Moss Rehabilitation Hospital

OBJECTIVE: The aim of this study was to assess the safety and performance of ReWalk in enabling people with paraplegia due to spinal cord injury to carry out routine ambulatory functions. DESIGN: This was an open, noncomparative, nonrandomized study of the safety and performance of the ReWalk powered exoskeleton. All 12 subjects have completed the active intervention; three remain in long-term follow-up. RESULTS: After training, all subjects were able to independently transfer and walk, without human assistance while using the ReWalk, for at least 50 to 100 m continuously, for a period of at least 5 to 10 mins continuously and with velocities ranging from 0.03 to 0.45 m/sec (mean, 0.25 m/sec). Excluding two subjects with considerably reduced walking abilities, average distances and velocities improved significantly. Some subjects reported improvements in pain, bowel and bladder function, and spasticity during the trial. All subjects had strong positive comments regarding the emotional/psychosocial benefits of the use of ReWalk. CONCLUSIONS: ReWalk holds considerable potential as a safe ambulatory powered orthosis for motor-complete thoracic-level spinal cord injury patients. Most subjects achieved a level of walking proficiency close to that needed for limited community ambulation. A high degree of performance variability was observed across individuals. Some of this variability was explained by level of injury, but other factors have not been completely identified. Further development and application of this rehabilitation tool to other diagnoses are expected in the future.

BACKGROUND: Amantadine hydrochloride is one of the most commonly prescribed medications for patients with prolonged disorders of consciousness after traumatic brain injury. Preliminary studies have suggested that amantadine may promote functional recovery. METHODS: We enrolled 184 patients who were in a vegetative or minimally conscious state 4 to 16 weeks after traumatic brain injury and who were receiving inpatient rehabilitation. Patients were randomly assigned to receive amantadine or placebo for 4 weeks and were followed for 2 weeks after the treatment was discontinued. The rate of functional recovery on the Disability Rating Scale (DRS; range, 0 to 29, with higher scores indicating greater disability) was compared over the 4 weeks of treatment (primary outcome) and during the 2-week washout period with the use of mixed-effects regression models. RESULTS: During the 4-week treatment period, recovery was significantly faster in the amantadine group than in the placebo group, as measured by the DRS score (difference in slope, 0.24 points per week; P=0.007), indicating a benefit with respect to the primary outcome measure. In a prespecified subgroup analysis, the treatment effect was similar for patients in a vegetative state and those in a minimally conscious state. The rate of improvement in the amantadine group slowed during the 2 weeks after treatment (weeks 5 and 6) and was significantly slower than the rate in the placebo group (difference in slope, 0.30 points per week; P=0.02). The overall improvement in DRS scores between baseline and week 6 (2 weeks after treatment was discontinued) was similar in the two groups. There were no significant differences in the incidence of serious adverse events. CONCLUSIONS: Amantadine accelerated the pace of functional recovery during active treatment in patients with post-traumatic disorders of consciousness. (Funded by the National Institute on Disability and Rehabilitation Research; ClinicalTrials.gov number, NCT00970944.).

Motor learning encompasses a wide range of phenomena, ranging from relatively low-level mechanisms for maintaining calibration of our movements, to making high-level cognitive decisions about how to act in a novel situation. We survey the major existing approaches to characterizing motor learning at both the behavioral and neural level. In particular, we critically review two long-standing paradigms used in motor learning research-adaptation and sequence learning. We discuss the extent to which these paradigms can be considered models of motor skill acquisition, defined as the incremental improvement in our ability to rapidly select and then precisely execute appropriate actions, and conclude that they fall short of doing so. We then discuss two classes of emerging research paradigms-learning of arbitrary visuomotor mappings de novo and learning to execute movements with improved acuity-that more effectively address the acquisition of motor skill. Future work will be needed to determine the degree to which laboratory-based studies of skill, as described in this review, will relate to true expertise, which is likely dependent on the effects of practice on multiple cognitive processes that go beyond traditional sensorimotor neural architecture. © 2019 American Physiological Society. Compr Physiol 9:613-663, 2019.

