Sports-Related Concussion in Collegiate Athletes: The Potential Benefits of Using Graded Neuropsychological Tests With High Ceilings.

OBJECTIVE: Sports-related concussion management in collegiate athletes has been focused on return-to-play. However, resuming schoolwork without a gradual stepwise reintroduction contributes to symptom exacerbation, delayed recovery, and adverse academic performance. Return-to-learn guidelines are limited by a lack of sensitivity in methods monitoring cognitive function. This study evaluated 2 neuropsychological tests, the Sternberg test and the Paced Auditory Serial Addition Test (PASAT), with high ceilings for sensitivity to deficits in speed of information processing, cognitive efficiency, and complex attention. SETTING: Academic center research laboratory. PARTICIPANTS: We recruited 56 male and female collegiate contact and noncontact sports athletes. They were categorized into as follows: (1) nonconcussed (n = 23; 7F, 16M); (2) chronic (n = 21; 4F, 17M), at least 1 year from their last concussion; and (3) acute (n = 12; 1F, 11M), within 2 weeks from concussion. DESIGN: Observational cohort study. MAIN MEASURES: The PASAT assesses complex attention. The Sternberg test examines processing speed and cognitive efficiency. Cognitive difficulty increases with progression through the tasks for both the PASAT and the Sternberg test. The mean outcome differences of the 3 groups (nonconcussed, acute, and chronic) across the 3 or 4 conditions (difficulty level) were measured with repeated-measures analysis of variance and subsequent pairwise comparison. RESULTS: For processing speed (Sternberg reaction time), the acute group responded slower than the chronic group on the medium (P = .021, Bonferroni corrected) and hard difficulty tasks (P = .030, Bonferroni corrected). For cognitive efficiency (Sternberg reaction time variability), the acute group had increased reaction time variability compared with the chronic group on the medium difficulty task (P = .04, Bonferroni corrected). For complex attention (PASAT omissions), there was a difference between the acute and nonconcussed groups on the moderate-hard difficulty trial (P = .023, least significant difference [LSD] corrected) and between the acute and chronic groups for hard difficulty trial (P = .020, LSD corrected). The acute group performed worse, with progressively shorter interstimulus intervals. CONCLUSION: Neuropsychological testing without ceiling effects can capture higher-level cognitive dysfunction and use of such tests can contribute to the understanding of how collegiate athletes are affected by SRC. Future studies can investigate optimal testing batteries that include neuropsychological testing with high ceilings and whether the pattern of performance has implications for the return-to-learn process after SRC in the college setting.

Altered corticomotor latencies but normal motor neuroplasticity in concussed athletes.

Persistent cognitive, affective, and motor symptoms have been associated with sports-related concussions including several neurophysiological changes in the primary motor cortex. In particular, previous research has provided some evidence of altered latencies of the corticomotor pathway and altered motor neuroplasticity. However, to date, no studies have assessed these neurophysiological metrics in a common group of athletes across different phases of injury and recovery. In this study corticomotor latencies and neuroplasticity were assessed in collegiate athletes with or without a history of prior concussion across two different phases of injury: either in an acute state of concussion (within 2 wk of injury) or in a chronic state of concussion (more than 1 yr after injury). Corticomotor latencies were determined by measuring the motor evoked potential (MEP) onset time, and motor neuroplasticity was assessed by measuring MEP amplitudes following application of anodal transcranial direct current stimulation (tDCS) over the primary motor cortex (M1). We found that concussed athletes had slower corticomotor latencies than nonconcussed athletes, and corticomotor latency was also positively correlated with the number of prior concussions. In contrast, there was no evidence of altered motor neuroplasticity in athletes regardless of concussion history. These findings suggest concussions may lead to permanent changes in the corticospinal tract that are exacerbated by repeated injury.NEW & NOTEWORTHY We are the first to assess corticomotor latencies and motor neuroplasticity in a common group of collegiate athletes across different phases of injury and recovery. We found that the number of concussions an individual sustains negatively impacts corticomotor latencies with a higher number of prior concussions correlating positively with longer latencies. Our findings indicate that concussions may lead to permanent changes in the corticospinal tract that are exacerbated by repeated injury.

Transcranial Direct Current Stimulation in Pediatric Motor Disorders: A Systematic Review and Meta-analysis.

