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Sample records for cortical activation modulates

  1. A Circuit for Motor Cortical Modulation of Auditory Cortical Activity

    PubMed Central

    Nelson, Anders; Schneider, David M.; Takatoh, Jun; Sakurai, Katsuyasu; Wang, Fan

    2013-01-01

    Normal hearing depends on the ability to distinguish self-generated sounds from other sounds, and this ability is thought to involve neural circuits that convey copies of motor command signals to various levels of the auditory system. Although such interactions at the cortical level are believed to facilitate auditory comprehension during movements and drive auditory hallucinations in pathological states, the synaptic organization and function of circuitry linking the motor and auditory cortices remain unclear. Here we describe experiments in the mouse that characterize circuitry well suited to transmit motor-related signals to the auditory cortex. Using retrograde viral tracing, we established that neurons in superficial and deep layers of the medial agranular motor cortex (M2) project directly to the auditory cortex and that the axons of some of these deep-layer cells also target brainstem motor regions. Using in vitro whole-cell physiology, optogenetics, and pharmacology, we determined that M2 axons make excitatory synapses in the auditory cortex but exert a primarily suppressive effect on auditory cortical neuron activity mediated in part by feedforward inhibition involving parvalbumin-positive interneurons. Using in vivo intracellular physiology, optogenetics, and sound playback, we also found that directly activating M2 axon terminals in the auditory cortex suppresses spontaneous and stimulus-evoked synaptic activity in auditory cortical neurons and that this effect depends on the relative timing of motor cortical activity and auditory stimulation. These experiments delineate the structural and functional properties of a corticocortical circuit that could enable movement-related suppression of auditory cortical activity. PMID:24005287

  2. A circuit for motor cortical modulation of auditory cortical activity.

    PubMed

    Nelson, Anders; Schneider, David M; Takatoh, Jun; Sakurai, Katsuyasu; Wang, Fan; Mooney, Richard

    2013-09-04

    Normal hearing depends on the ability to distinguish self-generated sounds from other sounds, and this ability is thought to involve neural circuits that convey copies of motor command signals to various levels of the auditory system. Although such interactions at the cortical level are believed to facilitate auditory comprehension during movements and drive auditory hallucinations in pathological states, the synaptic organization and function of circuitry linking the motor and auditory cortices remain unclear. Here we describe experiments in the mouse that characterize circuitry well suited to transmit motor-related signals to the auditory cortex. Using retrograde viral tracing, we established that neurons in superficial and deep layers of the medial agranular motor cortex (M2) project directly to the auditory cortex and that the axons of some of these deep-layer cells also target brainstem motor regions. Using in vitro whole-cell physiology, optogenetics, and pharmacology, we determined that M2 axons make excitatory synapses in the auditory cortex but exert a primarily suppressive effect on auditory cortical neuron activity mediated in part by feedforward inhibition involving parvalbumin-positive interneurons. Using in vivo intracellular physiology, optogenetics, and sound playback, we also found that directly activating M2 axon terminals in the auditory cortex suppresses spontaneous and stimulus-evoked synaptic activity in auditory cortical neurons and that this effect depends on the relative timing of motor cortical activity and auditory stimulation. These experiments delineate the structural and functional properties of a corticocortical circuit that could enable movement-related suppression of auditory cortical activity.

  3. Lateral entorhinal modulation of piriform cortical activity and fine odor discrimination.

    PubMed

    Chapuis, Julie; Cohen, Yaniv; He, Xiaobin; Zhang, Zhijan; Jin, Sen; Xu, Fuqiang; Wilson, Donald A

    2013-08-14

    The lateral entorhinal cortex (LEC) receives direct input from olfactory bulb mitral cells and piriform cortical pyramidal cells and is the gateway for olfactory input to the hippocampus. However, the LEC also projects back to the piriform cortex and olfactory bulb. Activity in the LEC is shaped by input from the perirhinal cortices, hippocampus, and amygdala, and thus could provide a rich contextual modulation of cortical odor processing. The present study further explored LEC feedback to anterior piriform cortex by examining how LEC top-down input modulates anterior piriform cortex odor evoked activity in rats. Retrograde viral tracing confirmed rich LEC projections to both the olfactory bulb and piriform cortices. In anesthetized rats, reversible lesions of the ipsilateral LEC increased anterior piriform cortical single-unit spontaneous activity. In awake animals performing an odor discrimination task, unilateral LEC reversible lesions enhanced ipsilateral piriform cortical local field potential oscillations during odor sampling, with minimal impact on contralateral activity. Bilateral LEC reversible lesions impaired discrimination performance on a well learned, difficult odor discrimination task, but had no impact on a well learned simple odor discrimination task. The simple discrimination task was impaired by bilateral reversible lesions of the anterior piriform cortex. Given the known function of LEC in working memory and multisensory integration, these results suggest it may serve as a powerful top-down modulator of olfactory cortical function and odor perception. Furthermore, the results provide potential insight into how neuropathology in the entorhinal cortex could contribute to early olfactory deficits seen in Alzheimer's disease.

  4. Subthalamic stimulation modulates cortical motor network activity and synchronization in Parkinson's disease.

    PubMed

    Weiss, Daniel; Klotz, Rosa; Govindan, Rathinaswamy B; Scholten, Marlieke; Naros, Georgios; Ramos-Murguialday, Ander; Bunjes, Friedemann; Meisner, Christoph; Plewnia, Christian; Krüger, Rejko; Gharabaghi, Alireza

    2015-03-01

    Dynamic modulations of large-scale network activity and synchronization are inherent to a broad spectrum of cognitive processes and are disturbed in neuropsychiatric conditions including Parkinson's disease. Here, we set out to address the motor network activity and synchronization in Parkinson's disease and its modulation with subthalamic stimulation. To this end, 20 patients with idiopathic Parkinson's disease with subthalamic nucleus stimulation were analysed on externally cued right hand finger movements with 1.5-s interstimulus interval. Simultaneous recordings were obtained from electromyography on antagonistic muscles (right flexor digitorum and extensor digitorum) together with 64-channel electroencephalography. Time-frequency event-related spectral perturbations were assessed to determine cortical and muscular activity. Next, cross-spectra in the time-frequency domain were analysed to explore the cortico-cortical synchronization. The time-frequency modulations enabled us to select a time-frequency range relevant for motor processing. On these time-frequency windows, we developed an extension of the phase synchronization index to quantify the global cortico-cortical synchronization and to obtain topographic differentiations of distinct electrode sites with respect to their contributions to the global phase synchronization index. The spectral measures were used to predict clinical and reaction time outcome using regression analysis. We found that movement-related desynchronization of cortical activity in the upper alpha and beta range was significantly facilitated with 'stimulation on' compared to 'stimulation off' on electrodes over the bilateral parietal, sensorimotor, premotor, supplementary-motor, and prefrontal areas, including the bilateral inferior prefrontal areas. These spectral modulations enabled us to predict both clinical and reaction time improvement from subthalamic stimulation. With 'stimulation on', interhemispheric cortico-cortical

  5. Subthalamic stimulation modulates cortical motor network activity and synchronization in Parkinson’s disease

    PubMed Central

    Klotz, Rosa; Govindan, Rathinaswamy B.; Scholten, Marlieke; Naros, Georgios; Ramos-Murguialday, Ander; Bunjes, Friedemann; Meisner, Christoph; Plewnia, Christian; Krüger, Rejko

    2015-01-01

    Dynamic modulations of large-scale network activity and synchronization are inherent to a broad spectrum of cognitive processes and are disturbed in neuropsychiatric conditions including Parkinson’s disease. Here, we set out to address the motor network activity and synchronization in Parkinson’s disease and its modulation with subthalamic stimulation. To this end, 20 patients with idiopathic Parkinson’s disease with subthalamic nucleus stimulation were analysed on externally cued right hand finger movements with 1.5-s interstimulus interval. Simultaneous recordings were obtained from electromyography on antagonistic muscles (right flexor digitorum and extensor digitorum) together with 64-channel electroencephalography. Time-frequency event-related spectral perturbations were assessed to determine cortical and muscular activity. Next, cross-spectra in the time-frequency domain were analysed to explore the cortico-cortical synchronization. The time-frequency modulations enabled us to select a time-frequency range relevant for motor processing. On these time-frequency windows, we developed an extension of the phase synchronization index to quantify the global cortico-cortical synchronization and to obtain topographic differentiations of distinct electrode sites with respect to their contributions to the global phase synchronization index. The spectral measures were used to predict clinical and reaction time outcome using regression analysis. We found that movement-related desynchronization of cortical activity in the upper alpha and beta range was significantly facilitated with ‘stimulation on’ compared to ‘stimulation off’ on electrodes over the bilateral parietal, sensorimotor, premotor, supplementary-motor, and prefrontal areas, including the bilateral inferior prefrontal areas. These spectral modulations enabled us to predict both clinical and reaction time improvement from subthalamic stimulation. With ‘stimulation on’, interhemispheric cortico-cortical

  6. Temporal changes in cortical activation during conditioned pain modulation (CPM), a LORETA study.

    PubMed

    Moont, Ruth; Crispel, Yonatan; Lev, Rina; Pud, Dorit; Yarnitsky, David

    2011-07-01

    For most healthy subjects, both subjective pain ratings and pain-evoked potentials are attenuated under conditioned pain modulation (CPM; formerly termed diffuse noxious inhibitory controls, or DNIC). Although essentially spinal-bulbar, this inhibition is under cortical control. This is the first study to observe temporal as well as spatial changes in cortical activations under CPM. Specifically, we aimed to investigate the interplay of areas involved in the perception and processing of pain and those involved in controlling descending inhibition. We examined brief consecutive poststimulus time windows of 50 ms using a method of source-localization from pain evoked potentials, sLORETA. This enabled determination of dynamic changes in localized cortical generators evoked by phasic noxious heat stimuli to the left volar forearm in healthy young males, with and without conditioning hot-water pain to the right hand. We found a CPM effect characterized by an initial increased activation in the orbitofrontal cortex (OFC) and amygdala at 250-300 ms poststimulus, which was correlated with the extent of psychophysical pain reduction. This was followed by reduced activations in the primary and secondary somatosensory cortices, supplementary motor area, posterior insula, and anterior cingulate cortex from 400 ms poststimulus. Our findings show that the prefrontal pain-controlling areas of OFC and amygdala increase their activity in parallel with subjective pain reduction under CPM, and that this increased activity occurs prior to reductions in activations of the pain sensory areas. In conclusion, achieving pain inhibition by the CPM process seems to be under control of the OFC and the amygdala.

  7. Transcranial Direct Current Stimulation Modulates Cortical Neuronal Activity in Alzheimer's Disease.

    PubMed

    Marceglia, Sara; Mrakic-Sposta, Simona; Rosa, Manuela; Ferrucci, Roberta; Mameli, Francesca; Vergari, Maurizio; Arlotti, Mattia; Ruggiero, Fabiana; Scarpini, Elio; Galimberti, Daniela; Barbieri, Sergio; Priori, Alberto

    2016-01-01

    . Our findings disclosed that tDCS induces significant modulations in the cortical EEG activity in AD patients. The abnormal pattern of EEG activity observed in AD during memory processing is partially reversed by applying anodal tDCS, suggesting that anodal tDCS benefits in AD patients during working memory tasks are supported by the modulation of cortical activity.

  8. Transcranial Direct Current Stimulation Modulates Cortical Neuronal Activity in Alzheimer's Disease

    PubMed Central

    Marceglia, Sara; Mrakic-Sposta, Simona; Rosa, Manuela; Ferrucci, Roberta; Mameli, Francesca; Vergari, Maurizio; Arlotti, Mattia; Ruggiero, Fabiana; Scarpini, Elio; Galimberti, Daniela; Barbieri, Sergio; Priori, Alberto

    2016-01-01

    . Our findings disclosed that tDCS induces significant modulations in the cortical EEG activity in AD patients. The abnormal pattern of EEG activity observed in AD during memory processing is partially reversed by applying anodal tDCS, suggesting that anodal tDCS benefits in AD patients during working memory tasks are supported by the modulation of cortical activity. PMID:27065792

  9. Active engagement improves primary auditory cortical neurons' ability to discriminate temporal modulation.

    PubMed

    Niwa, Mamiko; Johnson, Jeffrey S; O'Connor, Kevin N; Sutter, Mitchell L

    2012-07-04

    The effect of attention on single neuron responses in the auditory system is unresolved. We found that when monkeys discriminated temporally amplitude modulated (AM) from unmodulated sounds, primary auditory cortical (A1) neurons better discriminated those sounds than when the monkeys were not discriminating them. This was observed for both average firing rate and vector strength (VS), a measure of how well neurons temporally follow the stimulus' temporal modulation. When data were separated by nonsynchronized and synchronized responses, the firing rate of nonsynchronized responses best distinguished AM- noise from unmodulated noise, followed by VS for synchronized responses, with firing rate for synchronized neurons providing the poorest AM discrimination. Firing rate-based AM discrimination for synchronized neurons, however, improved most with task engagement, showing that the least sensitive code in the passive condition improves the most with task engagement. Rate coding improved due to larger increases in absolute firing rate at higher modulation depths than for lower depths and unmodulated sounds. Relative to spontaneous activity (which increased with engagement), the response to unmodulated sounds decreased substantially. The temporal coding improvement--responses more precisely temporally following a stimulus when animals were required to attend to it--expands the framework of possible mechanisms of attention to include increasing temporal precision of stimulus following. These findings provide a crucial step to understanding the coding of temporal modulation and support a model in which rate and temporal coding work in parallel, permitting a multiplexed code for temporal modulation, and for a complementary representation of rate and temporal coding.

  10. Pathways for fear perception: modulation of amygdala activity by thalamo-cortical systems.

    PubMed

    Das, Pritha; Kemp, Andrew H; Liddell, Belinda J; Brown, Kerri J; Olivieri, Gloria; Peduto, Anthony; Gordon, Evian; Williams, Leanne M

    2005-05-15

    Effective perception of fear signals is crucial for human survival and the importance of the amygdala in this process is well documented. Animal, lesion and neuroimaging studies indicate that incoming sensory signals of fear travel from thalamus to amygdala via two neural pathways: a direct subcortical route and an indirect pathway via the sensory cortex. Other lines of research have demonstrated prefrontal modulation of the amygdala. However, no study to date has examined the prefrontal modulation of the thalamo-cortico-amygdala pathways in vivo. We used psychophysiological and physiophysiological interactions to examine the functional connectivity within thalamus, amygdala and sensory (inferior occipital, fusiform) cortices, and the modulation of these networks by the anterior cingulate cortex (ACC). Functional magnetic resonance imaging (fMRI) data were acquired for 28 healthy control subjects during a fear perception task, with neutral as the 'baseline' control condition. Main effect analysis, using a region of interest (ROI) approach, confirmed that these regions are part of a distributed neural system for fear perception. Psychophysiological interactions revealed an inverse functional connectivity between occipito-temporal visual regions and the left amygdala, but a positive connectivity between these visual region and the right amygdala, suggesting that there is a hemispheric specialization in the transfer of fear signals from sensory cortices to amygdala. Physiophysiological interactions revealed a dorsal-ventral division in ACC modulation of the thalamus-sensory cortex pathway. While the dorsal ACC showed a positive modulation of this pathway, the ventral ACC exhibited an inverse relationship. In addition, both the dorsal and ventral ACC showed an inverse interaction with the direct thalamus-amygdala pathway. These findings suggest that thalamo-amygdala and cortical regions are involved in a dynamic interplay, with functional differentiation in both

  11. Generation of field potentials and modulation of their dynamics through volume integration of cortical activity.

    PubMed

    Kajikawa, Yoshinao; Schroeder, Charles E

    2015-01-01

    Field potentials (FPs) recorded within the brain, often called "local field potentials" (LFPs), are useful measures of net synaptic activity in a neuronal ensemble. However, due to volume conduction, FPs spread beyond regions of underlying synaptic activity, and thus an "LFP" signal may not accurately reflect the temporal patterns of synaptic activity in the immediately surrounding neuron population. To better understand the physiological processes reflected in FPs, we explored the relationship between the FP and its membrane current generators using current source density (CSD) analysis in conjunction with a volume conductor model. The model provides a quantitative description of the spatiotemporal summation of immediate local and more distant membrane currents to produce the FP. By applying the model to FPs in the macaque auditory cortex, we have investigated a critical issue that has broad implications for FP research. We have shown that FP responses in particular cortical layers are differentially susceptible to activity in other layers. Activity in the supragranular layers has the strongest contribution to FPs in other cortical layers, and infragranular FPs are most susceptible to contributions from other layers. To define the physiological processes generating FPs recorded in loci of relatively weak synaptic activity, strong effects produced by synaptic events in the vicinity have to be taken into account. While outlining limitations and caveats inherent to FP measurements, our results also suggest specific peak and frequency band components of FPs can be related to activity in specific cortical layers. These results may help improving the interpretability of FPs.

  12. Sensorimotor modulation of human cortical swallowing pathways

    PubMed Central

    Hamdy, Shaheen; Aziz, Qasim; Rothwell, John C; Hobson, Anthony; Thompson, David G

    1998-01-01

    Transcranial magnetic stimulation over motor areas of cerebral cortex in man can activate short latency bilateral cortical projections to the pharynx and oesophagus. In the present paper we investigate the interaction between pathways from each hemisphere and explore how activity in these pathways is modulated by afferent feedback from the face, pharynx and oesophagus.Comparison of unilateral and bilateral stimulation (using interstimulus intervals (ISIs) of 1, 5 or 10 ms between shocks) showed spatial summation of responses from each hemisphere at an ISI of 1 ms, indicating that cortical efferents project onto a shared population of target neurones. Such summation was not evident at ISIs of 5 or 10 ms. There was little evidence for transcallosal inhibition of responses from each hemisphere, as described for limb muscles.Single stimuli applied to the vagus nerve in the neck or the supraorbital nerve, which alone produce intermediate (onset 20-30 ms) and long (50-70 ms) latency reflex responses in the pharynx and oesophagus, were used to condition the cortical responses. Compared with rest, responses evoked by cortical stimulation were facilitated when they were timed to coincide with the late part of the reflex. The onset latency was reduced during both parts of the reflex response. No facilitation was observed with subthreshold reflex stimuli.Single electrical stimuli applied to the pharynx or oesophagus had no effect on the response to cortical stimulation. However, trains of stimuli at frequencies varying from 0.2 to 10 Hz decreased the latency of the cortically evoked responses without consistently influencing their amplitudes. The effect was site specific: pharyngeal stimulation shortened both pharyngeal and oesophageal response latencies, whereas oesophageal stimulation shortened only the oesophageal response latencies.Cortical swallowing motor pathways from each hemisphere interact and their excitability is modulated in a site-specific manner by sensory

  13. Acute Modulation of Cortical Glutamate and GABA Content by Physical Activity.

    PubMed

    Maddock, Richard J; Casazza, Gretchen A; Fernandez, Dione H; Maddock, Michael I

    2016-02-24

    Converging evidence demonstrates that physical activity evokes a brain state characterized by distinctive changes in brain metabolism and cortical function. Human studies have shown that physical activity leads to a generalized increase in electroencephalography power across regions and frequencies, and a global increase in brain nonoxidative metabolism of carbohydrate substrates. This nonoxidative consumption of carbohydrate has been hypothesized to include increased de novo synthesis of amino acid neurotransmitters, especially glutamate and GABA. Here, we conducted a series of proton magnetic resonance spectroscopy studies in human volunteers before and after vigorous exercise (≥80% of predicted maximal heart rate). Results showed that the resonance signals of both glutamate and GABA increased significantly in the visual cortex following exercise. We further demonstrated a similar increase in glutamate following exercise in an executive region, the anterior cingulate cortex. The increase in glutamate was similar when using echo times of 30 and 144 ms, indicating that exercise-related T2 relaxation effects across this range of relaxation times did not account for the findings. In addition, we found preliminary evidence that more physical activity during the preceding week predicts higher resting glutamate levels. Overall, the results are consistent with an exercise-induced expansion of the cortical pools of glutamate and GABA, and add to a growing understanding of the distinctive brain state associated with physical activity. A more complete understanding of this brain state may reveal important insights into mechanisms underlying the beneficial effects of physical exercise in neuropsychiatric disorders, neurorehabilitation, aging, and cognition.

  14. The role of reading activity on the modulation of motor cortical outputs to the reading hand in Braille readers.

    PubMed

    Pascual-Leone, A; Wassermann, E M; Sadato, N; Hallett, M

    1995-12-01

    We studied the cortical motor output maps of the first dorsal interosseous (FDI) of both hands and the abductor digiti minimi of the reading hand in 6 blind proficient Braille readers. The maps were generated using transcranial magnetic stimulation. We compared the maps obtained on a day in which they worked as Braille proofreaders (reading Braille for approximately 6 hours) with the maps obtained on a day they took off from work. On the work day, the maps for the FDI of the reading hand were significantly larger after the working shift than in the morning after having been off work for 2 days. These changes were not seen for the same muscle on the day off work or on any of the 2 days in the other two muscles studied. These results illustrate the rapid modulation in motor cortical outputs in relation to preceding activity and emphasize the importance of precise timing in studies of the neurophysiological correlates of skill acquisition.

  15. Cortical activities of single-trial P300 amplitudes modulated by memory load using simultaneous EEG-fMRI

    NASA Astrophysics Data System (ADS)

    Zhang, Qiushi; Zhao, Xiaojie; Zhu, Chaozhe; Yang, Xueqian; Yao, Li

    2015-03-01

    The functional magnetic resonance imaging (fMRI) researches on working memory have found that activation of cortical areas appeared dependent on memory load, and event-related potentials (ERP) studies have demonstrated that amplitudes of P300 decreased significantly when working memory load increased. However, the cortical activities related with P300 amplitudes under different memory loads remains unclear. Joint fMRI and EEG analysis which fusions the time and spatial information in simultaneous EEG-fMRI recording can reveal the regional activation at each ERP time point. In this paper, we first used wavelet transform to obtain the single-trial amplitudes of P300 caused by a digital N-back task in the simultaneous EEG-fMRI recording as the ERP feature sequences. Then the feature sequences in 1-back condition and 3-back condition were introduced into general linear model (GLM) separately as parametric modulations to compare the cortical activation under different memory loads. The results showed that the average amplitudes of P300 in 3-back significantly decreased than that in 1-back, and the activities induced by ERP feature sequences in 3-back also significantly decreased than that in the 1-back, including the insular, anterior cingulate cortex, right inferior frontal gyrus, and medial frontal gyrus, which were relevant to the storage, monitoring, and manipulation of information in working memory task. Moreover, the difference in the activation caused by ERP feature showed a positive correlation with the difference in behavioral performance. These findings demonstrated the locations of P300 amplitudes differences modulated by the memory load and its relationship with the behavioral performance.

  16. Brief wide-field photostimuli evoke and modulate oscillatory reverberating activity in cortical networks

    PubMed Central

    Pulizzi, Rocco; Musumeci, Gabriele; Van den Haute, Chris; Van De Vijver, Sebastiaan; Baekelandt, Veerle; Giugliano, Michele

    2016-01-01

    Cell assemblies manipulation by optogenetics is pivotal to advance neuroscience and neuroengineering. In in vivo applications, photostimulation often broadly addresses a population of cells simultaneously, leading to feed-forward and to reverberating responses in recurrent microcircuits. The former arise from direct activation of targets downstream, and are straightforward to interpret. The latter are consequence of feedback connectivity and may reflect a variety of time-scales and complex dynamical properties. We investigated wide-field photostimulation in cortical networks in vitro, employing substrate-integrated microelectrode arrays and long-term cultured neuronal networks. We characterized the effect of brief light pulses, while restricting the expression of channelrhodopsin to principal neurons. We evoked robust reverberating responses, oscillating in the physiological gamma frequency range, and found that such a frequency could be reliably manipulated varying the light pulse duration, not its intensity. By pharmacology, mathematical modelling, and intracellular recordings, we conclude that gamma oscillations likely emerge as in vivo from the excitatory-inhibitory interplay and that, unexpectedly, the light stimuli transiently facilitate excitatory synaptic transmission. Of relevance for in vitro models of (dys)functional cortical microcircuitry and in vivo manipulations of cell assemblies, we give for the first time evidence of network-level consequences of the alteration of synaptic physiology by optogenetics. PMID:27099182

  17. Extrathalamic Modulation of Cortical Function

    DTIC Science & Technology

    1990-07-27

    and c7rtico-cortical systems. For example, we have shown that primate LC-NA neurons are more acti during waking than sleep and exhibit bursts of...infusion needle. Infusion of the alpha-adrenergic agonist clonidine (CLON), in concentrations ranging from 5-20 uM (67-270pg/50 nl injection...ind hippocampal EEG (HEEG) typically exhibit activity similar to that of a lightly sleeping animal. However, periods of "waking" EEG are sometimes

  18. Lactate modulates the activity of primary cortical neurons through a receptor-mediated pathway.

    PubMed

    Bozzo, Luigi; Puyal, Julien; Chatton, Jean-Yves

    2013-01-01

    Lactate is increasingly described as an energy substrate of the brain. Beside this still debated metabolic role, lactate may have other effects on brain cells. Here, we describe lactate as a neuromodulator, able to influence the activity of cortical neurons. Neuronal excitability of mouse primary neurons was monitored by calcium imaging. When applied in conjunction with glucose, lactate induced a decrease in the spontaneous calcium spiking frequency of neurons. The effect was reversible and concentration dependent (IC50 ∼4.2 mM). To test whether lactate effects are dependent on energy metabolism, we applied the closely related substrate pyruvate (5 mM) or switched to different glucose concentrations (0.5 or 10 mM). None of these conditions reproduced the effect of lactate. Recently, a Gi protein-coupled receptor for lactate called HCA1 has been introduced. To test if this receptor is implicated in the observed lactate sensitivity, we incubated cells with pertussis toxin (PTX) an inhibitor of Gi-protein. PTX prevented the decrease of neuronal activity by L-lactate. Moreover 3,5-dyhydroxybenzoic acid, a specific agonist of the HCA1 receptor, mimicked the action of lactate. This study indicates that lactate operates a negative feedback on neuronal activity by a receptor-mediated mechanism, independent from its intracellular metabolism.

  19. Lactate Modulates the Activity of Primary Cortical Neurons through a Receptor-Mediated Pathway

    PubMed Central

    Bozzo, Luigi; Puyal, Julien; Chatton, Jean-Yves

    2013-01-01

    Lactate is increasingly described as an energy substrate of the brain. Beside this still debated metabolic role, lactate may have other effects on brain cells. Here, we describe lactate as a neuromodulator, able to influence the activity of cortical neurons. Neuronal excitability of mouse primary neurons was monitored by calcium imaging. When applied in conjunction with glucose, lactate induced a decrease in the spontaneous calcium spiking frequency of neurons. The effect was reversible and concentration dependent (IC50 ∼4.2 mM). To test whether lactate effects are dependent on energy metabolism, we applied the closely related substrate pyruvate (5 mM) or switched to different glucose concentrations (0.5 or 10 mM). None of these conditions reproduced the effect of lactate. Recently, a Gi protein-coupled receptor for lactate called HCA1 has been introduced. To test if this receptor is implicated in the observed lactate sensitivity, we incubated cells with pertussis toxin (PTX) an inhibitor of Gi-protein. PTX prevented the decrease of neuronal activity by L-lactate. Moreover 3,5-dyhydroxybenzoic acid, a specific agonist of the HCA1 receptor, mimicked the action of lactate. This study indicates that lactate operates a negative feedback on neuronal activity by a receptor-mediated mechanism, independent from its intracellular metabolism. PMID:23951229

  20. Simulating Cortical Feedback Modulation as Changes in Excitation and Inhibition in a Cortical Circuit Model

    PubMed Central

    Murray, John D.; McCormick, David A.

    2016-01-01

    Abstract Cortical feedback pathways are hypothesized to distribute context-dependent signals during flexible behavior. Recent experimental work has attempted to understand the mechanisms by which cortical feedback inputs modulate their target regions. Within the mouse whisker sensorimotor system, cortical feedback stimulation modulates spontaneous activity and sensory responsiveness, leading to enhanced sensory representations. However, the cellular mechanisms underlying these effects are currently unknown. In this study we use a simplified neural circuit model, which includes two recurrent excitatory populations and global inhibition, to simulate cortical modulation. First, we demonstrate how changes in the strengths of excitation and inhibition alter the input–output processing responses of our model. Second, we compare these responses with experimental findings from cortical feedback stimulation. Our analyses predict that enhanced inhibition underlies the changes in spontaneous and sensory evoked activity observed experimentally. More generally, these analyses provide a framework for relating cellular and synaptic properties to emergent circuit function and dynamic modulation. PMID:27595137

  1. Serotonin modulation of cortical neurons and networks

    PubMed Central

    Celada, Pau; Puig, M. Victoria; Artigas, Francesc

    2013-01-01

    The serotonergic pathways originating in the dorsal and median raphe nuclei (DR and MnR, respectively) are critically involved in cortical function. Serotonin (5-HT), acting on postsynaptic and presynaptic receptors, is involved in cognition, mood, impulse control and motor functions by (1) modulating the activity of different neuronal types, and (2) varying the release of other neurotransmitters, such as glutamate, GABA, acetylcholine and dopamine. Also, 5-HT seems to play an important role in cortical development. Of all cortical regions, the frontal lobe is the area most enriched in serotonergic axons and 5-HT receptors. 5-HT and selective receptor agonists modulate the excitability of cortical neurons and their discharge rate through the activation of several receptor subtypes, of which the 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT3 subtypes play a major role. Little is known, however, on the role of other excitatory receptors moderately expressed in cortical areas, such as 5-HT2C, 5-HT4, 5-HT6, and 5-HT7. In vitro and in vivo studies suggest that 5-HT1A and 5-HT2A receptors are key players and exert opposite effects on the activity of pyramidal neurons in the medial prefrontal cortex (mPFC). The activation of 5-HT1A receptors in mPFC hyperpolarizes pyramidal neurons whereas that of 5-HT2A receptors results in neuronal depolarization, reduction of the afterhyperpolarization and increase of excitatory postsynaptic currents (EPSCs) and of discharge rate. 5-HT can also stimulate excitatory (5-HT2A and 5-HT3) and inhibitory (5-HT1A) receptors in GABA interneurons to modulate synaptic GABA inputs onto pyramidal neurons. Likewise, the pharmacological manipulation of various 5-HT receptors alters oscillatory activity in PFC, suggesting that 5-HT is also involved in the control of cortical network activity. A better understanding of the actions of 5-HT in PFC may help to develop treatments for mood and cognitive disorders associated with an abnormal function of the frontal lobe

  2. Serotonin modulation of cortical neurons and networks.

    PubMed

    Celada, Pau; Puig, M Victoria; Artigas, Francesc

    2013-01-01

    The serotonergic pathways originating in the dorsal and median raphe nuclei (DR and MnR, respectively) are critically involved in cortical function. Serotonin (5-HT), acting on postsynaptic and presynaptic receptors, is involved in cognition, mood, impulse control and motor functions by (1) modulating the activity of different neuronal types, and (2) varying the release of other neurotransmitters, such as glutamate, GABA, acetylcholine and dopamine. Also, 5-HT seems to play an important role in cortical development. Of all cortical regions, the frontal lobe is the area most enriched in serotonergic axons and 5-HT receptors. 5-HT and selective receptor agonists modulate the excitability of cortical neurons and their discharge rate through the activation of several receptor subtypes, of which the 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT3 subtypes play a major role. Little is known, however, on the role of other excitatory receptors moderately expressed in cortical areas, such as 5-HT2C, 5-HT4, 5-HT6, and 5-HT7. In vitro and in vivo studies suggest that 5-HT1A and 5-HT2A receptors are key players and exert opposite effects on the activity of pyramidal neurons in the medial prefrontal cortex (mPFC). The activation of 5-HT1A receptors in mPFC hyperpolarizes pyramidal neurons whereas that of 5-HT2A receptors results in neuronal depolarization, reduction of the afterhyperpolarization and increase of excitatory postsynaptic currents (EPSCs) and of discharge rate. 5-HT can also stimulate excitatory (5-HT2A and 5-HT3) and inhibitory (5-HT1A) receptors in GABA interneurons to modulate synaptic GABA inputs onto pyramidal neurons. Likewise, the pharmacological manipulation of various 5-HT receptors alters oscillatory activity in PFC, suggesting that 5-HT is also involved in the control of cortical network activity. A better understanding of the actions of 5-HT in PFC may help to develop treatments for mood and cognitive disorders associated with an abnormal function of the frontal lobe.

  3. ACTIVITY IN CORTICAL MIDLINE STRUCTURES IS MODULATED BY SELF-CONSTRUAL CHANGES DURING ACCULTURATION

    PubMed Central

    Chen, Pin-Hao A.; Wagner, Dylan D.; Kelley, William M.; Heatherton, Todd F.

    2015-01-01

    Recent immigrants to another culture generally experience a period of acculturation during which they show self-construal changes. Here, we examine how this acculturation period alters brain activity associated with self-referential cognition. Twenty-seven native Chinese-speaking recent immigrants completed a trait-judgment task in which they judged whether a series of psychological traits applied to themselves and, separately, whether these traits applied to their mothers. Participants were scanned at two intervals: within the first two months of their arrival in the United States (Time 1), and also six months after the initial scan (Time 2). Results already revealed a significant self-vs.-mother differentiation at Time 1 in the medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC). However, at time 2, this pattern diverged depending on whether immigrants became more or less like their original culture. That is to say, for immigrants who became less like Easterners, the self vs. mother difference remained, whereas for participants who became even more like Easterners, the self vs. mother difference in cortical midline structures disappeared. These findings support the notion that self-construal changes during the process of acculturation are reflected in the relative engagement of brain structures implicated in self-referential processing (i.e., MPFC and PCC) when judging traits with reference to oneself or a close other. PMID:26236572

  4. tDCS Modulates Visual Gamma Oscillations and Basal Alpha Activity in Occipital Cortices: Evidence from MEG.

    PubMed

    Wilson, Tony W; McDermott, Timothy J; Mills, Mackenzie S; Coolidge, Nathan M; Heinrichs-Graham, Elizabeth

    2017-03-10

    Transcranial direct-current stimulation (tDCS) is now a widely used method for modulating the human brain, but the resulting physiological effects are not understood. Recent studies have combined magnetoencephalography (MEG) with simultaneous tDCS to evaluate online changes in occipital alpha and gamma oscillations, but no study to date has quantified the offline (i.e., after tDCS) alterations in these responses. Thirty-five healthy adults received active or sham anodal tDCS to the occipital cortices, and then completed a visual stimulation paradigm during MEG that is known to elicit robust gamma and alpha oscillations. The resulting MEG data were imaged and peak voxel time series were extracted to evaluate tDCS effects. We found that tDCS to the occipital increased the amplitude of local gamma oscillations, and basal alpha levels during the baseline. tDCS was also associated with network-level effects, including increased gamma oscillations in the prefrontal cortex, parietal, and other visual attention regions. Finally, although tDCS did not modulate peak gamma frequency, this variable was inversely correlated with gamma amplitude, which is consistent with a GABA-gamma link. In conclusion, tDCS alters gamma oscillations and basal alpha levels. The net offline effects on gamma activity are consistent with the view that anodal tDCS decreases local GABA.

  5. Cortical Axons, Isolated in Channels, Display Activity-Dependent Signal Modulation as a Result of Targeted Stimulation.

    PubMed

    Lewandowska, Marta K; Radivojević, Miloš; Jäckel, David; Müller, Jan; Hierlemann, Andreas R

    2016-01-01

    Mammalian cortical axons are extremely thin processes that are difficult to study as a result of their small diameter: they are too narrow to patch while intact, and super-resolution microscopy is needed to resolve single axons. We present a method for studying axonal physiology by pairing a high-density microelectrode array with a microfluidic axonal isolation device, and use it to study activity-dependent modulation of axonal signal propagation evoked by stimulation near the soma. Up to three axonal branches from a single neuron, isolated in different channels, were recorded from simultaneously using 10-20 electrodes per channel. The axonal channels amplified spikes such that propagations of individual signals along tens of electrodes could easily be discerned with high signal to noise. Stimulation from 10 up to 160 Hz demonstrated similar qualitative results from all of the cells studied: extracellular action potential characteristics changed drastically in response to stimulation. Spike height decreased, spike width increased, and latency increased, as a result of reduced propagation velocity, as the number of stimulations and the stimulation frequencies increased. Quantitatively, the strength of these changes manifested itself differently in cells at different frequencies of stimulation. Some cells' signal fidelity fell to 80% already at 10 Hz, while others maintained 80% signal fidelity at 80 Hz. Differences in modulation by axonal branches of the same cell were also seen for different stimulation frequencies, starting at 10 Hz. Potassium ion concentration changes altered the behavior of the cells causing propagation failures at lower concentrations and improving signal fidelity at higher concentrations.

  6. Cortical Axons, Isolated in Channels, Display Activity-Dependent Signal Modulation as a Result of Targeted Stimulation

    PubMed Central

    Lewandowska, Marta K.; Radivojević, Miloš; Jäckel, David; Müller, Jan; Hierlemann, Andreas R.

    2016-01-01

    Mammalian cortical axons are extremely thin processes that are difficult to study as a result of their small diameter: they are too narrow to patch while intact, and super-resolution microscopy is needed to resolve single axons. We present a method for studying axonal physiology by pairing a high-density microelectrode array with a microfluidic axonal isolation device, and use it to study activity-dependent modulation of axonal signal propagation evoked by stimulation near the soma. Up to three axonal branches from a single neuron, isolated in different channels, were recorded from simultaneously using 10–20 electrodes per channel. The axonal channels amplified spikes such that propagations of individual signals along tens of electrodes could easily be discerned with high signal to noise. Stimulation from 10 up to 160 Hz demonstrated similar qualitative results from all of the cells studied: extracellular action potential characteristics changed drastically in response to stimulation. Spike height decreased, spike width increased, and latency increased, as a result of reduced propagation velocity, as the number of stimulations and the stimulation frequencies increased. Quantitatively, the strength of these changes manifested itself differently in cells at different frequencies of stimulation. Some cells' signal fidelity fell to 80% already at 10 Hz, while others maintained 80% signal fidelity at 80 Hz. Differences in modulation by axonal branches of the same cell were also seen for different stimulation frequencies, starting at 10 Hz. Potassium ion concentration changes altered the behavior of the cells causing propagation failures at lower concentrations and improving signal fidelity at higher concentrations. PMID:27013945

  7. Pain modulation in waking and hypnosis in women: event-related potentials and sources of cortical activity.

    PubMed

    De Pascalis, Vilfredo; Varriale, Vincenzo; Cacace, Immacolata

    2015-01-01

    Using a strict subject selection procedure, we tested in High and Low Hypnotizable subjects (HHs and LHs) whether treatments of hypoalgesia and hyperalgesia, as compared to a relaxation-control, differentially affected subjective pain ratings and somatosensory event-related potentials (SERPs) during painful electric stimulation. Treatments were administered in waking and hypnosis conditions. LHs showed little differentiation in pain and distress ratings between hypoalgesia and hyperalgesia treatments, whereas HHs showed a greater spread in the instructed direction. HHs had larger prefrontal N140 and P200 waves of the SERPs during hypnotic hyperalgesia as compared to relaxation-control treatment. Importantly, HHs showed significant smaller frontocentral N140 and frontotemporal P200 waves during hypnotic hypoalgesia. LHs did not show significant differences for these SERP waves among treatments in both waking and hypnosis conditions. Source localization (sLORETA) method revealed significant activations of the bilateral primary somatosensory (BA3), middle frontal gyrus (BA6) and anterior cingulate cortices (BA24). Activity of these contralateral regions significantly correlated with subjective numerical pain scores for control treatment in waking condition. Moreover, multivariate regression analyses distinguished the contralateral BA3 as the only region reflecting a stable pattern of pain coding changes across all treatments in waking and hypnosis conditions. More direct testing showed that hypnosis reduced the strength of the association of pain modulation and brain activity changes at BA3. sLORETA in HHs revealed, for the N140 wave, that during hypnotic hyperalgesia, there was an increased activity within medial, supramarginal and superior frontal gyri, and cingulated gyrus (BA32), while for the P200 wave, activity was increased in the superior (BA22), middle (BA37), inferior temporal (BA19) gyri and superior parietal lobule (BA7). Hypnotic hypoalgesia in HHs, for N

  8. Pain Modulation in Waking and Hypnosis in Women: Event-Related Potentials and Sources of Cortical Activity

    PubMed Central

    De Pascalis, Vilfredo; Varriale, Vincenzo; Cacace, Immacolata

    2015-01-01

    Using a strict subject selection procedure, we tested in High and Low Hypnotizable subjects (HHs and LHs) whether treatments of hypoalgesia and hyperalgesia, as compared to a relaxation-control, differentially affected subjective pain ratings and somatosensory event-related potentials (SERPs) during painful electric stimulation. Treatments were administered in waking and hypnosis conditions. LHs showed little differentiation in pain and distress ratings between hypoalgesia and hyperalgesia treatments, whereas HHs showed a greater spread in the instructed direction. HHs had larger prefrontal N140 and P200 waves of the SERPs during hypnotic hyperalgesia as compared to relaxation-control treatment. Importantly, HHs showed significant smaller frontocentral N140 and frontotemporal P200 waves during hypnotic hypoalgesia. LHs did not show significant differences for these SERP waves among treatments in both waking and hypnosis conditions. Source localization (sLORETA) method revealed significant activations of the bilateral primary somatosensory (BA3), middle frontal gyrus (BA6) and anterior cingulate cortices (BA24). Activity of these contralateral regions significantly correlated with subjective numerical pain scores for control treatment in waking condition. Moreover, multivariate regression analyses distinguished the contralateral BA3 as the only region reflecting a stable pattern of pain coding changes across all treatments in waking and hypnosis conditions. More direct testing showed that hypnosis reduced the strength of the association of pain modulation and brain activity changes at BA3. sLORETA in HHs revealed, for the N140 wave, that during hypnotic hyperalgesia, there was an increased activity within medial, supramarginal and superior frontal gyri, and cingulated gyrus (BA32), while for the P200 wave, activity was increased in the superior (BA22), middle (BA37), inferior temporal (BA19) gyri and superior parietal lobule (BA7). Hypnotic hypoalgesia in HHs, for N

  9. Cortical commands in active touch.

    PubMed

    Brecht, Michael

    2006-01-01

    The neocortex is an enormous network of extensively interconnected neurons. It has become clear that the computations performed by individual cortical neurons will critically depend on the quantitative composition of cortical activity. Here we discuss quantitative aspects of cortical activity and modes of cortical processing in the context of rodent active touch. Through in vivo whole-cell recordings one observes widespread subthreshold and very sparse evoked action potential (AP) activity in the somatosensory cortex both for passive whisker deflection in anaesthetized animals and during active whisker movements in awake animals. Neurons of the somatosensory cortex become either suppressed during whisking or activated by an efference copy of whisker movement signal that depolarize cells at certain phases of the whisking cycle. To probe the read out of cortical motor commands we applied intracellular stimulation in rat whisker motor cortex. We find that APs in individual cortical neurons can evoke long sequences of small whisker movements. The capacity of an individual neuron to evoke movements is most astonishing given the large number of neurons in whisker motor cortex. Thus, few cortical APs may suffice to control motor behaviour and such APs can be translated into action with the utmost precision. We conclude that there is very widespread subthreshold cortical activity and very sparse, highly specific cortical AP activity.

  10. In search of augmentation at human SI: Somatosensory cortical responses to stimulus trains and their modulation by motor activity.

    PubMed

    Huttunen, Juha

    2010-05-17

    In many animal preparations, repeated stimulation at ca. 10 Hz in thalamic nuclei leads to rapid changes in the cortical evoked responses, known as the augmenting response. The present study was undertaken to evaluate whether anything similar to the augmenting response can be observed in awake human subjects when a peripheral nerve is stimulated, and whether a possible human correlate of augmenting would be modified when the subject is engaged in an active motor task. Somatosensory-evoked magnetic fields (SEFs) were recorded in healthy human subjects in response to stimulus trains (15 pulses at 10 Hz) applied to the left median nerve. SEFs were recorded in a resting condition and during a finger-tapping task performed with the stimulated hand. In the resting condition, the most marked change in the SEF configuration was a reduction of the P35m deflection and a concurrent enhancement of the N45m deflection during the 1st few stimuli of the trains. Another conspicuous feature was a prolongation of the latencies of the N45m and P60m deflections toward the end of the train. In the motor task, the response modulation during the pulse trains was in general similar to the resting condition. The most notable difference was that the P35m amplitude was markedly reduced already for the 1st pulse of the train when compared with rest. Also, the latencies of N45m and P60m were not prolonged during the train. We discuss the possibility that the reduction of P35m and a concurrent increase of N45m during a pulse train constitute a human analogue to the augmenting response, and suggest that these changes may reflect a decrease of inhibitory postsynaptic potentials (IPSPs, P35m) and an increase of secondary excitatory postsynaptic potentials (N45m) during stimulus train presentation. The reduction of P35m during motor activity compared with rest already at the beginning of stimulus trains suggests that postsynaptic IPSPs in response to afferent stimulation are reduced during active

  11. Sleep modulates cortical connectivity and excitability in humans: Direct evidence from neural activity induced by single-pulse electrical stimulation.

    PubMed

    Usami, Kiyohide; Matsumoto, Riki; Kobayashi, Katsuya; Hitomi, Takefumi; Shimotake, Akihiro; Kikuchi, Takayuki; Matsuhashi, Masao; Kunieda, Takeharu; Mikuni, Nobuhiro; Miyamoto, Susumu; Fukuyama, Hidenao; Takahashi, Ryosuke; Ikeda, Akio

    2015-11-01

    Sleep-induced changes in human brain connectivity/excitability and their physiologic basis remain unclear, especially in the frontal lobe. We investigated sleep-induced connectivity and excitability changes in 11 patients who underwent chronic implantation of subdural electrodes for epilepsy surgery. Single-pulse electrical stimuli were directly injected to a part of the cortices, and cortico-cortical evoked potentials (CCEPs) and CCEP-related high-gamma activities (HGA: 100-200 Hz) were recorded from adjacent and remote cortices as proxies of effective connectivity and induced neuronal activity, respectively. HGA power during the initial CCEP component (N1) correlated with the N1 size itself across all states investigated. The degree of cortical connectivity and excitability changed during sleep depending on sleep stage, approximately showing dichotomy of awake vs. non-rapid eye movement (REM) [NREM] sleep. On the other hand, REM sleep partly had properties of both awake and NREM sleep, placing itself in the intermediate state between them. Compared with the awake state, single-pulse stimulation especially during NREM sleep induced increased connectivity (N1 size) and neuronal excitability (HGA increase at N1), which was immediately followed by intense inhibition (HGA decrease). The HGA decrease was temporally followed by the N2 peak (the second CCEP component), and then by HGA re-increase during sleep across all lobes. This HGA rebound or re-increase of neuronal synchrony was largest in the frontal lobe compared with the other lobes. These properties of sleep-induced changes of the cortex may be related to unconsciousness during sleep and frequent nocturnal seizures in frontal lobe epilepsy.

  12. Extrathalamic Modulation of Cortical Function

    DTIC Science & Technology

    1993-09-15

    active during waking than sleep and exhibit bursts of activity during increases in attentiveness. We have also previously demonstrated that the...non-target stimuli. Data were obtained following the systemic administration of placebo or clonidine , an a2-noradrenergic agonist that suppresses LC...activity and NA release. Clonidine significantly decreased the area and increased the latency of the P300-like potential that occurred following target

  13. LIM Kinase 1 Modulates Cortical Actin and CXCR4 Cycling and Is Activated by HIV-1 to Initiate Viral Infection*

    PubMed Central

    Vorster, Paul J.; Guo, Jia; Yoder, Alyson; Wang, Weifeng; Zheng, Yanfang; Xu, Xuehua; Yu, Dongyang; Spear, Mark; Wu, Yuntao

    2011-01-01

    Almost all viral pathogens utilize a cytoskeleton for their entry and intracellular transport. In HIV-1 infection, binding of the virus to blood resting CD4 T cells initiates a temporal course of cortical actin polymerization and depolymerization, a process mimicking the chemotactic response initiated from chemokine receptors. The actin depolymerization has been suggested to promote viral intracellular migration through cofilin-mediated actin treadmilling. However, the role of the virus-mediated actin polymerization in HIV infection is unknown, and the signaling molecules involved remain unidentified. Here we describe a pathogenic mechanism for triggering early actin polymerization through HIV-1 envelope-mediated transient activation of the LIM domain kinase (LIMK), a protein that phosphorylates cofilin. We demonstrate that HIV-mediated LIMK activation is through gp120-triggered transient activation of the Rack-PAK-LIMK pathway, and that knockdown of LIMK through siRNA decreases filamentous actin, increases CXCR4 trafficking, and diminishes viral DNA synthesis. These results suggest that HIV-mediated early actin polymerization may directly regulate the CXCR4 receptor during viral entry and is involved in viral DNA synthesis. Furthermore, we also demonstrate that in resting CD4 T cells, actin polymerization can be triggered through transient treatment with a pharmacological agent, okadaic acid, that activates LIMK and promotes HIV latent infection of resting CD4 T cells. Taken together, our results suggest that HIV hijacks LIMK to control the cortical actin dynamics for the initiation of viral infection of CD4 T cells. PMID:21321123

  14. Extrathalmic Modulation of Cortical Function

    DTIC Science & Technology

    1991-09-06

    agonist, clonidine , in doses that are known to suppress the electroohy- siologica-l activity of LC neurons. Clonidine significantly decreased the area and...decreased power in the * upper beta range (20-40 Hz) which leaving performance unaffected. Administration of clonidine , however, had no effect on the... clonidine , in doses * that are known to suppress the electrophysiological activity of LC neurons. In this study, ERPs, EEG, and behavioral performance

  15. Mortality salience modulates cortical responses to painful somatosensory stimulation: Evidence from slow wave and delta band activity.

    PubMed

    Valentini, Elia; Koch, Katharina; Nicolardi, Valentina; Aglioti, Salvatore Maria

    2015-10-15

    Social psychology studies show that awareness of one's eventual death profoundly influences human cognition and behaviour by inducing defensive reactions against end-of-life-related anxiety. Much less is known about the impact of reminders of mortality on brain activity. Here we tested whether reminders of mortality can induce a modulation of the slow electroencephalographic activity triggered by somatosensory nociceptive or auditory threatening stimulation and if this modulation is related to mood and anxiety as well as personality traits. We found a specific slow wave (SW) modulation only for nociceptive stimulation and only following mortality salience induction (compared to reminders of an important failed exam). The enhancement of SW negativity at the scalp vertex was associated with increased state anxiety and negative mood, whereas higher self-esteem was associated with reduced SW amplitude. In addition, mortality salience was linked to an increased amplitude of frontal delta band, which was correlated also with increased positive mood and higher self-esteem. The results indicate that SW and delta spectral activity may represent both proximal and distal defences associated with reminders of death and that neurophysiological correlates of somatosensory representation of painful and threatening stimuli may be useful for existential neuroscience studies.

  16. Modulation of cortical activity during comprehension of familiar and unfamiliar text topics in speed reading and speed listening

    PubMed Central

    Buchweitz, Augusto; Mason, Robert A.; Meschyan, Gayane; Keller, Timothy A.; Just, Marcel Adam

    2014-01-01

    Brain activation associated with normal and speeded comprehension of expository texts on familiar and unfamiliar topics was investigated in reading and listening. The goal was to determine how brain activation and the comprehension processes it reflects are modulated by comprehension speed and topic familiarity. Passages on more familiar topics differentially activated a set of areas in the anterior temporal lobe and medial frontal gyrus, areas often associated with text-level integration processes, which we interpret to reflect integration of previous knowledge with the passage content. Passages presented at the faster presentation resulted in more activation of a network of frontal areas associated with strategic and working-memory processes (as well as visual or auditory sensory-related regions), which we interpret to reflect maintenance of local coherence among briefly available passage segments. The implications of this research is to demonstrate how the brain system for text comprehension adapts to varying perceptual and knowledge conditions. PMID:25463816

  17. Striatal prediction error modulates cortical coupling.

    PubMed

    den Ouden, Hanneke E M; Daunizeau, Jean; Roiser, Jonathan; Friston, Karl J; Stephan, Klaas E

    2010-03-03

    Both perceptual inference and motor responses are shaped by learned probabilities. For example, stimulus-induced responses in sensory cortices and preparatory activity in premotor cortex reflect how (un)expected a stimulus is. This is in accordance with predictive coding accounts of brain function, which posit a fundamental role of prediction errors for learning and adaptive behavior. We used functional magnetic resonance imaging and recent advances in computational modeling to investigate how (failures of) learned predictions about visual stimuli influence subsequent motor responses. Healthy volunteers discriminated visual stimuli that were differentially predicted by auditory cues. Critically, the predictive strengths of cues varied over time, requiring subjects to continuously update estimates of stimulus probabilities. This online inference, modeled using a hierarchical Bayesian learner, was reflected behaviorally: speed and accuracy of motor responses increased significantly with predictability of the stimuli. We used nonlinear dynamic causal modeling to demonstrate that striatal prediction errors are used to tune functional coupling in cortical networks during learning. Specifically, the degree of striatal trial-by-trial prediction error activity controls the efficacy of visuomotor connections and thus the influence of surprising stimuli on premotor activity. This finding substantially advances our understanding of striatal function and provides direct empirical evidence for formal learning theories that posit a central role for prediction error-dependent plasticity.

  18. Endocannabinoid modulation of cortical up-states and NREM sleep.

    PubMed

    Pava, Matthew J; den Hartog, Carolina R; Blanco-Centurion, Carlos; Shiromani, Priyattam J; Woodward, John J

    2014-01-01

    Up-/down-state transitions are a form of network activity observed when sensory input into the cortex is diminished such as during non-REM sleep. Up-states emerge from coordinated signaling between glutamatergic and GABAergic synapses and are modulated by systems that affect the balance between inhibition and excitation. We hypothesized that the endocannabinoid (EC) system, a neuromodulatory system intrinsic to the cortical microcircuitry, is an important regulator of up-states and sleep. To test this hypothesis, up-states were recorded from layer V/VI pyramidal neurons in organotypic cultures of wild-type or CB1R knockout (KO) mouse prefrontal cortex. Activation of the cannabinoid 1 receptor (CB1) with exogenous agonists or by blocking metabolism of endocannabinoids, anandamide or 2-arachidonoyl glycerol, increased up-state amplitude and facilitated action potential discharge during up-states. The CB1 agonist also produced a layer II/III-selective reduction in synaptic GABAergic signaling that may underlie its effects on up-state amplitude and spiking. Application of CB1 antagonists revealed that an endogenous EC tone regulates up-state duration. Paradoxically, the duration of up-states in CB1 KO cultures was increased suggesting that chronic absence of EC signaling alters cortical activity. Consistent with increased cortical excitability, CB1 KO mice exhibited increased wakefulness as a result of reduced NREM sleep and NREM bout duration. Under baseline conditions, NREM delta (0.5-4 Hz) power was not different in CB1 KO mice, but during recovery from forced sleep deprivation, KO mice had reduced NREM delta power and increased sleep fragmentation. Overall, these findings demonstrate that the EC system actively regulates cortical up-states and important features of NREM sleep such as its duration and low frequency cortical oscillations.

  19. Visual-induced expectations modulate auditory cortical responses

    PubMed Central

    van Wassenhove, Virginie; Grzeczkowski, Lukasz

    2015-01-01

    Active sensing has important consequences on multisensory processing (Schroeder et al., 2010). Here, we asked whether in the absence of saccades, the position of the eyes and the timing of transient color changes of visual stimuli could selectively affect the excitability of auditory cortex by predicting the “where” and the “when” of a sound, respectively. Human participants were recorded with magnetoencephalography (MEG) while maintaining the position of their eyes on the left, right, or center of the screen. Participants counted color changes of the fixation cross while neglecting sounds which could be presented to the left, right, or both ears. First, clear alpha power increases were observed in auditory cortices, consistent with participants' attention directed to visual inputs. Second, color changes elicited robust modulations of auditory cortex responses (“when” prediction) seen as ramping activity, early alpha phase-locked responses, and enhanced high-gamma band responses in the contralateral side of sound presentation. Third, no modulations of auditory evoked or oscillatory activity were found to be specific to eye position. Altogether, our results suggest that visual transience can automatically elicit a prediction of “when” a sound will occur by changing the excitability of auditory cortices irrespective of the attended modality, eye position or spatial congruency of auditory and visual events. To the contrary, auditory cortical responses were not significantly affected by eye position suggesting that “where” predictions may require active sensing or saccadic reset to modulate auditory cortex responses, notably in the absence of spatial orientation to sounds. PMID:25705174

  20. Stimulating forebrain communications: Slow sinusoidal electric fields over frontal cortices dynamically modulate hippocampal activity and cortico-hippocampal interplay during slow-wave states.

    PubMed

    Greenberg, Anastasia; Whitten, Tara A; Dickson, Clayton T

    2016-06-01

    Slow-wave states are characterized by the most global physiological phenomenon in the mammalian brain, the large-amplitude slow oscillation (SO; ~1Hz) composed of alternating states of activity (ON/UP states) and silence (OFF/DOWN states) at the network and single cell levels. The SO is cortically generated and appears as a traveling wave that can propagate across the cortical surface and can invade the hippocampus. This cortical rhythm is thought to be imperative for sleep-dependent memory consolidation, potentially through increased interactions with the hippocampus. The SO is correlated with learning and its presumed enhancement via slow rhythmic electrical field stimulation improves subsequent mnemonic performance. However, the mechanism by which such field stimulation influences the dynamics of ongoing cortico-hippocampal communication is unknown. Here we show - using multi-site recordings in urethane-anesthetized rats - that sinusoidal electrical field stimulation applied to the frontal region of the cerebral cortex creates a platform for improved cortico-hippocampal communication. Moderate-intensity field stimulation entrained hippocampal slow activity (likely by way of the temporoammonic pathway) and also increased sharp-wave ripples, the signature memory replay events of the hippocampus, and further increased cortical spindles. Following cessation of high-intensity stimulation, SO interactions in the cortical-to-hippocampal direction were reduced, while the reversed hippocampal-to-cortical communication at both SO and gamma bandwidths was enhanced. Taken together, these findings suggest that cortical field stimulation may function to boost memory consolidation by strengthening cortico-hippocampal and hippocampo-cortical interplay at multiple nested frequencies in an intensity-dependent fashion.

  1. Persistence and storage of activity patterns in spiking recurrent cortical networks: modulation of sigmoid signals by after-hyperpolarization currents and acetylcholine

    PubMed Central

    Palma, Jesse; Grossberg, Stephen; Versace, Massimiliano

    2012-01-01

    Many cortical networks contain recurrent architectures that transform input patterns before storing them in short-term memory (STM). Theorems in the 1970's showed how feedback signal functions in rate-based recurrent on-center off-surround networks control this process. A sigmoid signal function induces a quenching threshold below which inputs are suppressed as noise and above which they are contrast-enhanced before pattern storage. This article describes how changes in feedback signaling, neuromodulation, and recurrent connectivity may alter pattern processing in recurrent on-center off-surround networks of spiking neurons. In spiking neurons, fast, medium, and slow after-hyperpolarization (AHP) currents control sigmoid signal threshold and slope. Modulation of AHP currents by acetylcholine (ACh) can change sigmoid shape and, with it, network dynamics. For example, decreasing signal function threshold and increasing slope can lengthen the persistence of a partially contrast-enhanced pattern, increase the number of active cells stored in STM, or, if connectivity is distance-dependent, cause cell activities to cluster. These results clarify how cholinergic modulation by the basal forebrain may alter the vigilance of category learning circuits, and thus their sensitivity to predictive mismatches, thereby controlling whether learned categories code concrete or abstract features, as predicted by Adaptive Resonance Theory. The analysis includes global, distance-dependent, and interneuron-mediated circuits. With an appropriate degree of recurrent excitation and inhibition, spiking networks maintain a partially contrast-enhanced pattern for 800 ms or longer after stimuli offset, then resolve to no stored pattern, or to winner-take-all (WTA) stored patterns with one or multiple winners. Strengthening inhibition prolongs a partially contrast-enhanced pattern by slowing the transition to stability, while strengthening excitation causes more winners when the network

  2. Degraded attentional modulation of cortical neural populations in strabismic amblyopia

    PubMed Central

    Hou, Chuan; Kim, Yee-Joon; Lai, Xin Jie; Verghese, Preeti

    2016-01-01

    Behavioral studies have reported reduced spatial attention in amblyopia, a developmental disorder of spatial vision. However, the neural populations in the visual cortex linked with these behavioral spatial attention deficits have not been identified. Here, we use functional MRI–informed electroencephalography source imaging to measure the effect of attention on neural population activity in the visual cortex of human adult strabismic amblyopes who were stereoblind. We show that compared with controls, the modulatory effects of selective visual attention on the input from the amblyopic eye are substantially reduced in the primary visual cortex (V1) as well as in extrastriate visual areas hV4 and hMT+. Degraded attentional modulation is also found in the normal-acuity fellow eye in areas hV4 and hMT+ but not in V1. These results provide electrophysiological evidence that abnormal binocular input during a developmental critical period may impact cortical connections between the visual cortex and higher level cortices beyond the known amblyopic losses in V1 and V2, suggesting that a deficit of attentional modulation in the visual cortex is an important component of the functional impairment in amblyopia. Furthermore, we find that degraded attentional modulation in V1 is correlated with the magnitude of interocular suppression and the depth of amblyopia. These results support the view that the visual suppression often seen in strabismic amblyopia might be a form of attentional neglect of the visual input to the amblyopic eye. PMID:26885628

  3. Reliability of cortical activity during natural stimulation

    PubMed Central

    Hasson, Uri; Malach, Rafael; Heeger, David J.

    2009-01-01

    Response reliability is complementary to more conventional measurements of response amplitudes, and can reveal phenomena that response amplitudes do not. Here we review studies that measured reliability of cortical activity within or between human subjects in response to naturalistic stimulation (e.g., free viewing of movies). Despite the seemingly uncontrolled nature of the task, some of these complex stimuli evoke highly reliable, selective, and time-locked activity in many brain areas, including some brain regions that often do not show much response modulation with conventional experimental protocols. This activity provides an opportunity to address novel questions concerning natural vision, temporal scale of processing, memory, and the neural basis of inter-group differences. PMID:20004608

  4. Reconciling Coherent Oscillation with Modulation of Irregular Spiking Activity in Selective Attention: Gamma-Range Synchronization between Sensory and Executive Cortical Areas

    PubMed Central

    Ardid, Salva; Wang, Xiao-Jing; Gomez-Cabrero, David; Compte, Albert

    2010-01-01

    In this computational work, we investigated gamma-band synchronization across cortical circuits associated with selective attention. The model explicitly instantiates a reciprocally connected loop of spiking neurons between a sensory-type (area MT) and an executive-type (prefrontal/parietal) cortical circuit (the source area for top-down attentional signaling). Moreover, unlike models in which neurons behave as clock-like oscillators, in our model single-cell firing is highly irregular (close to Possion) while local field potential exhibits a population rhythm. In this “sparsely synchronized oscillatory” regime, the model reproduces and clarifies multiple observations from behaving animals. Top-down attentional inputs have a profound effect on network oscillatory dynamics while only modestly affecting single-neuron spiking statistics. In addition, attentional synchrony modulations are highly selective: Inter-areal neuronal coherence occurs only when there is a close match between the preferred feature of neurons, the attended feature and the presented stimulus, a prediction that is experimentally testable. When inter-areal coherence was abolished attention-induced gain modulations of sensory neurons were slightly reduced. Therefore, our model reconciles the rate and synchronization effects, and suggests that interareal coherence contributes to large-scale neuronal computation in the brain through modest enhancement of rate modulations as well as a pronounced attention-specific enhancement of neural synchrony. PMID:20181583

  5. Cortical actin regulation modulates vascular contractility and compliance in veins

    PubMed Central

    Saphirstein, Robert J; Gao, Yuan Z; Lin, Qian Qian; Morgan, Kathleen G

    2015-01-01

    Abstract The literature on arterial mechanics is extensive, but far less is known about mechanisms controlling mechanical properties of veins. We use here a multi-scale approach to identify subcellular sources of venous stiffness. Portal vein tissue displays a severalfold decrease in passive stiffness compared to aortic tissues. The α-adrenergic agonist phenylephrine (PE) increased tissue stress and stiffness, both attenuated by cytochalasin D (CytoD) and PP2, inhibitors of actin polymerization and Src activity, respectively. We quantify, for the first time, cortical cellular stiffness in freshly isolated contractile vascular smooth muscle cells using magnetic microneedle technology. Cortical stiffness is significantly increased by PE and CytoD inhibits this increase but, surprisingly, PP2 does not. No detectable change in focal adhesion size, measured by immunofluorescence of FAK and zyxin, accompanies the PE-induced changes in cortical stiffness. Probing with phospho-specific antibodies confirmed activation of FAK/Src and ERK pathways and caldesmon phosphorylation. Thus, venous tissue stiffness is regulated both at the level of the smooth muscle cell cortex, via cortical actin polymerization, and by downstream smooth muscle effectors of Src/ERK signalling pathways. These findings identify novel potential molecular targets for the modulation of venous capacitance and venous return in health and disease. Key points Most cardiovascular research focuses on arterial mechanisms of disease, largely ignoring venous mechanisms. Here we examine ex vivo venous stiffness, spanning tissue to molecular levels, using biomechanics and magnetic microneedle technology, and show for the first time that venous stiffness is regulated by a molecular actin switch within the vascular smooth muscle cell in the wall of the vein. This switch connects the contractile apparatus within the cell to adhesion structures and facilitates stiffening of the vessel wall, regulating blood flow return

  6. Higher cortical modulation of pain perception in the human brain: Psychological determinant.

    PubMed

    Chen, Andrew Cn

    2009-10-01

    Pain perception and its genesis in the human brain have been reviewed recently. In the current article, the reports on pain modulation in the human brain were reviewed from higher cortical regulation, i.e. top-down effect, particularly studied in psychological determinants. Pain modulation can be examined by gene therapy, physical modulation, pharmacological modulation, psychological modulation, and pathophysiological modulation. In psychological modulation, this article examined (a) willed determination, (b) distraction, (c) placebo, (d) hypnosis, (e) meditation, (f) qi-gong, (g) belief, and (h) emotions, respectively, in the brain function for pain modulation. In each, the operational definition, cortical processing, neuroimaging, and pain modulation were systematically deliberated. However, not all studies had featured the brain modulation processing but rather demonstrated potential effects on human pain. In our own studies on the emotional modulation on human pain, we observed that emotions could be induced from music melodies or pictures perception for reduction of tonic human pain, mainly in potentiation of the posterior alpha EEG fields, likely resulted from underneath activities of precuneous in regulation of consciousness, including pain perception. To sum, higher brain functions become the leading edge research in all sciences. How to solve the information bit of thinking and feeling in the brain can be the greatest challenge of human intelligence. Application of higher cortical modulation of human pain and suffering can lead to the progress of social humanity and civilization.

  7. TAAR1 Modulates Cortical Glutamate NMDA Receptor Function.

    PubMed

    Espinoza, Stefano; Lignani, Gabriele; Caffino, Lucia; Maggi, Silvia; Sukhanov, Ilya; Leo, Damiana; Mus, Liudmila; Emanuele, Marco; Ronzitti, Giuseppe; Harmeier, Anja; Medrihan, Lucian; Sotnikova, Tatyana D; Chieregatti, Evelina; Hoener, Marius C; Benfenati, Fabio; Tucci, Valter; Fumagalli, Fabio; Gainetdinov, Raul R

    2015-08-01

    Trace Amine-Associated Receptor 1 (TAAR1) is a G protein-coupled receptor expressed in the mammalian brain and known to influence subcortical monoaminergic transmission. Monoamines, such as dopamine, also play an important role within the prefrontal cortex (PFC) circuitry, which is critically involved in high-o5rder cognitive processes. TAAR1-selective ligands have shown potential antipsychotic, antidepressant, and pro-cognitive effects in experimental animal models; however, it remains unclear whether TAAR1 can affect PFC-related processes and functions. In this study, we document a distinct pattern of expression of TAAR1 in the PFC, as well as altered subunit composition and deficient functionality of the glutamate N-methyl-D-aspartate (NMDA) receptors in the pyramidal neurons of layer V of PFC in mice lacking TAAR1. The dysregulated cortical glutamate transmission in TAAR1-KO mice was associated with aberrant behaviors in several tests, indicating a perseverative and impulsive phenotype of mutants. Conversely, pharmacological activation of TAAR1 with selective agonists reduced premature impulsive responses observed in the fixed-interval conditioning schedule in normal mice. Our study indicates that TAAR1 plays an important role in the modulation of NMDA receptor-mediated glutamate transmission in the PFC and related functions. Furthermore, these data suggest that the development of TAAR1-based drugs could provide a novel therapeutic approach for the treatment of disorders related to aberrant cortical functions.

  8. TAAR1 Modulates Cortical Glutamate NMDA Receptor Function

    PubMed Central

    Espinoza, Stefano; Lignani, Gabriele; Caffino, Lucia; Maggi, Silvia; Sukhanov, Ilya; Leo, Damiana; Mus, Liudmila; Emanuele, Marco; Ronzitti, Giuseppe; Harmeier, Anja; Medrihan, Lucian; Sotnikova, Tatyana D; Chieregatti, Evelina; Hoener, Marius C; Benfenati, Fabio; Tucci, Valter; Fumagalli, Fabio; Gainetdinov, Raul R

    2015-01-01

    Trace Amine-Associated Receptor 1 (TAAR1) is a G protein-coupled receptor expressed in the mammalian brain and known to influence subcortical monoaminergic transmission. Monoamines, such as dopamine, also play an important role within the prefrontal cortex (PFC) circuitry, which is critically involved in high-o5rder cognitive processes. TAAR1-selective ligands have shown potential antipsychotic, antidepressant, and pro-cognitive effects in experimental animal models; however, it remains unclear whether TAAR1 can affect PFC-related processes and functions. In this study, we document a distinct pattern of expression of TAAR1 in the PFC, as well as altered subunit composition and deficient functionality of the glutamate N-methyl-D-aspartate (NMDA) receptors in the pyramidal neurons of layer V of PFC in mice lacking TAAR1. The dysregulated cortical glutamate transmission in TAAR1-KO mice was associated with aberrant behaviors in several tests, indicating a perseverative and impulsive phenotype of mutants. Conversely, pharmacological activation of TAAR1 with selective agonists reduced premature impulsive responses observed in the fixed-interval conditioning schedule in normal mice. Our study indicates that TAAR1 plays an important role in the modulation of NMDA receptor-mediated glutamate transmission in the PFC and related functions. Furthermore, these data suggest that the development of TAAR1-based drugs could provide a novel therapeutic approach for the treatment of disorders related to aberrant cortical functions. PMID:25749299

  9. Modulation of anxiety by cortical serotonin 1A receptors

    PubMed Central

    Piszczek, Lukasz; Piszczek, Agnieszka; Kuczmanska, Joanna; Audero, Enrica; Gross, Cornelius T.

    2015-01-01

    Serotonin (5-HT) plays an important role in the modulation of behavior across animal species. The serotonin 1A receptor (Htr1a) is an inhibitory G-protein coupled receptor that is expressed both on serotonin and non-serotonin neurons in mammals. Mice lacking Htr1a show increased anxiety behavior suggesting that its activation by serotonin has an anxiolytic effect. This outcome can be mediated by either Htr1a population present on serotonin (auto-receptor) or non-serotonin neurons (hetero-receptor), or both. In addition, both transgenic and pharmacological studies have shown that serotonin acts on Htr1a during development to modulate anxiety in adulthood, demonstrating a function for this receptor in the maturation of anxiety circuits in the brain. However, previous studies have been equivocal about which Htr1a population modulates anxiety behavior, with some studies showing a role of Htr1a hetero-receptor and others implicating the auto-receptor. In particular, cell-type specific rescue and suppression of Htr1a expression in either forebrain principal neurons or brainstem serotonin neurons reached opposite conclusions about the role of the two populations in the anxiety phenotype of the knockout. One interpretation of these apparently contradictory findings is that the modulating role of these two populations depends on each other. Here we use a novel Cre-dependent inducible allele of Htr1a in mice to show that expression of Htr1a in cortical principal neurons is sufficient to modulate anxiety. Together with previous findings, these results support a hetero/auto-receptor interaction model for Htr1a function in anxiety. PMID:25759645

  10. Cortical entrainment to music and its modulation by expertise

    PubMed Central

    Doelling, Keith B.; Poeppel, David

    2015-01-01

    Recent studies establish that cortical oscillations track naturalistic speech in a remarkably faithful way. Here, we test whether such neural activity, particularly low-frequency (<8 Hz; delta–theta) oscillations, similarly entrain to music and whether experience modifies such a cortical phenomenon. Music of varying tempi was used to test entrainment at different rates. In three magnetoencephalography experiments, we recorded from nonmusicians, as well as musicians with varying years of experience. Recordings from nonmusicians demonstrate cortical entrainment that tracks musical stimuli over a typical range of tempi, but not at tempi below 1 note per second. Importantly, the observed entrainment correlates with performance on a concurrent pitch-related behavioral task. In contrast, the data from musicians show that entrainment is enhanced by years of musical training, at all presented tempi. This suggests a bidirectional relationship between behavior and cortical entrainment, a phenomenon that has not previously been reported. Additional analyses focus on responses in the beta range (∼15–30 Hz)—often linked to delta activity in the context of temporal predictions. Our findings provide evidence that the role of beta in temporal predictions scales to the complex hierarchical rhythms in natural music and enhances processing of musical content. This study builds on important findings on brainstem plasticity and represents a compelling demonstration that cortical neural entrainment is tightly coupled to both musical training and task performance, further supporting a role for cortical oscillatory activity in music perception and cognition. PMID:26504238

  11. Cortical entrainment to music and its modulation by expertise.

    PubMed

    Doelling, Keith B; Poeppel, David

    2015-11-10

    Recent studies establish that cortical oscillations track naturalistic speech in a remarkably faithful way. Here, we test whether such neural activity, particularly low-frequency (<8 Hz; delta-theta) oscillations, similarly entrain to music and whether experience modifies such a cortical phenomenon. Music of varying tempi was used to test entrainment at different rates. In three magnetoencephalography experiments, we recorded from nonmusicians, as well as musicians with varying years of experience. Recordings from nonmusicians demonstrate cortical entrainment that tracks musical stimuli over a typical range of tempi, but not at tempi below 1 note per second. Importantly, the observed entrainment correlates with performance on a concurrent pitch-related behavioral task. In contrast, the data from musicians show that entrainment is enhanced by years of musical training, at all presented tempi. This suggests a bidirectional relationship between behavior and cortical entrainment, a phenomenon that has not previously been reported. Additional analyses focus on responses in the beta range (∼15-30 Hz)-often linked to delta activity in the context of temporal predictions. Our findings provide evidence that the role of beta in temporal predictions scales to the complex hierarchical rhythms in natural music and enhances processing of musical content. This study builds on important findings on brainstem plasticity and represents a compelling demonstration that cortical neural entrainment is tightly coupled to both musical training and task performance, further supporting a role for cortical oscillatory activity in music perception and cognition.

