Ethan R. Buch

Noninvasive cortical stimulation enhances motor skill acquisition over multiple days through an effect on consolidation

Motor skills can take weeks to months to acquire and can diminish over time in the absence of continued practice. Thus, strategies that enhance skill acquisition or retention are of great scientific and practical interest. Here we investigated the effect of noninvasive cortical stimulation on the extended time course of learning a novel and challenging motor skill task. A skill measure was chosen to reflect shifts in the tasks speed–accuracy tradeoff function (SAF), which prevented us from falsely interpreting variations in position along an unchanged SAF as a change in skill. Subjects practiced over 5 consecutive days while receiving transcranial direct current stimulation (tDCS) over the primary motor cortex (M1). Using the skill measure, we assessed the impact of anodal (relative to sham) tDCS on both within-day (online) and between-day (offline) effects and on the rate of forgetting during a 3-month follow-up (long-term retention). There was greater total (online plus offline) skill acquisition with anodal tDCS compared to sham, which was mediated through a selective enhancement of offline effects. Anodal tDCS did not change the rate of forgetting relative to sham across the 3-month follow-up period, and consequently the skill measure remained greater with anodal tDCS at 3 months. This prolonged enhancement may hold promise for the rehabilitation of brain injury. Furthermore, these findings support the existence of a consolidation mechanism, susceptible to anodal tDCS, which contributes to offline effects but not to online effects or long-term retention.

Think to Move: a Neuromagnetic Brain-Computer Interface (BCI) System for Chronic Stroke

Background and Purpose— Stroke is a leading cause of long-term motor disability among adults. Present rehabilitative interventions are largely unsuccessful in improving the most severe cases of motor impairment, particularly in relation to hand function. Here we tested the hypothesis that patients experiencing hand plegia as a result of a single, unilateral subcortical, cortical or mixed stroke occurring at least 1 year previously, could be trained to operate a mechanical hand orthosis through a brain-computer interface (BCI). Methods— Eight patients with chronic hand plegia resulting from stroke (residual finger extension function rated on the Medical Research Council scale=0/5) were recruited from the Stroke Neurorehabilitation Clinic, Human Cortical Physiology Section of the National Institute for Neurological Disorders and Stroke (NINDS) (n=5) and the Clinic of Neurology of the University of Tübingen (n=3). Diagnostic MRIs revealed single, unilateral subcortical, cortical or mixed lesions in all patients. A magnetoencephalography-based BCI system was used for this study. Patients participated in between 13 to 22 training sessions geared to volitionally modulate &mgr; rhythm amplitude originating in sensorimotor areas of the cortex, which in turn raised or lowered a screen cursor in the direction of a target displayed on the screen through the BCI interface. Performance feedback was provided visually in real-time. Successful trials (in which the cursor made contact with the target) resulted in opening/closing of an orthosis attached to the paralyzed hand. Results— Training resulted in successful BCI control in 6 of 8 patients. This control was associated with increased range and specificity of &mgr; rhythm modulation as recorded from sensors overlying central ipsilesional (4 patients) or contralesional (2 patients) regions of the array. Clinical scales used to rate hand function showed no significant improvement after training. Conclusions— These results suggest that volitional control of neuromagnetic activity features recorded over central scalp regions can be achieved with BCI training after stroke, and used to control grasping actions through a mechanical hand orthosis.

Noninvasive brain stimulation: from physiology to network dynamics and back

Noninvasive brain stimulation techniques have been widely used for studying the physiology of the CNS, identifying the functional role of specific brain structures and, more recently, exploring large-scale network dynamics. Here we review key findings that contribute to our understanding of the mechanisms underlying the physiological and behavioral effects of these techniques. We highlight recent innovations using noninvasive stimulation to investigate global brain network dynamics and organization. New combinations of these techniques, in conjunction with neuroimaging, will further advance the utility of their application.