OBJECTIVE: To systematically examine the safety and effectiveness of transcranial direct current stimulation (tDCS) interventions in pediatric motor disorders. DATA SOURCES: PubMed, EMBASE, Cochrane, CINAHL, Web of Science, and ProQuest databases were searched from inception to August 2018. STUDY SELECTION: tDCS randomized controlled trials (RCTs), observational studies, conference proceedings, and dissertations in pediatric motor disorders were included. Two authors independently screened articles based on predefined inclusion criteria. DATA EXTRACTION: Data related to participant demographics, intervention, and outcomes were extracted by 2 authors. Quality assessment was independently performed by 2 authors. DATA SYNTHESIS: A total of 23 studies involving a total of 391 participants were included. There was no difference in dropout rates between active (1 of 144) and sham (1 of 144) tDCS groups, risk difference 0.0, 95% confidence interval (-.05 to .04). Across studies, the most common adverse effects in the active group were tingling (17.2%), discomfort (8.02%), itching (6.79%), and skin redness (4%). Across 3 studies in children with cerebral palsy, tDCS significantly improved gait velocity (MD=.23; 95% confidence interval [0.13-0.34]; P<.0005), stride length (MD=0.10; 95% confidence interval [0.05-0.15]; P<.0005), and cadence (MD=15.7; 95% confidence interval [9.72-21.68]; P<.0005). Mixed effects were found on balance, upper extremity function, and overflow movements in dystonia. CONCLUSION: Based on the studies reviewed, tDCS is a safe technique in pediatric motor disorders and may improve some gait measures and involuntary movements. Research to date in pediatric motor disorders shows limited effectiveness in improving balance and upper extremity function. tDCS may serve as a potential adjunct to pediatric rehabilitation; to better understand if tDCS is beneficial for pediatric motor disorders, more well-designed RCTs are needed.

Cerebellar direct current stimulation enhances on-line motor skill acquisition through an effect on accuracy.

The cerebellum is involved in the update of motor commands during error-dependent learning. Transcranial direct current stimulation (tDCS), a form of noninvasive brain stimulation, has been shown to increase cerebellar excitability and improve learning in motor adaptation tasks. Although cerebellar involvement has been clearly demonstrated in adaptation paradigms, a type of task that heavily relies on error-dependent motor learning mechanisms, its role during motor skill learning, a behavior that likely involves error-dependent as well as reinforcement and strategic mechanisms, is not completely understood. Here, in humans, we delivered cerebellar tDCS to modulate its activity during novel motor skill training over the course of 3 d and assessed gains during training (on-line effects), between days (off-line effects), and overall improvement. We found that excitatory anodal tDCS applied over the cerebellum increased skill learning relative to sham and cathodal tDCS specifically by increasing on-line rather than off-line learning. Moreover, the larger skill improvement in the anodal group was predominantly mediated by reductions in error rate rather than changes in movement time. These results have important implications for using cerebellar tDCS as an intervention to speed up motor skill acquisition and to improve motor skill accuracy, as well as to further our understanding of cerebellar function.

Reversal of long-term potentiation-like plasticity processes after motor learning disrupts skill retention.

Plasticity of synaptic connections in the primary motor cortex (M1) is thought to play an essential role in learning and memory. Human and animal studies have shown that motor learning results in long-term potentiation (LTP)-like plasticity processes, namely potentiation of M1 and a temporary occlusion of additional LTP-like plasticity. Moreover, biochemical processes essential for LTP are also crucial for certain types of motor learning and memory. Thus, it has been speculated that the occlusion of LTP-like plasticity after learning, indicative of how much LTP was used to learn, is essential for retention. Here we provide supporting evidence of it in humans. Induction of LTP-like plasticity can be abolished using a depotentiation protocol (DePo) consisting of brief continuous theta burst stimulation. We used transcranial magnetic stimulation to assess whether application of DePo over M1 after motor learning affected (1) occlusion of LTP-like plasticity and (2) retention of motor skill learning. We found that the magnitude of motor memory retention is proportional to the magnitude of occlusion of LTP-like plasticity. Moreover, DePo stimulation over M1, but not over a control site, reversed the occlusion of LTP-like plasticity induced by motor learning and disrupted skill retention relative to control subjects. Altogether, these results provide evidence of a link between occlusion of LTP-like plasticity and retention and that this measure could be used as a biomarker to predict retention. Importantly, attempts to reverse the occlusion of LTP-like plasticity after motor learning comes with the cost of reducing retention of motor learning.