OBJECTIVES: The objective of the study was to evaluate the safety and tolerance of use of the ReWalk™ exoskeleton ambulation system in people with spinal cord injury. Measures of functional ambulation were also assessed and correlated to neurological spinal cord level, age, and duration since injury. STUDY DESIGN: Case series observational study. SETTING: A national spinal cord injury centre. METHODS: Six volunteer participants were recruited from the follow-up outpatient clinic. Safety was assessed with regard to falls, status of the skin, status of the spine and joints, blood pressure, pulse, and electrocardiography (ECG). Pain and fatigue were graded by the participants using a visual analogue scale pre- and post-training. Participants completed a 10-statement questionnaire regarding safety, comfort, and secondary medical effects. After being able to walk 100 m, timed up and go, distance walked in 6 minutes and 10-m timed walk were measured. RESULTS: There were no adverse safety events. Use of the system was generally well tolerated, with no increase in pain and a moderate level of fatigue after use. Individuals with lower level of spinal cord injury performed walking more efficiently. CONCLUSION: Volunteer participants were able to ambulate with the ReWalk™ for a distance of 100 m, with no adverse effects during the course of an average of 13-14 training sessions. The participants were generally positive regarding the use of the system.

Network science provides theoretical, computational, and empirical tools that can be used to understand the structure and function of the human brain in novel ways using simple concepts and mathematical representations. Network neuroscience is a rapidly growing field that is providing considerable insight into human structural connectivity, functional connectivity while at rest, changes in functional networks over time (dynamics), and how these properties differ in clinical populations. In addition, a number of studies have begun to quantify network characteristics in a variety of cognitive processes and provide a context for understanding cognition from a network perspective. In this review, we outline the contributions of network science to cognitive neuroscience. We describe the methodology of network science as applied to the particular case of neuroimaging data and review its uses in investigating a range of cognitive functions including sensory processing, language, emotion, attention, cognitive control, learning, and memory. In conclusion, we discuss current frontiers and the specific challenges that must be overcome to integrate these complementary disciplines of network science and cognitive neuroscience. Increased communication between cognitive neuroscientists and network scientists could lead to significant discoveries under an emerging scientific intersection known as cognitive network neuroscience.

The sixth edition of the foundational reference on cognitive neuroscience, with entirely new material that covers the latest research, experimental approaches, and measurement methodologies. Each edition of this classic reference has proved to be a benchmark in the developing field of cognitive neuroscience. The sixth edition of The Cognitive Neurosciences continues to chart new directions in the study of the biological underpinnings of complex cognition—the relationship between the structural and physiological mechanisms of the nervous system and the psychological reality of the mind. It offers entirely new material, reflecting recent advances in the field, covering the latest research, experimental approaches, and measurement methodologies. This sixth edition treats such foundational topics as memory, attention, and language, as well as other areas, including computational models of cognition, reward and decision making, social neuroscience, scientific ethics, and methods advances. Over the last twenty-five years, the cognitive neurosciences have seen the development of sophisticated tools and methods, including computational approaches that generate enormous data sets. This volume deploys these exciting new instruments but also emphasizes the value of theory, behavior, observation, and other time-tested scientific habits. Section editorsSarah-Jayne Blakemore and Ulman Lindenberger, Kalanit Grill-Spector and Maria Chait, Tomás Ryan and Charan Ranganath, Sabine Kastner and Steven Luck, Stanislas Dehaene and Josh McDermott, Rich Ivry and John Krakauer, Daphna Shohamy and Wolfram Schultz, Danielle Bassett and Nikolaus Kriegeskorte, Marina Bedny and Alfonso Caramazza, Liina Pylkkänen and Karen Emmorey, Mauricio Delgado and Elizabeth Phelps, Anjan Chatterjee and Adina Roskies