Cortical and subcortical interactions during action reprogramming and their related white matter pathways

The right inferior frontal gyrus (rIFG) and the presupplementary motor area (pre-SMA) have been identified with cognitive control—the top-down influence on other brain areas when nonroutine behavior is required. It has been argued that they “inhibit” habitual motor responses when environmental changes mean a different response should be made. However, whether such “inhibition” can be equated with inhibitory physiological interactions has been unclear, as has the areas’ relationship with each other and the anatomical routes by which they influence movement execution. Paired-pulse transcranial magnetic stimulation (ppTMS) was applied over rIFG and primary motor cortex (M1) or over pre-SMA and M1 to measure their interactions, at a subsecond scale, during either inhibition and reprogramming of actions or during routine action selection. Distinct patterns of functional interaction between pre-SMA and M1 and between rIFG and M1 were found that were specific to action reprogramming trials; at a physiological level, direct influences of pre-SMA and rIFG on M1 were predominantly facilitatory and inhibitory, respectively. In a subsequent experiment, it was shown that the rIFGs inhibitory influence was dependent on pre-SMA. A third experiment showed that pre-SMA and rIFG influenced M1 at two time scales. By regressing white matter fractional anisotropy from diffusion-weighted magnetic resonance images against TMS-measured functional connectivity, it was shown that short-latency (6 ms) and longer latency (12 ms) influences were mediated by cortico-cortical and subcortical pathways, respectively, with the latter passing close to the subthalamic nucleus.

Short-Latency Influence of Medial Frontal Cortex on Primary Motor Cortex during Action Selection under Conflict

Medial frontal cortex (MFC) is crucial when actions have to be inhibited, reprogrammed, or selected under conflict, but the precise mechanism by which it operates is unclear. Importantly, how and when the MFC influences the primary motor cortex (M1) during action selection is unknown. Using paired-pulse transcranial magnetic stimulation, we investigated functional connectivity between the presupplementary motor area (pre-SMA) part of MFC and M1. We found that functional connectivity increased in a manner dependent on cognitive context: pre-SMA facilitated the motor evoked-potential elicited by M1 stimulation only during action reprogramming, but not when otherwise identical actions were made in the absence of conflict. The effect was anatomically specific to pre-SMA; it was not seen when adjacent brain regions were stimulated. We discuss implications for the anatomical pathways mediating the observed effects.

A Network Centered on Ventral Premotor Cortex Exerts Both Facilitatory and Inhibitory Control over Primary Motor Cortex during Action Reprogramming

Ventral premotor cortex (PMv) is widely accepted to exert an important influence over primary motor cortex (M1) when hand movements are made. Although study of these interactions has typically focused on their excitatory nature, given its strong connections with both ventral and opercular frontal regions, one feature of the influence of PMv over M1 may be inhibitory. Paired-pulse transcranial magnetic stimulation (ppTMS) was used to examine functional interactions between human PMv and M1 during the selection and reprogramming of a naturalistic goal-directed action. One of two cylinders was illuminated on each trial. It was then grasped and picked up. On some trials, however, subjects had to reprogram the action as the illuminated cylinder was switched off and the other illuminated simultaneously with reach initiation. At a neurophysiological level, the PMv paired-pulse effect (PPE) on M1 corticospinal activity was facilitatory after the initial target presentation and during movement initiation. When reprogramming was required, however, the PPE became strongly inhibitory. This context-dependent change from facilitation to inhibition occurred within 75 ms of the change of target. Behaviorally, PMv-M1 ppTMS disrupted reprogramming. Diffusion-weighted magnetic resonance image scans were taken of each subject. Intersubject differences in the facilitation–inhibition contrast of PMv-M1 interactions were correlated with fractional anisotropy of white-matter in ventral prefrontal, premotor, and intraparietal brain areas. These results suggest that a network of brain areas centered on PMv inhibits M1 corticospinal activity associated with undesired movements when action plans change.

Rewiring the brain: potential role of the premotor cortex in motor control, learning, and recovery of function following brain injury.

The brain is a plastic organ with a capability to reorganize in response to behavior and/or injury. Following injury to the motor cortex or emergent corticospinal pathways, recovery of function depends on the capacity of surviving anatomical resources to recover and repair in response to task-specific training. One such area implicated in poststroke reorganization to promote recovery of upper extremity recovery is the premotor cortex (PMC). This study reviews the role of distinct subdivisions of PMC: dorsal (PMd) and ventral (PMv) premotor cortices as critical anatomical and physiological nodes within the neural networks for the control and learning of goal-oriented reach and grasp actions in healthy individuals and individuals with stroke. Based on evidence emerging from studies of intrinsic and extrinsic connectivity, transcranial magnetic stimulation, functional neuroimaging, and experimental studies in animals and humans, the authors propose 2 distinct patterns of reorganization that differentially engage ipsilesional and contralesional PMC. Research directions that may offer further insights into the role of PMC in motor control, learning, and poststroke recovery are also proposed. This research may facilitate neuroplasticity for maximal recovery of function following brain injury.

