Showing papers in "Journal of Neurophysiology in 2011"

The organization of the human cerebral cortex estimated by intrinsic functional connectivity

Abstract: Information processing in the cerebral cortex involves interactions among distributed areas. Anatomical connectivity suggests that certain areas form local hierarchical relations such as within the visual system. Other connectivity patterns, particularly among association areas, suggest the presence of large-scale circuits without clear hierarchical relations. In this study the organization of networks in the human cerebrum was explored using resting-state functional connectivity MRI. Data from 1,000 subjects were registered using surface-based alignment. A clustering approach was employed to identify and replicate networks of functionally coupled regions across the cerebral cortex. The results revealed local networks confined to sensory and motor cortices as well as distributed networks of association regions. Within the sensory and motor cortices, functional connectivity followed topographic representations across adjacent areas. In association cortex, the connectivity patterns often showed abrupt transitions between network boundaries. Focused analyses were performed to better understand properties of network connectivity. A canonical sensory-motor pathway involving primary visual area, putative middle temporal area complex (MT+), lateral intraparietal area, and frontal eye field was analyzed to explore how interactions might arise within and between networks. Results showed that adjacent regions of the MT+ complex demonstrate differential connectivity consistent with a hierarchical pathway that spans networks. The functional connectivity of parietal and prefrontal association cortices was next explored. Distinct connectivity profiles of neighboring regions suggest they participate in distributed networks that, while showing evidence for interactions, are embedded within largely parallel, interdigitated circuits. We conclude by discussing the organization of these large-scale cerebral networks in relation to monkey anatomy and their potential evolutionary expansion in humans to support cognition.

Brain activity at rest: A multiscale hierarchical functional organization

Abstract: Spontaneous brain activity was mapped with functional MRI (fMRI) in a sample of 180 subjects while in a conscious resting-state condition. With the use of independent component analysis (ICA) of each individual fMRI signal and classification of the ICA-defined components across subjects, a set of 23 resting-state networks (RNs) was identified. Functional connectivity between each pair of RNs was assessed using temporal correlation analyses in the 0.01- to 0.1-Hz frequency band, and the corresponding set of correlation coefficients was used to obtain a hierarchical clustering of the 23 RNs. At the highest hierarchical level, we found two anticorrelated systems in charge of intrinsic and extrinsic processing, respectively. At a lower level, the intrinsic system appears to be partitioned in three modules that subserve generation of spontaneous thoughts (M1a; default mode), inner maintenance and manipulation of information (M1b), and cognitive control and switching activity (M1c), respectively. The extrinsic system was found to be made of two distinct modules: one including primary somatosensory and auditory areas and the dorsal attentional network (M2a) and the other encompassing the visual areas (M2b). Functional connectivity analyses revealed that M1b played a central role in the functioning of the intrinsic system, whereas M1c seems to mediate exchange of information between the intrinsic and extrinsic systems.

Distinct functions for direct and transthalamic corticocortical connections

Abstract: Essentially all cortical areas receive thalamic inputs and send outputs to lower motor centers. Cortical areas communicate with each other by means of direct corticocortical and corticothalamocortical pathways, often organized in parallel. We distinguish these functionally, stressing that the transthalamic pathways are class 1 (formerly known as “driver”) pathways capable of transmitting information, whereas the direct pathways vary, being either class 2 (formerly known as “modulator”) or class 1. The transthalamic pathways provide a thalamic gate that can be open or closed (and otherwise more subtly modulated), and these inputs to the thalamus are generally branches of axons with motor functions. Thus the transthalamic corticocortical pathways that can be gated carry information about the cortical processing in one cortical area and also about the motor instructions currently being issued from that area and copied to other cortical areas.

