Leonardo G Cohen

National Institutes of Health | NIH · Human Cortical Physiology and Neurorehabilitation Section

Activities of daily living rely on our ability to acquire new motor skills composed of precise action sequences. Early learning of a new sequential skill is characterized by steep performance improvements that develop predominantly during rest intervals interspersed with practice, a form of rapid consolidation. Here, we ask if the millisecond level...

Activities of daily living rely on our ability to acquire new motor skills composed of precise action sequences. Early learning of a new sequential skill is characterized by steep performance improvements that develop predominantly during rest intervals interspersed with practice, a form of rapid consolidation. Here, we ask if the millisecond level...

Background and Objectives At least 15% of patients who recover from acute severe acute respiratory syndrome coronavirus 2 infection experience lasting symptoms (“Long-COVID”) including “brain fog” and deficits in declarative memory. It is not known if Long-COVID affects patients' ability to form and retain procedural motor skill memories. The objec...

Background and Aims The purpose of this Third Stroke Recovery and Rehabilitation Roundtable (SRRR3) was to develop consensus recommendations to address outstanding barriers for the translation of preclinical and clinical research using the non-invasive brain stimulation (NIBS) techniques Transcranial Magnetic Stimulation (TMS) and Transcranial Dire...

Background and Aims The purpose of this Third Stroke Recovery and Rehabilitation Roundtable (SRRR3) was to develop consensus recommendations to address outstanding barriers for the translation of preclinical and clinical research using the non-invasive brain stimulation (NIBS) techniques Transcranial Magnetic Stimulation (TMS) and Transcranial Dire...

When humans begin learning new motor skills, they typically display early rapid performance improvements. It is not well understood how knowledge acquired during this early skill learning period generalizes to new, related skills. Here, we addressed this question by investigating factors influencing generalization of early learning from a skill A t...

Human skills are composed of sequences of individual actions performed with utmost precision. When occasional errors occur, they may have serious consequences, for example, when pilots are manually landing a plane. In such cases, the ability to predict an error before it occurs would clearly be advantageous. Here, we asked whether it is possible to...

Various levels of somatotopic organization are present throughout the human nervous system. However, this organization can change when needed based on environmental demands, a phenomenon known as neuroplasticity. Neuroplasticity can occur when learning a new motor skill, adjusting to life after blindness, or following a stroke. Following an injury,...

Abundant evidence shows that consolidated memories are susceptible to modifications following their reactivation through reconsolidation. Processes of memory consolidation and reconsolidation have been commonly documented after hours or days. Motivated by studies showing rapid consolidation in early stages of skill acquisition, here we asked whethe...

Neuroplasticity follows nervous system injury in the presence or absence of rehabilitative treatments. Rehabilitative interventions can be used to modulate adaptive neuroplasticity, reducing motor impairment and improving activities of daily living in patients with brain lesions. Learning principles guide some rehabilitative interventions. While ba...

Previous work suggests that transcranial random noise stimulation (tRNS) over the prefrontal cortex could influence inhibitory control. Nevertheless, the specific neural mechanisms underlying this proposed effect have not been investigated. Here, we aimed at exploring behavioral and neurophysiological effects of tRNS applied over bilateral inferior...

Introduction Repetitive peripheral sensory stimulation (RPSS) followed by 4-hour task-specific training (TST) improves upper limb motor function in subjects with stroke who experience moderate to severe motor upper limb impairments. Here, we compared effects of RPSS vs sham followed by a shorter duration of training in subjects with moderate to sev...

Knowing when the brain learns is crucial for both the comprehension of memory formation and consolidation and for developing new training and neurorehabilitation strategies in healthy and patient populations. Recently, a rapid form of offline learning developing during short rest periods has been shown to account for most of procedural learning, le...

The introduction of rest intervals interspersed with practice strengthens wakeful consolidation of skill. The mechanisms by which the brain binds discrete action representations into consolidated, highly temporally resolved skill sequences during waking rest are not known. To address this question, we recorded magnetoencephalography (MEG) during ac...

Behavioral research in cognitive and human systems neuroscience has been largely carried out in-person in laboratory settings. Underpowering and lack of reproducibility due to small sample sizes have weakened conclusions of these investigations. In other disciplines, such as neuroeconomics and social sciences, crowdsourcing has been extensively uti...

Background Skill learning engages offline activity in the primary motor cortex (M1). Sensorimotor cortical activity oscillates between excitatory trough and inhibitory peak phases of the mu (8–12 Hz) rhythm. We recently showed that these mu phases influence the magnitude and direction of neuroplasticity induction within M1. However, the contributio...