Non-invasive brain stimulation in neurorehabilitation: local and distant effects for motor recovery.

Non-invasive brain stimulation (NIBS) may enhance motor recovery after neurological injury through the causal induction of plasticity processes. Neurological injury, such as stroke, often results in serious long-term physical disabilities, and despite intensive therapy, a large majority of brain injury survivors fail to regain full motor function. Emerging research suggests that NIBS techniques, such as transcranial magnetic (TMS) and direct current (tDCS) stimulation, in association with customarily used neurorehabilitative treatments, may enhance motor recovery. This paper provides a general review on TMS and tDCS paradigms, the mechanisms by which they operate and the stimulation techniques used in neurorehabilitation, specifically stroke. TMS and tDCS influence regional neural activity underlying the stimulation location and also distant interconnected network activity throughout the brain. We discuss recent studies that document NIBS effects on global brain activity measured with various neuroimaging techniques, which help to characterize better strategies for more accurate NIBS stimulation. These rapidly growing areas of inquiry may hold potential for improving the effectiveness of NIBS-based interventions for clinical rehabilitation.

Distributed and causal influence of frontal operculum in task control

It has been suggested that the frontal operculum (fO) is a key node in a network for exerting control over cognitive processes. How it exerts this influence, however, has been unclear. Here, using the complementary approaches of functional MRI and transcranial magnetic stimulation, we have shown that the fO regulates increases and decreases of activity in multiple occipitotemporal cortical areas when task performance depended on directing attention to different classes of stimuli held in memory. Only one region, the fO, was significantly more active when subjects selectively attended to a single stimulus so that it determined task performance. The stimuli that guided task performance could belong to three categories—houses, body parts, and faces—associated with three occipitotemporal regions. On each trial, the pattern of functional correlation between the fO and the three occipitotemporal regions became either positive or negative, depending on which stimulus was to be attended and which ignored. Activation of the fO preceded both activity increases and decreases in the occipitotemporal cortex. The causal dependency of the distributed occipitotemporal pattern of activity increases and decreases on the fO was demonstrated by showing that transcranial magnetic stimulation–mediated interference of the fO diminished top-down selective attentional modulation in the occipitotemporal cortex, but it did not alter bottom-up activation of the same areas to the same stimuli when they were presented in isolation. The fOs prominence in cognitive control may stem from a role in regulating the level of activity of representations in posterior brain areas that are relevant or irrelevant, respectively, for response selection.

Physiological regulation of thinking: brain–computer interface (BCI) research

The discovery of event-related desynchronization (ERD) and event-related synchronization (ERS) by Pfurtscheller paved the way for the development of brain-computer interfaces (BCIs). BCIs allow control of computers or external devices with the regulation of brain activity only. Two different research traditions produced two different types of BCIs: invasive BCIs, realized with implanted electrodes in brain tissue and noninvasive BCIs using electrophysiological recordings in humans such as electroencephalography (EEG) and magnetoencephalography (MEG) and metabolic changes such as functional magnetic resonance imaging (fMRI) and near infrared spectroscopy (NIRS). Clinical applications were reserved with few exceptions for the noninvasive approach: communication with the completely paralyzed and locked-in syndrome with slow cortical potentials (SCPs), sensorimotor rhythms (SMRs), and P300 and restoration of movement and cortical reorganization in high spinal cord lesions and chronic stroke. It was demonstrated that noninvasive EEG-based BCIs allow brain-derived communication in paralyzed and locked-in patients. Movement restoration was achieved with noninvasive BCIs based on SMRs control in single cases with spinal cord lesions and chronic stroke. At present no firm conclusion about the clinical utility of BCI for the control of voluntary movement can be made. Invasive multielectrode BCIs in otherwise healthy animals allowed execution of reaching, grasping, and force variations from spike patterns and extracellular field potentials. Whether invasive approaches allow superior brain control of motor responses compared to noninvasive BCI with intelligent peripheral devices and electrical muscle stimulation and EMG feedback remains to be demonstrated. The newly developed fMRI-BCIs and NIRS-BCIs offer promise for the learned regulation of emotional disorders and also disorders of small children (in the case of NIRS).