of the M. pneumoniae genome were determined. The results show that RepMP1 appears at least 10 times and RepMP2 at least 8 times in the genome. The repeated elements are dispersed on the chromosome and, in three cases, linked to each other by a homologous DNA sequence of 400 bp. The elements themselves are 300 bp (for RepMP1) and 150 bp (for RepMP2) long showing a high degree of homology. One copy of RepMP2 is a translated part of the gene for the major cytadhesin protein P1 which is responsible for the adsorption of M. pneumoniae to its host cell. Images PMID:3138660

  1. Secretin stimulation test (image)

    MedlinePlus

    ... secrete a fluid with a high concentration of bicarbonate. This fluid neutralizes the acidity from the stomach ... pancreas (for example chronic pancreatitis, cystic fibrosis, pancreatic cancer) may have abnormal pancreatic function.

  2. Activation of histamine H3 receptor decreased cytoplasmic Ca(2+) imaging during electrical stimulation in the skeletal myotubes.

    PubMed

    Chen, Yan; Paavola, Jere; Stegajev, Vasili; Stark, Holger; Chazot, Paul L; Wen, Jian Guo; Konttinen, Yrjö T

    2015-05-05

    Histamine is a neurotransmitter and chemical mediator in multiple physiological processes. Histamine H3 receptor is expressed in the nervous system, heart, and gastrointestinal tract; however, little is known about H3 receptor in skeletal muscle. The aim of this study was to investigate the role of H3 receptor in skeletal myotubes. The expression of H3 receptor and myosin heavy chain (MHC), a late myogenesis marker, was assessed by real-time PCR and immunostaining in C2C12 skeletal myogenesis and adult mid-urethral skeletal muscle tissues. H3 receptor mRNA showed a significant increase upon differentiation of C2C12 into myotubes: 1-, 26-, 91-, and 182-fold at days 0, 2, 4, and 6, respectively. H3 receptor immunostaining in differentiated C2C12 cells and adult skeletal muscles was positive and correlated with that of MHC. The functional role of H3receptor in differentiated myotubes was assessed using an H3 receptor agonist, (R)-a-methylhistamine ((R)-α-MeHA). Ca(2+) imaging, stimulated by electric pacing, was decreased by 55% after the treatment of mature C2C12 myotubes with 1μM (R)-α-MeHA for 10min and 20min, while treatment with 100nm (R)-α-MeHA for 5min caused 45% inhibition. These results suggested that H3 receptor may participate in the maintenance of the relaxed state and prevention of over-contraction in mature differentiated myotubes. The elucidation of the role of H3R in skeletal myogenesis and adult skeletal muscle may open a new direction in the treatment of skeletal muscle disorders, such as muscle weakness, atrophy, and myotonia in motion systems or peri-urethral skeletal muscle tissues.

  3. A novel combinational approach of microstimulation and bioluminescence imaging to study the mechanisms of action of cerebral electrical stimulation in mice.

    PubMed

    Arsenault, Dany; Drouin-Ouellet, Janelle; Saint-Pierre, Martine; Petrou, Petros; Dubois, Marilyn; Kriz, Jasna; Barker, Roger A; Cicchetti, Antonio; Cicchetti, Francesca

    2015-05-15

    Deep brain stimulation (DBS) is used to treat a number of neurological conditions and is currently being tested to intervene in neuropsychiatric conditions. However, a better understanding of how it works would ensure that side effects could be minimized and benefits optimized. We have thus developed a unique device to perform brain stimulation (BS) in mice and to address fundamental issues related to this methodology in the pre-clinical setting. This new microstimulator prototype was specifically designed to allow simultaneous live bioluminescence imaging of the mouse brain, allowing real time assessment of the impact of stimulation on cerebral tissue. We validated the authenticity of this tool in vivo by analysing the expression of toll-like receptor 2 (TLR2), corresponding to the microglial response, in the stimulated brain regions of TLR2-fluc-GFP transgenic mice, which we further corroborated with post-mortem analyses in these animals as well as in human brains of patients who underwent DBS to treat their Parkinson's disease. In the present study, we report on the development of the first BS device that allows for simultaneous live in vivo imaging in mice. This tool opens up a whole new range of possibilities that allow a better understanding of BS and how to optimize its effects through its use in murine models of disease.