The introduction of rest intervals interspersed with practice strengthens wakeful consolidation of skill. The mechanisms by which the brain binds discrete action representations into consolidated, highly temporally-resolved skill sequences during waking rest are not known. To address this question, we recorded magnetoencephalography (MEG) during ac...

Background: Repetitive peripheral sensory stimulation (RPSS) followed by 4- hour task-specific training improves upper limb motor function in subjects with stroke who experience moderate to severe motor upper limb impairments. Obectives: Here, we compared effects of RPSS versus sham followed by a shorter duration of training in subjects with modera...

Performance improvements during early human motor skill learning are suggested to be driven by short periods of rest during practice, at the scale of seconds. To reveal the unknown mechanisms behind these “micro-offline” gains, we leveraged the sampling power offered by online crowdsourcing (cumulative N over all experiments = 951). First, we repli...

Background: Neural oscillations reflect rapidly changing brain excitability states. We have demonstrated previously with EEG-triggered transcranial magnetic stimulation (TMS) of human motor cortex that the positive vs. negative peak of the sensorimotor μ-oscillation reflect corticospinal low-vs. high-excitability states. In vitro experiments showe...

Background: Repetitive peripheral nerve sensory stimulation (RPSS) has emerged as a potential adjuvant strategy to motor training in stroke rehabilitation. The aim of this study is to test the hypothesis that 3 h sessions of active RPSS associated with functional electrical stimulation (FES) and task-specific training (TST) distributed three times...

The beta rhythm (15–30 Hz) is a prominent signal of sensorimotor cortical activity. This rhythm is not sustained but occurs non-rhythmically as brief events of a few (1–2) oscillatory cycles. Recent work on the relationship between these events and sensorimotor performance suggests that they are the biologically relevant elements of the beta rhythm...

Objective: The majority of patients with stroke survive the acute episode and live with enduring disability. Effective therapies to support recovery of motor function after stroke are yet to be developed. Key to this development is the identification of neurophysiologic signals that mark recovery and are suitable and susceptible to interventional...

Background: Response inhibition refers to the ability to stop an on-going action quickly when it is no longer appropriate. Previous studies showed that transcranial direct current stimulation (tDCS) applied with the anode over the right inferior frontal cortex (rIFC), a critical node of the fronto-basal ganglia inhibitory network, improved respons...

Controlling advanced robotic systems with brain signals promises substantial improvements in health care, for example, to restore intuitive control of hand movements after severe stroke or spinal cord injuries (SCI). However, such integrated, brain- or neural-controlled robotic systems have yet to enter broader clinical use or daily life environmen...

Noninvasive delivery of alternating electrical currents to temporal and prefrontal brain regions improves working memory and reverses age-related changes in brain dynamics in the elderly, report Reinhart and Nguyen in this issue of Nature Neuroscience. They also report a similar effect in young adults with poor working memory performance.

The beta rhythm (15-30 Hz) is a prominent signal of sensorimotor cortical activity. This rhythm is not sustained but occurs non-rhythmically as brief events of a few (1-2) oscillatory cycles. Recent work on the relationship between these events and sensorimotor performance suggests that beta events are the biologically relevant elements of the beta...

The brain strengthens memories through consolidation, defined as resistance to interference (stabilization) or performance improvements between the end of a practice session and the beginning of the next (offline gains) [1]. Typically, consolidation has been measured hours or days after the completion of training [2], but the same concept may apply...

Working memory is our ability to select and temporarily hold information as needed for complex cognitive operations. The temporal dynamics of sustained and transient neural activity supporting the selection and holding of memory content is not known. To address this problem, we recorded magnetoencephalography in healthy participants performing a re...

Self-initiated voluntary acts, such as pressing a button, are preceded by a surface-negative electrical brain potential, the Bereitschaftspotential (BP), that can be recorded over the human scalp using electroencephalography (EEG). While the BP’s early component (BP1, generated in the supplementary and cingulate motor area) was linked to motivation...

Working memory is our ability to select and temporarily hold information as needed for complex cognitive operations. The temporal dynamics of sustained and transient neural activity supporting the selection and holding of memory content is not known. To address this problem, we recorded magnetoencephalography (MEG) in healthy participants performin...

Background: Brain-machine interfaces (BMIs) have been recently proposed as a new tool to induce functional recovery in stroke patients. Objective: Here we evaluated long-term effects of BMI training and physiotherapy in motor function of severely paralyzed chronic stroke patients 6 months after intervention. Methods: A total of 30 chronic stro...

