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BACKGROUND: A neuropsychological screening instrument sensitive to neuropsychological deficits associated with Alzheimer's disease (AD) and patients with frontotemporal dementia (FTD) would be valuable for diagnostic evaluation. METHODS: The Philadelphia Brief Assessment of Cognition (PBAC) assesses working memory/executive control, language, visuospatial operations, verbal/visual episodic memory, and behavior/social comportment and can be administered and scored in 15-20 min. Participants included 149 patients with AD and four groups of FTD patients - i.e., patients with a decline in social comportment, personality, and executive functioning (SOC/EXEC), semantic dementia (SemD), progressive nonfluent aphasia (PNFA), and corticobasal syndrome (CBS). RESULTS: The total PBAC score correlated with the Mini-Mental State Examination. Between-group analysis of PBAC subscales and the results of logistic regression analyses produced substantial between-group differences, emphasizing the sensitivity of the test to differentiate dementia subtypes. AD patients were impaired on tests of episodic memory, SOC/EXEC patients were impaired on a measure of social comportment/behavioral disturbance, PNFA patients obtained low scores on tests of working memory/executive control, SemD patients obtained lower scores on language-mediated measures, and CBS patients were impaired on visuospatial/visual memory tests. CONCLUSION: These data support the usefulness of the PBAC as a relatively brief screening test of overall dementia severity across a wide range of dementia patients. [ABSTRACT FROM AUTHOR]

We present data from a patient with a progressive fluent aphasia, BA, who exhibited a severe verbal impairment but a relatively preserved access to knowledge from pictures. She exhibited surface dyslexia and dysgraphia and was impaired in the production of the past tense of irregular verbs and the plural form of irregular nouns. She exhibited a mild-moderate impairment in auditory and visual lexical decision tasks that, we argue, was explicable on the basis of a semantic deficit. Knowledge of numbers and body parts was largely preserved even when on tasks involving verbal stimuli. On the basis of this and other evidence, we argue for a distributed, multi-modality system for semantic memory in which information is stored in different brain regions and in different representational formats. [ABSTRACT FROM AUTHOR]

Discusses a research on the subtypes of optic ataxia (OA), a disorder of visually guided reaching which is usually attributed to the disconnection of visual information from motor systems. Proposed non-foveal subtype of OA; Cause of the fundamental deficit in OA; Pathologic linkage of systems mediating spatio-motor tranformations for the eye and hand.

Closing-in behavior (CIB) is characterized by the placement of the graphic copy near (Near CIB) or even on the top of (Overlap CIB) the stimulus to be reproduced. Although CIB has received little attention in the literature, Sergio Della Sala and colleagues made important contributions to the understanding of the phenomenon. They noted that CIB is often observed in Alzheimer's Disease but is also present in other forms of dementia and mild cognitive impairment and stroke; they argued that CIB may reflect a deficit in executive function, rather than working memory, and that the phenomenon occurs more frequently in dual task conditions. Importantly, they demonstrated that CIB may not be specific to copying but may instead reflect a general deficit in decoupling movement location from the focus of attention. In the present study, we explored these observations in a mixed sample of 106 participants (AD n = 37, frontal stroke n = 25, other forms of dementia n = 24, and normal controls n = 20). First, we confirmed that CIB is equally common in AD, other forms of dementia and frontal stroke. Second, we confirmed the association between CIB and executive function deficits. Third, we showed that individuals with CIB are more likely to exhibit the phenomenon in dual task situations, in which line-drawing is associated with an unrelated secondary task (tapping, counting, or counting backward). The present work supports and extends the contributions of Della Sala and colleagues demonstrating that CIB is enhanced when the general attentional load of the task increases., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Stimuli that potentially require a rapid defensive or avoidance action can appear from the periphery at any time in natural environments. de Wit et al. ( Cortex 127: 120-130, 2020) recently reported novel evidence suggestive of a fundamental neural mechanism that allows organisms to effectively deal with such situations. In the absence of any task, motor cortex excitability was found to be greater whenever gaze was directed away from either hand. If modulation of cortical excitability as a function of gaze location is a fundamental principle of brain organization, then one would expect its operation to be present outside of motor cortex, including brain regions involved in perception. To test this hypothesis, we applied single-pulse transcranial magnetic stimulation (TMS) to the right lateral occipital lobe while participants directed their eyes to the left, straight-ahead, or to the right, and reported the presence or absence of a phosphene. No external stimuli were presented. Cortical excitability as reflected by the proportion of trials on which phosphenes were elicited from stimulation of the right visual cortex was greater with eyes deviated to the right as compared with the left. In conjunction with our previous findings of change in motor cortex excitability when gaze and effector are not aligned, this eye position-driven change in visual cortex excitability presumably serves to facilitate the detection of stimuli and subsequent readiness to act in nonfoveated regions of space. The existence of this brain-wide mechanism has clear adaptive value given the unpredictable nature of natural environments in which human beings are situated and have evolved. NEW & NOTEWORTHY For many complex tasks, humans focus attention on the site relevant to the task at hand. Humans evolved and live in dangerous environments, however, in which threats arise from outside the attended site; this fact necessitates a process by which the periphery is monitored. Using single-pulse transcranial magnetic stimulation (TMS), we demonstrated for the first time that eye position modulates visual cortex excitability. We argue that this underlies at least in part what we term "surveillance attention."