Motor learning interference is proportional to occlusion of LTP-like plasticity.

Learning interference occurs when learning something new causes forgetting of an older memory (retrograde interference) or when learning a new task disrupts learning of a second subsequent task (anterograde interference). This phenomenon, described in cognitive, sensory, and motor domains, limits our ability to learn multiple tasks in close succession. It has been suggested that the source of interference is competition of neural resources, although the neuronal mechanisms are unknown. Learning induces long-term potentiation (LTP), which can ultimately limit the ability to induce further LTP, a phenomenon known as occlusion. In humans we quantified the magnitude of occlusion of anodal transcranial direct current stimulation-induced increased excitability after learning a skill task as an index of the amount of LTP-like plasticity used. We found that retention of a newly acquired skill, as reflected by performance in the second day of practice, is proportional to the magnitude of occlusion. Moreover, the degree of behavioral interference was correlated with the magnitude of occlusion. Individuals with larger occlusion after learning the first skill were (1) more resilient to retrograde interference and (2) experienced larger anterograde interference when training a second task, as expressed by decreased performance of the learned skill in the second day of practice. This effect was not observed if sufficient time elapsed between training the two skills and LTP-like occlusion was not present. These findings suggest competition of LTP-like plasticity is a factor that limits the ability to remember multiple tasks trained in close succession.

Anodal cerebellar t-DCS impacts skill learning and transfer on a robotic surgery training task.

The cerebellum has demonstrated a critical role during adaptation in motor learning. However, the extent to which it can contribute to the skill acquisition of complex real-world tasks remains unclear. One particularly challenging application in terms of motor activities is robotic surgery, which requires surgeons to complete complex multidimensional visuomotor tasks through a remotely operated robot. Given the need for high skill proficiency and the lack of haptic feedback, there is a pressing need for understanding and improving skill development. We investigated the effect of cerebellar transcranial direct current stimulation applied during the execution of a robotic surgery training task. Study participants received either real or sham stimulation while performing a needle driving task in a virtual (simulated) and a real-world (actual surgical robot) setting. We found that cerebellar stimulation significantly improved performance compared to sham stimulation at fast (more demanding) execution speeds in both virtual and real-world training settings. Furthermore, participants that received cerebellar stimulation more effectively transferred the skills they acquired during virtual training to the real world. Our findings underline the potential of non-invasive brain stimulation to enhance skill learning and transfer in real-world relevant tasks and, more broadly, its potential for improving complex motor learning.

Clinical Implementation of Noninvasive Brain Stimulation in an Outpatient Neurorehabilitation Program.

ABSTRACT: Motor, speech, and cognitive impairments are the most common consequences of neurological disorders. There has been an increasing interest in the use of noninvasive brain stimulation techniques such as transcranial direct current stimulation and transcranial magnetic stimulation to augment the effects of neurorehabilitation. Numerous research studies have shown that transcranial direct current stimulation and transcranial magnetic stimulation are highly promising neuromodulation tools that can work as adjuvants to standard neurorehabilitation services, including physical therapy, occupational therapy, and speech-language pathology. However, to date, there are vast differences in methodology in studies including noninvasive brain stimulation parameters, patient characteristics, time point of intervention after injury, and outcome measures, making it difficult to translate and implement transcranial direct current stimulation and transcranial magnetic stimulation in the clinical setting. Despite this, a series of principles are thought to underlie the effectiveness of noninvasive brain stimulation techniques. We developed a noninvasive brain stimulation rehabilitation program using these principles to provide best practices for applying transcranial direct current stimulation and/or transcranial magnetic stimulation as rehabilitation adjuvants in the clinical setting to help improve neurorehabilitation outcomes. This article outlines our approach, philosophy, and experience.

Shared Control of Bimanual Robotic Limbs With a Brain-Machine Interface for Self-Feeding.