  12. Broadcasting of cortical activity to the olfactory bulb.

    PubMed

    Boyd, Alison M; Kato, Hiroyuki K; Komiyama, Takaki; Isaacson, Jeffry S

    2015-02-24

    Odor representations are initially formed in the olfactory bulb, which contains a topographic glomerular map of odor molecular features. The bulb transmits sensory information directly to piriform cortex, where it is encoded by distributed ensembles of pyramidal cells without spatial order. Intriguingly, piriform cortex pyramidal cells project back to the bulb, but the information contained in this feedback projection is unknown. Here, we use imaging in awake mice to directly monitor activity in the presynaptic boutons of cortical feedback fibers. We show that the cortex provides the bulb with a rich array of information for any individual odor and that cortical feedback is dependent on brain state. In contrast to the stereotyped, spatial arrangement of olfactory bulb glomeruli, cortical inputs tuned to different odors commingle and indiscriminately target individual glomerular channels. Thus, the cortex modulates early odor representations by broadcasting sensory information diffusely onto spatially ordered bulbar circuits.

  13. Tissue-type Plasminogen Activator (tPA) Modulates the Postsynaptic Response of Cerebral Cortical Neurons to the Presynaptic Release of Glutamate

    PubMed Central

    Jeanneret, Valerie; Wu, Fang; Merino, Paola; Torre, Enrique; Diaz, Ariel; Cheng, Lihong; Yepes, Manuel

    2016-01-01

    Tissue-type plasminogen activator (tPA) is a serine proteinase released by the presynaptic terminal of cerebral cortical neurons following membrane depolarization (Echeverry et al., 2010). Recent studies indicate that the release of tPA triggers the synaptic vesicle cycle and promotes the exocytosis (Wu et al., 2015) and endocytic retrieval (Yepes et al., 2016) of glutamate-containing synaptic vesicles. Here we used electron microscopy, proteomics, quantitative phosphoproteomics, biochemical analyses with extracts of the postsynaptic density (PSD), and an animal model of cerebral ischemia with mice overexpressing neuronal tPA to study whether the presynaptic release of tPA also has an effect on the postsynaptic terminal. We found that tPA has a bidirectional effect on the composition of the PSD of cerebral cortical neurons that is independent of the generation of plasmin and the presynaptic release of glutamate, but depends on the baseline level of neuronal activity and the extracellular concentrations of calcium (Ca2+). Accordingly, in neurons that are either inactive or incubated with low Ca2+ concentrations tPA induces phosphorylation and accumulation in the PSD of the Ca2+/calmodulin-dependent protein kinase IIα (pCaMKIIα), followed by pCaMKIIα-mediated phosphorylation and synaptic recruitment of GluR1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. In contrast, in neurons with previously increased baseline levels of pCaMKIIα in the PSD due to neuronal depolarization in vivo or incubation with high concentrations of either Ca2+ or glutamate in vitro, tPA induces pCaMKIIα and pGluR1 dephosphorylation and their subsequent removal from the PSD. We found that these effects of tPA are mediated by synaptic N-methyl-D-aspartate (NMDA) receptors and cyclin-dependent kinase 5 (Cdk5)-induced phosphorylation of the protein phosphatase 1 (PP1) at T320. Our data indicate that by regulating the pCaMKIIα/PP1 balance in the PSD tPA acts

  14. Cortical Hubs Form a Module for Multisensory Integration on Top of the Hierarchy of Cortical Networks

    PubMed Central

    Zamora-López, Gorka; Zhou, Changsong; Kurths, Jürgen

    2009-01-01

    Sensory stimuli entering the nervous system follow particular paths of processing, typically separated (segregated) from the paths of other modal information. However, sensory perception, awareness and cognition emerge from the combination of information (integration). The corticocortical networks of cats and macaque monkeys display three prominent characteristics: (i) modular organisation (facilitating the segregation), (ii) abundant alternative processing paths and (iii) the presence of highly connected hubs. Here, we study in detail the organisation and potential function of the cortical hubs by graph analysis and information theoretical methods. We find that the cortical hubs form a spatially delocalised, but topologically central module with the capacity to integrate multisensory information in a collaborative manner. With this, we resolve the underlying anatomical substrate that supports the simultaneous capacity of the cortex to segregate and to integrate multisensory information. PMID:20428515

  15. Cortical hubs form a module for multisensory integration on top of the hierarchy of cortical networks.

    PubMed

    Zamora-López, Gorka; Zhou, Changsong; Kurths, Jürgen

    2010-01-01

    Sensory stimuli entering the nervous system follow particular paths of processing, typically separated (segregated) from the paths of other modal information. However, sensory perception, awareness and cognition emerge from the combination of information (integration). The corticocortical networks of cats and macaque monkeys display three prominent characteristics: (i) modular organisation (facilitating the segregation), (ii) abundant alternative processing paths and (iii) the presence of highly connected hubs. Here, we study in detail the organisation and potential function of the cortical hubs by graph analysis and information theoretical methods. We find that the cortical hubs form a spatially delocalised, but topologically central module with the capacity to integrate multisensory information in a collaborative manner. With this, we resolve the underlying anatomical substrate that supports the simultaneous capacity of the cortex to segregate and to integrate multisensory information.

  16. Modulation of cortical excitability and interhemispheric inhibition prior to rhythmic unimanual contractions.

    PubMed

    Sharples, Simon A; Kalmar, Jayne M

    2012-09-30

    The objective of this study was to investigate premotor modulation of motor cortical excitability between rhythmic unimanual finger contractions. Applying TMS at rest prior to an anticipated contraction provides a measure of cortical excitability that reflects premotor modulatory drive and is uncontaminated by the alterations in spinal and cortical excitability that occur during muscle activation. We hypothesized that premotor structures contribute to unimanual movement through the modulation of intracortical and interhemispheric inhibitory circuits within the primary motor cortex and that this premotor modulation would be evident at rest between contractions. Thus, we used transcranial magnetic stimulation (TMS) to assess short interval intracortical inhibition (SICI) and interhemispheric inhibition (IHI) in a 500-ms epoch prior to a planned contraction of the right FDI in 10 participants (21.4±1.9 years). These measures of inhibition were made in three different states: (1) at complete rest (with no plan to contract), (2) at rest between rhythmic contractions, and (3) during low level contractions. Cortical excitability was enhanced prior to a contraction and during a contraction compared to at rest (F₂,₁₈=758.3, p<0.001). IHI was also increased prior to a contraction compared to at rest and during a contraction while SICI was only reduced during a contraction (F₂,₃₈=30.3, p<0.001).We used this pre-contraction protocol to investigate the cortical mechanisms of unimanual control. However, this protocol would be a useful tool to investigate any neuromuscular adaptation that may occur as a result of altered premotor modulation of cortical excitability, such as neuromuscular fatigue, training and movement disorders.

  17. Cortical influences on brainstem circuitry responsible for conditioned pain modulation in humans.

    PubMed

    Youssef, Andrew M; Macefield, Vaughan G; Henderson, Luke A

    2016-07-01

    Conditioned pain modulation (CPM) is a powerful endogenous analgesic mechanism which can completely inhibit incoming nociceptor signals at the primary synapse. The circuitry responsible for CPM lies within the brainstem and involves the subnucleus reticularis dorsalis (SRD). While the brainstem is critical for CPM, the cortex can significantly modulate its expression, likely via the brainstem circuitry critical for CPM. Since higher cortical regions such as the anterior, mid-cingulate, and dorsolateral prefrontal cortices are activated by noxious stimuli and show reduced activations during other analgesic responses, we hypothesized that these regions would display reduced responses during CPM analgesia. Furthermore, we hypothesized that functional connectivity strength between these cortical regions and the SRD would be stronger in those that express CPM analgesia compared with those that do not. We used functional magnetic resonance imaging to determine sites recruited during CPM expression and their influence on the SRD. A lack of CPM analgesia was associated with greater signal intensity increases during each test stimulus in the presence of the conditioning stimulus compared to test stimuli alone in the mid-cingulate and dorsolateral prefrontal cortices and increased functional connectivity with the SRD. In contrast, those subjects exhibiting CPM analgesia showed no change in the magnitude of signal intensity increases in these cortical regions or strength of functional connectivity with the SRD. These data suggest that during multiple or widespread painful stimuli, engagement of the prefrontal and cingulate cortices prevents the generation of CPM analgesia, raising the possibility altered responsiveness in these cortical regions underlie the reduced CPM observed in individuals with chronic pain. Hum Brain Mapp 37:2630-2644, 2016. © 2016 Wiley Periodicals, Inc.

  18. COMMUNICATION: Folate and S-adenosylmethionine modulate synaptic activity in cultured cortical neurons: acute differential impact on normal and apolipoprotein-deficient mice

    NASA Astrophysics Data System (ADS)

    Serra, Michael; Chan, Amy; Dubey, Maya; Gilman, Vladimir; Shea, Thomas B.

    2008-12-01

    Folate deficiency is accompanied by a decline in the cognitive neurotransmitter acetylcholine and a decline in cognitive performance in mice lacking apolipoprotein E (ApoE-/- mice), a low-density lipoprotein that regulates aspects of lipid metabolism. One direct consequence of folate deficiency is a decline in S-adenosylmethionine (SAM). Since dietary SAM supplementation maintains acetylcholine levels and cognitive performance in the absence of folate, we examined herein the impact of folate and SAM on neuronal synaptic activity. Embryonic cortical neurons from mice expressing or lacking ApoE (ApoE+/+ or -/-, respectively) were cultured for 1 month on multi-electrode arrays, and signaling was recorded. ApoE+/+ cultures displayed significantly more frequent spontaneous signals than ApoE-/- cultures. Supplementation with 166 µm SAM (not normally present in culture medium) increased signal frequency and decreased signal amplitude in ApoE+/+ cultures. SAM also increased the frequency of tightly clustered signal bursts. Folate deprivation reversibly reduced signal frequency in ApoE+/+ cultures; SAM supplementation maintained signal frequency despite folate deprivation. These findings support the importance of dietary supplementation with folate and SAM on neuronal health. Supplementation with 166 µm SAM did not alter signaling in ApoE-/- cultures, which may be a reflection of the reduced SAM levels in ApoE-/- mice. The differential impact of SAM on ApoE+/+ and -/- neurons underscores the combined impact of nutritional and genetic deficiencies on neuronal homeostasis.

  19. Perceptual Incongruence Influences Bistability and Cortical Activation

    PubMed Central

    Brouwer, Gijs Joost; Tong, Frank; Hagoort, Peter; van Ee, Raymond

    2009-01-01

    We employed a parametric psychophysical design in combination with functional imaging to examine the influence of metric changes in perceptual incongruence on perceptual alternation rates and cortical responses. Subjects viewed a bistable stimulus defined by incongruent depth cues; bistability resulted from incongruence between binocular disparity and monocular perspective cues that specify different slants (slant rivalry). Psychophysical results revealed that perceptual alternation rates were positively correlated with the degree of perceived incongruence. Functional imaging revealed systematic increases in activity that paralleled the psychophysical results within anterior intraparietal sulcus, prior to the onset of perceptual alternations. We suggest that this cortical activity predicts the frequency of subsequent alternations, implying a putative causal role for these areas in initiating bistable perception. In contrast, areas implicated in form and depth processing (LOC and V3A) were sensitive to the degree of slant, but failed to show increases in activity when these cues were in conflict. PMID:19333385

  20. Depression of cortical activity in humans by mild hypercapnia.

    PubMed

    Thesen, Thomas; Leontiev, Oleg; Song, Tao; Dehghani, Nima; Hagler, Donald J; Huang, Mingxiong; Buxton, Richard; Halgren, Eric

    2012-03-01

    The effects of neural activity on cerebral hemodynamics underlie human brain imaging with functional magnetic resonance imaging and positron emission tomography. However, the threshold and characteristics of the converse effects, wherein the cerebral hemodynamic and metabolic milieu influence neural activity, remain unclear. We tested whether mild hypercapnia (5% CO2 ) decreases the magnetoencephalogram response to auditory pattern recognition and visual semantic tasks. Hypercapnia induced statistically significant decreases in event-related fields without affecting behavioral performance. Decreases were observed in early sensory components in both auditory and visual modalities as well as later cognitive components related to memory and language. Effects were distributed across cortical regions. Decreases were comparable in evoked versus spontaneous spectral power. Hypercapnia is commonly used with hemodynamic models to calibrate the blood oxygenation level-dependent response. Modifying model assumptions to incorporate the current findings produce a modest but measurable decrease in the estimated cerebral metabolic rate for oxygen change with activation. Because under normal conditions, low cerebral pH would arise when bloodflow is unable to keep pace with neuronal activity, the cortical depression observed here may reflect a homeostatic mechanism by which neuronal activity is adjusted to a level that can be sustained by available bloodflow. Animal studies suggest that these effects may be mediated by pH-modulating presynaptic adenosine receptors. Although the data is not clear, comparable changes in cortical pH to those induced here may occur during sleep apnea, sleep, and exercise. If so, these results suggest that such activities may in turn have generalized depressive effects on cortical activity.

  1. Depression of Cortical Activity in Humans by Mild Hypercapnia

    PubMed Central

    Thesen, Thomas; Leontiev, Oleg; Song, Tao; Dehghani, Nima; Hagler, Donald J; Huang, Mingxiong; Buxton, Richard; Halgren, Eric

    2013-01-01

    The effects of neural activity on cerebral hemodynamics underlie human brain imaging with functional magnetic resonance imaging and positron emission tomography. However, the threshold and characteristics of the converse effects, wherein the cerebral hemodynamic and metabolic milieu influence neural activity, remain unclear. We tested whether mild hypercapnia (5% CO2) decreases the magnetoencephalogram response to auditory pattern recognition and visual semantic tasks. Hypercapnia induced statistically significant decreases in event-related fields without affecting behavioral performance. Decreases were observed in early sensory components in both auditory and visual modalities as well as later cognitive components related to memory and language. Effects were distributed across cortical regions. Decreases were comparable in evoked versus spontaneous spectral power. Hypercapnia is commonly used with hemodynamic models to calibrate the blood oxygenation level-dependent response. Modifying model assumptions to incorporate the current findings produce a modest but measurable decrease in the estimated cerebral metabolic rate for oxygen change with activation. Because under normal conditions, low cerebral pH would arise when bloodflow is unable to keep pace with neuronal activity, the cortical depression observed here may reflect a homeostatic mechanism by which neuronal activity is adjusted to a level that can be sustained by available bloodflow. Animal studies suggest that these effects may be mediated by pH-modulating presynaptic adenosine receptors. Although the data is not clear, comparable changes in cortical pH to those induced here may occur during sleep apnea, sleep, and exercise. If so, these results suggest that such activities may in turn have generalized depressive effects on cortical activity. PMID:21500313

  2. Task-relevant modulation of primary somatosensory cortex suggests a prefrontal-cortical sensory gating system.

    PubMed

    Schaefer, Michael; Heinze, Hans-Jochen; Rotte, Michael

    2005-08-01

    Increasing evidence suggests that somatosensory information is modulated cortically for task-specific sensory inflow: Several studies report short-term adaptation of representational maps in primary somatosensory cortex (SI) due to attention or induced by task-related motor activity such as handwriting. Recently, it has been hypothesized that the frontal or prefrontal cortex may modulate SI. In order to test this hypothesis, we studied the functional organization of SI while subjects performed the Tower of Hanoi task. This task is known to be related to activation of frontal or prefrontal areas. The functional organization of SI while performing the Tower of Hanoi task was compared to the organization of SI during performing the same movements but without the Tower of Hanoi task and with rest. Topography of SI was assessed using neuromagnetic source imaging based on tactile stimulation of the first (D1) and fifth digits (D5). Performing the Tower of Hanoi task was accompanied by plastic changes in SI as indicated by significant shifts in the cortical representations of D1 and D5: They moved further apart during the Tower of Hanoi task compared to the control task containing the same movements but without the cognitive characteristic. Thus, we conclude that SI maps undergo dynamic modulation depending on motor tasks with different cognitive demands. The results suggest that this short-term plasticity may be regulated by a prefrontal-cortical sensory gating system.

  3. Demixing Population Activity in Higher Cortical Areas

    PubMed Central

    Machens, Christian K.

    2009-01-01

    Neural responses in higher cortical areas often display a baffling complexity. In animals performing behavioral tasks, single neurons will typically encode several parameters simultaneously, such as stimuli, rewards, decisions, etc. When dealing with this large heterogeneity of responses, cells are conventionally classified into separate response categories using various statistical tools. However, this classical approach usually fails to account for the distributed nature of representations in higher cortical areas. Alternatively, principal component analysis (PCA) or related techniques can be employed to reduce the complexity of a data set while retaining the distributional aspect of the population activity. These methods, however, fail to explicitly extract the task parameters from the neural responses. Here we suggest a coordinate transformation that seeks to ameliorate these problems by combining the advantages of both methods. Our basic insight is that variance in neural firing rates can have different origins (such as changes in a stimulus, a reward, or the passage of time), and that, instead of lumping them together, as PCA does, we need to treat these sources separately. We present a method that seeks an orthogonal coordinate transformation such that the variance captured from different sources falls into orthogonal subspaces and is maximized within these subspaces. Using simulated examples, we show how this approach can be used to demix heterogeneous neural responses. Our method may help to lift the fog of response heterogeneity in higher cortical areas. PMID:21031029

  4. Doping the Mind: Dopaminergic Modulation of Prefrontal Cortical Cognition.

    PubMed

    Ranganath, Ajit; Jacob, Simon N

    2016-12-01

    The prefrontal cortex is the center of cognitive control. Processing in prefrontal cortical circuits enables us to direct attention to behaviorally relevant events; to memorize, structure, and categorize information; and to learn new concepts. The prefrontal cortex receives strong projections from midbrain neurons that use dopamine as a transmitter. In this article, we review the crucial role dopamine plays as a modulator of prefrontal cognitive functions, in the primate brain in particular. Following a summary of the anatomy and physiology of the midbrain dopamine system, we focus on recent studies that investigated dopaminergic effects in prefrontal cortex at the cellular level. We then discuss how unregulated prefrontal dopamine signaling could contribute to major disorders of cognition. The studies highlighted in this review demonstrate the powerful influence dopamine exerts on the mind.

  5. Satb1 is an activity-modulated transcription factor required for the terminal differentiation and connectivity of medial ganglionic eminence-derived cortical interneurons.

    PubMed

    Close, Jennie; Xu, Han; De Marco García, Natalia; Batista-Brito, Renata; Rossignol, Elsa; Rudy, Bernardo; Fishell, Gord

    2012-12-05

    Although previous work identified transcription factors crucial for the specification and migration of parvalbumin (PV)-expressing and somatostatin (SST)-expressing interneurons, the intrinsic factors required for the terminal differentiation, connectivity, and survival of these cell types remain uncharacterized. Here we demonstrate that, within subpopulations of cortical interneurons, Satb1 (special AT-rich binding protein) promotes terminal differentiation, connectivity, and survival in interneurons that express PV and SST. We find that conditional removal of Satb1 in mouse interneurons results in the loss of a majority of SST-expressing cells across all cortical layers, as well as some PV-expressing cells in layers IV and VI, by postnatal day 21. SST-expressing cells initially migrate to the cortex in Satb1 mutant mice, but receive reduced levels of afferent input and begin to die during the first postnatal week. Electrophysiological characterization indicates that loss of Satb1 function in interneurons results in a loss of functional inhibition of excitatory principal cells. These data suggest that Satb1 is required for medial ganglionic eminence-derived interneuron differentiation, connectivity, and survival.

  6. Global cortical activity predicts shape of hand during grasping

    PubMed Central

    Agashe, Harshavardhan A.; Paek, Andrew Y.; Zhang, Yuhang; Contreras-Vidal, José L.

    2015-01-01

    Recent studies show that the amplitude of cortical field potentials is modulated in the time domain by grasping kinematics. However, it is unknown if these low frequency modulations persist and contain enough information to decode grasp kinematics in macro-scale activity measured at the scalp via electroencephalography (EEG). Further, it is unclear as to whether joint angle velocities or movement synergies are the optimal kinematics spaces to decode. In this offline decoding study, we infer from human EEG, hand joint angular velocities as well as synergistic trajectories as subjects perform natural reach-to-grasp movements. Decoding accuracy, measured as the correlation coefficient (r) between the predicted and actual movement kinematics, was r = 0.49 ± 0.02 across 15 hand joints. Across the first three kinematic synergies, decoding accuracies were r = 0.59 ± 0.04, 0.47 ± 0.06, and 0.32 ± 0.05. The spatial-temporal pattern of EEG channel recruitment showed early involvement of contralateral frontal-central scalp areas followed by later activation of central electrodes over primary sensorimotor cortical areas. Information content in EEG about the grasp type peaked at 250 ms after movement onset. The high decoding accuracies in this study are significant not only as evidence for time-domain modulation in macro-scale brain activity, but for the field of brain-machine interfaces as well. Our decoding strategy, which harnesses the neural “symphony” as opposed to local members of the neural ensemble (as in intracranial approaches), may provide a means of extracting information about motor intent for grasping without the need for penetrating electrodes and suggests that it may be soon possible to develop non-invasive neural interfaces for the control of prosthetic limbs. PMID:25914616

  7. Striatal dopamine and glutamate receptors modulate methamphetamine-induced cortical Fos expression

    PubMed Central

    Gross, Noah B.; Marshall, John F.

    2009-01-01

    Methamphetamine (mAMPH) is a psychostimulant drug that increases extracellular levels of monoamines throughout the brain. It has previously been observed that a single injection of mAMPH increases immediate early gene (IEG) expression in both the striatum and cerebral cortex. Moreover, this effect is modulated by dopamine and glutamate receptors since systemic administration of dopamine or glutamate antagonists has been found to alter mAMPH-induced striatal and cortical IEG expression. However, because dopamine and glutamate receptors are found in extra-striatal as well as striatal brain regions, studies employing systemic injection of dopamine or glutamate antagonists fail to localize the effects of mAMPH-induced activation. In the present experiments, the roles of striatal dopamine and glutamate receptors in mAMPH-induced gene expression in the striatum and cerebral cortex were examined. The nuclear expression of Fos, the protein product of the IEG c-fos, was quantified in both the striatum and the cortex of animals receiving intrastriatal dopamine or glutamate antagonist administration. Intrastriatal infusion of dopamine (D1 or D2) or glutamate [N-methyl-D-aspartic acid (NMDA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)] antagonists affected not only mAMPH-induced striatal, but also cortical, Fos expression. Overall, the effects of the antagonists occurred dose-dependently, in both the infused and non-infused hemispheres, with greater influences occurring in the infused hemisphere. Finally, unilateral intrastriatal infusion of dopamine or glutamate antagonists changed the behavior of the rats from characteristic mAMPH-induced stereotypy to rotation ipsilateral to the infusion. These results demonstrate that mAMPH’s actions on striatal dopamine and glutamate receptors modulate the widespread cortical activation induced by mAMPH. It is hypothesized that dopamine release from nigrostriatal terminals modulates activity within striatal

  8. Correlation between Cortical State and Locus Coeruleus Activity: Implications for Sensory Coding in Rat Barrel Cortex

    PubMed Central

    Fazlali, Zeinab; Ranjbar-Slamloo, Yadollah; Adibi, Mehdi; Arabzadeh, Ehsan

    2016-01-01

    Cortical state modulates the background activity of cortical neurons, and their evoked response to sensory stimulation. Multiple mechanisms are involved in switching between cortical states including various neuromodulatory systems. Locus Coeruleus (LC) is one of the major neuromodulatory nuclei in the brainstem with widespread projections throughout the brain and modulates the activity of cells and networks. Here, we quantified the link between the LC spontaneous activity, cortical state and sensory processing in the rat vibrissal somatosensory “barrel” cortex (BC). We simultaneously recorded unit activity from LC and BC along with prefrontal electroencephalogram (EEG) while presenting brief whisker deflections under urethane anesthesia. The ratio of low to high frequency components of EEG (referred to as the L/H ratio) was employed to identify cortical state. We found that the spontaneous activity of LC units exhibited a negative correlation with the L/H ratio. Cross-correlation analysis revealed that changes in LC firing preceded changes in the cortical state: the correlation of the LC firing profile with the L/H ratio was maximal at an average lag of −1.2 s. We further quantified BC neuronal responses to whisker stimulation during the synchronized and desynchronized states. In the desynchronized state, BC neurons showed lower stimulus detection threshold, higher response fidelity, and shorter response latency. The most prominent change was observed in the late phase of BC evoked activity (100–400 ms post stimulus onset): almost every BC unit exhibited a greater late response during the desynchronized state. Categorization of the BC evoked responses based on LC activity (into high and low LC discharge rates) resulted in highly similar response profiles compared to categorization based on the cortical state (low and high L/H ratios). These findings provide evidence for the involvement of the LC neuromodulatory system in desynchronization of cortical state

  9. Modulating epigenetic mechanisms: the diverse functions of Ski during cortical development.

    PubMed

    Baranek, Constanze; Atanasoski, Suzana

    2012-07-01

    In the developing forebrain, neural stem and progenitor cells generate a large variety of neurons with specific functions in the mature cortex. A central issue is to understand the roles of transcriptional networks and regulatory pathways that control these complex developmental processes. The proto-oncogene Ski is a transcriptional regulator linked to the human 1p36 deletion syndrome, which involves a set of phenotypes including nervous system defects. Ski shows a dynamic expression pattern during cortical development and, accordingly, the phenotype of Ski-deficient cortices is complex, involving altered cell cycle characteristics of neural progenitors, disturbed timing of neurogenesis and mis-specification of projection neurons. Ski is likely to play a role in various pathways by virtue of its ability to interact with a range of signaling molecules, thereby modulating transcriptional activity of corresponding target genes. Ski regulates proliferation and differentiation of various cell types, and more recent data from my laboratory demonstrates that Ski is also involved in the specification of cortical projection neurons. This Point-of-View elucidates the role of Ski as an essential linker between sequence-specific transcription factors and non-DNA binding cofactors with chromatin modifying activities. In particular, it puts forward the hypothesis that the diverse functions of Ski as a co-repressor might be related to its association with distinct HDAC-complexes.

  10. Active Chemical Thermodynamics promoted by activity of cortical actin

    NASA Astrophysics Data System (ADS)

    Bhattacharya, Bhaswati; Chaudhuri, Abhishek; Gowrishankar, Kripa; Rao, Madan

    2011-03-01

    The spatial distribution and dynamics of formation and breakup of the nanoclusters of cell surface proteins is controlled by the active remodeling dynamics of the underlying cortical actin. To explain these observations, we have proposed a novel mechanism of nanoclustering, involving the transient binding to and advection along constitutively occuring ``asters'' of cortical actin. We study the consequences of such active actin-based clustering, in the context of chemical reactions involving conformational changes of cell surface proteins. We find that the active remodeling of cortical actin, can give rise to a dramatic increase in efficiency and extent of conformational spread, even at low levels of expression at the cell surface. We define a activity temperature (τa) arising due to actin activities which can be used to describe chemical thermodynamics of the system. We plot TTT (time-temparature-transformation) curves and compute the Arrhenius factors which depend on τa . With this, the active asters can be treated as enzymes whose enzymatic reaction rate can be related to the activity.

  11. Abnormal dopaminergic modulation of striato-cortical networks underlies levodopa-induced dyskinesias in humans.

    PubMed

    Herz, Damian M; Haagensen, Brian N; Christensen, Mark S; Madsen, Kristoffer H; Rowe, James B; Løkkegaard, Annemette; Siebner, Hartwig R

    2015-06-01

    Dopaminergic signalling in the striatum contributes to reinforcement of actions and motivational enhancement of motor vigour. Parkinson's disease leads to progressive dopaminergic denervation of the striatum, impairing the function of cortico-basal ganglia networks. While levodopa therapy alleviates basal ganglia dysfunction in Parkinson's disease, it often elicits involuntary movements, referred to as levodopa-induced peak-of-dose dyskinesias. Here, we used a novel pharmacodynamic neuroimaging approach to identify the changes in cortico-basal ganglia connectivity that herald the emergence of levodopa-induced dyskinesias. Twenty-six patients with Parkinson's disease (age range: 51-84 years; 11 females) received a single dose of levodopa and then performed a task in which they had to produce or suppress a movement in response to visual cues. Task-related activity was continuously mapped with functional magnetic resonance imaging. Dynamic causal modelling was applied to assess levodopa-induced modulation of effective connectivity between the pre-supplementary motor area, primary motor cortex and putamen when patients suppressed a motor response. Bayesian model selection revealed that patients who later developed levodopa-induced dyskinesias, but not patients without dyskinesias, showed a linear increase in connectivity between the putamen and primary motor cortex after levodopa intake during movement suppression. Individual dyskinesia severity was predicted by levodopa-induced modulation of striato-cortical feedback connections from putamen to the pre-supplementary motor area (Pcorrected = 0.020) and primary motor cortex (Pcorrected = 0.044), but not feed-forward connections from the cortex to the putamen. Our results identify for the first time, aberrant dopaminergic modulation of striatal-cortical connectivity as a neural signature of levodopa-induced dyskinesias in humans. We argue that excessive striato-cortical connectivity in response to levodopa produces an

  12. Unilateral Left-Hand Contractions Produce Widespread Depression of Cortical Activity after Their Execution.

    PubMed

    Cross-Villasana, Fernando; Gröpel, Peter; Doppelmayr, Michael; Beckmann, Jürgen

    2015-01-01

    The execution of unilateral hand contractions before performance has been reported to produce behavioral aftereffects in various tasks. These effects have been regularly attributed to an induced shift in activation asymmetry to the contralateral hemisphere produced by the contractions. An alternative explanation proposes a generalized state of reduced bilateral cortical activity following unilateral hand contractions. The current experiment contrasted the above explanation models and tested the state of cortical activity after the termination of unilateral hand contractions. Twenty right-handed participants performed hand contractions in two blocks, one for each hand. Using electroencephalogram (EEG), the broad alpha band and its asymmetry between hemispheres before, during, and after hand contractions were analyzed. During contractions, significant bilateral decrease in alpha amplitudes (indicating cortical activation) emerged for both hands around sensory-motor regions. After contractions, alpha amplitudes increased significantly over the whole scalp when compared to baseline, but only for the left hand. No modulation of hemispheric asymmetry was observed at any phase. The results suggest that unilateral hand contractions produce a state of reduced cortical activity after their termination, which is more pronounced if the left hand was used. Consequently, we propose that the reduced cortical activity (and not the persistent activation asymmetry) may facilitate engagement in subsequent behavior, probably due to preventing interference from other, nonessential cortical regions.

  13. D2 dopamine receptors modulate neuronal resonance in subthalamic nucleus and cortical high-voltage spindles through HCN channels.

    PubMed

    Yang, Chen; Yan, Zhiqiang; Zhao, Bo; Wang, Julei; Gao, Guodong; Zhu, Junling; Wang, Wenting

    2016-06-01

    The high-voltage spindles (HVSs), one of the characteristic oscillations that include theta frequencies in the basal ganglia (BG)-cortical system, are involved in immobile behavior and show increasing power in Parkinson's disease (PD). Our previous results suggested that the D2 dopamine receptor might be involved in HVSs modulations in a rat model of PD. Membrane resonance is one of the cellular mechanisms of network oscillation; therefore, we investigated how dopamine modulates the theta frequency membrane resonance of neurons in the subthalamic nucleus (STN), a central pacemaker of BG, and whether such changes in STN neurons subsequently alter HVSs in the BG-cortical system. In particular, we tested whether dopamine modulates HVSs through hyperpolarization-activated cyclic nucleotide-gated (HCN) channels-dependent membrane resonance in STN neurons. We found that an antagonist of D2 receptors, but not of D1 receptors, inhibited membrane resonance and HCN currents of STN neurons through a G-protein activity in acute brain slices. Our further in vivo experiments using local injection of a D2 receptor antagonist or an HCN blocker in STNs of free-moving rats showed an increase in HVSs power and correlation in the BG-cortical system. Local injection of lamotrigine, an HCN agonist, counteracted the effect induced by the D2 antagonist. Taken together, our results revealed a potential cellular mechanism underlying HVSs activity modulation in the BG-cortical system, i.e. tuning HCN activities in STN neurons through dopamine D2 receptors. Our findings might lead to a new direction in PD treatment by providing promising new drug targets for HVSs activity modulation.

  14. Dynamics of auditory cortical activity during behavioural engagement and auditory perception

    PubMed Central

    Carcea, Ioana; Insanally, Michele N.; Froemke, Robert C.

    2017-01-01

    Behavioural engagement can enhance sensory perception. However, the neuronal mechanisms by which behavioural states affect stimulus perception remain poorly understood. Here we record from single units in auditory cortex of rats performing a self-initiated go/no-go auditory task. Self-initiation transforms cortical tuning curves and bidirectionally modulates stimulus-evoked activity patterns and improves auditory detection and recognition. Trial self-initiation decreases the rate of spontaneous activity in the majority of recorded cells. Optogenetic disruption of cortical activity before and during tone presentation shows that these changes in evoked and spontaneous activity are important for sound perception. Thus, behavioural engagement can prepare cortical circuits for sensory processing by dynamically changing sound representation and by controlling the pattern of spontaneous activity. PMID:28176787

  15. Dynamics of auditory cortical activity during behavioural engagement and auditory perception.

    PubMed

    Carcea, Ioana; Insanally, Michele N; Froemke, Robert C

    2017-02-08

    Behavioural engagement can enhance sensory perception. However, the neuronal mechanisms by which behavioural states affect stimulus perception remain poorly understood. Here we record from single units in auditory cortex of rats performing a self-initiated go/no-go auditory task. Self-initiation transforms cortical tuning curves and bidirectionally modulates stimulus-evoked activity patterns and improves auditory detection and recognition. Trial self-initiation decreases the rate of spontaneous activity in the majority of recorded cells. Optogenetic disruption of cortical activity before and during tone presentation shows that these changes in evoked and spontaneous activity are important for sound perception. Thus, behavioural engagement can prepare cortical circuits for sensory processing by dynamically changing sound representation and by controlling the pattern of spontaneous activity.

  16. Early development of synchrony in cortical activations in the human

    PubMed Central

    Koolen, N.; Dereymaeker, A.; Räsänen, O.; Jansen, K.; Vervisch, J.; Matic, V.; Naulaers, G.; De Vos, M.; Van Huffel, S.; Vanhatalo, S.

    2016-01-01

    Early intermittent cortical activity is thought to play a crucial role in the growth of neuronal network development, and large scale brain networks are known to provide the basis for higher brain functions. Yet, the early development of the large scale synchrony in cortical activations is unknown. Here, we tested the hypothesis that the early intermittent cortical activations seen in the human scalp EEG show a clear developmental course during the last trimester of pregnancy, the period of intensive growth of cortico-cortical connections. We recorded scalp EEG from altogether 22 premature infants at post-menstrual age between 30 and 44 weeks, and the early cortical synchrony was quantified using recently introduced activation synchrony index (ASI). The developmental correlations of ASI were computed for individual EEG signals as well as anatomically and mathematically defined spatial subgroups. We report two main findings. First, we observed a robust and statistically significant increase in ASI in all cortical areas. Second, there were significant spatial gradients in the synchrony in fronto-occipital and left-to-right directions. These findings provide evidence that early cortical activity is increasingly synchronized across the neocortex. The ASI-based metrics introduced in our work allow direct translational comparison to in vivo animal models, as well as hold promise for implementation as a functional developmental biomarker in future research on human neonates. PMID:26876605

  17. Postural challenge affects motor cortical activity in young and old adults.

    PubMed

    Papegaaij, Selma; Taube, Wolfgang; van Keeken, Helco G; Otten, Egbert; Baudry, Stéphane; Hortobágyi, Tibor

    2016-01-01

    When humans voluntarily activate a muscle, intracortical inhibition decreases. Such a decrease also occurs in the presence of a postural challenge and more so with increasing age. Here, we examined age-related changes in motor cortical activity during postural and non-postural contractions with varying levels of postural challenge. Fourteen young (age 22) and twelve old adults (age 70) performed three conditions: (1) voluntary contraction of the soleus muscle in sitting and (2) leaning forward while standing with and (3) without being supported. Subthreshold transcranial magnetic stimulation was applied to the soleus motor area suppressing ongoing EMG, as an index of motor cortical activity. The area of EMG suppression was ~60% smaller (p<0.05) in unsupported vs. supported leaning and sitting, with no difference between these latter two conditions (p>0.05). Even though in absolute terms young compared with old adults leaned farther (p=0.018), there was no age effect or an age by condition interaction in EMG suppression. Leaning closer to the maximum without support correlated with less EMG suppression (rho=-0.44, p=0.034). We conclude that the critical factor in modulating motor cortical activity was postural challenge and not contraction aim or posture. Age did not affect the motor control strategy as quantified by the modulation of motor cortical activity, but the modulation appeared at a lower task difficulty with increasing age.

  18. The influence of natural scene dynamics on auditory cortical activity.

    PubMed

    Chandrasekaran, Chandramouli; Turesson, Hjalmar K; Brown, Charles H; Ghazanfar, Asif A

    2010-10-20

    The efficient cortical encoding of natural scenes is essential for guiding adaptive behavior. Because natural scenes and network activity in cortical circuits share similar temporal scales, it is necessary to understand how the temporal structure of natural scenes influences network dynamics in cortical circuits and spiking output. We examined the relationship between the structure of natural acoustic scenes and its impact on network activity [as indexed by local field potentials (LFPs)] and spiking responses in macaque primary auditory cortex. Natural auditory scenes led to a change in the power of the LFP in the 2-9 and 16-30 Hz frequency ranges relative to the ongoing activity. In contrast, ongoing rhythmic activity in the 9-16 Hz range was essentially unaffected by the natural scene. Phase coherence analysis showed that scene-related changes in LFP power were at least partially attributable to the locking of the LFP and spiking activity to the temporal structure in the scene, with locking extending up to 25 Hz for some scenes and cortical sites. Consistent with distributed place and temporal coding schemes, a key predictor of phase locking and power changes was the overlap between the spectral selectivity of a cortical site and the spectral structure of the scene. Finally, during the processing of natural acoustic scenes, spikes were locked to LFP phase at frequencies up to 30 Hz. These results are consistent with an idea that the cortical representation of natural scenes emerges from an interaction between network activity and stimulus dynamics.

  19. Asymmetric frontal cortical activity and negative affective responses to ostracism.

    PubMed

    Peterson, Carly K; Gravens, Laura C; Harmon-Jones, Eddie

    2011-06-01

    Ostracism arouses negative affect. However, little is known about variables that influence the intensity of these negative affective responses. Two studies fill this void by incorporating work on approach- and withdrawal-related emotional states and their associated cortical activations. Study 1 found that following ostracism anger related directly to relative left frontal cortical activation. Study 2 used unilateral hand contractions to manipulate frontal cortical activity prior to an ostracizing event. Right-hand contractions, compared to left-hand contractions, caused greater relative left frontal cortical activation during the hand contractions as well as ostracism. Also, right-hand contractions caused more self-reported anger in response to being ostracized. Within-condition correlations revealed patterns of associations between ostracism-induced frontal asymmetry and emotive responses to ostracism consistent with Study 1. Taken together, these results suggest that asymmetrical frontal cortical activity is related to angry responses to ostracism, with greater relative left frontal cortical activity being associated with increased anger.

  20. Auditory midbrain processing is differentially modulated by auditory and visual cortices: An auditory fMRI study.

    PubMed

    Gao, Patrick P; Zhang, Jevin W; Fan, Shu-Juan; Sanes, Dan H; Wu, Ed X

    2015-12-01

    gain modulation is mediated primarily through direct projections and they point to future investigations of the differential roles of the direct and indirect projections in corticofugal modulation. In summary, our imaging findings demonstrate the large-scale descending influences, from both the auditory and visual cortices, on sound processing in different IC subdivisions. They can guide future studies on the coordinated activity across multiple regions of the auditory network, and its dysfunctions.

  1. A New Role for TIMP-1 in Modulating Neurite Outgrowth and Morphology of Cortical Neurons

    PubMed Central

    Ould-yahoui, Adlane; Tremblay, Evelyne; Sbai, Oualid; Ferhat, Lotfi; Bernard, Anne; Charrat, Eliane; Gueye, Yatma; Lim, Ngee Han; Brew, Keith; Risso, Jean-Jacques; Dive, Vincent; Khrestchatisky, Michel; Rivera, Santiago

    2009-01-01

    Background Tissue inhibitor of metalloproteinases-1 (TIMP-1) displays pleiotropic activities, both dependent and independent of its inhibitory activity on matrix metalloproteinases (MMPs). In the central nervous system (CNS), TIMP-1 is strongly upregulated in reactive astrocytes and cortical neurons following excitotoxic/inflammatory stimuli, but no information exists on its effects on growth and morphology of cortical neurons. Principal Findings We found that 24 h incubation with recombinant TIMP-1 induced a 35% reduction in neurite length and significantly increased growth cones size and the number of F-actin rich microprocesses. TIMP-1 mediated reduction in neurite length affected both dendrites and axons after 48 h treatment. The effects on neurite length and morphology were not elicited by a mutated form of TIMP-1 inactive against MMP-1, -2 and -3, and still inhibitory for MMP-9, but were mimicked by a broad spectrum MMP inhibitor. MMP-9 was poorly expressed in developing cortical neurons, unlike MMP-2 which was present in growth cones and whose selective inhibition caused neurite length reductions similar to those induced by TIMP-1. Moreover, TIMP-1 mediated changes in cytoskeleton reorganisation were not accompanied by modifications in the expression levels of actin, βIII-tubulin, or microtubule assembly regulatory protein MAP2c. Transfection-mediated overexpression of TIMP-1 dramatically reduced neuritic arbour extension in the absence of detectable levels of released extracellular TIMP-1. Conclusions Altogether, TIMP-1 emerges as a modulator of neuronal outgrowth and morphology in a paracrine and autrocrine manner through the inhibition, at least in part, of MMP-2 and not MMP-9. These findings may help us understand the role of the MMP/TIMP system in post-lesion pre-scarring conditions. PMID:20011518

  2. Sensory incongruence leading to hand disownership modulates somatosensory cortical processing.

    PubMed

    Otsuru, Naofumi; Hashizume, Akira; Nakamura, Daichi; Endo, Yuuki; Inui, Koji; Kakigi, Ryusuke; Yuge, Louis

    2014-09-01

    The sense of body ownership is based on integration of multimodal sensory information, including tactile sensation, proprioception, and vision. Distorted body ownership contributes to the development of chronic pain syndromes and possibly symptoms of psychiatric disease. However, the effects of disownership on cortical processing of somatosensory information are unknown. In the present study, we created a "disownership" condition in healthy individuals by manipulating the visual information indicating the location of the subject's own left hand using a mirror box and examined the influence of this disownership on cortical responses to electrical stimulation of the left index finger using magnetoencephalography (MEG). The event-related magnetic field in the right primary somatosensory cortex at approximately 50 msec (M50) after stimulus was enhanced under the disownership condition. The present results suggest that M50 reflects a cortical incongruence detection mechanism involving integration of sensory inputs from visual and proprioceptive systems. This signal may be valuable for future studies of the mechanisms underlying sense of body ownership and the role that disrupted sense of ownership has in neurological disease.

  3. Oxytocin modulates female sociosexual behavior through a specific class of prefrontal cortical interneurons

    PubMed Central

    Nakajima, Miho; Görlich, Andreas; Heintz, Nathaniel

    2014-01-01

    SUMMARY Human imaging studies have revealed that intranasal administration of the “prosocial” hormone oxytocin (OT) activates the frontal cortex, and that this action of OT correlates with enhanced brain function in autism. Here we report the discovery of a population of somatostatin (Sst) positive, regular spiking interneurons that express the oxytocin receptor (OxtrINs). Silencing of OxtrINs in the medial prefrontal cortex (mPFC) of female mice resulted in loss of social interest in male mice specifically during the sexually receptive phase of the estrous cycle. This sociosexual deficit was also present in mice in which the Oxtr gene was conditionally deleted from the mPFC, and in control mice infused with an Oxtr antagonist. Our data demonstrate a gender, cell type and state specific role for OT/Oxtr signaling in the mPFC, and identify a latent cortical circuit element that may modulate other complex social behaviors in response to OT. PMID:25303526

  4. Laminar profile of spontaneous and evoked theta: Rhythmic modulation of cortical processing during word integration.

    PubMed

    Halgren, Eric; Kaestner, Erik; Marinkovic, Ksenija; Cash, Sydney S; Wang, Chunmao; Schomer, Donald L; Madsen, Joseph R; Ulbert, Istvan

    2015-09-01

    Theta may play a central role during language understanding and other extended cognitive processing, providing an envelope for widespread integration of participating cortical areas. We used linear microelectrode arrays in epileptics to define the circuits generating theta in inferotemporal, perirhinal, entorhinal, prefrontal and anterior cingulate cortices. In all locations, theta was generated by excitatory current sinks in middle layers which receive predominantly feedforward inputs, alternating with sinks in superficial layers which receive mainly feedback/associative inputs. Baseline and event-related theta were generated by indistinguishable laminar profiles of transmembrane currents and unit-firing. Word presentation could reset theta phase, permitting theta to contribute to late event-related potentials, even when theta power decreases relative to baseline. Limited recordings during sentence reading are consistent with rhythmic theta activity entrained by a given word modulating the neural background for the following word. These findings show that theta occurs spontaneously, and can be momentarily suppressed, reset and synchronized by words. Theta represents an alternation between feedforward/divergent and associative/convergent processing modes that may temporally organize sustained processing and optimize the timing of memory formation. We suggest that words are initially encoded via a ventral feedforward stream which is lexicosemantic in the anteroventral temporal lobe; its arrival may trigger a widespread theta rhythm which integrates the word within a larger context.

  5. Contributions of Subsurface Cortical Modulations to Discrimination of Executed and Imagined Grasp Forces through Stereoelectroencephalography

    PubMed Central

    Murphy, Brian A.; Miller, Jonathan P.; Gunalan, Kabilar; Ajiboye, A. Bolu

    2016-01-01

    Stereoelectroencephalographic (SEEG) depth electrodes have the potential to record neural activity from deep brain structures not easily reached with other intracranial recording technologies. SEEG electrodes were placed through deep cortical structures including central sulcus and insular cortex. In order to observe changes in frequency band modulation, participants performed force matching trials at three distinct force levels using two different grasp configurations: a power grasp and a lateral pinch. Signals from these deeper structures were found to contain information useful for distinguishing force from rest trials as well as different force levels in some participants. High frequency components along with alpha and beta bands recorded from electrodes located near the primary motor cortex wall of central sulcus and electrodes passing through sensory cortex were found to be the most useful for classification of force versus rest although one participant did have significant modulation in the insular cortex. This study electrophysiologically corroborates with previous imaging studies that show force-related modulation occurs inside of central sulcus and insular cortex. The results of this work suggest that depth electrodes could be useful tools for investigating the functions of deeper brain structures as well as showing that central sulcus and insular cortex may contain neural signals that could be used for control of a grasp force BMI. PMID:26963246

  6. Mesoscopic Patterns of Neural Activity Support Songbird Cortical Sequences

    PubMed Central

    Guitchounts, Grigori; Velho, Tarciso; Lois, Carlos; Gardner, Timothy J.

    2015-01-01

    Time-locked sequences of neural activity can be found throughout the vertebrate forebrain in various species and behavioral contexts. From “time cells” in the hippocampus of rodents to cortical activity controlling movement, temporal sequence generation is integral to many forms of learned behavior. However, the mechanisms underlying sequence generation are not well known. Here, we describe a spatial and temporal organization of the songbird premotor cortical microcircuit that supports sparse sequences of neural activity. Multi-channel electrophysiology and calcium imaging reveal that neural activity in premotor cortex is correlated with a length scale of 100 µm. Within this length scale, basal-ganglia–projecting excitatory neurons, on average, fire at a specific phase of a local 30 Hz network rhythm. These results show that premotor cortical activity is inhomogeneous in time and space, and that a mesoscopic dynamical pattern underlies the generation of the neural sequences controlling song. PMID:26039895

  7. Mesoscopic patterns of neural activity support songbird cortical sequences.

    PubMed

    Markowitz, Jeffrey E; Liberti, William A; Guitchounts, Grigori; Velho, Tarciso; Lois, Carlos; Gardner, Timothy J

    2015-06-01

    Time-locked sequences of neural activity can be found throughout the vertebrate forebrain in various species and behavioral contexts. From "time cells" in the hippocampus of rodents to cortical activity controlling movement, temporal sequence generation is integral to many forms of learned behavior. However, the mechanisms underlying sequence generation are not well known. Here, we describe a spatial and temporal organization of the songbird premotor cortical microcircuit that supports sparse sequences of neural activity. Multi-channel electrophysiology and calcium imaging reveal that neural activity in premotor cortex is correlated with a length scale of 100 µm. Within this length scale, basal-ganglia-projecting excitatory neurons, on average, fire at a specific phase of a local 30 Hz network rhythm. These results show that premotor cortical activity is inhomogeneous in time and space, and that a mesoscopic dynamical pattern underlies the generation of the neural sequences controlling song.

  8. Variation at NRG1 genotype related to modulation of small-world properties of the functional cortical network.

    PubMed

    Lubeiro, Alba; Gomez-Pilar, Javier; Martín, Oscar; Palomino, Aitor; Fernández, Myriam; González-Pinto, Ana; Poza, Jesús; Hornero, Roberto; Molina, Vicente

    2017-02-01

    Functional brain networks possess significant small-world (SW) properties. Genetic variation relevant to both inhibitory and excitatory transmission may contribute to modulate these properties. In healthy controls, genotypic variation in Neuregulin 1 (NRG1) related to the risk of psychosis (risk alleles) would contribute to functional SW modulation of the cortical network. Electroencephalographic activity during an odd-ball task was recorded in 144 healthy controls. Then, small-worldness (SWn) was calculated in five frequency bands (i.e., theta, alpha, beta1, beta2 and gamma) for baseline (from -300 to the stimulus onset) and response (150-450 ms post-target stimulus) windows. The SWn modulation was defined as the difference in SWn between both windows. Association between SWn modulation and carrying the risk allele for three single nucleotide polymorphisms (SNP) of NRG1 (i.e., rs6468119, rs6994992 and rs7005606) was assessed. A significant association between three SNPs of NRG1 and the SWn modulation was found, specifically: NRG1 rs6468119 in alpha and beta1 bands; NRG1 rs6994992 in theta band; and NRG1 rs7005606 in theta and beta1 bands. Genetic variation at NRG1 may influence functional brain connectivity through the modulation of SWn properties of the cortical network.

  9. Input-Dependent Frequency Modulation of Cortical Gamma Oscillations Shapes Spatial Synchronization and Enables Phase Coding

    PubMed Central

    Lowet, Eric; Roberts, Mark; Hadjipapas, Avgis; Peter, Alina; van der Eerden, Jan; De Weerd, Peter

    2015-01-01

    Fine-scale temporal organization of cortical activity in the gamma range (∼25–80Hz) may play a significant role in information processing, for example by neural grouping (‘binding’) and phase coding. Recent experimental studies have shown that the precise frequency of gamma oscillations varies with input drive (e.g. visual contrast) and that it can differ among nearby cortical locations. This has challenged theories assuming widespread gamma synchronization at a fixed common frequency. In the present study, we investigated which principles govern gamma synchronization in the presence of input-dependent frequency modulations and whether they are detrimental for meaningful input-dependent gamma-mediated temporal organization. To this aim, we constructed a biophysically realistic excitatory-inhibitory network able to express different oscillation frequencies at nearby spatial locations. Similarly to cortical networks, the model was topographically organized with spatially local connectivity and spatially-varying input drive. We analyzed gamma synchronization with respect to phase-locking, phase-relations and frequency differences, and quantified the stimulus-related information represented by gamma phase and frequency. By stepwise simplification of our models, we found that the gamma-mediated temporal organization could be reduced to basic synchronization principles of weakly coupled oscillators, where input drive determines the intrinsic (natural) frequency of oscillators. The gamma phase-locking, the precise phase relation and the emergent (measurable) frequencies were determined by two principal factors: the detuning (intrinsic frequency difference, i.e. local input difference) and the coupling strength. In addition to frequency coding, gamma phase contained complementary stimulus information. Crucially, the phase code reflected input differences, but not the absolute input level. This property of relative input-to-phase conversion, contrasting with latency

  10. Input-dependent frequency modulation of cortical gamma oscillations shapes spatial synchronization and enables phase coding.

    PubMed

    Lowet, Eric; Roberts, Mark; Hadjipapas, Avgis; Peter, Alina; van der Eerden, Jan; De Weerd, Peter

    2015-02-01

    Fine-scale temporal organization of cortical activity in the gamma range (∼25-80Hz) may play a significant role in information processing, for example by neural grouping ('binding') and phase coding. Recent experimental studies have shown that the precise frequency of gamma oscillations varies with input drive (e.g. visual contrast) and that it can differ among nearby cortical locations. This has challenged theories assuming widespread gamma synchronization at a fixed common frequency. In the present study, we investigated which principles govern gamma synchronization in the presence of input-dependent frequency modulations and whether they are detrimental for meaningful input-dependent gamma-mediated temporal organization. To this aim, we constructed a biophysically realistic excitatory-inhibitory network able to express different oscillation frequencies at nearby spatial locations. Similarly to cortical networks, the model was topographically organized with spatially local connectivity and spatially-varying input drive. We analyzed gamma synchronization with respect to phase-locking, phase-relations and frequency differences, and quantified the stimulus-related information represented by gamma phase and frequency. By stepwise simplification of our models, we found that the gamma-mediated temporal organization could be reduced to basic synchronization principles of weakly coupled oscillators, where input drive determines the intrinsic (natural) frequency of oscillators. The gamma phase-locking, the precise phase relation and the emergent (measurable) frequencies were determined by two principal factors: the detuning (intrinsic frequency difference, i.e. local input difference) and the coupling strength. In addition to frequency coding, gamma phase contained complementary stimulus information. Crucially, the phase code reflected input differences, but not the absolute input level. This property of relative input-to-phase conversion, contrasting with latency codes

  11. Modulation of sensitivity to alcohol by cortical and thalamic brain regions

    PubMed Central

    Jaramillo, Anel A.; Randall, Patrick A.; Frisbee, Suzanne; Besheer, Joyce

    2017-01-01

    The nucleus accumbens core (AcbC) is a key brain region known to regulate the discriminative stimulus/interoceptive effects of alcohol. As such, the goal of the present work was to identify AcbC projection regions that may also modulate sensitivity to alcohol. Accordingly, AcbC afferent projections were identified in behaviorally naïve rats using a retrograde tracer which led to the focus on the medial prefrontal cortex (mPFC), insular cortex (IC) and rhomboid thalamic nucleus (Rh). Next, to examine the possible role of these brain regions in modulating sensitivity to alcohol, neuronal response to alcohol in rats trained to discriminate alcohol (1 g/kg, intragastric [IG]) vs. water was examined using a two-lever drug discrimination task. As such, rats were administered water or alcohol (1g/kg, IG) and brain tissue was processed for c-Fos immunoreactivity (IR), a marker of neuronal activity. Alcohol decreased c-Fos IR in the mPFC, IC, Rh, and AcbC. Lastly, site-specific pharmacological inactivation with muscimol+baclofen (GABAA agonist+GABAB agonist) was used to determine the functional role of the mPFC, IC and Rh in modulating the interoceptive effects of alcohol in rats trained to discriminate alcohol (1 g/kg, IG) vs. water. mPFC inactivation resulted in full substitution for the alcohol training dose, and IC and Rh inactivation produced partial alcohol-like effects, demonstrating the importance of these regions, with known projections to the AcbC, in modulating sensitivity to alcohol. Together, these data demonstrate a site of action of alcohol and the recruitment of cortical/thalamic regions in modulating sensitivity to the interoceptive effects of alcohol. PMID:27543844

  12. Modulation of sensitivity to alcohol by cortical and thalamic brain regions.

    PubMed

    Jaramillo, Anel A; Randall, Patrick A; Frisbee, Suzanne; Besheer, Joyce

    2016-10-01

    The nucleus accumbens core (AcbC) is a key brain region known to regulate the discriminative stimulus/interoceptive effects of alcohol. As such, the goal of the present work was to identify AcbC projection regions that may also modulate sensitivity to alcohol. Accordingly, AcbC afferent projections were identified in behaviorally naïve rats using a retrograde tracer which led to the focus on the medial prefrontal cortex (mPFC), insular cortex (IC) and rhomboid thalamic nucleus (Rh). Next, to examine the possible role of these brain regions in modulating sensitivity to alcohol, neuronal response to alcohol in rats trained to discriminate alcohol (1 g/kg, intragastric [IG]) vs. water was examined using a two-lever drug discrimination task. As such, rats were administered water or alcohol (1 g/kg, IG) and brain tissue was processed for c-Fos immunoreactivity (IR), a marker of neuronal activity. Alcohol decreased c-Fos IR in the mPFC, IC, Rh and AcbC. Lastly, site-specific pharmacological inactivation with muscimol + baclofen (GABAA agonist + GABAB agonist) was used to determine the functional role of the mPFC, IC and Rh in modulating the interoceptive effects of alcohol in rats trained to discriminate alcohol (1 g/kg, IG) vs. water. mPFC inactivation resulted in full substitution for the alcohol training dose, and IC and Rh inactivation produced partial alcohol-like effects, demonstrating the importance of these regions, with known projections to the AcbC, in modulating sensitivity to alcohol. Together, these data demonstrate a site of action of alcohol and the recruitment of cortical/thalamic regions in modulating sensitivity to the interoceptive effects of alcohol.

  13. Visual cortical activity reflects faster accumulation of information from cortically blind fields

    PubMed Central

    Martin, Tim; Das, Anasuya; Huxlin, Krystel R.

    2012-01-01

    Brain responses (from functional magnetic resonance imaging) and components of information processing were investigated in nine cortically blind observers performing a global direction discrimination task. Three of these subjects had responses in perilesional cortex in response to blind field stimulation, whereas the others did not. We used the EZ-diffusion model of decision making to understand how cortically blind subjects make a perceptual decision on stimuli presented within their blind field. We found that these subjects had slower accumulation of information in their blind fields as compared with their good fields and to intact controls. Within cortically blind subjects, activity in perilesional tissue, V3A and hMT+ was associated with a faster accumulation of information for deciding direction of motion of stimuli presented in the blind field. This result suggests that the rate of information accumulation is a critical factor in the degree of impairment in cortical blindness and varies greatly among affected individuals. Retraining paradigms that seek to restore visual functions might benefit from focusing on increasing the rate of information accumulation. PMID:23169923

  14. Amygdala activation for eye contact despite complete cortical blindness.

    PubMed

    Burra, Nicolas; Hervais-Adelman, Alexis; Kerzel, Dirk; Tamietto, Marco; de Gelder, Beatrice; Pegna, Alan J

    2013-06-19

    Cortical blindness refers to the loss of vision that occurs after destruction of the primary visual cortex. Although there is no sensory cortex and hence no conscious vision, some cortically blind patients show amygdala activation in response to facial or bodily expressions of emotion. Here we investigated whether direction of gaze could also be processed in the absence of any functional visual cortex. A well-known patient with bilateral destruction of his visual cortex and subsequent cortical blindness was investigated in an fMRI paradigm during which blocks of faces were presented either with their gaze directed toward or away from the viewer. Increased right amygdala activation was found in response to directed compared with averted gaze. Activity in this region was further found to be functionally connected to a larger network associated with face and gaze processing. The present study demonstrates that, in human subjects, the amygdala response to eye contact does not require an intact primary visual cortex.

  15. Ghrelin accelerates synapse formation and activity development in cultured cortical networks

    PubMed Central

    2014-01-01

    Background While ghrelin was initially related to appetite stimulation and growth hormone secretion, it also has a neuroprotective effect in neurodegenerative diseases and regulates cognitive function. The cellular basis of those processes is related to synaptic efficacy and plasticity. Previous studies have shown that ghrelin not only stimulates synapse formation in cultured cortical neurons and hippocampal slices, but also alters some of the electrophysiological properties of neurons in the hypothalamus, amygdala and other subcortical areas. However, direct evidence for ghrelin’s ability to modulate the activity in cortical neurons is not available yet. In this study, we investigated the effect of acylated ghrelin on the development of the activity level and activity patterns in cortical neurons, in relation to its effect on synaptogenesis. Additionally, we quantitatively evaluated the expression of the receptor for acylated ghrelin – growth hormone secretagogue receptor-1a (GHSR-1a) during development. Results We performed electrophysiology and immunohistochemistry on dissociated cortical cultures from neonates, treated chronically with acylated ghrelin. On average 76 ± 4.6% of the cortical neurons expressed GHSR-1a. Synapse density was found to be much higher in ghrelin treated cultures than in controls across all age groups (1, 2 or 3 weeks). In all cultures (control and ghrelin treated), network activity gradually increased until it reached a maximum after approximately 3 weeks, followed by a slight decrease towards a plateau. During early developmental stages (1–2 weeks), the activity was much higher in ghrelin treated cultures and consequently, they reached the plateau value almost a week earlier than controls. Conclusions Acylated ghrelin leads to earlier network formation and activation in cultured cortical neuronal networks, the latter being a possibly consequence of accelerated synaptogenesis. PMID:24742241

  16. Cortical neuronal activity does not regulate sleep homeostasis.

    PubMed

    Qiu, M-H; Chen, M C; Lu, J

    2015-06-25

    The neural substrate of sleep homeostasis is unclear, but both cortical and subcortical structures are thought to be involved in sleep regulation. To test whether prior neuronal activity in the cortex or in subcortical regions drives sleep rebound, we systemically administered atropine (100mg/kg) to rats, producing a dissociated state with slow-wave cortical electroencephalogram (EEG) but waking behavior (e.g. locomotion). Atropine injections during the light period produced 6h of slow-wave cortical EEG but also subcortical arousal. Afterward, rats showed a significant increase in non-rapid eye movement (NREM) sleep, compared to the same period on a baseline day. Consistent with the behavioral and cortical EEG state produced by systemic atropine, c-Fos expression was low in the cortex but high in multiple subcortical arousal systems. These data suggest that subcortical arousal and behavior are sufficient to drive sleep homeostasis, while a sleep-like pattern of cortical activity is not sufficient to satisfy sleep homeostasis.

  17. Differences in Dopaminergic Modulation to Motor Cortical Plasticity between Parkinson's Disease and Multiple System Atrophy

    PubMed Central

    Kawashima, Shoji; Ueki, Yoshino; Mima, Tatsuya; Fukuyama, Hidenao; Ojika, Kosei; Matsukawa, Noriyuki

    2013-01-01

    Dopamine modulates the synaptic plasticity in the primary motor cortex (M1). To evaluate whether the functioning of the cortico-striatal circuit is necessary for this modulation, we applied a paired associative stimulation (PAS) protocol that comprised an electric stimulus to the right median nerve at the wrist and subsequent transcranial magnetic stimulation of the left M1, to 10 patients with Parkinson's disease (PD) and 10 with multiple system atrophy of the parkinsonian type (MSA-P) with and without dopamine replacement therapy (-on/off). To investigate the M1 function, motor-evoked potentials (MEPs) were measured before and after the PAS. In both patient groups without medication, the PAS protocol failed to increase the averaged amplitude of MEPs. The dopamine replacement therapy in PD, but not in MSA-P effectively restored the PAS-induced MEP increase. This suggests that not the existence of dopamine itself but the activation of cortico-striatal circuit might play an important role for cortical plasticity in the human M1. PMID:23658735

  18. Differences in dopaminergic modulation to motor cortical plasticity between Parkinson's disease and multiple system atrophy.

    PubMed

    Kawashima, Shoji; Ueki, Yoshino; Mima, Tatsuya; Fukuyama, Hidenao; Ojika, Kosei; Matsukawa, Noriyuki

    2013-01-01

    Dopamine modulates the synaptic plasticity in the primary motor cortex (M1). To evaluate whether the functioning of the cortico-striatal circuit is necessary for this modulation, we applied a paired associative stimulation (PAS) protocol that comprised an electric stimulus to the right median nerve at the wrist and subsequent transcranial magnetic stimulation of the left M1, to 10 patients with Parkinson's disease (PD) and 10 with multiple system atrophy of the parkinsonian type (MSA-P) with and without dopamine replacement therapy (-on/off). To investigate the M1 function, motor-evoked potentials (MEPs) were measured before and after the PAS. In both patient groups without medication, the PAS protocol failed to increase the averaged amplitude of MEPs. The dopamine replacement therapy in PD, but not in MSA-P effectively restored the PAS-induced MEP increase. This suggests that not the existence of dopamine itself but the activation of cortico-striatal circuit might play an important role for cortical plasticity in the human M1.

  19. Rapid modulation of synaptogenesis and spinogenesis by 17β-estradiol in primary cortical neurons

    PubMed Central

    Sellers, Katherine J.; Erli, Filippo; Raval, Pooja; Watson, Iain A.; Chen, Ding; Srivastava, Deepak P.

    2015-01-01

    In the mammalian forebrain, the majority of excitatory synapses occur on dendritic spines. Changes in the number of these structures is important for brain development, plasticity and the refinement of neuronal circuits. The formation of excitatory synapses involves the coordinated formation of dendritic spines and targeting of multi-protein complexes to nascent connections. Recent studies have demonstrated that the estrogen 17β-estradiol (E2) can rapidly increase the number of dendritic spines, an effect consistent with the ability of E2 to rapidly influence cognitive function. However, the molecular composition of E2-induced spines and whether these protrusions form synaptic connections has not been fully elucidated. Moreover, which estrogen receptor(s) (ER) mediate these spine-morphogenic responses are not clear. Here, we report that acute E2 treatment results in the recruitment of postsynaptic density protein 95 (PSD-95) to novel dendritic spines. In addition neuroligin 1 (Nlg-1) and the NMDA receptor subunit GluN1 are recruited to nascent synapses in cortical neurons. The presence of these synaptic proteins at nascent synapses suggests that the machinery to allow pre- and post-synapses to form connections are present in E2-induced spines. We further demonstrate that E2 treatment results in the rapid and transient activation of extracellular signal-regulated kinase 1/2 (ERK1/2), Akt and the mammalian target of rapamycin (mTOR) signaling pathways. However, only ERK1/2 and Akt are required for E2-mediated spinogenesis. Using synthetic receptor modulators, we further demonstrate that activation of the estrogen receptor beta (ERβ) but not alpha (ERα) mimics rapid E2-induced spinogenesis and synaptogenesis. Taken together these findings suggest that in primary cortical neurons, E2 signaling via ERβ, but not through ERα, is capable of remodeling neuronal circuits by increasing the number of excitatory synapses. PMID:25926772

  20. Secondary instabilities modulate cortical complexity in the mammalian brain

    NASA Astrophysics Data System (ADS)

    Budday, Silvia; Steinmann, Paul; Kuhl, Ellen

    2015-10-01

    Disclosing the origin of convolutions in the mammalian brain remains a scientific challenge. Primary folds form before we are born: they are static, well defined and highly preserved across individuals. Secondary folds occur and disappear throughout our entire lifetime: they are dynamic, irregular and highly variable among individuals. While extensive research has improved our understanding of primary folding in the mammalian brain, secondary folding remains understudied and poorly understood. Here, we show that secondary instabilities can explain the increasing complexity of our brain surface as we age. Using the nonlinear field theories of mechanics supplemented by the theory of finite growth, we explore the critical conditions for secondary instabilities. We show that with continuing growth, our brain surface continues to bifurcate into increasingly complex morphologies. Our results suggest that even small geometric variations can have a significant impact on surface morphogenesis. Secondary bifurcations, and with them morphological changes during childhood and adolescence, are closely associated with the formation and loss of neuronal connections. Understanding the correlation between neuronal connectivity, cortical thickness, surface morphology and ultimately behaviour, could have important implications on the diagnostics, classification and treatment of neurological disorders.

  1. Secondary instabilities modulate cortical complexity in the mammalian brain

    PubMed Central

    Budday, Silvia; Steinmann, Paul; Kuhl, Ellen

    2015-01-01

    Disclosing the origin of convolutions in the mammalian brain remains a scientific challenge. Primary folds form before we are born: they are static, well defined, and highly preserved across individuals. Secondary folds occur and disappear throughout our entire life time: they are dynamic, irregular, and highly variable among individuals. While extensive research has improved our understanding of primary folding in the mammalian brain, secondary folding remains understudied and poorly understood. Here, we show that secondary instabilities can explain the increasing complexity of our brain surface as we age. Using the nonlinear field theories of mechanics supplemented by the theory of finite growth, we explore the critical conditions for secondary instabilities. We show that with continuing growth, our brain surface continues to bifurcate into increasingly complex morphologies. Our results suggest that even small geometric variations can have a significant impact on surface morphogenesis. Secondary bifurcations, and with them morphological changes during childhood and adolescence, are closely associated with the formation and loss of neuronal connections. Understanding the correlation between neuronal connectivity, cortical thickness, surface morphology, and ultimately behavior, could have important implications on the diagnostics, classification, and treatment of neurological disorders. PMID:26523123

  2. Enhancing effects of flavored nutritive stimuli on cortical swallowing network activity

    PubMed Central

    Babaei, Arash; Kern, Mark; Antonik, Stephen; Mepani, Rachel; Ward, B. Douglas; Li, Shi-Jiang; Hyde, James

    2010-01-01

    A better understanding of the central control of the physiology of deglutition is necessary for devising interventions aimed at correcting pathophysiological conditions of swallowing. Positive modulation of the cortical swallowing network can have clinical ramifications in dysphagia due to central nervous system deficits. Our aim was to determine the effect of nutritive sensory input on the cortical swallowing network. In 14 healthy right-handed volunteers, we utilized a paradigm-driven protocol to quantify the number of activated voxels and their signal intensity within the left hemispheric cortical swallowing network by high-resolution functional MRI (fMRI) during five different swallowing conditions. Swallowing conditions included a dry swallow (saliva) and natural water-, lemon-, popcorn-, and chocolate-flavored liquid swallows. Each flavored liquid was presented simultaneously by its image, scent, and taste in random order and tested over three runs. fMRIs were analyzed in a blinded fashion. Average fMRI blood oxygenation level-dependent signal intensity and number of activated voxels during swallowing concurrent with nutritive gustatory, olfactory, and visual stimulations were significantly increased compared with dry/natural water swallows throughout the cortical swallowing network (P < 0.001 and P < 0.05, respectively). Subregion analysis showed the increased activity for flavored liquids in prefrontal, cingulate gyrus, and sensory/motor cortex, but not in precuneus and insula. Concurrent gustatory, olfactory, and visual nutritive stimulation enhances the activity of the cortical swallowing network. This finding may have clinical implications in management of swallowing disorders due to cortical lesions. PMID:20508154

  3. Age-Related Variability in Cortical Activity during Language Processing

    ERIC Educational Resources Information Center

    Fridriksson, Julius; Morrow, K. Leigh; Moser, Dana; Baylis, Gordon C.

    2006-01-01

    Purpose: The present study investigated the extent of cortical activity during overt picture naming using functional magnetic resonance imaging (fMRI). Method: Participants comprised 20 healthy, adult participants with ages ranging from 20 to 82 years. While undergoing fMRI, participants completed a picture-naming task consisting of 60…

  4. Electromyographic activation reveals cortical and sub-cortical dissociation during emergence from general anesthesia.

    PubMed

    Hight, Darren F; Voss, Logan J; García, Paul S; Sleigh, Jamie W

    2016-07-21

    During emergence from anesthesia patients regain their muscle tone (EMG). In a typical population of surgical patients the actual volatile gas anesthetic concentrations in the brain (CeMAC) at which EMG activation occurs remains unknown, as is whether EMG activation at higher CeMACs is correlated with subsequent severe pain, or with cortical activation. Electroencephalographic (EEG) and EMG activity was recorded from the forehead of 273 patients emerging from general anesthesia following surgery. We determined CeMAC at time of EMG activation and at return of consciousness. Pain was assessed immediately after return of consciousness using an 11 point numerical rating scale. The onset of EMG activation during emergence was associated with neither discernible muscle movement nor with the presence of exogenous stimulation in half the patients. EMG activation could be modelled as two distinct processes; termed high- and low-CeMAC (occurring higher or lower than 0.07 CeMAC). Low-CeMAC activation was typically associated with simultaneous EMG activation and consciousness, and the presence of a laryngeal mask. In contrast, high-CeMAC EMG activation occurred independently of return of consciousness, and was not associated with severe post-operative pain, but was more common in the presence of an endotracheal tube. Patients emerging from general anesthesia with an endotracheal tube in place are more likely to have an EMG activation at higher CeMAC concentrations. These activations are not associated with subsequent high-pain, nor with cortical arousal, as evidenced by continuing delta waves in the EEG. Conversely, patients emerging from general anesthesia with a laryngeal mask demonstrate marked neural inertia-EMG activation occurs at a low CeMAC, and is closely temporally associated with return of consciousness.