Introduction: Peripheral sensory stimulation (PSS) administered for 2 hours prior to intensive task-oriented motor training delivered for 4 hours, over 10 days, leads to clinically significant benefits in subjects with stroke and moderate to severe upper limb motor impairment, compared to sham PSS. Whether similar results can be obtained with less...

Background: Ambulation is an essential aspect of daily living and is often impaired after brain and spinal cord injuries. Despite the implementation of standard neurorehabilitative care, locomotor recovery is often incomplete. Objective: In this randomized, sham-controlled, double-blind, parallel design study, we aimed to determine if anodal transc...

Reconsolidation theory posits that upon retrieval, consolidated memories are destabilized and need to be restabilized in order to persist. It has been suggested that experience with a competitive task immediately after memory retrieval may interrupt these restabilization processes leading to memory loss. Indeed, using a motor sequence learning para...

Stroke is the leading cause of severe lasting adult disability around the world. Despite efforts to standardize post-stroke care and rehabilitation a significant percentage of patients remain permanently disabled. Life expectancy after stroke is on the rise in part due to improvements in health care. Hence, it is necessary to develop cost efficient...

The frontal lobe plays a crucial role in human motor behavior. It is one of the last areas of the brain to mature, especially the prefrontal regions. After a brief historical perspective on the perceived dichotomy between the view of the brain as a static organ and that of a plastic, constantly changing structure, we discuss the stability/plasticit...

[This corrects the article DOI: 10.1371/journal.pbio.1002593.].

Patient F. Receiver operating characteristic (ROC) curve of the binary support vector machine (SVM) classifier. (A) Training and (B) feedback sessions. Each circle in the ROC curve space represents false positive rate (FPR) versus true positive rate (TPR) for each session. Sessions with the same coordinate points in the ROC space are represented by...

Patient F. Contingency table formed using the average of all the training sessions. S4 Table data is located at https://doi.org/10.5281/zenodo.1419151; https://doi.org/10.5281/zenodo.192398. (XLSX)

Patient F. Contingency table formed using the average of all the feedback sessions. S5 Table data is located at https://doi.org/10.5281/zenodo.1419151; https://doi.org/10.5281/zenodo.192400. (XLSX)

The link between the local structure of the primary motor cortex and motor function has been well documented. However, motor function relies on a network of interconnected brain regions and the link between the structural properties characterizing these distributed brain networks and motor function remains poorly understood. Here, we examined wheth...

Oscillatory activity within sensorimotor networks is characterized by time-varying changes in phase and power. The influence of interactions between sensorimotor oscillatory phase and power on human motor function, like corticospinal output, is unknown. We addressed this gap in knowledge by delivering transcranial magnetic stimulation (TMS) to the...

Background: Enhancement of sensory input in the form of repetitive peripheral sensory stimulation (RPSS) can enhance excitability of the motor cortex and upper limb performance. Objective: To perform a systematic review and meta-analysis of effects of RPSS compared with control stimulation on improvement of motor outcomes in the upper limb of su...

OBJECTIVE Transcranial magnetic stimulation (TMS) is extensively used in basic and clinical neuroscience. Previous work has shown substantial residual variability in TMS effects even despite use of on-line visual feedback monitoring of coil position. Here, we aimed to evaluate if off-line denoising of variability induced by neuronavigated coil posi...

Non-invasive brain stimulation (NIBS) has been widely explored as a way to safely modulate brain activity and alter human performance for nearly three decades. Research using NIBS has grown exponentially within the last decade with promising results across a variety of clinical and healthy populations. However, recent work has shown high inter-indi...

Background: Motor training alone or combined with transcranial direct current stimulation (tDCS) positioned over the motor cortex (M1) improves motor function in chronic stroke. Currently, understanding of how tDCS influences the process of motor skill learning after stroke is lacking. Objective: To assess the effects of tDCS on the stages of mo...

Self-initiated voluntary acts, such as pressing a button, are preceded by a negative electrical brain potential, the Bereitschaftspotential (BP), that can be recorded over the human scalp using electroencephalography (EEG). Up to now, the BP required to initiate voluntary acts has only been recorded under well-controlled laboratory conditions. It i...

Objective: To perform a systematic review and meta-analysis of effects of RPSS compared to control stimulation on improvement of motor impairments in the upper limb of subjects with stroke. Methods: We searched studies published between 1948 until July, 2016 and selected eight studies that applied a specific paradigm of stimulation (trains of 1 mi...

Abstract TP153: Repetitive Peripheral Sensory Stimulation in Stroke: a Systematic Review and Meta-Analysis Adriana B Conforto , Sarah Anjos , Arnaldo Silva , Juliana Conti , André G Machado , and Leonardo G Cohen Originally published22 Jan 2018Stroke. 2018;49:ATP153 Abstract Background: Enhancement of sensory input in the form of repetitive periph...