Advances in intelligent robotic systems and brain-machine interfaces (BMI) have helped restore functionality and independence to individuals living with sensorimotor deficits; however, tasks requiring bimanual coordination and fine manipulation continue to remain unsolved given the technical complexity of controlling multiple degrees of freedom (DOF) across multiple limbs in a coordinated way through a user input. To address this challenge, we implemented a collaborative shared control strategy to manipulate and coordinate two Modular Prosthetic Limbs (MPL) for performing a bimanual self-feeding task. A human participant with microelectrode arrays in sensorimotor brain regions provided commands to both MPLs to perform the self-feeding task, which included bimanual cutting. Motor commands were decoded from bilateral neural signals to control up to two DOFs on each MPL at a time. The shared control strategy enabled the participant to map his four-DOF control inputs, two per hand, to as many as 12 DOFs for specifying robot end effector position and orientation. Using neurally-driven shared control, the participant successfully and simultaneously controlled movements of both robotic limbs to cut and eat food in a complex bimanual self-feeding task. This demonstration of bimanual robotic system control via a BMI in collaboration with intelligent robot behavior has major implications for restoring complex movement behaviors for those living with sensorimotor deficits.

Characteristics and stability of sensorimotor activity driven by isolated-muscle group activation in a human with tetraplegia.

Understanding the cortical representations of movements and their stability can shed light on improved brain-machine interface (BMI) approaches to decode these representations without frequent recalibration. Here, we characterize the spatial organization (somatotopy) and stability of the bilateral sensorimotor map of forearm muscles in an incomplete-high spinal-cord injury study participant implanted bilaterally in the primary motor and sensory cortices with Utah microelectrode arrays (MEAs). We built representation maps by recording bilateral multiunit activity (MUA) and surface electromyography (EMG) as the participant executed voluntary contractions of the extensor carpi radialis (ECR), and attempted motions in the flexor carpi radialis (FCR), which was paralytic. To assess stability, we repeatedly mapped and compared left- and right-wrist-extensor-related activity throughout several sessions, comparing somatotopy of active electrodes, as well as neural signals both at the within-electrode (multiunit) and cross-electrode (network) levels. Wrist motions showed significant activation in motor and sensory cortical electrodes. Within electrodes, firing strength stability diminished as the time increased between consecutive measurements (hours within a session, or days across sessions), with higher stability observed in sensory cortex than in motor, and in the contralateral hemisphere than in the ipsilateral. However, we observed no differences at network level, and no evidence of decoding instabilities for wrist EMG, either across timespans of hours or days, or across recording area. While map stability differs between brain area and hemisphere at multiunit/electrode level, these differences are nullified at ensemble level.

Intracortical Somatosensory Stimulation to Elicit Fingertip Sensations in an Individual With Spinal Cord Injury.

BACKGROUND AND OBJECTIVES: The restoration of touch to fingers and fingertips is critical to achieving dexterous neuroprosthetic control for individuals with sensorimotor dysfunction. However, localized fingertip sensations have not been evoked via intracortical microstimulation (ICMS). METHODS: Using a novel intraoperative mapping approach, we implanted electrode arrays in the finger areas of left and right somatosensory cortex and delivered ICMS over a 2-year period in a human participant with spinal cord injury. RESULTS: Stimulation evoked tactile sensations in 8 fingers, including fingertips, spanning both hands. Evoked percepts followed expected somatotopic arrangements. The subject was able to reliably identify up to 7 finger-specific sites spanning both hands in a finger discrimination task. The size of the evoked percepts was on average 33% larger than a finger pad, as assessed via manual markings of a hand image. The size of the evoked percepts increased modestly with increased stimulation intensity, growing 21% as pulse amplitude increased from 20 to 80 µA. Detection thresholds were estimated on a subset of electrodes, with estimates of 9.2 to 35 µA observed, roughly consistent with prior studies. DISCUSSION: These results suggest that ICMS can enable the delivery of consistent and localized fingertip sensations during object manipulation by neuroprostheses for individuals with somatosensory deficits. CLINICALTRIALSGOV IDENTIFIER: NCT03161067.

Disrupting the ventral premotor cortex interferes with the contribution of action observation to use-dependent plasticity.