  5. Targeted, noninvasive blockade of cortical neuronal activity

    NASA Astrophysics Data System (ADS)

    McDannold, Nathan; Zhang, Yongzhi; Power, Chanikarn; Arvanitis, Costas D.; Vykhodtseva, Natalia; Livingstone, Margaret

    2015-11-01

    Here we describe a novel method to noninvasively modulate targeted brain areas through the temporary disruption of the blood-brain barrier (BBB) via focused ultrasound, enabling focal delivery of a neuroactive substance. Ultrasound was used to locally disrupt the BBB in rat somatosensory cortex, and intravenous administration of GABA then produced a dose-dependent suppression of somatosensory-evoked potentials in response to electrical stimulation of the sciatic nerve. No suppression was observed 1-5 days afterwards or in control animals where the BBB was not disrupted. This method has several advantages over existing techniques: it is noninvasive; it is repeatable via additional GABA injections; multiple brain regions can be affected simultaneously; suppression magnitude can be titrated by GABA dose; and the method can be used with freely behaving subjects. We anticipate that the application of neuroactive substances in this way will be a useful tool for noninvasively mapping brain function, and potentially for surgical planning or novel therapies.

  6. Dynamical activities of primary somatosensory cortices studied by magnetoencephalography

    NASA Astrophysics Data System (ADS)

    Kishida, Kuniharu

    2009-11-01

    A blind identification method of transfer functions in feedback systems is introduced for examination of dynamical activities of cortices by magnetoencephalography study. Somatosensory activities are examined in 5 Hz periodical median nerve stimulus. In the present paper, we will try two careful preprocessing procedures for the identification method to obtain impulse responses between primary somatosensory cortices. Time series data of the somatosensory evoked field are obtained by using a blind source separation of the T/k type (fractional) decorrelation method. Time series data of current dipoles of primary somatosensory cortices are transformed from the time series data of the somatosensory evoked field by the inverse problem. Fluctuations of current dipoles of them are obtained after elimination of deterministic periodical evoked waveforms. An identification method based on feedback system theory is used for estimation of transfer functions in a feedback model from obtained fluctuations of currents dipoles of primary somatosensory cortices. Dynamical activities between them are presented by Bode diagrams of transfer functions and their impulse responses: the time delay of about 30 ms via corpus callosum is found in the impulse response of identified transfer function.

  7. Methylphenidate (MPH) promotes visual cortical activation in healthy adults in a cued visuomotor task.

    PubMed

    Hodzhev, Yordan; Yordanova, Juliana; Diruf, Martin; Kratz, Oliver; Moll, Gunter H; Kolev, Vasil; Heinrich, Hartmut

    2012-11-01

    Seeking for the mechanisms by which methylphenidate (MPH) improves behavior has demonstrated that MPH modulates excitability in the primary motor cortex. However, little is known about the influence of MPH on top-down controlled mechanisms in the sensory domain. The present study explored the effects of MPH on the activation of visual cortices in healthy adults who performed a cued visuo-motor task in a double-blind placebo-controlled crossover design. Two distinct measures, posterior alpha power and occipital slow cortical potentials (SCPs), were used to reflect raise in excitability and attention-based activation of visual cortical areas. According to the results, performance parameters (reaction time, response variance and error rate) were not affected by MPH. At the neurophysiologic level reflected by reduced alpha power, MPH increased the overall excitability of the occipital cortex, but not the parietal cortex. Before the cued response, MPH reduced alpha power and increased SCPs only before right hand responses, mostly at the right occipital location. It can be concluded that in visuo-motor tasks, MPH has the potency of adjusting the background excitation/inhibition balance of visual areas. Additionally, MPH may raise the attention controlled activation of visual cortical regions, especially during increased response control.

  8. Different categories of living and non-living sound-sources activate distinct cortical networks.

    PubMed

    Engel, Lauren R; Frum, Chris; Puce, Aina; Walker, Nathan A; Lewis, James W

    2009-10-01

    With regard to hearing perception, it remains unclear as to whether, or the extent to which, different conceptual categories of real-world sounds and related categorical knowledge are differentially represented in the brain. Semantic knowledge representations are reported to include the major divisions of living versus non-living things, plus more specific categories including animals, tools, biological motion, faces, and places-categories typically defined by their characteristic visual features. Here, we used functional magnetic resonance imaging (fMRI) to identify brain regions showing preferential activity to four categories of action sounds, which included non-vocal human and animal actions (living), plus mechanical and environmental sound-producing actions (non-living). The results showed a striking antero-posterior division in cortical representations for sounds produced by living versus non-living sources. Additionally, there were several significant differences by category, depending on whether the task was category-specific (e.g. human or not) versus non-specific (detect end-of-sound). In general, (1) human-produced sounds yielded robust activation in the bilateral posterior superior temporal sulci independent of task. Task demands modulated activation of left lateralized fronto-parietal regions, bilateral insular cortices, and sub-cortical regions previously implicated in observation-execution matching, consistent with "embodied" and mirror-neuron network representations subserving recognition. (2) Animal action sounds preferentially activated the bilateral posterior insulae. (3) Mechanical sounds activated the anterior superior temporal gyri and parahippocampal cortices. (4) Environmental sounds preferentially activated dorsal occipital and medial parietal cortices. Overall, this multi-level dissociation of networks for preferentially representing distinct sound-source categories provides novel support for grounded cognition models that may underlie

  9. Stimuli Reduce the Dimensionality of Cortical Activity

    PubMed Central

    Mazzucato, Luca; Fontanini, Alfredo; La Camera, Giancarlo

    2016-01-01

    The activity of ensembles of simultaneously recorded neurons can be represented as a set of points in the space of firing rates. Even though the dimension of this space is equal to the ensemble size, neural activity can be effectively localized on smaller subspaces. The dimensionality of the neural space is an important determinant of the computational tasks supported by the neural activity. Here, we investigate the dimensionality of neural ensembles from the sensory cortex of alert rats during periods of ongoing (inter-trial) and stimulus-evoked activity. We find that dimensionality grows linearly with ensemble size, and grows significantly faster during ongoing activity compared to evoked activity. We explain these results using a spiking network model based on a clustered architecture. The model captures the difference in growth rate between ongoing and evoked activity and predicts a characteristic scaling with ensemble size that could be tested in high-density multi-electrode recordings. Moreover, we present a simple theory that predicts the existence of an upper bound on dimensionality. This upper bound is inversely proportional to the amount of pair-wise correlations and, compared to a homogeneous network without clusters, it is larger by a factor equal to the number of clusters. The empirical estimation of such bounds depends on the number and duration of trials and is well predicted by the theory. Together, these results provide a framework to analyze neural dimensionality in alert animals, its behavior under stimulus presentation, and its theoretical dependence on ensemble size, number of clusters, and correlations in spiking network models. PMID:26924968

  10. Stimuli Reduce the Dimensionality of Cortical Activity.

    PubMed

    Mazzucato, Luca; Fontanini, Alfredo; La Camera, Giancarlo

    2016-01-01

    The activity of ensembles of simultaneously recorded neurons can be represented as a set of points in the space of firing rates. Even though the dimension of this space is equal to the ensemble size, neural activity can be effectively localized on smaller subspaces. The dimensionality of the neural space is an important determinant of the computational tasks supported by the neural activity. Here, we investigate the dimensionality of neural ensembles from the sensory cortex of alert rats during periods of ongoing (inter-trial) and stimulus-evoked activity. We find that dimensionality grows linearly with ensemble size, and grows significantly faster during ongoing activity compared to evoked activity. We explain these results using a spiking network model based on a clustered architecture. The model captures the difference in growth rate between ongoing and evoked activity and predicts a characteristic scaling with ensemble size that could be tested in high-density multi-electrode recordings. Moreover, we present a simple theory that predicts the existence of an upper bound on dimensionality. This upper bound is inversely proportional to the amount of pair-wise correlations and, compared to a homogeneous network without clusters, it is larger by a factor equal to the number of clusters. The empirical estimation of such bounds depends on the number and duration of trials and is well predicted by the theory. Together, these results provide a framework to analyze neural dimensionality in alert animals, its behavior under stimulus presentation, and its theoretical dependence on ensemble size, number of clusters, and correlations in spiking network models.

  11. Stereotypic wheel running decreases cortical activity in mice

    PubMed Central

    Fisher, Simon P.; Cui, Nanyi; McKillop, Laura E.; Gemignani, Jessica; Bannerman, David M.; Oliver, Peter L.; Peirson, Stuart N.; Vyazovskiy, Vladyslav V.

    2016-01-01

    Prolonged wakefulness is thought to gradually increase ‘sleep need' and influence subsequent sleep duration and intensity, but the role of specific waking behaviours remains unclear. Here we report the effect of voluntary wheel running during wakefulness on neuronal activity in the motor and somatosensory cortex in mice. We find that stereotypic wheel running is associated with a substantial reduction in firing rates among a large subpopulation of cortical neurons, especially at high speeds. Wheel running also has longer-term effects on spiking activity across periods of wakefulness. Specifically, cortical firing rates are significantly higher towards the end of a spontaneous prolonged waking period. However, this increase is abolished when wakefulness is dominated by running wheel activity. These findings indicate that wake-related changes in firing rates are determined not only by wake duration, but also by specific waking behaviours. PMID:27748455

  12. Molecular Correlates of Cortical Network Modulation by Long-Term Sensory Experience in the Adult Rat Barrel Cortex

    ERIC Educational Resources Information Center

    Vallès, Astrid; Granic, Ivica; De Weerd, Peter; Martens, Gerard J. M.

    2014-01-01

    Modulation of cortical network connectivity is crucial for an adaptive response to experience. In the rat barrel cortex, long-term sensory stimulation induces cortical network modifications and neuronal response changes of which the molecular basis is unknown. Here, we show that long-term somatosensory stimulation by enriched environment…

  13. Plasticity of recurring spatiotemporal activity patterns in cortical networks

    NASA Astrophysics Data System (ADS)

    Madhavan, Radhika; Chao, Zenas C.; Potter, Steve M.

    2007-09-01

    How do neurons encode and store information for long periods of time? Recurring patterns of activity have been reported in various cortical structures and were suggested to play a role in information processing and memory. To study the potential role of bursts of action potentials in memory mechanisms, we investigated patterns of spontaneous multi-single-unit activity in dissociated rat cortical cultures in vitro. Spontaneous spikes were recorded from networks of approximately 50 000 neurons and glia cultured on a grid of 60 extracellular substrate- embedded electrodes (multi-electrode arrays). These networks expressed spontaneous culture- wide bursting from approximately one week in vitro. During bursts, a large portion of the active electrodes showed elevated levels of firing. Spatiotemporal activity patterns within spontaneous bursts were clustered using a correlation-based clustering algorithm, and the occurrences of these burst clusters were tracked over several hours. This analysis revealed spatiotemporally diverse bursts occurring in well-defined patterns, which remained stable for several hours. Activity evoked by strong local tetanic stimulation resulted in significant changes in the occurrences of spontaneous bursts belonging to different clusters, indicating that the dynamical flow of information in the neuronal network had been altered. The diversity of spatiotemporal structure and long-term stability of spontaneous bursts together with their plastic nature strongly suggests that such network patterns could be used as codes for information transfer and the expression of memories stored in cortical networks.

  14. Individual differences in attentional modulation of cortical responses correlate with selective attention performance.

    PubMed

    Choi, Inyong; Wang, Le; Bharadwaj, Hari; Shinn-Cunningham, Barbara

    2014-08-01

    Many studies have shown that attention modulates the cortical representation of an auditory scene, emphasizing an attended source while suppressing competing sources. Yet, individual differences in the strength of this attentional modulation and their relationship with selective attention ability are poorly understood. Here, we ask whether differences in how strongly attention modulates cortical responses reflect differences in normal-hearing listeners' selective auditory attention ability. We asked listeners to attend to one of three competing melodies and identify its pitch contour while we measured cortical electroencephalographic responses. The three melodies were either from widely separated pitch ranges ("easy trials"), or from a narrow, overlapping pitch range ("hard trials"). The melodies started at slightly different times; listeners attended either the leading or lagging melody. Because of the timing of the onsets, the leading melody drew attention exogenously. In contrast, attending the lagging melody required listeners to direct top-down attention volitionally. We quantified how attention amplified auditory N1 response to the attended melody and found large individual differences in the N1 amplification, even though only correctly answered trials were used to quantify the ERP gain. Importantly, listeners with the strongest amplification of N1 response to the lagging melody in the easy trials were the best performers across other types of trials. Our results raise the possibility that individual differences in the strength of top-down gain control reflect inherent differences in the ability to control top-down attention.

  15. Computational Study of Subdural Cortical Stimulation: Effects of Simulating Anisotropic Conductivity on Activation of Cortical Neurons

    PubMed Central

    Seo, Hyeon; Kim, Donghyeon; Jun, Sung Chan

    2015-01-01

    Subdural cortical stimulation (SuCS) is an appealing method in the treatment of neurological disorders, and computational modeling studies of SuCS have been applied to determine the optimal design for electrotherapy. To achieve a better understanding of computational modeling on the stimulation effects of SuCS, the influence of anisotropic white matter conductivity on the activation of cortical neurons was investigated in a realistic head model. In this paper, we constructed pyramidal neuronal models (layers 3 and 5) that showed primary excitation of the corticospinal tract, and an anatomically realistic head model reflecting complex brain geometry. The anisotropic information was acquired from diffusion tensor magnetic resonance imaging (DT-MRI) and then applied to the white matter at various ratios of anisotropic conductivity. First, we compared the isotropic and anisotropic models; compared to the isotropic model, the anisotropic model showed that neurons were activated in the deeper bank during cathodal stimulation and in the wider crown during anodal stimulation. Second, several popular anisotropic principles were adapted to investigate the effects of variations in anisotropic information. We observed that excitation thresholds varied with anisotropic principles, especially with anodal stimulation. Overall, incorporating anisotropic conductivity into the anatomically realistic head model is critical for accurate estimation of neuronal responses; however, caution should be used in the selection of anisotropic information. PMID:26057524

  16. Correlated activity supports efficient cortical processing

    PubMed Central

    Hung, Chou P.; Cui, Ding; Chen, Yueh-peng; Lin, Chia-pei; Levine, Matthew R.

    2015-01-01

    Visual recognition is a computational challenge that is thought to occur via efficient coding. An important concept is sparseness, a measure of coding efficiency. The prevailing view is that sparseness supports efficiency by minimizing redundancy and correlations in spiking populations. Yet, we recently reported that “choristers”, neurons that behave more similarly (have correlated stimulus preferences and spontaneous coincident spiking), carry more generalizable object information than uncorrelated neurons (“soloists”) in macaque inferior temporal (IT) cortex. The rarity of choristers (as low as 6% of IT neurons) indicates that they were likely missed in previous studies. Here, we report that correlation strength is distinct from sparseness (choristers are not simply broadly tuned neurons), that choristers are located in non-granular output layers, and that correlated activity predicts human visual search efficiency. These counterintuitive results suggest that a redundant correlational structure supports efficient processing and behavior. PMID:25610392

  17. The enhanced cortical activation induced by transcranial direct current stimulation during hand movements.

    PubMed

    Kwon, Yong Hyun; Jang, Sung Ho

    2011-04-01

    The aim of this study is to evaluate whether tDCS applied on the primary motor cortex (M1) in company with hand movements could enhance cortical activation, using functional MRI (fMRI). Twelve right-handed normal subjects were recruited. Real tDCS and sham tDCS with hand movements were applied during fMRI scanning. Subjects performed grasp-release hand movements at a metronome-guided frequency of 1Hz, while direct current with 1.0mA was delivered to the primary motor cortex. The averaged cortical map and the intensity index were compared between real tDCS with hand movements and sham tDCS with hand movements. Our result showed that cortical activation on the primary sensorimotor cortex was observed under both of two conditions; real tDCS with hand movements and sham tDCS with hand movements. Voxel count and peak intensity were 365.10±227.23 and 5.66±1.97, respectively, in the left primary sensorimotor cortex during real tDCS with right hand movements; in contrast, those were 182.20±117.88 and 4.12±0.88, respectively, during sham tDCS with right hand movements. Significant differences in voxel count and peak intensity were observed between real tDCS and sham tDCS (p<0.05). We found that anodal tDCS application during motor task enhanced cortical activation on the underlying targeted motor cortex, compared with the same motor task without tDCS. Therefore, it seemed that tDCS induced more cortical activity and modulated brain function when concurrently applied with motor task.

  18. Network-state modulation of power-law frequency-scaling in visual cortical neurons.

    PubMed

    El Boustani, Sami; Marre, Olivier; Béhuret, Sébastien; Baudot, Pierre; Yger, Pierre; Bal, Thierry; Destexhe, Alain; Frégnac, Yves

    2009-09-01

    Various types of neural-based signals, such as EEG, local field potentials and intracellular synaptic potentials, integrate multiple sources of activity distributed across large assemblies. They have in common a power-law frequency-scaling structure at high frequencies, but it is still unclear whether this scaling property is dominated by intrinsic neuronal properties or by network activity. The latter case is particularly interesting because if frequency-scaling reflects the network state it could be used to characterize the functional impact of the connectivity. In intracellularly recorded neurons of cat primary visual cortex in vivo, the power spectral density of V(m) activity displays a power-law structure at high frequencies with a fractional scaling exponent. We show that this exponent is not constant, but depends on the visual statistics used to drive the network. To investigate the determinants of this frequency-scaling, we considered a generic recurrent model of cortex receiving a retinotopically organized external input. Similarly to the in vivo case, our in computo simulations show that the scaling exponent reflects the correlation level imposed in the input. This systematic dependence was also replicated at the single cell level, by controlling independently, in a parametric way, the strength and the temporal decay of the pairwise correlation between presynaptic inputs. This last model was implemented in vitro by imposing the correlation control in artificial presynaptic spike trains through dynamic-clamp techniques. These in vitro manipulations induced a modulation of the scaling exponent, similar to that observed in vivo and predicted in computo. We conclude that the frequency-scaling exponent of the V(m) reflects stimulus-driven correlations in the cortical network activity. Therefore, we propose that the scaling exponent could be used to read-out the "effective" connectivity responsible for the dynamical signature of the population signals measured

  19. Stochastic Resonance Modulates Neural Synchronization within and between Cortical Sources

    PubMed Central

    Ward, Lawrence M.; MacLean, Shannon E.; Kirschner, Aaron

    2010-01-01

    Neural synchronization is a mechanism whereby functionally specific brain regions establish transient networks for perception, cognition, and action. Direct addition of weak noise (fast random fluctuations) to various neural systems enhances synchronization through the mechanism of stochastic resonance (SR). Moreover, SR also occurs in human perception, cognition, and action. Perception, cognition, and action are closely correlated with, and may depend upon, synchronized oscillations within specialized brain networks. We tested the hypothesis that SR-mediated neural synchronization occurs within and between functionally relevant brain areas and thus could be responsible for behavioral SR. We measured the 40-Hz transient response of the human auditory cortex to brief pure tones. This response arises when the ongoing, random-phase, 40-Hz activity of a group of tuned neurons in the auditory cortex becomes synchronized in response to the onset of an above-threshold sound at its “preferred” frequency. We presented a stream of near-threshold standard sounds in various levels of added broadband noise and measured subjects' 40-Hz response to the standards in a deviant-detection paradigm using high-density EEG. We used independent component analysis and dipole fitting to locate neural sources of the 40-Hz response in bilateral auditory cortex, left posterior cingulate cortex and left superior frontal gyrus. We found that added noise enhanced the 40-Hz response in all these areas. Moreover, added noise also increased the synchronization between these regions in alpha and gamma frequency bands both during and after the 40-Hz response. Our results demonstrate neural SR in several functionally specific brain regions, including areas not traditionally thought to contribute to the auditory 40-Hz transient response. In addition, we demonstrated SR in the synchronization between these brain regions. Thus, both intra- and inter-regional synchronization of neural activity are

  20. Molecular correlates of cortical network modulation by long-term sensory experience in the adult rat barrel cortex

    PubMed Central

    Vallès, Astrid; Granic, Ivica; De Weerd, Peter; Martens, Gerard J.M.

    2014-01-01

    Modulation of cortical network connectivity is crucial for an adaptive response to experience. In the rat barrel cortex, long-term sensory stimulation induces cortical network modifications and neuronal response changes of which the molecular basis is unknown. Here, we show that long-term somatosensory stimulation by enriched environment up-regulates cortical expression of neuropeptide mRNAs and down-regulates immediate-early gene (IEG) mRNAs specifically in the barrel cortex, and not in other brain regions. The present data suggest a central role of neuropeptides in the fine-tuning of sensory cortical circuits by long-term experience. PMID:25171421

  1. Acupuncture modulates cortical thickness and functional connectivity in knee osteoarthritis patients

    PubMed Central

    Chen, Xiaoyan; Spaeth, Rosa B.; Retzepi, Kallirroi; Ott, Daniel; Kong, Jian

    2014-01-01

    In this study, we investigated cortical thickness and functional connectivity across longitudinal acupuncture treatments in patients with knee osteoarthritis (OA). Over a period of four weeks (six treatments), we collected resting state functional magnetic resonance imaging (fMRI) scans from 30 patients before their first, third and sixth treatments. Clinical outcome showed a significantly greater Knee Injury and Osteoarthritis Outcome Score (KOOS) pain score (improvement) with verum acupuncture compared to the sham acupuncture. Longitudinal cortical thickness analysis showed that the cortical thickness at left posterior medial prefrontal cortex (pMPFC) decreased significantly in the sham group across treatment sessions as compared with verum group. Resting state functional connectivity (rsFC) analysis using the left pMPFC as a seed showed that after longitudinal treatments, the rsFC between the left pMPFC and the rostral anterior cingulate cortex (rACC), medial frontal pole (mFP) and periaquiduct grey (PAG) are significantly greater in the verum acupuncture group as compared with the sham group. Our results suggest that acupuncture may achieve its therapeutic effect on knee OA pain by preventing cortical thinning and decreases in functional connectivity in major pain related areas, therefore modulating pain in the descending pain modulatory pathway. PMID:25258037

  2. Golli Myelin Basic Proteins Modulate Voltage-Operated Ca(++) Influx and Development in Cortical and Hippocampal Neurons.

    PubMed

    Vt, Cheli; DA, Santiago González; V, Spreuer; V, Handley; At, Campagnoni; Pm, Paez

    2016-10-01

    The golli proteins, products of the myelin basic protein gene, are widely expressed in oligodendrocyte progenitor cells and neurons during the postnatal development of the brain. While golli appears to be important for oligodendrocyte migration and differentiation, its function in neuronal development is completely unknown. We have found that golli proteins function as new and novel modulators of voltage-operated Ca(++) channels (VOCCs) in neurons. In vitro, golli knock-out (KO) neurons exhibit decreased Ca(++) influx after plasma membrane depolarization and a substantial maturational delay. Increased expression of golli proteins enhances L-type Ca(++) entry and processes outgrowth in cortical neurons, and pharmacological activation of L-type Ca(++) channels stimulates maturation and prevents cell death in golli-KO neurons. In situ, Ca(++) influx mediated by L-type VOCCs was significantly decreased in cortical and hippocampal neurons of the golli-KO brain. These Ca(++) alterations affect cortical and hippocampal development and the proliferation and survival of neural progenitor cells during the postnatal development of the golli-KO brain. The CA1/3 sections and the dentate gyrus of the hippocampus were reduced in the golli-KO mice as well as the density of dendrites in the somatosensory cortex. Furthermore, the golli-KO mice display abnormal behavior including deficits in episodic memory and reduced anxiety. Because of the expression of the golli proteins within neurons in learning and memory centers of the brain, this work has profound implication in neurodegenerative diseases and neurological disorders.

  3. Modulation of cortical motor evoked potential after stroke during electrical stimulation of the lateral cerebellar nucleus

    PubMed Central

    Park, Hyun-Joo; Furmaga, Havan; Cooperrider, Jessica; Gale, John T.; Baker, Kenneth B.; Machado, Andre G.

    2015-01-01

    Background Deep brain stimulation (DBS) targeting the dentato-thalamo-cortical (DTC) pathway at its origin in the lateral cerebellar nucleus (LCN) has been shown to enhance motor recovery in a rodent model of cortical ischemia. LCN DBS also yielded frequency specific changes in motor cortex excitability in the normal brain, indexed by motor evoked potential (MEP) amplitude. Objective To investigate the effect of cortical stroke on cortical motor excitability in a rodent ischemia model and to measure the effects of LCN DBS on post-ischemia excitability as a function of stimulation parameters. Methods Adult Sprague-Dawley rats were divided into two groups: naïve and stroke, with cortical ischemia induced through multiple, unilateral endothelin-1 injections. All animals were implanted with a bipolar electrode in the LCN opposite the affected hemisphere. MEPs were elicited from the affected hemisphere using intracortical microstimulation (ICMS) techniques. Multiple LCN DBS parameters were examined, including isochronal stimulation at 20, 30, 50, and 100 Hz as well as a novel burst stimulation pattern. Results ICMS-evoked MEPs were reduced in stroke (n=10) relative to naïve (n=12) animals. However, both groups showed frequency-dependent augmentation of cortical excitability in response to LCN DBS. In the naïve group, LCN DBS increased MEPs by 22–58%, while in the stroke group, MEPs were enhanced by 9–41% compared to OFF DBS conditions. Conclusions Activation of the DTC pathway increases cortical excitability in both naïve and post-stroke animals. These effects may underlie, at least partially, functional reorganization and therapeutic benefits associated with chronic LCN DBS in post-stroke animals. PMID:26215752

  4. Dopamine replacement modulates oscillatory coupling between premotor and motor cortical areas in Parkinson's disease.

    PubMed

    Herz, Damian Marc; Florin, Esther; Christensen, Mark Schram; Reck, Christiane; Barbe, Michael Thomas; Tscheuschler, Maike Karoline; Tittgemeyer, Marc; Siebner, Hartwig Roman; Timmermann, Lars

    2014-11-01

    Efficient neural communication between premotor and motor cortical areas is critical for manual motor control. Here, we used high-density electroencephalography to study cortical connectivity in patients with Parkinson's disease (PD) and age-matched healthy controls while they performed repetitive movements of the right index finger at maximal repetition rate. Multiple source beamformer analysis and dynamic causal modeling were used to assess oscillatory coupling between the lateral premotor cortex (lPM), supplementary motor area (SMA), and primary motor cortex (M1) in the contralateral hemisphere. Elderly healthy controls showed task-related modulation in connections from lPM to SMA and M1, mainly within the γ-band (>30 Hz). Nonmedicated PD patients also showed task-related γ-γ coupling from lPM to M1, but γ coupling from lPM to SMA was absent. Levodopa reinstated physiological γ-γ coupling from lPM to SMA and significantly strengthened coupling in the feedback connection from M1 to lPM expressed as β-β as well as θ-β coupling. Enhancement in cross-frequency θ-β coupling from M1 to lPM was correlated with levodopa-induced improvement in motor function. The results show that PD is associated with an altered neural communication between premotor and motor cortical areas, which can be modulated by dopamine replacement.

  5. Serotonin Signaling Modulates the Effects of Familial Risk for Depression on Cortical Thickness

    PubMed Central

    Bansal, Ravi; Peterson, Bradley S.; Gingrich, Jay; Hao, Xuejun; Odgerel, Zagaa; Warner, Virginia; Wickramaratne, Priya J.; Talati, Ardesheer; Ansorge, Mark; Brown, Alan S.; Sourander, Andre; Weissman, Myrna M.

    2016-01-01

    Depression is a highly familial and a heritable illness that is more prevalent in the biological offspring of the depressed individuals than in the general population. In a 3-generation, 30-year, longitudinal study of individuals at either a high(HR) or a low(LR) familial risk for depression, we previously showed cortical thinning in the right hemisphere was an endophenotype for the familial risk. In this study, we assessed whether the effects of familial risk were modulated by the serotonin-transporter-linked polymorphic region (5-HTTLPR). We measured cortical thickness using MRI of the brain and associated it with 5-HTTLPR polymorphism in 76 HR and 53 LR individuals. We studied the effects of genotype and gene-by-risk interaction on cortical thickness while controlling for the confounding effects of age and gender, and for the familial relatedness by applying a variance component model with random effects for genotype. The results showed significant effects of gene-by-risk interaction on thickness: The “s” allele was associated with thinner cortex in the LR individuals whereas with thicker cortex in the HR individuals. The opposing gene effects across the two risk groups were likely due to either epistatic effects and/or differing modulation of the neural plasticity by the altered 5-HT signaling in utero. PMID:26774425

  6. Self-organizing model of motor cortical activities during drawing

    NASA Astrophysics Data System (ADS)

    Lin, Siming H.; Si, Jennie; Schwartz, Andrew B.

    1996-05-01

    The population vector algorithm has been developed to combine the simultaneous direction- related activities of a population of motor cortical neurons to predict the trajectory of the arm movement. In our study, we consider a self-organizing model of a neural representation of the arm trajectory based on neuronal discharge rates. Self-organizing feature mapping (SOFM) is used to select the optimal set of weights in the model to determine the contribution of individual neuron to the overall movement. The correspondence between the movement directions and the discharge patterns of the motor cortical neurons is established in the output map. The topology preserving property of the SOFM is used to analyze real recorded data of a behavior monkey. The data used in this analysis were taken while the monkey was drawing spirals and doing the center out movement. Using such a statistical model, the monkey's arm moving directions could be well predicted based on the motor cortex neuronal firing information.

  7. Chaos-induced modulation of reliability boosts output firing rate in downstream cortical areas

    NASA Astrophysics Data System (ADS)

    Tiesinga, P. H.

    2004-03-01

    The reproducibility of neural spike train responses to an identical stimulus across different presentations (trials) has been studied extensively. Reliability, the degree of reproducibility of spike trains, was found to depend in part on the amplitude and frequency content of the stimulus [J. Hunter and J. Milton, J. Neurophysiol. 90, 387 (2003)]. The responses across different trials can sometimes be interpreted as the response of an ensemble of similar neurons to a single stimulus presentation. How does the reliability of the activity of neural ensembles affect information transmission between different cortical areas? We studied a model neural system consisting of two ensembles of neurons with Hodgkin-Huxley-type channels. The first ensemble was driven by an injected sinusoidal current that oscillated in the gamma-frequency range (40 Hz) and its output spike trains in turn drove the second ensemble by fast excitatory synaptic potentials with short term depression. We determined the relationship between the reliability of the first ensemble and the response of the second ensemble. In our paradigm the neurons in the first ensemble were initially in a chaotic state with unreliable and imprecise spike trains. The neurons became entrained to the oscillation and responded reliably when the stimulus power was increased by less than 10%. The firing rate of the first ensemble increased by 30%, whereas that of the second ensemble could increase by an order of magnitude. We also determined the response of the second ensemble when its input spike trains, which had non-Poisson statistics, were replaced by an equivalent ensemble of Poisson spike trains. The resulting output spike trains were significantly different from the original response, as assessed by the metric introduced by Victor and Purpura [J. Neurophysiol. 76, 1310 (1996)]. These results are a proof of principle that weak temporal modulations in the power of gamma-frequency oscillations in a given cortical area

  8. Different categories of living and non-living sound-sources activate distinct cortical networks

    PubMed Central

    Engel, Lauren R.; Frum, Chris; Puce, Aina; Walker, Nathan A.; Lewis, James W.

    2009-01-01

    With regard to hearing perception, it remains unclear as to whether, or the extent to which, different conceptual categories of real-world sounds and related categorical knowledge are differentially represented in the brain. Semantic knowledge representations are reported to include the major divisions of living versus non-living things, plus more specific categories including animals, tools, biological motion, faces, and places—categories typically defined by their characteristic visual features. Here, we used functional magnetic resonance imaging (fMRI) to identify brain regions showing preferential activity to four categories of action sounds, which included non-vocal human and animal actions (living), plus mechanical and environmental sound-producing actions (non-living). The results showed a striking antero-posterior division in cortical representations for sounds produced by living versus non-living sources. Additionally, there were several significant differences by category, depending on whether the task was category-specific (e.g. human or not) versus non-specific (detect end-of-sound). In general, (1) human-produced sounds yielded robust activation in the bilateral posterior superior temporal sulci independent of task. Task demands modulated activation of left-lateralized fronto-parietal regions, bilateral insular cortices, and subcortical regions previously implicated in observation-execution matching, consistent with “embodied” and mirror-neuron network representations subserving recognition. (2) Animal action sounds preferentially activated the bilateral posterior insulae. (3) Mechanical sounds activated the anterior superior temporal gyri and parahippocampal cortices. (4) Environmental sounds preferentially activated dorsal occipital and medial parietal cortices. Overall, this multi-level dissociation of networks for preferentially representing distinct sound-source categories provides novel support for grounded cognition models that may

  9. Modulation of Specific Sensory Cortical Areas by Segregated Basal Forebrain Cholinergic Neurons Demonstrated by Neuronal Tracing and Optogenetic Stimulation in Mice

    PubMed Central

    Chaves-Coira, Irene; Barros-Zulaica, Natali; Rodrigo-Angulo, Margarita; Núñez, Ángel

    2016-01-01

    Neocortical cholinergic activity plays a fundamental role in sensory processing and cognitive functions. Previous results have suggested a refined anatomical and functional topographical organization of basal forebrain (BF) projections that may control cortical sensory processing in a specific manner. We have used retrograde anatomical procedures to demonstrate the existence of specific neuronal groups in the BF involved in the control of specific sensory cortices. Fluoro-Gold (FlGo) and Fast Blue (FB) fluorescent retrograde tracers were deposited into the primary somatosensory (S1) and primary auditory (A1) cortices in mice. Our results revealed that the BF is a heterogeneous area in which neurons projecting to different cortical areas are segregated into different neuronal groups. Most of the neurons located in the horizontal limb of the diagonal band of Broca (HDB) projected to the S1 cortex, indicating that this area is specialized in the sensory processing of tactile stimuli. However, the nucleus basalis magnocellularis (B) nucleus shows a similar number of cells projecting to the S1 as to the A1 cortices. In addition, we analyzed the cholinergic effects on the S1 and A1 cortical sensory responses by optogenetic stimulation of the BF neurons in urethane-anesthetized transgenic mice. We used transgenic mice expressing the light-activated cation channel, channelrhodopsin-2, tagged with a fluorescent protein (ChR2-YFP) under the control of the choline-acetyl transferase promoter (ChAT). Cortical evoked potentials were induced by whisker deflections or by auditory clicks. According to the anatomical results, optogenetic HDB stimulation induced more extensive facilitation of tactile evoked potentials in S1 than auditory evoked potentials in A1, while optogenetic stimulation of the B nucleus facilitated either tactile or auditory evoked potentials equally. Consequently, our results suggest that cholinergic projections to the cortex are organized into segregated

  10. Modulation of NMDA and AMPA-mediated synaptic transmission by CB1 receptors in frontal cortical pyramidal cells.

    PubMed

    Li, Qiang; Yan, Haidun; Wilson, Wilkie A; Swartzwelder, H Scott

    2010-06-25

    Although the endogenous cannabinoid system modulates a variety of physiological and pharmacological processes, the specific role of cannabinoid CB1 receptors in the modulation of glutamatergic neurotransmission and neural plasticity is not well understood. Using whole-cell patch clamp recording techniques, evoked or spontaneous excitatory postsynaptic currents (eEPSCs or sEPSCs) were recorded from visualized, layer II/III pyramidal cells in frontal cortical slices from rat brain. Bath application of the CB1 receptor agonist, WIN 55212-2 (WIN), reduced the amplitude of NMDA receptor-mediated EPSCs in a concentration-dependent manner. When co-applied with the specific CB1 antagonists, AM251 or AM281, WIN did not suppress NMDA receptor-mediated EPSCs. WIN also reduced the amplitude of evoked AMPA receptor-mediated EPSCs, an effect that was also reversed by AM251. Both the frequency and amplitude of spontaneous AMPA receptor-mediated EPSCs were significantly reduced by WIN. In contrast, WIN reduced the frequency, but not the amplitude of miniature EPSCs, suggesting that the suppression of glutamatergic activity by CB1 receptors in the frontal neocortex is mediated by a presynaptic mechanism. Taken together, these data indicate a critical role for endocannabinoid signaling in the regulation of excitatory synaptic transmission in frontal neocortex, and suggest a possible neuronal mechanism whereby THC regulates cortical function.

  11. Modulation by cyclic AMP and phorbol myristate acetate of cephaloridine-induced injury in rat renal cortical slices.

    PubMed

    Kohda, Y; Gemba, M

    2001-01-01

    Intracellular signaling pathways of cAMP and protein kinase C (PKC) have been suggested to modulate the generation of free radicals. We investigated the effects of cAMP and phorbol myristate acetate (PMA), a PKC activator, on cephaloridine (CER)-induced renal cell injury, which has been reported to be due to the generation of free radicals. Incubation of rat renal cortical slices with CER resulted in increases in lipid peroxidation and lactate dehydrogenase (LDH) release and in decreases in gluconeogenesis and p-aminohippurate (PAH) accumulation in rat renal cortical slices, suggesting free radical-induced injury in slices exposed to CER. A derivative of cAMP ameliorated not only the increase in lipid peroxidation but also the renal cell damage induced by CER. This amelioration by a cAMP derivative of lipid peroxidation and renal cell damage caused by CER was blocked by KT 5720, a protein kinase A (PKA) inhibitor. Lipid peroxidation and the indices of cell injury were increased by PMA. PMA also enhanced CER-induced lipid peroxidation and cell damage in the slices. This enhancement by PMA of CER-induced injury was blocked by H-7, a PKC inhibitor. These results indicated that intracellular signaling pathways of cAMP and PKC modulate free radical-mediated nephrotoxicity induced by CER.

  12. 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.

  13. Specific modulation of spinal and cortical excitabilities during lengthening and shortening submaximal and maximal contractions in plantar flexor muscles.

    PubMed

    Duclay, Julien; Pasquet, Benjamin; Martin, Alain; Duchateau, Jacques

    2014-12-15

    This study investigated the influence of the torque produced by plantar flexor muscles on cortical and spinal excitability during lengthening and shortening voluntary contractions. To that purpose, modulations of motor-evoked potential (MEP) and Hoffmann (H) reflex were compared in the soleus (SOL) and medial gastrocnemius (MG) during anisometric submaximal and maximal voluntary contraction (MVC) of the plantar flexor muscles. For the submaximal shortening and lengthening contractions, the target torque was set at 50% of their respective MVC force. The results indicate that the amplitudes of both MEP and H-reflex responses, normalized to the maximal M wave, were significantly (P < 0.05) lower during lengthening compared with shortening submaximal contraction. For these two parameters, the reduction reached, respectively, 22.1 and 31.9% for the SOL and 34.5 and 29.3% for the MG. During MVC, normalized MEP and H reflex of the SOL were both reduced significantly by 19.9% (P < 0.05) and 29.9% (P < 0.001) during lengthening and shortening contraction, respectively, whereas no significant change (P > 0.05) was observed for MG. In addition, the silent period in the ongoing electromyogram (EMG) activity following the MEP was significantly (P < 0.01) briefer during lengthening than shortening contractions but did not differ (P > 0.05) between contraction intensities and muscles. Together, these results indicate that cortical and spinal mechanisms involved in the modulation of muscle activation during shortening and lengthening contractions differ between synergistic muscles according to the torque produced. Data further document previous studies reporting that the specific modulation of muscle activation during lengthening contraction is not torque dependent.

  14. Macroeconomic Activity Module - NEMS Documentation

    EIA Publications

    2016-01-01

    Documents the objectives, analytical approach, and development of the National Energy Modeling System (NEMS) Macroeconomic Activity Module (MAM) used to develop the Annual Energy Outlook for 2016 (AEO2016). The report catalogues and describes the module assumptions, computations, methodology, parameter estimation techniques, and mainframe source code

  15. Cortical activity predicts good variation in human motor output.

    PubMed

    Babikian, Sarine; Kanso, Eva; Kutch, Jason J

    2017-02-04

    Human movement patterns have been shown to be particularly variable if many combinations of activity in different muscles all achieve the same task goal (i.e., are goal-equivalent). The nervous system appears to automatically vary its output among goal-equivalent combinations of muscle activity to minimize muscle fatigue or distribute tissue loading, but the neural mechanism of this "good" variation is unknown. Here we use a bimanual finger task, electroencephalography (EEG), and machine learning to determine if cortical signals can predict goal-equivalent variation in finger force output. 18 healthy participants applied left and right index finger forces to repeatedly perform a task that involved matching a total (sum of right and left) finger force. As in previous studies, we observed significantly more variability in goal-equivalent muscle activity across task repetitions compared to variability in muscle activity that would not achieve the goal: participants achieved the task in some repetitions with more right finger force and less left finger force (right > left) and in other repetitions with less right finger force and more left finger force (left > right). We found that EEG signals from the 500 milliseconds (ms) prior to each task repetition could make a significant prediction of which repetitions would have right > left and which would have left > right. We also found that cortical maps of sites contributing to the prediction contain both motor and pre-motor representation in the appropriate hemisphere. Thus, goal-equivalent variation in motor output may be implemented at a cortical level.

  16. Aging process alters hippocampal and cortical secretase activities of Wistar rats.

    PubMed

    Bertoldi, Karine; Cechinel, Laura Reck; Schallenberger, Bruna; Meireles, Louisiana; Basso, Carla; Lovatel, Gisele Agustini; Bernardi, Lisiane; Lamers, Marcelo Lazzaron; Siqueira, Ionara Rodrigues

    2017-01-15

    A growing body of evidence has demonstrated amyloid plaques in aged brain; however, little attention has been given to amyloid precursor protein (APP) processing machinery during the healthy aging process. The amyloidogenic and non-amyloidogenic pathways, represented respectively by β- and α-secretases (BACE and TACE), are responsible for APP cleavage. Our working hypothesis is that the normal aging process could imbalance amyloidogenic and non-amyloidogenic pathways specifically BACE and TACE activities. Besides, although it has been showed that exercise can modulate secretase activities in Alzheimer Disease models the relationship between exercise effects and APP processing during healthy aging process is rarely studied. Our aim was to investigate the aging process and the exercise effects on cortical and hippocampal BACE and TACE activities and aversive memory performance. Young adult and aged Wistar rats were subjected to an exercise protocol (20min/day for 2 weeks) and to inhibitory avoidance task. Biochemical parameters were evaluated 1h and 18h after the last exercise session in order to verify transitory and delayed exercise effects. Aged rats exhibited impaired aversive memory and diminished cortical TACE activity. Moreover, an imbalance between TACE and BACE activities in favor of BACE activity was observed in aged brain. Moderate treadmill exercise was unable to alter secretase activities in any brain areas or time points evaluated. Our results suggest that aging-related aversive memory decline is partly linked to decreased cortical TACE activity. Additionally, an imbalance between secretase activities can be related to the higher vulnerability to neurodegenerative diseases induced by aging.

  17. Alteration of Electro-Cortical Activity in Microgravity

    NASA Astrophysics Data System (ADS)

    Schneider, Stefan; Brummer, Vera; Carnahan, Heather; Askew, Christopher D.; Guardiera, Simon; Struder, Heiko K.

    2008-06-01

    There is growing interest in the effects of weightlessness on central nervous system (CNS) activity. Due to technical and logistical limitations it presently seems impossible to apply imaging techniques as fMRI or PET in weightless environments e.g. on ISS or during parabolic flights. Within this study we evaluated changes in brain cortical activity using low resolution brain electromagnetic tomography (LORETA) during parabolic flights. Results showed a distinct inhibition of right frontal area activity >12Hz during phases of microgravity compared to normal gravity. We conclude that the inhibition of high frequency frontal activity during microgravity may serve as a marker of emotional anxiety and/or indisposition associated with weightlessness. This puts a new light on the debate as to whether cognitive and sensorimotor impairments are attributable to primary physiological effects or secondary psychological effects of a weightless environment.

  18. EEG frequency tagging to explore the cortical activity related to the tactile exploration of natural textures

    PubMed Central

    Moungou, Athanasia; Thonnard, Jean-Louis; Mouraux, André

    2016-01-01

    When sliding our fingertip against a textured surface, complex vibrations are produced in the skin. It is increasingly recognised that the neural transduction and processing of these vibrations plays an important role in the dynamic tactile perception of textures. The aim of the present study was to develop a novel means to tag the cortical activity related to the processing of these vibrations, by periodically modulating the amplitude of texture exploration-induced vibrations such as to record a steady-state evoked potential (SS-EP). The EEG was recorded while the right index fingertip was scanned against four different textures using a constant exploration velocity. Amplitude modulation of the elicited vibrations was achieved by periodically modulating the force applied against the finger. Frequency analysis of the recorded EEG signals showed that modulation of the vibrations induced by the fingertip-texture interactions elicited an SS-EP at the frequency of modulation (3 Hz) as well as its second harmonic (6 Hz), maximal over parietal regions contralateral to the stimulated side. Textures generating stronger vibrations also generated SS-EPs of greater magnitude. Our results suggest that frequency tagging using SS-EPs can be used to isolate and explore the brain activity related to the tactile exploration of natural textures. PMID:26853820

  19. Requirement of ERK activation for visual cortical plasticity.

    PubMed

    Di Cristo, G; Berardi, N; Cancedda, L; Pizzorusso, T; Putignano, E; Ratto, G M; Maffei, L

    2001-06-22

    Experience-dependent plasticity in the developing visual cortex depends on electrical activity and molecular signals involved in stabilization or removal of inputs. Extracellular signal-regulated kinase 1,2 (also called p42/44 mitogen-activated protein kinase) activation in the cortex is regulated by both factors. We show that two different inhibitors of the ERK pathway suppress the induction of two forms of long-term potentiation (LTP) in rat cortical slices and that their intracortical administration to monocularly deprived rats prevents the shift in ocular dominance towards the nondeprived eye. These results demonstrate that the ERK pathway is necessary for experience-dependent plasticity and for LTP of synaptic transmission in the developing visual cortex.

  20. Spontaneous cortical activity in awake monkeys composed of neuronal avalanches.

    PubMed

    Petermann, Thomas; Thiagarajan, Tara C; Lebedev, Mikhail A; Nicolelis, Miguel A L; Chialvo, Dante R; Plenz, Dietmar

    2009-09-15

    Spontaneous neuronal activity is an important property of the cerebral cortex but its spatiotemporal organization and dynamical framework remain poorly understood. Studies in reduced systems--tissue cultures, acute slices, and anesthetized rats--show that spontaneous activity forms characteristic clusters in space and time, called neuronal avalanches. Modeling studies suggest that networks with this property are poised at a critical state that optimizes input processing, information storage, and transfer, but the relevance of avalanches for fully functional cerebral systems has been controversial. Here we show that ongoing cortical synchronization in awake rhesus monkeys carries the signature of neuronal avalanches. Negative LFP deflections (nLFPs) correlate with neuronal spiking and increase in amplitude with increases in local population spike rate and synchrony. These nLFPs form neuronal avalanches that are scale-invariant in space and time and with respect to the threshold of nLFP detection. This dimension, threshold invariance, describes a fractal organization: smaller nLFPs are embedded in clusters of larger ones without destroying the spatial and temporal scale-invariance of the dynamics. These findings suggest an organization of ongoing cortical synchronization that is scale-invariant in its three fundamental dimensions--time, space, and local neuronal group size. Such scale-invariance has ontogenetic and phylogenetic implications because it allows large increases in network capacity without a fundamental reorganization of the system.

  1. Abstract art and cortical motor activation: an EEG study

    PubMed Central

    Umilta', M. Alessandra; Berchio, Cristina; Sestito, Mariateresa; Freedberg, David; Gallese, Vittorio

    2012-01-01

    The role of the motor system in the perception of visual art remains to be better understood. Earlier studies on the visual perception of abstract art (from Gestalt theory, as in Arnheim, 1954 and 1988, to balance preference studies as in Locher and Stappers, 2002, and more recent work by Locher et al., 2007; Redies, 2007, and Taylor et al., 2011), neglected the question, while the field of neuroesthetics (Ramachandran and Hirstein, 1999; Zeki, 1999) mostly concentrated on figurative works. Much recent work has demonstrated the multimodality of vision, encompassing the activation of motor, somatosensory, and viscero-motor brain regions. The present study investigated whether the observation of high-resolution digitized static images of abstract paintings by Lucio Fontana is associated with specific cortical motor activation in the beholder's brain. Mu rhythm suppression was evoked by the observation of original art works but not by control stimuli (as in the case of graphically modified versions of these works). Most interestingly, previous visual exposure to the stimuli did not affect the mu rhythm suppression induced by their observation. The present results clearly show the involvement of the cortical motor system in the viewing of static abstract art works. PMID:23162456

  2. Plasminogen activator activity in cortical granules of bovine oocytes during in vitro maturation.

    PubMed

    Rekkas, Constantinos A; Besenfelder, Urban; Havlicek, Vitezslav; Vainas, Emmanuel; Brem, Gottfried

    2002-04-15

    In this study, we provide evidence that plasminogen activator of tissue-type (t-PA), at least, is present in extracts of bovine oocyte cortical granules, and that its activity varies significantly with the duration of oocyte in vitro maturation. Cortical granules were collected from bovine oocytes by means of micromanipulation, after 0, 12, or 24 h of IVM. Our results show that plasminogen activator activity of cortical granule extracts was significantly higher after 24 h of IVM than after 12 h of IVM or before IVM. This activity was apparently due, at least partly, to tissue-type plasminogen activator as shown immunologically. No evidence was found for the presence of urokinase-type plasminogen activator, plasminogen activator inhibitors or plasmin inhibitors in bovine oocyte cortical granule extracts. Our findings further support the hypothesis that t-PA activity of oocyte origin may have a role in oocyte maturation or fertilization, as well as in post-fertilization events, such as cortical reaction and formation of the zona block to polyspermy.

  3. Levodopa influences striatal activity but does not affect cortical hyper-activity in Parkinson's disease.

    PubMed

    Martinu, K; Degroot, C; Madjar, C; Strafella, A P; Monchi, O

    2012-02-01

    Motor studies of Parkinson's disease (PD) have shown cortical hypo-activity in relation to nigrostriatal dopamine depletion. Cognitive studies also identified increased cortical activity in PD. We have previously suggested that the hypo-activity/hyper-activity patterns observed in PD are related to the striatal contribution. Tasks that recruit the striatum in control participants are associated with cortical hypo-activity in patients with PD, whereas tasks that do not result in cortical hyper-activity. The putamen, a structure affected by the neurodegeneration observed in PD, shows increased activation for externally-triggered (ET) and self-initiated (SI) movements. The first goal of this study was to evaluate the effect of levodopa on the putamen's response to ET and SI movements. Our second goal was to assess the effect of levodopa on the hypo-activity/hyper-activity patterns in cortical areas. Patients with PD on and off levodopa and healthy volunteers performed SI, ET and control finger movements during functional magnetic resonance imaging. Healthy participants displayed significant differences in putamen activity in ET and SI movements. These differences were reduced in patients off medication, with non-task-specific increases in activity after levodopa administration. Furthermore, the ventrolateral prefrontal cortex showed significant increases in activity during SI movements in healthy controls, whereas it was hypo-active in PD. This region showed significantly increased activity during ET movements in patients off medication. Levodopa had no effect on this discrepancy. Our results suggest that dopamine replacement therapy has a non-task-specific effect on motor corticostriatal regions, and support the hypothesis that increases and decreases in cortical activity in PD are related to the mesocortical dopamine pathway imbalance.

  4. Monitoring for target objects: activation of right frontal and parietal cortices with increasing time on task.

    PubMed

    Coull, J T; Frackowiak, R S; Frith, C D

    1998-12-01

    The right prefrontal and parietal cortices have been implicated in attentional processing in both neuropsychological and functional neuroimaging literature. However, attention is a heterogeneous collection of processes, each of which may be underpinned by different neural networks. These attentional networks may interact, such that engaging one type of attentional process could influence the efficiency of another via overlapping neural substrates. We investigated the hypothesis that right frontal and parietal cortices provide the neuroanatomical location of the functional interaction between sustained attention and the process of selectively monitoring for target objects. Six healthy volunteers performed one of two tasks which required either selective or non-selective responding. The task lasted continuously for 18 min, during which time 3 Positron Emission Tomography (PET) scans were acquired for each task. This was repeated to obtain 12 PET measurements of regional cerebral blood flow (rCBF) for each subject. The right inferior frontal and parietal cortices were differentially activated by increasing time on task during the selective (S) vs non-selective (NS) task. Specifically, rCBF decreased with increasing time spent performing the NS task but not the S task. This result suggests that the normal deactivation in these areas as time on task increases is counteracted by the extra cognitive demands of selectively responding to target objects. Therefore, we have confirmed our hypothesis that right frontal and parietal cortices provide the neuroanatomical location for the modulation of object selection by sustained attention. We also identified the neuroanatomical correlates of each process separately, and confirmed earlier reports of prefrontal cortex and anterior cingulate activation associated with selective responding, and a fronto-parietal-thalamic network associated with sustained attention.

  5. Epileptiform activity in the mouse visual cortex interferes with cortical processing in connected areas

    PubMed Central

    Petrucco, L.; Pracucci, E.; Brondi, M.; Ratto, G. M.; Landi, S.

    2017-01-01

    Epileptiform activity is associated with impairment of brain function even in absence of seizures, as demonstrated by failures in various testing paradigm in presence of hypersynchronous interictal spikes (ISs). Clinical evidence suggests that cognitive deficits might be directly caused by the anomalous activity rather than by its underlying etiology. Indeed, we seek to understand whether ISs interfere with neuronal processing in connected areas not directly participating in the hypersynchronous activity in an acute model of epilepsy. Here we cause focal ISs in the visual cortex of anesthetized mice and we determine that, even if ISs do not invade the opposite hemisphere, the local field potential is subtly disrupted with a modulation of firing probability imposed by the contralateral IS activity. Finally, we find that visual processing is altered depending on the temporal relationship between ISs and stimulus presentation. We conclude that focal ISs interact with normal cortical dynamics far from the epileptic focus, disrupting endogenous oscillatory rhythms and affecting information processing. PMID:28071688

  6. Localization of visually evoked cortical activity in humans.

    PubMed

    Srebro, R

    1985-03-01

    The locations of cortical activity evoked by visual stimuli presented at different positions in the visual field are deduced from the scalp topography of visually evoked potentials in humans. To accomplish this, the Laplacian evoked potential is measured using a multi-electrode array. It is shown that the Laplacian response has the following useful attributes for this purpose. It is reference-free. Its spatial resolution is approximately 2 cm referred to the surface of the cortex. Its spatial sensitivity characteristic is that of a spatial band-pass filter. It is relatively insensitive to source--sink configurations that are oriented tangentially to the surface of the scalp. Only modest assumptions about the source--sink configuration are required to obtain a unique inversion of the scalp topography. Stimuli consisting of checkerboard-filled octant or annular octant segments are presented as appearance-disappearance pulses at sixteen different positions in the visual field in randomized order. The locations of evoked cortical activity in the occipital, parietal and temporal lobes are represented on a Mercator projection map for each octant or octant segment stimulated. Lower hemifield stimuli activate cortex which lies mainly on the convexity of the occipital lobe contralateral to the side of stimulus presentation in the visual field. The more peripheral the stimulus is in the visual field, the more rostral is the location of the active cortex. The rostral-to-caudal location of the evoked activity varies from subject to subject by as much as 3 cm on the surface of the occipital cortex. Furthermore, in any single subject there is a substantial amount of hemispheric asymmetry. Upper hemifield stimuli activate cortex that lies on the extreme caudal pole of the occipital lobe. This activity is relatively weak, and in some subjects it is almost unmeasurable. It is suggested that the representation of the upper hemifield in the cortex lies mostly on the inferior and

  7. Prefrontal cortical network activity: Opposite effects of psychedelic hallucinogens and D1/D5 dopamine receptor activation.

    PubMed

    Lambe, E K; Aghajanian, G K

    2007-03-30

    The fine-tuning of network activity provides a modulating influence on how information is processed and interpreted in the brain. Here, we use brain slices of rat prefrontal cortex to study how recurrent network activity is affected by neuromodulators known to alter normal cortical function. We previously determined that glutamate spillover and stimulation of extrasynaptic N-methyl-d-aspartic acid (NMDA) receptors are required to support hallucinogen-induced cortical network activity. Since microdialysis studies suggest that psychedelic hallucinogens and dopamine D1/D5 receptor agonists have opposite effects on extracellular glutamate in prefrontal cortex, we hypothesized that these two families of psychoactive drugs would have opposite effects on cortical network activity. We found that network activity can be enhanced by 2,5-dimethoxy-4-iodoamphetamine (DOI) (a psychedelic hallucinogen that is a partial agonist of 5-HT(2A/2C) receptors) and suppressed by the selective D1/D5 agonist SKF 38393. This suppression could be mimicked by direct activation of adenylyl cyclase with forskolin or by addition of a cAMP analog. These findings are consistent with previous work showing that activation of adenylyl cyclase can upregulate neuronal glutamate transporters, thereby decreasing synaptic spillover of glutamate. Consistent with this hypothesis, a low concentration of the glutamate transporter inhibitor threo-beta-benzoylaspartic acid (TBOA) restored electrically-evoked recurrent activity in the presence of a selective D1/D5 agonist, whereas recurrent activity in the presence of a low level of the GABA(A) antagonist bicuculline was not resistant to suppression by the D1/D5 agonist. The tempering of network UP states by D1/D5 receptor activation may have implications for the proposed use of D1/D5 agonists in the treatment of schizophrenia.

  8. Human Temporal Cortical Single Neuron Activity during Language: A Review

    PubMed Central

    Ojemann, George A.

    2013-01-01

    Findings from recordings of human temporal cortical single neuron activity during several measures of language, including object naming and word reading are reviewed and related to changes in activity in the same neurons during recent verbal memory and verbal associative learning measures, in studies conducted during awake neurosurgery for the treatment of epilepsy. The proportion of neurons changing activity with language tasks was similar in either hemisphere. Dominant hemisphere activity was characterized by relative inhibition, some of which occurred during overt speech, possibly to block perception of one’s own voice. However, the majority seems to represent a dynamic network becoming active with verbal memory encoding and especially verbal learning, but inhibited during performance of overlearned language tasks. Individual neurons are involved in different networks for different aspects of language, including naming or reading and naming in different languages. The majority of the changes in activity were tonic sustained shifts in firing. Patterned phasic activity for specific language items was very infrequently recorded. Human single neuron recordings provide a unique perspective on the biologic substrate for language, for these findings are in contrast to many of the findings from other techniques for investigating this. PMID:24961418

  9. Loss of Consciousness Is Associated with Stabilization of Cortical Activity

    PubMed Central

    Solovey, Guillermo; Alonso, Leandro M.; Yanagawa, Toru; Fujii, Naotaka; Magnasco, Marcelo O.; Cecchi, Guillermo A.

    2015-01-01

    What aspects of neuronal activity distinguish the conscious from the unconscious brain? This has been a subject of intense interest and debate since the early days of neurophysiology. However, as any practicing anesthesiologist can attest, it is currently not possible to reliably distinguish a conscious state from an unconscious one on the basis of brain activity. Here we approach this problem from the perspective of dynamical systems theory. We argue that the brain, as a dynamical system, is self-regulated at the boundary between stable and unstable regimes, allowing it in particular to maintain high susceptibility to stimuli. To test this hypothesis, we performed stability analysis of high-density electrocorticography recordings covering an entire cerebral hemisphere in monkeys during reversible loss of consciousness. We show that, during loss of consciousness, the number of eigenmodes at the edge of instability decreases smoothly, independently of the type of anesthetic and specific features of brain activity. The eigenmodes drift back toward the unstable line during recovery of consciousness. Furthermore, we show that stability is an emergent phenomenon dependent on the correlations among activity in different cortical regions rather than signals taken in isolation. These findings support the conclusion that dynamics at the edge of instability are essential for maintaining consciousness and provide a novel and principled measure that distinguishes between the conscious and the unconscious brain. SIGNIFICANCE STATEMENT What distinguishes brain activity during consciousness from that observed during unconsciousness? Answering this question has proven difficult because neither consciousness nor lack thereof have universal signatures in terms of most specific features of brain activity. For instance, different anesthetics induce different patterns of brain activity. We demonstrate that loss of consciousness is universally and reliably associated with stabilization

  10. Asymmetric effects of activating and inactivating cortical interneurons

    PubMed Central

    Phillips, Elizabeth AK; Hasenstaub, Andrea R

    2016-01-01

    Bidirectional manipulations – activation and inactivation – are widely used to identify the functions supported by specific cortical interneuron types. Implicit in much of this work is the notion that tonic activation and inactivation will both produce valid, internally consistent insights into interneurons’ computational roles. Here, using single-unit recordings in auditory cortex of awake mice, we show that this may not generally hold true. Optogenetically manipulating somatostatin-positive (Sst+) or parvalbumin-positive (Pvalb+) interneurons while recording tone-responses showed that Sst+ inactivation increased response gain, while Pvalb+ inactivation weakened tuning and decreased information transfer, implying that these neurons support delineable computational functions. But activating Sst+ and Pvalb+ interneurons revealed no such differences. We used a simple network model to understand this asymmetry, and showed how relatively small changes in key parameters, such as spontaneous activity or strength of the light manipulation, determined whether activation and inactivation would produce consistent or paradoxical conclusions regarding interneurons’ computational functions. DOI: http://dx.doi.org/10.7554/eLife.18383.001 PMID:27719761

  11. Sensory stimuli reduce the dimensionality of cortical activity

    NASA Astrophysics Data System (ADS)

    Mazzucato, Luca; Fontanini, Alfredo; La Camera, Giancarlo

    Neural ensembles in alert animals generate complex patterns of activity. Although cortical activity unfolds in a space whose dimension is equal to the number of neurons, it is often restricted to a lower dimensional subspace. Dimensionality is the minimal number of dimensions that accurately capture neural dynamics, and may be related to the computational tasks supported by the neural circuit. Here, we investigate the dimensionality of neural ensembles from the insular cortex of alert rats during periods of `ongoing' (spontaneous) and stimulus-evoked activity. We find that the dimensionality grows with ensemble size, and does so significantly faster during ongoing compared to evoked activity. We explain both results using a recurrent spiking network with clustered architecture, and obtain analytical results on the dependence of dimensionality on ensemble size, number of clusters, and pair-wise noise correlations. The theory predicts a characteristic scaling with ensemble size and the existence of an upper bound on dimensionality, which grows with the number of clusters and decreases with the amount of noise correlations. To our knowledge, this is the first mechanistic model of neural dimensionality in cortex during both spontaneous and evoked activity.

  12. Local and thalamic origins of correlated ongoing and sensory-evoked cortical activities

    PubMed Central

    Cohen-Kashi Malina, Katayun; Mohar, Boaz; Rappaport, Akiva N.; Lampl, Ilan

    2016-01-01

    Thalamic inputs of cells in sensory cortices are outnumbered by local connections. Thus, it was suggested that robust sensory response in layer 4 emerges due to synchronized thalamic activity. To investigate the role of both inputs in the generation of correlated cortical activities, we isolated the thalamic excitatory inputs of cortical cells by optogenetically silencing cortical firing. In anaesthetized mice, we measured the correlation between isolated thalamic synaptic inputs of simultaneously patched nearby layer 4 cells of the barrel cortex. Here we report that in contrast to correlated activity of excitatory synaptic inputs in the intact cortex, isolated thalamic inputs exhibit lower variability and asynchronous spontaneous and sensory-evoked inputs. These results are further supported in awake mice when we recorded the excitatory inputs of individual cortical cells simultaneously with the local field potential in a nearby site. Our results therefore indicate that cortical synchronization emerges by intracortical coupling. PMID:27615520

  13. Five-dimensional neuroimaging: Localization of the time-frequency dynamics of cortical activity

    PubMed Central

    Dalal, Sarang S.; Guggisberg, Adrian G.; Edwards, Erik; Sekihara, Kensuke; Findlay, Anne M.; Canolty, Ryan T.; Berger, Mitchel S.; Knight, Robert T.; Barbaro, Nicholas M.; Kirsch, Heidi E.; Nagarajan, Srikantan S.

    2008-01-01

    The spatiotemporal dynamics of cortical oscillations across human brain regions remain poorly understood because of a lack of adequately validated methods for reconstructing such activity from noninvasive electrophysiological data. In this paper, we present a novel adaptive spatial filtering algorithm optimized for robust source time-frequency reconstruction from magnetoencephalography (MEG) and electroencephalography (EEG) data. The efficacy of the method is demonstrated with simulated sources and is also applied to real MEG data from a self-paced finger movement task. The algorithm reliably reveals modulations both in the beta band (12–30 Hz) and high gamma band (65–90 Hz) in sensorimotor cortex. The performance is validated by both across-subjects statistical comparisons and by intracranial electrocorticography (ECoG) data from two epilepsy patients. Interestingly, we also reliably observed high frequency activity (30–300 Hz) in the cerebellum, though with variable locations and frequencies across subjects. The proposed algorithm is highly parallelizable and runs efficiently on modern high performance computing clusters. This method enables the ultimate promise of MEG and EEG for five-dimensional imaging of space, time, and frequency activity in the brain and renders it applicable for widespread studies of human cortical dynamics during cognition. PMID:18356081

  14. Attention Modulates the Auditory Cortical Processing of Spatial and Category Cues in Naturalistic Auditory Scenes.

    PubMed

    Renvall, Hanna; Staeren, Noël; Barz, Claudia S; Ley, Anke; Formisano, Elia

    2016-01-01

    This combined fMRI and MEG study investigated brain activations during listening and attending to natural auditory scenes. We first recorded, using in-ear microphones, vocal non-speech sounds, and environmental sounds that were mixed to construct auditory scenes containing two concurrent sound streams. During the brain measurements, subjects attended to one of the streams while spatial acoustic information of the scene was either preserved (stereophonic sounds) or removed (monophonic sounds). Compared to monophonic sounds, stereophonic sounds evoked larger blood-oxygenation-level-dependent (BOLD) fMRI responses in the bilateral posterior superior temporal areas, independent of which stimulus attribute the subject was attending to. This finding is consistent with the functional role of these regions in the (automatic) processing of auditory spatial cues. Additionally, significant differences in the cortical activation patterns depending on the target of attention were observed. Bilateral planum temporale and inferior frontal gyrus were preferentially activated when attending to stereophonic environmental sounds, whereas when subjects attended to stereophonic voice sounds, the BOLD responses were larger at the bilateral middle superior temporal gyrus and sulcus, previously reported to show voice sensitivity. In contrast, the time-resolved MEG responses were stronger for mono- than stereophonic sounds in the bilateral auditory cortices at ~360 ms after the stimulus onset when attending to the voice excerpts within the combined sounds. The observed effects suggest that during the segregation of auditory objects from the auditory background, spatial sound cues together with other relevant temporal and spectral cues are processed in an attention-dependent manner at the cortical locations generally involved in sound recognition. More synchronous neuronal activation during monophonic than stereophonic sound processing, as well as (local) neuronal inhibitory mechanisms in

  15. Attention Modulates the Auditory Cortical Processing of Spatial and Category Cues in Naturalistic Auditory Scenes

    PubMed Central

    Renvall, Hanna; Staeren, Noël; Barz, Claudia S.; Ley, Anke; Formisano, Elia

    2016-01-01

    This combined fMRI and MEG study investigated brain activations during listening and attending to natural auditory scenes. We first recorded, using in-ear microphones, vocal non-speech sounds, and environmental sounds that were mixed to construct auditory scenes containing two concurrent sound streams. During the brain measurements, subjects attended to one of the streams while spatial acoustic information of the scene was either preserved (stereophonic sounds) or removed (monophonic sounds). Compared to monophonic sounds, stereophonic sounds evoked larger blood-oxygenation-level-dependent (BOLD) fMRI responses in the bilateral posterior superior temporal areas, independent of which stimulus attribute the subject was attending to. This finding is consistent with the functional role of these regions in the (automatic) processing of auditory spatial cues. Additionally, significant differences in the cortical activation patterns depending on the target of attention were observed. Bilateral planum temporale and inferior frontal gyrus were preferentially activated when attending to stereophonic environmental sounds, whereas when subjects attended to stereophonic voice sounds, the BOLD responses were larger at the bilateral middle superior temporal gyrus and sulcus, previously reported to show voice sensitivity. In contrast, the time-resolved MEG responses were stronger for mono- than stereophonic sounds in the bilateral auditory cortices at ~360 ms after the stimulus onset when attending to the voice excerpts within the combined sounds. The observed effects suggest that during the segregation of auditory objects from the auditory background, spatial sound cues together with other relevant temporal and spectral cues are processed in an attention-dependent manner at the cortical locations generally involved in sound recognition. More synchronous neuronal activation during monophonic than stereophonic sound processing, as well as (local) neuronal inhibitory mechanisms in

  16. Cortical Activation Patterns of Bodily Attention triggered by Acupuncture Stimulation

    PubMed Central

    Jung, Won-Mo; Lee, In-Seon; Wallraven, Christian; Ryu, Yeon-Hee; Park, Hi-Joon; Chae, Younbyoung

    2015-01-01

    We investigated commonalities and differences in brain responses to enhanced bodily attention around acupuncture points with and without stimulation. Fourteen participants received acupuncture needles at both PC6 and HT7 acupoints in the left hand. To enhance bodily attention to acupoints, participants responded to the locations of stimulations in a two-alternative forced choice task. Two fMRI scans were taken in a block design: session 1 labeled with manual stimulation (genuine stimulation) and session 2 labeled with electro-acupuncture (pseudo-stimulation). To compare cortical activation patterns, data were analyzed using the Freesurfer software package. Both genuine-and pseudo-stimulation resulted in brain activations in the insula, anterior cingulate cortex, secondary somatosensory cortex, superior parietal cortex, and brain deactivation in the medial prefrontal cortex, posterior cingulate cortex, inferior parietal cortex, and the parahippocampus. Genuine acupuncture stimulation exhibited greater brain activation in the posterior insula, posterior operculum and the caudal part of the anterior cingulate cortex, compared with pseudo-stimulation. We demonstrated that enhanced bodily attention triggered by genuine acupuncture stimulation can activate the salience network and deactivate the default mode network regardless of the type of stimulation. The component of enhanced attention to a certain part of the body is significant in the brain response to acupuncture stimulation. PMID:26211895

  17. Exercising self-control increases relative left frontal cortical activation.

    PubMed

    Schmeichel, Brandon J; Crowell, Adrienne; Harmon-Jones, Eddie

    2016-02-01

    Self-control refers to the capacity to override or alter a predominant response tendency. The current experiment tested the hypothesis that exercising self-control temporarily increases approach motivation, as revealed by patterns of electrical activity in the prefrontal cortex. Participants completed a writing task that did vs did not require them to exercise self-control. Then they viewed pictures known to evoke positive, negative or neutral affect. We assessed electroencephalographic (EEG) activity while participants viewed the pictures, and participants reported their trait levels of behavioral inhibition system (BIS) and behavioral activation system (BAS) sensitivity at the end of the study. We found that exercising (vs not exercising) self-control increased relative left frontal cortical activity during picture viewing, particularly among individuals with relatively higher BAS than BIS, and particularly during positive picture viewing. A similar but weaker pattern emerged during negative picture viewing. The results suggest that exercising self-control temporarily increases approach motivation, which may help to explain the aftereffects of self-control (i.e. ego depletion).

  18. Modeling vocalization with ECoG cortical activity recorded during vocal production in the macaque monkey.

    PubMed

    Fukushima, Makoto; Saunders, Richard C; Fujii, Naotaka; Averbeck, Bruno B; Mishkin, Mortimer

    2014-01-01

    Vocal production is an example of controlled motor behavior with high temporal precision. Previous studies have decoded auditory evoked cortical activity while monkeys listened to vocalization sounds. On the other hand, there have been few attempts at decoding motor cortical activity during vocal production. Here we recorded cortical activity during vocal production in the macaque with a chronically implanted electrocorticographic (ECoG) electrode array. The array detected robust activity in motor cortex during vocal production. We used a nonlinear dynamical model of the vocal organ to reduce the dimensionality of `Coo' calls produced by the monkey. We then used linear regression to evaluate the information in motor cortical activity for this reduced representation of calls. This simple linear model accounted for circa 65% of the variance in the reduced sound representations, supporting the feasibility of using the dynamical model of the vocal organ for decoding motor cortical activity during vocal production.

  19. Effects of Alprazolam on Cortical Activity and Tremors in Patients with Essential Tremor

    PubMed Central

    Ibáñez, Jaime; González de la Aleja, Jesús; Gallego, Juan A.; Romero, Juan P.; Saíz-Díaz, Rosana A.; Benito-León, Julián; Rocon, Eduardo

    2014-01-01

    Background Essential tremor (ET) is characterised by postural and action tremors with a frequency of 4–12 Hz. Previous studies suggest that the tremor activity originates in the cerebello-thalamocortical pathways. Alprazolam is a short-acting benzodiazepine that attenuates tremors in ET. The mechanisms that mediate the therapeutic action of alprazolam are unknown; however, in healthy subjects, benzodiazepines increase cortical beta activity. In this study, we investigated the effect of alprazolam both on beta and tremor-related cortical activity and on alterations in tremor presentation in ET patients. Therefore, we characterised the dynamics of tremor and cortical activity in ET patients after alprazolam intake. Methods We recorded hand tremors and contralateral cortical activity in four recordings before and after a single dose of alprazolam. We then computed the changes in tremors, cortico-muscular coherence, and cortical activity at the tremor frequency and in the beta band. Results Alprazolam significantly attenuated tremors (EMG: 76.2±22.68%), decreased cortical activity in the tremor frequency range and increased cortical beta activity in all patients (P<0.05). At the same time, the cortico-muscular coherence at the tremor frequency became non-significant (P<0.05). We also found a significant correlation (r = 0.757, P<0.001) between the reduction in tremor severity and the increased ratio of cortical activity in the beta band to the activity observed in the tremor frequency range. Conclusions This study provides the first quantitative analysis of tremor reduction following alprazolam intake. We observed that the tremor severity decreased in association with an increased ratio of beta to tremor-related cortical activity. We hypothesise that the increase in cortical beta activity may act as a blocking mechanism and may dampen the pathological oscillatory activity, which in turn attenuates the observed tremor. PMID:24667763

  20. Valence of physical stimuli, not housing conditions, affects behaviour and frontal cortical brain activity in sheep.

    PubMed

    Vögeli, Sabine; Lutz, Janika; Wolf, Martin; Wechsler, Beat; Gygax, Lorenz

    2014-07-01

    Modulation of short-term emotions by long-term mood is little understood but relevant to understand the affective system and of importance in respect to animal welfare: a negative mood might taint experiences, whilst a positive mood might alleviate single negative events. To induce different mood states in sheep housing conditions were varied. Fourteen ewes were group-housed in an unpredictable, stimulus-poor and 15 ewes in a predictable, stimulus-rich environment. Sheep were tested individually for mood in a behavioural cognitive bias paradigm. Also, their reactions to three physical stimuli thought to differ in their perceived valence were observed (negative: pricking, intermediate: slight pressure, positive: kneading). General behaviour, activity, ear movements and positions, and haemodynamic changes in the cortical brain were recorded during stimulations. Generalised mixed-effects models and model probabilities based on the BIC (Bayesian information criterion) were used. Only weak evidence for mood difference was found. Sheep from the unpredictable, stimulus-poor housing condition had a somewhat more negative cognitive bias, showed slightly more aversive behaviour, were slightly more active and moved their ears somewhat more. Sheep most clearly differentiated the negative from the intermediate and positive stimulus in that they exhibited more aversive behaviour, less nibbling, were more active, showed more ear movements, more forward ear postures, fewer backward ear postures, and a stronger decrease in deoxyhaemoglobin when subjected to the negative stimulus. In conclusion, sheep reacted towards stimuli according to their presumed valence but their mood was not strongly influenced by housing conditions. Therefore, behavioural reactions and cortical brain activity towards the stimuli were hardly modulated by housing conditions.