Mapping brain networks in awake mice using combined optical neural control and fMRI

Abstract: Behaviors and brain disorders involve neural circuits that are widely distributed in the brain. The ability to map the functional connectivity of distributed circuits, and to assess how this connectivity evolves over time, will be facilitated by methods for characterizing the network impact of activating a specific subcircuit, cell type, or projection pathway. We describe here an approach using high-resolution blood oxygenation level-dependent (BOLD) functional MRI (fMRI) of the awake mouse brain-to measure the distributed BOLD response evoked by optical activation of a local, defined cell class expressing the light-gated ion channel channelrhodopsin-2 (ChR2). The utility of this opto-fMRI approach was explored by identifying known cortical and subcortical targets of pyramidal cells of the primary somatosensory cortex (SI) and by analyzing how the set of regions recruited by optogenetically driven SI activity differs between the awake and anesthetized states. Results showed positive BOLD responses in a distributed network that included secondary somatosensory cortex (SII), primary motor cortex (MI), caudoputamen (CP), and contralateral SI (c-SI). Measures in awake compared with anesthetized mice (0.7% isoflurane) showed significantly increased BOLD response in the local region (SI) and indirectly stimulated regions (SII, MI, CP, and c-SI), as well as increased BOLD signal temporal correlations between pairs of regions. These collective results suggest opto-fMRI can provide a controlled means for characterizing the distributed network downstream of a defined cell class in the awake brain. Opto-fMRI may find use in examining causal links between defined circuit elements in diverse behaviors and pathologies.

Indexing the graded allocation of visuospatial attention using anticipatory alpha oscillations

Abstract: Lateralization in the desynchronization of anticipatory occipitoparietal alpha (8–12 Hz) oscillations has been implicated in the allocation of selective visuospatial attention. Previous studies have demonstrated that small changes in the lateralization of alpha-band activity are predictive of behavioral performance but have not directly investigated how flexibly alpha lateralization is linked to top-down attentional goals. To address this question, we presented participants with cues providing varying degrees of spatial certainty about the location at which a target would appear. Time-frequency analysis of EEG data demonstrated that manipulating spatial certainty led to graded changes in the extent to which alpha oscillations were lateralized over the occipitoparietal cortex during the cue-target interval. We found that individual differences in alpha desynchronization contralateral to attention predicted reaction times, event-related potential measures of perceptual processing of targets, and beta-band (15–25 Hz) activity typically associated with response preparation. These results support the hypothesis that anticipatory alpha modulation is a plausible neural mechanism underlying the allocation of visuospatial attention and is under flexible top-down control.

Modulation of motor cortex neuronal networks by rTMS: comparison of local and remote effects of six different protocols of stimulation

Abstract: Repetitive transcranial magnetic stimulation (rTMS) of human motor cortex can produce long-lasting changes in the excitability of excitatory and inhibitory neuronal networks. The effects of rTMS de...

Integration of Visual and Tactile Signals From the Hand in the Human Brain: An fMRI Study

Abstract: In the non-human primate brain, a number of multisensory areas have been described where individual neurons respond to visual, tactile and bimodal visuotactile stimulation of the upper limb. It has been shown that such bimodal neurons can integrate sensory inputs in a linear or nonlinear fashion. In humans, activity in a similar set of brain regions has been associated with visuotactile stimulation of the hand. However, little is known about how these areas integrate visual and tactile information. In this functional magnetic resonance imaging experiment, we employed tactile, visual, and visuotactile stimulation of the right hand in an ecologically valid setup where participants were looking directly at their upper limb. We identified brain regions that were activated by both visual and tactile stimuli as well as areas exhibiting greater activity in the visuotactile condition than in both unisensory ones. The posterior and inferior parietal, dorsal, and ventral premotor cortices, as well as the cerebellum, all showed evidence of multisensory linear (additive) responses. Nonlinear, superadditive responses were observed in the cortex lining the left anterior intraparietal sulcus, the insula, dorsal premotor cortex, and, subcortically, the putamen. These results identify a set of candidate frontal, parietal and subcortical regions that integrate visual and tactile information for the multisensory perception of one's own hand.

Time course of the induction of homeostatic plasticity generated by repeated transcranial direct current stimulation of the human motor cortex.

Abstract: Several mechanisms have been proposed that control the amount of plasticity in neuronal circuits and guarantee dynamic stability of neuronal networks. Homeostatic plasticity suggests that the ease ...

Neural decoding of treadmill walking from noninvasive electroencephalographic signals.