Action observation (AO), observing another individual perform an action, has been implicated in several higher cognitive processes including forming basic motor memories. Previous work has shown that physical practice (PP) results in cortical motor representational changes, referred to as use-dependent plasticity (UDP), and that AO combined with PP potentiates UDP in both healthy adults and stroke patients. In humans, AO results in activation of the ventral premotor cortex (PMv), however, whether this PMv activation has a functional contribution to UDP is not known. Here, we studied the effects disruption of PMv has on UDP when subjects performed PP combined with AO (PP + AO). Subjects participated in two randomized crossover sessions measuring the amount of UDP resulting from PP + AO while receiving disruptive (1 Hz) TMS over the fMRI-activated PMv or over frontal cortex (Sham). We found that, unlike the sham session, disruptive TMS over PMv reduced the beneficial contribution of AO to UDP. To ensure that disruption of PMv was specifically interfering with the contribution of AO and not PP, subjects completed two more control sessions where they performed only PP while receiving disruptive TMS over PMv or frontal cortex. We found that the magnitude of UDP for both control sessions was similar to PP + AO with TMS over PMv. These findings suggest that the fMRI activation found in PMv during AO studies is functionally relevant to task performance, at least for the beneficial effects that AO exerts over motor training.

Intracortical microstimulation of somatosensory cortex enables object identification through perceived sensations.

Advances in brain-machine interfaces have helped restore function and independence for individuals with sensorimotor deficits; however, providing efficient and effective sensory feedback remains challenging. Intracortical microstimulation (ICMS) of sensorimotor brain regions is a promising technique for providing bioinspired sensory feedback. In a human participant with chronically-implanted microelectrode arrays, we provided ICMS to the primary somatosensory cortex to generate tactile percepts in his hand. In a 3-choice object identification task, the participant identified virtual objects using tactile sensory feedback and no visual information. We evaluated three different stimulation paradigms, each with a different weighting of the grip force and its derivative, to explore the potential benefits of a more bioinspired stimulation strategy. In all paradigms, the participant's ability to identify the objects was above-chance, with object identification accuracy reaching 80% correct when using only sustained grip force feedback and 76.7% when using equal weighting of both sustained grip force and its derivative. These results demonstrate that bioinspired ICMS can provide sensory feedback that is functionally beneficial in sensorimotor tasks. Designing more efficient stimulation paradigms is important because it will allow us to 1) provide safer stimulation delivery methods that reduce overall injected charge without sacrificing function and 2) more effectively transmit sensory information to promote intuitive integration and usage by the human body.

Novel intraoperative online functional mapping of somatosensory finger representations for targeted stimulating electrode placement: technical note.

Defining eloquent cortex intraoperatively, traditionally performed by neurosurgeons to preserve patient function, can now help target electrode implantation for restoring function. Brain-machine interfaces (BMIs) have the potential to restore upper-limb motor control to paralyzed patients but require accurate placement of recording and stimulating electrodes to enable functional control of a prosthetic limb. Beyond motor decoding from recording arrays, precise placement of stimulating electrodes in cortical areas associated with finger and fingertip sensations allows for the delivery of sensory feedback that could improve dexterous control of prosthetic hands. In this study, the authors demonstrated the use of a novel intraoperative online functional mapping (OFM) technique with high-density electrocorticography to localize finger representations in human primary somatosensory cortex. In conjunction with traditional pre- and intraoperative targeting approaches, this technique enabled accurate implantation of stimulating microelectrodes, which was confirmed by postimplantation intracortical stimulation of finger and fingertip sensations. This work demonstrates the utility of intraoperative OFM and will inform future studies of closed-loop BMIs in humans.

Repeated Concussions Impair Behavioral and Neurophysiological Changes in the Motor Learning System.

Background. Concussions affect nearly 3 million people a year and are the leading cause of traumatic brain injury-related emergency department visits among youth. Evidence shows neuromotor regions are sensitive to concussive events and that motor symptoms may be the earliest clinical manifestations of neurodegenerative traumatic brain injuries. However, little is known about the effects repeated concussions play on motor learning. Namely, how does concussion acuity (time since injury) affect different behavioral and neurophysiological components of motor learning? Methods. Using a 3-pronged approach, we assessed (1) behavioral measures of motor learning, (2) neurophysiological measures underlying retention of motor learning known as occlusion, and (3) quantitative survey data capturing affective symptoms of each participant. Collegiate student athletes were stratified across 3 groups depending on their concussion history: (1) NonCon, no history of concussion; (2) Chronic, chronic-state of concussion (>1 year postinjury), or (3) Acute, acute state of concussion (<2 weeks postinjury). Results. We found that athletes in both the acute and chronic state of injury following a concussion had impaired retention and aberrant occlusion in motor skill learning as compared with athletes with no history of concussion. Moreover, higher numbers of previous concussions (regardless of the time since injury) correlated with more severe behavioral and neurophysiological motor impairments by specifically hindering neurophysiological mechanisms of learning to affect behavior. Conclusions. These results indicate the presence of motor learning impairment that is evident within 2 weeks postinjury. Our findings have significant implications for the prognosis of concussion and emphasize the need for prevention, but can also direct more relevant rehabilitation treatment targets.