  1. Cortical Reinstatement Mediates the Relationship Between Content-Specific Encoding Activity and Subsequent Recollection Decisions

    PubMed Central

    Gordon, Alan M.; Rissman, Jesse; Kiani, Roozbeh; Wagner, Anthony D.

    2014-01-01

    Episodic recollection entails the conscious remembrance of event details associated with previously encountered stimuli. Recollection depends on both the establishment of cortical representations of event features during stimulus encoding and the cortical reinstatement of these representations at retrieval. Here, we used multivoxel pattern analyses of functional magnetic resonance imaging data to examine how cortical and hippocampal activity at encoding and retrieval drive recollective memory decisions. During encoding, words were associated with face or scene source contexts. At retrieval, subjects were cued to recollect the source associate of each presented word. Neurally derived estimates of encoding strength and pattern reinstatement in occipitotemporal cortex were computed for each encoding and retrieval trial, respectively. Analyses demonstrated that (1) cortical encoding strength predicted subsequent memory accuracy and reaction time, (2) encoding strength predicted encoding-phase hippocampal activity, and (3) encoding strength and retrieval-phase hippocampal activity predicted the magnitude of cortical reinstatement. Path analyses further indicated that cortical reinstatement partially mediated both the effect of cortical encoding strength and the effect of retrieval-phase hippocampal activity on subsequent source memory performance. Taken together, these results indicate that memory-guided decisions are driven in part by a pathway leading from hippocampally linked cortical encoding of event attributes to hippocampally linked cortical reinstatement at retrieval. PMID:23921785

  2. Bioreactor Transient Exposure Activates Specific Neurotrophic Pathway in Cortical Neurons

    NASA Astrophysics Data System (ADS)

    Zimmitti, V.; Benedetti, E.; Caracciolo, V.; Sebastiani, P.; Di Loreto, S.

    2010-02-01

    Altered gravity forces might influence neuroplasticity and can provoke changes in biochemical mechanisms. In this contest, neurotrophins have a pivotal role, particularly nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF). A suspension of dissociated cortical cells from rat embryos was exposed to 24 h of microgravity before plating in normal adherent culture system. Expression and transductional signalling pathways of NGF and BDNF were assessed at the end of maturational process (8-10 days in vitro). Rotating wall vessel bioreactor (RWV) pre-exposition did not induce changes in NGF expression and its high affinity receptor TrkA. On the contrary both BDNF expression and its high affinity receptor TrkB were strongly up-regulated, inducing Erk-5, but not Erk-1/2 activation and, in turn, MEF2C over-expression and activation. According to our previous and present results, we postulate that relatively short microgravitational stimuli, applied to neural cells during the developmental stage, exert a long time activation of specific neurotrophic pathways.

  3. The cortical activation pattern during bilateral arm raising movements

    PubMed Central

    Jang, Sung Ho; Seo, Jung Pyo; Lee, Seung-Hyun; Jin, Sang-Hyun; Yeo, Sang Seok

    2017-01-01

    Bilateral arm raising movements have been used in brain rehabilitation for a long time. However, no study has been reported on the effect of these movements on the cerebral cortex. In this study, using functional near infrared spectroscopy (fNIRS), we attempted to investigate cortical activation generated during bilateral arm raising movements. Ten normal subjects were recruited for this study. fNIRS was performed using an fNIRS system with 49 channels. Bilateral arm raising movements were performed in sitting position at the rate of 0.5 Hz. We measured values of oxyhemoglobin and total hemoglobin in five regions of interest: the primary sensorimotor cortex, premotor cortex, supplementary motor area, prefrontal cortex, and posterior parietal cortex. During performance of bilateral arm raising movements, oxyhemoglobin and total hemoglobin values in the primary sensorimotor cortex, premotor cortex, supplementary motor area, and prefrontal cortex were similar, but higher in these regions than those in the prefrontal cortex. We observed activation of the arm somatotopic areas of the primary sensorimotor cortex and premotor cortex in both hemispheres during bilateral arm raising movements. According to this result, bilateral arm raising movements appeared to induce large-scale neuronal activation and therefore arm raising movements would be good exercise for recovery of brain functions.

  4. A Novel Modulator of Kv3 Potassium Channels Regulates the Firing of Parvalbumin-Positive Cortical Interneurons.

    PubMed

    Rosato-Siri, Marcelo D; Zambello, Erika; Mutinelli, Chiara; Garbati, Nicoletta; Benedetti, Roberto; Aldegheri, Laura; Graziani, Francesca; Virginio, Caterina; Alvaro, Giuseppe; Large, Charles H

    2015-09-01

    Kv3.1 and Kv3.2 high voltage-activated potassium channels, which display fast activation and deactivation kinetics, are known to make a crucial contribution to the fast-spiking phenotype of certain neurons. Pharmacological experiments show that the blockade of native Kv3 currents with low concentrations of tetraethylammonium or 4-aminopyridine impairs the expression of this firing phenotype. In particular, Kv3 channels are highly expressed by fast-spiking, parvalbumin-positive interneurons in corticolimbic brain circuits, which modulate the synchronization of cortical circuits and the generation of brain rhythms. Here, we describe a novel small molecule, (5R)-5-ethyl-3-(6-{[4-methyl-3-(methyloxy)phenyl]oxy}-3-pyridinyl)-2,4-imidazolidinedione (AUT1), which modulates Kv3.1 and Kv3.2 channels in human recombinant and rodent native neurons. AUT1 increased whole currents mediated by human Kv3.1b and Kv3.2a channels, with a concomitant leftward shift in the voltage dependence of activation. A less potent effect was observed on hKv3.3 currents. In mouse somatosensory cortex slices in vitro, AUT1 rescued the fast-spiking phenotype of parvalbumin-positive-fast-spiking interneurons following an impairment of their firing capacity by blocking a proportion of Kv3 channels with a low concentration of tetraethylammonium. Notably, AUT1 had no effect on interneuron firing when applied alone. Together, these data confirm the role played by Kv3 channels in the regulation of the firing phenotype of somatosensory interneurons and suggest that AUT1 and other Kv3 modulators could represent a new and promising therapeutic approach to the treatment of disorders associated with dysfunction of inhibitory feedback in corticolimbic circuits, such as schizophrenia.

  5. Cortical Activation During Levitation and Tentacular Movements of Corticobasal Syndrome

    PubMed Central

    Onofrj, Marco; Bonanni, Laura; Pizzi, Stefano Delli; Caulo, Massimo; Onofrj, Valeria; Thomas, Astrid; Tartaro, Armando; Franciotti, Raffaella

    2015-01-01

    Abstract Levitation and tentacular movements (LTM) are considered specific, yet rare (30%), features of Corticobasal Syndrome (CBS), and are erroneously classified as alien hand. Our study focuses on these typical involuntary movements and aims to highlight possible neural correlates. LTM were recognizable during functional magnetic resonance imaging (fMRI) in 4 of 19 CBS patients. FMRI activity was evaluated with an activation recognition program for movements, during LTM, consisting of levitaton and finger writhing, and compared with the absence of movement (rest) and voluntary movements (VM), similar to LTM, of affected and unaffected arm-hand. FMRI acquisition blocks were balanced in order to match LTM blocks with rest and VM conditions. In 1 of the 4 patients, fMRI was acquired only during LTM and with a different equipment. Despite variable intensity and range of involuntary movements, evidenced by videos, fMRI showed, during LTM, a significant (P<0.05–0.001) activation only of the contralateral primary motor cortex (M1). Voluntary movements of the affected and unaffected arm elicited the known network including frontal, supplementary, sensory-motor cortex, and cerebellum. Willed movements of the LTM-affected arm induced higher and wider activation of contralateral M1 compared with the unaffected arm. The isolated activation of M1 suggests that LTM is a cortical disinhibition symptom, not involving a network. Higher activation of M1 during VM confirms that M1 excitability changes occur in CBS. Our study calls, finally, attention to the necessity to separate LTM from other alien hand phenomena. PMID:26559277

  6. Cortical Activation During Levitation and Tentacular Movements of Corticobasal Syndrome.

    PubMed

    Onofrj, Marco; Bonanni, Laura; Delli Pizzi, Stefano; Caulo, Massimo; Onofrj, Valeria; Thomas, Astrid; Tartaro, Armando; Franciotti, Raffaella

    2015-11-01

    Levitation and tentacular movements (LTM) are considered specific, yet rare (30%), features of Corticobasal Syndrome (CBS), and are erroneously classified as alien hand. Our study focuses on these typical involuntary movements and aims to highlight possible neural correlates.LTM were recognizable during functional magnetic resonance imaging (fMRI) in 4 of 19 CBS patients. FMRI activity was evaluated with an activation recognition program for movements, during LTM, consisting of levitaton and finger writhing, and compared with the absence of movement (rest) and voluntary movements (VM), similar to LTM, of affected and unaffected arm-hand. FMRI acquisition blocks were balanced in order to match LTM blocks with rest and VM conditions. In 1 of the 4 patients, fMRI was acquired only during LTM and with a different equipment.Despite variable intensity and range of involuntary movements, evidenced by videos, fMRI showed, during LTM, a significant (P<0.05-0.001) activation only of the contralateral primary motor cortex (M1). Voluntary movements of the affected and unaffected arm elicited the known network including frontal, supplementary, sensory-motor cortex, and cerebellum. Willed movements of the LTM-affected arm induced higher and wider activation of contralateral M1 compared with the unaffected arm.The isolated activation of M1 suggests that LTM is a cortical disinhibition symptom, not involving a network. Higher activation of M1 during VM confirms that M1 excitability changes occur in CBS. Our study calls, finally, attention to the necessity to separate LTM from other alien hand phenomena.

  7. Primary and multisensory cortical activity is correlated with audiovisual percepts.

    PubMed

    Benoit, Margo McKenna; Raij, Tommi; Lin, Fa-Hsuan; Jääskeläinen, Iiro P; Stufflebeam, Steven

    2010-04-01

    Incongruent auditory and visual stimuli can elicit audiovisual illusions such as the McGurk effect where visual /ka/ and auditory /pa/ fuse into another percept such as/ta/. In the present study, human brain activity was measured with adaptation functional magnetic resonance imaging to investigate which brain areas support such audiovisual illusions. Subjects viewed trains of four movies beginning with three congruent /pa/ stimuli to induce adaptation. The fourth stimulus could be (i) another congruent /pa/, (ii) a congruent /ka/, (iii) an incongruent stimulus that evokes the McGurk effect in susceptible individuals (lips /ka/ voice /pa/), or (iv) the converse combination that does not cause the McGurk effect (lips /pa/ voice/ ka/). This paradigm was predicted to show increased release from adaptation (i.e. stronger brain activation) when the fourth movie and the related percept was increasingly different from the three previous movies. A stimulus change in either the auditory or the visual stimulus from /pa/ to /ka/ (iii, iv) produced within-modality and cross-modal responses in primary auditory and visual areas. A greater release from adaptation was observed for incongruent non-McGurk (iv) compared to incongruent McGurk (iii) trials. A network including the primary auditory and visual cortices, nonprimary auditory cortex, and several multisensory areas (superior temporal sulcus, intraparietal sulcus, insula, and pre-central cortex) showed a correlation between perceiving the McGurk effect and the fMRI signal, suggesting that these areas support the audiovisual illusion.

  8. HTR2 Receptors in a Songbird Premotor Cortical-Like Area Modulate Spectral Characteristics of Zebra Finch Song

    PubMed Central

    Wood, William E.; Roseberry, Thomas K.; Perkel, David J.

    2013-01-01

    Serotonin [5-hydroxytryptamine (5-HT)] is involved in modulating an array of complex behaviors including learning, depression, and circadian rhythms. Additionally, HTR2 receptors on layer V pyramidal neurons are thought to mediate the actions of psychedelic drugs; the native function of these receptors at this site, however, remains unknown. Previously, we found that activation of HTR2 receptors in the zebra finch forebrain song premotor structure the robust nucleus of the arcopallium (RA) led to increased excitation, and that endogenous 5-HT could roughly double spontaneous firing rate. Here, using in vivo single-unit recordings, we found that direct application of 5-HT to these same RA projection neurons, which are analogous to layer V cortical pyramidal neurons, caused a significant increase in the number of action potentials per song-related burst, and a dramatic decrease in signal-to-noise ratio. Injection of the serotonergic neurotoxin 5,7-dihydroxytryptamine into the third ventricle greatly reduced telencephalic 5-HT and resulted in decreased fundamental frequency of harmonic syllables as well as increased goodness of pitch. Both of these results can be explained by the observed actions of 5-HT on RA projection neurons, and both effects recovered to baseline within 2 weeks following the toxin injection. These results show that 5-HT is involved in modulating spectral properties of song, likely via effects on RA projection neurons, but that adult zebra finches can partially compensate for this deficit within 7 d. PMID:23407949

  9. Cortical Modulation of Motor Control Biofeedback among the Elderly with High Fall Risk during a Posture Perturbation Task with Augmented Reality

    PubMed Central

    Chang, Chun-Ju; Yang, Tsui-Fen; Yang, Sai-Wei; Chern, Jen-Suh

    2016-01-01

    The cerebral cortex provides sensorimotor integration and coordination during motor control of daily functional activities. Power spectrum density based on electroencephalography (EEG) has been employed as an approach that allows an investigation of the spatial–temporal characteristics of neuromuscular modulation; however, the biofeedback mechanism associated with cortical activation during motor control remains unclear among elderly individuals. Thirty one community-dwelling elderly participants were divided into low fall-risk potential (LF) and high fall-risk potential (HF) groups based upon the results obtained from a receiver operating characteristic analysis of the ellipse area of the center of pressure. Electroencephalography (EEG) was performed while the participants stood on a 6-degree-of-freedom Stewart platform, which generated continuous perturbations and done either with or without the virtual reality scene. The present study showed that when there was visual stimulation and poor somatosensory coordination, a higher level of cortical response was activated in order to keep postural balance. The elderly participants in the LF group demonstrated a significant and strong correlation between postural-related cortical regions; however, the elderly individuals in the HF group did not show such a relationship. Moreover, we were able to clarify the roles of various brainwave bands functioning in motor control. Specifically, the gamma and beta bands in the parietal–occipital region facilitate the high-level cortical modulation and sensorimotor integration, whereas the theta band in the frontal–central region is responsible for mediating error detection during perceptual motor tasks. Finally, the alpha band is associated with processing visual challenges in the occipital lobe.With a variety of motor control demands, increment in brainwave band coordination is required to maintain postural stability. These investigations shed light on the cortical modulation

  10. Cortical Modulation of Motor Control Biofeedback among the Elderly with High Fall Risk during a Posture Perturbation Task with Augmented Reality.

    PubMed

    Chang, Chun-Ju; Yang, Tsui-Fen; Yang, Sai-Wei; Chern, Jen-Suh

    2016-01-01

    The cerebral cortex provides sensorimotor integration and coordination during motor control of daily functional activities. Power spectrum density based on electroencephalography (EEG) has been employed as an approach that allows an investigation of the spatial-temporal characteristics of neuromuscular modulation; however, the biofeedback mechanism associated with cortical activation during motor control remains unclear among elderly individuals. Thirty one community-dwelling elderly participants were divided into low fall-risk potential (LF) and high fall-risk potential (HF) groups based upon the results obtained from a receiver operating characteristic analysis of the ellipse area of the center of pressure. Electroencephalography (EEG) was performed while the participants stood on a 6-degree-of-freedom Stewart platform, which generated continuous perturbations and done either with or without the virtual reality scene. The present study showed that when there was visual stimulation and poor somatosensory coordination, a higher level of cortical response was activated in order to keep postural balance. The elderly participants in the LF group demonstrated a significant and strong correlation between postural-related cortical regions; however, the elderly individuals in the HF group did not show such a relationship. Moreover, we were able to clarify the roles of various brainwave bands functioning in motor control. Specifically, the gamma and beta bands in the parietal-occipital region facilitate the high-level cortical modulation and sensorimotor integration, whereas the theta band in the frontal-central region is responsible for mediating error detection during perceptual motor tasks. Finally, the alpha band is associated with processing visual challenges in the occipital lobe.With a variety of motor control demands, increment in brainwave band coordination is required to maintain postural stability. These investigations shed light on the cortical modulation of

  11. Gaming is related to enhanced working memory performance and task-related cortical activity.

    PubMed

    Moisala, M; Salmela, V; Hietajärvi, L; Carlson, S; Vuontela, V; Lonka, K; Hakkarainen, K; Salmela-Aro, K; Alho, K

    2017-01-15

    Gaming experience has been suggested to lead to performance enhancements in a wide variety of working memory tasks. Previous studies have, however, mostly focused on adult expert gamers and have not included measurements of both behavioral performance and brain activity. In the current study, 167 adolescents and young adults (aged 13-24 years) with different amounts of gaming experience performed an n-back working memory task with vowels, with the sensory modality of the vowel stream switching between audition and vision at random intervals. We studied the relationship between self-reported daily gaming activity, working memory (n-back) task performance and related brain activity measured using functional magnetic resonance imaging (fMRI). The results revealed that the extent of daily gaming activity was related to enhancements in both performance accuracy and speed during the most demanding (2-back) level of the working memory task. This improved working memory performance was accompanied by enhanced recruitment of a fronto-parietal cortical network, especially the dorsolateral prefrontal cortex. In contrast, during the less demanding (1-back) level of the task, gaming was associated with decreased activity in the same cortical regions. Our results suggest that a greater degree of daily gaming experience is associated with better working memory functioning and task difficulty-dependent modulation in fronto-parietal brain activity already in adolescence and even when non-expert gamers are studied. The direction of causality within this association cannot be inferred with certainty due to the correlational nature of the current study.

  12. Human cortical activity evoked by the assignment of authenticity when viewing works of art.

    PubMed

    Huang, Mengfei; Bridge, Holly; Kemp, Martin J; Parker, Andrew J

    2011-01-01

    The expertise of others is a major social influence on our everyday decisions and actions. Many viewers of art, whether expert or naïve, are convinced that the full esthetic appreciation of an artwork depends upon the assurance that the work is genuine rather than fake. Rembrandt portraits provide an interesting image set for testing this idea, as there is a large number of them and recent scholarship has determined that quite a few fakes and copies exist. Use of this image set allowed us to separate the brain's response to images of genuine and fake pictures from the brain's response to external advice about the authenticity of the paintings. Using functional magnetic resonance imaging, viewing of artworks assigned as "copy," rather than "authentic," evoked stronger responses in frontopolar cortex (FPC), and right precuneus, regardless of whether the portrait was actually genuine. Advice about authenticity had no direct effect on the cortical visual areas responsive to the paintings, but there was a significant psycho-physiological interaction between the FPC and the lateral occipital area, which suggests that these visual areas may be modulated by FPC. We propose that the activation of brain networks rather than a single cortical area in this paradigm supports the art scholars' view that esthetic judgments are multi-faceted and multi-dimensional in nature.

  13. Kv1.2 mediates heterosynaptic modulation of direct cortical synaptic inputs in CA3 pyramidal cells

    PubMed Central

    Hyun, Jung Ho; Eom, Kisang; Lee, Kyu-Hee; Bae, Jin Young; Bae, Yong Chul; Kim, Myoung-Hwan; Kim, Sooyun; Ho, Won-Kyung; Lee, Suk-Ho

    2015-01-01

    A short high frequency stimulation of mossy fibres (MFs) induces long-term potentiation (LTP) of direct cortical or perforant path (PP) synaptic inputs in hippocampal CA3 pyramidal cells (CA3-PCs). However, the cellular mechanism underlying this heterosynaptic modulation remains elusive. Previously, we reported that repetitive somatic firing at 10 Hz downregulates Kv1.2 in the CA3-PCs. Here, we show that MF inputs induce similar somatic firing and downregulation of Kv1.2 in the CA3-PCs. The effect of Kv1.2 downregulation was specific to PP synaptic inputs that arrive at distal apical dendrites. We found that the somatodendritic expression of Kv1.2 is polarized to distal apical dendrites. Compartmental simulations based on this finding suggested that passive normalization of synaptic inputs and polarized distributions of dendritic ionic channels may facilitate the activation of dendritic Na+ channels preferentially at distal apical dendrites. Indeed, partial block of dendritic Na+ channels using 10 nm tetrodotoxin brought back the enhanced PP-evoked excitatory postsynaptic potentials (PP-EPSPs) to the baseline level. These results indicate that activity-dependent downregulation of Kv1.2 in CA3-PCs mediates MF-induced heterosynaptic LTP of PP-EPSPs by facilitating activation of Na+ channels at distal apical dendrites. PMID:26047212

  14. Regulation of Persistent Activity by Background Inhibition in an In Vitro Model of a Cortical Microcircuit

    PubMed Central

    Fellous, Jean-Marc; Sejnowski, Terrence J.

    2010-01-01

    We combined in vitro intracellular recording from prefrontal cortical neurons with simulated synaptic activity of a layer 5 prefrontal microcircuit using a dynamic clamp. During simulated in vivo background conditions, the cell responded to a brief depolarization with a sequence of spikes that outlasted the depolarization, mimicking the activity of a cell recorded during the delay period of a working memory task in the behaving monkey. The onset of sustained activity depended on the number of action potentials elicited by the cue-like depolarization. Too few spikes failed to provide enough NMDA drive to elicit sustained reverberations; too many spikes activated a slow intrinsic hyperpolarization current that prevented spiking; an intermediate number of spikes produced sustained activity. When high dopamine levels were simulated by depolarizing the cell and by increasing the amount of NMDA current, the cell exhibited spontaneous ‘up-states’ that terminated by the activation of a slow intrinsic hyperpolarizing current. The firing rate during the delay period could be effectively modulated by the standard deviation of the inhibitory background synaptic noise without significant changes in the background firing rate before cue onset. These results suggest that the balance between fast feedback inhibition and slower AMPA and NMDA feedback excitation is critical in initiating persistent activity and that the maintenance of persistent activity may be regulated by the amount of correlated background inhibition. PMID:14576214

  15. Locus Coeruleus α-Adrenergic–Mediated Activation of Cortical Astrocytes In Vivo

    PubMed Central

    He, Wei; Nedergaard, Maiken

    2008-01-01

    The locus coeruleus (LC) provides the sole source of norepinephrine (NE) to the cortex for modulation of cortical synaptic activity in response to salient sensory information. NE has been shown to improve signal-to-noise ratios, sharpen receptive fields and function in learning, memory, and cognitive performance. Although LC-mediated effects on neurons have been addressed, involvement of astrocytes has thus far not been demonstrated in these neuromodulatory functions. Here we show for the 1st time in live mice, that astrocytes exhibit rapid Ca2+ increases in response to electrical stimulation of the LC. Additionally, robust peripheral stimulation known to result in phasic LC activity leads to Ca2+ responses in astrocytes throughout sensory cortex that are independent of sensory-driven glutamate-dependent pathways. Furthermore, the astrocytic Ca2+ transients are competitively modulated by α2-specific agonist/antagonist combinations known to impact LC output, are sensitive to the LC-specific neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, and are inhibited locally by an α-adrenergic antagonist. Future investigations of LC function must therefore consider the possibility that LC neuromodulatory effects are in part derived from activation of astrocytes. PMID:18372288

  16. Knowledge About Sounds—Context-Specific Meaning Differently Activates Cortical Hemispheres, Auditory Cortical Fields, and Layers in House Mice

    PubMed Central

    Geissler, Diana B.; Schmidt, H. Sabine; Ehret, Günter

    2016-01-01

    Activation of the auditory cortex (AC) by a given sound pattern is plastic, depending, in largely unknown ways, on the physiological state and the behavioral context of the receiving animal and on the receiver's experience with the sounds. Such plasticity can be inferred when house mouse mothers respond maternally to pup ultrasounds right after parturition and naïve females have to learn to respond. Here we use c-FOS immunocytochemistry to quantify highly activated neurons in the AC fields and layers of seven groups of mothers and naïve females who have different knowledge about and are differently motivated to respond to acoustic models of pup ultrasounds of different behavioral significance. Profiles of FOS-positive cells in the AC primary fields (AI, AAF), the ultrasonic field (UF), the secondary field (AII), and the dorsoposterior field (DP) suggest that activation reflects in AI, AAF, and UF the integration of sound properties with animal state-dependent factors, in the higher-order field AII the news value of a given sound in the behavioral context, and in the higher-order field DP the level of maternal motivation and, by left-hemisphere activation advantage, the recognition of the meaning of sounds in the given context. Anesthesia reduced activation in all fields, especially in cortical layers 2/3. Thus, plasticity in the AC is field-specific preparing different output of AC fields in the process of perception, recognition and responding to communication sounds. Further, the activation profiles of the auditory cortical fields suggest the differentiation between brains hormonally primed to know (mothers) and brains which acquired knowledge via implicit learning (naïve females). In this way, auditory cortical activation discriminates between instinctive (mothers) and learned (naïve females) cognition. PMID:27013959

  17. Knowledge About Sounds-Context-Specific Meaning Differently Activates Cortical Hemispheres, Auditory Cortical Fields, and Layers in House Mice.

    PubMed

    Geissler, Diana B; Schmidt, H Sabine; Ehret, Günter

    2016-01-01

    Activation of the auditory cortex (AC) by a given sound pattern is plastic, depending, in largely unknown ways, on the physiological state and the behavioral context of the receiving animal and on the receiver's experience with the sounds. Such plasticity can be inferred when house mouse mothers respond maternally to pup ultrasounds right after parturition and naïve females have to learn to respond. Here we use c-FOS immunocytochemistry to quantify highly activated neurons in the AC fields and layers of seven groups of mothers and naïve females who have different knowledge about and are differently motivated to respond to acoustic models of pup ultrasounds of different behavioral significance. Profiles of FOS-positive cells in the AC primary fields (AI, AAF), the ultrasonic field (UF), the secondary field (AII), and the dorsoposterior field (DP) suggest that activation reflects in AI, AAF, and UF the integration of sound properties with animal state-dependent factors, in the higher-order field AII the news value of a given sound in the behavioral context, and in the higher-order field DP the level of maternal motivation and, by left-hemisphere activation advantage, the recognition of the meaning of sounds in the given context. Anesthesia reduced activation in all fields, especially in cortical layers 2/3. Thus, plasticity in the AC is field-specific preparing different output of AC fields in the process of perception, recognition and responding to communication sounds. Further, the activation profiles of the auditory cortical fields suggest the differentiation between brains hormonally primed to know (mothers) and brains which acquired knowledge via implicit learning (naïve females). In this way, auditory cortical activation discriminates between instinctive (mothers) and learned (naïve females) cognition.

  18. Primary and Multisensory Cortical Activity is Correlated with Audiovisual Percepts

    PubMed Central

    Benoit, Margo McKenna; Raij, Tommi; Lin, Fa-Hsuan; Jääskeläinen, Iiro P.; Stufflebeam, Steven

    2012-01-01

    Incongruent auditory and visual stimuli can elicit audiovisual illusions such as the McGurk effect where visual /ka/ and auditory /pa/ fuse into another percept such as/ta/. In the present study, human brain activity was measured with adaptation functional magnetic resonance imaging to investigate which brain areas support such audiovisual illusions. Subjects viewed trains of four movies beginning with three congruent /pa/ stimuli to induce adaptation. The fourth stimulus could be (i) another congruent /pa/, (ii) a congruent /ka/, (iii) an incongruent stimulus that evokes the McGurk effect in susceptible individuals (lips /ka/ voice /pa/), or (iv) the converse combination that does not cause the McGurk effect (lips /pa/ voice/ ka/). This paradigm was predicted to show increased release from adaptation (i.e. stronger brain activation) when the fourth movie and the related percept was increasingly different from the three previous movies. A stimulus change in either the auditory or the visual stimulus from /pa/ to /ka/ (iii, iv) produced within-modality and cross-modal responses in primary auditory and visual areas. A greater release from adaptation was observed for incongruent non-McGurk (iv) compared to incongruent McGurk (iii) trials. A network including the primary auditory and visual cortices, nonprimary auditory cortex, and several multisensory areas (superior temporal sulcus, intraparietal sulcus, insula, and pre-central cortex) showed a correlation between perceiving the McGurk effect and the fMRI signal, suggesting that these areas support the audiovisual illusion. PMID:19780040

  19. Cortical and corticospinal output modulations during reaching movements with varying directions and magnitudes of interaction torques.

    PubMed

    Asmussen, M J; Bailey, A Z; Nelson, A J

    2015-12-17

    The neural command required to coordinate a multi-joint movement is inherently complex. During multi-joint movement of the limb, the force created from movement at one joint may create a torque at a second joint known as an interaction torque. Interaction torques may be assistive or resistive thereby aiding or opposing the motion of the second joint, respectively. For movement to be effectively controlled, the central nervous system should modulate neural output to the muscles to appropriately account for interaction torques. The present study examined the neural output from the primary motor cortex before and during reaching movements that required different combinations of assistive and resistive interaction torques occurring at the shoulder and elbow joints. Using transcranial magnetic stimulation to probe neural output from the primary motor cortex, results indicate that corticospinal output controlling the upper arm is related to resistive interaction torques occurring at the shoulder joint. Further, cortical output to bi-articular muscles is associated with interaction torque and this may be driven by the fact that these muscles are in an advantageous position to control torques produced between inter-connection segments. Humans have a tendency to avoid reaching movements that involve resistive interaction torques and this may be driven by the requirement of increased neural output associated with these movements.

  20. Modulation of [3H]diazepam binding in rat cortical membranes by GABAA agonists.

    PubMed

    Wong, E H; Iversen, L L

    1985-04-01

    GABAA receptor agonists modulate [3H]diazepam binding in rat cortical membranes with different efficacies. At 23 degrees C, the relative potencies for enhancement of [3H]diazepam binding by agonists parallel their potencies in inhibiting [3H]gamma-aminobutyric acid [( 3H]GABA) binding. The agonist concentrations needed for enhancement of [3H]diazepam binding are up to 35 times higher than for [3H]GABA binding and correspond closely to the concentrations required for displacement of [3H]bicuculline methochloride (BMC) binding. The maximum enhancement of [3H]diazepam varied among agonists: muscimol = GABA greater than isoguvacine greater than 3-aminopropane sulphonic acid (3APS) = imidazoleacetic acid (IAA) greater than 4,5,6,7-tetrahydroisoxazolo (4,5,6)-pyridin-3-ol (THIP) = taurine greater than piperidine 4-sulphonic acid (P4S). At 37 degrees C, the potencies of agonists remained unchanged, but isoguvacine, 3 APS, and THIP acquired efficacies similar to GABA, whereas IAA, taurine, and P4S maintained their partial agonist profiles. At both temperatures the agonist-induced enhancement of [3H]diazepam binding was reversible by bicuculline methobromide and by the steroid GABA antagonist RU 5135. These results stress the importance of studying receptor-receptor interaction under near-physiological conditions and offer an in vitro assay that may predict the agonist status of putative GABA receptor ligands.

  1. Mechanisms underlying intensity-dependent changes in cortical selectivity for frequency-modulated sweeps.

    PubMed

    Razak, K A

    2012-04-01

    Frequency-modulated (FM) sweeps are common components of species-specific vocalizations. The intensity of FM sweeps can cover a wide range in the natural environment, but whether intensity affects neural selectivity for FM sweeps is unclear. Bats, such as the pallid bat, which use FM sweeps for echolocation, are suited to address this issue, because the intensity of echoes will vary with target distance. In this study, FM sweep rate selectivity of pallid bat auditory cortex neurons was measured using downward sweeps at different intensities. Neurons became more selective for FM sweep rates present in the bat's echolocation calls as intensity increased. Increased selectivity resulted from stronger inhibition of responses to slower sweep rates. The timing and bandwidth of inhibition generated by frequencies on the high side of the excitatory tuning curve [sideband high-frequency inhibition (HFI)] shape rate selectivity in cortical neurons in the pallid bat. To determine whether intensity-dependent changes in FM rate selectivity were due to altered inhibition, the timing and bandwidth of HFI were quantified at multiple intensities using the two-tone inhibition paradigm. HFI arrived faster relative to excitation as sound intensity increased. The bandwidth of HFI also increased with intensity. The changes in HFI predicted intensity-dependent changes in FM rate selectivity. These data suggest that neural selectivity for a sweep parameter is not static but shifts with intensity due to changes in properties of sideband inhibition.

  2. Dopamine Modulation of Emotional Processing in Cortical and Subcortical Neural Circuits: Evidence for a Final Common Pathway in Schizophrenia?

    PubMed Central

    2007-01-01

    The neural regulation of emotional perception, learning, and memory is essential for normal behavioral and cognitive functioning. Many of the symptoms displayed by individuals with schizophrenia may arise from fundamental disturbances in the ability to accurately process emotionally salient sensory information. The neurotransmitter dopamine (DA) and its ability to modulate neural regions involved in emotional learning, perception, and memory formation has received considerable research attention as a potential final common pathway to account for the aberrant emotional regulation and psychosis present in the schizophrenic syndrome. Evidence from both human neuroimaging studies and animal-based research using neurodevelopmental, behavioral, and electrophysiological techniques have implicated the mesocorticolimbic DA circuit as a crucial system for the encoding and expression of emotionally salient learning and memory formation. While many theories have examined the cortical-subcortical interactions between prefrontal cortical regions and subcortical DA substrates, many questions remain as to how DA may control emotional perception and learning and how disturbances linked to DA abnormalities may underlie the disturbed emotional processing in schizophrenia. Beyond the mesolimbic DA system, increasing evidence points to the amygdala-prefrontal cortical circuit as an important processor of emotionally salient information and how neurodevelopmental perturbances within this circuitry may lead to dysregulation of DAergic modulation of emotional processing and learning along this cortical-subcortical emotional processing circuit. PMID:17519393

  3. Cortical Spectral Activity and Connectivity during Active and Viewed Arm and Leg Movement

    PubMed Central

    Kline, Julia E.; Huang, Helen J.; Snyder, Kristine L.; Ferris, Daniel P.

    2016-01-01

    Active and viewed limb movement activate many similar neural pathways, however, to date most comparison studies have focused on subjects making small, discrete movements of the hands and feet. The purpose of this study was to determine if high-density electroencephalography (EEG) could detect differences in cortical activity and connectivity during active and viewed rhythmic arm and leg movements in humans. Our primary hypothesis was that we would detect similar but weaker electrocortical spectral fluctuations and effective connectivity fluctuations during viewed limb exercise compared to active limb exercise due to the similarities in neural recruitment. A secondary hypothesis was that we would record stronger cortical spectral fluctuations for arm exercise compared to leg exercise, because rhythmic arm exercise would be more dependent on supraspinal control than rhythmic leg exercise. We recorded EEG data while ten young healthy subjects exercised on a recumbent stepper with: (1) both arms and legs, (2) just legs, and (3) just arms. Subjects also viewed video playback of themselves or another individual performing the same exercises. We performed independent component analysis, dipole fitting, spectral analysis, and effective connectivity analysis on the data. Cortical areas comprising the premotor and supplementary motor cortex, the anterior cingulate, the posterior cingulate, and the parietal cortex exhibited significant spectral fluctuations during rhythmic limb exercise. These fluctuations tended to be greater for the arms exercise conditions than for the legs only exercise condition, which suggests that human rhythmic arm movements are under stronger cortical control than rhythmic leg movements. We did not find consistent spectral fluctuations in these areas during the viewed conditions, but effective connectivity fluctuated at harmonics of the exercise frequency during both active and viewed rhythmic limb exercise. The right premotor and supplementary motor

  4. Correlation of fingertip shear force direction with somatosensory cortical activity in monkey

    PubMed Central

    Fortier-Poisson, Pascal; Langlais, Jean-Sébastien

    2015-01-01

    To examine the activity of somatosensory cortex (S1) neurons to self-generated shear forces on the index and thumb, two monkeys were trained to grasp a stationary metal tab with a key grip and exert forces without the fingers slipping in one of four orthogonal directions for 1 s. A majority (∼85%) of slowly adapting and rapidly adapting (RA) S1 neurons had activity modulated with shear force direction. The cells were recorded mainly in areas 1 and 2 of the S1, although some area 3b neurons also responded to shear direction or magnitude. The preferred shear vectors were distributed in every direction, with tuning arcs varying from 50° to 170°. Some RA neurons sensitive to dynamic shear force direction also responded to static shear force but within a narrower range, suggesting that the direction of the shear force may influence the adaptation rate. Other neurons were modulated with shear forces in diametrically opposite directions. The directional sensitivity of S1 cortical neurons is consistent with recordings from cutaneous afferents showing that shear direction, even without slip, is a powerful stimulus to S1 neurons. PMID:26467520

  5. Accommodative response and cortical activity during sustained attention.

    PubMed

    Poltavski, Dmitri V; Biberdorf, David; Petros, Thomas V

    2012-06-15

    Greater accommodative lag and vergence deficits have been linked to attentional deficits similar to those observed in Attention Deficit Hyperactivity Disorder (ADHD). The purpose of the present study was to assess the effect of accommodative-vergence stress on a measure of sustained attention (Conners CPT) used in the diagnosis of ADHD. Twenty-seven normal non-ADHD adults completed the Conners CPT twice: wearing -2.00 D lenses and normally (without the -2.00 D lenses) in a counterbalanced order with at least 24 h between the sessions. Simultaneous recording of participants' dynamic accommodative responses was performed from the right eye using the Grand Seiko WAM-5500 auto-refractor and electroencephalographic activity (EEG) in the left prefrontal region using the Neurosky Mindset headset. The results demonstrated a significantly greater accommodative lag in the -2.00 D stress condition and a significantly poorer performance on the Conners CPT as indexed by slower reaction time, greater standard error of hit reaction time, grater response variability, poorer stimulus detectability and a greater number of perseverations. No differences were observed on measures of EEG in the theta (4-7 Hz), alpha (8-12 Hz), and beta (12-20 Hz) bands. Moreover, when directly juxtaposed with each EEG band in multiple linear regression analyses, greater accommodative lag in the stress condition was significantly associated with a greater probability of clinical classification on the Conners CPT, and was also marginally predictive of the number of omissions recorded in the stress condition. The results demonstrated that sustained attention can be influenced by such factors as accommodative-vergence stress and suggest that bottom-up processes can contribute to and potentially exacerbate attentional problems in individuals with ADHD. The study also showed that cortical dysfunction (while sufficient) may not be a necessary condition for attentional deficits.

  6. Orexin-dependent activation of layer VIb enhances cortical network activity and integration of non-specific thalamocortical inputs.

    PubMed

    Hay, Y Audrey; Andjelic, Sofija; Badr, Sammy; Lambolez, Bertrand

    2015-11-01

    Neocortical layer VI is critically involved in thalamocortical activity changes during the sleep/wake cycle. It receives dense projections from thalamic nuclei sensitive to the wake-promoting neuropeptides orexins, and its deepest part, layer VIb, is the only cortical lamina reactive to orexins. This convergence of wake-promoting inputs prompted us to investigate how layer VIb can modulate cortical arousal, using patch-clamp recordings and optogenetics in rat brain slices. We found that the majority of layer VIb neurons were excited by nicotinic agonists and orexin through the activation of nicotinic receptors containing α4-α5-β2 subunits and OX2 receptor, respectively. Specific effects of orexin on layer VIb neurons were potentiated by low nicotine concentrations and we used this paradigm to explore their intracortical projections. Co-application of nicotine and orexin increased the frequency of excitatory post-synaptic currents in the ipsilateral cortex, with maximal effect in infragranular layers and minimal effect in layer IV, as well as in the contralateral cortex. The ability of layer VIb to relay thalamocortical inputs was tested using photostimulation of channelrhodopsin-expressing fibers from the orexin-sensitive rhomboid nucleus in the parietal cortex. Photostimulation induced robust excitatory currents in layer VIa neurons that were not pre-synaptically modulated by orexin, but exhibited a delayed, orexin-dependent, component. Activation of layer VIb by orexin enhanced the reliability and spike-timing precision of layer VIa responses to rhomboid inputs. These results indicate that layer VIb acts as an orexin-gated excitatory feedforward loop that potentiates thalamocortical arousal.

  7. Inferring deep-brain activity from cortical activity using functional near-infrared spectroscopy.

    PubMed

    Liu, Ning; Cui, Xu; Bryant, Daniel M; Glover, Gary H; Reiss, Allan L

    2015-03-01

    Functional near-infrared spectroscopy (fNIRS) is an increasingly popular technology for studying brain function because it is non-invasive, non-irradiating and relatively inexpensive. Further, fNIRS potentially allows measurement of hemodynamic activity with high temporal resolution (milliseconds) and in naturalistic settings. However, in comparison with other imaging modalities, namely fMRI, fNIRS has a significant drawback: limited sensitivity to hemodynamic changes in deep-brain regions. To overcome this limitation, we developed a computational method to infer deep-brain activity using fNIRS measurements of cortical activity. Using simultaneous fNIRS and fMRI, we measured brain activity in 17 participants as they completed three cognitive tasks. A support vector regression (SVR) learning algorithm was used to predict activity in twelve deep-brain regions using information from surface fNIRS measurements. We compared these predictions against actual fMRI-measured activity using Pearson's correlation to quantify prediction performance. To provide a benchmark for comparison, we also used fMRI measurements of cortical activity to infer deep-brain activity. When using fMRI-measured activity from the entire cortex, we were able to predict deep-brain activity in the fusiform cortex with an average correlation coefficient of 0.80 and in all deep-brain regions with an average correlation coefficient of 0.67. The top 15% of predictions using fNIRS signal achieved an accuracy of 0.7. To our knowledge, this study is the first to investigate the feasibility of using cortical activity to infer deep-brain activity. This new method has the potential to extend fNIRS applications in cognitive and clinical neuroscience research.

  8. Social hierarchies and emotions: cortical prefrontal activity, facial feedback (EMG), and cognitive performance in a dynamic interaction.

    PubMed

    Balconi, Michela; Pagani, Silvia

    2015-04-01

    In the present research, we manipulated the perceived superior/inferior status during a competitive cognitive task. In two experiments, we created an explicit and strongly reinforced social hierarchy based on incidental rating on an attentional task. Based on our hypotheses, social rank may influence nonverbal cues (such as facial mimic related to emotional response), cortical lateralized activity in frontal areas (brain oscillations), and cognitive outcomes in response to rank modulation. Thus, the facial mimic (corrugators vs. zygomatic muscle activity), frequency bands (delta, theta, alpha, beta), and real cognitive performance [(error rate (ER); response times (RTs)] were considered. Specifically, a peer-group comparison was enrolled and an improved (experiment 1, N = 29) or decreased (experiment 2, N = 31) performance was artificially manipulated by the experimenter. Results showed a significant improved cognitive performance (decreased ER and RTs), an increased zygomatic activity (positive emotions), and a more prefrontal left-lateralized cortical response in the case of a perceived increased social ranking. On the contrary, a significant decreased cognitive performance (increased ER and RTs), an increased corrugators activity (negative emotions), and a less left-lateralized cortical response were observed as a consequence of a perceived decreased social ranking. Moreover, the correlational values revealed a consistent trend between behavioral (RTs) and EMG and EEG measures for both experiments. The present results suggest that social status not only guides social behavior, but it also influences cognitive processes and subjects' performance.

  9. Swallow-related cerebral cortical activity maps are not specific to deglutition.

    PubMed

    Kern, M; Birn, R; Jaradeh, S; Jesmanowicz, A; Cox, R; Hyde, J; Shaker, R

    2001-04-01

    Cortical representation of swallow-related motor tasks has not been systematically investigated. In this study, we elucidated and compared these cortical representations to those of volitional swallow using block-trial and single-trial methods. Fourteen volunteers were studied by functional magnetic resonance imaging. Cortical activation during both swallowing and swallow-related motor tasks that can be performed independent of swallowing, such as jaw clenching, lip pursing, and tongue rolling, was found in four general areas: the anterior cingulate, motor/premotor cortex, insula, and occipital/parietal region corresponding to Brodmann's areas 7, 19, and 31. Regions of activity, volume of activated voxels, and increases in signal intensity were found to be similar between volitional swallow and swallow-related motor tasks. These findings, using both block-trial and single-trial techniques, suggest that cerebral cortical regions activated during swallowing may not be specific to deglutitive function.

  10. Cortical alpha activity predicts the confidence in an impending action

    PubMed Central

    Kubanek, Jan; Hill, N. Jeremy; Snyder, Lawrence H.; Schalk, Gerwin

    2015-01-01

    When we make a decision, we experience a degree of confidence that our choice may lead to a desirable outcome. Recent studies in animals have probed the subjective aspects of the choice confidence using confidence-reporting tasks. These studies showed that estimates of the choice confidence substantially modulate neural activity in multiple regions of the brain. Building on these findings, we investigated the neural representation of the confidence in a choice in humans who explicitly reported the confidence in their choice. Subjects performed a perceptual decision task in which they decided between choosing a button press or a saccade while we recorded EEG activity. Following each choice, subjects indicated whether they were sure or unsure about the choice. We found that alpha activity strongly encodes a subject's confidence level in a forthcoming button press choice. The neural effect of the subjects' confidence was independent of the reaction time and independent of the sensory input modeled as a decision variable. Furthermore, the effect is not due to a general cognitive state, such as reward expectation, because the effect was specifically observed during button press choices and not during saccade choices. The neural effect of the confidence in the ensuing button press choice was strong enough that we could predict, from independent single trial neural signals, whether a subject was going to be sure or unsure of an ensuing button press choice. In sum, alpha activity in human cortex provides a window into the commitment to make a hand movement. PMID:26283892

  11. Pharmacological and ionic characterizations of the muscarinic receptors modulating (/sup 3/H)acetylcholine release from rat cortical synaptosomes

    SciTech Connect

    Meyer, E.M.; Otero, D.H.

    1985-05-01

    The muscarinic receptors that modulate acetylcholine release from rat cortical synaptosomes were characterized with respect to sensitivity to drugs that act selectively at M1 or M2 receptor subtypes, as well as to changes in ionic strength and membrane potential. The modulatory receptors appear to be of the M2 type, since they are activated by carbachol, acetylcholine, methacholine, oxotremorine, and bethanechol, but not by pilocarpine, and are blocked by atropine, scopolamine, and gallamine (at high concentrations), but not by pirenzepine or dicyclomine. The ED50S for carbachol, acetylcholine, and oxotremorine are less than 10 microM, suggesting that the high affinity state of the receptor is functional. High ionic strength induced by raising the NaCl concentration has no effect on agonist (oxotremorine) potency, but increases the efficacy of this compound, which disagrees with receptor-binding studies. On the other hand, depolarization with either KCl or with veratridine (20 microM) reduces agonist potencies by approximately an order of magnitude, suggesting a potential mechanism for receptor regulation.

  12. GABAA Receptor-Mediated Activity in a Model of Cortical Dysplasia

    DTIC Science & Technology

    2012-06-29

    a model of cortical dysplasia" Name of Candidate: Joseph Abbah Doctor of Philosophy Degree June 29, 2012 DISSERTATION AND ABSTRACT APPROVED...receptor-mediated activity in a model of cortical dysplasia’ is appropriately acknowledged and, beyond brief excerpts, is with the permission of the...certifies that the use of any copyrighted material in this dissertation manuscript entitled: “GABAA receptor-mediated activity in a model of

  13. Different Modulation of Common Motor Information in Rat Primary and Secondary Motor Cortices

    PubMed Central

    Saiki, Akiko; Kimura, Rie; Samura, Toshikazu; Fujiwara-Tsukamoto, Yoko; Sakai, Yutaka; Isomura, Yoshikazu

    2014-01-01

    Rodents have primary and secondary motor cortices that are involved in the execution of voluntary movements via their direct and parallel projections to the spinal cord. However, it is unclear whether the rodent secondary motor cortex has any motor function distinct from the primary motor cortex to properly control voluntary movements. In the present study, we quantitatively examined neuronal activity in the caudal forelimb area (CFA) of the primary motor cortex and rostral forelimb area (RFA) of the secondary motor cortex in head-fixed rats performing forelimb movements (pushing, holding, and pulling a lever). We found virtually no major differences between CFA and RFA neurons, regardless of neuron subtypes, not only in their basal spiking properties but also in the time-course, amplitude, and direction preference of their functional activation for simple forelimb movements. However, the RFA neurons, as compared with the CFA neurons, showed obviously a greater susceptibility of their functional activation to an alteration in a behavioral situation, a 'rewarding' response that leads to reward or a 'consummatory' response that follows reward water, which might be accompanied by some internal adaptations without affecting the motor outputs. Our results suggest that, although the CFA and RFA neurons commonly process fundamental motor information to properly control forelimb movements, the RFA neurons may be functionally differentiated to integrate motor information with internal state information for an adaptation to goal-directed behaviors. PMID:24893154

  14. Dynamic modulation of shared sensory and motor cortical rhythms mediates speech and non-speech discrimination performance

    PubMed Central

    Bowers, Andrew L.; Saltuklaroglu, Tim; Harkrider, Ashley; Wilson, Matt; Toner, Mary A.

    2014-01-01

    Oscillatory models of speech processing have proposed that rhythmic cortical oscillations in sensory and motor regions modulate speech sound processing from the bottom-up via phase reset at low frequencies (3–10 Hz) and from the top-down via the disinhibition of alpha/beta rhythms (8–30 Hz). To investigate how the proposed rhythms mediate perceptual performance, electroencephalographic (EEG) was recorded while participants passively listened to or actively identified speech and tone-sweeps in a two-force choice in noise discrimination task presented at high and low signal-to-noise ratios. EEG data were decomposed using independent component analysis and clustered across participants using principle component methods in EEGLAB. Left and right hemisphere sensorimotor and posterior temporal lobe clusters were identified. Alpha and beta suppression was associated with active tasks only in sensorimotor and temporal clusters. In posterior temporal clusters, increases in phase reset at low frequencies were driven by the quality of bottom-up acoustic information for speech and non-speech stimuli, whereas phase reset in sensorimotor clusters was associated with top-down active task demands. A comparison of correct discrimination trials to those identified at chance showed an earlier performance related effect for the left sensorimotor cluster relative to the left-temporal lobe cluster during the syllable discrimination task only. The right sensorimotor cluster was associated with performance related differences for tone–sweep stimuli only. Findings are consistent with internal model accounts suggesting that early efferent sensorimotor models transmitted along alpha and beta channels reflect a release from inhibition related to active attention to auditory discrimination. Results are discussed in the broader context of dynamic, oscillatory models of cognition proposing that top-down internally generated states interact with bottom-up sensory processing to enhance task

  15. Attention modulates spatial priority maps in the human occipital, parietal and frontal cortices

    PubMed Central

    Sprague, Thomas C.; Serences, John T.

    2014-01-01

    Computational theories propose that attention modulates the topographical landscape of spatial ‘priority’ maps in regions of visual cortex so that the location of an important object is associated with higher activation levels. While single-unit recording studies have demonstrated attention-related increases in the gain of neural responses and changes in the size of spatial receptive fields, the net effect of these modulations on the topography of region-level priority maps has not been investigated. Here, we used fMRI and a multivariate encoding model to reconstruct spatial representations of attended and ignored stimuli using activation patterns across entire visual areas. These reconstructed spatial representations reveal the influence of attention on the amplitude and size of stimulus representations within putative priority maps across the visual hierarchy. Our results suggest that attention increases the amplitude of stimulus representations in these spatial maps, particularly in higher visual areas, but does not substantively change their size. PMID:24212672

  16. Distinct activated cortical areas and volumes in Uygur-Chinese bilinguals

    PubMed Central

    Jiang, Mei; Yang, Li-Xia; Jia, Lin; Shi, Xin; Wang, Hong; Wang, Lin-yun; Abaydulla, Yari; Zhu, Li-Na; Jia, Wen-Xiao

    2015-01-01

    Objective The aim of this study is to evaluate variations in cortical activation in early and late Uygur-Chinese bilinguals from the Xinjiang Uygur Autonomous Region of China. Methodology: During a semantic judgment task with visual stimulation by a single Chinese or Uygur word, functional magnetic resonance imaging (fMRI) was performed. The fMRI data regarding activated cortical areas and volumes by both languages were analyzed. Results The first language (L1) and second language (L2) activated language-related hemispheric regions, including the left inferior frontal and parietal cortices, and L1 specifically activated the left middle temporal gyrus. For both L1 and L2, cortical activation was greater in the left hemisphere, and there was no significant difference in the lateralization index (LI) between the two languages (p > 0.05). Although the total activated cortical areas were larger in early than late bilinguals, the activation volumes were not significantly different. Conclusion Activated brains areas in early and late fluent bilinguals largely overlapped. However, these areas were more scattered upon presentation of L2 than L1, and L1 had a more specific pattern of activation than L2. For both languages, the left hemisphere was dominant. We found that L2 proficiency level rather than age of acquisition had a greater influence on which brain areas were activated with semantic processing. PMID:28123807

  17. Cortical hyperpolarization-activated depolarizing current takes part in the generation of focal paroxysmal activities

    PubMed Central

    Timofeev, Igor; Bazhenov, Maxim; Sejnowski, Terrence; Steriade, Mircea

    2002-01-01

    During paroxysmal neocortical oscillations, sudden depolarization leading to the next cycle occurs when the majority of cortical neurons are hyperpolarized. Both the Ca2+-dependent K+ currents (IK(Ca)) and disfacilitation play critical roles in the generation of hyperpolarizing potentials. In vivo experiments and computational models are used here to investigate whether the hyperpolarization-activated depolarizing current (Ih) in cortical neurons also contributes to the generation of paroxysmal onsets. Hyperpolarizing current pulses revealed a depolarizing sag in ≈20% of cortical neurons. Intracellular recordings from glial cells indirectly indicated an increase in extracellular potassium concentration ([K+]o) during paroxysmal activities, leading to a positive shift in the reversal potential of K+-mediated currents, including Ih. In the paroxysmal neocortex, ≈20% of neurons show repolarizing potentials originating from hyperpolarizations associated with depth-electroencephalogram positive waves of spike-wave complexes. The onset of these repolarizing potentials corresponds to maximal [K+]o as estimated from dual simultaneous impalements from neurons and glial cells. Computational models showed how, after the increased [K+]o, the interplay between Ih, IK(Ca), and a persistent Na+ current, INa(P), could organize paroxysmal oscillations at a frequency of 2–3 Hz. PMID:12089324

  18. Vestibular activation differentially modulates human early visual cortex and V5/MT excitability and response entropy.

    PubMed

    Seemungal, Barry M; Guzman-Lopez, Jessica; Arshad, Qadeer; Schultz, Simon R; Walsh, Vincent; Yousif, Nada

    2013-01-01

    Head movement imposes the additional burdens on the visual system of maintaining visual acuity and determining the origin of retinal image motion (i.e., self-motion vs. object-motion). Although maintaining visual acuity during self-motion is effected by minimizing retinal slip via the brainstem vestibular-ocular reflex, higher order visuovestibular mechanisms also contribute. Disambiguating self-motion versus object-motion also invokes higher order mechanisms, and a cortical visuovestibular reciprocal antagonism is propounded. Hence, one prediction is of a vestibular modulation of visual cortical excitability and indirect measures have variously suggested none, focal or global effects of activation or suppression in human visual cortex. Using transcranial magnetic stimulation-induced phosphenes to probe cortical excitability, we observed decreased V5/MT excitability versus increased early visual cortex (EVC) excitability, during vestibular activation. In order to exclude nonspecific effects (e.g., arousal) on cortical excitability, response specificity was assessed using information theory, specifically response entropy. Vestibular activation significantly modulated phosphene response entropy for V5/MT but not EVC, implying a specific vestibular effect on V5/MT responses. This is the first demonstration that vestibular activation modulates human visual cortex excitability. Furthermore, using information theory, not previously used in phosphene response analysis, we could distinguish between a specific vestibular modulation of V5/MT excitability from a nonspecific effect at EVC.

  19. Mesoscale infraslow spontaneous membrane potential fluctuations recapitulate high-frequency activity cortical motifs.

    PubMed

    Chan, Allen W; Mohajerani, Majid H; LeDue, Jeffrey M; Wang, Yu Tian; Murphy, Timothy H

    2015-07-20

    Neuroimaging of spontaneous, resting-state infraslow (<0.1 Hz) brain activity has been used to reveal the regional functional organization of the brain and may lead to the identification of novel biomarkers of neurological disease. However, these imaging studies generally rely on indirect measures of neuronal activity and the nature of the neuronal activity correlate remains unclear. Here we show, using wide-field, voltage-sensitive dye imaging, the mesoscale spatiotemporal structure and pharmacological dependence of spontaneous, infraslow cortical activity in anaesthetized and awake mice. Spontaneous infraslow activity is regionally distinct, correlates with electroencephalography and local field potential recordings, and shows bilateral symmetry between cortical hemispheres. Infraslow activity is attenuated and its functional structure abolished after treatment with voltage-gated sodium channel and glutamate receptor antagonists. Correlation analysis reveals patterns of infraslow regional connectivity that are analogous to cortical motifs observed from higher-frequency spontaneous activity and reflect the underlying framework of intracortical axonal projections.

  20. Mesoscale infraslow spontaneous membrane potential fluctuations recapitulate high-frequency activity cortical motifs

    PubMed Central

    Chan, Allen W.; Mohajerani, Majid H.; LeDue, Jeffrey M.; Wang, Yu Tian; Murphy, Timothy H.

    2016-01-01

    Neuroimaging of spontaneous, resting-state infraslow (<0.1 Hz) brain activity has been used to reveal the regional functional organization of the brain and may lead to the identification of novel biomarkers of neurological disease. However, these imaging studies generally rely on indirect measures of neuronal activity and the nature of the neuronal activity correlate remains unclear. Here we show, using wide-field, voltage-sensitive dye imaging, the mesoscale spatiotemporal structure and pharmacological dependence of spontaneous, infraslow cortical activity in anaesthetized and awake mice. Spontaneous infraslow activity is regionally distinct, correlates with electroencephalography and local field potential recordings, and shows bilateral symmetry between cortical hemispheres. Infraslow activity is attenuated and its functional structure abolished after treatment with voltage-gated sodium channel and glutamate receptor antagonists. Correlation analysis reveals patterns of infraslow regional connectivity that are analogous to cortical motifs observed from higher-frequency spontaneous activity and reflect the underlying framework of intracortical axonal projections. PMID:26190168

  1. Personality correlates (BAS-BIS), self-perception of social ranking, and cortical (alpha frequency band) modulation in peer-group comparison.

    PubMed

    Balconi, Michela; Pagani, Silvia

    2014-06-22

    The perception and interpretation of social hierarchies are a key part of our social life. In the present research we considered the activation of cortical areas, mainly the prefrontal cortex, related to social ranking perception in conjunction with some personality components (BAS - Behavioral Activation System - and BIS - Behavioral Inhibition System). In two experiments we manipulated the perceived superior/inferior status during a competitive cognitive task. Indeed, we created an explicit and strongly reinforced social hierarchy based on incidental rating in an attentional task. Specifically, a peer group comparison was undertaken and improved (Experiment 1) or decreased (Experiment 2) performance was artificially manipulated by the experimenter. For each experiment two groups were compared, based on a BAS and BIS dichotomy. Alpha band modulation in prefrontal cortex, behavioral measures (performance: error rate, ER; response times, RTs), and self-perceived ranking were considered. Repeated measures ANOVAs and regression analyses showed in Experiment 1 a significant improved cognitive performance (decreased ER and RTs) and higher self-perceived ranking in high-BAS participants. Moreover, their prefrontal activity was increased within the left side (alpha band decreasing). Conversely, in Experiment 2 a significant decreased cognitive performance (increased ER and RTs) and lower self-perceived ranking was observed in higher-BIS participants. Their prefrontal right activity was increased in comparison with higher BAS. The regression analyses confirmed the significant predictive role of alpha band modulation with respect of subjects' performance and self-perception of social ranking, differently for BAS/BIS components. The present results suggest that social status perception is directly modulated by cortical activity and personality correlates.

  2. EEG sleep slow-wave activity as a mirror of cortical maturation.

    PubMed

    Buchmann, Andreas; Ringli, Maya; Kurth, Salomé; Schaerer, Margot; Geiger, Anja; Jenni, Oskar G; Huber, Reto

    2011-03-01

    Deep (slow wave) sleep shows extensive maturational changes from childhood through adolescence, which is reflected in a decrease of sleep depth measured as the activity of electroencephalographic (EEG) slow waves. This decrease in sleep depth is paralleled by massive synaptic remodeling during adolescence as observed in anatomical studies, which supports the notion that adolescence represents a sensitive period for cortical maturation. To assess the relationship between slow-wave activity (SWA) and cortical maturation, we acquired sleep EEG and magnetic resonance imaging data in children and adolescents between 8 and 19 years. We observed a tight relationship between sleep SWA and a variety of indexes of cortical maturation derived from magnetic resonance (MR) images. Specifically, gray matter volumes in regions correlating positively with the activity of slow waves largely overlapped with brain areas exhibiting an age-dependent decrease in gray matter. The positive relationship between SWA and cortical gray matter was present also for power in other frequency ranges (theta, alpha, sigma, and beta) and other vigilance states (theta during rapid eye movement sleep). Our findings indicate a strong relationship between sleep EEG activity and cortical maturation. We propose that in particular, sleep SWA represents a good marker for structural changes in neuronal networks reflecting cortical maturation during adolescence.

  3. Active cortical innervation protects striatal neurons from slow degeneration in culture.

    PubMed

    Fishbein, Ianai; Segal, Menahem

    2011-03-01

    Spiny striatal GABAergic neurons receive most of their excitatory input from the neocortex. In culture, striatal neurons form inhibitory connections, but the lack of intrinsic excitatory afferents prevents the development of spontaneous network activity. Addition of cortical neurons to the striatal culture provides the necessary excitatory input to the striatal neurons, and in the presence of these neurons, striatal cultures do express spontaneous network activity. We have confirmed that cortical neurons provide excitatory drive to striatal neurons in culture using paired recording from cortical and striatal neurons. In the presence of tetrodotoxin (TTX), which blocks action potential discharges, the connections between cortical and striatal neurons are still formed, and in fact synaptic currents generated between them when TTX is removed are far larger than in control, undrugged cultures. Interestingly, the continuous presence of TTX in the co-culture caused striatal cell death. These observations indicate that the mere presence of cortical neurons is not sufficient to preserve striatal neurons in culture, but their synchronous activity, triggered by cortical excitatory synapses, is critical for the maintenance of viability of striatal neurons. These results have important implications for understanding the role of activity in neurodegenerative diseases of the striatum.

  4. Performance of a concurrent cognitive task modifies pre- and post-perturbation-evoked cortical activity.

    PubMed

    Mochizuki, George; Boe, Shaun G; Marlin, Amanda; McIlroy, William E

    2017-02-16

    Preparation for postural instability engages cortical resources that serve to optimize compensatory balance responses. Engagement of these cortical resources in cognitive dual-task activities may impact the ability to appropriately prepare and optimize responses to instability. The purpose of this study was to determine whether cognitive dual-task activities influenced cortical activity preceding and following postural instability. Postural instability was induced using a lean-and-release paradigm in 10 healthy participants. Perturbations were either temporally predictable (PRED) or unpredictable (UNPRED) and presented with (COG) or without a cognitive dual-task, presented in blocks of trials. The electroencephalogram was recorded from multiple frontal electrode sites. EEG data were averaged over 25-35 trials across conditions. Area under the curve of pre-perturbation cortical activity and peak latency and amplitude of post-perturbation cortical activity were quantified at the Cz site and compared across conditions. Performance of the concurrent cognitive task reduced the mean (SE) magnitude of pre-perturbation cortical activity in advance of predictable bouts of postural instability (PRED: 18.7(3.0)mVms; PRED-COG; 14.0(2.3)mVms). While the level of cognitive load influenced the amplitude of the post-perturbation N1 potential in the predictable conditions, there were no changes in N1 with a cognitive dual task during unpredictable conditions (PRED: -32.1(3.2)µV; PRED-COG: -50.8(8.4)µV; UNPRED: -65.0(12.2)µV; UNPRED-COG: -64.2(12.7)µV). Performance of the cognitive task delayed and reduced the magnitude of the initial gastrocnemius response. The findings indicate that pre- and post-perturbation cortical activity is affected by a cognitive distractor when postural instability is temporally predictable. Distraction also influences associated muscle responses.

  5. Cerebral-cortical networking and activation increase as a function of cognitive-motor task difficulty.

    PubMed

    Rietschel, Jeremy C; Miller, Matthew W; Gentili, Rodolphe J; Goodman, Ronald N; McDonald, Craig G; Hatfield, Bradley D

    2012-05-01

    Excessive increases in task difficulty typically result in marked attenuation of cognitive-motor performance. The psychomotor efficiency hypothesis suggests that poor performance is mediated by non-essential neural activity and cerebral cortical networking (inefficient cortical dynamics). This phenomenon may underlie the inverse relationship between excessive task difficulty and performance. However, investigation of the psychomotor efficiency hypothesis as it relates to task difficulty has not been conducted. The present study used electroencephalography (EEG) to examine cerebral cortical dynamics while participants were challenged with both Easy and Hard conditions during a cognitive-motor task (Tetris(®)). In accord with the psychomotor efficiency hypothesis, it was predicted that with increases in task difficulty, participants would demonstrate greater 'neural effort,' as indexed by EEG spectral power and cortical networking (i.e., EEG coherence) between the premotor (motor planning) region and sensory, executive, and motor regions. Increases in neural activation and cortical networking were observed during the Hard condition relative to the Easy condition, thus supporting the psychomotor efficiency hypothesis. To further determine the unique contributions of cognitive versus sensory-motor demands, a control experiment was conducted in which cognitive demand was increased while sensory-motor demand was held constant. This experiment revealed that regionally specific neural activation was influenced by changes in cognitive demand, whereas cortical networking to the motor planning region was sensitive only to changes in sensory-motor demand. Crucially, the present study is the first, to our knowledge, to characterize the separate impact of cognitive versus sensory-motor demands on cerebral cortical dynamics. The findings further inform the dynamics of the cortical processes that underlie the quality of cognitive-motor performance particularly with regard to task

  6. Caloric restriction stimulates autophagy in rat cortical neurons through neuropeptide Y and ghrelin receptors activation

    PubMed Central

    Carmo-Silva, Sara; Botelho, Mariana; de Almeida, Luís Pereira; Cavadas, Cláudia

    2016-01-01

    Caloric restriction is an anti-aging intervention known to extend lifespan in several experimental models, at least in part, by stimulating autophagy. Caloric restriction increases neuropeptide Y (NPY) in the hypothalamus and plasma ghrelin, a peripheral gut hormone that acts in hypothalamus to modulate energy homeostasis. NPY and ghrelin have been shown to be neuroprotective in different brain areas and to induce several physiological modifications similar to those induced by caloric restriction. However, the effect of NPY and ghrelin in autophagy in cortical neurons is currently not known. Using a cell culture of rat cortical neurons we investigate the involvement of NPY and ghrelin in caloric restriction-induced autophagy. We observed that a caloric restriction mimetic cell culture medium stimulates autophagy in rat cortical neurons and NPY or ghrelin receptor antagonists blocked this effect. On the other hand, exogenous NPY or ghrelin stimulate autophagy in rat cortical neurons. Moreover, NPY mediates the stimulatory effect of ghrelin on autophagy in rat cortical neurons. Since autophagy impairment occurs in aging and age-related neurodegenerative diseases, NPY and ghrelin synergistic effect on autophagy stimulation may suggest a new strategy to delay aging process. PMID:27441412

  7. Cortical current density oscillations in the motor cortex are correlated with muscular activity during pedaling exercise.

    PubMed

    Schneider, S; Rouffet, D M; Billaut, F; Strüder, H K

    2013-01-03

    Despite modern imaging techniques, assessing and localizing changes in brain activity during whole-body exercise is still challenging. Using an active electroencephalography (EEG) system in combination with source localization algorithms, this study aimed to localize brain cortical oscillations patterns in the motor cortex and to correlate these with surface electromyography (EMG)-detected muscular activity during pedaling exercise. Eight subjects performed 2-min isokinetic (90 rpm) cycling bouts at intensities ranging from 1 to 5 Wkg(-1) body mass on a cycle ergometer. These bouts were interspersed by a minimum of 2 min of passive rest to limit to development of peripheral muscle fatigue. Brain cortical activity within the motor cortex was analyzed using a 32-channel active EEG system combined with source localization algorithms. EMG activity was recorded from seven muscles on each lower limb. EEG and EMG activity revealed comparatively stable oscillations across the different exercise intensities. More importantly, the oscillations in cortical activity within the motor cortex were significantly correlated with EMG activity during the high-intensity cycling bouts. This study demonstrates that it is possible to localize oscillations in brain cortical activity during moderate- to high-intensity cycling exercise using EEG in combination with source localization algorithms, and that these oscillations match the activity of the active muscles in time and amplitude. Results of this study might help to further evaluate the effects of central vs. peripheral fatigue during exercise.

  8. Shifts of Gamma Phase across Primary Visual Cortical Sites Reflect Dynamic Stimulus-Modulated Information Transfer

    PubMed Central

    Besserve, Michel; Lowe, Scott C.; Logothetis, Nikos K.; Schölkopf, Bernhard; Panzeri, Stefano

    2015-01-01

    Distributed neural processing likely entails the capability of networks to reconfigure dynamically the directionality and strength of their functional connections. Yet, the neural mechanisms that may allow such dynamic routing of the information flow are not yet fully understood. We investigated the role of gamma band (50–80 Hz) oscillations in transient modulations of communication among neural populations by using measures of direction-specific causal information transfer. We found that the local phase of gamma-band rhythmic activity exerted a stimulus-modulated and spatially-asymmetric directed effect on the firing rate of spatially separated populations within the primary visual cortex. The relationships between gamma phases at different sites (phase shifts) could be described as a stimulus-modulated gamma-band wave propagating along the spatial directions with the largest information transfer. We observed transient stimulus-related changes in the spatial configuration of phases (compatible with changes in direction of gamma wave propagation) accompanied by a relative increase of the amount of information flowing along the instantaneous direction of the gamma wave. These effects were specific to the gamma-band and suggest that the time-varying relationships between gamma phases at different locations mark, and possibly causally mediate, the dynamic reconfiguration of functional connections. PMID:26394205

  9. Reduced modulation of scanpaths in response to task demands in posterior cortical atrophy.

    PubMed

    Shakespeare, Timothy J; Pertzov, Yoni; Yong, Keir X X; Nicholas, Jennifer; Crutch, Sebastian J

    2015-02-01

    A difficulty in perceiving visual scenes is one of the most striking impairments experienced by patients with the clinico-radiological syndrome posterior cortical atrophy (PCA). However whilst a number of studies have investigated perception of relatively simple experimental stimuli in these individuals, little is known about multiple object and complex scene perception and the role of eye movements in posterior cortical atrophy. We embrace the distinction between high-level (top-down) and low-level (bottom-up) influences upon scanning eye movements when looking at scenes. This distinction was inspired by Yarbus (1967), who demonstrated how the location of our fixations is affected by task instructions and not only the stimulus' low level properties. We therefore examined how scanning patterns are influenced by task instructions and low-level visual properties in 7 patients with posterior cortical atrophy, 8 patients with typical Alzheimer's disease, and 19 healthy age-matched controls. Each participant viewed 10 scenes under four task conditions (encoding, recognition, search and description) whilst eye movements were recorded. The results reveal significant differences between groups in the impact of test instructions upon scanpaths. Across tasks without a search component, posterior cortical atrophy patients were significantly less consistent than typical Alzheimer's disease patients and controls in where they were looking. By contrast, when comparing search and non-search tasks, it was controls who exhibited lowest between-task similarity ratings, suggesting they were better able than posterior cortical atrophy or typical Alzheimer's disease patients to respond appropriately to high-level needs by looking at task-relevant regions of a scene. Posterior cortical atrophy patients had a significant tendency to fixate upon more low-level salient parts of the scenes than controls irrespective of the viewing task. The study provides a detailed characterisation of

  10. Mitochondrial activity and brain functions during cortical depolarization

    NASA Astrophysics Data System (ADS)

    Mayevsky, Avraham; Sonn, Judith

    2008-12-01

    Cortical depolarization (CD) of the cerebral cortex could be developed under various pathophysiological conditions. In animal models, CD was recorded under partial or complete ischemia as well as when cortical spreading depression (SD) was induced externally or by internal stimulus. The development of CD in patients and the changes in various metabolic parameters, during CD, was rarely reported. Brain metabolic, hemodynamic, ionic and electrical responses to the CD event are dependent upon the O2 balance in the tissue. When the O2 balance is negative (i.e. ischemia), the CD process will be developed due to mitochondrial dysfunction, lack of energy and the inhibition of Na+-K+-ATPase. In contradiction, when oxygen is available (i.e. normoxia) the development of CD after induction of SD will accelerate mitochondrial respiration for retaining ionic homeostasis and normal brain functions. We used the multiparametric monitoring approach that enable real time monitoring of mitochondrial NADH redox state, microcirculatory blood flow and oxygenation, extracellular K+, Ca2+, H+ levels, DC steady potential and electrocorticogram (ECoG). This monitoring approach, provide a unique tool that has a significant value in analyzing the pathophysiology of the brain when SD developed under normoxia, ischemia, or hypoxia. We applied the same monitoring approach to patients suffered from severe head injury or exposed to neurosurgical procedures.