Abstract: Chronic recordings from ensembles of cortical neurons in primary motor and somatosensory areas in rhesus macaques provide accurate information about bipedal locomotion (Fitzsimmons NA, Lebedev MA, Peikon ID, Nicolelis MA. Front Integr Neurosci 3: 3, 2009). Here we show that the linear and angular kinematics of the ankle, knee, and hip joints during both normal and precision (attentive) human treadmill walking can be inferred from noninvasive scalp electroencephalography (EEG) with decoding accuracies comparable to those from neural decoders based on multiple single-unit activities (SUAs) recorded in nonhuman primates. Six healthy adults were recorded. Participants were asked to walk on a treadmill at their self-selected comfortable speed while receiving visual feedback of their lower limbs (i.e., precision walking), to repeatedly avoid stepping on a strip drawn on the treadmill belt. Angular and linear kinematics of the left and right hip, knee, and ankle joints and EEG were recorded, and neural decoders were designed and optimized with cross-validation procedures. Of note, the optimal set of electrodes of these decoders were also used to accurately infer gait trajectories in a normal walking task that did not require subjects to control and monitor their foot placement. Our results indicate a high involvement of a fronto-posterior cortical network in the control of both precision and normal walking and suggest that EEG signals can be used to study in real time the cortical dynamics of walking and to develop brain-machine interfaces aimed at restoring human gait function.

A spatial explicit strategy reduces error but interferes with sensorimotor adaptation

Abstract: Although sensorimotor adaptation is typically thought of as an implicit form of learning, it has been shown that participants who gain explicit awareness of the nature of the perturbation during adaptation exhibit more learning than those who do not With rare exceptions, however, explicit awareness is typically polled at the end of the study Here, we provided participants with either an explicit spatial strategy or no instructions before learning Early in learning, explicit instructions greatly reduced movement errors but also resulted in increased trial-to-trial variability and longer reaction times Late in adaptation, performance was indistinguishable between the explicit and implicit groups, but the mechanisms underlying performance improvements remained fundamentally different, as revealed by catch trials The progression of implicit recalibration in the explicit group was modulated by the use of an explicit strategy: these participants showed a lower level of recalibration as well as decreased aftereffects This phenomenon may be due to the reduced magnitude of errors made to the target during adaptation or inhibition of implicit learning mechanisms by explicit processing

Removal of Spurious Correlations Between Spikes and Local Field Potentials

Abstract: Single neurons carry out important sensory and motor functions related to the larger networks in which they are embedded. Understanding the relationships between single-neuron spiking and network a...

Cross-orientation suppression in human visual cortex

Abstract: Cross-orientation suppression was measured in human primary visual cortex (V1) to test the normalization model. Subjects viewed vertical target gratings (of varying contrasts) with or without a superimposed horizontal mask grating (fixed contrast). We used functional magnetic resonance imaging (fMRI) to measure the activity in each of several hypothetical channels (corresponding to subpopulations of neurons) with different orientation tunings and fit these orientation-selective responses with the normalization model. For the V1 channel maximally tuned to the target orientation, responses increased with target contrast but were suppressed when the horizontal mask was added, evident as a shift in the contrast gain of this channel's responses. For the channel maximally tuned to the mask orientation, a constant baseline response was evoked for all target contrasts when the mask was absent; responses decreased with increasing target contrast when the mask was present. The normalization model provided a good fit to the contrast-response functions with and without the mask. In a control experiment, the target and mask presentations were temporally interleaved, and we found no shift in contrast gain, i.e., no evidence for suppression. We conclude that the normalization model can explain cross-orientation suppression in human visual cortex. The approach adopted here can be applied broadly to infer, simultaneously, the responses of several subpopulations of neurons in the human brain that span particular stimulus or feature spaces, and characterize their interactions. In addition, it allows us to investigate how stimuli are represented by the inferred activity of entire neural populations.