Single-arm, open-label, dose escalation phase I study to evaluate the safety and feasibility of transcranial direct current stimulation with electroencephalography biomarkers in paediatric disorders of consciousness: a study protocol.

INTRODUCTION: Children with disorders of consciousness (DOC) represent the highest end of the acquired brain injury (ABI) severity spectrum for survivors and experience a multitude of functional impairments. Current clinical management in DOC uses behavioural evaluation measures and interventions that fail to (1) describe the physiological consequences of ABI and (2) elicit functional gains. In paediatric DOC, there is a critical need to develop evidence-based interventions to promote recovery of basic responses to improve rehabilitation and aid decision-making for medical teams and caregivers. The purpose of this investigation is to examine the safety, tolerability and feasibility of transcranial direct current stimulation (tDCS) in children with DOC. METHODS AND ANALYSIS: This study is an open-label dose escalation trial evaluating the safety, tolerability and feasibility of tDCS in 10 children (5-17 years) receiving inpatient rehabilitation for DOC. This study will follow a modified rule-based design, allowing for intrapatient escalation, where a cohort of patients will be assigned to an initial tDCS current of 0.5 or 1 mA based on participant's head circumference and according to the safety data available in other paediatric populations. The subsequent assignment of increased current (1 or 2 mA) according to the prespecified rules will be based on the clinical observation of adverse events in the patients. The study will include up to three, 20 min sessions of anodal tDCS (sham, 0.5 or 1 mA, 1 or 2 mA) applied over the dorsolateral prefrontal cortex. The primary outcomes are adverse events, pain associated with tDCS and intolerable disruption of inpatient care. Secondary outcomes are changes in electroencephalography (EEG) phase-locking and event-related potential components and the Coma Recovery Scale-Revised total score from prestimulation to poststimulation. ETHICS AND DISSEMINATION: The Johns Hopkins IRB (#IRB00174966) approved this study. Trial results will be disseminated through journals and conferences. REGISTRATION NUMBER: NCT03618849.

Connecting clinical aspects to corticomotor excitability in restless legs syndrome: a TMS study.

We assessed corticomotor excitability in the primary motor cortex (M1) of participants with moderate-to-severe restless legs syndrome (RLS) symptoms using transcranial magnetic stimulation (TMS) in relation to the clinical and sleep aspects of the disease. Thirty-five participants (20 F; mean age: 59.23 ± 1.66 years; range: 42-78 years) affected by primary RLS (off medications) and 31 age-matched controls (19 F; mean age: 57.90 ± 1.50 years; range: 43-79 years) underwent TMS following two nights of polysomnography (PSG). Paired-pulse TMS measures [short-interval intracortical inhibition (SICI), long-interval intracortical inhibition (LICI), and intracortical facilitation (ICF)] of the dominant M1hand and M1leg muscles were collected and analyzed in relation to clinical features of RLS and PSG. We found decreased corticomotor excitability in M1hand, whereas it was increased in M1leg, which was greater in patients with more severe RLS. Participants with RLS with a history of dopamine-agonist-induced symptom augmentation showed decreased LICI (reduced inhibition) compared to nonaugmented participants with RLS for M1leg. None of the TMS measures (M1hand or M1leg) correlated with the PSG parameters. This study shows hyperexcitability in M1leg, and this appears related to RLS disease severity and decreased excitability in M1hand. The results provide new insight into the complex neurobiology of RLS, particularly in more advanced stages of the disease.

Static field influences on transcranial magnetic stimulation: considerations for TMS in the scanner environment.