  11. Nanoscale laminin coating modulates cortical scarring response around implanted silicon microelectrode arrays

    NASA Astrophysics Data System (ADS)

    He, Wei; McConnell, George C.; Bellamkonda, Ravi V.

    2006-12-01

    Neural electrodes could significantly enhance the quality of life for patients with sensory and/or motor deficits as well as improve our understanding of brain functions. However, long-term electrical connectivity between neural tissue and recording sites is compromised by the development of astroglial scar around the recording probes. In this study we investigate the effect of a nanoscale laminin (LN) coating on Si-based neural probes on chronic cortical tissue reaction in a rat model. Tissue reaction was evaluated after 1 day, 1 week, and 4 weeks post-implant for coated and uncoated probes using immunohistochemical techniques to evaluate activated microglia/macrophages (ED-1), astrocytes (GFAP) and neurons (NeuN). The coating did not have an observable effect on neuronal density or proximity to the electrode surface. However, the response of microglia/macrophages and astrocytes was altered by the coating. One day post-implant, we observed an ~60% increase in ED-1 expression near LN-coated probe sites compared with control uncoated probe sites. Four weeks post-implant, we observed an ~20% reduction in ED-1 expression along with an ~50% reduction in GFAP expression at coated relative to uncoated probe sites. These results suggest that LN has a stimulatory effect on early microglia activation, accelerating the phagocytic function of these cells. This hypothesis is further supported by the increased mRNA expression of several pro-inflammatory cytokines (TNF-α, IL-1 and IL-6) in cultured microglia on LN-bound Si substrates. LN immunostaining of coated probes immediately after insertion and retrieval demonstrates that the coating integrity is not compromised by the shear force during insertion. We speculate, based on these encouraging results, that LN coating of Si neural probes could potentially improve chronic neural recordings through dispersion of the astroglial scar.

  12. Submillimeter Confocal Imaging Active Module

    NASA Technical Reports Server (NTRS)

    Hong, John; Mehdi, Imran; Siegel, Peter; Chattopadhyay, Goutam; Cwik, Thomas; Rowell, Mark; Hacker, John

    2009-01-01

    The term submillimeter confocal imaging active module (SCIAM) denotes a proposed airborne coherent imaging radar system that would be suitable for use in reconnaissance, surveillance, and navigation. The development of the SCIAM would include utilization and extension of recent achievements in monolithic microwave integrated circuits capable of operating at frequencies up to and beyond a nominal radio frequency of 340 GHz. Because the SCIAM would be primarily down-looking (in contradistinction to primarily side-looking), it could be useful for imaging shorter objects located between taller ones (for example, objects on streets between buildings). The SCIAM would utilize a confocal geometry to obtain high cross-track resolution, and would be amenable to synthetic-aperture processing of its output to obtain high along-track resolution. The SCIAM (see figure) would include multiple (two in the initial version) antenna apertures, separated from each other by a cross-track baseline of suitable length (e.g., 1.6 m). These apertures would both transmit the illuminating radar pulses and receive the returns. A common reference oscillator would generate a signal at a controllable frequency of (340 GHz + (Delta)f)/N, where (Delta)f is an instantaneous swept frequency difference and N is an integer. The output of this oscillator would be fed to a frequency- multiplier-and-power-amplifier module to obtain a signal, at 340 GHz + (Delta)f, that would serve as both the carrier signal for generating the transmitted pulses and a local-oscillator (LO) signal for a receiver associated with each antenna aperture. Because duplexers in the form of circulators or transmit/receive (T/R) switches would be lossy and extremely difficult to implement, the antenna apertures would be designed according to a spatial-diplexing scheme, in which signals would be coupled in and out via separate, adjacent transmitting and receiving feed horns. This scheme would cause the transmitted and received beams

  13. Differential modulation of STN-cortical and cortico-muscular coherence by movement and levodopa in Parkinson's disease.

    PubMed

    Hirschmann, J; Özkurt, T E; Butz, M; Homburger, M; Elben, S; Hartmann, C J; Vesper, J; Wojtecki, L; Schnitzler, A

    2013-03-01

    Previous research suggests that oscillatory coupling between cortex, basal ganglia and muscles plays an important role in motor behavior. Furthermore, there is evidence that oscillatory coupling is altered in patients with movement disorders such as Parkinson's disease (PD). In this study, we performed simultaneous magnetoencephalography (MEG), local field potential (LFP) and electromyogram (EMG) recordings in PD patients selected for therapeutic subthalamic nucleus (STN) stimulation. Patients were recorded (i) after withdrawal of anti-parkinsonian medication (OFF) and (ii) after levodopa administration (ON). We analyzed STN-cortical and cortico-muscular coherence during static forearm contraction and repetitive hand movement in order to evaluate modulations of coherence by movement and medication. Based on previous results from studies investigating resting state coherence in PD patients, we selected primary motor cortex (M1) and superior temporal gyrus (STG) as regions of interest. We found beta coherence between M1 and STN to be suppressed by administration of levodopa. M1-muscular coherence was strongly reduced in the alpha and beta band during repetitive movement compared to static contraction, but was unaffected by administration of levodopa. Strong STG-STN but not STG-muscular coherence could be observed in the alpha band. Coherence with STG was modulated neither by movement nor by medication. Finally, we found both M1-STN and M1-muscular beta coherence to be negatively correlated with UPDRS akinesia and rigidity sub-scores in the OFF state. The present study provides new insights into the functional roles of STN-cortical and cortico-muscular coherence and their relationship to PD symptoms. The results indicate that STN-cortical and cortico-muscular coupling are correlated, but can be modulated independently. Moreover, they show differences in their frequency-specific topography. We conclude that they represent partly independent sub-loops within the motor

  14. Screening with an NMNAT2-MSD platform identifies small molecules that modulate NMNAT2 levels in cortical neurons

    PubMed Central

    Ali, Yousuf O.; Bradley, Gillian; Lu, Hui-Chen

    2017-01-01

    Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) is a key neuronal maintenance factor and provides potent neuroprotection in numerous preclinical models of neurological disorders. NMNAT2 is significantly reduced in Alzheimer’s, Huntington’s, Parkinson’s diseases. Here we developed a Meso Scale Discovery (MSD)-based screening platform to quantify endogenous NMNAT2 in cortical neurons. The high sensitivity and large dynamic range of this NMNAT2-MSD platform allowed us to screen the Sigma LOPAC library consisting of 1280 compounds. This library had a 2.89% hit rate, with 24 NMNAT2 positive and 13 negative modulators identified. Western analysis was conducted to validate and determine the dose-dependency of identified modulators. Caffeine, one identified NMNAT2 positive-modulator, when systemically administered restored NMNAT2 expression in rTg4510 tauopathy mice to normal levels. We confirmed in a cell culture model that four selected positive-modulators exerted NMNAT2-specific neuroprotection against vincristine-induced cell death while four selected NMNAT2 negative modulators reduced neuronal viability in an NMNAT2-dependent manner. Many of the identified NMNAT2 positive modulators are predicted to increase cAMP concentration, suggesting that neuronal NMNAT2 levels are tightly regulated by cAMP signaling. Taken together, our findings indicate that the NMNAT2-MSD platform provides a sensitive phenotypic screen to detect NMNAT2 in neurons. PMID:28266613

  15. Relationship between motor activity-related cortical potential and voluntary muscle activation.

    PubMed

    Siemionow, V; Yue, G H; Ranganathan, V K; Liu, J Z; Sahgal, V

    2000-08-01

    The purpose of this study was to investigate the relationship between EEG-derived motor activity-related cortical potential (MRCP) and voluntary muscle activation. Eight healthy volunteers participated in two experimental sessions. In one session, subjects performed isometric elbow-flexion contractions at four intensity levels [10%, 35%, 60%, and 85% maximal voluntary contraction (MVC)]. In another session, a given elbow-flexion force (35% MVC) was generated at three different rates (slow, intermediate, and fast). Thirty to 40 contractions were performed at each force level or rate. EEG signals were recorded from the scalp overlying the supplementary motor area (SMA) and contralateral sensorimotor cortex, and EMG signals were recorded from the skin surface overlying the belly of the biceps brachii and brachioradialis muscles during all contractions. In each trial, the force was used as the triggering signal for MRCP averaging. MRCP amplitude was measured from the beginning to the peak of the negative slope. The magnitude of MRCP from both EEG recording locations (sensorimotor cortex and SMA) was highly correlated with elbow-flexion force, rate of rising of force, and muscle EMG signals. These results suggest that MRCP represents cortical motor commands that scale the level of muscle activation.

  16. Spatiotemporal regulation of chemical reaction kinetics of cell surface molecules by active remodeling of cortical actin

    NASA Astrophysics Data System (ADS)

    Bhattacharyya, Bhaswati; Chaudhuri, Abhishek; Gowrishankar, Kripa; Mayor, Satyajit; Rao, Madan

    2010-03-01

    Cell surface proteins such as lipid tethered GPI-anchored proteins and Ras-proteins are distributed as monomers and nanoclusters on the surface of living cells. Recent work from our laboratory suggests that the spatial distribution and dynamics of formation and breakup of these nanoclusters is controlled by the active remodeling dynamics of the underlying cortical actin. To explain these observations, we propose a novel mechanism of nanoclustering, involving the transient binding to and advection along constitutively occuring ``asters'' of cortical actin. Here we study the consequences of such active actin based clustering, in the context of chemical reactions involving conformational changes of cell surface proteins. We find that active remodeling of cortical actin, can give rise to a dramatic increase in the reaction efficiency and output levels. In general, such actin driven clustering of membrane proteins could be a cellular mechanism to spatiotemporally regulate and amplify local chemical reaction rates, in the context of signalling and endocytosis.

  17. Pathological ponto-cerebello-thalamo-cortical activations in primary orthostatic tremor during lying and stance.

    PubMed

    Schöberl, Florian; Feil, Katharina; Xiong, Guoming; Bartenstein, Peter; la Fougére, Christian; Jahn, Klaus; Brandt, Thomas; Strupp, Michael; Dieterich, Marianne; Zwergal, Andreas

    2017-01-01

    Primary orthostatic tremor is a rare neurological disease characterized mainly by a high frequency tremor of the legs while standing. The aim of this study was to identify the common core structures of the oscillatory circuit in orthostatic tremor and how it is modulated by changes of body position. Ten patients with orthostatic tremor and 10 healthy age-matched control subjects underwent a standardized neurological and neuro-ophthalmological examination including electromyographic and posturographic recordings. Task-dependent changes of cerebral glucose metabolism during lying and standing were measured in all subjects by sequential (18)F-fluorodeoxyglucose-positron emission tomography on separate days. Results were compared between groups and conditions. All the orthostatic tremor patients, but no control subject, showed the characteristic 13-18 Hz tremor in coherent muscles during standing, which ceased in the supine position. While lying, patients had a significantly increased regional cerebral glucose metabolism in the pontine tegmentum, the posterior cerebellum (including the dentate nuclei), the ventral intermediate and ventral posterolateral nucleus of the thalamus, and the primary motor cortex bilaterally compared to controls. Similar glucose metabolism changes occurred with clinical manifestation of the tremor during standing. The glucose metabolism was relatively decreased in mesiofrontal cortical areas (i.e. the medial prefrontal cortex, supplementary motor area and anterior cingulate cortex) and the bilateral anterior insula in orthostatic tremor patients while lying and standing. The mesiofrontal hypometabolism correlated with increased body sway in posturography. This study confirms and further elucidates ponto-cerebello-thalamo-primary motor cortical activations underlying primary orthostatic tremor, which presented consistently in a group of patients. Compared to other tremor disorders one characteristic feature in orthostatic tremor seems to be

  18. Sfr1, a Tetrahymena thermophila Sfi1 Repeat Protein, Modulates the Production of Cortical Row Basal Bodies

    PubMed Central

    Heydeck, Westley; Stemm-Wolf, Alexander J.; Knop, Janin; Poh, Christina C.

    2016-01-01

    ABSTRACT Basal bodies are essential microtubule-based structures that template, anchor, and orient cilia at the cell surface. Cilia act primarily in the generation of directional fluid flow and sensory reception, both of which are utilized for a broad spectrum of cellular processes. Although basal bodies contribute to vital cell functions, the molecular contributors of their assembly and maintenance are poorly understood. Previous studies of the ciliate Tetrahymena thermophila revealed important roles for two centrin family members in basal body assembly, separation of new basal bodies, and stability. Here, we characterize the basal body function of a centrin-binding protein, Sfr1, in Tetrahymena. Sfr1 is part of a large family of 13 proteins in Tetrahymena that contain Sfi1 repeats (SFRs), a motif originally identified in Saccharomyces cerevisiae Sfi1 that binds centrin. Sfr1 is the only SFR protein in Tetrahymena that localizes to all cortical row and oral apparatus basal bodies. In addition, Sfr1 resides predominantly at the microtubule scaffold from the proximal cartwheel to the distal transition zone. Complete genomic knockout of SFR1 (sfr1Δ) causes a significant increase in both cortical row basal body density and the number of cortical rows, contributing to an overall overproduction of basal bodies. Reintroduction of Sfr1 into sfr1Δ mutant cells leads to a marked reduction of cortical row basal body density and the total number of cortical row basal bodies. Therefore, Sfr1 directly modulates cortical row basal body production. This study reveals an inhibitory role for Sfr1, and potentially centrins, in Tetrahymena basal body production. IMPORTANCE Basal bodies and centrioles are structurally similar and, when rendered dysfunctional as a result of improper assembly or maintenance, are associated with human diseases. Centrins are conserved and abundant components of both structures whose basal body and centriolar functions remain incompletely understood

  19. PKCδ regulates cortical radial migration by stabilizing the Cdk5 activator p35

    PubMed Central

    Zhao, Chun-tao; Li, Kun; Li, Jun-tao; Zheng, Wang; Liang, Xu-jun; Geng, An-qi; Li, Ning; Yuan, Xiao-bing

    2009-01-01

    Cyclin-dependent kinase 5 (Cdk5) and its activator p35 are critical for radial migration and lamination of cortical neurons. However, how this kinase is regulated by extracellular and intracellular signals during cortical morphogenesis remains unclear. Here, we show that PKCδ, a member of novel PKC expressing in cortical neurons, could stabilize p35 by direct phosphorylation. PKCδ attenuated the degradation of p35 but not its mutant derivative, which could not be phosphorylated by PKCδ. Down-regulation of PKCδ by in utero electroporation of specific small interference RNA (siRNA) severely impaired the radial migration of cortical neurons. This migration defect was similar to that caused by down-regulation of p35 and could be prevented by cotransfection with the wild-type but not the mutant p35. Furthermore, PKCδ could be activated by the promigratory factor brain-derived neurotrophic factor (BDNF) and was required for the activation of Cdk5 by BDNF. Both PKCδ and p35 were required for the promigratory effect of BDNF on cultured newborn neurons. Thus, PKCδ may promote cortical radial migration through maintaining the proper level of p35 in newborn neurons. PMID:19965374

  20. Age-related differences in cortical activity during a visuo-spatial working memory task with facial stimuli.

    PubMed

    Belham, Flávia Schechtman; Satler, Corina; Garcia, Ana; Tomaz, Carlos; Gasbarri, Antonella; Rego, Artur; Tavares, Maria Clotilde H

    2013-01-01

    Emotion, importantly displayed by facial expressions, is one of the most significant memory modulators. The interaction between memory and the different emotional valences change across lifespan, while young adults (YA) are expected to better recall negative events (Negativity Bias Hypothesis), older adults (OA) tend to focus on positive stimuli (Positivity Effect Hypothesis). This research work aims at verifying whether cortical electrical activity of these two age groups would also be differently influenced by emotional valences in a visuo-spatial working memory task. 27 YA (13 males) and 25 OA (14 males), all healthy volunteers, underwent electroencephalographic recordings (21 scalp electrodes montage), while performing the Spatial Delayed Recognition Span Task using a touch screen with different stimuli categories: neutral, positive and negative faces and geometric pictures. YA obtained higher scores than OA, and showed higher activation of theta and alpha bands in the frontal and midline regions, besides a more evident right-hemispheric asymmetry on alpha band when compared to OA. For both age groups, performance in the task was worse for positive faces than to negative and to neutral faces. Facial stimuli induced a better performance and higher alpha activation on the pre-frontal region for YA, and on the midline, occipital and left temporal regions for OA when compared to geometric figures. The superior performance of YA was expected due to the natural cognitive deficits connected to ageing, as was a better performance with facial stimuli due to the evolutionary importance of faces. These results were related to cortical activity on areas of importance for action-planning, decision making and sustained attention. Taken together, they are in accordance with the Negativity Bias but do not support the Positivity Effect. The methodology used was able to identify age-related differences in cortical activity during emotional mnemonic processing and may be

  1. Age-Related Differences in Cortical Activity during a Visuo-Spatial Working Memory Task with Facial Stimuli

    PubMed Central

    Belham, Flávia Schechtman; Satler, Corina; Garcia, Ana; Tomaz, Carlos; Gasbarri, Antonella; Rego, Artur; Tavares, Maria Clotilde H.

    2013-01-01

    Emotion, importantly displayed by facial expressions, is one of the most significant memory modulators. The interaction between memory and the different emotional valences change across lifespan, while young adults (YA) are expected to better recall negative events (Negativity Bias Hypothesis), older adults (OA) tend to focus on positive stimuli (Positivity Effect Hypothesis). This research work aims at verifying whether cortical electrical activity of these two age groups would also be differently influenced by emotional valences in a visuo-spatial working memory task. 27 YA (13 males) and 25 OA (14 males), all healthy volunteers, underwent electroencephalographic recordings (21 scalp electrodes montage), while performing the Spatial Delayed Recognition Span Task using a touch screen with different stimuli categories: neutral, positive and negative faces and geometric pictures. YA obtained higher scores than OA, and showed higher activation of theta and alpha bands in the frontal and midline regions, besides a more evident right-hemispheric asymmetry on alpha band when compared to OA. For both age groups, performance in the task was worse for positive faces than to negative and to neutral faces. Facial stimuli induced a better performance and higher alpha activation on the pre-frontal region for YA, and on the midline, occipital and left temporal regions for OA when compared to geometric figures. The superior performance of YA was expected due to the natural cognitive deficits connected to ageing, as was a better performance with facial stimuli due to the evolutionary importance of faces. These results were related to cortical activity on areas of importance for action-planning, decision making and sustained attention. Taken together, they are in accordance with the Negativity Bias but do not support the Positivity Effect. The methodology used was able to identify age-related differences in cortical activity during emotional mnemonic processing and may be

  2. Cortical bitufted, horizontal, and Martinotti cells preferentially express and secrete reelin into perineuronal nets, nonsynaptically modulating gene expression

    PubMed Central

    Pesold, Christine; Liu, Wen Sheng; Guidotti, Alessandro; Costa, Erminio; Caruncho, Hector J.

    1999-01-01

    Reelin (Reln) is a protein with some structural analogies with other extracellular matrix proteins that functions in the regulation of neuronal migration during the development of cortical laminated structures. In the cortex of adult animals, Reln is expressed primarily in γ-aminobutyric acid (GABA)ergic neurons and is secreted into perineuronal nets. However, only 50–60% of GABAergic interneurons express Reln. We have characterized this subpopulation of cortical GABAergic neurons that expresses Reln by using two strategies: (i) a double immunolabeling procedure to determine the colocalization of Reln with neuropeptides and Ca2+-binding proteins and (ii) a combination of Golgi staining and Reln immunolabeling to determine the morphology of the rat cortical cells that store Reln. Many interneurons that express Neuropeptide Y (NPY) or somatostatin (but none of those that express parvalbumin) are Reln-immunopositive. A small population of calbindin-positive interneurons and very few calretinin-positive cells express Reln immunopositivity. Golgi staining revealed that layer I horizontal cells, layer II–V bitufted neurons, and some deep cortical layer Martinotti cells express Reln. Basket and chandelier cells are often immunopositive to parvalbumin, but never to Reln. Although Reln is secreted by GABAergic neurons, its target are not the GABA receptors, but rather may be extrasynaptically located in perineuronal nets and concerned with the modulation of neuronal plasticity. Dab1, the target adapter protein that presumably mediates transcription regulation via the extrasynaptic actions of Reln, is expressed predominantly in pyramidal neurons, but it can also be detected in a small population of GABAergic neurons that are neither horizontal nor bitufted neurons. PMID:10077664

  3. Endocannabinoids modulate cortical development by configuring Slit2/Robo1 signaling

    PubMed Central

    Alpár, Alán; Tortoriello, Giuseppe; Calvigioni, Daniela; Niphakis, Micah J; Milenkovic, Ivan; Bakker, Joanne; Cameron, Gary A; Hanics, János; Morris, Claudia V; Fuzik, János; Kovacs, Gabor G; Cravatt, Benjamin F; Parnavelas, John G; Andrews, William D; Hurd, Yasmin L; Keimpema, Erik; Harkany, Tibor

    2014-01-01

    Local environmental cues are indispensable for axonal growth and guidance during brain circuit formation. Here, we combine genetic and pharmacological tools, as well as systems neuroanatomy in human fetuses and mouse models, to study the role of endocannabinoid and Slit/Robo signaling in axonal growth. We show that excess 2-arachidonoylglycerol, an endocannabinoid affecting directional axonal growth, triggers corpus callosum enlargement due to errant CB1 cannabinoid receptor (CB1R)-containing corticofugal axon spreading. This phenotype mechanistically relies on the premature differentiation and end-feet proliferation of CB2R-expressing oligodendrocytes. We further show the dependence of both axonal Robo1 positioning and oligodendroglial Slit2 production on cell-type specific cannabinoid receptor activation. Accordingly, Robo1 and/or Slit2 manipulation limits endocannabinoid modulation of axon guidance. We conclude that endocannabinoids can configure focal Slit2/Robo1 signaling to modulate directional axonal growth, which may provide a basis for understanding impaired brain wiring associated with metabolic deficits and prenatal drug exposure. PMID:25030704

  4. Observation of implied motion in a work of art modulates cortical connectivity and plasticity

    PubMed Central

    Concerto, Carmen; Infortuna, Carmenrita; Mineo, Ludovico; Pereira, Manuel; Freedberg, David; Chusid, Eileen; Aguglia, Eugenio; Battaglia, Fortunato

    2016-01-01

    Following the discovery of mirror neurons, much attention has been de-voted to understanding the neural responses evoked by observation of implied motion in works of art. Neuroimaging studies have demonstrated that dorsal premotor cortex (PMd) is commonly involved during observation of movements but the role of the inhibitory and excitatory connections between PMd and primary motor cortex (M1) during observation of implied motion remains uncertain. In this study, using high and low frequency repetitive transcranial magnetic stimulation (rTMS), we examined PMd–M1 connectivity and plasticity during observation of Michelangelo’s frescos with and without implied motion (Sistine Chapel, 1508–1512). We found that observation of implied motion in a painting specifically reduces the activity of inhibitory PMd–M1 connections. On the contrary PMd–M1 facilitatory connections, as examined by means of 5-Hz rTMS, were not modulated during observation of the painting. Our data suggest that observation of implied motion in a painting modulates PMd–M1 connectivity and plasticity. These results are consistent with the hypothesis that art with implied motion might be used as a plasticity-based intervention in rehabilitation. PMID:27807519

  5. Auditory Cortical Activity During Cochlear Implant-Mediated Perception of Spoken Language, Melody, and Rhythm

    PubMed Central

    Molloy, Anne T.; Jiradejvong, Patpong; Braun, Allen R.

    2009-01-01

    Despite the significant advances in language perception for cochlear implant (CI) recipients, music perception continues to be a major challenge for implant-mediated listening. Our understanding of the neural mechanisms that underlie successful implant listening remains limited. To our knowledge, this study represents the first neuroimaging investigation of music perception in CI users, with the hypothesis that CI subjects would demonstrate greater auditory cortical activation than normal hearing controls. H215O positron emission tomography (PET) was used here to assess auditory cortical activation patterns in ten postlingually deafened CI patients and ten normal hearing control subjects. Subjects were presented with language, melody, and rhythm tasks during scanning. Our results show significant auditory cortical activation in implant subjects in comparison to control subjects for language, melody, and rhythm. The greatest activity in CI users compared to controls was seen for language tasks, which is thought to reflect both implant and neural specializations for language processing. For musical stimuli, PET scanning revealed significantly greater activation during rhythm perception in CI subjects (compared to control subjects), and the least activation during melody perception, which was the most difficult task for CI users. These results may suggest a possible relationship between auditory performance and degree of auditory cortical activation in implant recipients that deserves further study. PMID:19662456

  6. Behavioral activation system modulation on brain activation during appetitive and aversive stimulus processing

    PubMed Central

    Ventura-Campos, Noelia; Sanjuán-Tomás, Ana; Belloch, Vicente; Parcet, Maria-Antònia; Ávila, César

    2010-01-01

    The reinforcement sensitivity theory (RST) proposed the behavioral activation system (BAS) as a neurobehavioral system that is dependent on dopamine-irrigated structures and that mediates the individual differences in sensitivity and reactivity to appetitive stimuli associated with BAS-related personality traits. Theoretical developments propose that high BAS sensitivity is associated with both enhanced appetitive stimuli processing and the diminished processing of aversive stimuli. The objective of this study was to analyze how individual differences in BAS functioning were associated with brain activation during erotic and aversive picture processing while subjects were involved in a simple goal-directed task. Forty-five male participants took part in this study. The task activation results confirm the activation of the reward and punishment brain-related structures while viewing erotic and aversive pictures, respectively. The SR scores show a positive correlation with activation of the left lateral prefrontal cortex, the mesial prefrontal cortex and the right occipital cortex while viewing erotic pictures, and a negative correlation with the right lateral prefrontal cortex and the left occipital cortex while viewing aversive pictures. In summary, the SR scores modulate the activity of the cortical areas in the prefrontal and the occipital cortices that are proposed to modulate the BAS and the BIS-FFFS. PMID:20147458

  7. Auditory Selective Attention Reveals Preparatory Activity in Different Cortical Regions for Selection Based on Source Location and Source Pitch

    PubMed Central

    Lee, Adrian K. C.; Rajaram, Siddharth; Xia, Jing; Bharadwaj, Hari; Larson, Eric; Hämäläinen, Matti S.; Shinn-Cunningham, Barbara G.

    2012-01-01

    In order to extract information in a rich environment, we focus on different features that allow us to direct attention to whatever source is of interest. The cortical network deployed during spatial attention, especially in vision, is well characterized. For example, visuospatial attention engages a frontoparietal network including the frontal eye fields (FEFs), which modulate activity in visual sensory areas to enhance the representation of an attended visual object. However, relatively little is known about the neural circuitry controlling attention directed to non-spatial features, or to auditory objects or features (either spatial or non-spatial). Here, using combined magnetoencephalography (MEG) and anatomical information obtained from MRI, we contrasted cortical activity when observers attended to different auditory features given the same acoustic mixture of two simultaneous spoken digits. Leveraging the fine temporal resolution of MEG, we establish that activity in left FEF is enhanced both prior to and throughout the auditory stimulus when listeners direct auditory attention to target location compared to when they focus on target pitch. In contrast, activity in the left posterior superior temporal sulcus (STS), a region previously associated with auditory pitch categorization, is greater when listeners direct attention to target pitch rather than target location. This differential enhancement is only significant after observers are instructed which cue to attend, but before the acoustic stimuli begin. We therefore argue that left FEF participates more strongly in directing auditory spatial attention, while the left STS aids auditory object selection based on the non-spatial acoustic feature of pitch. PMID:23335874

  8. Active combustion flow modulation valve

    DOEpatents

    Hensel, John Peter; Black, Nathaniel; Thorton, Jimmy Dean; Vipperman, Jeffrey Stuart; Lambeth, David N; Clark, William W

    2013-09-24

    A flow modulation valve has a slidably translating hollow armature with at least one energizable coil wound around and fixably attached to the hollow armature. The energizable coil or coils are influenced by at least one permanent magnet surrounding the hollow armature and supported by an outer casing. Lorentz forces on the energizable coils which are translated to the hollow armature, increase or decrease the flow area to provide flow throttling action. The extent of hollow armature translation depends on the value of current supplied and the direction of translation depends on the direction of current flow. The compact nature of the flow modulation valve combined with the high forces afforded by the actuator design provide a flow modulation valve which is highly responsive to high-rate input control signals.

  9. Alzheimer risk genes modulate the relationship between plasma apoE and cortical PiB binding

    PubMed Central

    Lazaris, Andreas; Hwang, Kristy S.; Goukasian, Naira; Ramirez, Leslie M.; Eastman, Jennifer; Blanken, Anna E.; Teng, Edmond; Gylys, Karen; Cole, Greg; Saykin, Andrew J.; Shaw, Leslie M.; Trojanowski, John Q.; Jagust, William J.; Weiner, Michael W.

    2015-01-01

    Objective: We investigated the association between apoE protein plasma levels and brain amyloidosis and the effect of the top 10 Alzheimer disease (AD) risk genes on this association. Methods: Our dataset consisted of 18 AD, 52 mild cognitive impairment, and 3 cognitively normal Alzheimer's Disease Neuroimaging Initiative 1 (ADNI1) participants with available [11C]-Pittsburgh compound B (PiB) and peripheral blood protein data. We used cortical pattern matching to study associations between plasma apoE and cortical PiB binding and the effect of carrier status for the top 10 AD risk genes. Results: Low plasma apoE was significantly associated with high PiB SUVR, except in the sensorimotor and entorhinal cortex. For BIN1 rs744373, the association was observed only in minor allele carriers. For CD2AP rs9349407 and CR1 rs3818361, the association was preserved only in minor allele noncarriers. We did not find evidence for modulation by CLU, PICALM, ABCA7, BIN1, and MS4A6A. Conclusions: Our data show that BIN1 rs744373, CD2AP rs9349407, and CR1 rs3818361 genotypes modulate the association between apoE protein plasma levels and brain amyloidosis, implying a potential epigenetic/downstream interaction. PMID:27066559

  10. Investigating Emotional Top Down Modulation of Ambiguous Faces by Single Pulse TMS on Early Visual Cortices

    PubMed Central

    Yaple, Zachary A.; Vakhrushev, Roman; Jolij, Jacob

    2016-01-01

    Top-down processing is a mechanism in which memory, context and expectation are used to perceive stimuli. For this study we investigated how emotion content, induced by music mood, influences perception of happy and sad emoticons. Using single pulse TMS we stimulated right occipital face area (rOFA), primary visual cortex (V1) and vertex while subjects performed a face-detection task and listened to happy and sad music. At baseline, incongruent audio-visual pairings decreased performance, demonstrating dependence of emotion while perceiving ambiguous faces. However, performance of face identification decreased during rOFA stimulation regardless of emotional content. No effects were found between Cz and V1 stimulation. These results suggest that while rOFA is important for processing faces regardless of emotion, V1 stimulation had no effect. Our findings suggest that early visual cortex activity may not integrate emotional auditory information with visual information during emotion top-down modulation of faces. PMID:27445674

  11. Activation of protein kinase Ceta triggers cortical granule exocytosis in Xenopus oocytes.

    PubMed

    Gundersen, Cameron B; Kohan, Sirus A; Chen, Qian; Iagnemma, Joseph; Umbach, Joy A

    2002-03-15

    Previous work has shown that phorbol esters or diacylglycerol trigger cortical granule exocytosis in Xenopus oocytes. We sought to identify the isoform(s) of protein kinase C (PKC) that mediate(s) this regulated secretory event. Because this process is initiated by lipid activators of PKC but is independent of calcium ions, we focused on the family of novel (calcium-independent) PKCs. Pharmacological investigations using Gö6976 and Gö6983 tended to exclude PKCdelta, epsilon and mu as secretory triggers. Subcellular fractionation and immunoblot data revealed that these oocytes expressed all five members of the novel PKC family, but it was only PKCeta that colocalized with cortical granules. Finally, expression of wild type or constitutively active forms of PKCdelta and eta strongly supported the conclusion that it is PKCeta that initiates cortical granule exocytosis in these cells. These observations represent an important step in identifying the mechanism of secretory triggering in this system.

  12. Development of coherent neuronal activity patterns in mammalian cortical networks: common principles and local hetereogeneity.

    PubMed

    Egorov, Alexei V; Draguhn, Andreas

    2013-01-01

    Many mammals are born in a very immature state and develop their rich repertoire of behavioral and cognitive functions postnatally. This development goes in parallel with changes in the anatomical and functional organization of cortical structures which are involved in most complex activities. The emerging spatiotemporal activity patterns in multi-neuronal cortical networks may indeed form a direct neuronal correlate of systemic functions like perception, sensorimotor integration, decision making or memory formation. During recent years, several studies--mostly in rodents--have shed light on the ontogenesis of such highly organized patterns of network activity. While each local network has its own peculiar properties, some general rules can be derived. We therefore review and compare data from the developing hippocampus, neocortex and--as an intermediate region--entorhinal cortex. All cortices seem to follow a characteristic sequence starting with uncorrelated activity in uncoupled single neurons where transient activity seems to have mostly trophic effects. In rodents, before and shortly after birth, cortical networks develop weakly coordinated multineuronal discharges which have been termed synchronous plateau assemblies (SPAs). While these patterns rely mostly on electrical coupling by gap junctions, the subsequent increase in number and maturation of chemical synapses leads to the generation of large-scale coherent discharges. These patterns have been termed giant depolarizing potentials (GDPs) for predominantly GABA-induced events or early network oscillations (ENOs) for mostly glutamatergic bursts, respectively. During the third to fourth postnatal week, cortical areas reach their final activity patterns with distinct network oscillations and highly specific neuronal discharge sequences which support adult behavior. While some of the mechanisms underlying maturation of network activity have been elucidated much work remains to be done in order to fully

  13. Applications of brain blood flow imaging in behavioral neurophysiology: cortical field activation hypothesis

    SciTech Connect

    Roland, P.E.

    1985-01-01

    The /sup 133/xenon intracarotid method for rCBF measurements has been a very useful method for functional mapping and functional dissection of the cerebral cortex in humans. With this method it has been shown that different types of cortical information treatment activate different cortical areas and furthermore that sensory and motor functions of the cerebral cortex could be dissected into anatomical and informational subcomponents by behavioral manipulations. The brain organizes its own activity. One of the principles of organization was that the brain could recruit in advance cortical fields that were expected to participate in a certain type of information operation. During brain work in awake human beings the cerebral cortex was activated in fields that, projected on the cerebral surface, most often had a size greater than 3 CM/sup 2/. Such activated fields appeared no matter which type of information processing was going on in the brain: during planning and execution of voluntary movements, during preparation for sensory information processing, and during sensory information processing, as well as during cognitive brain work and retrieval of specific memories. Therefore, it was hypothesized that cortical field activation was the physiological manifestation of normal brain work in awake humans.

  14. Pancortins interact with amyloid precursor protein and modulate cortical cell migration

    PubMed Central

    Rice, Heather C.; Townsend, Matthew; Bai, Jilin; Suth, Seiyam; Cavanaugh, William; Selkoe, Dennis J.; Young-Pearse, Tracy L.

    2012-01-01

    Neuronal precursor cell migration in the developing mammalian brain is a complex process requiring the coordinated interaction of numerous proteins. We have recently shown that amyloid precursor protein (APP) plays a role in migration into the cortical plate through its interaction with two cytosolic signaling proteins, disabled 1 (DAB1) and disrupted in schizophrenia 1 (DISC1). In order to identify extracellular factors that may signal through APP to regulate migration, we performed an unbiased mass spectrometry-based screen for factors that bind to the extracellular domain of APP in the rodent brain. Through this screen, we identified an interaction between APP and pancortins, proteins expressed throughout the developing and mature cerebral cortex. Via co-immunoprecipitation, we show that APP interacts with all four of the mammalian pancortin isoforms (AMY, AMZ, BMY, BMZ). We demonstrate that the BMZ and BMY isoforms of pancortin can specifically reduce β-secretase- but not α-secretase-mediated cleavage of endogenous APP in cell culture, suggesting a biochemical consequence of the association between pancortins and APP. Using in utero electroporation to overexpress and knock down specific pancortin isoforms, we reveal a novel role for pancortins in migration into the cortical plate. Interestingly, we observe opposing roles for alternate pancortin isoforms, with AMY overexpression and BMZ knock down both preventing proper migration of neuronal precursor cells. Finally, we show that BMZ can partially rescue a loss of APP expression and that APP can rescue effects of AMY overexpression, suggesting that pancortins act in conjunction with APP to regulate entry into the cortical plate. Taken together, these results suggest a biochemical and functional interaction between APP and pancortins, and reveal a previously unidentified role for pancortins in mammalian cortical development. PMID:22992957

  15. Histamine release in the basal forebrain mediates cortical activation through cholinergic neurons.

    PubMed

    Zant, Janneke C; Rozov, Stanislav; Wigren, Henna-Kaisa; Panula, Pertti; Porkka-Heiskanen, Tarja

    2012-09-19

    The basal forebrain (BF) is a key structure in regulating both cortical activity and sleep homeostasis. It receives input from all ascending arousal systems and is particularly highly innervated by histaminergic neurons. Previous studies clearly point to a role for histamine as a wake-promoting substance in the BF. We used in vivo microdialysis and pharmacological treatments in rats to study which electroencephalogram (EEG) spectral properties are associated with histamine-induced wakefulness and whether this wakefulness is followed by increased sleep and increased EEG delta power during sleep. We also investigated which BF neurons mediate histamine-induced cortical activation. Extracellular BF histamine levels rose immediately and remained constant throughout a 6 h period of sleep deprivation, returning to baseline levels immediately afterward. During the spontaneous sleep-wake cycle, we observed a strong correlation between wakefulness and extracellular histamine concentrations in the BF, which was unaffected by the time of day. The perfusion of histamine into the BF increased wakefulness and cortical activity without inducing recovery sleep. The perfusion of a histamine receptor 1 antagonist into the BF decreased both wakefulness and cortical activity. Lesioning the BF cholinergic neurons abolished these effects. Together, these results show that activation of the cholinergic BF by histamine is important in sustaining a high level of cortical activation, and that a lack of activation of the cholinergic BF by histamine may be important in initiating and maintaining nonrapid eye movement sleep. The level of histamine release is tightly connected to behavioral state, but conveys no information about sleep pressure.

  16. Positive modulation of AMPA receptors increases neurotrophin expression by hippocampal and cortical neurons.

    PubMed

    Lauterborn, J C; Lynch, G; Vanderklish, P; Arai, A; Gall, C M

    2000-01-01

    This study investigated whether positive modulators of AMPA-type glutamate receptors influence neurotrophin expression by forebrain neurons. Treatments with the ampakine CX614 markedly and reversibly increased brain-derived neurotrophic factor (BDNF) mRNA and protein levels in cultured rat entorhinal/hippocampal slices. Acute effects of CX614 were dose dependent over the range in which the drug increased synchronous neuronal discharges; threshold concentrations for acute responses had large effects on mRNA content when applied for 3 d. Comparable results were obtained with a second, structurally distinct ampakine CX546. Ampakine-induced upregulation was broadly suppressed by AMPA, but not NMDA, receptor antagonists and by reducing transmitter release. Antagonism of L-type voltage-sensitive calcium channels blocked induction in entorhinal cortex but not hippocampus. Prolonged infusions of suprathreshold ampakine concentrations produced peak BDNF mRNA levels at 12 hr and a return to baseline levels by 48 hr. In contrast, BDNF protein remained elevated throughout a 48 hr incubation with the drug. Nerve growth factor mRNA levels also were increased by ampakines but with a much more rapid return to control levels during chronic administration. Finally, intraperitoneal injections of CX546 increased hippocampal BDNF mRNA levels in aged rats and middle-aged mice. The present results provide evidence of regional differences in mechanisms via which activity regulates neurotrophin expression. Moreover, these data establish that changes in synaptic potency produce sufficient network level physiological effects for inducing neurotrophin genes, indicate that the response becomes refractory during prolonged ampakine exposure, and raise the possibility of using positive AMPA modulators to regulate neurotrophin levels in aged brain.

  17. Interaction of electrically evoked activity with intrinsic dynamics of cultured cortical networks with and without functional fast GABAergic synaptic transmission

    PubMed Central

    Baltz, Thomas; Voigt, Thomas

    2015-01-01

    The modulation of neuronal activity by means of electrical stimulation is a successful therapeutic approach for patients suffering from a variety of central nervous system disorders. Prototypic networks formed by cultured cortical neurons represent an important model system to gain general insights in the input–output relationships of neuronal tissue. These networks undergo a multitude of developmental changes during their maturation, such as the excitatory–inhibitory shift of the neurotransmitter GABA. Very few studies have addressed how the output properties to a given stimulus change with ongoing development. Here, we investigate input–output relationships of cultured cortical networks by probing cultures with and without functional GABAAergic synaptic transmission with a set of stimulation paradigms at various stages of maturation. On the cellular level, low stimulation rates (<15 Hz) led to reliable neuronal responses; higher rates were increasingly ineffective. Similarly, on the network level, lowest stimulation rates (<0.1 Hz) lead to maximal output rates at all ages, indicating a network wide refractory period after each stimulus. In cultures aged 3 weeks and older, a gradual recovery of the network excitability within tens of milliseconds was in contrast to an abrupt recovery after about 5 s in cultures with absent GABAAergic synaptic transmission. In these GABA deficient cultures evoked responses were prolonged and had multiple discharges. Furthermore, the network excitability changed periodically, with a very slow spontaneous change of the overall network activity in the minute range, which was not observed in cultures with absent GABAAergic synaptic transmission. The electrically evoked activity of cultured cortical networks, therefore, is governed by at least two potentially interacting mechanisms: A refractory period in the order of a few seconds and a very slow GABA dependent oscillation of the network excitability. PMID:26236196

  18. CNTF-Treated Astrocyte Conditioned Medium Enhances Large-Conductance Calcium-Activated Potassium Channel Activity in Rat Cortical Neurons.

    PubMed

    Sun, Meiqun; Liu, Hongli; Xu, Huanbai; Wang, Hongtao; Wang, Xiaojing

    2016-08-01

    Seizure activity is linked to astrocyte activation as well as dysfunctional cortical neuron excitability produced from changes in calcium-activated potassium (KCa) channel function. Ciliary neurotrophic factor-treated astrocyte conditioned medium (CNTF-ACM) can be used to investigate the peripheral effects of activated astrocytes upon cortical neurons. However, CNTF-ACM's effect upon KCa channel activity in cultured cortical neurons has not yet been investigated. Whole-cell patch clamp recordings were performed in rat cortical neurons to evaluate CNTF-ACM's effects upon charybdotoxin-sensitive large-conductance KCa (BK) channel currents and apamin-sensitive small-conductance KCa (SK) channel current. Biotinylation and RT-PCR were applied to assess CNTF-ACM's effects upon the protein and mRNA expression, respectively, of the SK channel subunits SK2 and SK3 and the BK channel subunits BKα1 and BKβ3. An anti-fibroblast growth factor-2 (FGF-2) monoclonal neutralizing antibody was used to assess the effects of the FGF-2 component of CNTF-ACM. CNTF-ACM significantly increased KCa channel current density, which was predominantly attributable to gains in BK channel activity (p < 0.05). CNTF-ACM produced a significant increase in BKα1 and BKβ3 expression (p < 0.05) but had no significant effect upon SK2 or SK3 expression (p > 0.05). Blocking FGF-2 produced significant reductions in KCa channel current density (p > 0.05) as well as BKα1 and BKβ3 expression in CNTF-ACM-treated neurons (p > 0.05). CNTF-ACM significantly enhances BK channel activity in rat cortical neurons and that FGF-2 is partially responsible for these effects. CNTF-induced astrocyte activation results in secretion of neuroactive factors which may affect neuronal excitability and resultant seizure activity in mammalian cortical neurons.

  19. Functional differences in epigenetic modulators-superiority of mercaptoacetamide-based histone deacetylase inhibitors relative to hydroxamates in cortical neuron neuroprotection studies.

    PubMed

    Kozikowski, Alan P; Chen, Yufeng; Gaysin, Arsen; Chen, Bin; D'Annibale, Melissa A; Suto, Carla M; Langley, Brett C

    2007-06-28

    We compare the ability of two structurally different classes of epigenetic modulators, namely, histone deacetylase (HDAC) inhibitors containing either a hydroxamate or a mercaptoacetamide as the zinc binding group, to protect cortical neurons in culture from oxidative stress-induced death. This study reveals that some of the mercaptoacetamide-based HDAC inhibitors are fully protective, whereas the hydroxamates show toxicity at higher concentrations. Our present results appear to be consistent with the possibility that the mercaptoacetamide-based HDAC inhibitors interact with a different subset of the HDAC isozymes [less activity at HDAC1 and 2 correlates with less inhibitor toxicity], or alternatively, are interacting selectively with only the cytoplasmic HDACs that are crucial for protection from oxidative stress.

  20. Visualization of an actively bleeding cortical vessel into the subdural space by CT angiography.

    PubMed

    Dalfino, John C; Boulos, Alan S

    2010-10-01

    Spontaneous subdural hematomas of arterial origin are rare with only a few published case reports in the literature. In the CT era, vessel imaging of extra-axial hematomas is not commonly performed. In this case report we present a patient with a large, spontaneous acute subdural hematoma that demonstrated active contrast extravasation from a small cortical vessel on CT angiography. During surgical evacuation the vessel was confirmed to be a small cortical artery that was bulging through the arachnoid membrane and bleeding into the subdural space. The historical, radiographic, and clinical aspects of this unusual cause of subdural hematoma are discussed.

  1. Magnetoencephalographic Analysis of Cortical Activity in Adults with and without Down Syndrome

    ERIC Educational Resources Information Center

    Virji-Babul, N.; Cheung, T.; Weeks, D.; Herdman, A. T.; Cheyne, D.

    2007-01-01

    Background: This preliminary study served as a pilot for an ongoing analysis of spectral power in adults with Down syndrome (DS) using a 151 channel whole head magnetoencephalography (MEG). The present study is the first step for examining and comparing cortical responses during spontaneous and task related activity in DS. Method: Cortical…

  2. Research on acupuncture points and cortical functional activation position in cats by infrared imaging detection

    NASA Astrophysics Data System (ADS)

    Chen, Shuwang; Sha, Zhanyou; Wang, Shuhai; Wen, Huanming

    2007-12-01

    The research of the brain cognition is mainly to find out the activation position in brain according to the stimulation at present in the world. The research regards the animals as the experimental objects and explores the stimulation response on the cerebral cortex of acupuncture. It provides a new method, which can detect the activation position on the creatural cerebral cortex directly by middle-far infrared imaging. According to the theory of local temperature situation, the difference of cortical temperature maybe associate with the excitement of cortical nerve cells, the metabolism of local tissue and the local hemal circulation. Direct naked detection of temperature variety on cerebral cortex is applied by middle and far infrared imaging technology. So the activation position is ascertained. The effect of stimulation response is superior to other indirect methods. After removing the skulls on the head, full of cerebral cortex of a cat are exposed. By observing the infrared images and measuring the temperatures of the visual cerebral cortex during the process of acupuncturing, the points are used to judge the activation position. The variety in the cortical functional sections is corresponding to the result of the acupuncture points in terms of infrared images and temperatures. According to experimental results, we know that the variety of a cortical functional section is corresponding to a special acupuncture point exactly.

  3. Sex Differences in Mental Rotation and Cortical Activation Patterns: Can Training Change Them?

    ERIC Educational Resources Information Center

    Jausovec, Norbert; Jausovec, Ksenija

    2012-01-01

    In two experiments the neuronal mechanisms of sex differences in mental rotation were investigated. In Experiment 1 cortical activation was studied in women and men with similar levels of mental rotation ability (high, and average to low), who were equalized with respect to general intelligence. Sex difference in neuroelectric patterns of brain…

  4. Cortical Activity Differs During Nicotine Deprivation versus Satiation in Heavy Smokers

    PubMed Central

    Evans, David E.; Sutton, Steven K.; Oliver, Jason A.; Drobes, David J.

    2015-01-01

    Rationale Research suggests that nicotine deprivation among smokers is associated with lesser resting cortical activity (i.e., greater power density in theta and alpha-1 EEG bands and lesser power in beta bands). These changes in cortical activity may be indicative of withdrawal-related cognitive deficits, yet the markers of differences in cortical activity are not well-established. Objective To clarify the EEG frequency bands affected by nicotine deprivation and assess prospective moderators Method 124 heavy smokers visited the laboratory on two occasions following overnight smoking/nicotine deprivation. Prior to collecting three minutes of resting EEG data, participants smoked two very low nicotine cigarettes (< .05 mg nicotine yield) at one session and two moderate nicotine cigarettes (.60 mg nicotine yield) at the other. Results Theta and alpha-1 band (4–7 & 8–10 Hz) was greater in the very low nicotine (deprivation) relative to higher nicotine (satiation) condition. There were no condition differences in the beta-1 and beta-2 bands (14–20 & 21–30 Hz). Conclusions Greater slow wave resting EEG may serve as a reliable marker of decreased cortical activity during smoking deprivation and, in turn, of withdrawal-related deficits in cognitive functioning. This research may inform the development of adjunct strategies for smoking cessation. PMID:25491928

  5. The Estimation of Cortical Activity for Brain-Computer Interface: Applications in a Domotic Context

    PubMed Central

    Babiloni, F.; Cincotti, F.; Marciani, M.; Salinari, S.; Astolfi, L.; Tocci, A.; Aloise, F.; Fallani, F. De Vico; Bufalari, S.; Mattia, D.

    2007-01-01

    In order to analyze whether the use of the cortical activity, estimated from noninvasive EEG recordings, could be useful to detect mental states related to the imagination of limb movements, we estimate cortical activity from high-resolution EEG recordings in a group of healthy subjects by using realistic head models. Such cortical activity was estimated in region of interest associated with the subject's Brodmann areas by using a depth-weighted minimum norm technique. Results showed that the use of the cortical-estimated activity instead of the unprocessed EEG improves the recognition of the mental states associated to the limb movement imagination in the group of normal subjects. The BCI methodology presented here has been used in a group of disabled patients in order to give them a suitable control of several electronic devices disposed in a three-room environment devoted to the neurorehabilitation. Four of six patients were able to control several electronic devices in this domotic context with the BCI system. PMID:18350134

  6. The estimation of cortical activity for brain-computer interface: applications in a domotic context.

    PubMed

    Babiloni, F; Cincotti, F; Marciani, M; Salinari, S; Astolfi, L; Tocci, A; Aloise, F; De Vico Fallani, F; Bufalari, S; Mattia, D

    2007-01-01

    In order to analyze whether the use of the cortical activity, estimated from noninvasive EEG recordings, could be useful to detect mental states related to the imagination of limb movements, we estimate cortical activity from high-resolution EEG recordings in a group of healthy subjects by using realistic head models. Such cortical activity was estimated in region of interest associated with the subject's Brodmann areas by using a depth-weighted minimum norm technique. Results showed that the use of the cortical-estimated activity instead of the unprocessed EEG improves the recognition of the mental states associated to the limb movement imagination in the group of normal subjects. The BCI methodology presented here has been used in a group of disabled patients in order to give them a suitable control of several electronic devices disposed in a three-room environment devoted to the neurorehabilitation. Four of six patients were able to control several electronic devices in this domotic context with the BCI system.

  7. Downregulation of Parvalbumin at Cortical GABA Synapses Reduces Network Gamma Oscillatory Activity

    PubMed Central

    Volman, Vladislav; Behrens, M. Margarita; Sejnowski, Terrence J.

    2012-01-01

    Postmortem and functional imaging studies of patients with psychiatric disorders, including schizophrenia, are consistent with a dysfunction of interneurons leading to compromised inhibitory control of network activity. Parvalbumin (PV)-expressing, fast-spiking interneurons interacting with pyramidal neurons generate cortical gamma oscillations (30 – 80 Hz) that synchronize cortical activity during cognitive processing. In postmortem studies of schizophrenia patients, these interneurons show reduced PV and glutamic acid decarboxylase 67 (GAD67), an enzyme that synthesizes GABA, but the consequences of this downregulation are unclear. We developed a biophysically realistic and detailed computational model of a cortical circuit including asynchronous release from GABAergic interneurons to investigate how reductions in PV and GABA affect gamma oscillations induced by sensory stimuli. Networks with reduced GABA were disinhibited and had altered gamma oscillations in response to stimulation; PV-deficient GABA synapses had increased asynchronous release of GABA, which decreased the level of excitation and reduced gamma-band activity. Combined reductions of PV and GABA resulted in a diminished gamma-band oscillatory activity in response to stimuli, similar to that observed in schizophrenia patients. Our results suggest a mechanism by which reduced GAD67 and PV in fast-spiking interneurons may contribute to cortical dysfunction in schizophrenia and related psychiatric disorders. PMID:22159125

  8. Turning a Negative into a Positive: Ascending GABAergic Control of Cortical Activation and Arousal

    PubMed Central

    Brown, Ritchie E.; McKenna, James T.

    2015-01-01

    Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain. Recent technological advances have illuminated the role of GABAergic neurons in control of cortical arousal and sleep. Sleep-promoting GABAergic neurons in the preoptic hypothalamus are well-known. Less well-appreciated are GABAergic projection neurons in the brainstem, midbrain, hypothalamus, and basal forebrain, which paradoxically promote arousal and fast electroencephalographic (EEG) rhythms. Thus, GABA is not purely a sleep-promoting neurotransmitter. GABAergic projection neurons in the brainstem nucleus incertus and ventral tegmental nucleus of Gudden promote theta (4–8 Hz) rhythms. Ventral tegmental area GABAergic neurons, neighboring midbrain dopamine neurons, project to the frontal cortex and nucleus accumbens. They discharge faster during cortical arousal and regulate reward. Thalamic reticular nucleus GABAergic neurons initiate sleep spindles in non-REM sleep. In addition, however, during wakefulness, they tonically regulate the activity of thalamocortical neurons. Other GABAergic inputs to the thalamus arising in the globus pallidus pars interna, substantia nigra pars reticulata, zona incerta, and basal forebrain regulate motor activity, arousal, attention, and sensory transmission. Several subpopulations of cortically projecting GABAergic neurons in the basal forebrain project to the thalamus and neocortex and preferentially promote cortical gamma-band (30–80 Hz) activity and wakefulness. Unlike sleep-active GABAergic neurons, these ascending GABAergic neurons are fast-firing neurons which disinhibit and synchronize the activity of their forebrain targets, promoting the fast EEG rhythms typical of conscious states. They are prominent targets of GABAergic hypnotic agents. Understanding the properties of ascending GABAergic neurons may lead to novel treatments for diseases involving disorders of cortical activation and wakefulness. PMID:26124745

  9. Bigelow Expandable Activity Module (BEAM) Monitoring System

    NASA Technical Reports Server (NTRS)

    Wells, Nathan

    2017-01-01

    What is Bigelow Expandable Activity Module (BEAM)? The Bigelow Expandable Activity Module (BEAM) is an expandable habitat technology demonstration on ISS; increase human-rated inflatable structure Technology Readiness Level (TRL) to level 9. NASA managed ISS payload project in partnership with Bigelow Aerospace. Launched to ISS on Space X 8 (April 8th, 2016). Fully expanded on May 28th, 2016. Jeff Williams/Exp. 48 Commander first entered BEAM on June 5th, 2016.

  10. Neuromagnetic Abnormality of Motor Cortical Activation and Phases of Headache Attacks in Childhood Migraine

    PubMed Central

    Xiang, Jing; deGrauw, Xinyao; Korman, Abraham M.; Allen, Janelle R.; O'Brien, Hope L.; Kabbouche, Marielle A.; Powers, Scott W.; Hershey, Andrew D.

    2013-01-01

    The cerebral cortex serves a primary role in the pathogenesis of migraine. This aberrant brain activation in migraine can be noninvasively detected with magnetoencephalography (MEG). The objective of this study was to investigate the differences in motor cortical activation between attacks (ictal) and pain free intervals (interictal) in children and adolescents with migraine using both low- and high-frequency neuromagnetic signals. Thirty subjects with an acute migraine and 30 subjects with a history of migraine, while pain free, were compared to age- and gender-matched controls using MEG. Motor cortical activation was elicited by a standardized, validated finger-tapping task. Low-frequency brain activation (1∼50 Hz) was analyzed with waveform measurements and high-frequency oscillations (65–150 Hz) were analyzed with wavelet-based beamforming. MEG waveforms showed that the ictal latency of low-frequency brain activation was significantly delayed as compared with controls, while the interictal latency of brain activation was similar to that of controls. The ictal amplitude of low-frequency brain activation was significantly increased as compared with controls, while the interictal amplitude of brain activation was similar to that of controls. The ictal source power of high-frequency oscillations was significantly stronger than that of the controls, while the interictal source power of high-frequency oscillations was significantly weaker than that of controls. The results suggest that aberrant low-frequency brain activation in migraine during a headache attack returned to normal interictally. However, high-frequency oscillations changed from ictal hyper-activation to interictal hypo-activation. Noninvasive assessment of cortical abnormality in migraine with MEG opens a new window for developing novel therapeutic strategies for childhood migraine by maintaining a balanced cortical excitability. PMID:24386250

  11. Diffusion of GPI-anchored proteins is influenced by the activity of dynamic cortical actin.

    PubMed

    Saha, Suvrajit; Lee, Il-Hyung; Polley, Anirban; Groves, Jay T; Rao, Madan; Mayor, Satyajit

    2015-11-05

    Molecular diffusion at the surface of living cells is believed to be predominantly driven by thermal kicks. However, there is growing evidence that certain cell surface molecules are driven by the fluctuating dynamics of cortical cytoskeleton. Using fluorescence correlation spectroscopy, we measure the diffusion coefficient of a variety of cell surface molecules over a temperature range of 24-37 °C. Exogenously incorporated fluorescent lipids with short acyl chains exhibit the expected increase of diffusion coefficient over this temperature range. In contrast, we find that GPI-anchored proteins exhibit temperature-independent diffusion over this range and revert to temperature-dependent diffusion on cell membrane blebs, in cells depleted of cholesterol, and upon acute perturbation of actin dynamics and myosin activity. A model transmembrane protein with a cytosolic actin-binding domain also exhibits the temperature-independent behavior, directly implicating the role of cortical actin. We show that diffusion of GPI-anchored proteins also becomes temperature dependent when the filamentous dynamic actin nucleator formin is inhibited. However, changes in cortical actin mesh size or perturbation of branched actin nucleator Arp2/3 do not affect this behavior. Thus cell surface diffusion of GPI-anchored proteins and transmembrane proteins that associate with actin is driven by active fluctuations of dynamic cortical actin filaments in addition to thermal fluctuations, consistent with expectations from an "active actin-membrane composite" cell surface.

  12. Diffusion of GPI-anchored proteins is influenced by the activity of dynamic cortical actin

    PubMed Central

    Saha, Suvrajit; Lee, Il-Hyung; Polley, Anirban; Groves, Jay T.; Rao, Madan; Mayor, Satyajit

    2015-01-01

    Molecular diffusion at the surface of living cells is believed to be predominantly driven by thermal kicks. However, there is growing evidence that certain cell surface molecules are driven by the fluctuating dynamics of cortical cytoskeleton. Using fluorescence correlation spectroscopy, we measure the diffusion coefficient of a variety of cell surface molecules over a temperature range of 24–37°C. Exogenously incorporated fluorescent lipids with short acyl chains exhibit the expected increase of diffusion coefficient over this temperature range. In contrast, we find that GPI-anchored proteins exhibit temperature-independent diffusion over this range and revert to temperature-dependent diffusion on cell membrane blebs, in cells depleted of cholesterol, and upon acute perturbation of actin dynamics and myosin activity. A model transmembrane protein with a cytosolic actin-binding domain also exhibits the temperature-independent behavior, directly implicating the role of cortical actin. We show that diffusion of GPI-anchored proteins also becomes temperature dependent when the filamentous dynamic actin nucleator formin is inhibited. However, changes in cortical actin mesh size or perturbation of branched actin nucleator Arp2/3 do not affect this behavior. Thus cell surface diffusion of GPI-anchored proteins and transmembrane proteins that associate with actin is driven by active fluctuations of dynamic cortical actin filaments in addition to thermal fluctuations, consistent with expectations from an “active actin-membrane composite” cell surface. PMID:26378258

  13. Simultaneous measurement of neuronal activity and cortical hemodynamics by unshielded magnetoencephalography and near-infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Seki, Yusuke; Miyashita, Tsuyoshi; Kandori, Akihiko; Maki, Atsushi; Koizumi, Hideaki

    2012-10-01

    The correlation between neuronal activity and cortical hemodynamics, namely, neurovascular coupling (NVC), is important to shed light on the mechanism of a variety of brain functions or neuronal diseases. NVC can be studied by simultaneously measuring neuronal activity and cortical hemodynamics. Consequently, noninvasive measurements of the NVC have been widely studied using both electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). However, electromagnetic interference between EEG and fMRI is still a major problem. On the other hand, near-infrared spectroscopy (NIRS) is another promising tool for detecting cortical hemodynamics because it can be combined with EEG or magnetoencephalography (MEG) without any electromagnetic interference. Accordingly, in the present study, a simultaneous measurement system-combining an unshielded MEG using a two-dimensional gradiometer based on a low-T superconducting quantum interference device (SQUID) and an NIRS using nonmagnetic thin probes-was developed. This combined system was used to simultaneously measure both an auditory-evoked magnetic field and blood flow change in the auditory cortex. It was experimentally demonstrated that the combined unshielded MEG/NIRS system can simultaneously measure neuronal activity and cortical hemodynamics.

  14. Simultaneous measurement of neuronal activity and cortical hemodynamics by unshielded magnetoencephalography and near-infrared spectroscopy.

    PubMed

    Seki, Yusuke; Miyashita, Tsuyoshi; Kandori, Akihiko; Maki, Atsushi; Koizumi, Hideaki

    2012-10-01

    The correlation between neuronal activity and cortical hemodynamics, namely, neurovascular coupling (NVC), is important to shed light on the mechanism of a variety of brain functions or neuronal diseases. NVC can be studied by simultaneously measuring neuronal activity and cortical hemodynamics. Consequently, noninvasive measurements of the NVC have been widely studied using both electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). However, electromagnetic interference between EEG and fMRI is still a major problem. On the other hand, near-infrared spectroscopy (NIRS) is another promising tool for detecting cortical hemodynamics because it can be combined with EEG or magnetoencephalography (MEG) without any electromagnetic interference. Accordingly, in the present study, a simultaneous measurement system-combining an unshielded MEG using a two-dimensional gradiometer based on a low-Tc superconducting quantum interference device (SQUID) and an NIRS using nonmagnetic thin probes-was developed. This combined system was used to simultaneously measure both an auditory-evoked magnetic field and blood flow change in the auditory cortex. It was experimentally demonstrated that the combined unshielded MEG/NIRS system can simultaneously measure neuronal activity and cortical hemodynamics.

  15. Performance Based Education. Technology Activity Modules.

    ERIC Educational Resources Information Center

    Custer, Rodney L., Ed.

    These Technology Activity Modules are designed to serve as an implementation resource for technology education teachers as they integrate technology education with Missouri's Academic Performance Standards and provide a source of activities and activity ideas that can be used to integrate and reinforce learning across the curriculum. The modules…

  16. Optogenetic micro-electrocorticography for modulating and localizing cerebral cortex activity

    NASA Astrophysics Data System (ADS)

    Richner, Thomas J.; Thongpang, Sanitta; Brodnick, Sarah K.; Schendel, Amelia A.; Falk, Ryan W.; Krugner-Higby, Lisa A.; Pashaie, Ramin; Williams, Justin C.

    2014-02-01

    Objective. Spatial localization of neural activity from within the brain with electrocorticography (ECoG) and electroencephalography remains a challenge in clinical and research settings, and while microfabricated ECoG (micro-ECoG) array technology continues to improve, complementary methods to simultaneously modulate cortical activity while recording are needed. Approach. We developed a neural interface utilizing optogenetics, cranial windowing, and micro-ECoG arrays fabricated on a transparent polymer. This approach enabled us to directly modulate neural activity at known locations around micro-ECoG arrays in mice expressing Channelrhodopsin-2. We applied photostimuli varying in time, space and frequency to the cortical surface, and we targeted multiple depths within the cortex using an optical fiber while recording micro-ECoG signals. Main results. Negative potentials of up to 1.5 mV were evoked by photostimuli applied to the entire cortical window, while focally applied photostimuli evoked spatially localized micro-ECoG potentials. Two simultaneously applied focal stimuli could be separated, depending on the distance between them. Photostimuli applied within the cortex with an optical fiber evoked more complex micro-ECoG potentials with multiple positive and negative peaks whose relative amplitudes depended on the depth of the fiber. Significance. Optogenetic ECoG has potential applications in the study of epilepsy, cortical dynamics, and neuroprostheses.

  17. Matrix stiffness modulates formation and activity of neuronal networks of controlled architectures.

    PubMed

    Lantoine, Joséphine; Grevesse, Thomas; Villers, Agnès; Delhaye, Geoffrey; Mestdagh, Camille; Versaevel, Marie; Mohammed, Danahe; Bruyère, Céline; Alaimo, Laura; Lacour, Stéphanie P; Ris, Laurence; Gabriele, Sylvain

    2016-05-01

    The ability to construct easily in vitro networks of primary neurons organized with imposed topologies is required for neural tissue engineering as well as for the development of neuronal interfaces with desirable characteristics. However, accumulating evidence suggests that the mechanical properties of the culture matrix can modulate important neuronal functions such as growth, extension, branching and activity. Here we designed robust and reproducible laminin-polylysine grid micropatterns on cell culture substrates that have similar biochemical properties but a 100-fold difference in Young's modulus to investigate the role of the matrix rigidity on the formation and activity of cortical neuronal networks. We found that cell bodies of primary cortical neurons gradually accumulate in circular islands, whereas axonal extensions spread on linear tracks to connect circular islands. Our findings indicate that migration of cortical neurons is enhanced on soft substrates, leading to a faster formation of neuronal networks. Furthermore, the pre-synaptic density was two times higher on stiff substrates and consistently the number of action potentials and miniature synaptic currents was enhanced on stiff substrates. Taken together, our results provide compelling evidence to indicate that matrix stiffness is a key parameter to modulate the growth dynamics, synaptic density and electrophysiological activity of cortical neuronal networks, thus providing useful information on scaffold design for neural tissue engineering.

  18. Cortical activity differs between position- and force-control knee extension tasks.

    PubMed

    Poortvliet, Peter C; Tucker, Kylie J; Finnigan, Simon; Scott, Dion; Sowman, Paul; Hodges, Paul W

    2015-12-01

    Neural control differs between position- and force-control tasks as evident from divergent effects of fatigue and pain. Unlike force-control tasks, position-control tasks focus on a postural goal to maintain a joint angle. Cortical involvement is suggested to be less during postural control, but whether this differs between position- and force-control paradigms remains unclear. Coherence estimates the functional communication between spatially distinct active regions within the cortex (cortico-cortical coherence; CCC) and between the cortex and muscles (corticomuscular coherence; CMC). We investigated whether cortical involvement differed between force-control and more posturally focused, position-control tasks. Seventeen adults performed position- and force-control knee extensor efforts at a submaximal load (10 % maximum voluntary contraction). Surface electromyography was recorded from the right knee extensor and flexor muscles and brain activity using electroencephalography (EEG). CCC and CMC in the beta (13-30 Hz) and gamma (30-45 Hz) frequency bands were calculated between combinations of intra- and inter-hemispheric pairs of electrodes, and between four EEG electrodes that approximated the left motor cortical area, and right knee extensor EMG, respectively. Differences in EEG power and muscle activity were also calculated. CCC was greater across distributed regions in the force-control task. Beta EEG power in the left hemisphere was higher for the position-control task. Although averaged CMC data differed between tasks, there was no task difference for individual CMC data. Muscle activity and force did not differ between tasks. The results demonstrate differential cortical contributions to control force- versus position-control tasks. This might contribute to differences in performance outcomes of these tasks that have been shown previously.

  19. The slowed brain: cortical oscillatory activity in hepatic encephalopathy.

    PubMed

    Butz, Markus; May, Elisabeth S; Häussinger, Dieter; Schnitzler, Alfons

    2013-08-15

    Oscillatory activity of the human brain has received growing interest as a key mechanism of large-scale integration across different brain regions. Besides a crucial role of oscillatory activity in the emergence of other neurological and psychiatric diseases, recent evidence indicates a key role in the pathophysiology of hepatic encephalopathy (HE). This review summarizes the current knowledge on pathological alterations of oscillatory brain activity in association with liver dysfunction and HE in the context of spontaneous brain activity, motor symptoms, sensory processing, and attention. The existing literature demonstrates a prominent slowing of the frequency of oscillatory activity as shown for spontaneous brain activity at rest, with respect to deficits of motor behavior and motor symptoms, and in the context of visual attention processes. The observed slowing extends across different subsystems of the brain and has been confirmed across different frequency bands, providing evidence for ubiquitous changes of oscillatory activity in HE. For example, the frequency of cortico-muscular coherence in HE patients appears at the frequency of the mini-asterixis (⩽12Hz), while cirrhotics without overt signs of HE show coherence similar to healthy subjects, i.e. at 13-30Hz. Interestingly, the so-called critical flicker frequency (CFF) as a measure of the processing of an oscillating visual stimulus has emerged as a useful tool to quantify HE disease severity, correlating with behavioral and neurophysiological alterations. Moreover, the CFF reliably distinguishes patients with manifest HE from cirrhotics without any signs of HE and healthy controls using a cut-off frequency of 39Hz. In conclusion, oscillatory activity is globally slowed in HE in close association with HE symptoms and disease severity. Although the underlying causal mechanisms are not yet understood, these results indicate that pathological changes of oscillatory activity play an important role in the

  20. BDNF-modulated spatial organization of Cajal-Retzius and GABAergic neurons in the marginal zone plays a role in the development of cortical organization.

    PubMed

    Alcántara, Soledad; Pozas, Esther; Ibañez, Carlos F; Soriano, Eduardo

    2006-04-01

    The present study utilizes nestin-BDNF transgenic mice, which offer a model for early increased brain-derived neurotrophic factor (BDNF) signalling, to examine the role of BDNF in the development of cortical architecture. Our results demonstrate that the premature and homogeneous expression of BDNF, while preserving tangential migration from the ganglionic eminence to the cortex, impairs the final radial migration of GABAergic neurons, as well as their integration in the appropriate cortical layers. Moreover, Cajal-Retzius (CR) cells and GABAergic neurons segregate in the cortical marginal zone (MZ) in response to BDNF signalling, leading to an alternating pattern and a columnar cortical organization, within which the migration of different neuronal populations is specifically affected. These results suggest that both CR and GABAergic neurons play a role in directing the radial migration of late-generated cortical neurons, and that the spatial distribution of these cells in the MZ is critical for the development of correct cortical organization. In addition, reelin secreted by CR cells in the MZ is not sufficient to direct the migration of late-born neurons to the upper cortical layers, which most likely requires the presence of reelin-secreting interneurons in layers V-VI. We propose that in addition to modulating reelin expression, BDNF regulates the patched distribution of CR and GABAergic neurons in the MZ, and that this spatial distribution is involved in the formation of anatomical and/or functional columns and convoluted structures.

  1. Dampened hippocampal oscillations and enhanced spindle activity in an asymptomatic model of developmental cortical malformations

    PubMed Central

    Cid, Elena; Gomez-Dominguez, Daniel; Martin-Lopez, David; Gal, Beatriz; Laurent, François; Ibarz, Jose M.; Francis, Fiona; Menendez de la Prida, Liset

    2014-01-01

    Developmental cortical malformations comprise a large spectrum of histopathological brain abnormalities and syndromes. Their genetic, developmental and clinical complexity suggests they should be better understood in terms of the complementary action of independently timed perturbations (i.e., the multiple-hit hypothesis). However, understanding the underlying biological processes remains puzzling. Here we induced developmental cortical malformations in offspring, after intraventricular injection of methylazoxymethanol (MAM) in utero in mice. We combined extensive histological and electrophysiological studies to characterize the model. We found that MAM injections at E14 and E15 induced a range of cortical and hippocampal malformations resembling histological alterations of specific genetic mutations and transplacental mitotoxic agent injections. However, in contrast to most of these models, intraventricularly MAM-injected mice remained asymptomatic and showed no clear epilepsy-related phenotype as tested in long-term chronic recordings and with pharmacological manipulations. Instead, they exhibited a non-specific reduction of hippocampal-related brain oscillations (mostly in CA1); including theta, gamma and HFOs; and enhanced thalamocortical spindle activity during non-REM sleep. These data suggest that developmental cortical malformations do not necessarily correlate with epileptiform activity. We propose that the intraventricular in utero MAM approach exhibiting a range of rhythmopathies is a suitable model for multiple-hit studies of associated neurological disorders. PMID:24782720

  2. Dampened hippocampal oscillations and enhanced spindle activity in an asymptomatic model of developmental cortical malformations.

    PubMed

    Cid, Elena; Gomez-Dominguez, Daniel; Martin-Lopez, David; Gal, Beatriz; Laurent, François; Ibarz, Jose M; Francis, Fiona; Menendez de la Prida, Liset

    2014-01-01

    Developmental cortical malformations comprise a large spectrum of histopathological brain abnormalities and syndromes. Their genetic, developmental and clinical complexity suggests they should be better understood in terms of the complementary action of independently timed perturbations (i.e., the multiple-hit hypothesis). However, understanding the underlying biological processes remains puzzling. Here we induced developmental cortical malformations in offspring, after intraventricular injection of methylazoxymethanol (MAM) in utero in mice. We combined extensive histological and electrophysiological studies to characterize the model. We found that MAM injections at E14 and E15 induced a range of cortical and hippocampal malformations resembling histological alterations of specific genetic mutations and transplacental mitotoxic agent injections. However, in contrast to most of these models, intraventricularly MAM-injected mice remained asymptomatic and showed no clear epilepsy-related phenotype as tested in long-term chronic recordings and with pharmacological manipulations. Instead, they exhibited a non-specific reduction of hippocampal-related brain oscillations (mostly in CA1); including theta, gamma and HFOs; and enhanced thalamocortical spindle activity during non-REM sleep. These data suggest that developmental cortical malformations do not necessarily correlate with epileptiform activity. We propose that the intraventricular in utero MAM approach exhibiting a range of rhythmopathies is a suitable model for multiple-hit studies of associated neurological disorders.