Common muscle synergies for control of center of mass and force in nonstepping and stepping postural behaviors

Abstract: We investigated muscle activity, ground reaction forces, and center of mass (CoM) acceleration in two different postural behaviors for standing balance control in humans to determine whether common neural mechanisms are used in different postural tasks. We compared nonstepping responses, where the base of support is stationary and balance is recovered by returning CoM back to its initial position, with stepping responses, where the base of support is enlarged and balance is recovered by pushing the CoM away from the initial position. In response to perturbations of the same direction, these two postural behaviors resulted in different muscle activity and ground reaction forces. We hypothesized that a common pool of muscle synergies producing consistent task-level biomechanical functions is used to generate different postural behaviors. Two sets of support-surface translations in 12 horizontal-plane directions were presented, first to evoke stepping responses and then to evoke nonstepping responses. Electromyographs in 16 lower back and leg muscles of the stance leg were measured. Initially (∼100-ms latency), electromyographs, CoM acceleration, and forces were similar in nonstepping and stepping responses, but these diverged in later time periods (∼200 ms), when stepping occurred. We identified muscle synergies using non-negative matrix factorization and functional muscle synergies that quantified correlations between muscle synergy recruitment levels and biomechanical outputs. Functional muscle synergies that produce forces to restore CoM position in nonstepping responses were also used to displace the CoM during stepping responses. These results suggest that muscle synergies represent common neural mechanisms for CoM movement control under different dynamic conditions: stepping and nonstepping postural responses.

Impulses of activation but not motor modules are preserved in the locomotion of subacute stroke patients

Abstract: It has been hypothesized that the coordinated activation of muscles is controlled by the central nervous system by means of a small alphabet of control signals (also referred to as activation signa...

Consistency of muscle synergies during pedaling across different mechanical constraints

Abstract: The purpose of the present study was to determine whether muscle synergies are constrained by changes in the mechanics of pedaling. The decomposition algorithm used to identify muscle synergies was...

Neural correlates of cognitive control of reaching movements in the dorsal premotor cortex of rhesus monkeys

Abstract: Canceling a pending movement is a hallmark of voluntary behavioral control because it allows us to quickly adapt to unattended changes either in the external environment or in our thoughts. The countermanding paradigm allows the study of inhibitory processes of motor acts by requiring the subject to withhold planned movements in response to an infrequent stop-signal. At present the neural processes underlying the inhibitory control of arm movements are mostly unknown. We recorded the activity of single units in the rostral and caudal portion of the dorsal premotor cortex (PMd) of monkeys trained in a countermanding reaching task. We found that among neurons with a movement-preparatory activity, about one-third exhibit a modulation before the behavioral estimate of the time it takes to cancel a planned movement. Hence these neurons exhibit a pattern of activity suggesting that PMd plays a critical role in the brain networks involved in the control of arm movement initiation and suppression.

A closed-loop human simulator for investigating the role of feedback control in brain-machine interfaces

Abstract: Neural prosthetic systems seek to improve the lives of severely disabled people by decoding neural activity into useful behavioral commands. These systems and their decoding algorithms are typically developed “offline,” using neural activity previously gathered from a healthy animal, and the decoded movement is then compared with the true movement that accompanied the recorded neural activity. However, this offline design and testing may neglect important features of a real prosthesis, most notably the critical role of feedback control, which enables the user to adjust neural activity while using the prosthesis. We hypothesize that understanding and optimally designing high-performance decoders require an experimental platform where humans are in closed-loop with the various candidate decode systems and algorithms. It remains unexplored the extent to which the subject can, for a particular decode system, algorithm, or parameter, engage feedback and other strategies to improve decode performance. Closed-loop testing may suggest different choices than offline analyses. Here we ask if a healthy human subject, using a closed-loop neural prosthesis driven by synthetic neural activity, can inform system design. We use this online prosthesis simulator (OPS) to optimize “online” decode performance based on a key parameter of a current state-of-the-art decode algorithm, the bin width of a Kalman filter. First, we show that offline and online analyses indeed suggest different parameter choices. Previous literature and our offline analyses agree that neural activity should be analyzed in bins of 100- to 300-ms width. OPS analysis, which incorporates feedback control, suggests that much shorter bin widths (25–50 ms) yield higher decode performance. Second, we confirm this surprising finding using a closed-loop rhesus monkey prosthetic system. These findings illustrate the type of discovery made possible by the OPS, and so we hypothesize that this novel testing approach will help in the design of prosthetic systems that will translate well to human patients.

The influence of predicted arm biomechanics on decision making.

Abstract: There is considerable debate on the extent to which biomechanical properties of movements are taken into account before and during voluntary movements. For example, while several models have descri...