BACKGROUND: Transcranial magnetic stimulation (TMS) can be combined with functional magnetic resonance imaging (fMRI) to simultaneously manipulate and monitor human cortical responses. Although tremendous efforts have been directed at characterizing the impact of TMS on image acquisition, the influence of the scanner's static field on the TMS coil has received limited attention. OBJECTIVE/HYPOTHESIS: The aim of this study was to characterize the influence of the scanner's static field on TMS. We hypothesized that spatial variations in the static field could account for TMS field variations in the scanner environment. METHODS: Using an MRI-compatible TMS coil, we estimated TMS field strengths based on TMS-induced voltage changes measured in a search coil. We compared peak field strengths obtained with the TMS coil positioned at different locations (B0 field vs fringe field) and orientations in the static field. We also measured the scanner's static field to derive a field map to account for TMS field variations. RESULTS: TMS field strength scaled depending on coil location and orientation with respect to the static field. Larger TMS field variations were observed in fringe field regions near the gantry as compared to regions inside the bore or further removed from the bore. The scanner's static field also exhibited the greatest spatial variations in fringe field regions near the gantry. CONCLUSIONS: The scanner's static field influences TMS fields and spatial variations in the static field correlate with TMS field variations. Coil orientation changes in the B0 field did not result in substantial TMS field variations. TMS field variations can be minimized by delivering TMS in the bore or outside of the 0-70 cm region from the bore entrance.

Increased use-dependent plasticity in chronic insomnia.

STUDY OBJECTIVES: During normal sleep several neuroplasticity changes occur, some of which are considered to be fundamental to strengthen memories. Given the evidence linking sleep to neuroplasticity, it is conceivable that individuals with chronic sleep disruption, such as patients with chronic insomnia (CI), would experience abnormalities in neuroplastic processes during daytime. Protocols testing use-dependent plasticity (UDP), one of the mechanisms underlying formation of motor memories traces, provide a sensitive measure to assess neuroplasticity in the context of motor training. DESIGN AND PARTICIPANTS: A well-established transcranial magnetic stimulation (TMS) paradigm was used to evaluate the ability of patients with CI and age-matched good sleeper controls to undergo UDP. We also investigated the effect of insomnia on intracortical motor excitability measures reflecting GABAergic and glutamatergic mechanisms. SETTING: Human Brain Physiology Laboratory, Johns Hopkins Medical Institutions. MEASUREMENTS AND RESULTS: We found that patients with CI experienced increased UDP changes relative to controls. This effect was not due to differences in motor training. In addition, patients with CI showed enhanced intracortical facilitation relative to controls, in the absence of changes in intracortical inhibitory measures. CONCLUSION: This study provides the first evidence that patients with chronic insomnia have an increased plasticity response to physical exercise, possibly due to larger activation of glutamatergic mechanisms. This suggests a heightened state of neuroplasticity, which may reflect a form of maladaptive plasticity, similar to what has been described in dystonia patients and chronic phantom pain after amputation. These results could lead to development of novel treatments for chronic insomnia.

Impaired perception of temporal fine structure and musical timbre in cochlear implant users.

Cochlear implant (CI) users demonstrate severe limitations in perceiving musical timbre, a psychoacoustic feature of sound responsible for 'tone color' and one's ability to identify a musical instrument. The reasons for this limitation remain poorly understood. In this study, we sought to examine the relative contributions of temporal envelope and fine structure for timbre judgments, in light of the fact that speech processing strategies employed by CI systems typically employ envelope extraction algorithms. We synthesized "instrumental chimeras" that systematically combined variable amounts of envelope and fine structure in 25% increments from two different source instruments with either sustained or percussive envelopes. CI users and normal hearing (NH) subjects were presented with 150 chimeras and asked to determine which instrument the chimera more closely resembled in a single-interval two-alternative forced choice task. By combining instruments with similar and dissimilar envelopes, we controlled the valence of envelope for timbre identification and compensated for envelope reconstruction from fine structure information. Our results show that NH subjects utilize envelope and fine structure interchangeably, whereas CI subjects demonstrate overwhelming reliance on temporal envelope. When chimeras were created from dissimilar envelope instrument pairs, NH subjects utilized a combination of envelope (p = 0.008) and fine structure information (p = 0.009) to make timbre judgments. In contrast, CI users utilized envelope information almost exclusively to make timbre judgments (p < 0.001) and ignored fine structure information (p = 0.908). Interestingly, when the value of envelope as a cue was reduced, both NH subjects and CI users utilized fine structure information to make timbre judgments (p < 0.001), although the effect was quite weak in CI users. Our findings confirm that impairments in fine structure processing underlie poor perception of musical timbre in CI users.