  3. Variations in Acetylcholinesterase Activity within Human Cortical Pyramidal Neurons Across Age and Cognitive Trajectories.

    PubMed

    Janeczek, Monica; Gefen, Tamar; Samimi, Mehrnoosh; Kim, Garam; Weintraub, Sandra; Bigio, Eileen; Rogalski, Emily; Mesulam, M-Marsel; Geula, Changiz

    2017-03-01

    We described an extensive network of cortical pyramidal neurons in the human brain with abundant acetylcholinesterase (AChE) activity. Emergence of these neurons during childhood/adolescence, attainment of highest density in early adulthood, and virtual absence in other species led us to hypothesize involvement of AChE within these neurons in higher cortical functions. The current study quantified the density and staining intensity of these neurons using histochemical procedures. Few faintly stained AChE-positive cortical pyramidal neurons were observed in children/adolescents. These neurons attained their highest density and staining intensity in young adulthood. Compared with the young adult group, brains of cognitively normal elderly displayed no significant change in numerical density but a significant decrease in staining intensity of AChE-positive cortical pyramidal neurons. Brains of elderly above age 80 with unusually preserved memory performance (SuperAgers) showed significantly lower staining intensity and density of these neurons when compared with same-age peers. Conceivably, low levels of AChE activity could enhance the impact of acetylcholine on pyramidal neurons to counterbalance other involutional factors that mediate the decline of memory capacity during average aging. We cannot yet tell if elderly with superior memory capacity have constitutively low neuronal AChE levels or if this feature reflects adaptive neuroplasticity.

  4. Modulation of motor cortical outputs to the reading hand of braille readers.

    PubMed

    Pascual-Leone, A; Cammarota, A; Wassermann, E M; Brasil-Neto, J P; Cohen, L G; Hallett, M

    1993-07-01

    We used focal transcranial magnetic stimulation to map the motor cortical areas targeting the first dorsal interosseous and the abductor digiti minimi muscles bilaterally in 10 proficient braille readers and 10 blind controls who were matched for age (mean, 50.6 yr) and age at time of blindness (mean, 7.5 yr). The proficient braille readers had learned braille at age 8 to 14 years and used it daily for 5 to 10 hours. Controls had not learned braille until age 17 to 21 years and used it daily for < 1 hour. In the controls, motor representations of the right and left first dorsal interosseous and abductor digiti minimi muscles were not significantly different. However, in the proficient braille readers, the representation of the first dorsal interosseous muscle in the reading hand was significantly larger than that in the nonreading hand or in either hand of the controls. Conversely, the representation of the abductor digiti minimi muscle in the reading hand was significantly smaller than that in the nonreading hand or in either hand of the controls. These differences were not due to differences in motor thresholds. Our results suggest that the cortical representation of the reading finger in proficient braille readers is enlarged at the expense of the representation of other fingers.

  5. Modulation of spike timing by sensory deprivation during induction of cortical map plasticity.

    PubMed

    Celikel, Tansu; Szostak, Vanessa A; Feldman, Daniel E

    2004-05-01

    Deprivation-induced plasticity of sensory cortical maps involves long-term potentiation (LTP) and depression (LTD) of cortical synapses, but how sensory deprivation triggers LTP and LTD in vivo is unknown. Here we tested whether spike timing-dependent forms of LTP and LTD are involved in this process. We measured spike trains from neurons in layer 4 (L4) and layers 2 and 3 (L2/3) of rat somatosensory cortex before and after acute whisker deprivation, a manipulation that induces whisker map plasticity involving LTD at L4-to-L2/3 (L4-L2/3) synapses. Whisker deprivation caused an immediate reversal of firing order for most L4 and L2/3 neurons and a substantial decorrelation of spike trains, changes known to drive timing-dependent LTD at L4-L2/3 synapses in vitro. In contrast, spike rate changed only modestly. Thus, whisker deprivation is likely to drive map plasticity by spike timing-dependent mechanisms.

  6. Onset timing of cross-sensory activations and multisensory interactions in auditory and visual sensory cortices.

    PubMed

    Raij, Tommi; Ahveninen, Jyrki; Lin, Fa-Hsuan; Witzel, Thomas; Jääskeläinen, Iiro P; Letham, Benjamin; Israeli, Emily; Sahyoun, Cherif; Vasios, Christos; Stufflebeam, Steven; Hämäläinen, Matti; Belliveau, John W

    2010-05-01

    Here we report early cross-sensory activations and audiovisual interactions at the visual and auditory cortices using magnetoencephalography (MEG) to obtain accurate timing information. Data from an identical fMRI experiment were employed to support MEG source localization results. Simple auditory and visual stimuli (300-ms noise bursts and checkerboards) were presented to seven healthy humans. MEG source analysis suggested generators in the auditory and visual sensory cortices for both within-modality and cross-sensory activations. fMRI cross-sensory activations were strong in the visual but almost absent in the auditory cortex; this discrepancy with MEG possibly reflects the influence of acoustical scanner noise in fMRI. In the primary auditory cortices (Heschl's gyrus) the onset of activity to auditory stimuli was observed at 23 ms in both hemispheres, and to visual stimuli at 82 ms in the left and at 75 ms in the right hemisphere. In the primary visual cortex (Calcarine fissure) the activations to visual stimuli started at 43 ms and to auditory stimuli at 53 ms. Cross-sensory activations thus started later than sensory-specific activations, by 55 ms in the auditory cortex and by 10 ms in the visual cortex, suggesting that the origins of the cross-sensory activations may be in the primary sensory cortices of the opposite modality, with conduction delays (from one sensory cortex to another) of 30-35 ms. Audiovisual interactions started at 85 ms in the left auditory, 80 ms in the right auditory and 74 ms in the visual cortex, i.e., 3-21 ms after inputs from the two modalities converged.

  7. Onset timing of cross-sensory activations and multisensory interactions in auditory and visual sensory cortices

    PubMed Central

    Raij, Tommi; Ahveninen, Jyrki; Lin, Fa-Hsuan; Witzel, Thomas; Jääskeläinen, Iiro P.; Letham, Benjamin; Israeli, Emily; Sahyoun, Cherif; Vasios, Christos; Stufflebeam, Steven; Hämäläinen, Matti; Belliveau, John W.

    2010-01-01

    Here we report early cross-sensory activations and audiovisual interactions at the visual and auditory cortices using magnetoencephalography (MEG) to obtain accurate timing information. Data from an identical fMRI experiment were employed to support MEG source localization results. Simple auditory and visual stimuli (300-ms noise bursts and checkerboards) were presented to seven healthy humans. MEG source analysis suggested generators in the auditory and visual sensory cortices for both within-modality and cross-sensory activations. fMRI cross-sensory activations were strong in the visual but almost absent in the auditory cortex; this discrepancy with MEG possibly reflects influence of acoustical scanner noise in fMRI. In the primary auditory cortices (Heschl’s gyrus) onset of activity to auditory stimuli was observed at 23 ms in both hemispheres, and to visual stimuli at 82 ms in the left and at 75 ms in the right hemisphere. In the primary visual cortex (Calcarine fissure) the activations to visual stimuli started at 43 ms and to auditory stimuli at 53 ms. Cross-sensory activations thus started later than sensory-specific activations, by 55 ms in the auditory cortex and by 10 ms in the visual cortex, suggesting that the origins of the cross-sensory activations may be in the primary sensory cortices of the opposite modality, with conduction delays (from one sensory cortex to another) of 30–35 ms. Audiovisual interactions started at 85 ms in the left auditory, 80 ms in the right auditory, and 74 ms in the visual cortex, i.e., 3–21 ms after inputs from both modalities converged. PMID:20584181

  8. Biophysical Model of Cortical Network Activity and the Influence of Electrical Stimulation

    DTIC Science & Technology

    2015-11-13

    parameters for seizure disruption using neural network simulations, Biological Cybernetics (08 2007) W.S. Anderson, P. Kudela, S. Weinberg, G.K...Bergey, P.J. Franaszczuk. Phase-dependent stimulation effects on bursting activity in a neural network cortical simulation, Epilepsy Research (07 2008...Epilepsy Research (06 2011) WS Anderson, F Azhar. Predicting Single-Neuron Activity in Locally Connected Networks , Neural Computation (05 2011

  9. Sleep active cortical neurons expressing neuronal nitric oxide synthase are active after both acute sleep deprivation and chronic sleep restriction.

    PubMed

    Zielinski, M R; Kim, Y; Karpova, S A; Winston, S; McCarley, R W; Strecker, R E; Gerashchenko, D

    2013-09-05

    Non-rapid eye movement (NREM) sleep electroencephalographic (EEG) delta power (~0.5-4 Hz), also known as slow wave activity (SWA), is typically enhanced after acute sleep deprivation (SD) but not after chronic sleep restriction (CSR). Recently, sleep-active cortical neurons expressing neuronal nitric oxide synthase (nNOS) were identified and associated with enhanced SWA after short acute bouts of SD (i.e., 6h). However, the relationship between cortical nNOS neuronal activity and SWA during CSR is unknown. We compared the activity of cortical neurons expressing nNOS (via c-Fos and nNOS immuno-reactivity, respectively) and sleep in rats in three conditions: (1) after 18-h of acute SD; (2) after five consecutive days of sleep restriction (SR) (18-h SD per day with 6h ad libitum sleep opportunity per day); (3) and time-of-day matched ad libitum sleep controls. Cortical nNOS neuronal activity was enhanced during sleep after both 18-h SD and 5 days of SR treatments compared to control treatments. SWA and NREM sleep delta energy (the product of NREM sleep duration and SWA) were positively correlated with enhanced cortical nNOS neuronal activity after 18-h SD but not 5days of SR. That neurons expressing nNOS were active after longer amounts of acute SD (18h vs. 6h reported in the literature) and were correlated with SWA further suggest that these cells might regulate SWA. However, since these neurons were active after CSR when SWA was not enhanced, these findings suggest that mechanisms downstream of their activation are altered during CSR.

  10. Selection of independent components based on cortical mapping of electromagnetic activity

    NASA Astrophysics Data System (ADS)

    Chan, Hui-Ling; Chen, Yong-Sheng; Chen, Li-Fen

    2012-10-01

    Independent component analysis (ICA) has been widely used to attenuate interference caused by noise components from the electromagnetic recordings of brain activity. However, the scalp topographies and associated temporal waveforms provided by ICA may be insufficient to distinguish functional components from artifactual ones. In this work, we proposed two component selection methods, both of which first estimate the cortical distribution of the brain activity for each component, and then determine the functional components based on the parcellation of brain activity mapped onto the cortical surface. Among all independent components, the first method can identify the dominant components, which have strong activity in the selected dominant brain regions, whereas the second method can identify those inter-regional associating components, which have similar component spectra between a pair of regions. For a targeted region, its component spectrum enumerates the amplitudes of its parceled brain activity across all components. The selected functional components can be remixed to reconstruct the focused electromagnetic signals for further analysis, such as source estimation. Moreover, the inter-regional associating components can be used to estimate the functional brain network. The accuracy of the cortical activation estimation was evaluated on the data from simulation studies, whereas the usefulness and feasibility of the component selection methods were demonstrated on the magnetoencephalography data recorded from a gender discrimination study.

  11. Sensory and decision-related activity propagate in a cortical feedback loop during touch perception

    PubMed Central

    Kwon, Sung Eun; Yang, Hongdian; Minamisawa, Genki; O’Connor, Daniel H.

    2016-01-01

    The brain transforms physical sensory stimuli into meaningful perceptions. In animals making choices about sensory stimuli, neuronal activity in successive cortical stages reflects a progression from sensation to decision. Feedforward and feedback pathways connecting cortical areas are critical for this transformation. However, the computational roles of these pathways are poorly understood because pathway-specific activity has rarely been monitored during a perceptual task. Using cellular-resolution, pathway-specific imaging, we measured neuronal activity across primary (S1) and secondary (S2) somatosensory cortices of mice performing a tactile detection task. S1 encoded the stimulus better than S2, while S2 activity more strongly reflected perceptual choice. S1 neurons projecting to S2 fed forward activity that predicted choice. Activity encoding touch and choice propagated in an S1–S2 loop along feedforward and feedback axons. Our results suggest that sensory inputs converge into a perceptual outcome as feedforward computations are reinforced in a feedback loop. PMID:27437910

  12. Improved estimation of human cortical activity and connectivity with the multimodal integration of neuroelectric and hemodynamic data.

    PubMed

    Babiloni, F; Mattia, D; Basilisco, A; Astolfi, L; Cincotti, F; Ding, L; Christine, K; Sweeney, J; Edgar, J C; Miller, G A; He, B

    2005-01-01

    In the last decade, the possibility to noninvasively estimate cortical activity and connectivity has been highlighted by the application of the techniques known as high resolution EEG. These techniques include a subject's multi-compartment head model (scalp, skull, dura mater, cortex) constructed from individual magnetic resonance images, multi-dipole source model, and regularized linear inverse source estimates of cortical current density. More recently, it has proved as the use of information from the hemodynamic responses of the cortical areas as revealed by block-designed (strength of activated voxels) fMRI improves dramatically the estimates of cortical activity and connectivity. Here, we present some applications of such estimation in two set of high resolution EEG and fMRI data, related to the motor (finger tapping) and cognitive (Stroop) tasks. We observed that the proposed technology was able to unveil the direction of the information flow between the cortical regions of interest.

  13. Resonant antidromic cortical circuit activation as a consequence of high-frequency subthalamic deep-brain stimulation.

    PubMed

    Li, S; Arbuthnott, G W; Jutras, M J; Goldberg, J A; Jaeger, D

    2007-12-01

    Deep brain stimulation (DBS) is an effective treatment of Parkinson's disease (PD) for many patients. The most effective stimulation consists of high-frequency biphasic stimulation pulses around 130 Hz delivered between two active sites of an implanted depth electrode to the subthalamic nucleus (STN-DBS). Multiple studies have shown that a key effect of STN-DBS that correlates well with clinical outcome is the reduction of synchronous and oscillatory activity in cortical and basal ganglia networks. We hypothesized that antidromic cortical activation may provide an underlying mechanism responsible for this effect, because stimulation is usually performed in proximity to cortical efferent pathways. We show with intracellular cortical recordings in rats that STN-DBS did in fact lead to antidromic spiking of deep layer cortical neurons. Furthermore, antidromic spikes triggered a dampened oscillation of local field potentials in cortex with a resonant frequency around 120 Hz. The amplitude of antidromic activation was significantly correlated with an observed suppression of slow wave and beta band activity during STN-DBS. These findings were seen in ketamine-xylazine or isoflurane anesthesia in both normal and 6-hydroxydopamine (6-OHDA)-lesioned rats. Thus antidromic resonant activation of cortical microcircuits may make an important contribution toward counteracting the overly synchronous and oscillatory activity characteristic of cortical activity in PD.

  14. Pattern of trauma determines the threshold for epileptic activity in a model of cortical deafferentation

    PubMed Central

    Volman, Vladislav; Bazhenov, Maxim; Sejnowski, Terrence J.

    2011-01-01

    Epileptic activity often occurs in the cortex after a latent period after head trauma; this delay has been attributed to the destabilizing influence of homeostatic synaptic scaling and changes in intrinsic properties. However, the impact of the spatial organization of cortical trauma on epileptogenesis is poorly understood. We addressed this question by analyzing the dynamics of a large-scale biophysically realistic cortical network model subjected to different patterns of trauma. Our results suggest that the spatial pattern of trauma can greatly affect the propensity for developing posttraumatic epileptic activity. For the same fraction of lesioned neurons, spatially compact trauma resulted in stronger posttraumatic elevation of paroxysmal activity than spatially diffuse trauma. In the case of very severe trauma, diffuse distribution of a small number of surviving intact neurons alleviated posttraumatic epileptogenesis. We suggest that clinical evaluation of the severity of brain trauma should take into account the spatial pattern of the injured cortex. PMID:21896754

  15. Cortical connective field estimates from resting state fMRI activity.

    PubMed

    Gravel, Nicolás; Harvey, Ben; Nordhjem, Barbara; Haak, Koen V; Dumoulin, Serge O; Renken, Remco; Curčić-Blake, Branislava; Cornelissen, Frans W

    2014-01-01

    One way to study connectivity in visual cortical areas is by examining spontaneous neural activity. In the absence of visual input, such activity remains shaped by the underlying neural architecture and, presumably, may still reflect visuotopic organization. Here, we applied population connective field (CF) modeling to estimate the spatial profile of functional connectivity in the early visual cortex during resting state functional magnetic resonance imaging (RS-fMRI). This model-based analysis estimates the spatial integration between blood-oxygen level dependent (BOLD) signals in distinct cortical visual field maps using fMRI. Just as population receptive field (pRF) mapping predicts the collective neural activity in a voxel as a function of response selectivity to stimulus position in visual space, CF modeling predicts the activity of voxels in one visual area as a function of the aggregate activity in voxels in another visual area. In combination with pRF mapping, CF locations on the cortical surface can be interpreted in visual space, thus enabling reconstruction of visuotopic maps from resting state data. We demonstrate that V1 ➤ V2 and V1 ➤ V3 CF maps estimated from resting state fMRI data show visuotopic organization. Therefore, we conclude that-despite some variability in CF estimates between RS scans-neural properties such as CF maps and CF size can be derived from resting state data.

  16. Cortical connective field estimates from resting state fMRI activity

    PubMed Central

    Gravel, Nicolás; Harvey, Ben; Nordhjem, Barbara; Haak, Koen V.; Dumoulin, Serge O.; Renken, Remco; Ćurčić-Blake, Branislava; Cornelissen, Frans W.

    2014-01-01

    One way to study connectivity in visual cortical areas is by examining spontaneous neural activity. In the absence of visual input, such activity remains shaped by the underlying neural architecture and, presumably, may still reflect visuotopic organization. Here, we applied population connective field (CF) modeling to estimate the spatial profile of functional connectivity in the early visual cortex during resting state functional magnetic resonance imaging (RS-fMRI). This model-based analysis estimates the spatial integration between blood-oxygen level dependent (BOLD) signals in distinct cortical visual field maps using fMRI. Just as population receptive field (pRF) mapping predicts the collective neural activity in a voxel as a function of response selectivity to stimulus position in visual space, CF modeling predicts the activity of voxels in one visual area as a function of the aggregate activity in voxels in another visual area. In combination with pRF mapping, CF locations on the cortical surface can be interpreted in visual space, thus enabling reconstruction of visuotopic maps from resting state data. We demonstrate that V1 ➤ V2 and V1 ➤ V3 CF maps estimated from resting state fMRI data show visuotopic organization. Therefore, we conclude that—despite some variability in CF estimates between RS scans—neural properties such as CF maps and CF size can be derived from resting state data. PMID:25400541

  17. Thalamic stimulation largely elicits orthodromic, rather than antidromic, cortical activation in an auditory thalamocortical slice.

    PubMed

    Rose, H J; Metherate, R

    2001-01-01

    Stimulation of the medial geniculate body in an auditory thalamocortical slice elicits a short-latency current sink in the middle cortical layers, as would be expected following activation of thalamocortical relay neurons. However, corticothalamic neurons can have axon collaterals that project to the middle layers, thus, a middle-layer current sink could also result from antidromic activation of corticothalamic neurons and their axon collaterals. The likelihood of thalamic stimulation activating corticothalamic neurons would be reduced substantially if the corticothalamic pathway was not well preserved in the slice, and/or if the threshold for antidromic activation was significantly higher than for orthodromic activation. To determine the prevalence and threshold of antidromic activation, we recorded intracellularly from day 14-17 mouse brain slices containing infragranular cortical neurons while stimulating the medial geniculate or thalamocortical pathway. Antidromic spikes were confirmed by spike collision and characterized according to spike latency "jitter" and the ability to follow a high-frequency (100 Hz) stimulus train. The ability to follow a 100-Hz tetanus was a reliable indicator of antidromic activation, but both antidromic and orthodromic spikes could have low jitter. Thalamic stimulation produced antidromic activation in two of 69 infragranular cortical neurons (<3%), indicating the presence of antidromic activity, but implying a limited corticothalamic connection in the slice. Antidromic spikes in 13 additional neurons were obtained by stimulating axons in the thalamocortical pathway. The antidromic threshold averaged 214+/-40.6 microA (range 6-475 microA), over seven times the orthodromic threshold for medial geniculate-evoked responses in layer IV extracellular (28+/-5.4 microA) or intracellular (27+/-5.6 microA) recordings. We conclude that medial geniculate stimulation activates relatively few corticothalamic neurons. Conversely, low

  18. Impact of Acetazolamide and CPAP on Cortical Activity in Obstructive Sleep Apnea Patients

    PubMed Central

    Stadelmann, Katrin; Latshang, Tsogyal D.; Nussbaumer-Ochsner, Yvonne; Tarokh, Leila; Ulrich, Silvia; Kohler, Malcolm; Bloch, Konrad E.; Achermann, Peter

    2014-01-01

    Study Objectives 1) To investigate the impact of acetazolamide, a drug commonly prescribed for altitude sickness, on cortical oscillations in patients with obstructive sleep apnea syndrome (OSAS). 2) To examine alterations in the sleep EEG after short-term discontinuation of continuous positive airway pressure (CPAP) therapy. Design Data from two double-blind, placebo-controlled randomized cross-over design studies were analyzed. Setting Polysomnographic recordings in sleep laboratory at 490 m and at moderate altitudes in the Swiss Alps: 1630 or 1860 m and 2590 m. Patients Study 1: 39 OSAS patients. Study 2: 41 OSAS patients. Interventions Study 1: OSAS patients withdrawn from treatment with CPAP. Study 2: OSAS patients treated with autoCPAP. Treatment with acetazolamide (500–750 mg) or placebo at moderate altitudes. Measurements and Results An evening dose of 500 mg acetazolamide reduced slow-wave activity (SWA; approximately 10%) and increased spindle activity (approximately 10%) during non-REM sleep. In addition, alpha activity during wake after lights out was increased. An evening dose of 250 mg did not affect these cortical oscillations. Discontinuation of CPAP therapy revealed a reduction in SWA (5–10%) and increase in beta activity (approximately 25%). Conclusions The higher evening dose of 500 mg acetazolamide showed the “spectral fingerprint” of Benzodiazepines, while 250 mg acetazolamide had no impact on cortical oscillations. However, both doses had beneficial effects on oxygen saturation and sleep quality. PMID:24710341

  19. Changes in Mice Brain Spontaneous Electrical Activity during Cortical Spreading Depression due to Mobile Phone Radiation

    PubMed Central

    Sallam, Samera M.; Mohamed, Ehab I.; Dawood, Abdel-Fattah B.

    2008-01-01

    The objective of the present study was to investigate changes in spontaneous EEG activity during cortical spreading depression (CSD) in mice brain. The cortical region of anaesthetized mice were exposed to the electromagnetic fields (EMFs) emitted from a mobile phone (MP, 935.2-960.2 MHz, 41.8 mW/cm2). The effect of EMFs on EEG was investigated before and after exposure to different stimuli (MP, 2% KCl, and MP & 2% KCl). The records of brain spontaneous EEG activity, slow potential changes (SPC), and spindle shaped firings were obtained through an interfaced computer. The results showed increases in the amplitude of evoked spindles by about 87%, 17%, and 226% for MP, 2% KCl, and MP & 2% KCl; respectively, as compared to values for the control group. These results showed that the evoked spindle is a more sensitive indicator of the effect of exposure to EMFs from MP. PMID:23675079

  20. Simultaneous modulation of retrieval by dopaminergic D(1), beta-noradrenergic, serotonergic-1A and cholinergic muscarinic receptors in cortical structures of the rat.

    PubMed

    Barros, D M; Mello e Souza, T; De David, T; Choi, H; Aguzzoli, A; Madche, C; Ardenghi, P; Medina, J H; Izquierdo, I

    2001-09-28

    Retrieval of inhibitory avoidance has been recently shown to require intact glutamate receptors, protein kinases A and C and mitogen-activated protein kinase in the CA1 region of the rat hippocampus and in the entorhinal, posterior parietal and anterior cingulate cortex. These enzymatic activities are known to be modulated by dopamine D(1), beta-noradrenergic, 5HT1A and cholinergic muscarinic receptors. Here we study the effect on retrieval of this task of well-known agonists and antagonists of these receptors infused in the same brain cortical regions and into the basolateral amygdala, in rats. The drugs used were SKF38393 (D(1) agonist), noradrenaline, 8-HO-DPAT (5HT1A agonist), oxotremorine (muscarinic agonist), SCH23390 (D(1) antagonist), timolol (beta antagonist), NAN-190 (5HT1A antagonist) and scopolamine (muscarinic antagonist). All were studied at two different dose levels. The localised infusion of SKF38393, noradrenaline, NAN-190 and oxotremorine into any of the cortical structures mentioned 10 min prior to a 24-h retention test session of one-trial step-down inhibitory avoidance enhanced retention test performance. SCH2330, timolol, 8-HO-DPAT and scopolamine hindered retention test performance. In the basolateral amygdala only an enhancing effect of noradrenaline and an inhibitory effect of timolol were seen. Three hours after the infusions, retention test performance returned to normal in all cases. None of the treatments affected locomotion or rearing in an open field or behaviour in the elevated plus maze. Therefore, their effects on retention testing can be attributed to an influence on retrieval. In conclusion, memory retrieval of this apparently simple task requires the participation of CA1, entorhinal, posterior parietal and anterior cingulate cortex, and is strongly modulated by, dopaminergic D(1), beta-noradrenergic, muscarinic cholinergic and 5HT1A receptors in the four areas. The first three types of receptor enhance, and the latter inhibits

  1. Cortical activation associated with muscle synergies of the human male pelvic floor.

    PubMed

    Asavasopon, Skulpan; Rana, Manku; Kirages, Daniel J; Yani, Moheb S; Fisher, Beth E; Hwang, Darryl H; Lohman, Everett B; Berk, Lee S; Kutch, Jason J

    2014-10-08

    Human pelvic floor muscles have been shown to operate synergistically with a wide variety of muscles, which has been suggested to be an important contributor to continence and pelvic stability during functional tasks. However, the neural mechanism of pelvic floor muscle synergies remains unknown. Here, we test the hypothesis that activation in motor cortical regions associated with pelvic floor activation are part of the neural substrate for such synergies. We first use electromyographic recordings to extend previous findings and demonstrate that pelvic floor muscles activate synergistically during voluntary activation of gluteal muscles, but not during voluntary activation of finger muscles. We then show, using functional magnetic resonance imaging (fMRI), that a region of the medial wall of the precentral gyrus consistently activates during both voluntary pelvic floor muscle activation and voluntary gluteal activation, but not during voluntary finger activation. We finally confirm, using transcranial magnetic stimulation, that the fMRI-identified medial wall region is likely to generate pelvic floor muscle activation. Thus, muscle synergies of the human male pelvic floor appear to involve activation of motor cortical areas associated with pelvic floor control.

  2. Cortical Activation Associated with Muscle Synergies of the Human Male Pelvic Floor

    PubMed Central

    Asavasopon, Skulpan; Rana, Manku; Kirages, Daniel J.; Yani, Moheb S.; Fisher, Beth E.; Hwang, Darryl H.; Lohman, Everett B.; Berk, Lee S.

    2014-01-01

    Human pelvic floor muscles have been shown to operate synergistically with a wide variety of muscles, which has been suggested to be an important contributor to continence and pelvic stability during functional tasks. However, the neural mechanism of pelvic floor muscle synergies remains unknown. Here, we test the hypothesis that activation in motor cortical regions associated with pelvic floor activation are part of the neural substrate for such synergies. We first use electromyographic recordings to extend previous findings and demonstrate that pelvic floor muscles activate synergistically during voluntary activation of gluteal muscles, but not during voluntary activation of finger muscles. We then show, using functional magnetic resonance imaging (fMRI), that a region of the medial wall of the precentral gyrus consistently activates during both voluntary pelvic floor muscle activation and voluntary gluteal activation, but not during voluntary finger activation. We finally confirm, using transcranial magnetic stimulation, that the fMRI-identified medial wall region is likely to generate pelvic floor muscle activation. Thus, muscle synergies of the human male pelvic floor appear to involve activation of motor cortical areas associated with pelvic floor control. PMID:25297107

  3. Patterns of cortical activity during the observation of Public Service Announcements and commercial advertisings

    PubMed Central

    2010-01-01

    Background In the present research we were interested to study the cerebral activity of a group of healthy subjects during the observation a documentary intermingled by a series of TV advertisements. In particular, we desired to examine whether Public Service Announcements (PSAs) are able to elicit a different pattern of activity, when compared with a different class of commercials, and correlate it with the memorization of the showed stimuli, as resulted from a following subject’s verbal interview. Methods We recorded the EEG signals from a group of 15 healthy subjects and applied the High Resolution EEG techniques in order to estimate and map their Power Spectral Density (PSD) on a realistic cortical model. The single subjects’ activities have been z-score transformed and then grouped to define four different datasets, related to subjects who remembered and forgotten the PSAs and to subjects who remembered and forgotten cars commercials (CAR) respectively, which we contrasted to investigate cortical areas involved in this encoding process. Results The results we here present show that the cortical activity elicited during the observation of the TV commercials that were remembered (RMB) is higher and localized in the left frontal brain areas when compared to the activity elicited during the vision of the TV commercials that were forgotten (FRG) in theta and gamma bands for both categories of advertisements (PSAs and CAR). Moreover, the cortical maps associated with the PSAs also show an increase of activity in the alpha and beta band. Conclusions In conclusion, the TV advertisements that will be remembered by the experimental population have increased their cerebral activity, mainly in the left hemisphere. These results seem to be congruent with and well inserted in the already existing literature, on this topic, related to the HERA model. The different pattern of activity in different frequency bands elicited by the observation of PSAs may be justified by the

  4. Dynamics of Electrocorticographic (ECoG) Activity in Human Temporal and Frontal Cortical Areas During Music Listening

    DTIC Science & Technology

    2012-04-14

    REPORT Dynamics of electrocorticographic (ECoG) activity in human temporal and frontal cortical areas during music listening 14. ABSTRACT 16. SECURITY...information about the sound intensity of music . ECoG activity in the high gamma band recorded from the posterior part of the superior temporal 1. REPORT...ECoG) activity in human temporal and frontal cortical areas during music listening Report Title ABSTRACT Previous studies demonstrated that brain

  5. Genetic Feedback Regulation of Frontal Cortical Neuronal Ensembles Through Activity-Dependent Arc Expression and Dopaminergic Input

    PubMed Central

    Mastwal, Surjeet; Cao, Vania; Wang, Kuan Hong

    2016-01-01

    Mental functions involve coordinated activities of specific neuronal ensembles that are embedded in complex brain circuits. Aberrant neuronal ensemble dynamics is thought to form the neurobiological basis of mental disorders. A major challenge in mental health research is to identify these cellular ensembles and determine what molecular mechanisms constrain their emergence and consolidation during development and learning. Here, we provide a perspective based on recent studies that use activity-dependent gene Arc/Arg3.1 as a cellular marker to identify neuronal ensembles and a molecular probe to modulate circuit functions. These studies have demonstrated that the transcription of Arc is activated in selective groups of frontal cortical neurons in response to specific behavioral tasks. Arc expression regulates the persistent firing of individual neurons and predicts the consolidation of neuronal ensembles during repeated learning. Therefore, the Arc pathway represents a prototypical example of activity-dependent genetic feedback regulation of neuronal ensembles. The activation of this pathway in the frontal cortex starts during early postnatal development and requires dopaminergic (DA) input. Conversely, genetic disruption of Arc leads to a hypoactive mesofrontal dopamine circuit and its related cognitive deficit. This mutual interaction suggests an auto-regulatory mechanism to amplify the impact of neuromodulators and activity-regulated genes during postnatal development. Such a mechanism may contribute to the association of mutations in dopamine and Arc pathways with neurodevelopmental psychiatric disorders. As the mesofrontal dopamine circuit shows extensive activity-dependent developmental plasticity, activity-guided modulation of DA projections or Arc ensembles during development may help to repair circuit deficits related to neuropsychiatric disorders. PMID:27999532

  6. Genetic Feedback Regulation of Frontal Cortical Neuronal Ensembles Through Activity-Dependent Arc Expression and Dopaminergic Input.

    PubMed

    Mastwal, Surjeet; Cao, Vania; Wang, Kuan Hong

    2016-01-01

    Mental functions involve coordinated activities of specific neuronal ensembles that are embedded in complex brain circuits. Aberrant neuronal ensemble dynamics is thought to form the neurobiological basis of mental disorders. A major challenge in mental health research is to identify these cellular ensembles and determine what molecular mechanisms constrain their emergence and consolidation during development and learning. Here, we provide a perspective based on recent studies that use activity-dependent gene Arc/Arg3.1 as a cellular marker to identify neuronal ensembles and a molecular probe to modulate circuit functions. These studies have demonstrated that the transcription of Arc is activated in selective groups of frontal cortical neurons in response to specific behavioral tasks. Arc expression regulates the persistent firing of individual neurons and predicts the consolidation of neuronal ensembles during repeated learning. Therefore, the Arc pathway represents a prototypical example of activity-dependent genetic feedback regulation of neuronal ensembles. The activation of this pathway in the frontal cortex starts during early postnatal development and requires dopaminergic (DA) input. Conversely, genetic disruption of Arc leads to a hypoactive mesofrontal dopamine circuit and its related cognitive deficit. This mutual interaction suggests an auto-regulatory mechanism to amplify the impact of neuromodulators and activity-regulated genes during postnatal development. Such a mechanism may contribute to the association of mutations in dopamine and Arc pathways with neurodevelopmental psychiatric disorders. As the mesofrontal dopamine circuit shows extensive activity-dependent developmental plasticity, activity-guided modulation of DA projections or Arc ensembles during development may help to repair circuit deficits related to neuropsychiatric disorders.

  7. Procedure for recording the simultaneous activity of single neurons distributed across cortical areas during sensory discrimination

    PubMed Central

    Hernández, Adrián; Nácher, Verónica; Luna, Rogelio; Alvarez, Manuel; Zainos, Antonio; Cordero, Silvia; Camarillo, Liliana; Vázquez, Yuriria; Lemus, Luis; Romo, Ranulfo

    2008-01-01

    We report a procedure for recording the simultaneous activity of single neurons distributed across five cortical areas in behaving monkeys. The procedure consists of a commercially available microdrive adapted to a commercially available neural data collection system. The critical advantage of this procedure is that, in each cortical area, a configuration of seven microelectrodes spaced 250–500 μm can be inserted transdurally and each can be moved independently in the z axis. For each microelectrode, the data collection system can record the activity of up to five neurons together with the local field potential (LFP). With this procedure, we normally monitor the simultaneous activity of 70–100 neurons while trained monkeys discriminate the difference in frequency between two vibrotactile stimuli. Approximately 20–60 of these neurons have response properties previously reported in this task. The neuronal recordings show good signal-to-noise ratio, are remarkably stable along a 1-day session, and allow testing several protocols. Microelectrodes are removed from the brain after a 1-day recording session, but are reinserted again the next day by using the same or different x-y microelectrode array configurations. The fact that microelectrodes can be moved in the z axis during the recording session and that the x-y configuration can be changed from day to day maximizes the probability of studying simultaneous interactions, both local and across distant cortical areas, between neurons associated with the different components of this task. PMID:18946031

  8. TUMOR NECROSIS FACTOR α: ACTIVITY DEPENDENT EXPRESSION AND PROMOTION OF CORTICAL COLUMN SLEEP IN RATS

    PubMed Central

    Churchill, L.; Rector, D.M.; Yasuda, K.; Fix, C.; Rojas, M.J.; Yasuda, T.; Krueger, J.M.

    2008-01-01

    Cortical surface evoked potentials (SEPs) are larger during sleep and characterize a sleep-like state in cortical columns. Since tumor necrosis factor alpha (TNF) may be involved in sleep regulation and is produced as a consequence of waking activity, we tested the hypothesis that direct application of TNF to the cortex will induce a sleep-like state within cortical columns and enhance SEP amplitudes. We found that microinjection of TNF onto the surface of the somatosensory cortex enhanced whisker stimulation-induced SEP amplitude relative to a control heat-inactivated TNF microinjection. We also determined if whisker stimulation enhanced endogenous TNF expression. TNF immunoreactivity (IR) was visualized after 2 h of bilateral deflection of a single whisker bilaterally. The number of TNF-IR cells increased in layers II–IV of the activated somatosensory barrel column. In two separate studies, unilateral deflection of multiple whiskers for 2 h increased the number of TNF-IR cells in layers II–V in columns that also exhibited enhanced Fos-IR. TNF-IR also colocalized with NeuN-IR suggesting that TNF expression was in neurons. Collectively these data are consistent with the hypotheses that TNF is produced in response to neural activity and in turn enhances the probability of a local sleep-like state as determined by increases in SEP amplitudes. PMID:18694809

  9. Temporal and spatial patterns of cortical activation during assisted lower limb movement.

    PubMed

    Wieser, M; Haefeli, J; Bütler, L; Jäncke, L; Riener, R; Koeneke, S

    2010-05-01

    Human gait is a complex process in the central nervous system that results from the integrity of various mechanisms, including different cortical and subcortical structures. In the present study, we investigated cortical activity during lower limb movement using EEG. Assisted by a dynamic tilt table, all subjects performed standardized stepping movements in an upright position. Source localization of the movement-related potential in relation to spontaneous EEG showed activity in brain regions classically associated with human gait such as the primary motor cortex, the premotor cortex, the supplementary motor cortex, the cingulate cortex, the primary somatosensory cortex and the somatosensory association cortex. Further, we observed a task-related power decrease in the alpha and beta frequency band at electrodes overlying the leg motor area. A temporal activation and deactivation of the involved brain regions as well as the chronological sequence of the movement-related potential could be mapped to specific phases of the gait-like leg movement. We showed that most cortical capacity is needed for changing the direction between the flexion and extension phase. An enhanced understanding of the human gait will provide a basis to improve applications in the field of neurorehabilitation and brain-computer interfaces.

  10. Cerebellar theta burst stimulation modulates the neural activity of interconnected parietal and motor areas

    PubMed Central

    Casula, Elias Paolo; Pellicciari, Maria Concetta; Ponzo, Viviana; Stampanoni Bassi, Mario; Veniero, Domenica; Caltagirone, Carlo; Koch, Giacomo

    2016-01-01

    Voluntary movement control and execution are regulated by the influence of the cerebellar output over different interconnected cortical areas, through dentato-thalamo connections. In the present study we applied transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to directly assess the effects of cerebellar theta-burst stimulation (TBS) over the controlateral primary motor cortex (M1) and posterior parietal cortex (PPC) in a group of healthy volunteers. We found a TBS-dependent bidirectional modulation over TMS-evoked activity; specifically, cTBS increased whereas iTBS decreased activity between 100 and 200 ms after TMS, in a similar manner over both M1 and PPC areas. On the oscillatory domain, TBS induced specific changes over M1 natural frequencies of oscillation: TMS-evoked alpha activity was decreased by cTBS whereas beta activity was enhanced by iTBS. No effects were observed after sham stimulation. Our data provide novel evidence showing that the cerebellum exerts its control on the cortex likely by impinging on specific set of interneurons dependent on GABA-ergic activity. We show that cerebellar TBS modulates cortical excitability of distant interconnected cortical areas by acting through common temporal, spatial and frequency domains. PMID:27796359

  11. Reversible Information Flow across the Medial Temporal Lobe: The Hippocampus Links Cortical Modules during Memory Retrieval

    PubMed Central

    Cooper, Elisa; Henson, Richard N.

    2013-01-01

    A simple cue can be sufficient to elicit vivid recollection of a past episode. Theoretical models suggest that upon perceiving such a cue, disparate episodic elements held in neocortex are retrieved through hippocampal pattern completion. We tested this fundamental assumption by applying functional magnetic resonance imaging (fMRI) while objects or scenes were used to cue participants' recall of previously paired scenes or objects, respectively. We first demonstrate functional segregation within the medial temporal lobe (MTL), showing domain specificity in perirhinal and parahippocampal cortices (for object-processing vs scene-processing, respectively), but domain generality in the hippocampus (retrieval of both stimulus types). Critically, using fMRI latency analysis and dynamic causal modeling, we go on to demonstrate functional integration between these MTL regions during successful memory retrieval, with reversible signal flow from the cue region to the target region via the hippocampus. This supports the claim that the human hippocampus provides the vital associative link that integrates information held in different parts of cortex. PMID:23986252

  12. Enhanced cortical excitability in grapheme-color synesthesia and its modulation.

    PubMed

    Terhune, Devin Blair; Tai, Sarah; Cowey, Alan; Popescu, Tudor; Cohen Kadosh, Roi

    2011-12-06

    Synesthesia is an unusual condition characterized by the over-binding of two or more features and the concomitant automatic and conscious experience of atypical, ancillary images or perceptions. Previous research suggests that synesthetes display enhanced modality-specific perceptual processing, but it remains unclear whether enhanced processing contributes to conscious awareness of color photisms. In three experiments, we investigated whether grapheme-color synesthesia is characterized by enhanced cortical excitability in primary visual cortex and the role played by this hyperexcitability in the expression of synesthesia. Using transcranial magnetic stimulation, we show that synesthetes display 3-fold lower phosphene thresholds than controls during stimulation of the primary visual cortex. We next used transcranial direct current stimulation to discriminate between two competing hypotheses of the role of hyperexcitability in the expression of synesthesia. We demonstrate that synesthesia can be selectively augmented with cathodal stimulation and attenuated with anodal stimulation of primary visual cortex. A control task revealed that the effect of the brain stimulation was specific to the experience of synesthesia. These results indicate that hyperexcitability acts as a source of noise in visual cortex that influences the availability of the neuronal signals underlying conscious awareness of synesthetic photisms.

  13. The relationship of approach/avoidance motivation and asymmetric frontal cortical activity: A review of studies manipulating frontal asymmetry.

    PubMed

    Kelley, Nicholas J; Hortensius, Ruud; Schutter, Dennis J L G; Harmon-Jones, Eddie

    2017-03-10

    The balance between activity in the left and right frontal cortex, commonly referred to as asymmetric frontal cortical activity, has served as a proxy for an organism's motivational direction (i.e., approach vs. avoidance). Many studies have examined the influence of the manipulation of motivational direction on asymmetrical frontal cortical activity and found results consistent with the idea that greater relative left (right) frontal cortical activity is associated with approach (avoidance) motivation. We critically review literature employing physical (versus psychological) manipulations of frontal asymmetry using a variety of methodologies including neurofeedback training, muscular contractions, and non-invasive brain stimulation. These reviewed methods allow us to make stronger causal inferences regarding the role of asymmetric frontal cortical activity in approach and avoidance motivation.

  14. Different cortical activation patterns during voluntary eccentric and concentric muscle contractions: an fMRI study.

    PubMed

    Kwon, Yong-Hyun; Park, Ji-Won

    2011-01-01

    Concentric and eccentric muscle contractions have distinct differences in their neuromuscular and neurophysiologic characteristics. However, although many evidences regarding the features of these types of muscle contraction have emerged, there have been few neuroimaging studies to compare the two types of contractions. Therefore, we investigated whether cortical activity associated with eccentric contraction of the wrist extensors differed from that of concentric contraction, using functional MRI (fMRI). Fifteen right-handed healthy subjects were enrolled in this study. During 4 repeating blocks of eccentric and concentric muscle contraction paradigms, the brain was scanned with fMRI. The differences in the BOLD signal intensities during the performance of eccentric and concentric exercise were compared in the predetermined regions of interest. Our findings revealed that many cortical areas associated with motor performance were activated, including the primary motor area, the inferior parietal lobe, the pre-supplementary area (pre-SMA), the anterior cingulate cortex, the prefrontal area, and the cerebellum. In addition, lower signal intensities were seen in the right primary motor cortex and right cerebellum during eccentric contractions compared with concentric contractions, whereas higher signal intensities were detected in other cortical areas during eccentric contractions. In the study, we demonstrated that eccentric and concentric muscle contractions induced quite different patterns of cortical activity respectively. These findings might be attributed to different strategy of neuro-motor processing and a higher level of cognitive demand for the performance of motor task with a higher degree of difficulty such as that required during eccentric contractions in comparison of concentric contractions.

  15. Early Category-Specific Cortical Activation Revealed by Visual Stimulus Inversion

    PubMed Central

    Meeren, Hanneke K. M.; Hadjikhani, Nouchine; Ahlfors, Seppo P.; Hämäläinen, Matti S.; de Gelder, Beatrice

    2008-01-01

    Visual categorization may already start within the first 100-ms after stimulus onset, in contrast with the long-held view that during this early stage all complex stimuli are processed equally and that category-specific cortical activation occurs only at later stages. The neural basis of this proposed early stage of high-level analysis is however poorly understood. To address this question we used magnetoencephalography and anatomically-constrained distributed source modeling to monitor brain activity with millisecond-resolution while subjects performed an orientation task on the upright and upside-down presented images of three different stimulus categories: faces, houses and bodies. Significant inversion effects were found for all three stimulus categories between 70–100-ms after picture onset with a highly category-specific cortical distribution. Differential responses between upright and inverted faces were found in well-established face-selective areas of the inferior occipital cortex and right fusiform gyrus. In addition, early category-specific inversion effects were found well beyond visual areas. Our results provide the first direct evidence that category-specific processing in high-level category-sensitive cortical areas already takes place within the first 100-ms of visual processing, significantly earlier than previously thought, and suggests the existence of fast category-specific neocortical routes in the human brain. PMID:18946504

  16. Extracting Kinematic Parameters for Monkey Bipedal Walking from Cortical Neuronal Ensemble Activity

    PubMed Central

    Fitzsimmons, Nathan A.; Lebedev, Mikhail A.; Peikon, Ian D.; Nicolelis, Miguel A. L.

    2009-01-01

    The ability to walk may be critically impacted as the result of neurological injury or disease. While recent advances in brain–machine interfaces (BMIs) have demonstrated the feasibility of upper-limb neuroprostheses, BMIs have not been evaluated as a means to restore walking. Here, we demonstrate that chronic recordings from ensembles of cortical neurons can be used to predict the kinematics of bipedal walking in rhesus macaques – both offline and in real time. Linear decoders extracted 3D coordinates of leg joints and leg muscle electromyograms from the activity of hundreds of cortical neurons. As more complex patterns of walking were produced by varying the gait speed and direction, larger neuronal populations were needed to accurately extract walking patterns. Extraction was further improved using a switching decoder which designated a submodel for each walking paradigm. We propose that BMIs may one day allow severely paralyzed patients to walk again. PMID:19404411

  17. A novel inhibitory nucleo-cortical circuit controls cerebellar Golgi cell activity

    PubMed Central

    Ankri, Lea; Husson, Zoé; Pietrajtis, Katarzyna; Proville, Rémi; Léna, Clément; Yarom, Yosef; Dieudonné, Stéphane; Uusisaari, Marylka Yoe

    2015-01-01

    The cerebellum, a crucial center for motor coordination, is composed of a cortex and several nuclei. The main mode of interaction between these two parts is considered to be formed by the inhibitory control of the nuclei by cortical Purkinje neurons. We now amend this view by showing that inhibitory GABA-glycinergic neurons of the cerebellar nuclei (CN) project profusely into the cerebellar cortex, where they make synaptic contacts on a GABAergic subpopulation of cerebellar Golgi cells. These spontaneously firing Golgi cells are inhibited by optogenetic activation of the inhibitory nucleo-cortical fibers both in vitro and in vivo. Our data suggest that the CN may contribute to the functional recruitment of the cerebellar cortex by decreasing Golgi cell inhibition onto granule cells. DOI: http://dx.doi.org/10.7554/eLife.06262.001 PMID:25965178

  18. Status of Japanese Experiment Module (JEM) activities

    NASA Technical Reports Server (NTRS)

    1991-01-01

    The current status of the JEM activities are presented in graphic form. The JEM spacecraft configuration is presented. The JEM configuration consist of the Pressurized Module, the Exposed Facility, the Experiment Logistics Module which consist of a pressurized section and an exposed section; and the Remote Manipulator System. The master schedule of the space station is given. Also the development tests of the structure and mechanism, the electrical power system, the data management system, the thermal control system, the environment control system, the experiment support system, and the remote manipulator system are listed.

  19. Physiologically motivated multiplex Kuramoto model describes phase diagram of cortical activity.

    PubMed

    Sadilek, Maximilian; Thurner, Stefan

    2015-05-21

    We derive a two-layer multiplex Kuramoto model from Wilson-Cowan type physiological equations that describe neural activity on a network of interconnected cortical regions. This is mathematically possible due to the existence of a unique, stable limit cycle, weak coupling, and inhibitory synaptic time delays. We study the phase diagram of this model numerically as a function of the inter-regional connection strength that is related to cerebral blood flow, and a phase shift parameter that is associated with synaptic GABA concentrations. We find three macroscopic phases of cortical activity: background activity (unsynchronized oscillations), epileptiform activity (highly synchronized oscillations) and resting-state activity (synchronized clusters/chaotic behaviour). Previous network models could hitherto not explain the existence of all three phases. We further observe a shift of the average oscillation frequency towards lower values together with the appearance of coherent slow oscillations at the transition from resting-state to epileptiform activity. This observation is fully in line with experimental data and could explain the influence of GABAergic drugs both on gamma oscillations and epileptic states. Compared to previous models for gamma oscillations and resting-state activity, the multiplex Kuramoto model not only provides a unifying framework, but also has a direct connection to measurable physiological parameters.

  20. Biophysical modeling of tonic cortical electrical activity in attention deficit hyperactivity disorder.

    PubMed

    Rowe, D L; Robinson, P A; Lazzaro, I L; Powles, R C; Gordon, E; Williams, L M

    2005-09-01

    Psychophysiological theories characterize Attention Deficit Hyperactivity Disorder (ADHD) in terms of cortical hypoarousal and a lack of inhibition of irrelevant sensory input, drawing on evidence of abnormal electroencephalographic (EEG) delta-theta activity. To investigate the mechanisms underlying this disorder a biophysical model of the cortex was used to fit and replicate the EEGs from 54 ADHD adolescents and their control subjects. The EEG abnormalities in ADHD were accounted for by the model's neurophysiological parameters as follows: (i) dendritic response times were increased, (ii) intrathalamic activity involving the thalamic reticular nucleus (TRN) was increased, consistent with enhanced delta-theta activity, and (iii) intracortical activity was increased, consistent with slow wave (<1 Hz) abnormalities. The longer dendritic response time is consistent with the increase in the activity of inhibitory cells types, particularly in the TRN, and therefore reduced arousal. The increase in intracortical activity may also reflect an increase in background activity or cortical noise within neocortical circuits. In terms of neurochemistry, these findings may be accounted for by disturbances in the cholinergic and/or noradrenergic systems. To the knowledge of the authors, this is the first study to use a detailed biophysical model of the brain to elucidate the neurophysiological mechanisms underlying tonic abnormalities in ADHD.

  1. Altered Cortical Activation in Adolescents With Acute Migraine: A Magnetoencephalography Study

    PubMed Central

    Xiang, Jing; deGrauw, Xinyao; Korostenskaja, Milena; Korman, Abraham M.; O’Brien, Hope L.; Kabbouche, Marielle A.; Powers, Scott W.; Hershey, Andrew D.

    2013-01-01

    To quantitatively assess cortical dysfunction in pediatric migraine, 31 adolescents with acute migraine and age- and gender-matched controls were studied using a magnetoencephalography (MEG) system at a sampling rate of 6,000 Hz. Neuromagnetic brain activation was elicited by a finger-tapping task. The spectral and spatial signatures of magnetoencephalography data in 5 to 2,884 Hz were analyzed using Morlet wavelet and beamformers. Compared with controls, 31 migraine subjects during their headache attack phases (ictal) showed significantly prolonged latencies of neuromagnetic activation in 5 to 30 Hz, increased spectral power in 100 to 200 Hz, and a higher likelihood of neuromagnetic activation in the supplementary motor area, the occipital and ipsilateral sensorimotor cortices, in 2,200 to 2,800 Hz. Of the 31 migraine subjects, 16 migraine subjects during their headache-free phases (interictal) showed that there were no significant differences between interictal and control MEG data except that interictal spectral power in 100 to 200 Hz was significantly decreased. The results demonstrated that migraine subjects had significantly aberrant ictal brain activation, which can normalize interictally. The spread of abnormal ictal brain activation in both low- and high-frequency ranges triggered by movements may play a key role in the cascade of migraine attacks. Perspective This is the first study focusing on the spectral and spatial signatures of cortical dysfunction in adolescents with migraine using MEG signals in a frequency range of 5 to 2,884 Hz. This analyzing aberrant brain activation may be important for developing new therapeutic interventions for migraine in the future. PMID:23792072

  2. Modulation of early cortical processing during divided attention to non-contiguous locations.

    PubMed

    Frey, Hans-Peter; Schmid, Anita M; Murphy, Jeremy W; Molholm, Sophie; Lalor, Edmund C; Foxe, John J

    2014-05-01

    We often face the challenge of simultaneously attending to multiple non-contiguous regions of space. There is ongoing debate as to how spatial attention is divided under these situations. Whereas, for several years, the predominant view was that humans could divide the attentional spotlight, several recent studies argue in favor of a unitary spotlight that rhythmically samples relevant locations. Here, this issue was addressed by the use of high-density electrophysiology in concert with the multifocal m-sequence technique to examine visual evoked responses to multiple simultaneous streams of stimulation. Concurrently, we assayed the topographic distribution of alpha-band oscillatory mechanisms, a measure of attentional suppression. Participants performed a difficult detection task that required simultaneous attention to two stimuli in contiguous (undivided) or non-contiguous parts of space. In the undivided condition, the classic pattern of attentional modulation was observed, with increased amplitude of the early visual evoked response and increased alpha amplitude ipsilateral to the attended hemifield. For the divided condition, early visual responses to attended stimuli were also enhanced, and the observed multifocal topographic distribution of alpha suppression was in line with the divided attention hypothesis. These results support the existence of divided attentional spotlights, providing evidence that the corresponding modulation occurs during initial sensory processing time-frames in hierarchically early visual regions, and that suppressive mechanisms of visual attention selectively target distracter locations during divided spatial attention.

  3. High gamma power in ECoG reflects cortical electrical stimulation effects on unit activity in layers V/VI

    NASA Astrophysics Data System (ADS)

    Yazdan-Shahmorad, Azadeh; Kipke, Daryl R.; Lehmkuhle, Mark J.

    2013-12-01

    Objective. Cortical electrical stimulation (CES) has been used extensively in experimental neuroscience to modulate neuronal or behavioral activity, which has led this technique to be considered in neurorehabilitation. Because the cortex and the surrounding anatomy have irregular geometries as well as inhomogeneous and anisotropic electrical properties, the mechanism by which CES has therapeutic effects is poorly understood. Therapeutic effects of CES can be improved by optimizing the stimulation parameters based on the effects of various stimulation parameters on target brain regions. Approach. In this study we have compared the effects of CES pulse polarity, frequency, and amplitude on unit activity recorded from rat primary motor cortex with the effects on the corresponding local field potentials (LFP), and electrocorticograms (ECoG). CES was applied at the surface of the cortex and the unit activity and LFPs were recorded using a penetrating electrode array, which was implanted below the stimulation site. ECoGs were recorded from the vicinity of the stimulation site. Main results. Time-frequency analysis of LFPs following CES showed correlation of gamma frequencies with unit activity response in all layers. More importantly, high gamma power of ECoG signals only correlated with the unit activity in lower layers (V-VI) following CES. Time-frequency correlations, which were found between LFPs, ECoGs and unit activity, were frequency- and amplitude-dependent. Significance. The signature of the neural activity observed in LFP and ECoG signals provides a better understanding of the effects of stimulation on network activity, representative of large numbers of neurons responding to stimulation. These results demonstrate that the neurorehabilitation and neuroprosthetic applications of CES targeting layered cortex can be further improved by using field potential recordings as surrogates to unit activity aimed at optimizing stimulation efficacy. Likewise, the signatures

  4. Complementary Role of Frontoparietal Activity and Cortical Pattern Similarity in Successful Episodic Memory Encoding

    PubMed Central

    Xue, Gui; Dong, Qi; Chen, Chuansheng; Lu, Zhong-Lin; Mumford, Jeanette A.; Poldrack, Russell A.

    2013-01-01

    One central goal in cognitive neuroscience of learning and memory is to characterize the neural processes that lead to long-lasting episodic memory. In addition to the stronger frontoparietal activity, greater category- or item-specific cortical representation during encoding, as measured by pattern similarity (PS), is also associated with better subsequent episodic memory. Nevertheless, it is unknown whether frontoparietal activity and cortical PS reflect distinct mechanisms. To address this issue, we reanalyzed previous data (Xue G, Dong Q, Chen C, Lu ZL, Mumford JA, Poldrack RA. 2010. Greater neural pattern similarity across repetitions is associated with better memory. Science. 330:97, Experiment 3) using a novel approach based on combined activation-based and information-based analyses. The results showed that across items, stronger frontoparietal activity was associated with greater PS in distributed brain regions, including those where the PS was predictive of better subsequent memory. Nevertheless, the item-specific PS was still associated with later episodic memory after controlling the effect of frontoparietal activity. Our results suggest that one possible mechanism of frontoparietal activity on episodic memory encoding is via enhancing PS, resulting in more unique and consistent input to the medial temporal lobe. In addition, they suggest that PS might index additional processes, such as pattern reinstatement as a result of study-phase retrieval, that contribute to episodic memory encoding. PMID:22645250

  5. Impact of calcium-activated potassium channels on NMDA spikes in cortical layer 5 pyramidal neurons

    PubMed Central

    Bock, Tobias

    2016-01-01

    Active electrical events play an important role in shaping signal processing in dendrites. As these events are usually associated with an increase in intracellular calcium, they are likely to be under the control of calcium-activated potassium channels. Here, we investigate the impact of calcium-activated potassium channels on N-methyl-d-aspartate (NMDA) receptor-dependent spikes, or NMDA spikes, evoked by glutamate iontophoresis onto basal dendrites of cortical layer 5 pyramidal neurons. We found that small-conductance calcium-activated potassium channels (SK channels) act to reduce NMDA spike amplitude but at the same time, also decrease the iontophoretic current required for their generation. This SK-mediated decrease in NMDA spike threshold was dependent on R-type voltage-gated calcium channels and indicates a counterintuitive, excitatory effect of SK channels on NMDA spike generation, whereas the capacity of SK channels to suppress NMDA spike amplitude is in line with the expected inhibitory action of potassium channels on dendritic excitability. Large-conductance calcium-activated potassium channels had no significant impact on NMDA spikes, indicating that these channels are either absent from basal dendrites or not activated by NMDA spikes. These experiments reveal complex and opposing interactions among NMDA receptors, SK channels, and voltage-gated calcium channels in basal dendrites of cortical layer 5 pyramidal neurons during NMDA spike generation, which are likely to play an important role in regulating the way these neurons integrate the thousands of synaptic inputs they receive. PMID:26936985

  6. Prior probabilities modulate cortical surprise responses: A study of event-related potentials.

    PubMed

    Seer, Caroline; Lange, Florian; Boos, Moritz; Dengler, Reinhard; Kopp, Bruno

    2016-07-01

    The human brain predicts events in its environment based on expectations, and unexpected events are surprising. When probabilistic contingencies in the environment are precisely instructed, the individual can form expectations based on quantitative probabilistic information ('inference-based learning'). In contrast, when probabilistic contingencies are imprecisely instructed, expectations are formed based on the individual's cumulative experience ('experience-based learning'). Here, we used the urn-ball paradigm to investigate how variations in prior probabilities and in the precision of information about these priors modulate choice behavior and event-related potential (ERP) correlates of surprise. In the urn-ball paradigm, participants are repeatedly forced to infer hidden states responsible for generating observable events, given small samples of factual observations. We manipulated prior probabilities of the states, and we rendered the priors calculable or incalculable, respectively. The analysis of choice behavior revealed that the tendency to consider prior probabilities when making decisions about hidden states was stronger when prior probabilities were calculable, at least in some of our participants. Surprise-related P3b amplitudes were observed in both the calculable and the incalculable prior probability condition. In contrast, calculability of prior probabilities modulated anteriorly distributed ERP amplitudes: when prior probabilities were calculable, surprising events elicited enhanced P3a amplitudes. However, when prior probabilities were incalculable, surprise was associated with enhanced N2 amplitudes. Furthermore, interindividual variability in reliance on prior probabilities was associated with attenuated P3b surprise responses under calculable in comparison to incalculable prior probabilities. Our results suggest two distinct neural systems for probabilistic learning that are recruited depending on contextual cues such as the precision of

  7. Changes in Cortical Activity During Real and Imagined Movements: an ERP Study

    PubMed Central

    Machado, Sergio; Arias-Carrión, Oscar; Paes, Flávia; Ribeiro, Pedro; Cagy, Mauricio; Piedade, Roberto; Almada, Leonardo Ferreira; Anghinah, Renato; Basile, Luis; Moro, Maria Francesca; Orsini, Marco; Silva, Julio Guilherme; Silva, Adriana Cardoso; Nardi, Antonio E.

    2013-01-01

    This study aims to compare the topographic distribution of cortical activation between real and imagined movement through event-related potential (ERP). We are specifically interested in identifying, the topographic distribution of activated areas, the intensity of activated areas, and the temporal occurrence of these activations on preparation and motor response phases. Twelve healthy and right handed subjects were instructed to perform a task under real and imagery conditions. The task was performed simultaneously to electroencephalographic (EEG) recording. When compared the conditions, we found a statistically significant difference in favor of real condition revealed by performing an unpaired t-test with multiple corrections of Bonferroni, demonstrating negative activity on electrode C3 and positive activity on the electrode C4 only in motor response phase. These findings revealed similar functional connections established during real and imagery conditions, suggesting that there are common neural substrate and similar properties of functional integration shared by conditions. PMID:24358049

  8. Changes in Cortical Activity During Real and Imagined Movements: an ERP Study.

    PubMed

    Machado, Sergio; Arias-Carrión, Oscar; Paes, Flávia; Ribeiro, Pedro; Cagy, Mauricio; Piedade, Roberto; Almada, Leonardo Ferreira; Anghinah, Renato; Basile, Luis; Moro, Maria Francesca; Orsini, Marco; Silva, Julio Guilherme; Silva, Adriana Cardoso; Nardi, Antonio E

    2013-11-15

    This study aims to compare the topographic distribution of cortical activation between real and imagined movement through event-related potential (ERP). We are specifically interested in identifying, the topographic distribution of activated areas, the intensity of activated areas, and the temporal occurrence of these activations on preparation and motor response phases. Twelve healthy and right handed subjects were instructed to perform a task under real and imagery conditions. The task was performed simultaneously to electroencephalographic (EEG) recording. When compared the conditions, we found a statistically significant difference in favor of real condition revealed by performing an unpaired t-test with multiple corrections of Bonferroni, demonstrating negative activity on electrode C3 and positive activity on the electrode C4 only in motor response phase. These findings revealed similar functional connections established during real and imagery conditions, suggesting that there are common neural substrate and similar properties of functional integration shared by conditions.

  9. Venlafaxine treatment after endothelin-1-induced cortical stroke modulates growth factor expression and reduces tissue damage in rats.

    PubMed

    Zepeda, Rodrigo; Contreras, Valentina; Pissani, Claudia; Stack, Katherine; Vargas, Macarena; Owen, Gareth I; Lazo, Oscar M; Bronfman, Francisca C

    2016-08-01

    Neuromodulators, such as antidepressants, may contribute to neuroprotection by modulating growth factor expression to exert anti-inflammatory effects and to support neuronal plasticity after stroke. Our objective was to study whether early treatment with venlafaxine, a serotonin-norepinephrine reuptake inhibitor, modulates growth factor expression and positively contributes to reducing the volume of infarcted brain tissue resulting in increased functional recovery. We studied the expression of BDNF, FGF2 and TGF-β1 by examining their mRNA and protein levels and cellular distribution using quantitative confocal microscopy at 5 days after venlafaxine treatment in control and infarcted brains. Venlafaxine treatment did not change the expression of these growth factors in sham rats. In infarcted rats, BDNF mRNA and protein levels were reduced, while the mRNA and protein levels of FGF2 and TGF-β1 were increased. Venlafaxine treatment potentiated all of the changes that were induced by cortical stroke alone. In particular, increased levels of FGF2 and TGF-β1 were observed in astrocytes at 5 days after stroke induction, and these increases were correlated with decreased astrogliosis (measured by GFAP) and increased synaptophysin immunostaining at twenty-one days after stroke in venlafaxine-treated rats. Finally, we show that venlafaxine reduced infarct volume after stroke resulting in increased functional recovery, which was measured using ladder rung motor tests, at 21 days after stroke. Our results indicate that the early oral administration of venlafaxine positively contributes to neuroprotection during the acute and late events that follow stroke.

  10. Correlated activity of cortical neurons survives extensive removal of feedforward sensory input

    PubMed Central

    Shapcott, Katharine A.; Schmiedt, Joscha T.; Saunders, Richard C.; Maier, Alexander; Leopold, David A.; Schmid, Michael C.

    2016-01-01

    A fundamental property of brain function is that the spiking activity of cortical neurons is variable and that some of this variability is correlated between neurons. Correlated activity not due to the stimulus arises from shared input but the neuronal circuit mechanisms that result in these noise correlations are not fully understood. Here we tested in the visual system if correlated variability in mid-level area V4 of visual cortex is altered following extensive lesions of primary visual cortex (V1). To this end we recorded longitudinally the neuronal correlations in area V4 of two behaving macaque monkeys before and after a V1 lesion while the monkeys fixated a grey screen. We found that the correlations of neuronal activity survived the lesions in both monkeys. In one monkey, the correlation of multi-unit spiking signals was strongly increased in the first week post-lesion, while in the second monkey, correlated activity was slightly increased, but not greater than some week-by-week fluctuations observed. The typical drop-off of inter-neuronal correlations with cortical distance was preserved after the lesion. Therefore, as V4 noise correlations remain without feedforward input from V1, these results suggest instead that local and/or feedback input seem to be necessary for correlated activity. PMID:27721468

  11. fNIRS: An Emergent Method to Document Functional Cortical Activity during Infant Movements

    PubMed Central

    Nishiyori, Ryota

    2016-01-01

    The neural basis underlying the emergence of goal-directed actions in infants has been severely understudied, with minimal empirical evidence for hypotheses proposed. This was largely due to the technological constraints of traditional neuroimaging techniques. Recently, functional near-infrared spectroscopy (fNIRS) technology has emerged as a tool developmental scientists are finding useful to examine cortical activity, particularly in young children and infants due to its greater tolerance to movements than other neuroimaging techniques. fNIRS provides an opportunity to finally begin to examine the neural underpinnings as infants develop goal-directed actions. In this methodological paper, I will outline the utility, challenges, and outcomes of using fNIRS to measure the changes in cortical activity as infants reach for an object. I will describe the advantages and limitations of the technology, the setup I used to study primary motor cortex activity during infant reaching, and example steps in the analyses processes. I will present exemplar data to illustrate the feasibility of this technique to quantify changes in hemodynamic activity as infants move. The viability of this research method opens the door to expanding studies of the development of neural activity related to goal-directed actions in infants. I encourage others to share details of techniques used, as well, including analyticals, to help this neuroimaging technology grow as others, such as EEG and fMRI have. PMID:27148141

  12. Effects of Skilled Training on Sleep Slow Wave Activity and Cortical Gene Expression in the Rat

    PubMed Central

    Hanlon, Erin C.; Faraguna, Ugo; Vyazovskiy, Vladyslav V.; Tononi, Giulio; Cirelli, Chiara

    2009-01-01

    Study Objective: The best characterized marker of sleep homeostasis is the amount of slow wave activity (SWA, 0.5–4 Hz) during NREM sleep. SWA increases as a function of previous waking time and declines during sleep, but the underlying mechanisms remain unclear. We have suggested that SWA homeostasis is linked to synaptic potentiation associated with learning during wakefulness. Indeed, studies in rodents and humans found that SWA increases after manipulations that presumably enhance synaptic strength, but the evidence remains indirect. Here we trained rats in skilled reaching, a task known to elicit long-term potentiation in the trained motor cortex, and immediately after learning measured SWA and cortical protein levels of c-fos and Arc, 2 activity-dependent genes involved in motor learning. Design: Intracortical local field potential recordings and training on reaching task. Setting: Basic sleep research laboratory. Patients or Participants: Long Evans adult male rats. Interventions: N/A Measurements and Results: SWA increased post-training in the trained cortex (the frontal cortex contralateral to the limb used to learn the task), with smaller or no increase in other cortical areas. This increase was reversible within 1 hour, specific to NREM sleep, and positively correlated with changes in performance during the prior training session, suggesting that it reflects plasticity and not just motor activity. Fos and Arc levels were higher in the trained relative to untrained motor cortex immediately after training, but this asymmetry was no longer present after 1 hour of sleep. Conclusion: Learning to reach specifically affects gene expression in the trained motor cortex and, in the same area, increases sleep need as measured by a local change in SWA. Citation: Hanlon EC; Faraguna U; Vyazovskiy VV; Tononi G; Cirelli C. Effects of skilled training on sleep slow wave activity and cortical gene expression in the rat. SLEEP 2009;32(6):719-729. PMID:19544747

  13. Neonatal taurine and alanine modulate anxiety-like behavior and decelerate cortical spreading depression in rats previously suckled under different litter sizes.

    PubMed

    Francisco, Elian da Silva; Guedes, Rubem Carlos Araújo

    2015-11-01

    The amino acids taurine and alanine play a role in several physiological processes, including behavior and the electrical activity of the brain. In this study, we investigated the effect of treatment with taurine or alanine on anxiety-like behavior and the excitability-dependent phenomenon known as cortical spreading depression (CSD), using rats suckled in litters with 9 and 15 pups (groups L9 and L15). From postnatal days 7 to 27, the animals received per gavage 300 mg/kg/day of taurine or alanine or both. At 28 days, we tested the animals in the elevated plus maze, and at 33-35 days, we recorded CSD and analyzed its velocity of propagation, amplitude, and duration. Compared with water-treated controls, the L9 groups treated with taurine or alanine displayed anxiolytic behavior (higher number of entries in the open arms; p < 0.05), and reduced CSD velocity (p < 0.001). The effect of both amino acids on CSD was also found in the L15 groups and in five additional L9 groups (naïve, water, taurine, alanine, or both) treated at adulthood (90-110 days). The L15 condition resulted in smaller durations and higher CSD velocities compared with the L9 condition. Besides reinforcing previous evidence of behavioral modulation by taurine and alanine, our data are the first confirmation that treatment with these amino acids decelerates CSD regardless of lactation conditions (normal versus unfavorable lactation) or age at amino acid administration (young versus adult). The results suggest a modulating role for both amino acids on anxiety behavior and neuronal electrical activity.

  14. Stimulus expectancy modulates inferior frontal gyrus and premotor cortex activity in auditory perception.

    PubMed

    Osnes, Berge; Hugdahl, Kenneth; Hjelmervik, Helene; Specht, Karsten

    2012-04-01

    In studies on auditory speech perception, participants are often asked to perform active tasks, e.g. decide whether the perceived sound is a speech sound or not. However, information about the stimulus, inherent in such tasks, may induce expectations that cause altered activations not only in the auditory cortex, but also in frontal areas such as inferior frontal gyrus (IFG) and motor cortices, even in the absence of an explicit task. To investigate this, we applied spectral mixes of a flute sound and either vowels or specific music instrument sounds (e.g. trumpet) in an fMRI study, in combination with three different instructions. The instructions either revealed no information about stimulus features, or explicit information about either the music instrument or the vowel features. The results demonstrated that, besides an involvement of posterior temporal areas, stimulus expectancy modulated in particular a network comprising IFG and premotor cortices during this passive listening task.

  15. Changes in Motor-Related Cortical Activity Following Deep Brain Stimulation for Parkinson’s Disease Detected by Functional Near Infrared Spectroscopy: A Pilot Study

    PubMed Central

    Morishita, Takashi; Higuchi, Masa-aki; Saita, Kazuya; Tsuboi, Yoshio; Abe, Hiroshi; Inoue, Tooru

    2016-01-01

    It remains unclear how deep brain stimulation (DBS) modulates the global neuronal network involving cortical activity. We aimed to evaluate changes in cortical activity in six (two men; four women) patients with Parkinson’s disease (PD) who underwent unilateral globus pallidus interna (GPI) DBS surgery using a multi-channel near infrared spectroscopy (NIRS) system. As five of the patients were right-handed, DBS was performed on the left in these five cases. The mean age was 66.8 ± 4.0 years. The unified Parkinson’s disease rating scale (UPDRS) motor scores were evaluated at baseline and 1- and 6-month follow-up. Task-related NIRS experiments applying the block design were performed at baseline and 1-month follow-up. The mean of the total UPDRS motor score was 48.5 ± 11.1 in the off-medication state preoperatively. Postoperatively, total UPDRS motor scores improved to 26.8 ± 16.6 (p < 0.05) and 22.2 ± 8.6 (p < 0.05) at 1- and 6-month follow-up, respectively. A task-related NIRS experiment showed a postoperative increase in the cortical activity of the prefrontal cortex comparable to the preoperative state. To our knowledge, this is the first study to use a multi-channel NIRS system for PD patients treated with DBS. In this pilot study, we showed changes in motor-associated cortical activities following DBS surgery. Therapeutic DBS was concluded to have promoted the underlying neuronal network remodeling. PMID:28018196

  16. Mice lacking p35, a neuronal specific activator of Cdk5, display cortical lamination defects, seizures, and adult lethality.