Analysis of error types provides useful information about the stages and processes involved in normal and aphasic word production. In picture naming, semantic errors (horse for goat) generally result from something having gone awry in lexical access such that the right concept was mapped to the wrong word. This study used the new lesion analysis technique known as voxel-based lesion-symptom mapping to investigate the locus of lesions that give rise to semantic naming errors. Semantic errors were obtained from 64 individuals with post-stroke aphasia, who also underwent high-resolution structural brain scans. Whole brain voxel-based lesion-symptom mapping was carried out to determine where lesion status predicted semantic error rate. The strongest associations were found in the left anterior to mid middle temporal gyrus. This area also showed strong and significant effects in further analyses that statistically controlled for deficits in pre-lexical, conceptualization processes that might have contributed to semantic error production. This study is the first to demonstrate a specific and necessary role for the left anterior temporal lobe in mapping concepts to words in production. We hypothesize that this role consists in the conveyance of fine-grained semantic distinctions to the lexical system. Our results line up with evidence from semantic dementia, the convergence zone framework and meta-analyses of neuroimaging studies on word production. At the same time, they cast doubt on the classical linkage of semantic error production to lesions in and around Wernicke's area.

To produce a word, the intended word must be selected from a competing set of other words. In other domains where competition affects the selection process, the left inferior frontal gyrus (LIFG) responds to competition among incompatible representations. The aim of this study was to test whether the LIFG is necessary for resolution of competition in word production. Using a methodological approach applying the same rigorous analytic methods to neuropsychological data as is done with neuroimaging data, we compared brain activation patterns in normal speakers (using fMRI) with the results of lesion-deficit correlations in aphasic speakers who performed the same word production task designed to elicit competition during lexical selection. The degree of activation of the LIFG in normal speakers and damage to the LIFG in aphasic speakers was associated with performance on the production task. These convergent findings provide strong support for the hypothesis that the region of cortex commonly known as Broca's area (i.e., the posterior LIFG) serves to bias competitive interactions during language production.

Adult human cognition is supported by systems of brain regions, or modules, that are functionally coherent at rest and collectively activated by distinct task requirements. However, an understanding of how the formation of these modules supports evolving cognitive capabilities has not been delineated. Here, we quantify the formation of network modules in a sample of 780 youth (aged 8-22 y) who were studied as part of the Philadelphia Neurodevelopmental Cohort. We demonstrate that the brain's functional network organization changes in youth through a process of modular evolution that is governed by the specific cognitive roles of each system, as defined by the balance of within- vs. between-module connectivity. Moreover, individual variability in these roles is correlated with cognitive performance. Collectively, these results suggest that dynamic maturation of network modules in youth may be a critical driver for the development of cognition.

The aim of this systematic review was to critically evaluate the evidence on interventions for depression following traumatic brain injury (TBI) and provide recommendations for clinical practice and future research. We reviewed pharmacological, other biological, psychotherapeutic, and rehabilitation interventions for depression following TBI from the following data sources: PubMed, CINAHL, PsycINFO, ProQuest, Web of Science, and Google Scholar. We included studies written in English published since 1980 investigating depression and depressive symptomatology in adults with TBI; 658 articles were identified. After reviewing the abstracts, 57 articles met the inclusion criteria. In addition to studies describing interventions designed to treat depression, we included intervention studies in which depressive symptoms were reported as a secondary outcome. At the end of a full review in which two independent reviewers extracted data, 26 articles met the final criteria that included reporting data on participants with TBI, and using validated depression diagnostic or severity measures pre- and post-treatment. Three external reviewers also examined the study methods and evidence tables, adding 1 article, for a total of 27 studies. Evidence was classified based on American Academy of Neurology criteria. The largest pharmacological study enrolled 54 patients, and none of the psychotherapeutic/rehabilitation interventions prospectively targeted depression. This systematic review documents that there is a paucity of randomized controlled trials for depression following TBI. Serotonergic antidepressants and cognitive behavioral interventions appear to have the best preliminary evidence for treating depression following TBI. More research is needed to provide evidence-based treatment recommendations for depression following TBI.