Molecular basis for the high THIP/gaboxadol sensitivity of extrasynaptic GABAA receptors

Abstract: Extrasynaptic GABAA receptors (eGABARs) allow ambient GABA to tonically regulate neuronal excitability and are implicated as targets for ethanol and anesthetics. These receptors are thought to be h...

Changes in the neural control of a complex motor sequence during learning

Abstract: The acquisition of complex motor sequences often proceeds through trial-and-error learning, requiring the deliberate exploration of motor actions and the concomitant evaluation of the resulting performance. Songbirds learn their song in this manner, producing highly variable vocalizations as juveniles. As the song improves, vocal variability is gradually reduced until it is all but eliminated in adult birds. In the present study we examine how the motor program underlying such a complex motor behavior evolves during learning by recording from the robust nucleus of the arcopallium (RA), a motor cortex analog brain region. In young birds, neurons in RA exhibited highly variable firing patterns that throughout development became more precise, sparse, and bursty. We further explored how the developing motor program in RA is shaped by its two main inputs: LMAN, the output nucleus of a basal ganglia-forebrain circuit, and HVC, a premotor nucleus. Pharmacological inactivation of LMAN during singing made the song-aligned firing patterns of RA neurons adultlike in their stereotypy without dramatically affecting the spike statistics or the overall firing patterns. Removing the input from HVC, on the other hand, resulted in a complete loss of stereotypy of both the song and the underlying motor program. Thus our results show that a basal ganglia-forebrain circuit drives motor exploration required for trial-and-error learning by adding variability to the developing motor program. As learning proceeds and the motor circuits mature, the relative contribution of LMAN is reduced, allowing the premotor input from HVC to drive an increasingly stereotyped song.

Endogenous modulation of low frequency oscillations by temporal expectations

Abstract: Recent studies have associated increasing temporal expectations with synchronization of higher frequency oscillations and suppression of lower frequencies. In this experiment, we explore a proposal that low-frequency oscillations provide a mechanism for regulating temporal expectations. We used a speeded Go/No-go task and manipulated temporal expectations by changing the probability of target presentation after certain intervals. Across two conditions, the temporal conditional probability of target events differed substantially at the first of three possible intervals. We found that reactions times differed significantly at this first interval across conditions, decreasing with higher temporal expectations. Interestingly, the power of theta activity (4–8 Hz), distributed over central midline sites, also differed significantly across conditions at this first interval. Furthermore, we found a transient coupling between theta phase and beta power after the first interval in the condition with high temporal expectation for targets at this time point. Our results suggest that the adjustments in theta power and the phase-power coupling between theta and beta contribute to a central mechanism for controlling neural excitability according to temporal expectations.

Probing for hemispheric specialization for motor skill learning: a transcranial direct current stimulation study.

Abstract: Convergent findings point to a left-sided specialization for the representation of learned actions in right-handed humans, but it is unknown whether analogous hemispheric specialization exists for motor skill learning. In the present study, we explored this question by comparing the effects of anodal transcranial direct current stimulation (tDCS) over either left or right motor cortex (M1) on motor skill learning in either hand, using a tDCS montage to better isolate stimulation to one hemisphere. Results were compared with those previously found with a montage more commonly used in the field. Six groups trained for three sessions on a visually guided sequential pinch force modulation task with their right or left hand and received right M1, left M1, or sham tDCS. A linear mixed-model analysis for motor skill showed a significant main effect for stimulation group (left M1, right M1, sham) but not for hand (right, left) or their interaction. Left M1 tDCS induced significantly greater skill learning than sham when hand data were combined, a result consistent not only with the hypothesized left hemisphere specialization for motor skill learning but also with possible increased left M1 responsiveness to tDCS. The unihemispheric montage effect size was one-half that of the more common montage, and subsequent power analysis indicated that 75 subjects per group would be needed to detect differences seen with only 12 subjects with the customary bihemispheric montage.

Subglottal pressure, tracheal airflow, and intrinsic laryngeal muscle activity during rat ultrasound vocalization.