    PubMed

    Chae, T; Kwon, Y T; Bronson, R; Dikkes, P; Li, E; Tsai, L H

    1997-01-01

    The adult mammalian cortex is characterized by a distinct laminar structure generated through a well-defined pattern of neuronal migration. Successively generated neurons are layered in an "inside-out" manner to produce six cortical laminae. We demonstrate here that p35, the neuronal-specific activator of cyclin-dependent kinase 5, plays a key role in proper neuronal migration. Mice lacking p35, and thus p35/cdk5 kinase activity, display severe cortical lamination defects and suffer from sporadic adult lethality and seizures. Histological examination reveals that the mutant mice lack the characteristic laminated structure of the cortex. Neuronal birth-dating experiments indicate a reversed packing order of cortical neurons such that earlier born neurons reside in superficial layers and later generated neurons occupy deep layers. The phenotype of p35 mutant mice thus demonstrates that the formation of cortical laminar structure depends on the action of the p35/cdk5 kinase.

  17. Cortical activation during visual illusory walking in persons with spinal cord injury: A pilot study

    PubMed Central

    Eick, John; Richardson, Elizabeth J.

    2014-01-01

    Objective To determine the location of cortical activation during a visual illusion walking paradigm, a recently proposed treatment for spinal cord injury (SCI)-related neuropathic pain, in persons with SCI compared to able-bodied controls. Design Pilot experimental fMRI trial. Setting Outpatient rehabilitation clinic. Participants Three persons with paraplegia and five able bodied participants were included in this study. Interventions Not applicable. Main Outcome Measures Cortical activation as measured by blood oxygenation-level dependent (BOLD) method of fMRI. Results During visually illusory walking, there was significant activation in the somatosensory cortex among those with SCI. In contrast, able-bodied participants showed little to no significant activation in this area, but rather, in the frontal and pre-motor areas. Conclusions Treatment modalities for SCI-related neuropathic pain that are based on sensory input paradigms such as virtual or visual illusory walking may work by targeting somatosensory cortex, an area that has been previously found to functionally reorganize following SCI. PMID:25461820

  18. Clinacanthus nutans Extracts Modulate Epigenetic Link to Cytosolic Phospholipase A2 Expression in SH-SY5Y Cells and Primary Cortical Neurons.

    PubMed

    Tan, Charlene Siew-Hon; Ho, Christabel Fung-Yih; Heng, Swan-Ser; Wu, Jui-Sheng; Tan, Benny Kwong-Huat; Ng, Yee-Kong; Sun, Grace Y; Lin, Teng-Nan; Ong, Wei-Yi

    2016-09-01

    Clinacanthus nutans Lindau (C. nutans), commonly known as Sabah Snake Grass in southeast Asia, is widely used in folk medicine due to its analgesic, antiviral, and anti-inflammatory properties. Our recent study provided evidence for the regulation of cytosolic phospholipase A2 (cPLA2) mRNA expression by epigenetic factors (Tan et al. in Mol Neurobiol. doi: 10.1007/s12035-015-9314-z , 2015). This enzyme catalyzes the release of arachidonic acid from glycerophospholipids, and formation of pro-inflammatory eicosanoids or toxic lipid peroxidation products such as 4-hydroxynonenal. In this study, we examined the effects of C. nutans ethanol leaf extracts on epigenetic regulation of cPLA2 mRNA expression in SH-SY5Y human neuroblastoma cells and mouse primary cortical neurons. C. nutans modulated induction of cPLA2 expression in SH-SY5Y cells by histone deacetylase (HDAC) inhibitors, MS-275, MC-1568, and TSA. C. nutans extracts also inhibited histone acetylase (HAT) activity. Levels of cPLA2 mRNA expression were increased in primary cortical neurons subjected to 0.5-h oxygen-glucose deprivation injury (OGD). This increase was significantly inhibited by C. nutans treatment. Treatment of primary neurons with the HDAC inhibitor MS-275 augmented OGD-induced cPLA2 mRNA expression, and this increase was modulated by C. nutans extracts. OGD-stimulated increase in cPLA2 mRNA expression was also reduced by a Tip60 HAT inhibitor, NU9056. In view of a key role of cPLA2 in the production of pro-inflammatory eicosanoids and free radical damage, and the fact that epigenetic effects on genes are often long-lasting, results suggest a role for C. nutans and phytochemicals to inhibit the production of arachidonic acid-derived pro-inflammatory eicosanoids and chronic inflammation, through epigenetic regulation of cPLA2 expression.

  19. Pulse Wave Amplitude Drops during Sleep are Reliable Surrogate Markers of Changes in Cortical Activity

    PubMed Central

    Delessert, Alexandre; Espa, Fabrice; Rossetti, Andrea; Lavigne, Gilles; Tafti, Mehdi; Heinzer, Raphael

    2010-01-01

    Background: During sleep, sudden drops in pulse wave amplitude (PWA) measured by pulse oximetry are commonly associated with simultaneous arousals and are thought to result from autonomic vasoconstriction. In the present study, we determine whether PWA drops were associated with changes in cortical activity as determined by EEG spectral analysis. Methods: A 20% decrease in PWA was chosen as a minimum for a drop. A total of 1085 PWA drops from 10 consecutive sleep recordings were analyzed. EEG spectral analysis was performed over 5 consecutive epochs of 5 seconds: 2 before, 1 during, and 2 after the PWA drop. EEG spectral analysis was performed over delta, theta, alpha, sigma, and beta frequency bands. Within each frequency band, power density was compared across the five 5-sec epochs. Presence or absence of visually scored EEG arousals were adjudicated by an investigator blinded to the PWA signal and considered associated with PWA drop if concomitant. Results: A significant increase in EEG power density in all EEG frequency bands was found during PWA drops (P < 0.001) compared to before and after drop. Even in the absence of visually scored arousals, PWA drops were associated with a significant increase in EEG power density (P < 0.001) in most frequency bands. Conclusions: Drops in PWA are associated with a significant increase in EEG power density, suggesting that these events can be used as a surrogate for changes in cortical activity during sleep. This approach may prove of value in scoring respiratory events on limited-channel (type III) portable monitors. Citation: Delessert A; Espa F; Rossetti A; Lavigne G; Tafti M; Heinzer R. Pulse wave amplitude drops during sleep are reliable surrogate markers of changes in cortical activity. SLEEP 2010;33(12):1687-1692. PMID:21120131

  20. Potentiation of spontaneous and evoked cortical electrical activity after spreading depression: in vivo analysis in well-nourished and malnourished rats.

    PubMed

    de Souza, Thays Kallyne Marinho; e Silva, Mariana Barros; Gomes, André Ricardson; de Oliveira, Hélio Magalhães; Moraes, Renato Barros; de Freitas Barbosa, Catão Temístocles; Guedes, Rubem Carlos Araújo

    2011-10-01

    Cortical spreading depression (CSD) is influenced by brain excitability and is related to neurological diseases, such as epilepsy. In vitro evidence indicates that neuronal electrical activity is potentiated after CSD. Malnutrition can cause electrophysiological changes in the brain, both in animals and in humans. Here, we investigated in vivo whether CSD potentiates the amplitude of electrocorticogram (ECoG) and of transcallosal evoked responses in adult well-nourished (W), early-malnourished (M), and food-restricted rats. ECoG amplitudes were compared before and after CSD, at two parietal regions (designated the anterior and posterior regions). In the anterior region, post-CSD amplitudes of the ECoG waves were 13-23% higher (P < 0.05) than the pre-CSD values in all groups. In the posterior region, amplitudes increased 22% in the M group only (P < 0.05). In a fourth CSD-free group, ECoG amplitude did not change during the four recording hours. Transcallosal electrically evoked cortical responses also increased 21.5 ± 9.6% and 41.8 ± 28.5%, after CSD, in the W and M conditions, respectively, as compared to pre-CSD values. The data support the hypothesis of an in vivo CSD potentiation on cortical excitability as recorded by spontaneous and evoked electrical activity and modulation by nutritional status.

  1. Cognitively Engaging Activity Is Associated with Greater Cortical and Subcortical Volumes

    PubMed Central

    Seider, Talia R.; Fieo, Robert A.; O’Shea, Andrew; Porges, Eric C.; Woods, Adam J.; Cohen, Ronald A.

    2016-01-01

    As the population ages and dementia becomes a growing healthcare concern, it is increasingly important to identify targets for intervention to delay or attenuate cognitive decline. Research has shown that the most successful interventions aim at altering lifestyle factors. Thus, this study examined how involvement in physical, cognitive, and social activity is related to brain structure in older adults. Sixty-five adults (mean age = 71.4 years, standard deviation = 8.9) received the Community Healthy Activities Model Program for Seniors (CHAMPS), a questionnaire that polls everyday activities in which older adults may be involved, and also underwent structural magnetic resonance imaging. Stepwise regression with backward selection was used to predict weekly time spent in either social, cognitive, light physical, or heavy physical activity from the volume of one of the cortical or subcortical regions of interest (corrected by intracranial volume) as well as age, education, and gender as control variables. Regressions revealed that more time spent in cognitive activity was associated with greater volumes of all brain regions studied: total cortex (β = 0.289, p = 0.014), frontal (β = 0.276, p = 0.019), parietal (β = 0.305, p = 0.009), temporal (β = 0.275, p = 0.020), and occipital (β = 0.256, p = 0.030) lobes, and thalamus (β = 0.310, p = 0.010), caudate (β = 0.233, p = 0.049), hippocampus (β = 0.286, p = 0.017), and amygdala (β = 0.336, p = 0.004). These effects remained even after accounting for the positive association between cognitive activity and education. No other activity variable was associated with brain volumes. Results indicate that time spent in cognitively engaging activity is associated with greater cortical and subcortical brain volume. Findings suggest that interventions aimed at increasing levels of cognitive activity may delay cognitive consequences of aging and decrease the risk of developing dementia. PMID:27199740

  2. Auditory Cortex Basal Activity Modulates Cochlear Responses in Chinchillas

    PubMed Central

    León, Alex; Elgueda, Diego; Silva, María A.; Hamamé, Carlos M.; Delano, Paul H.

    2012-01-01

    Background The auditory efferent system has unique neuroanatomical pathways that connect the cerebral cortex with sensory receptor cells. Pyramidal neurons located in layers V and VI of the primary auditory cortex constitute descending projections to the thalamus, inferior colliculus, and even directly to the superior olivary complex and to the cochlear nucleus. Efferent pathways are connected to the cochlear receptor by the olivocochlear system, which innervates outer hair cells and auditory nerve fibers. The functional role of the cortico-olivocochlear efferent system remains debated. We hypothesized that auditory cortex basal activity modulates cochlear and auditory-nerve afferent responses through the efferent system. Methodology/Principal Findings Cochlear microphonics (CM), auditory-nerve compound action potentials (CAP) and auditory cortex evoked potentials (ACEP) were recorded in twenty anesthetized chinchillas, before, during and after auditory cortex deactivation by two methods: lidocaine microinjections or cortical cooling with cryoloops. Auditory cortex deactivation induced a transient reduction in ACEP amplitudes in fifteen animals (deactivation experiments) and a permanent reduction in five chinchillas (lesion experiments). We found significant changes in the amplitude of CM in both types of experiments, being the most common effect a CM decrease found in fifteen animals. Concomitantly to CM amplitude changes, we found CAP increases in seven chinchillas and CAP reductions in thirteen animals. Although ACEP amplitudes were completely recovered after ninety minutes in deactivation experiments, only partial recovery was observed in the magnitudes of cochlear responses. Conclusions/Significance These results show that blocking ongoing auditory cortex activity modulates CM and CAP responses, demonstrating that cortico-olivocochlear circuits regulate auditory nerve and cochlear responses through a basal efferent tone. The diversity of the obtained effects

  3. Activity Changes Induced by Spatio-Temporally Correlated Stimuli in Cultured Cortical Networks

    NASA Astrophysics Data System (ADS)

    Takayama, Yuzo; Moriguchi, Hiroyuki; Jimbo, Yasuhiko

    Activity-dependent plasticity probably plays a key role in learning and memory in biological information processing systems. Though long-term potentiation and depression have been extensively studied in the filed of neuroscience, little is known on the mechanisms for integrating these modifications on network-wide activity changes. In this report, we studied effects of spatio-temporally correlated stimuli on the neuronal network activity. Rat cortical neurons were cultured on substrates with 64 embedded micro-electrodes and the evoked responses were extracellularly recorded and analyzed. We compared spatio-temporal patterns of the responses between before and after repetitive application of correlated stimuli. After the correlated stimuli, the networks showed significantly different responses from those in the initial states. The modified activity reflected structures of the repeatedly applied correlated stimuli. The results suggested that spatiotemporally correlated inputs systematically induced modification of synaptic strengths in neuronal networks, which could serve as an underlying mechanism of associative memory.

  4. Neural control of computer cursor velocity by decoding motor cortical spiking activity in humans with tetraplegia

    NASA Astrophysics Data System (ADS)

    Kim, Sung-Phil; Simeral, John D.; Hochberg, Leigh R.; Donoghue, John P.; Black, Michael J.

    2008-12-01

    Computer-mediated connections between human motor cortical neurons and assistive devices promise to improve or restore lost function in people with paralysis. Recently, a pilot clinical study of an intracortical neural interface system demonstrated that a tetraplegic human was able to obtain continuous two-dimensional control of a computer cursor using neural activity recorded from his motor cortex. This control, however, was not sufficiently accurate for reliable use in many common computer control tasks. Here, we studied several central design choices for such a system including the kinematic representation for cursor movement, the decoding method that translates neuronal ensemble spiking activity into a control signal and the cursor control task used during training for optimizing the parameters of the decoding method. In two tetraplegic participants, we found that controlling a cursor's velocity resulted in more accurate closed-loop control than controlling its position directly and that cursor velocity control was achieved more rapidly than position control. Control quality was further improved over conventional linear filters by using a probabilistic method, the Kalman filter, to decode human motor cortical activity. Performance assessment based on standard metrics used for the evaluation of a wide range of pointing devices demonstrated significantly improved cursor control with velocity rather than position decoding. Disclosure. JPD is the Chief Scientific Officer and a director of Cyberkinetics Neurotechnology Systems (CYKN); he holds stock and receives compensation. JDS has been a consultant for CYKN. LRH receives clinical trial support from CYKN.

  5. Progressive Brain Damage, Synaptic Reorganization and NMDA Activation in a Model of Epileptogenic Cortical Dysplasia

    PubMed Central

    Colciaghi, Francesca; Finardi, Adele; Nobili, Paola; Locatelli, Denise; Spigolon, Giada; Battaglia, Giorgio Stefano

    2014-01-01

    Whether severe epilepsy could be a progressive disorder remains as yet unresolved. We previously demonstrated in a rat model of acquired focal cortical dysplasia, the methylazoxymethanol/pilocarpine - MAM/pilocarpine - rats, that the occurrence of status epilepticus (SE) and subsequent seizures fostered a pathologic process capable of modifying the morphology of cortical pyramidal neurons and NMDA receptor expression/localization. We have here extended our analysis by evaluating neocortical and hippocampal changes in MAM/pilocarpine rats at different epilepsy stages, from few days after onset up to six months of chronic epilepsy. Our findings indicate that the process triggered by SE and subsequent seizures in the malformed brain i) is steadily progressive, deeply altering neocortical and hippocampal morphology, with atrophy of neocortex and CA regions and progressive increase of granule cell layer dispersion; ii) changes dramatically the fine morphology of neurons in neocortex and hippocampus, by increasing cell size and decreasing both dendrite arborization and spine density; iii) induces reorganization of glutamatergic and GABAergic networks in both neocortex and hippocampus, favoring excitatory vs inhibitory input; iv) activates NMDA regulatory subunits. Taken together, our data indicate that, at least in experimental models of brain malformations, severe seizure activity, i.e., SE plus recurrent seizures, may lead to a widespread, steadily progressive architectural, neuronal and synaptic reorganization in the brain. They also suggest the mechanistic relevance of glutamate/NMDA hyper-activation in the seizure-related brain pathologic plasticity. PMID:24587109

  6. The brain under self-control: modulation of inhibitory and monitoring cortical networks during hypnotic paralysis.

    PubMed

    Cojan, Yann; Waber, Lakshmi; Schwartz, Sophie; Rossier, Laurent; Forster, Alain; Vuilleumier, Patrik

    2009-06-25

    Brain mechanisms of hypnosis are poorly known. Cognitive accounts proposed that executive attentional systems may cause selective inhibition or disconnection of some mental operations. To assess motor and inhibitory brain circuits during hypnotic paralysis, we designed a go-no-go task while volunteers underwent functional magnetic resonance imaging (fMRI) in three conditions: normal state, hypnotic left-hand paralysis, and feigned paralysis. Preparatory activation arose in right motor cortex despite left hypnotic paralysis, indicating preserved motor intentions, but with concomitant increases in precuneus regions that normally mediate imagery and self-awareness. Precuneus also showed enhanced functional connectivity with right motor cortex. Right frontal areas subserving inhibition were activated by no-go trials in normal state and by feigned paralysis, but irrespective of motor blockade or execution during hypnosis. These results suggest that hypnosis may enhance self-monitoring processes to allow internal representations generated by the suggestion to guide behavior but does not act through direct motor inhibition.

  7. Influence of slow oscillation on hippocampal activity and ripples through cortico-hippocampal synaptic interactions, analyzed by a cortical-CA3-CA1 network model

    PubMed Central

    Taxidis, Jiannis; Mizuseki, Kenji; Mason, Robert; Owen, Markus R.

    2013-01-01

    Hippocampal sharp wave-ripple complexes (SWRs) involve the synchronous discharge of thousands of cells throughout the CA3-CA1-subiculum-entorhinal cortex axis. Their strong transient output affects cortical targets, rendering SWRs a possible means for memory transfer from the hippocampus to the neocortex for long-term storage. Neurophysiological observations of hippocampal activity modulation by the cortical slow oscillation (SO) during deep sleep and anesthesia, and correlations between ripples and UP states, support the role of SWRs in memory consolidation through a cortico-hippocampal feedback loop. We couple a cortical network exhibiting SO with a hippocampal CA3-CA1 computational network model exhibiting SWRs, in order to model such cortico-hippocampal correlations and uncover important parameters and coupling mechanisms controlling them. The cortical oscillatory output entrains the CA3 network via connections representing the mossy fiber input, and the CA1 network via the temporoammonic pathway (TA). The spiking activity in CA3 and CA1 is shown to depend on the excitation-to-inhibition ratio, induced by combining the two hippocampal inputs, with mossy fiber input controlling the UP-state correlation of CA3 population bursts and corresponding SWRs, whereas the temporoammonic input affects the overall CA1 spiking activity. Ripple characteristics and pyramidal spiking participation to SWRs are shaped by the strength of the Schaffer collateral drive. A set of in vivo recordings from the rat hippocampus confirms a model-predicted segregation of pyramidal cells into subgroups according to the SO state where they preferentially fire and their response to SWRs. These groups can potentially play distinct functional roles in the replay of spike sequences. PMID:23386827

  8. Nonlinear Coupling between Cortical Oscillations and Muscle Activity during Isotonic Wrist Flexion

    PubMed Central

    Yang, Yuan; Solis-Escalante, Teodoro; van de Ruit, Mark; van der Helm, Frans C. T.; Schouten, Alfred C.

    2016-01-01

    Coupling between cortical oscillations and muscle activity facilitates neuronal communication during motor control. The linear part of this coupling, known as corticomuscular coherence, has received substantial attention, even though neuronal communication underlying motor control has been demonstrated to be highly nonlinear. A full assessment of corticomuscular coupling, including the nonlinear part, is essential to understand the neuronal communication within the sensorimotor system. In this study, we applied the recently developed n:m coherence method to assess nonlinear corticomuscular coupling during isotonic wrist flexion. The n:m coherence is a generalized metric for quantifying nonlinear cross-frequency coupling as well as linear iso-frequency coupling. By using independent component analysis (ICA) and equivalent current dipole source localization, we identify four sensorimotor related brain areas based on the locations of the dipoles, i.e., the contralateral primary sensorimotor areas, supplementary motor area (SMA), prefrontal area (PFA) and posterior parietal cortex (PPC). For all these areas, linear coupling between electroencephalogram (EEG) and electromyogram (EMG) is present with peaks in the beta band (15–35 Hz), while nonlinear coupling is detected with both integer (1:2, 1:3, 1:4) and non-integer (2:3) harmonics. Significant differences between brain areas is shown in linear coupling with stronger coherence for the primary sensorimotor areas and motor association cortices (SMA, PFA) compared to the sensory association area (PPC); but not for the nonlinear coupling. Moreover, the detected nonlinear coupling is similar to previously reported nonlinear coupling of cortical activity to somatosensory stimuli. We suggest that the descending motor pathways mainly contribute to linear corticomuscular coupling, while nonlinear coupling likely originates from sensory feedback. PMID:27999537

  9. Nonlinear Coupling between Cortical Oscillations and Muscle Activity during Isotonic Wrist Flexion.

    PubMed

    Yang, Yuan; Solis-Escalante, Teodoro; van de Ruit, Mark; van der Helm, Frans C T; Schouten, Alfred C

    2016-01-01

    Coupling between cortical oscillations and muscle activity facilitates neuronal communication during motor control. The linear part of this coupling, known as corticomuscular coherence, has received substantial attention, even though neuronal communication underlying motor control has been demonstrated to be highly nonlinear. A full assessment of corticomuscular coupling, including the nonlinear part, is essential to understand the neuronal communication within the sensorimotor system. In this study, we applied the recently developed n:m coherence method to assess nonlinear corticomuscular coupling during isotonic wrist flexion. The n:m coherence is a generalized metric for quantifying nonlinear cross-frequency coupling as well as linear iso-frequency coupling. By using independent component analysis (ICA) and equivalent current dipole source localization, we identify four sensorimotor related brain areas based on the locations of the dipoles, i.e., the contralateral primary sensorimotor areas, supplementary motor area (SMA), prefrontal area (PFA) and posterior parietal cortex (PPC). For all these areas, linear coupling between electroencephalogram (EEG) and electromyogram (EMG) is present with peaks in the beta band (15-35 Hz), while nonlinear coupling is detected with both integer (1:2, 1:3, 1:4) and non-integer (2:3) harmonics. Significant differences between brain areas is shown in linear coupling with stronger coherence for the primary sensorimotor areas and motor association cortices (SMA, PFA) compared to the sensory association area (PPC); but not for the nonlinear coupling. Moreover, the detected nonlinear coupling is similar to previously reported nonlinear coupling of cortical activity to somatosensory stimuli. We suggest that the descending motor pathways mainly contribute to linear corticomuscular coupling, while nonlinear coupling likely originates from sensory feedback.

  10. Supine posture inhibits cortical activity: Evidence from Delta and Alpha EEG bands.

    PubMed

    Spironelli, Chiara; Busenello, Jessica; Angrilli, Alessandro

    2016-08-01

    Past studies have shown consistent evidence that body position significantly affects brain activity, revealing that both head-down and horizontal bed-rest are associated with cortical inhibition and altered perceptual and cognitive processing. The present study investigates the effects of body position on spontaneous, open-eyes, resting-state EEG cortical activity in 32 young women randomly assigned to one of two conditions, seated position (SP) or horizontal bed rest (BR). A between-group repeated-measure experimental design was used, EEG recordings were made from 38 scalp locations, and low-frequency (delta and alpha) amplitudes of the two groups were compared in four different conditions: when both groups (a) were seated (T0), (b) assumed two different body positions (seated vs. supine conditions, immediate [T1] and 120min later [T2]), and (c) were seated again (T3). Overall, the results showed no a priori between-group differences (T0) before experimental manipulation. As expected, delta amplitude, an index of cortical inhibition in awake resting participants, was significantly increased in group BR, revealing both rapid (T1) and mid-term (T2) inhibitory effects of supine or horizontal positions. Instead, the alpha band was highly sensitive to postural transitions, perhaps due to baroreceptor intervention and, unlike the delta band, underwent habituation and decreased after a 2-h bed rest. These results indicate clear-cut differences at rest between the seated and supine positions, thus supporting the view that the role of body position in the differences found between brain metabolic methods (fMRI and PET) in which participants lie horizontally, and EEG-MEG-TMS techniques with participants in a seated position, has been largely underestimated so far.

  11. Processing abstract language modulates motor system activity.

    PubMed

    Glenberg, Arthur M; Sato, Marc; Cattaneo, Luigi; Riggio, Lucia; Palumbo, Daniele; Buccino, Giovanni

    2008-06-01

    Embodiment theory proposes that neural systems for perception and action are also engaged during language comprehension. Previous neuroimaging and neurophysiological studies have only been able to demonstrate modulation of action systems during comprehension of concrete language. We provide neurophysiological evidence for modulation of motor system activity during the comprehension of both concrete and abstract language. In Experiment 1, when the described direction of object transfer or information transfer (e.g., away from the reader to another) matched the literal direction of a hand movement used to make a response, speed of responding was faster than when the two directions mismatched (an action-sentence compatibility effect). In Experiment 2, we used single-pulse transcranial magnetic stimulation to study changes in the corticospinal motor pathways to hand muscles while reading the same sentences. Relative to sentences that do not describe transfer, there is greater modulation of activity in the hand muscles when reading sentences describing transfer of both concrete objects and abstract information. These findings are discussed in relation to the human mirror neuron system.

  12. Acute effects of aerobic stretching, health and happiness improving movement exercise on cortical activity of children.

    PubMed

    Choi, Hyungsoo; Park, Sangjun; Kim, Kyekyoon Kevin; Lee, Kwanghee; Rhyu, Hyun-Seung

    2016-08-01

    Acute high-intensity physical exercise is known to improve cognitive performance of children, including those with attention-deficit/hyperactivity disorder (ADHD). In this work, we investigated the acute effect of an aerobic stretching and moderate-intensity, health and happiness improving movement (HHIM) exercise on the cortical activity of children with and without ADHD using electroencephalography (EEG). Children aged 12 to 14 yr with combined-type ADHD and age-matched healthy controls participated in the study, performing two individual movements (n=79, 35 controls) and a single exercise bout (n=45, 18 controls). electroencephalographic signals were recorded before and immediately after each movement, and before and after acute exercise under resting conditions, to obtain absolute and relative power estimates for the theta (3.5-8 Hz), alpha (8-12 Hz), sensory motor rhythm (12-16 Hz), and beta (16-25 Hz) bands. After acute HHIM exercise, all children showed significant changes in their relative EEG, mainly in the theta and alpha bands. Individual movements were found to influence relative theta, alpha and beta, and theta-to-beta ratios. He presents aerobic stretching HHIM exercise has demonstrated acute effect on the cortical activity of children.

  13. Cortical Activity during Perception of Musical Rhythm; Comparing Musicians and Non-musicians

    PubMed Central

    Habibi, Assal; Wirantana, Vinthia; Starr, Arnold

    2014-01-01

    This study investigates the effects of musical training on brain activity to violations of rhythmic expectancies. We recorded behavioral and event-related brain potential (ERP) responses of musicians and non-musicians to discrepancies of rhythm between pairs of unfamiliar melodies based on Western classical rules. Rhythm deviations in the second melody involved prolongation of a note, thus creating a delay in the subsequent note; the duration of the second note was consequently shorter because the offset time was unchanged. In the first melody, on the other hand, the two notes were of equal duration. Musicians detected rhythm deviations significantly better than non-musicians. A negative auditory cortical potential in response to the omitted stimulus was observed at a latency of 150–250 ms from where the note should have been. There were no significant differences of amplitude or latency between musicians and non-musicians. In contrast, the N100 and P200 to the delayed note after the omission were significantly greater in amplitude in musicians compared to non-musicians especially in frontal and frontal-central areas. These findings indicate that long term musical training enhances brain cortical activities involved in processing temporal irregularities of unfamiliar melodies. PMID:25512680

  14. Brain cortical activation during guitar-induced hand dystonia studied by functional MRI.

    PubMed

    Pujol, J; Roset-Llobet, J; Rosinés-Cubells, D; Deus, J; Narberhaus, B; Valls-Solé, J; Capdevila, A; Pascual-Leone, A

    2000-09-01

    Focal hand dystonia in musicians is a strongly task-related movement disorder. Typically, symptoms become apparent only when players execute specific overpracticed skilled exercises on their instrument. We therefore examined five guitarists with functional MRI during dystonic symptom provocation by means of an adapted guitar inside the magnet. The activation patterns obtained in comparable nondystonic guitarists and in the study patients when performing normal-hand exercise served as references. A 1.5-T system equipped with echo-speed gradients and single-shot echoplanar imaging software was used. Data acquisition was centered on the cortical motor system encompassed in eight contiguous slices. Dystonic musicians compared with both control situations showed a significantly larger activation of the contralateral primary sensorimotor cortex that contrasted with a conspicuous bilateral underactivation of premotor areas. Our results coincide with studies of other dystonia types in that they show an abnormal recruitment of cortical areas involved in the control of voluntary movement. However, they do suggest that the primary sensorimotor cortex, rather than being underactive in idiopathic dystonic patients, may be overactive when tested during full expression of the task-induced movement disorder.

  15. Self-selected conscious strategies do not modulate motor cortical output during action observation

    PubMed Central

    Obhi, Sukhvinder S.

    2015-01-01

    The human motor system is active not only when actions are performed but also when they are observed. Experimenters often manipulate aspects of the action or context to examine factors that influence this “mirror” response. However, little is known about the role of the observer's own top-down intentions and motivation. In this exploratory study, we investigated whether observers are able to exert conscious control over their mirror response, when they are explicitly instructed to either increase or decrease mirroring. Transcranial magnetic stimulation (TMS) was used to elicit motor-evoked potentials (MEPs) in a thumb abductor muscle as participants (n = 13) watched a video of a hand squeezing a rubber ball. The size of these MEPs, relative to the size of MEPs elicited during fixation cross observation, was taken as an index of mirroring. In an initial block of trials, participants were instructed to merely observe the actions presented. After the first block, the concept of mirroring was explained to the participants, and in the second and third blocks participants were instructed to either increase or decrease their mirror response. We did not instruct them about how to achieve this increase or decrease. Our results showed no difference in either facilitation or absolute motor excitability (i.e., nonnormalized MEP size) between the three blocks, indicating that individuals do not seem to be able to exert control over motor excitability during action observation, at least in the absence of a specific and maintained strategy. PMID:26311182

  16. Characterisation and imaging of cortical impedance changes during interictal and ictal activity in the anaesthetised rat

    PubMed Central

    Vongerichten, Anna N.; Santos, Gustavo Sato dos; Aristovich, Kirill; Avery, James; McEvoy, Andrew; Walker, Matthew; Holder, David S.

    2016-01-01

    Epilepsy affects approximately 50 million people worldwide, and 20–30% of these cases are refractory to antiepileptic drugs. Many patients with intractable epilepsy can benefit from surgical resection of the tissue generating the seizures; however, difficulty in precisely localising seizure foci has limited the number of patients undergoing surgery as well as potentially lowered its effectiveness. Here we demonstrate a novel imaging method for monitoring rapid changes in cerebral tissue impedance occurring during interictal and ictal activity, and show that it can reveal the propagation of pathological activity in the cortex. Cortical impedance was recorded simultaneously to ECoG using a 30-contact electrode mat placed on the exposed cortex of anaesthetised rats, in which interictal spikes (IISs) and seizures were induced by cortical injection of 4-aminopyridine (4-AP), picrotoxin or penicillin. We characterised the tissue impedance responses during IISs and seizures, and imaged these responses in the cortex using Electrical Impedance Tomography (EIT). We found a fast, transient drop in impedance occurring as early as 12 ms prior to the IISs, followed by a steep rise in impedance within ~ 120 ms of the IIS. EIT images of these impedance changes showed that they were co-localised and centred at a depth of 1 mm in the cortex, and that they closely followed the activity propagation observed in the surface ECoG signals. The fast, pre-IIS impedance drop most likely reflects synchronised depolarisation in a localised network of neurons, and the post-IIS impedance increase reflects the subsequent shrinkage of extracellular space caused by the intense activity. EIT could also be used to picture a steady rise in tissue impedance during seizure activity, which has been previously described. Thus, our results demonstrate that EIT can detect and localise different physiological changes during interictal and ictal activity and, in conjunction with ECoG, may in future

  17. Characterisation and imaging of cortical impedance changes during interictal and ictal activity in the anaesthetised rat.

    PubMed

    Vongerichten, Anna N; dos Santos, Gustavo Sato; Aristovich, Kirill; Avery, James; McEvoy, Andrew; Walker, Matthew; Holder, David S

    2016-01-01

    Epilepsy affects approximately 50 million people worldwide, and 20-30% of these cases are refractory to antiepileptic drugs. Many patients with intractable epilepsy can benefit from surgical resection of the tissue generating the seizures; however, difficulty in precisely localising seizure foci has limited the number of patients undergoing surgery as well as potentially lowered its effectiveness. Here we demonstrate a novel imaging method for monitoring rapid changes in cerebral tissue impedance occurring during interictal and ictal activity, and show that it can reveal the propagation of pathological activity in the cortex. Cortical impedance was recorded simultaneously to ECoG using a 30-contact electrode mat placed on the exposed cortex of anaesthetised rats, in which interictal spikes (IISs) and seizures were induced by cortical injection of 4-aminopyridine (4-AP), picrotoxin or penicillin. We characterised the tissue impedance responses during IISs and seizures, and imaged these responses in the cortex using Electrical Impedance Tomography (EIT). We found a fast, transient drop in impedance occurring as early as 12ms prior to the IISs, followed by a steep rise in impedance within ~120ms of the IIS. EIT images of these impedance changes showed that they were co-localised and centred at a depth of 1mm in the cortex, and that they closely followed the activity propagation observed in the surface ECoG signals. The fast, pre-IIS impedance drop most likely reflects synchronised depolarisation in a localised network of neurons, and the post-IIS impedance increase reflects the subsequent shrinkage of extracellular space caused by the intense activity. EIT could also be used to picture a steady rise in tissue impedance during seizure activity, which has been previously described. Thus, our results demonstrate that EIT can detect and localise different physiological changes during interictal and ictal activity and, in conjunction with ECoG, may in future improve the

  18. The frequency modulated auditory evoked response (FMAER), a technical advance for study of childhood language disorders: cortical source localization and selected case studies

    PubMed Central

    2013-01-01

    Background Language comprehension requires decoding of complex, rapidly changing speech streams. Detecting changes of frequency modulation (FM) within speech is hypothesized as essential for accurate phoneme detection, and thus, for spoken word comprehension. Despite past demonstration of FM auditory evoked response (FMAER) utility in language disorder investigations, it is seldom utilized clinically. This report's purpose is to facilitate clinical use by explaining analytic pitfalls, demonstrating sites of cortical origin, and illustrating potential utility. Results FMAERs collected from children with language disorders, including Developmental Dysphasia, Landau-Kleffner syndrome (LKS), and autism spectrum disorder (ASD) and also normal controls - utilizing multi-channel reference-free recordings assisted by discrete source analysis - provided demonstratrions of cortical origin and examples of clinical utility. Recordings from inpatient epileptics with indwelling cortical electrodes provided direct assessment of FMAER origin. The FMAER is shown to normally arise from bilateral posterior superior temporal gyri and immediate temporal lobe surround. Childhood language disorders associated with prominent receptive deficits demonstrate absent left or bilateral FMAER temporal lobe responses. When receptive language is spared, the FMAER may remain present bilaterally. Analyses based upon mastoid or ear reference electrodes are shown to result in erroneous conclusions. Serial FMAER studies may dynamically track status of underlying language processing in LKS. FMAERs in ASD with language impairment may be normal or abnormal. Cortical FMAERs can locate language cortex when conventional cortical stimulation does not. Conclusion The FMAER measures the processing by the superior temporal gyri and adjacent cortex of rapid frequency modulation within an auditory stream. Clinical disorders associated with receptive deficits are shown to demonstrate absent left or bilateral

  19. Cortical fMRI activation produced by attentive tracking of moving targets.

    PubMed

    Culham, J C; Brandt, S A; Cavanagh, P; Kanwisher, N G; Dale, A M; Tootell, R B

    1998-11-01

    Attention can be used to keep track of moving items, particularly when there are multiple targets of interest that cannot all be followed with eye movements. Functional magnetic resonance imaging (fMRI) was used to investigate cortical regions involved in attentive tracking. Cortical flattening techniques facilitated within-subject comparisons of activation produced by attentive tracking, visual motion, discrete attention shifts, and eye movements. In the main task, subjects viewed a display of nine green "bouncing balls" and used attention to mentally track a subset of them while fixating. At the start of each attentive-tracking condition, several target balls (e.g., 3/9) turned red for 2 s and then reverted to green. Subjects then used attention to keep track of the previously indicated targets, which were otherwise indistinguishable from the nontargets. Attentive-tracking conditions alternated with passive viewing of the same display when no targets had been indicated. Subjects were pretested with an eye-movement monitor to ensure they could perform the task accurately while fixating. For seven subjects, functional activation was superimposed on each individual's cortically unfolded surface. Comparisons between attentive tracking and passive viewing revealed bilateral activation in parietal cortex (intraparietal sulcus, postcentral sulcus, superior parietal lobule, and precuneus), frontal cortex (frontal eye fields and precentral sulcus), and the MT complex (including motion-selective areas MT and MST). Attentional enhancement was absent in early visual areas and weak in the MT complex. However, in parietal and frontal areas, the signal change produced by the moving stimuli was more than doubled when items were tracked attentively. Comparisons between attentive tracking and attention shifting revealed essentially identical activation patterns that differed only in the magnitude of activation. This suggests that parietal cortex is involved not only in discrete

  20. 5-HT7 receptor modulates GABAergic transmission in the rat dorsal raphe nucleus and controls cortical release of serotonin.

    PubMed

    Kusek, Magdalena; Sowa, Joanna; Kamińska, Katarzyna; Gołembiowska, Krystyna; Tokarski, Krzysztof; Hess, Grzegorz

    2015-01-01

    The 5-HT7 receptor is one of the several serotonin (5-HT) receptor subtypes that are expressed in the dorsal raphe nucleus (DRN). Some earlier findings suggested that 5-HT7 receptors in the DRN were localized on GABAergic interneurons modulating the activity of 5-HT projection neurons. The aim of the present study was to find out how the 5-HT7 receptor modulates the GABAergic synaptic input to putative 5-HT DRN neurons, and whether blockade of the 5-HT7 receptor would affect the release of 5-HT in the target structure. Male Wistar rats with microdialysis probes implanted in the prefrontal cortex (PFC) received injections of the 5-HT7 receptor antagonist (2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine hydrochloride (SB 269970), which induced an increase in the levels of 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA) in the PFC. In another set of experiments whole-cell recordings from presumed projection neurons were carried out using DRN slices. SB 269970 application resulted in depolarization and in an increase in the firing frequency of the cells. In order to activate 5-HT7 receptors, 5-carboxamidotryptamine (5-CT) was applied in the presence of N-[2-[4-(2-methoxyphenyl)-1piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide (WAY100635). Hyperpolarization of cells and a decrease in the firing frequency were observed after activation of the 5-HT7 receptor. Blockade of 5-HT7 receptors caused a decrease in the mean frequency of spontaneous inhibitory postsynaptic currents (sIPSCs), while its activation induced an increase. The mechanism of these effects appears to involve tonically-active 5-HT7 receptors modulating firing and/or GABA release from inhibitory interneurons which regulate the activity of DRN serotonergic projection neurons.

  1. Exploring the Nature of Cortical Recurrent Interactions

    NASA Astrophysics Data System (ADS)

    Morita, Kenji; Kalra, Rita; Aihara, Kazuyuki; Robinson, Hugh P. C.

    2011-09-01

    Fast rhythmic activity of neural population has been frequently observed in cortical circuits, and suggested to be associated with various cognitive functions including working memory and selective attention. However, precisely how recurrent synaptic interactions, that are prominent in these circuits, shape and/or modulate such population rhythm has not been fully elucidated. We have addressed this issue by combining electrophysiological and computational approaches.

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

    PubMed Central

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

    2016-01-01

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

  3. An EP2 Agonist Facilitates NMDA-Induced Outward Currents and Inhibits Dendritic Beading through Activation of BK Channels in Mouse Cortical Neurons

    PubMed Central

    Hayashi, Yoshinori; Morinaga, Saori; Liu, Xia; Zhang, Jing; Wu, Zhou; Yokoyama, Takeshi; Nakanishi, Hiroshi

    2016-01-01

    Prostaglandin E2 (PGE2), a major metabolite of arachidonic acid produced by cyclooxygenase pathways, exerts its bioactive responses by activating four E-prostanoid receptor subtypes, EP1, EP2, EP3, and EP4. PGE2 enables modulating N-methyl-D-aspartate (NMDA) receptor-mediated responses. However, the effect of E-prostanoid receptor agonists on large-conductance Ca2+-activated K+ (BK) channels, which are functionally coupled with NMDA receptors, remains unclear. Here, we showed that EP2 receptor-mediated signaling pathways increased NMDA-induced outward currents (INMDA-OUT), which are associated with the BK channel activation. Patch-clamp recordings from the acutely dissociated mouse cortical neurons revealed that an EP2 receptor agonist activated INMDA-OUT, whereas an EP3 receptor agonist reduced it. Agonists of EP1 or EP4 receptors showed no significant effects on INMDA-OUT. A direct perfusion of 3,5′-cyclic adenosine monophosphate (cAMP) through the patch pipette facilitated INMDA-OUT, which was abolished by the presence of protein kinase A (PKA) inhibitor. Furthermore, facilitation of INMDA-OUT caused by an EP2 receptor agonist was significantly suppressed by PKA inhibitor. Finally, the activation of BK channels through EP2 receptors facilitated the recovery phase of NMDA-induced dendritic beading in the primary cultured cortical neurons. These results suggest that a direct activation of BK channels by EP2 receptor-mediated signaling pathways plays neuroprotective roles in cortical neurons. PMID:27298516

  4. Swelling-activated taurine and creatine effluxes from rat cortical astrocytes are pharmacologically distinct.

    PubMed

    Bothwell, J H; Styles, P; Bhakoo, K K

    2002-01-15

    Primary cultures of rat cortical astrocytes undergo a swelling-activated loss of taurine and creatine. In this study, the pharmacological characteristics of the taurine and creatine efflux pathways were compared, and significant differences were shown to exist between the two. Both taurine and creatine effluxes were rapidly activated upon exposure of astrocytes to hypo-osmotic media, and rapidly inactivated upon their return to iso-osmotic media. The relative rates of taurine and creatine efflux depended upon the magnitude of the hypo-osmotic shock. Anion-transport inhibitors strongly inhibited taurine efflux, with the order of potency being NPPB > DIDS > niflumic acid. DIDS and NPPB had less of an inhibitory effect on creatine efflux, whereas tamoxifen and niflumic acid actually stimulated creatine efflux. These data are consistent with separate pathways for taurine and creatine loss during astrocyte swelling.

  5. Somatotopical relationships between cortical activity and reflex areas in reflexology: a functional magnetic resonance imaging study.

    PubMed

    Nakamaru, Tomomi; Miura, Naoki; Fukushima, Ai; Kawashima, Ryuta

    2008-12-19

    We examined the somatotopical relationship between cortical activity and sensory stimulation of reflex areas in reflexology using functional magnetic resonance imaging. Three reflex areas on the left foot, relating to the eye, shoulder, and small intestine were stimulated during the experiment. A statistical analysis showed that reflexological stimulation of the foot reflex areas corresponding to the eye, shoulder, and small intestine activated not only the somatosensory areas corresponding to the foot, but also the somatosensory areas corresponding to the eye, shoulder, and small intestine or neighboring body parts. Thus, the findings showed that reflexological stimulation induced a somatosensory process corresponding to the stimulated reflex area and that a neuroimaging approach can be used to examine the basis of reflexology effects.

  6. Consequences of Laughter Upon Trunk Compression and Cortical Activation: Linear and Polynomial Relations

    PubMed Central

    Svebak, Sven

    2016-01-01

    Results from two studies of biological consequences of laughter are reported. A proposed inhibitory brain mechanism was tested in Study 1. It aims to protect against trunk compression that can cause health hazards during vigorous laughter. Compression may be maximal during moderate durations and, for protective reasons, moderate in enduring vigorous laughs. Twenty-five university students volunteered to see a candid camera film. Laughter responses (LR) and the superimposed ha-responses were operationally assessed by mercury-filled strain gauges strapped around the trunk. On average, the thorax compression amplitudes exceeded those of the abdomen, and greater amplitudes were seen in the males than in the females after correction for resting trunk circumference. Regression analyses supported polynomial relations because medium LR durations were associated with particularly high thorax amplitudes. In Study 2, power changes were computed in the beta and alpha EEG frequency bands of the parietal cortex from before to after exposure to the comedy “Dinner for one” in 56 university students. Highly significant linear relations were calculated between the number of laughs and post-exposure cortical activation (increase of beta, decrease of alpha) due to high activation after frequent laughter. The results from Study 1 supported the hypothesis of a protective brain mechanism that is activated during long LRs to reduce the risk of harm to vital organs in the trunk cavity. The results in Study 2 supported a linear cortical activation and, thus, provided evidence for a biological correlate to the subjective experience of mental refreshment after laughter. PMID:27547260

  7. Investigating the effects of a sensorimotor rhythm-based BCI training on the cortical activity elicited by mental imagery

    NASA Astrophysics Data System (ADS)

    Toppi, J.; Risetti, M.; Quitadamo, L. R.; Petti, M.; Bianchi, L.; Salinari, S.; Babiloni, F.; Cincotti, F.; Mattia, D.; Astolfi, L.

    2014-06-01

    Objective. It is well known that to acquire sensorimotor (SMR)-based brain-computer interface (BCI) control requires a training period before users can achieve their best possible performances. Nevertheless, the effect of this training procedure on the cortical activity related to the mental imagery ability still requires investigation to be fully elucidated. The aim of this study was to gain insights into the effects of SMR-based BCI training on the cortical spectral activity associated with the performance of different mental imagery tasks. Approach. Linear cortical estimation and statistical brain mapping techniques were applied on high-density EEG data acquired from 18 healthy participants performing three different mental imagery tasks. Subjects were divided in two groups, one of BCI trained subjects, according to their previous exposure (at least six months before this study) to motor imagery-based BCI training, and one of subjects who were naive to any BCI paradigms. Main results. Cortical activation maps obtained for trained and naive subjects indicated different spectral and spatial activity patterns in response to the mental imagery tasks. Long-term effects of the previous SMR-based BCI training were observed on the motor cortical spectral activity specific to the BCI trained motor imagery task (simple hand movements) and partially generalized to more complex motor imagery task (playing tennis). Differently, mental imagery with spatial attention and memory content could elicit recognizable cortical spectral activity even in subjects completely naive to (BCI) training. Significance. The present findings contribute to our understanding of BCI technology usage and might be of relevance in those clinical conditions when training to master a BCI application is challenging or even not possible.

  8. Tissue-type plasminogen activator induces synaptic vesicle endocytosis in cerebral cortical neurons.

    PubMed

    Yepes, M; Wu, F; Torre, E; Cuellar-Giraldo, D; Jia, D; Cheng, L

    2016-04-05

    The release of the serine proteinase tissue-type plasminogen activator (tPA) from the presynaptic terminal of cerebral cortical neurons plays a central role in the development of synaptic plasticity, adaptation to metabolic stress and neuronal survival. Our earlier studies indicate that by inducing the recruitment of the cytoskeletal protein βII-spectrin and voltage-gated calcium channels to the active zone, tPA promotes Ca(2+)-dependent translocation of synaptic vesicles (SVs) to the synaptic release site where they release their load of neurotransmitters into the synaptic cleft. Here we used a combination of in vivo and in vitro experiments to investigate whether this effect leads to depletion of SVs in the presynaptic terminal. Our data indicate that tPA promotes SV endocytosis via a mechanism that does not require the conversion of plasminogen into plasmin. Instead, we show that tPA induces calcineurin-mediated dynamin I dephosphorylation, which is followed by dynamin I-induced recruitment of the actin-binding protein profilin II to the presynaptic membrane, and profilin II-induced F-actin formation. We report that this tPA-induced sequence of events leads to the association of newly formed SVs with F-actin clusters in the endocytic zone. In summary, the data presented here indicate that following the exocytotic release of neurotransmitters tPA activates the mechanism whereby SVs are retrieved from the presynaptic membrane and endocytosed to replenish the pool of vesicles available for a new cycle of exocytosis. Together, these results indicate that in murine cerebral cortical neurons tPA plays a central role coupling SVs exocytosis and endocytosis.

  9. Coherent Activity in Bilateral Parieto-Occipital Cortices during P300-BCI Operation.

    PubMed

    Takano, Kouji; Ora, Hiroki; Sekihara, Kensuke; Iwaki, Sunao; Kansaku, Kenji

    2014-01-01

    The visual P300 brain-computer interface (BCI), a popular system for electroencephalography (EEG)-based BCI, uses the P300 event-related potential to select an icon arranged in a flicker matrix. In earlier studies, we used green/blue (GB) luminance and chromatic changes in the P300-BCI system and reported that this luminance and chromatic flicker matrix was associated with better performance and greater subject comfort compared with the conventional white/gray (WG) luminance flicker matrix. To highlight areas involved in improved P300-BCI performance, we used simultaneous EEG-fMRI recordings and showed enhanced activities in bilateral and right lateralized parieto-occipital areas. Here, to capture coherent activities of the areas during P300-BCI, we collected whole-head 306-channel magnetoencephalography data. When comparing functional connectivity between the right and left parieto-occipital channels, significantly greater functional connectivity in the alpha band was observed under the GB flicker matrix condition than under the WG flicker matrix condition. Current sources were estimated with a narrow-band adaptive spatial filter, and mean imaginary coherence was computed in the alpha band. Significantly greater coherence was observed in the right posterior parietal cortex under the GB than under the WG condition. Re-analysis of previous EEG-based P300-BCI data showed significant correlations between the power of the coherence of the bilateral parieto-occipital cortices and their performance accuracy. These results suggest that coherent activity in the bilateral parieto-occipital cortices plays a significant role in effectively driving the P300-BCI.

  10. Modulation of ceramide synthase activity via dimerization.

    PubMed

    Laviad, Elad L; Kelly, Samuel; Merrill, Alfred H; Futerman, Anthony H

    2012-06-15

    Ceramide, the backbone of all sphingolipids, is synthesized by a family of ceramide synthases (CerS) that each use acyl-CoAs of defined chain length for N-acylation of the sphingoid long chain base. CerS mRNA expression and enzymatic activity do not always correlate with the sphingolipid acyl chain composition of a particular tissue, suggesting post-translational mechanism(s) of regulation of CerS activity. We now demonstrate that CerS activity can be modulated by dimer formation. Under suitable conditions, high M(r) CerS complexes can be detected by Western blotting, and various CerS co-immunoprecipitate. CerS5 activity is inhibited in a dominant-negative fashion by co-expression with catalytically inactive CerS5, and CerS2 activity is enhanced by co-expression with a catalytically active form of CerS5 or CerS6. In a constitutive heterodimer comprising CerS5 and CerS2, the activity of CerS2 depends on the catalytic activity of CerS5. Finally, CerS dimers are formed upon rapid stimulation of ceramide synthesis by curcumin. Together, these data demonstrate that ceramide synthesis can be regulated by the formation of CerS dimers and suggest a novel way to generate the acyl chain composition of ceramide (and downstream sphingolipids), which may depend on the interaction of CerS with each other.

  11. Conditioning of cortical neurons in cats with antidromic activation as the unconditioned stimulus.

    PubMed

    O'Brien, J H; Wilder, M B; Stevens, C D

    1977-08-01

    Single-cell activity was recorded from the postcruciate cortex of acutely prepared cats during a differential classical conditioning procedure. The conditioned stimuli (CS) were hind paw stimuli, and the unconditioned stimulus (US) was pyramidal tract stimulation that produced an antidromic response in the recorded cortical neuron. A control group was also examined in which the pyramidal stimulus was set below the threshold to produce an antidromic response. Clear differential conditioning was found for the experimental group, with antidromic activation of the neuron as the US. There was no evidence of differential conditioning in the control group without antidromic activation. Any activation of orthodromic pathways should have been the same in the control and experimental groups. The absence of conditioning in the control group demonstrated that orthodromic pathways were not contributing to the differential conditioning observed in the experimental group. This indicates that it was activation of the neuron produced by antidromic firing which was important for conditioning. All the evidence suggests that the site of learning was in the cortex. It is concluded that the the role of the US in conditioning may be simply to activate the neuron at an appropriate interval following the CS.

  12. Lempel-Ziv complexity of cortical activity during sleep and waking in rats.

    PubMed

    Abásolo, Daniel; Simons, Samantha; Morgado da Silva, Rita; Tononi, Giulio; Vyazovskiy, Vladyslav V

    2015-04-01

    Understanding the dynamics of brain activity manifested in the EEG, local field potentials (LFP), and neuronal spiking is essential for explaining their underlying mechanisms and physiological significance. Much has been learned about sleep regulation using conventional EEG power spectrum, coherence, and period-amplitude analyses, which focus primarily on frequency and amplitude characteristics of the signals and on their spatio-temporal synchronicity. However, little is known about the effects of ongoing brain state or preceding sleep-wake history on the nonlinear dynamics of brain activity. Recent advances in developing novel mathematical approaches for investigating temporal structure of brain activity based on such measures, as Lempel-Ziv complexity (LZC) can provide insights that go beyond those obtained with conventional techniques of signal analysis. Here, we used extensive data sets obtained in spontaneously awake and sleeping adult male laboratory rats, as well as during and after sleep deprivation, to perform a detailed analysis of cortical LFP and neuronal activity with LZC approach. We found that activated brain states-waking and rapid eye movement (REM) sleep are characterized by higher LZC compared with non-rapid eye movement (NREM) sleep. Notably, LZC values derived from the LFP were especially low during early NREM sleep after sleep deprivation and toward the middle of individual NREM sleep episodes. We conclude that LZC is an important and yet largely unexplored measure with a high potential for investigating neurophysiological mechanisms of brain activity in health and disease.

  13. An ECG-based Algorithm for the Automatic Identification of Autonomic Activations Associated with Cortical Arousal

    PubMed Central

    Basner, Mathias; Griefahn, Barbara; Müller, Uwe; Plath, Gernot; Samel, Alexander

    2007-01-01

    Objectives: EEG arousals are associated with autonomic activations. Visual EEG arousal scoring is time consuming and suffers from low interobserver agreement. We hypothesized that information on changes in heart rate alone suffice to predict the occurrence of cortical arousal. Methods: Two visual AASM EEG arousal scorings of 56 healthy subject nights (mean age 37.0 ± 12.8 years, 26 male) were obtained. For each of 5 heartbeats following the onset of 3581 consensus EEG arousals and of an equal number of control conditions, differences to a moving median were calculated and used to estimate likelihood ratios (LRs) for 10 categories of heartbeat differences. Comparable to 5 consecutive diagnostic tests, these LRs were used to calculate the probability of heart rate responses being associated with cortical arousals. Results: EEG and ECG arousal indexes agreed well across a wide range of decision thresholds, resulting in a receiver operating characteristic (ROC) with an area under the curve of 0.91. For the decision threshold chosen for the final analyses, a sensitivity of 68.1% and a specificity of 95.2% were obtained. ECG and EEG arousal indexes were poorly correlated (r = 0.19, P <0.001, ICC = 0.186), which could in part be attributed to 3 outliers. The Bland-Altman plot showed an unbiased estimation of EEG arousal indexes by ECG arousal indexes with a standard deviation of ± 7.9 arousals per hour sleep. In about two-thirds of all cases, ECG arousal scoring was matched by at least one (22.2%) or by both (42.5%) of the visual scorings. Sensitivity of the algorithm increased with increasing duration of EEG arousals. The ECG algorithm was also successfully validated with 30 different nights of 10 subjects (mean age 35.3 ▯ 13.6 years, 5 male). Conclusions: In its current version, the ECG algorithm cannot replace visual EEG arousal scoring. Sensitivity for detecting <10-s EEG arousals needs to be improved. However, in a nonclinical population, it may be valuable to

  14. Multichannel time domain fNIRS mapping of cortical activation and superficial systemic responses during neuromuscular electrical stimulation

    NASA Astrophysics Data System (ADS)

    Re, R.; Muthalib, M.; Zucchelli, L.; Perrey, S.; Contini, D.; Caffini, M.; Spinelli, L.; Kerr, G.; Torricelli, A.

    2013-06-01

    We recorded maps of cortical and systemic hemodynamic responses (oxy-hemoglobin, O2Hb and deoxy-hemoglobin, HHb) during incremental neuromuscular electrical stimulation (NMES) of the right forearm in nine subjects by a 32- channel time domain fNIRS (TD-fNIRS) instrument. Statistical parametric maps (SPM) relative to the different current stimulations (under and over the maximal tolerated intensity-MTI) versus the 10%MTI were generated. Exploiting the temporal information contained in the TD-fNIRS signal it was possible to create different maps referring to the deeper (cortical activations) and the more superficial (systemic changes) head layers. The increasing of the stimulation current on the right forearm muscle produced a significantly larger bilateral sensorimotor and prefrontal cortical activations (i.e. increase in the O2Hb and decrease in HHb) than the systemic changes. Physiological parameters (heart rate, breathing rate and skin conductance) were also monitored.

  15. Cortical activity and children's rituals, habits and other repetitive behavior: a visual P300 study.

    PubMed

    Evans, David W; Maliken, Ashley

    2011-10-10

    This study examines the link between children's repetitive, ritualistic, behavior and cortical brain activity. Twelve typically developing children between the ages of 6 and 12 years were administered two visual P300, oddball tasks with a 32-electrode electroencephalogram (EEG) system. One of the oddball tasks was specifically designed to reflect sensitivity to asymmetry, a phenomenon common in children and in a variety of disorders involving compulsive behavior. Parents completed the Childhood Routines Inventory. Children's repetitive, compulsive-like behaviors were strongly associated with faster processing of an asymmetrical target stimulus, even when accounting for their P300 latencies on a control task. The research punctuates the continuity between observed brain-behavior links in clinical disorders such as OCD and autism spectrum disorders, and normative variants of repetitive behavior.

  16. Excitatory synaptic transmission and network activity are depressed following mechanical injury in cortical neurons

    PubMed Central

    Goforth, Paulette B.; Ren, Jianhua; Schwartz, Benjamin S.

    2011-01-01

    In vitro and in vivo traumatic brain injury (TBI) alter the function and expression of glutamate receptors, yet the combined effect of these alterations on cortical excitatory synaptic transmission is unclear. We examined the effect of in vitro mechanical injury on excitatory synaptic function in cultured cortical neurons by assaying synaptically driven intracellular free calcium ([Ca2+]i) oscillations in small neuronal networks as well as spontaneous and miniature excitatory postsynaptic currents (mEPSCs). We show that injury decreased the incidence and frequency of spontaneous neuronal [Ca2+]i oscillations for at least 2 days post-injury. The amplitude of the oscillations was reduced immediately and 2 days post-injury, although a transient rebound at 4 h post-injury was observed due to increased activity of N-methyl-d-aspartate (NMDARs) and calcium-permeable α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (CP-AMPARs). Increased CP-AMPAR function was abolished by the inhibition of protein synthesis. In parallel, mEPSC amplitude decreased immediately, 4 h, and 2 days post-injury, with a transient increase in the contribution of synaptic CP-AMPARs observed at 4 h post-injury. Decreased mEPSC amplitude was evident after injury, even if NMDARs and CP-AMPARs were blocked pharmacologically, suggesting the decrease reflected alterations in synaptic Glur2-containing, calcium-impermeable AMPARs. Despite the transient increase in CP-AMPAR activity that we observed, the overriding effect of mechanical injury was long-term depression of excitatory neurotransmission that would be expected to contribute to the cognitive deficits of TBI. PMID:21346214

  17. Excitatory synaptic transmission and network activity are depressed following mechanical injury in cortical neurons.

    PubMed

    Goforth, Paulette B; Ren, Jianhua; Schwartz, Benjamin S; Satin, Leslie S

    2011-05-01

    In vitro and in vivo traumatic brain injury (TBI) alter the function and expression of glutamate receptors, yet the combined effect of these alterations on cortical excitatory synaptic transmission is unclear. We examined the effect of in vitro mechanical injury on excitatory synaptic function in cultured cortical neurons by assaying synaptically driven intracellular free calcium ([Ca(2+)](i)) oscillations in small neuronal networks as well as spontaneous and miniature excitatory postsynaptic currents (mEPSCs). We show that injury decreased the incidence and frequency of spontaneous neuronal [Ca(2+)](i) oscillations for at least 2 days post-injury. The amplitude of the oscillations was reduced immediately and 2 days post-injury, although a transient rebound at 4 h post-injury was observed due to increased activity of N-methyl-d-aspartate (NMDARs) and calcium-permeable α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (CP-AMPARs). Increased CP-AMPAR function was abolished by the inhibition of protein synthesis. In parallel, mEPSC amplitude decreased immediately, 4 h, and 2 days post-injury, with a transient increase in the contribution of synaptic CP-AMPARs observed at 4 h post-injury. Decreased mEPSC amplitude was evident after injury, even if NMDARs and CP-AMPARs were blocked pharmacologically, suggesting the decrease reflected alterations in synaptic Glur2-containing, calcium-impermeable AMPARs. Despite the transient increase in CP-AMPAR activity that we observed, the overriding effect of mechanical injury was long-term depression of excitatory neurotransmission that would be expected to contribute to the cognitive deficits of TBI.

  18. Nicotinic receptor activation in human cerebral cortical interneurons: a mechanism for inhibition and disinhibition of neuronal networks.

    PubMed

    Alkondon, M; Pereira, E F; Eisenberg, H M; Albuquerque, E X

    2000-01-01

    Cholinergic control of the activity of human cerebral cortical circuits has long been thought to be accounted for by the interaction of acetylcholine (ACh) with muscarinic receptors. Here we report the discovery of functional nicotinic receptors (nAChRs) in interneurons of the human cerebral cortex and discuss the physiological and clinical implications of these findings. The whole-cell mode of the patch-clamp technique was used to record responses triggered by U-tube application of the nonselective agonist ACh and of the alpha7-nAChR-selective agonist choline to interneurons visualized by means of infrared-assisted videomicroscopy in slices of the human cerebral cortex. Choline induced rapidly desensitizing whole-cell currents that, being sensitive to blockade by methyllycaconitine (MLA; 50 nM), were most likely subserved by an alpha7-like nAChR. In contrast, ACh evoked slowly decaying whole-cell currents that, being sensitive to blockade by dihydro-beta-erythroidine (DHbetaE; 10 microM), were most likely subserved by an alpha4beta2-like nAChR. Application of ACh (but not choline) to the slices also triggered GABAergic postsynaptic currents (PSCs). Evidence is provided that ACh-evoked PSCs are the result of activation of alpha4beta2-like nAChRs present in preterminal axon segments and/or in presynaptic terminals of interneurons. Thus, nAChRs can relay inhibitory and/or disinhibitory signals to pyramidal neurons and thereby modulate the activity of neuronal circuits in the human cerebral cortex. These mechanisms, which appear to be retained across species, can account for the involvement of nAChRs in cognitive functions and in certain neuropathological conditions.

  19. MRI-constrained spectral imaging of benzodiazepine modulation of spontaneous neuromagnetic activity in human cortex.

    PubMed

    Ahveninen, Jyrki; Lin, Fa-Hsuan; Kivisaari, Reetta; Autti, Taina; Hämäläinen, Matti; Stufflebeam, Steven; Belliveau, John W; Kähkönen, Seppo

    2007-04-01

    Spontaneous electromagnetic brain rhythms have been widely used in human neuropharmacology, but their applicability is complicated by the difficulties to localize their origins in the human cortex. Here, we used a novel multi-modal non-invasive imaging approach to localize lorazepam (30 microg/kg i.v.) modulation of cortical generators of spontaneous brain rhythms. Eight healthy subjects were measured with 306-channel magnetoencephalography (MEG) in a double-blind, randomized, placebo-controlled (saline), crossover design. For anatomically realistic source modeling, wavelet-transformed MEG data were combined with high-resolution MRI to constrain the current locations to the cortical mantle, after which individual data were co-registered to surface-based coordinate system for the calculation of group statistical parametric maps of drug effects. The distributed MRI-constrained MEG source estimates demonstrated decreased alpha (10 Hz) activity in and around the parieto-occipital sulcus and in the calcarine sulcus of the occipital lobe, following from increased GABA(A)-inhibition by lorazepam. Anatomically constrained spectral imaging displays the cortical loci of drug effects on oscillatory brain activity, providing a novel tool for human pharmacological neuroimaging.

  20. A biased activation theory of the cognitive and attentional modulation of emotion

    PubMed Central

    Rolls, Edmund T.

    2013-01-01

    Cognition can influence emotion by biasing neural activity in the first cortical region in which the reward value and subjective pleasantness of stimuli is made explicit in the representation, the orbitofrontal cortex (OFC). The same effect occurs in a second cortical tier for emotion, the anterior cingulate cortex (ACC). Similar effects are found for selective attention, to for example the pleasantness vs. the intensity of stimuli, which modulates representations of reward value and affect in the orbitofrontal and anterior cingulate cortices. The mechanisms for the effects of cognition and attention on emotion are top-down biased competition and top-down biased activation. Affective and mood states can in turn influence memory and perception, by backprojected biasing influences. Emotion-related decision systems operate to choose between gene-specified rewards such as taste, touch, and beauty. Reasoning processes capable of planning ahead with multiple steps held in working memory in the explicit system can allow the gene-specified rewards not to be selected, or to be deferred. The stochastic, noisy, dynamics of decision-making systems in the brain may influence whether decisions are made by the selfish-gene-specified reward emotion system, or by the cognitive reasoning system that explicitly calculates reward values that are in the interests of the individual, the phenotype. PMID:23508210

  1. Gender specific changes in cortical activation patterns during exposure to artificial gravity

    NASA Astrophysics Data System (ADS)

    Schneider, Stefan; Robinson, Ryan; Smith, Craig; von der Wiesche, Melanie; Goswami, Nandu

    2014-11-01

    Keeping astronauts healthy during long duration spaceflight remains a challenge. Artificial gravity (AG) generated by a short arm human centrifuges (SAHC) is proposed as the next generation of integrated countermeasure devices that will allow human beings to safely spend extended durations in space, although comparatively little is known about any psychological side effects of AG on brain function. 16 participants (8 male and 8 female, GENDER) were exposed to 10 min at a baseline gravitational load (G-Load) of +.03 Gz, then 10 min at +.6 Gz for females and +.8 Gz for males, before being exposed to increasing levels of AG in a stepped manner by increasing the acceleration by +.1 Gz every 3 min until showing signs of pre-syncope. EEG recordings were taken of brain activity during 2 min time periods at each AG level. Analysing the results of the mixed total population of participants by two way ANOVA, a significant effect of centrifugation on alpha and beta activity was found (p<.01). Furthermore results revealed a significant interaction between G-LOAD and GENDER alpha-activity (p<.01), but not for beta-activity. Although the increase in alpha and beta activity with G-LOAD does not reflect a general model of cortical arousal and therefore cannot support previous findings reporting that AG may be a cognitively arousing environment, the gender specific responses identified in this study may have wider implications for EEG and AG research.

  2. Dampened neural activity and abolition of epileptic-like activity in cortical slices by active ingredients of spices

    PubMed Central

    Pezzoli, Maurizio; Elhamdani, Abdeladim; Camacho, Susana; Meystre, Julie; González, Stephanie Michlig; le Coutre, Johannes; Markram, Henry

    2014-01-01

    Active ingredients of spices (AIS) modulate neural response in the peripheral nervous system, mainly through interaction with TRP channel/receptors. The present study explores how different AIS modulate neural response in layer 5 pyramidal neurons of S1 neocortex. The AIS tested are agonists of TRPV1/3, TRPM8 or TRPA1. Our results demonstrate that capsaicin, eugenol, menthol, icilin and cinnamaldehyde, but not AITC dampen the generation of APs in a voltage- and time-dependent manner. This effect was further tested for the TRPM8 ligands in the presence of a TRPM8 blocker (BCTC) and on TRPM8 KO mice. The observable effect was still present. Finally, the influence of the selected AIS was tested on in vitro gabazine-induced seizures. Results coincide with the above observations: except for cinnamaldehyde, the same AIS were able to reduce the number, duration of the AP bursts and increase the concentration of gabazine needed to elicit them. In conclusion, our data suggests that some of these AIS can modulate glutamatergic neurons in the brain through a TRP-independent pathway, regardless of whether the neurons are stimulated intracellularly or by hyperactive microcircuitry. PMID:25359561

  3. Dampened neural activity and abolition of epileptic-like activity in cortical slices by active ingredients of spices.

    PubMed

    Pezzoli, Maurizio; Elhamdani, Abdeladim; Camacho, Susana; Meystre, Julie; González, Stephanie Michlig; le Coutre, Johannes; Markram, Henry

    2014-10-31

    Active ingredients of spices (AIS) modulate neural response in the peripheral nervous system, mainly through interaction with TRP channel/receptors. The present study explores how different AIS modulate neural response in layer 5 pyramidal neurons of S1 neocortex. The AIS tested are agonists of TRPV1/3, TRPM8 or TRPA1. Our results demonstrate that capsaicin, eugenol, menthol, icilin and cinnamaldehyde, but not AITC dampen the generation of APs in a voltage- and time-dependent manner. This effect was further tested for the TRPM8 ligands in the presence of a TRPM8 blocker (BCTC) and on TRPM8 KO mice. The observable effect was still present. Finally, the influence of the selected AIS was tested on in vitro gabazine-induced seizures. Results coincide with the above observations: except for cinnamaldehyde, the same AIS were able to reduce the number, duration of the AP bursts and increase the concentration of gabazine needed to elicit them. In conclusion, our data suggests that some of these AIS can modulate glutamatergic neurons in the brain through a TRP-independent pathway, regardless of whether the neurons are stimulated intracellularly or by hyperactive microcircuitry.

  4. Scaffolds are 'active' regulators of signaling modules.

    PubMed

    Alexa, Anita; Varga, János; Reményi, Attila

    2010-11-01

    Signaling cascades, in addition to proteins with obvious signaling-relevant activities (e.g. protein kinases or receptors), also employ dedicated 'inactive' proteins whose functions appear to be the organization of the former components into higher order complexes through protein-protein interactions. The core function of signaling adaptors, anchors and scaffolds is the recruitment of proteins into one macromolecular complex. Several recent studies have demonstrated that the recruiter and the recruited molecules mutually influence each other in a scaffolded complex. This yields fundamentally novel properties for the signaling complex as a whole. Because these are not merely additive to the properties of the individual components, scaffolded signaling complexes may behave as functionally distinct modules.

  5. Effect of Anatomically Realistic Full-Head Model on Activation of Cortical Neurons in Subdural Cortical Stimulation—A Computational Study

    PubMed Central

    Seo, Hyeon; Kim, Donghyeon; Jun, Sung Chan

    2016-01-01

    Electrical brain stimulation (EBS) is an emerging therapy for the treatment of neurological disorders, and computational modeling studies of EBS have been used to determine the optimal parameters for highly cost-effective electrotherapy. Recent notable growth in computing capability has enabled researchers to consider an anatomically realistic head model that represents the full head and complex geometry of the brain rather than the previous simplified partial head model (extruded slab) that represents only the precentral gyrus. In this work, subdural cortical stimulation (SuCS) was found to offer a better understanding of the differential activation of cortical neurons in the anatomically realistic full-head model than in the simplified partial-head models. We observed that layer 3 pyramidal neurons had comparable stimulation thresholds in both head models, while layer 5 pyramidal neurons showed a notable discrepancy between the models; in particular, layer 5 pyramidal neurons demonstrated asymmetry in the thresholds and action potential initiation sites in the anatomically realistic full-head model. Overall, the anatomically realistic full-head model may offer a better understanding of layer 5 pyramidal neuronal responses. Accordingly, the effects of using the realistic full-head model in SuCS are compelling in computational modeling studies, even though this modeling requires substantially more effort. PMID:27273817

  6. Effect of Anatomically Realistic Full-Head Model on Activation of Cortical Neurons in Subdural Cortical Stimulation—A Computational Study

    NASA Astrophysics Data System (ADS)

    Seo, Hyeon; Kim, Donghyeon; Jun, Sung Chan

    2016-06-01

    Electrical brain stimulation (EBS) is an emerging therapy for the treatment of neurological disorders, and computational modeling studies of EBS have been used to determine the optimal parameters for highly cost-effective electrotherapy. Recent notable growth in computing capability has enabled researchers to consider an anatomically realistic head model that represents the full head and complex geometry of the brain rather than the previous simplified partial head model (extruded slab) that represents only the precentral gyrus. In this work, subdural cortical stimulation (SuCS) was found to offer a better understanding of the differential activation of cortical neurons in the anatomically realistic full-head model than in the simplified partial-head models. We observed that layer 3 pyramidal neurons had comparable stimulation thresholds in both head models, while layer 5 pyramidal neurons showed a notable discrepancy between the models; in particular, layer 5 pyramidal neurons demonstrated asymmetry in the thresholds and action potential initiation sites in the anatomically realistic full-head model. Overall, the anatomically realistic full-head model may offer a better understanding of layer 5 pyramidal neuronal responses. Accordingly, the effects of using the realistic full-head model in SuCS are compelling in computational modeling studies, even though this modeling requires substantially more effort.

  7. Modulating reproductive activity in stallions: a review.

    PubMed

    Stout, T A E

    2005-10-01

    Situations in which suppression or stimulation of reproductive activity in stallions has been attempted, or is desired, include resolution of the equine arteritis virus 'shedding' state, induction of testicular descent in inguinal cryptorchids, and the improvement of sperm production capacity and/or semen quality in sub-fertile stallions. However, the most common reason for wanting to modulate reproductive activity in a stallion is to alter the expression of sexual behaviour. In the case of intact stallions used for competitive or recreational purposes, the overt expression of sexual or aggressive behaviour can be distracting for both animal and owner and, in some cases, dangerous to all concerned. By the same token, a breeding stallion that displays little interest in mounting a mare/phantom, or is slow to achieve erection and/or ejaculation, can be extremely frustrating. This paper reviews the major pharmacological agents reported to usefully modify reproductive activity in stallions, and outlines their pros and cons when compared to training, management or surgical alternatives.