Lesion analysis is a classic approach to study brain functions. Because brain function is a result of coherent activations of a collection of functionally related voxels, lesion-symptom relations are generally contributed by multiple voxels simultaneously. Although voxel-based lesion-symptom mapping (VLSM) has made substantial contributions to the understanding of brain-behavior relationships, a better understanding of the brain-behavior relationship contributed by multiple brain regions needs a multivariate lesion-symptom mapping (MLSM). The purpose of this artilce was to develop an MLSM using a machine learning-based multivariate regression algorithm: support vector regression (SVR). In the proposed SVR-LSM, the symptom relation to the entire lesion map as opposed to each isolated voxel is modeled using a nonlinear function, so the intervoxel correlations are intrinsically considered, resulting in a potentially more sensitive way to examine lesion-symptom relationships. To explore the relative merits of VLSM and SVR-LSM we used both approaches in the analysis of a synthetic dataset. SVR-LSM showed much higher sensitivity and specificity for detecting the synthetic lesion-behavior relations than VLSM. When applied to lesion data and language measures from patients with brain damages, SVR-LSM reproduced the essential pattern of previous findings identified by VLSM and showed higher sensitivity than VLSM for identifying the lesion-behavior relations. Our data also showed the possibility of using lesion data to predict continuous behavior scores.

Research on treatment efficacy and effectiveness requires that the treatments of interest be objectively defined. Such definitions are relatively straightforward for pharmacologic and surgical treatments, in which the active ingredients can be specified in terms of chemical structure or anatomic result. Definitions of treatment are more difficult for the many experience-based interventions employed in rehabilitation. This has led to the criticism that much clinical rehabilitation research has characterized the treatments of interest as a "black box," allowing little insight into the active ingredients contained therein. Moreover, rehabilitation care may involve the simultaneous application of multiple different treatments, raising the question of whether to define the individual components or the service delivery system. In this article, we consider how the levels of analysis considered in rehabilitation (disease, impairment, activity, and participation) and the role of theory shape the definition of treatment, and we address the need to develop protocol-based treatments and tools to objectively verify their contents. Rigorous definition of rehabilitation treatments, supported by theory, will facilitate needed efficacy research, will allow replication of that research, and will ultimately foster dissemination of effective treatments into clinical practice.

Some accounts of body representations postulate a real-time representation of the body in space generated by proprioceptive, somatosensory, vestibular and other sensory inputs; this representation has often been termed the 'body schema'. To examine whether the body schema is influenced by peripheral factors such as pain, we asked patients with chronic unilateral arm pain to determine the laterality of pictured hands presented at different orientations. Previous chronometric findings suggest that performance on this task depends on the body schema, in that it appears to involve mentally rotating one's hand from its current position until it is aligned with the stimulus hand. We found that, as in previous investigations, participants' response times (RTs) reflected the degree of simulated movement as well as biomechanical constraints of the arm. Importantly, a significant interaction between the magnitude of mental rotation and limb was observed: RTs were longer for the painful arm than for the unaffected arm for large-amplitude imagined movements; controls exhibited symmetrical RTs. These findings suggest that the body schema is influenced by pain and that this task may provide an objective measure of pain.

Studies of patients with acquired cognitive deficits following brain damage and studies using contemporary neuroimaging techniques form two distinct streams of research on the neural basis of cognition. In this study, we combine high-quality structural neuroimaging analysis techniques and extensive behavioural assessment of patients with persistent acquired language deficits to study the neural basis of language. Our results reveal two major divisions within the language system—meaning versus form and recognition versus production—and their instantiation in the brain. Phonological form deficits are associated with lesions in peri-Sylvian regions, whereas semantic production and recognition deficits are associated with damage to the left anterior temporal lobe and white matter connectivity with frontal cortex, respectively. These findings provide a novel synthesis of traditional and contemporary views of the cognitive and neural architecture of language processing, emphasizing dual routes for speech processing and convergence of white matter tracts for semantic control and/or integration. Contemporary neuroimaging techniques are enabling precise analysis of structure–function relations in the brain. This study combines large-scale structural neuroimaging and behavioural analyses in patients with acquired aphasia to elucidate the neural organization of spoken language processing.