Animal models suggest that consolidated memories return to their labile state when reactivated and need to be restabilized through reconsolidation processes to persist. Consistent with this notion, post-reactivation pharmacological protein synthesis blockage results in mnemonic failure in hippocampus-dependent memories. It has been proposed that, i...

Background: Neuropsychiatric disorders are a leading source of disability and require novel treatments that target mechanisms of disease. As such disorders are thought to result from aberrant neuronal circuit activity, neuromodulation approaches are of increasing interest given their potential for manipulating circuits directly. Low intensity tran...

Background: Evolution of motor function during the first months after stroke is stereotypically bifurcated, consisting of either recovery to about 70% of maximum possible improvement ("proportional recovery, PROP") or in little to no improvement ("poor recovery, POOR"). There is currently no evidence that any rehabilitation treatment will prevent...

Being able to focus on a complex task and inhibit unwanted actions or interfering information (i.e., inhibitory control) are essential human cognitive abilities. However, it remains unknown the extent to which mild traumatic brain injury (mTBI) may impact these critical functions. In this study, seventeen patients and age-matched healthy controls (...

Introduction Interpretation of the extent of perfusion deficits in stroke MRI is highly dependent on the method used for analyzing the perfusion-weighted signal intensity time-series after gadolinium injection. In this study, we introduce a new model-free standardized method of temporal similarity perfusion (TSP) mapping for perfusion deficit detec...

Objectives: To evaluate effects of somatosensory stimulation in the form of repetitive peripheral nerve sensory stimulation (RPSS) in combination with transcranial direct current stimulation (tDCS), tDCS alone, RPSS alone, or sham RPSS + tDCS as add-on interventions to training of wrist extension with functional electrical stimulation (FES), in ch...

The link between the local structure of the primary motor cortex and motor function has been well documented. However, motor function relies on a network of interconnected brain regions and the link between the structural properties characterizing these distributed brain networks and motor function remains poorly understood. Here, we examined wheth...

Introduction: Despite the modest benefits of non-immersive virtual reality (VR) in small, single center studies, our largest trial (EVREST Muticentre) showed no significant difference in motor recovery when VR was compared to an active control. More crucial is to determine the presence of a treatment effect by evaluating respondents. Methods: Adult...

Despite partial success, communication has remained impossible for persons suffering from complete motor paralysis but intact cognitive and emotional processing, a state called complete locked-in state (CLIS). Based on a motor learning theoretical context and on the failure of neuroelectric brain–computer interface (BCI) communication attempts in C...

CWT and STFT true versus false recognition accuracies: the t-test was used to compare CWT and STFT recognition accuracies with mean fNIRS classification accuracy. S2 Table data is located at https://doi.org/10.5281/zenodo.192128. (XLSX)

Patient F. Contingency table formed using the average of all the feedback sessions. S5 Table data is located at https://doi.org/10.5281/zenodo.192400. (XLSX)

Patient B. Contingency table formed using the average of all the feedback sessions. S9 Table data is located at https://doi.org/10.5281/zenodo.192407. (XLSX)

Patient G. Contingency table formed using the average of all the training sessions. S6 Table data is located at https://doi.org/10.5281/zenodo.192401. (XLSX)

Patient B. Contingency table formed using the average of all the training sessions. S8 Table data is located at https://doi.org/10.5281/zenodo.192406. (XLSX)

A. Power spectrum density. Power spectrum density (PSD) of electroencephalographic (EEG) signal corresponding to YES (red solid trace) and NO (blue dashed trace) sentences’ ISI acquired from channel FC6 in patients F, G, B, and W. In each subplot, the x-axis is frequency in hertz and the y-axis is channel FC6 EEG in dB (μV2/Hz). S1A Fig data is loc...

Patient B. Receiver operating characteristic (ROC) curve of the binary support vector machine (SVM) classifier. The description of this figure is the same as described in S2 Fig. S4 Fig data is located at, https://doi.org/10.5281/zenodo.192406; https://doi.org/10.5281/zenodo.192407. (EPS)

EEG frequency domain analysis. (DOCX)

Receiver operating characteristic curve and semantic concordance rate. (DOCX)

Contingency table. (XLSX)

Patient F. Contingency table formed using the average of all the training sessions. S4 Table data is located at https://doi.org/10.5281/zenodo.192398. (XLSX)

Patient G. Contingency table formed using the average of all the feedback sessions. S7 Table data is located at https://doi.org/10.5281/zenodo.192402. (XLSX)