  4. Spinal Autofluorescent Flavoprotein Imaging in a Rat Model of Nerve Injury-Induced Pain and the Effect of Spinal Cord Stimulation

    PubMed Central

    Jongen, Joost L. M.; Smits, Helwin; Pederzani, Tiziana; Bechakra, Malik; Hossaini, Mehdi; Koekkoek, Sebastiaan K.; Huygen, Frank J. P. M.; De Zeeuw, Chris I.; Holstege, Jan C.; Joosten, Elbert A. J.

    2014-01-01

    Nerve injury may cause neuropathic pain, which involves hyperexcitability of spinal dorsal horn neurons. The mechanisms of action of spinal cord stimulation (SCS), an established treatment for intractable neuropathic pain, are only partially understood. We used Autofluorescent Flavoprotein Imaging (AFI) to study changes in spinal dorsal horn metabolic activity. In the Seltzer model of nerve-injury induced pain, hypersensitivity was confirmed using the von Frey and hotplate test. 14 Days after nerve-injury, rats were anesthetized, a bipolar electrode was placed around the affected sciatic nerve and the spinal cord was exposed by a laminectomy at T13. AFI recordings were obtained in neuropathic rats and a control group of naïve rats following 10 seconds of electrical stimulation of the sciatic nerve at C-fiber strength, or following non-noxious palpation. Neuropathic rats were then treated with 30 minutes of SCS or sham stimulation and AFI recordings were obtained for up to 60 minutes after cessation of SCS/sham. Although AFI responses to noxious electrical stimulation were similar in neuropathic and naïve rats, only neuropathic rats demonstrated an AFI-response to palpation. Secondly, an immediate, short-lasting, but strong reduction in AFI intensity and area of excitation occurred following SCS, but not following sham stimulation. Our data confirm that AFI can be used to directly visualize changes in spinal metabolic activity following nerve injury and they imply that SCS acts through rapid modulation of nociceptive processing at the spinal level. PMID:25279562

  5. Label-free real-time imaging of myelination in the Xenopus laevis tadpole by in vivo stimulated Raman scattering microscopy

    NASA Astrophysics Data System (ADS)

    Hu, Chun-Rui; Zhang, Delong; Slipchenko, Mikhail N.; Cheng, Ji-Xin; Hu, Bing

    2014-08-01

    The myelin sheath plays an important role as the axon in the functioning of the neural system, and myelin degradation is a hallmark pathology of multiple sclerosis and spinal cord injury. Electron microscopy, fluorescent microscopy, and magnetic resonance imaging are three major techniques used for myelin visualization. However, microscopic observation of myelin in living organisms remains a challenge. Using a newly developed stimulated Raman scattering microscopy approach, we report noninvasive, label-free, real-time in vivo imaging of myelination by a single-Schwann cell, maturation of a single node of Ranvier, and myelin degradation in the transparent body of the Xenopus laevis tadpole.

  6. Label-free real-time imaging of myelination in the Xenopus laevis tadpole by in vivo stimulated Raman scattering microscopy

    PubMed Central

    Hu, Chun-Rui; Zhang, Delong; Slipchenko, Mikhail N.; Cheng, Ji-Xin; Hu, Bing

    2014-01-01

    Abstract. The myelin sheath plays an important role as the axon in the functioning of the neural system, and myelin degradation is a hallmark pathology of multiple sclerosis and spinal cord injury. Electron microscopy, fluorescent microscopy, and magnetic resonance imaging are three major techniques used for myelin visualization. However, microscopic observation of myelin in living organisms remains a challenge. Using a newly developed stimulated Raman scattering microscopy approach, we report noninvasive, label-free, real-time in vivo imaging of myelination by a single-Schwann cell, maturation of a single node of Ranvier, and myelin degradation in the transparent body of the Xenopus laevis tadpole. PMID:25104411

  7. Circuit considerations for repetitive railguns

    SciTech Connect

    Honih, E.M.

    1986-01-01

    Railgun electromagnetic launchers have significant military and scientific potential. They provide direct conversion of electrical energy to projectile kinetic energy, and they offer the hope of achieving projectile velocities greatly exceeding the limits of conventional guns. With over 10 km/sec already demonstrated, railguns are attracting attention for tactical and strategic weapons systems and for scientific equation-of-state research. The full utilization of railguns will require significant improvements in every aspect of system design - projectile, barrel, and power source - to achieve operation on a large scale. This paper will review fundamental aspects of railguns, with emphasis on circuit considerations and repetitive operation.

  8. The neural correlates of picture naming facilitated by auditory repetition

    PubMed Centr