  8. Abnormal cortical sensory activation in dystonia: an fMRI study.

    PubMed

    Butterworth, Stephen; Francis, Sue; Kelly, Edward; McGlone, Francis; Bowtell, Richard; Sawle, Guy V

    2003-06-01

    Despite the obvious motor manifestations of focal dystonia, it is recognised that the sensory system plays an important role in this condition. This functional magnetic resonance imaging study examines the sensory representations of individual digits both within the subregions of the primary sensory cortex (SI) and in other nonprimary sensory areas. Patients with focal dystonia and controls were scanned during vibrotactile stimulation of both the index (digit 2) and little (digit 5) fingers of their dominant hand (which was the affected hand in all the dystonic subjects). The activation maps obtained were analysed for location, size, and magnitude of activation and three-dimensional (3-D) orientation of digit representations. Data from both groups were compared. There were significant differences in the average 3-D separation between the two digit representations in area 1 of SI between subject groups (9.6 +/- 1.2 mm for controls and 4.1 +/- 0.2 mm for dystonic subjects). There were also strong trends for reversed ordering of the representation of the two digits in both the secondary sensory cortex and posterior parietal area between the two groups. In addition, in dystonic subjects, there was significant under activation in the secondary somatosensory cortex (SII/area 40) for both digits and in the posterior parietal area for digit 5. These results indicate the presence of widespread activation abnormalities in the cortical sensory system in dystonia.

  9. Mapping of cortical activity in the first two decades of life: a high-density sleep electroencephalogram study.

    PubMed

    Kurth, Salomé; Ringli, Maya; Geiger, Anja; LeBourgeois, Monique; Jenni, Oskar G; Huber, Reto

    2010-10-06

    Evidence that electroencephalography (EEG) slow-wave activity (SWA) (EEG spectral power in the 1-4.5 Hz band) during non-rapid eye movement sleep (NREM) reflects plastic changes is increasing (Tononi and Cirelli, 2006). Regional assessment of gray matter development from neuroimaging studies reveals a posteroanterior trajectory of cortical maturation in the first three decades of life (Shaw et al., 2008). Our aim was to test whether this regional cortical maturation is reflected in regional changes of sleep SWA. We evaluated all-night high-density EEG (128 channels) in 55 healthy human subjects (2.4-19.4 years) and assessed age-related changes in NREM sleep topography. As in adults, we observed frequency-specific topographical distributions of sleep EEG power in all subjects. However, from early childhood to late adolescence, the location on the scalp showing maximal SWA underwent a shift from posterior to anterior regions. This shift along the posteroanterior axis was only present in the SWA frequency range and remained stable across the night. Changes in the topography of SWA during sleep parallel neuroimaging study findings indicating cortical maturation starts early in posterior areas and spreads rostrally over the frontal cortex. Thus, SWA might reflect the underlying processes of cortical maturation. In the future, sleep SWA assessments may be used as a clinical tool to detect aberrations in cortical maturation.

  10. cAMP-dependent protein kinase inhibits α7 nicotinic receptor activity in layer 1 cortical interneurons through activation of D1/D5 dopamine receptors

    PubMed Central

    Komal, Pragya; Estakhr, Jasem; Kamran, Melad; Renda, Anthony; Nashmi, Raad

    2015-01-01

    Phosphorylation of ion channels, including nicotinic acetylcholine receptors (nAChRs), by protein kinases plays a key role in the modification of synaptic transmission and neuronal excitability. α7 nAChRs are the second most prevalent nAChR subtype in the CNS following α4β2. Serine 365 in the M3–M4 cytoplasmic loop of the α7 nAChR is a phosphorylation site for protein kinase A (PKA). D1/D5 dopamine receptors signal through the adenylate cyclase–PKA pathway and play a key role in working memory and attention in the prefrontal cortex. Thus, we examined whether the dopaminergic system, mediated through PKA, functionally interacts with the α7-dependent cholinergic neurotransmission. In layer 1 interneurons of mouse prefrontal cortex, α7 nicotinic currents were decreased upon stimulation with 8-Br-cAMP, a PKA activator. In HEK 293T cells, dominant negative PKA abolished 8-Br-cAMP's effect of diminishing α7 nicotinic currents, while a constitutively active PKA catalytic subunit decreased α7 currents. In brain slices, the PKA inhibitor KT-5720 nullified 8-Br-cAMP's effect of attenuating α7 nicotinic responses, while applying a PKA catalytic subunit in the pipette solution decreased α7 currents. 8-Br-cAMP stimulation reduced surface expression of α7 nAChRs, but there was no change in single-channel conductance. The D1/D5 dopamine receptor agonist SKF 83822 similarly attenuated α7 nicotinic currents from layer 1 interneurons and this attenuation of nicotinic current was prevented by KT-5720. These results demonstrate that dopamine receptor-mediated activation of PKA negatively modulates nicotinic neurotransmission in prefrontal cortical interneurons, which may be a contributing mechanism of dopamine modulation of cognitive behaviours such as attention or working memory. PMID:25990637

  11. Current Physical Activity Is Independently Associated With Cortical Bone Size and Bone Strength in Elderly Swedish Women.

    PubMed

    Nilsson, Martin; Sundh, Daniel; Mellström, Dan; Lorentzon, Mattias

    2017-03-01

    Physical activity is believed to have the greatest effect on the skeleton if exerted early in life, but whether or not possible benefits of physical activity on bone microstructure or geometry remain at old age has not been investigated in women. The aim of this study was to investigate if physical activity during skeletal growth and young adulthood or at old age was associated with cortical geometry and trabecular microarchitecture in weight-bearing and non-weight-bearing bone, and areal bone mineral density (aBMD) in elderly women. In this population-based cross-sectional study 1013 women, 78.2 ± 1.6 (mean ± SD) years old, were included. Using high-resolution 3D pQCT (XtremeCT), cortical cross-sectional area (Ct.CSA), cortical thickness (Ct.Th), cortical periosteal perimeter (Ct.Pm), volumetric cortical bone density (D.Ct), trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp) were measured at the distal (14% level) and ultra-distal tibia and radius, respectively. aBMD was assessed using DXA (Hologic Discovery A) of the spine and hip. A standardized questionnaire was used to collect information about previous exercise and the Physical Activity Scale for the Elderly (PASE) was used for current physical activity. A linear regression model (including levels of exercise during skeletal growth and young adulthood [10 to 30 years of age], PASE score, and covariates) revealed that level of current physical activity was independently associated with Ct.CSA (β = 0.18, p < 0.001) and Ct.Th (β = 0.15, p < 0.001) at the distal tibia, Tb.Th (β = 0.11, p < 0.001) and BV/TV (β = 0.10, p = 0.001) at the ultra-distal tibia, and total hip aBMD (β = 0.10, p < 0.001). Current physical activity was independently associated with cortical bone size, in terms of thicker cortex but not larger periosteal circumference, and higher bone strength at the distal

  12. The relationship between brain cortical activity and brain oxygenation in the prefrontal cortex during hypergravity exposure.

    PubMed

    Smith, Craig; Goswami, Nandu; Robinson, Ryan; von der Wiesche, Melanie; Schneider, Stefan

    2013-04-01

    Artificial gravity has been proposed as a method to counteract the physiological deconditioning of long-duration spaceflight; however, the effects of hypergravity on the central nervous system has had little study. The study aims to investigate whether there is a relationship between prefrontal cortex brain activity and prefrontal cortex oxygenation during exposure to hypergravity. Twelve healthy participants were selected to undergo hypergravity exposure aboard a short-arm human centrifuge. Participants were exposed to hypergravity in the +Gz axis, starting from 0.6 +Gz for women, and 0.8 +Gz for men, and gradually increasing by 0.1 +Gz until the participant showed signs of syncope. Brain cortical activity was measured using electroencephalography (EEG) and localized to the prefrontal cortex using standard low-resolution brain electromagnetic tomography (LORETA). Prefrontal cortex oxygenation was measured using near-infrared spectroscopy (NIRS). A significant increase in prefrontal cortex activity (P < 0.05) was observed during hypergravity exposure compared with baseline. Prefrontal cortex oxygenation was significantly decreased during hypergravity exposure, with a decrease in oxyhemoglobin levels (P < 0.05) compared with baseline and an increase in deoxyhemoglobin levels (P < 0.05) with increasing +Gz level. No significant correlation was found between prefrontal cortex activity and oxy-/deoxyhemoglobin. It is concluded that the increase in prefrontal cortex activity observed during hypergravity was most likely not the result of increased +Gz values resulting in a decreased oxygenation produced through hypergravity exposure. No significant relationship between prefrontal cortex activity and oxygenation measured by NIRS concludes that brain activity during exposure to hypergravity may be difficult to measure using NIRS. Instead, the increase in prefrontal cortex activity might be attributable to psychological stress, which could pose a problem for the use of a

  13. Timing of cortical excitability changes during the reaction time of movements superimposed on tonic motor activity.

    PubMed

    Schneider, Cyril; Lavoie, Brigitte A; Barbeau, Hugues; Capaday, Charles

    2004-12-01

    Seated subjects were instructed to react to an auditory cue by simultaneously contracting the tibialis anterior (TA) muscle of each ankle isometrically. Focal transcranial magnetic stimulation of the leg area of the motor cortex (MCx) was used to determine the time course of changes in motor-evoked potential amplitude (MEP) during the reaction time (RT). In one condition the voluntary contraction was superimposed on tonic EMG activity maintained at 10% of maximal voluntary contraction. In the other condition the voluntary contraction was made starting from rest. MEPs in the TA contralateral to the stimulation coil were evoked at various times during the RT in each condition. These were compared to the control MEPs evoked during tonic voluntary activity or with the subject at rest. The RT was measured trial by trial from the EMG activity of the TA ipsilateral to the magnetic stimulus, taking into account the nearly constant time difference between the two sides. The MEPs became far greater than control MEPs during the RT (mean = 332%, SD = 44 %, of control MEPs, P < 0.001) without any measurable change in the background level of EMG activity. The onset of this facilitation occurred on average 12.80 ms (SD = 7.55 ms) before the RT. There was no difference in the onset of facilitation between the two conditions. Because MEPs were facilitated without a change in the background EMG activity, it is concluded that this facilitation is specifically due to an increase of MCx excitability just before voluntary muscle activation. This conclusion is further reinforced by the observation that MEPs evoked by near-threshold anodal stimuli to the MCx were not facilitated during the RT, in contrast to those evoked by near-threshold transcranial magnetic stimulation. However, several observations in the present and previous studies indicate that MEP amplitude may be more sensitive to alpha-motoneuron activity than to motor cortical neuron activity, an idea that has important

  14. Spatio-Temporal Progression of Cortical Activity Related to Continuous Overt and Covert Speech Production in a Reading Task

    PubMed Central

    Brumberg, Jonathan S.; Krusienski, Dean J.; Chakrabarti, Shreya; Gunduz, Aysegul; Brunner, Peter; Ritaccio, Anthony L.; Schalk, Gerwin

    2016-01-01

    How the human brain plans, executes, and monitors continuous and fluent speech has remained largely elusive. For example, previous research has defined the cortical locations most important for different aspects of speech function, but has not yet yielded a definition of the temporal progression of involvement of those locations as speech progresses either overtly or covertly. In this paper, we uncovered the spatio-temporal evolution of neuronal population-level activity related to continuous overt speech, and identified those locations that shared activity characteristics across overt and covert speech. Specifically, we asked subjects to repeat continuous sentences aloud or silently while we recorded electrical signals directly from the surface of the brain (electrocorticography (ECoG)). We then determined the relationship between cortical activity and speech output across different areas of cortex and at sub-second timescales. The results highlight a spatio-temporal progression of cortical involvement in the continuous speech process that initiates utterances in frontal-motor areas and ends with the monitoring of auditory feedback in superior temporal gyrus. Direct comparison of cortical activity related to overt versus covert conditions revealed a common network of brain regions involved in speech that may implement orthographic and phonological processing. Our results provide one of the first characterizations of the spatiotemporal electrophysiological representations of the continuous speech process, and also highlight the common neural substrate of overt and covert speech. These results thereby contribute to a refined understanding of speech functions in the human brain. PMID:27875590

  15. Cortical Activation Patterns during Long-Term Memory Retrieval of Visually or Haptically Encoded Objects and Locations

    ERIC Educational Resources Information Center

    Stock, Oliver; Roder, Brigitte; Burke, Michael; Bien, Siegfried; Rosler, Frank

    2009-01-01

    The present study used functional magnetic resonance imaging to delineate cortical networks that are activated when objects or spatial locations encoded either visually (visual encoding group, n = 10) or haptically (haptic encoding group, n = 10) had to be retrieved from long-term memory. Participants learned associations between auditorily…

  16. Cortical Regions Recruited for Complex Active-Learning Strategies and Action Planning Exhibit Rapid Reactivation during Memory Retrieval

    ERIC Educational Resources Information Center

    Voss, Joel L.; Galvan, Ashley; Gonsalves, Brian D.

    2011-01-01

    Memory retrieval can involve activity in the same sensory cortical regions involved in perception of the original event, and this neural "reactivation" has been suggested as an important mechanism of memory retrieval. However, it is still unclear if fragments of experience other than sensory information are retained and later reactivated during…

  17. Effects of Increasing Neuromuscular Electrical Stimulation Current Intensity on Cortical Sensorimotor Network Activation: A Time Domain fNIRS Study

    PubMed Central

    Zucchelli, Lucia; Perrey, Stephane; Contini, Davide; Caffini, Matteo; Spinelli, Lorenzo; Kerr, Graham; Quaresima, Valentina; Ferrari, Marco; Torricelli, Alessandro

    2015-01-01

    Neuroimaging studies have shown neuromuscular electrical stimulation (NMES)-evoked movements activate regions of the cortical sensorimotor network, including the primary sensorimotor cortex (SMC), premotor cortex (PMC), supplementary motor area (SMA), and secondary somatosensory area (S2), as well as regions of the prefrontal cortex (PFC) known to be involved in pain processing. The aim of this study, on nine healthy subjects, was to compare the cortical network activation profile and pain ratings during NMES of the right forearm wrist extensor muscles at increasing current intensities up to and slightly over the individual maximal tolerated intensity (MTI), and with reference to voluntary (VOL) wrist extension movements. By exploiting the capability of the multi-channel time domain functional near-infrared spectroscopy technique to relate depth information to the photon time-of-flight, the cortical and superficial oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin concentrations were estimated. The O2Hb and HHb maps obtained using the General Linear Model (NIRS-SPM) analysis method, showed that the VOL and NMES-evoked movements significantly increased activation (i.e., increase in O2Hb and corresponding decrease in HHb) in the cortical layer of the contralateral sensorimotor network (SMC, PMC/SMA, and S2). However, the level and area of contralateral sensorimotor network (including PFC) activation was significantly greater for NMES than VOL. Furthermore, there was greater bilateral sensorimotor network activation with the high NMES current intensities which corresponded with increased pain ratings. In conclusion, our findings suggest that greater bilateral sensorimotor network activation profile with high NMES current intensities could be in part attributable to increased attentional/pain processing and to increased bilateral sensorimotor integration in these cortical regions. PMID:26158464

  18. Large Scale Cortical Functional Networks Associated with Slow-Wave and Spindle-Burst-Related Spontaneous Activity

    PubMed Central

    McVea, David A.; Murphy, Timothy H.; Mohajerani, Majid H.

    2016-01-01

    Cortical sensory systems are active with rich patterns of activity during sleep and under light anesthesia. Remarkably, this activity shares many characteristics with those present when the awake brain responds to sensory stimuli. We review two specific forms of such activity: slow-wave activity (SWA) in the adult brain and spindle bursts in developing brain. SWA is composed of 0.5–4 Hz resting potential fluctuations. Although these fluctuations synchronize wide regions of cortex, recent large-scale imaging has shown spatial details of their distribution that reflect underlying cortical structural projections and networks. These networks are regulated, as prior awake experiences alter both the spatial and temporal features of SWA in subsequent sleep. Activity patterns of the immature brain, however, are very different from those of the adult. SWA is absent, and the dominant pattern is spindle bursts, intermittent high frequency oscillations superimposed on slower depolarizations within sensory cortices. These bursts are driven by intrinsic brain activity, which act to generate peripheral inputs, for example via limb twitches. They are present within developing sensory cortex before they are mature enough to exhibit directed movements and respond to external stimuli. Like in the adult, these patterns resemble those evoked by sensory stimulation when awake. It is suggested that spindle-burst activity is generated purposefully by the developing nervous system as a proxy for true external stimuli. While the sleep-related functions of both slow-wave and spindle-burst activity may not be entirely clear, they reflect robust regulated phenomena which can engage select wide-spread cortical circuits. These circuits are similar to those activated during sensory processing and volitional events. We highlight these two patterns of brain activity because both are prominent and well-studied forms of spontaneous activity that will yield valuable insights into brain function in

  19. Human trace fear conditioning: right-lateralized cortical activity supports trace-interval processes.

    PubMed

    Haritha, Abhishek T; Wood, Kimberly H; Ver Hoef, Lawrence W; Knight, David C

    2013-06-01

    Pavlovian conditioning requires the convergence and simultaneous activation of neural circuitry that supports conditioned stimulus (CS) and unconditioned stimulus (US) processes. However, in trace conditioning, the CS and US are separated by a period of time called the trace interval, and thus do not overlap. Therefore, determining brain regions that support associative learning by maintaining a CS representation during the trace interval is an important issue for conditioning research. Prior functional magnetic resonance imaging (fMRI) research has identified brain regions that support trace-conditioning processes. However, relatively little is known about whether this activity is specific to the trace CS, the trace interval, or both periods of time. The present study was designed to disentangle the hemodynamic response produced by the trace CS from that associated with the trace interval, in order to identify learning-related activation during these distinct components of a trace-conditioning trial. Trace-conditioned activity was observed within dorsomedial prefrontal cortex (PFC), dorsolateral PFC, insula, inferior parietal lobule (IPL), and posterior cingulate (PCC). Each of these regions showed learning-related activity during the trace CS, while trace-interval activity was only observed within a subset of these areas (i.e., dorsomedial PFC, PCC, right dorsolateral PFC, right IPL, right superior/middle temporal gyrus, and bilateral insula). Trace-interval activity was greater in right than in left dorsolateral PFC, IPL, and superior/middle temporal gyrus. These findings indicate that components of the prefrontal, cingulate, insular, and parietal cortices support trace-interval processes, as well as suggesting that a right-lateralized fronto-parietal circuit may play a unique role in trace conditioning.

  20. Revision of the DELFIC Particle Activity Module

    SciTech Connect

    Hooper, David A; Jodoin, Vincent J

    2010-09-01

    The Defense Land Fallout Interpretive Code (DELFIC) was originally released in 1968 as a tool for modeling fallout patterns and for predicting exposure rates. Despite the continual advancement of knowledge of fission yields, decay behavior of fission products, and biological dosimetry, the decay data and logic of DELFIC have remained mostly unchanged since inception. Additionally, previous code revisions caused a loss of conservation of radioactive nuclides. In this report, a new revision of the decay database and the Particle Activity Module is introduced and explained. The database upgrades discussed are replacement of the fission yields with ENDF/B-VII data as formatted in the Oak Ridge Isotope Generation (ORIGEN) code, revised decay constants, revised exposure rate multipliers, revised decay modes and branching ratios, and revised boiling point data. Included decay logic upgrades represent a correction of a flaw in the treatment of the fission yields, extension of the logic to include more complex decay modes, conservation of nuclides (including stable nuclides) at all times, and conversion of key variables to double precision for nuclide conservation. Finally, recommended future work is discussed with an emphasis on completion of the overall radiation physics upgrade, particularly for dosimetry, induced activity, decay of the actinides, and fractionation.

  1. It’s All in the Eyes: Subcortical and Cortical Activation during Grotesqueness Perception in Autism

    PubMed Central

    Zürcher, Nicole R.; Donnelly, Nick; Rogier, Ophélie; Russo, Britt; Hippolyte, Loyse; Hadwin, Julie; Lemonnier, Eric; Hadjikhani, Nouchine

    2013-01-01

    Atypical face processing plays a key role in social interaction difficulties encountered by individuals with autism. In the current fMRI study, the Thatcher illusion was used to investigate several aspects of face processing in 20 young adults with high-functioning autism spectrum disorder (ASD) and 20 matched neurotypical controls. “Thatcherized” stimuli were modified at either the eyes or the mouth and participants discriminated between pairs of faces while cued to attend to either of these features in upright and inverted orientation. Behavioral data confirmed sensitivity to the illusion and intact configural processing in ASD. Directing attention towards the eyes vs. the mouth in upright faces in ASD led to (1) improved discrimination accuracy; (2) increased activation in areas involved in social and emotional processing; (3) increased activation in subcortical face-processing areas. Our findings show that when explicitly cued to attend to the eyes, activation of cortical areas involved in face processing, including its social and emotional aspects, can be enhanced in autism. This suggests that impairments in face processing in autism may be caused by a deficit in social attention, and that giving specific cues to attend to the eye-region when performing behavioral therapies aimed at improving social skills may result in a better outcome. PMID:23342130

  2. Cortical topography of human anterior intraparietal cortex active during visually guided grasping.

    PubMed

    Frey, Scott H; Vinton, Deborah; Norlund, Roger; Grafton, Scott T

    2005-05-01

    Dexterous manual prehension requires successfully transforming sensory representations of an object's intrinsic spatial properties (e.g., shape) into motor plans for configuring the opposition space of the hand. In macaques, these sensorimotor transformations are accomplished in a circuit connecting the anterior intraparietal sulcus (area AIP) with inferior frontal cortex (area F5ab). Activation in the human anterior intraparietal sulcus (aIPS) during visually guided grasping suggests a homologue of macaque area AIP. If true, then despite individual variation in cortical topography, visually guided grasping should be consistently associated with focal activation at the junction of the IPS and postcentral sulcus. FMRI was used to test this hypothesis in 14 right-handed adults. Despite substantial variability in IPS topography, a contrast between pincer grasping vs. reaching to complex asymmetrical shapes revealed activation foci at the junction of the IPS and postcentral gyrus in all 14 individuals. This site is likely within the most superior, rostral aspect of Brodmann's area 40, corresponding to area PF or PDE as defined by von Economo and Koskinas, and area 86 as defined by Vogt and colleagues. In both humans and macaques this region appears to play a key role in visually guided grasping.

  3. Tissue-type plasminogen activator triggers the synaptic vesicle cycle in cerebral cortical neurons

    PubMed Central

    Wu, Fang; Torre, Enrique; Cuellar-Giraldo, David; Cheng, Lihong; Yi, Hong; Bichler, Edyta K; García, Paul S; Yepes, Manuel

    2015-01-01

    The active zone (AZ) is a thickening of the presynaptic membrane where exocytosis takes place. Chemical synapses contain neurotransmitter-loaded synaptic vesicles (SVs) that at rest are tethered away from the synaptic release site, but after the presynaptic inflow of Ca+2 elicited by an action potential translocate to the AZ to release their neurotransmitter load. We report that tissue-type plasminogen activator (tPA) is stored outside the AZ of cerebral cortical neurons, either intermixed with small clear-core vesicles or in direct contact with the presynaptic membrane. We found that cerebral ischemia-induced release of neuronal tPA, or treatment with recombinant tPA, recruits the cytoskeletal protein βII-spectrin to the AZ and promotes the binding of SVs to βII-spectrin, enlarging the population of SVs in proximity to the synaptic release site. This effect does not require the generation of plasmin and is followed by the recruitment of voltage gated calcium channels (VGCC) to the presynaptic terminal that leads to Ca+2-dependent synapsin I phosphorylation, freeing SVs to translocate to the AZ to deliver their neurotransmitter load. Our studies indicate that tPA activates the SV cycle and induces the structural and functional changes in the synapse that are required for successful neurotransmission. PMID:26126868

  4. Potassium channels control the interaction between active dendritic integration compartments in layer 5 cortical pyramidal neurons

    PubMed Central

    Harnett, Mark T.; Xu, Ning-Long; Magee, Jeffrey C.; Williams, Stephen R.

    2013-01-01

    Active dendritic synaptic integration enhances the computational power of neurons. Such nonlinear processing generates an object-localization signal in the apical dendritic tuft of layer 5B cortical pyramidal neurons during sensory-motor behaviour. Here we employ electrophysiological and optical approaches in brain-slices and behaving animals to investigate how excitatory synaptic input to this distal dendritic compartment influences neuronal output. We find that active dendritic integration throughout the apical dendritic tuft is highly compartmentalized by voltage-gated potassium (KV) channels. A high-density of both transient and sustained KV channels was observed in all apical dendritic compartments. These channels potently regulated the interaction between apical dendritic tuft, trunk, and axo-somatic integration zones to control neuronal output in vitro as well as the engagement of dendritic nonlinear processing in vivo during sensory-motor behaviour. Thus, KV channels dynamically tune the interaction between active dendritic integration compartments in layer 5B pyramidal neurons to shape behaviourally relevant neuronal computations. PMID:23931999

  5. EEG and FMRI coregistration to investigate the cortical oscillatory activities during finger movement.

    PubMed

    Formaggio, Emanuela; Storti, Silvia Francesca; Avesani, Mirko; Cerini, Roberto; Milanese, Franco; Gasparini, Anna; Acler, Michele; Pozzi Mucelli, Roberto; Fiaschi, Antonio; Manganotti, Paolo

    2008-12-01

    Electroencephalography combined with functional magnetic resonance imaging (EEG-fMRI) may be used to identify blood oxygenation level dependent (BOLD) signal changes associated with physiological and pathological EEG event. In this study we used EEG-fMRI to determine the possible correlation between topographical movement-related EEG changes in brain oscillatory activity recorded from EEG electrodes over the scalp and fMRI-BOLD cortical responses in motor areas during finger movement. Thirty-two channels of EEG were recorded in 9 subjects during eyes-open condition inside a 1.5 T magnetic resonance (MR) scanner using a MR-compatible EEG recording system. Off-line MRI artifact subtraction software was applied to obtain continuous EEG data during fMRI acquisition. For EEG data analysis we used the event-related-synchronization/desynchronization (ERS/ERD) approach to investigate where movement-related decreases in alpha and beta power are located. For image statistical analysis we used a general linear model (GLM) approach. There was a significant correlation between the positive-negative ratio of BOLD signal peaks and ERD values in the electrodes over the region of activation. We conclude that combined EEG-fMRI may be used to investigate movement-related oscillations of the human brain inside an MRI scanner and the movement-related changes in the EMG or EEG signals are useful to identify the brain activation sources responsible for BOLD-signal changes.

  6. Population decoding of motor cortical activity using a generalized linear model with hidden states.

    PubMed

    Lawhern, Vernon; Wu, Wei; Hatsopoulos, Nicholas; Paninski, Liam

    2010-06-15

    Generalized linear models (GLMs) have been developed for modeling and decoding population neuronal spiking activity in the motor cortex. These models provide reasonable characterizations between neural activity and motor behavior. However, they lack a description of movement-related terms which are not observed directly in these experiments, such as muscular activation, the subject's level of attention, and other internal or external states. Here we propose to include a multi-dimensional hidden state to address these states in a GLM framework where the spike count at each time is described as a function of the hand state (position, velocity, and acceleration), truncated spike history, and the hidden state. The model can be identified by an Expectation-Maximization algorithm. We tested this new method in two datasets where spikes were simultaneously recorded using a multi-electrode array in the primary motor cortex of two monkeys. It was found that this method significantly improves the model-fitting over the classical GLM, for hidden dimensions varying from 1 to 4. This method also provides more accurate decoding of hand state (reducing the mean square error by up to 29% in some cases), while retaining real-time computational efficiency. These improvements on representation and decoding over the classical GLM model suggest that this new approach could contribute as a useful tool to motor cortical decoding and prosthetic applications.

  7. Mapping cortical mesoscopic networks of single spiking cortical or sub-cortical neurons.

    PubMed

    Xiao, Dongsheng; Vanni, Matthieu P; Mitelut, Catalin C; Chan, Allen W; LeDue, Jeffrey M; Xie, Yicheng; Chen, Andrew Cn; Swindale, Nicholas V; Murphy, Timothy H

    2017-02-04

    Understanding the basis of brain function requires knowledge of cortical operations over wide-spatial scales, but also within the context of single neurons. In vivo, wide-field GCaMP imaging and sub-cortical/cortical cellular electrophysiology were used in mice to investigate relationships between spontaneous single neuron spiking and mesoscopic cortical activity. We make use of a rich set of cortical activity motifs that are present in spontaneous activity in anesthetized and awake animals. A mesoscale spike-triggered averaging procedure allowed the identification of motifs that are preferentially linked to individual spiking neurons by employing genetically targeted indicators of neuronal activity. Thalamic neurons predicted and reported specific cycles of wide-scale cortical inhibition/excitation. In contrast, spike-triggered maps derived from single cortical neurons yielded spatio-temporal maps expected for regional cortical consensus function. This approach can define network relationships between any point source of neuronal spiking and mesoscale cortical maps.

  8. Irreversible loss of a subpopulation of cortical interneurons in the absence of glutamatergic network activity.

    PubMed

    de Lima, Ana Dolabela; Opitz, Thoralf; Voigt, Thomas

    2004-06-01

    In the cerebral cortex of mammals, gamma-aminobutyric acid (GABA)ergic neurons represent 15-25% of all neurons, depending on the species and area being examined. Because converging evidence suggests that activity may play an important role in the neuritic maturation and synaptic function of GABAergic neurons, it is feasible that activity plays a role in the regulation of the proportion of GABAergic neurons. Here we provide direct evidence that early in cortical development activity blockade may deplete the network of a subpopulation of GABA immunoreactive neurons characterized by their small size and late generation in vitro. In a period of time coinciding with the emergence of synchronous network activity, the survival and morphological differentiation of GABAergic neurons was influenced by long-term blockade of synaptic activity. While GABA(A) receptor antagonists had a minor promoting effect on interneuronal survival during the second week in vitro, antagonists of ionotropic glutamate receptors strongly impaired survival and differentiation of immature GABAergic interneurons. Interneuronal loss was more severe when N-methyl-D-aspartate receptors were blocked than after blockade of alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA)/kainate receptors. The decrease in the density of GABAergic neurons was irreversible, but could be prevented by the simultaneous addition of brain-derived neurotrophic factor (BDNF). These results suggest that there is a narrow time window during neocortical development when glutamatergic activity, and specially NMDA receptor stimulation, is crucial to assure survival and maturation of a subpopulation of late developing GABAergic interneurons.

  9. Voluntary muscle and motor cortical activation during progressive exercise and passively induced hyperthermia.

    PubMed

    Périard, Julien D; Christian, Ryan J; Knez, Wade L; Racinais, Sébastien

    2014-01-01

    This study examined whether central fatigue was exacerbated by an increase in muscle contractile speed caused by passive hyperthermia (PaH) and whether exercise-induced hyperthermia (ExH) combined with related peripheral fatigue influenced this response. The ExH was induced by cycling at 60% of maximal oxygen uptake in 38°C conditions and the PaH by sitting in a 48°C climate chamber. Ten men performed brief (≈ 5 s) and sustained (30 s) maximal voluntary isometric contractions (MVCs) of the knee extensors at baseline (CON, ∼37.1°C) and during moderate (MOD, ≈ 38.5°C) and severe (SEV, ∼39.5°C) hyperthermia. Motor nerve and transcranial magnetic stimulation were used to assess voluntary muscle and cortical activation level, along with contractile properties. Brief MVC force decreased to a similar extent during SEV-ExH (-8%) and SEV-PaH (-6%; P < 0.05 versus CON). Sustained MVC force also decreased during MOD-ExH (-10%), SEV-ExH (-13%) and SEV-PaH (-7%; P < 0.01 versus CON). Motor nerve and cortical activation were reduced on reaching MOD (≈ 3%) and SEV (≈ 5%) ExH and PaH during the brief and sustained MVCs (P < 0.01 versus CON). Peak twitch force decreased on reaching SEV-ExH and SEV-PaH (P < 0.05 versus CON). Following transcranial magnetic stimulation, during the brief and sustained MVCs the peak muscle relaxation rate increased in ExH and PaH (P < 0.01 versus CON). The increase was greatest during the sustained contraction in SEV-PaH (P < 0.01), but this did not exacerbate central fatigue relative to ExH. These results indicate that during fatiguing cycling exercise in the heat, quadriceps peak relaxation rate increases. However, the centrally mediated rate of activation appears sufficient to overcome even the largest increase in muscle relaxation rate, seen during SEV-PaH.

  10. Locally formed dopamine inhibits Na sup + -K sup + -ATPase activity in rat renal cortical tubule cells

    SciTech Connect

    Seri, I.; Kone, B.C.; Gullans, S.R.; Aperia, A.; Brenner, B.M.; Ballermann, B.J. Karolinska Institute, Stockholm )

    1988-10-01

    Dopamine, generated locally from L-dopa, inhibits Na{sup +}-K{sup +}-ATPase in permeabilized rat proximal tubules under maximum transport rate conditions for sodium. To determine whether locally formed dopamine inhibits Na{sup +}-K{sup +}-ATPase activity in intact cortical tubule cells we studied the effect of L-dopa on ouabain-sensitive oxygen consumption rate ({dot Q}o{sub 2}) and {sup 86}Rb uptake in renal cortical tubule cell suspensions. L-Dopa did not affect ouabain-insensitive {dot Q}o{sub 2} or mitochondrial respiration. However, L-dopa inhibited ouabain-sensitive {dot Q}o{sub 2} in a concentration-dependent manner, with half-maximal inhibition (K{sub 0.5}) of 5 {times} 10{sup {minus}7} M and a maximal inhibition of 14.1 {plus minus} 1.5% at 10{sup {minus}4}M. L-Dopa also blunted the nystatin-stimulated {dot Q}o{sub 2} in a concentration-dependent manner, indicating the L-dopa directly inhibits Na{sup +}-K{sup +}-ATPase activity and not sodium entry. Ouabain-sensitive {sup 86}Rb uptake was also inhibited by L-dopa. Carbidopa, an inhibitor of the conversion of L-dopa to dopamine, eliminated the effect of L-dopa on ouabain-sensitive {dot Q}o{sub 2} and {sup 86}Rb uptake, indicating that dopamine rather than L-dopa was the active agent. The finding that the L-dopa concentration-response curve was shifted to the left by one order of magnitude in the presence of nystatin suggests that the inhibitory effect is enhanced when the intracellular sodium concentration is increased. By studying the effect of L-dopa on ouabain-sensitive {dot Q}o{sub 2} at increasing extracellular sodium concentrations in the presence of nystatin, the authors demonstrated that the inhibitory effect of locally formed dopamine on the Na{sup +}-K{sup +}-ATPase is indeed dependent on the sodium available for the enzyme and occurs in an uncompetitive manner.

  11. Dopamine modulates attentional control of auditory perception: DARPP-32 (PPP1R1B) genotype effects on behavior and cortical evoked potentials.

    PubMed

    Li, Shu-Chen; Passow, Susanne; Nietfeld, Wilfried; Schröder, Julia; Bertram, Lars; Heekeren, Hauke R; Lindenberger, Ulman

    2013-07-01

    Using a specific variant of the dichotic listening paradigm, we studied the influence of dopamine on attentional modulation of auditory perception by assessing effects of allelic variation of a single-nucleotide polymorphism (SNP) rs907094 in the DARPP-32 gene (dopamine and adenosine 3', 5'-monophosphate-regulated phosphoprotein 32 kilodations; also known as PPP1R1B) on behavior and cortical evoked potentials. A frequent DARPP-32 haplotype that includes the A allele of this SNP is associated with higher mRNA expression of DARPP-32 protein isoforms, striatal dopamine receptor function, and frontal-striatal connectivity. As we hypothesized, behaviorally the A homozygotes were more flexible in selectively attending to auditory inputs than any G carriers. Moreover, this genotype also affected auditory evoked cortical potentials that reflect early sensory and late attentional processes. Specifically, analyses of event-related potentials (ERPs) revealed that amplitudes of an early component of sensory selection (N1) and a late component (N450) reflecting attentional deployment for conflict resolution were larger in A homozygotes than in any G carriers. Taken together, our data lend support for dopamine's role in modulating auditory attention both during the early sensory selection and late conflict resolution stages.

  12. Bigelow Expandable Activity Module (BEAM) - ISS Inflatable Module Technology Demonstration

    NASA Technical Reports Server (NTRS)

    Dasgupta, Rajib; Munday, Steve; Valle, Gerard D.

    2014-01-01

    INNOVATION: BEAM is a pathway project demonstrating the design, fabrication, test, certification, integration, operation, on-orbit performance, and disposal of the first ever man-rated space inflatable structure. The groundwork laid through the BEAM project will support developing and launching a larger inflatable space structure with even greater mass per volume (M/V) advantages need for longer space missions. OVERVIEW: Inflatable structures have been shown to have much lower mass per volume ratios (M/V) when compared with conventional space structures. BEAM is an expandable structure, launched in a packed state, and then expanded once on orbit. It is a temporary experimental module to be used for gathering structural, thermal, and radiation data while on orbit. BEAM will be launched on Space X-8, be extracted from the dragon trunk, and will attach to ISS at Node 3- Aft. BEAM performance will be monitored over a two-year period and then BEAM will be jettison using the SSRMS.

  13. Effects of location and timing of co-activated neurons in the auditory midbrain on cortical activity: implications for a new central auditory prosthesis

    NASA Astrophysics Data System (ADS)

    Straka, Małgorzata M.; McMahon, Melissa; Markovitz, Craig D.; Lim, Hubert H.

    2014-08-01

    Objective. An increasing number of deaf individuals are being implanted with central auditory prostheses, but their performance has generally been poorer than for cochlear implant users. The goal of this study is to investigate stimulation strategies for improving hearing performance with a new auditory midbrain implant (AMI). Previous studies have shown that repeated electrical stimulation of a single site in each isofrequency lamina of the central nucleus of the inferior colliculus (ICC) causes strong suppressive effects in elicited responses within the primary auditory cortex (A1). Here we investigate if improved cortical activity can be achieved by co-activating neurons with different timing and locations across an ICC lamina and if this cortical activity varies across A1. Approach. We electrically stimulated two sites at different locations across an isofrequency ICC lamina using varying delays in ketamine-anesthetized guinea pigs. We recorded and analyzed spike activity and local field potentials across different layers and locations of A1. Results. Co-activating two sites within an isofrequency lamina with short inter-pulse intervals (<5 ms) could elicit cortical activity that is enhanced beyond a linear summation of activity elicited by the individual sites. A significantly greater extent of normalized cortical activity was observed for stimulation of the rostral-lateral region of an ICC lamina compared to the caudal-medial region. We did not identify any location trends across A1, but the most cortical enhancement was observed in supragranular layers, suggesting further integration of the stimuli through the cortical layers. Significance. The topographic organization identified by this study provides further evidence for the presence of functional zones across an ICC lamina with locations consistent with those identified by previous studies. Clinically, these results suggest that co-activating different neural populations in the rostral-lateral ICC rather

  14. Ignition's glow: Ultra-fast spread of global cortical activity accompanying local "ignitions" in visual cortex during conscious visual perception.

    PubMed

    Noy, N; Bickel, S; Zion-Golumbic, E; Harel, M; Golan, T; Davidesco, I; Schevon, C A; McKhann, G M; Goodman, R R; Schroeder, C E; Mehta, A D; Malach, R

    2015-09-01

    Despite extensive research, the spatiotemporal span of neuronal activations associated with the emergence of a conscious percept is still debated. The debate can be formulated in the context of local vs. global models, emphasizing local activity in visual cortex vs. a global fronto-parietal "workspace" as the key mechanisms of conscious visual perception. These alternative models lead to differential predictions with regard to the precise magnitude, timing and anatomical spread of neuronal activity during conscious perception. Here we aimed to test a specific aspect of these predictions in which local and global models appear to differ - namely the extent to which fronto-parietal regions modulate their activity during task performance under similar perceptual states. So far the main experimental results relevant to this debate have been obtained from non-invasive methods and led to conflicting interpretations. Here we examined these alternative predictions through large-scale intracranial measurements (Electrocorticogram - ECoG) in 43 patients and 4445 recording sites. Both ERP and broadband high frequency (50-150 Hz - BHF) responses were examined through the entire cortex during a simple 1-back visual recognition memory task. Our results reveal short latency intense visual responses, localized first in early visual cortex followed (at ∼200 ms) by higher order visual areas, but failed to show significant delayed (300 ms) visual activations. By contrast, oddball image repeat events, linked to overt motor responses, were associated with a significant increase in a delayed (300 ms) peak of BHF power in fronto-parietal cortex. Comparing BHF responses with ERP revealed an additional peak in the ERP response - having a similar latency to the well-studied P3 scalp EEG response. Posterior and temporal regions demonstrated robust visual category selectivity. An unexpected observation was that high-order visual cortex responses were essentially concurrent (at ∼200 ms

  15. Neural speech recognition: continuous phoneme decoding using spatiotemporal representations of human cortical activity

    NASA Astrophysics Data System (ADS)

    Moses, David A.; Mesgarani, Nima; Leonard, Matthew K.; Chang, Edward F.

    2016-10-01

    Objective. The superior temporal gyrus (STG) and neighboring brain regions play a key role in human language processing. Previous studies have attempted to reconstruct speech information from brain activity in the STG, but few of them incorporate the probabilistic framework and engineering methodology used in modern speech recognition systems. In this work, we describe the initial efforts toward the design of a neural speech recognition (NSR) system that performs continuous phoneme recognition on English stimuli with arbitrary vocabulary sizes using the high gamma band power of local field potentials in the STG and neighboring cortical areas obtained via electrocorticography. Approach. The system implements a Viterbi decoder that incorporates phoneme likelihood estimates from a linear discriminant analysis model and transition probabilities from an n-gram phonemic language model. Grid searches were used in an attempt to determine optimal parameterizations of the feature vectors and Viterbi decoder. Main results. The performance of the system was significantly improved by using spatiotemporal representations of the neural activity (as opposed to purely spatial representations) and by including language modeling and Viterbi decoding in the NSR system. Significance. These results emphasize the importance of modeling the temporal dynamics of neural responses when analyzing their variations with respect to varying stimuli and demonstrate that speech recognition techniques can be successfully leveraged when decoding speech from neural signals. Guided by the results detailed in this work, further development of the NSR system could have applications in the fields of automatic speech recognition and neural prosthetics.

  16. Pairing broadband noise with cortical stimulation induces extensive suppression of ascending sensory activity

    NASA Astrophysics Data System (ADS)

    Markovitz, Craig D.; Hogan, Patrick S.; Wesen, Kyle A.; Lim, Hubert H.

    2015-04-01

    Objective. The corticofugal system can alter coding along the ascending sensory pathway. Within the auditory system, electrical stimulation of the auditory cortex (AC) paired with a pure tone can cause egocentric shifts in the tuning of auditory neurons, making them more sensitive to the pure tone frequency. Since tinnitus has been linked with hyperactivity across auditory neurons, we sought to develop a new neuromodulation approach that could suppress a wide range of neurons rather than enhance specific frequency-tuned neurons. Approach. We performed experiments in the guinea pig to assess the effects of cortical stimulation paired with broadband noise (PN-Stim) on ascending auditory activity within the central nucleus of the inferior colliculus (CNIC), a widely studied region for AC stimulation paradigms. Main results. All eight stimulated AC subregions induced extensive suppression of activity across the CNIC that was not possible with noise stimulation alone. This suppression built up over time and remained after the PN-Stim paradigm. Significance. We propose that the corticofugal system is designed to decrease the brain’s input gain to irrelevant stimuli and PN-Stim is able to artificially amplify this effect to suppress neural firing across the auditory system. The PN-Stim concept may have potential for treating tinnitus and other neurological disorders.

  17. Pairing broadband noise with cortical stimulation induces extensive suppression of ascending sensory activity

    PubMed Central

    Markovitz, Craig D.; Hogan, Patrick S.; Wesen, Kyle A.; Lim, Hubert H.

    2015-01-01

    Objective The corticofugal system can alter coding along the ascending sensory pathway. Within the auditory system, electrical stimulation of the auditory cortex (AC) paired with a pure tone can cause egocentric shifts in the tuning of auditory neurons, making them more sensitive to the pure tone frequency. Since tinnitus has been linked with hyperactivity across auditory neurons, we sought to develop a new neuromodulation approach that could suppress a wide range of neurons rather than enhance specific frequency-tuned neurons. Approach We performed experiments in the guinea pig to assess the effects of cortical stimulation paired with broadband noise (PN-Stim) on ascending auditory activity within the central nucleus of the inferior colliculus (CNIC), a widely studied region for AC stimulation paradigms. Main results All eight stimulated AC regions induced extensive suppression of activity across the CNIC that was not possible with noise stimulation alone. This suppression built up over time and remained after the PN-Stim paradigm. Significance We propose that the corticofugal system is designed to decrease the brain’s input gain to irrelevant stimuli and PN-Stim is able to artificially amplify this effect to suppress neural firing across the auditory system. The PN-Stim concept may have potential for treating tinnitus and other neurological disorders. PMID:25686163

  18. Cortical Up State Activity Is Enhanced After Seizures: A Quantitative Analysis

    PubMed Central

    Gerkin, Richard C.; Clem, Roger L.; Shruti, Sonal; Kass, Robert E.; Barth, Alison L.

    2011-01-01

    In the neocortex, neurons participate in epochs of elevated activity, or Up states, during periods of quiescent wakefulness, slow-wave sleep, and general anesthesia. The regulation of firing during and between Up states is of great interest because it can reflect the underlying connectivity and excitability of neurons within the network. Automated analysis of the onset and characteristics of Up state firing across different experiments and conditions requires a robust and accurate method for Up state detection. Using measurements of membrane potential mean and variance calculated from whole-cell recordings of neurons from control and postseizure tissue, the authors have developed such a method. This quantitative and automated method is independent of cell- or condition-dependent variability in underlying noise or tonic firing activity. Using this approach, the authors show that Up state frequency and firing rates are significantly increased in layer 2/3 neocortical neurons 24 hours after chemo-convulsant-induced seizure. Down states in postseizure tissue show greater membrane-potential variance characterized by increased synaptic activity. Previously, the authors have found that postseizure increase in excitability is linked to a gain-of-function in BK channels, and blocking BK channels in vitro and in vivo can decrease excitability and eliminate seizures. Thus, the authors also assessed the effect of BK-channel antagonists on Up state properties in control and postseizure neurons. These data establish a robust and broadly applicable algorithm for Up state detection and analysis, provide a quantitative description of how prior seizures increase spontaneous firing activity in cortical networks, and show how BK-channel antagonists reduce this abnormal activity. PMID:21127407

  19. Phasic activation of the locus coeruleus enhances responses of primary sensory cortical neurons to peripheral receptive field stimulation.

    PubMed

    Waterhouse, B D; Moises, H C; Woodward, D J

    1998-04-20

    In the present study we examined the effects of phasic activation of the nucleus locus coeruleus (LC) on transmission of somatosensory information to the rat cerebral cortex. The rationale for this investigation was based on earlier findings that local microiontophoretic application of the putative LC transmitter, norepinephrine (NE), had facilitating actions on cortical neuronal responses to excitatory and inhibitory synaptic stimuli and more recent microdialysis experiments that have demonstrated increases in cortical levels of NE following phasic or tonic activation of LC. Glass micropipets were used to record the extracellular activity of single neurons in the somatosensory cortex of halothane-anesthetized rats. Somatosensory afferent pathways were activated by threshold level mechanical stimulation of the glabrous skin on the contralateral forepaw. Poststimulus time histograms were used to quantitate cortical neuronal responses before and at various time intervals after preconditioning burst activation of the ipsilateral LC. Excitatory and postexcitatory inhibitory responses to forepaw stimulation were enhanced when preceded by phasic activation of LC at conditioning intervals of 200-500 ms. These effects were anatomically specific in that they were only observed upon stimulation of brainstem sites close to (>150 micron) or within LC and were pharmacologically specific in that they were not consistently observed in animals where the LC-NE system had been disrupted by 6-OHDA pretreatment. Overall, these data suggest that following phasic activation of the LC efferent system, the efficacy of signal transmission through sensory networks in mammalian brain is enhanced.

  20. Genetic enhancement of visual learning by activation of protein kinase C pathways in small groups of rat cortical neurons.

    PubMed

    Zhang, Guo-Rong; Wang, Xiaodan; Kong, Lingxin; Lu, Xiu-Gui; Lee, Brian; Liu, Meng; Sun, Mei; Franklin, Corinna; Cook, Robert G; Geller, Alfred I

    2005-09-14

    Although learning and memory theories hypothesize that memories are encoded by specific circuits, it has proven difficult to localize learning within a cortical area. Neural network theories predict that activation of a small fraction of the neurons in a circuit can activate that circuit. Consequently, altering the physiology of a small group of neurons might potentiate a specific circuit and enhance learning, thereby localizing learning to that circuit. In this study, we activated protein kinase C (PKC) pathways in small groups of neurons in rat postrhinal (POR) cortex. We microinjected helper virus-free herpes simplex virus vectors that expressed a constitutively active PKC into POR cortex. This PKC was expressed predominantly in glutamatergic and GABAergic neurons in POR cortex. This intervention increased phosphorylation of five PKC substrates that play critical roles in neurotransmitter release (GAP-43 and dynamin) or glutamatergic neurotransmission (specific subunits of AMPA or NMDA receptors and myristoylated alanine-rich C kinase substrate). Additionally, activation of PKC pathways in cultured cortical neurons supported activation-dependent increases in release of glutamate and GABA. This intervention enhanced the learning rate and accuracy of visual object discriminations. In individual rats, the numbers of transfected neurons positively correlated with this learning. During learning, neuronal activity was increased in neurons proximal to the transfected neurons. These results demonstrate that potentiating small groups of glutamatergic and GABAergic neurons in POR cortex enhances visual object learning. More generally, these results suggest that learning can be mediated by specific cortical circuits.

  1. A role for cortical nNOS/NK1 neurons in coupling homeostatic sleep drive to EEG slow wave activity.

    PubMed

    Morairty, Stephen R; Dittrich, Lars; Pasumarthi, Ravi K; Valladao, Daniel; Heiss, Jaime E; Gerashchenko, Dmitry; Kilduff, Thomas S

    2013-12-10

    Although the neural circuitry underlying homeostatic sleep regulation is little understood, cortical neurons immunoreactive for neuronal nitric oxide synthase (nNOS) and the neurokinin-1 receptor (NK1) have been proposed to be involved in this physiological process. By systematically manipulating the durations of sleep deprivation and subsequent recovery sleep, we show that activation of cortical nNOS/NK1 neurons is directly related to non-rapid eye movement (NREM) sleep time, NREM bout duration, and EEG δ power during NREM sleep, an index of preexisting homeostatic sleep drive. Conversely, nNOS knockout mice show reduced NREM sleep time, shorter NREM bouts, and decreased power in the low δ range during NREM sleep, despite constitutively elevated sleep drive. Cortical NK1 neurons are still activated in response to sleep deprivation in these mice but, in the absence of nNOS, they are unable to up-regulate NREM δ power appropriately. These findings support the hypothesis that cortical nNOS/NK1 neurons translate homeostatic sleep drive into up-regulation of NREM δ power through an NO-dependent mechanism.

  2. Organizing Principles of Cortical Layer 6

    PubMed Central

    Briggs, Farran

    2009-01-01

    Neurons in the deepest layer of mammalian cerebral cortex are morphologically and physiological diverse and are situated in a strategic position to modulate neuronal activity locally and in other structures. The variety of neuronal circuits within which layer 6 neurons participate differs across species and cortical regions. However even amidst this diversity, common organizational features emerge. Examination of the anatomical and physiological characteristics of different classes of layer 6 neuron, each specialized to participate in distinct circuits, provides insight into the functional contributions of layer 6 neurons toward cortical information processing. PMID:20179784

  3. Effects of Amplitude Cueing on Postural Responses and Preparatory Cortical Activity of People with Parkinson’s Disease

    PubMed Central

    Smith, Beth A.; Jacobs, Jesse V.; Horak, Fay B.

    2014-01-01

    Background and Purpose Previously, we showed that persons with Parkinson’s disease (PD) were unable to modify their postural responses, which associated with cortical preparatory activity for anticipated postural perturbations.1 Here, we asked if participants with PD could modify their postural responses and cortical preparatory activity when cued to focus on increasing movement amplitude prior to a series of predictable postural perturbations. Methods Twelve participants with PD performed postural responses to 30 identical backward surface translations. We examined the effects of cueing them to focus on increasing movement amplitude by measuring postural responses (center-of-pressure (CoP) initial rate of change, automatic postural response (APR) stability, peak trunk flexion, peak ankle extension) and preparatory cortical activity (electroencephalographic (EEG) measures of contingent negative variation (CNV), alpha and beta event-related desynchronization (ERD)). Results Participants with PD modified their postural responses during the amplitude trials by increasing trunk flexion, slowing CoP initial rate of change and decreasing APR stability. However, no significant differences in CNV amplitude or alpha or beta ERD were observed with versus without amplitude cueing. Discussion and Conclusions Persons with PD were able to modify their feet-in-place postural responses with amplitude cueing. These changes were not associated with changes in cortical preparation during amplitude cue trials, suggesting that other regions or measures of brain function were responsible for changes in postural responses. Future studies are needed to determine the effects of long-term amplitude-cueing practice on cortical preparation and postural stability. PMID:25198870

  4. Electronic bypass of spinal lesions: activation of lower motor neurons directly driven by cortical neural signals

    PubMed Central

    2014-01-01

    Background Lower motor neurons in the spinal cord lose supraspinal inputs after complete spinal cord injury, leading to a loss of volitional control below the injury site. Extensive locomotor training with spinal cord stimulation can restore locomotion function after spinal cord injury in humans and animals. However, this locomotion is non-voluntary, meaning that subjects cannot control stimulation via their natural “intent”. A recent study demonstrated an advanced system that triggers a stimulator using forelimb stepping electromyographic patterns to restore quadrupedal walking in rats with spinal cord transection. However, this indirect source of “intent” may mean that other non-stepping forelimb activities may false-trigger the spinal stimulator and thus produce unwanted hindlimb movements. Methods We hypothesized that there are distinguishable neural activities in the primary motor cortex during treadmill walking, even after low-thoracic spinal transection in adult guinea pigs. We developed an electronic spinal bridge, called “Motolink”, which detects these neural patterns and triggers a “spinal” stimulator for hindlimb movement. This hardware can be head-mounted or carried in a backpack. Neural data were processed in real-time and transmitted to a computer for analysis by an embedded processor. Off-line neural spike analysis was conducted to calculate and preset the spike threshold for “Motolink” hardware. Results We identified correlated activities of primary motor cortex neurons during treadmill walking of guinea pigs with spinal cord transection. These neural activities were used to predict the kinematic states of the animals. The appropriate selection of spike threshold value enabled the “Motolink” system to detect the neural “intent” of walking, which triggered electrical stimulation of the spinal cord and induced stepping-like hindlimb movements. Conclusion We present a direct cortical “intent”-driven electronic spinal

  5. Activation of Wnt Signaling in Cortical Neurons Enhances Glucose Utilization through Glycolysis.

    PubMed

    Cisternas, Pedro; Salazar, Paulina; Silva-Álvarez, Carmen; Barros, L Felipe; Inestrosa, Nibaldo C

    2016-12-09

    The Wnt signaling pathway is critical for a number of functions in the central nervous system, including regulation of the synaptic cleft structure and neuroprotection against injury. Deregulation of Wnt signaling has been associated with several brain pathologies, including Alzheimer's disease. In recent years, it has been suggested that the Wnt pathway might act as a central integrator of metabolic signals from peripheral organs to the brain, which would represent a new role for Wnt signaling in cell metabolism. Energy metabolism is critical for normal neuronal function, which mainly depends on glucose utilization. Brain energy metabolism is important in almost all neurological disorders, to which a decrease in the capacity of the brain to utilize glucose has been linked. However, little is known about the relationship between Wnt signaling and neuronal glucose metabolism in the cellular context. In the present study, we found that acute treatment with the Wnt3a ligand induced a large increase in glucose uptake, without changes in the expression or localization of glucose transporter type 3. In addition, we observed that Wnt3a treatment increased the activation of the metabolic sensor Akt. Moreover, we observed an increase in the activity of hexokinase and in the glycolytic rate, and both processes were dependent on activation of the Akt pathway. Furthermore, we did not observe changes in the activity of glucose-6-phosphate dehydrogenase or in the pentose phosphate pathway. The effect of Wnt3a was independent of both the transcription of Wnt target genes and synaptic effects of Wnt3a. Together, our results suggest that Wnt signaling stimulates glucose utilization in cortical neurons through glycolysis to satisfy the high energy demand of these cells.

  6. Cortical activation associated with determination of depth order during transparent motion perception: A normalized integrative fMRI-MEG study.

    PubMed

    Natsukawa, Hiroaki; Kobayashi, Tetsuo

    2015-10-01

    When visual patterns drifting in different directions and/or at different speeds are superimposed on the same plane, observers perceive transparent surfaces on planes of different depths. This phenomenon is known as transparent motion perception. In this study, cortical activities were measured using functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) to reveal the cortical dynamics associated with determination of depth order during transparent motion perception. In addition, offline eye movement measurements were performed to determine the latencies of the start of both pursuit eye movements and depth attention that are important in determination of the depth order. MEG and fMRI data were analyzed by a normalized integrative fMRI-MEG method that enables reconstruction of time-varying dipole moments of activated regions from MEG signals. Statistical analysis of fMRI data was performed to identify activated regions. The activated regions were used as spatial constraints for the reconstruction using the integrative fMRI-MEG method. We focused on the period between latencies (216-405 ms) determined by eye movement experiment, which are related to determination of the depth order. The results of integrative analysis revealed that significant neural activities were observed in the visual association area, the human middle temporal area, the intraparietal sulcus, the lateral occipital cortex, and the anterior cingulate cortex between 216 and 405 ms. These results suggest that initial eye movement and accompanying cortical activations during focused duration play an important role in determining the depth order during transparent motion perception.

  7. Cortical activation in the processing of passive sentences in L1 and L2: an fMRI study.

    PubMed

    Yokoyama, Satoru; Okamoto, Hideyuki; Miyamoto, Tadao; Yoshimoto, Kei; Kim, Jungho; Iwata, Kazuki; Jeong, Hyeonjeong; Uchida, Shinya; Ikuta, Naho; Sassa, Yuko; Nakamura, Wataru; Horie, Kaoru; Sato, Shigeru; Kawashima, Ryuta

    2006-04-01

    The question of whether the bilingual brain processes a first and second language (L1 and L2, respectively) differently is a central issue in many psycholinguistic and neurolinguistic studies. This study used functional magnetic resonance imaging (fMRI) to investigate whether late bilinguals process structurally complex sentences in L1 and L2 in different cortical networks. For this purpose, we directly compared brain activity during the processing of active and passive sentences in both L1 and L2. We asked 36 healthy subjects to judge whether or not a presented sentence was semantically plausible. Both L1 and L2 activated the left hemispheric language-related regions such as the left inferior frontal, superior/middle temporal, and parietal cortices. However, we found different activation patterns between L1 and L2 in the processing of passive sentences. Passive sentences elicited greater activation than their active counterparts in the left pars triangularis, the premotor area, and the superior parietal lobule in Japanese, but not in English. Furthermore, there was a significant interaction between sentence type (active versus passive) and language (Japanese versus English) in the left pars orbitalis. The results of this study indicate that late bilinguals use similar cortical regions to comprehend both L1 and L2. However, when late bilinguals are presented with structurally complex sentences, the involvement of these regions differs between L1 and L2. These results suggest that, in addition to age of L2 acquisition and L2 proficiency, differences in grammatical construction affect cortical representation during the comprehension of L1 and L2.

  8. Pulse activity of populations of cortical neurons under microwave exposures of different intensity.

    PubMed

    Chizhenkova, R A

    2004-06-01

    In rabbit pulse flows of populations of cortical neurons were investigated prior to, during, and after 1-min microwave irradiation (wavelength 37.5 cm, power density 0.2-40 mW/cm2). It was found that the microwave irradiation produced shifts in mean values of interspike intervals and in the number of spike bursts. Peculiarities of rearrangements of pulse flows of cortical neurons were conditioned by an intensity of exposures.

  9. Space station group activities habitability module study

    NASA Technical Reports Server (NTRS)

    Nixon, David

    1986-01-01

    This study explores and analyzes architectural design approaches for the interior of the Space Station Habitability Module (originally defined as Habitability Module 1 in Space Station Reference Configuration Decription, JSC-19989, August 1984). In the Research Phase, architectural program and habitability design guidelines are specified. In the Schematic Design Phase, a range of alternative concepts is described and illustrated with drawings, scale-model photographs and design analysis evaluations. Recommendations are presented on the internal architectural, configuration of the Space Station Habitability Module for such functions as the wardroom, galley, exercise facility, library and station control work station. The models show full design configurations for on-orbit performance.

  10. EEG frequency tagging using ultra-slow periodic heat stimulation of the skin reveals cortical activity specifically related to C fiber thermonociceptors

    PubMed Central

    Colon, Elisabeth; Liberati, Giulia; Mouraux, André

    2017-01-01

    The recording of event-related brain potentials triggered by a transient heat stimulus is used extensively to study nociception and diagnose lesions or dysfunctions of the nociceptive system in humans. However, these responses are related exclusively to the activation of a specific subclass of nociceptive afferents: quickly-adapting thermonociceptors. In fact, except if the activation of Aδ fibers is avoided or if A fibers are blocked, these responses specifically reflect activity triggered by the activation of Type 2 quickly-adapting A fiber mechano-heat nociceptors (AMH-2). Here, we propose a novel method to isolate, in the human electroencephalogram (EEG), cortical activity related to the sustained periodic activation of heat-sensitive thermonociceptors, using very slow (0.2 Hz) and long-lasting (75 s) sinusoidal heat stimulation of the skin between baseline and 50°C. In a first experiment, we show that when such long-lasting thermal stimuli are applied to the hand dorsum of healthy volunteers, the slow rises and decreases of skin temperature elicit a consistent periodic EEG response at 0.2 Hz and its harmonics, as well as a periodic modulation of the magnitude of theta, alpha and beta band EEG oscillations. In a second experiment, we demonstrate using an A fiber block that these EEG responses are predominantly conveyed by unmyelinated C fiber nociceptors. The proposed approach constitutes a novel mean to study C fiber function in humans, and to explore the cortical processing of tonic heat pain in physiological and pathological conditions. PMID:27871921

  11. EEG frequency tagging using ultra-slow periodic heat stimulation of the skin reveals cortical activity specifically related to C fiber thermonociceptors.

    PubMed

    Colon, Elisabeth; Liberati, Giulia; Mouraux, André

    2017-02-01

    The recording of event-related brain potentials triggered by a transient heat stimulus is used extensively to study nociception and diagnose lesions or dysfunctions of the nociceptive system in humans. However, these responses are related exclusively to the activation of a specific subclass of nociceptive afferents: quickly-adapting thermonociceptors. In fact, except if the activation of Aδ fibers is avoided or if A fibers are blocked, these responses specifically reflect activity triggered by the activation of Type 2 quickly-adapting A fiber mechano-heat nociceptors (AMH-2). Here, we propose a novel method to isolate, in the human electroencephalogram (EEG), cortical activity related to the sustained periodic activation of heat-sensitive thermonociceptors, using very slow (0.2Hz) and long-lasting (75s) sinusoidal heat stimulation of the skin between baseline and 50°C. In a first experiment, we show that when such long-lasting thermal stimuli are applied to the hand dorsum of healthy volunteers, the slow rises and decreases of skin temperature elicit a consistent periodic EEG response at 0.2Hz and its harmonics, as well as a periodic modulation of the magnitude of theta, alpha and beta band EEG oscillations. In a second experiment, we demonstrate using an A fiber block that these EEG responses are predominantly conveyed by unmyelinated C fiber nociceptors. The proposed approach constitutes a novel mean to study C fiber function in humans, and to explore the cortical processing of tonic heat pain in physiological and pathological conditions.

  12. Movement-related cortical activation with voluntary pinch task: simultaneous monitoring of near-infrared spectroscopy signals and movement-related cortical potentials

    NASA Astrophysics Data System (ADS)

    Sato, Yosuke; Fukuda, Masafumi; Oishi, Makoto; Fujii, Yukihiko

    2012-07-01

    This study was designed to evaluate hemodynamic and electrophysiological motor cortex responses to voluntary finger pinching in humans, with simultaneous recording of near-infrared spectroscopy (NIRS) signals and movement-related cortical potentials (MRCP). Six healthy, right-handed subjects performed 100 trials of voluntary right-thumb index-finger pinching with about a 10-second interval at their own pace. Throughout the session, 48 regions over the bilateral motor cortex were assessed by NIRS, while MRCP and electromyogram (EMG) were simultaneously monitored. MRCP started 1536+/-58 ms before EMG onset and peaked 127+/-24 ms after EMG onset. NIRS data showed bilateral prefrontal cortex at 0.5+/-0.1 s before EMG onset and bilateral dorsal premotor cortex activations at 0.6+/-0.1 s before EMG onset. The hand area of the sensorimotor cortex was activated left-dominantly, seen obviously peaked at 3.7+/-0.2 s after EMG onset. The comparison between MRCP and NIRS results raised the possibility that the vascular response to neural activity occurs within 4 s with a voluntary pinch task. These results indicate that our technique allows detailed study of the motor control. Our method is a promising strategy for event-related motor control and neurovascular coupling studies.

  13. Cortical Midline Structures and Autobiographical-Self Processes: An Activation-Likelihood Estimation Meta-Analysis

    PubMed Central

    Araujo, Helder F.; Kaplan, Jonas; Damasio, Antonio

    2013-01-01

    The autobiographical-self refers to a mental state derived from the retrieval and assembly of memories regarding one’s biography. The process of retrieval and assembly, which can focus on biographical facts or personality traits or some combination thereof, is likely to vary according to the domain chosen for an experiment. To date, the investigation of the neural basis of this process has largely focused on the domain of personality traits using paradigms that contrasted the evaluation of one’s traits (self-traits) with those of another person’s (other-traits). This has led to the suggestion that cortical midline structures (CMSs) are specifically related to self states. Here, with the goal of testing this suggestion, we conducted activation-likelihood estimation (ALE) meta-analyses based on data from 28 neuroimaging studies. The ALE results show that both self-traits and other-traits engage CMSs; however, the engagement of medial prefrontal cortex is greater for self-traits than for other-traits, while the posteromedial cortex is more engaged for other-traits than for self-traits. These findings suggest that the involvement CMSs is not specific to the evaluation of one’s own traits, but also occurs during the evaluation of another person’s traits. PMID:24027520

  14. A mathematical model relating cortical oxygenated and deoxygenated hemoglobin flows and volumes to neural activity

    NASA Astrophysics Data System (ADS)

    Cornelius, Nathan R.; Nishimura, Nozomi; Suh, Minah; Schwartz, Theodore H.; Doerschuk, Peter C.

    2015-08-01

    Objective. To describe a toolkit of components for mathematical models of the relationship between cortical neural activity and space-resolved and time-resolved flows and volumes of oxygenated and deoxygenated hemoglobin motivated by optical intrinsic signal imaging (OISI). Approach. Both blood flow and blood volume and both oxygenated and deoxygenated hemoglobin and their interconversion are accounted for. Flow and volume are described by including analogies to both resistive and capacitive electrical circuit elements. Oxygenated and deoxygenated hemoglobin and their interconversion are described by generalization of Kirchhoff's laws based on well-mixed compartments. Main results. Mathematical models built from this toolkit are able to reproduce experimental single-stimulus OISI results that are described in papers from other research groups and are able to describe the response to multiple-stimuli experiments as a sublinear superposition of responses to the individual stimuli. Significance. The same assembly of tools from the toolkit but with different parameter values is able to describe effects that are considered distinctive, such as the presence or absence of an initial decrease in oxygenated hemoglobin concentration, indicating that the differences might be due to unique parameter values in a subject rather than different fundamental mechanisms.

  15. Nonlinear analysis and modeling of cortical activation and deactivation patterns in the immature fetal electrocorticogram

    NASA Astrophysics Data System (ADS)

    Schwab, Karin; Groh, Tobias; Schwab, Matthias; Witte, Herbert

    2009-03-01

    An approach combining time-continuous nonlinear stability analysis and a parametric bispectral method was introduced to better describe cortical activation and deactivation patterns in the immature fetal electroencephalogram (EEG). Signal models and data-driven investigations were performed to find optimal parameters of the nonlinear methods and to confirm the occurrence of nonlinear sections in the fetal EEG. The resulting measures were applied to the in utero electrocorticogram (ECoG) of fetal sheep at 0.7 gestation when organized sleep states were not developed and compared to previous results at 0.9 gestation. Cycling of the nonlinear stability of the fetal ECoG occurred already at this early gestational age, suggesting the presence of premature sleep states. This was accompanied by cycling of the time-variant biamplitude which reflected ECoG synchronization effects during premature sleep states associated with nonrapid eye movement sleep later in gestation. Thus, the combined nonlinear and time-variant approach was able to provide important insights into the properties of the immature fetal ECoG.

  16. Spatiotemporal imaging of cortical activation during verb generation and picture naming.

    PubMed

    Edwards, Erik; Nagarajan, Srikantan S; Dalal, Sarang S; Canolty, Ryan T; Kirsch, Heidi E; Barbaro, Nicholas M; Knight, Robert T

    2010-03-01

    One hundred and fifty years of neurolinguistic research has identified the key structures in the human brain that support language. However, neither the classic neuropsychological approaches introduced by Broca (1861) and Wernicke (1874), nor modern neuroimaging employing PET and fMRI has been able to delineate the temporal flow of language processing in the human brain. We recorded the electrocorticogram (ECoG) from indwelling electrodes over left hemisphere language cortices during two common language tasks, verb generation and picture naming. We observed that the very high frequencies of the ECoG (high-gamma, 70-160 Hz) track language processing with spatial and temporal precision. Serial progression of activations is seen at a larger timescale, showing distinct stages of perception, semantic association/selection, and speech production. Within the areas supporting each of these larger processing stages, parallel (or "incremental") processing is observed. In addition to the traditional posterior vs. anterior localization for speech perception vs. production, we provide novel evidence for the role of premotor cortex in speech perception and of Wernicke's and surrounding cortex in speech production. The data are discussed with regards to current leading models of speech perception and production, and a "dual ventral stream" hybrid of leading speech perception models is given.

  17. Comparisons between linear and nonlinear methods for decoding motor cortical activities of monkey.

    PubMed

    Xu, Kai; Wang, Yueming; Zhang, Shaomin; Zhao, Ting; Wang, Yiwen; Chen, Weidong; Zheng, Xiaoxiang

    2011-01-01

    Brain Machine Interfaces (BMI) aim at building a direct communication link between the neural system and external devices. The decoding of neuronal signals is one of the important steps in BMI systems. Existing decoding methods commonly fall into two categories, i.e., linear methods and nonlinear methods. This paper compares the performance between the two kinds of methods in the decoding of motor cortical activities of a monkey. Kalman filter (KF) is chosen as an example of linear methods, and General Regression Neural Network (GRNN) and Support Vector Regression (SVR) are two nonlinear approaches evaluated in our work. The experiments are conducted to reconstruct 2D trajectories in a center-out task. The correlation coefficient (CC) and the root mean square error (RMSE) are used to assess the performance. The experimental results show that GRNN and SVR achieve better performance than Kalman filter with average improvements of about 30% in CC and 40% in RMSE. This demonstrates that nonlinear models can better encode the relationship between the neuronal signals and response. In addition, GRNN and SVR are more effective than Kalman filter on noisy data.

  18. Acetylcholine stimulates cortical precursor cell proliferation in vitro via muscarinic receptor activation and MAP kinase phosphorylation.

    PubMed

    Ma, W; Maric, D; Li, B S; Hu, Q; Andreadis, J D; Grant, G M; Liu, Q Y; Shaffer, K M; Chang, Y H; Zhang, L; Pancrazio, J J; Pant, H C; Stenger, D A; Barker, J L

    2000-04-01

    Increasing evidence has shown that some neurotransmitters act as growth-regulatory signals during brain development. Here we report a role for the classical neurotransmitter acetylcholine (ACh) to stimulate proliferation of neural stem cells and stem cell-derived progenitor cells during neural cell lineage progression in vitro. Neuroepithelial cells in the ventricular zone of the embryonic rat cortex were found to express the m2 subtype of the muscarinic receptor. Neural precursor cells dissociated from the embryonic rat cortical neuroepithelium were expanded in culture with basic fibroblast growth factor (bFGF). reverse transcriptase-polymerase chain reaction (RT-PCR) revealed the presence of m2, m3 and m4 muscarinic receptor subtype transcripts, while immunocytochemistry demonstrated m2 protein. ACh and carbachol induced an increase in cytosolic Ca2+ and membrane currents in proliferating (BrdU+) cells, both of which were abolished by atropine. Exposure of bFGF-deprived precursor cells to muscarinic agonists not only increased both cell number and DNA synthesis, but also enhanced differentiation of neurons. These effects were blocked by atropine, indicating the involvement of muscarinic ACh receptors. The growth-stimulating effects were also antagonized by a panel of inhibitors of second messengers, including 1,2-bis-(O-aminophenoxy)-ethane-N,N,N', N'-tetraacetic acid (BAPTA-AM) to chelate cytosolic Ca2+, EGTA to complex extracellular Ca2+, pertussis toxin, which uncouples certain G-proteins, the protein kinase C inhibitor H7 and the mitogen-activated protein kinase (MAPK) inhibitor PD98059. Muscarinic agonists activated MAPK, which was significantly inhibited by atropine and the same panel of inhibitors. Thus, muscarinic receptors expressed by neural precursors transduce a growth-regulatory signal during neurogenesis via pathways involving pertussis toxin-sensitive G-proteins, Ca2+ signalling, protein kinase C activation, MAPK phosphorylation and DNA synthesis.

  19. The Voltage Activation of Cortical KCNQ Channels Depends on Global PIP2 Levels

    PubMed Central

    Kim, Kwang S.; Duignan, Kevin M.; Hawryluk, Joanna M.; Soh, Heun; Tzingounis, Anastasios V.

    2016-01-01

    The slow afterhyper