Abstract: Vocal production requires complex planning and coordination of respiratory, laryngeal, and vocal tract movements, which are incompletely understood in most mammals. Rats produce a variety of whistles in the ultrasonic range that are of communicative relevance and of importance as a model system, but the sources of acoustic variability were mostly unknown. The goal was to identify sources of fundamental frequency variability. Subglottal pressure, tracheal airflow, and electromyographic (EMG) data from two intrinsic laryngeal muscles were measured during 22-kHz and 50-kHz call production in awake, spontaneously behaving adult male rats. During ultrasound vocalization, subglottal pressure ranged between 0.8 and 1.9 kPa. Pressure differences between call types were not significant. The relation between fundamental frequency and subglottal pressure within call types was inconsistent. Experimental manipulations of subglottal pressure had only small effects on fundamental frequency. Tracheal airflow patterns were also inconsistently associated with frequency. Pressure and flow seem to play a small role in regulation of fundamental frequency. Muscle activity, however, is precisely regulated and very sensitive to alterations, presumably because of effects on resonance properties in the vocal tract. EMG activity of cricothyroid and thyroarytenoid muscle was tonic in calls with slow or no fundamental frequency modulations, like 22-kHz and flat 50-kHz calls. Both muscles showed brief high-amplitude, alternating bursts at rates up to 150 Hz during production of frequency-modulated 50-kHz calls. A differentiated and fine regulation of intrinsic laryngeal muscles is critical for normal ultrasound vocalization. Many features of the laryngeal muscle activation pattern during ultrasound vocalization in rats are shared with other mammals.

Relationships among low-frequency local field potentials, spiking activity, and three-dimensional reach and grasp kinematics in primary motor and ventral premotor cortices.

Abstract: A prominent feature of motor cortex field potentials during movement is a distinctive low-frequency local field potential (lf-LFP) (<4 Hz), referred to as the movement event-related potential (mEP)...

Motoneuron excitability and muscle spasms are regulated by 5-HT2B and 5-HT2C receptor activity.

Abstract: Immediately after spinal cord injury (SCI), a devastating paralysis results from the loss of brain stem and cortical innervation of spinal neurons that control movement, including a loss of seroton...

Modules in the brain stem and spinal cord underlying motor behaviors

Abstract: Previous studies using intact and spinalized animals have suggested that coordinated movements can be generated by appropriate combinations of muscle synergies controlled by the central nervous sys...

Pain-related deactivation of medial prefrontal cortical neurons involves mGluR1 and GABAA receptors

Abstract: Pain-related hyperactivity in the amygdala leads to deactivation of the medial prefrontal cortex (mPFC) and decision-making deficits. The mechanisms of pain-related inhibition of the mPFC are not y...

Regression-Based Identification of Behavior-Encoding Neurons During Large-Scale Optical Imaging of Neural Activity at Cellular Resolution

Abstract: The advent of methods for optical imaging of large-scale neural activity at cellular resolution in behaving animals presents the problem of identifying behavior-encoding cells within the resulting image time series. Rapid and precise identification of cells with particular neural encoding would facilitate targeted activity measurements and perturbations useful in characterizing the operating principles of neural circuits. Here we report a regression-based approach to semiautomatically identify neurons that is based on the correlation of fluorescence time series with quantitative measurements of behavior. The approach is illustrated with a novel preparation allowing synchronous eye tracking and two-photon laser scanning fluorescence imaging of calcium changes in populations of hindbrain neurons during spontaneous eye movement in the larval zebrafish. Putative velocity-to-position oculomotor integrator neurons were identified that showed a broad spatial distribution and diversity of encoding. Optical identification of integrator neurons was confirmed with targeted loose-patch electrical recording and laser ablation. The general regression-based approach we demonstrate should be widely applicable to calcium imaging time series in behaving animals.

Behavioral correlates of human hippocampal delta and theta oscillations during navigation

Abstract: Previous rodent studies demonstrate movement-related increases in theta oscillations, and recent evidence suggests that multiple navigationally relevant variables are reflected in this activity. Hu...

Slow and fast rhythms generated in the cerebral cortex of the anesthetized mouse.

Abstract: A characterization of the oscillatory activity in the cerebral cortex of the mouse was realized under ketamine anesthesia. Bilateral recordings were obtained from deep layers of primary visual, som...