Although ideomotor apraxia (IM) has been a topic of investigation since the early 20th century, progress in studying the disorder has been hindered by important (and sometimes unarticulated) differences in the underlying theoretical models of various investigative groups. As a result, it is difficult to draw conclusions about the expected performance of IM patients on various tests of praxis (e.g. pantomime, single object use, gesture imitation, and naturalistic action); the relationship of IM to ideational apraxia (IA); the degree to which specific error types are diagnostic of one or the other disorder; the relationship of semantic knowledge to gesture representations; and the role of spatiomotor systems external to the stored gesture representation system. Here an updated model of IM is presented, informed by recent physiological and functional neuroimaging literature, as a step towards resolving some of these concerns. The model is intended to lay the groundwork for future investigations of specific performance patterns in different subtypes of IM.

Lesion analysis in brain-injured populations complements what can be learned from functional neuroimaging. Voxel-based approaches to mapping lesion-behavior correlations in brain-injured populations are increasingly popular, and have the potential to leverage image analysis methods drawn from functional magnetic resonance imaging. However, power is a major concern for these studies, and is likely to vary regionally due to the distribution of lesion locations. Here, we outline general considerations for voxel-based methods, characterize the use of a nonparametric permutation test adapted from functional neuroimaging, and present methods for regional power analysis in lesion studies.

It is thought that semantic memory represents taxonomic information differently from thematic information. This study investigated the neural basis for the taxonomic-thematic distinction in a unique way. We gathered picture-naming errors from 86 individuals with poststroke language impairment (aphasia). Error rates were determined separately for taxonomic errors ("pear" in response to apple) and thematic errors ("worm" in response to apple), and their shared variance was regressed out of each measure. With the segmented lesions normalized to a common template, we carried out voxel-based lesion-symptom mapping on each error type separately. We found that taxonomic errors localized to the left anterior temporal lobe and thematic errors localized to the left temporoparietal junction. This is an indication that the contribution of these regions to semantic memory cleaves along taxonomic-thematic lines. Our findings show that a distinction long recognized in the psychological sciences is grounded in the structure and function of the human brain.

Attending Physiatrist, Drucker Brain Injury Center, Moss Rehab, Philadelphia, Pennsylvania (Laborde)

Executive function mediated by prefrontally driven distributed networks is frequently impaired by traumatic brain injury (TBI) as a result of diffuse axonal injury and focal lesions. In addition to executive cognitive functions such as planning and working memory, the effects of TBI impact social cognition and motivation processes. To encourage application of cognitive neuroscience methods to studying recovery from TBI, associated reorganization of function, and development of interventions, this article reviews the pathophysiology of TBI, critiques currently employed methods of assessing executive function, and evaluates promising interventions that reflect advances in cognitive neuroscience. Brain imaging to identify neural mechanisms mediating executive dysfunction and response to interventions following TBI is also discussed.

A number of conflicting claims have been advanced regarding the role of the left inferior frontal gyrus, inferior parietal lobe and posterior middle temporal gyrus in action recognition, driven in part by an ongoing debate about the capacities of putative mirror systems that match observed and planned actions. We report data from 43 left hemisphere stroke patients in two action recognition tasks in which they heard and saw an action word ('hammering') and selected from two videoclips the one corresponding to the word. In the spatial recognition task, foils contained errors of body posture or movement amplitude/timing. In the semantic recognition task, foils were semantically related (sawing). Participants also performed a comprehension control task requiring matching of the same verbs to objects (hammer). Using regression analyses controlling for both the comprehension control task and lesion volume, we demonstrated that performance in the semantic gesture recognition task was predicted by per cent damage to the posterior temporal lobe, whereas the spatial gesture recognition task was predicted by per cent damage to the inferior parietal lobule. A whole-brain voxel-based lesion symptom-mapping analysis suggested that the semantic and spatial gesture recognition tasks were associated with lesioned voxels in the posterior middle temporal gyrus and inferior parietal lobule, respectively. The posterior middle temporal gyrus appears to serve as a central node in the association of actions and meanings. The inferior parietal lobule, held to be a homologue of the monkey parietal mirror neuron system, is critical for encoding object-related postures and movements, a relatively circumscribed aspect of gesture recognition. The inferior frontal gyrus, on the other hand, was not predictive of performance in any task, suggesting that previous claims regarding its role in action recognition may require refinement.