Although behavioral evidence has shown that postural changes influence the ability to localize or detect tactile stimuli, little is known regarding the brain areas that modulate these effects. This 7T functional magnetic resonance imaging (fMRI) study explores the effects of touch of the hand as a function of hand location (right or left side of the body) and hand configuration (open or closed). We predicted that changes in hand configuration would be represented in contralateral primary somatosensory cortex (S1) and the anterior intraparietal area (aIPS), whereas change in position of the hand would be associated with alterations in activation in the superior parietal lobule. Multivoxel pattern analysis and a region of interest approach partially supported our predictions. Decoding accuracy for hand location was above chance level in superior parietal lobule (SPL) and in the anterior intraparietal (aIPS) area; above chance classification of hand configuration was observed in SPL and S1. This evidence confirmed the role of the parietal cortex in postural effects on touch and the possible role of S1 in coding the body form representation of the hand., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: As motor imagery is informed by the anticipated sensory consequences of action, including pain, we reasoned that motor imagery could provide a useful indicator of chronic back pain. We tested the hypothesis that mental motor imagery regarding body movements can provide a reliable assessment of low back pain., Methods: Eighty-five subjects with back pain and forty-five age-matched controls were shown two names of body parts and asked to indicate if they could imagine moving so that the named body parts touched. Three types of imagined movements were interrogated: movements of arms, movements of legs and movements requiring flexion and/or rotation of the low back., Results: Accuracy and reaction times were measured. Subjects with back pain were less likely to indicate that they could touch body parts than age-matched controls. The effect was observed only for those movements that required movement of the low back or legs, suggesting that the effect was not attributable to task difficulty or non-specific effects. There was an effect of pain severity. Compared to subjects with mild pain, subjects with severe pain were significantly less likely to indicate that they could move so that named body parts touched. There was a correlation between pain ratings and impaired performance for stimuli that involved the lower but not upper body., Discussion: As the Can They Touch task is quick, easy to administer and does not require an explicit judgment of pain severity, it may provide useful information to supplement the assessment of subjects with chronic pain., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Coslett, Medina, Goodman, Wang and Burkey.)

Background: Transcranial alternating current stimulation (tACS)-a noninvasive brain stimulation technique that modulates cortical oscillations in the brain-has shown the capacity to enhance working memory (WM) abilities in healthy individuals. The efficacy of tACS in the improvement of WM performance in healthy individuals is not yet fully understood., Objective/hypothesis: This meta-analysis aimed to systematically evaluate the efficacy of tACS in the enhancement of WM in healthy individuals and to assess moderators of response to stimulation. We hypothesized that active tACS would significantly enhance WM compared with sham. We further hypothesized that it would do so in a task-dependent manner and that differing stimulation parameters would affect response to tACS., Materials and Methods: Ten tACS studies met the inclusion criteria and provided 32 effects in the overall analysis. Random-effect models assessed mean change scores on WM tasks from baseline to poststimulation. The included studies involved varied in stimulation parameters, between-subject and within-subject study designs, and online vs offline tACS., Results: We observed a significant, heterogeneous, and moderate effect size for active tACS in the enhancement of WM performance over sham (Cohen's d = 0.5). Cognitive load, task domain, session number, and stimulation region showed a significant relationship between active tACS and enhanced WM behavior over sham., Conclusions: Our findings indicate that active tACS enhances WM performance in healthy individuals compared with sham. Future randomized controlled trials are needed to further explore key parameters, including personalized stimulation vs standardized electroencephalography frequencies and maintenance of tACS effects, and whether tACS-induced effects translate to populations with WM impairments., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Magnified vision of one's body part has been shown to improve tactile discrimination. We used an anesthetic cream (AC) to determine if somesthetic stimulation that alters the perception of the size of one's body would also improve two point-discrimination (2PD). In Experiment 1, application of AC caused an increase in perceived lip size and an improvement in a 2PD. As perceived lip size increased, subjects became more accurate in identifying that they had been touched in two locations. Experiment 2 confirmed this effect in a larger sample and introduced a control condition (no AC) that demonstrated that the change in performance was not attributable to practice or familiarity with the task. In Experiment 3, we showed that both AC and moisturizing cream improved subjects' ability to indicate that they had been touched in 2 locations, but the improvement was modulated by perceived lip size only for AC. These results support the idea that changes in the body representation influence 2PD., (© 2023. The Author(s).)

Transcranial magnetic stimulation (TMS) is used in several FDA-approved treatments and, increasingly, to treat neurological disorders in off-label uses. However, the mechanism by which TMS causes physiological change is unclear, as are the origins of response variability in the general population. Ideally, objective in vivo biomarkers could shed light on these unknowns and eventually inform personalized interventions. Continuous theta-burst stimulation (cTBS) is a form of TMS observed to reduce motor evoked potentials (MEPs) for 60 min or longer post-stimulation, although the consistency of this effect and its mechanism continue to be under debate. Here, we use glutamate-weighted chemical exchange saturation transfer (gluCEST) magnetic resonance imaging (MRI) at ultra-high magnetic field (7T) to measure changes in glutamate concentration at the site of cTBS. We find that the gluCEST signal in the ipsilateral hemisphere of the brain generally decreases in response to cTBS, whereas consistent changes were not detected in the contralateral region of interest (ROI) or in subjects receiving sham stimulation., (Copyright © 2022. Published by Elsevier Inc.)

Introduction: Lewy body diseases are pathologically characterized by α-synuclein pathology. Alzheimer's disease (AD) co-pathology can influence phenotypes. In vivo AD biomarkers can suggest the presence of this co-pathology in unusual cases, but pathological validation remains essential., Methods: This patient originally presented with corticobasal syndrome and later developed visual hallucinations and parkinsonism consistent with a synucleinopathy. The patient underwent CSF sampling, 18F-flortaucipir PET scanning, and brain donation with bilateral regions available for digital histological analysis., Results: CSF Aβ42 and t-tau were in the AD range. 18F-flortaucipir scanning showed right-lateralized retention in all lobes (t = 4.3-10.0, P  < .006). Neocortical stage Lewy body pathology and high levels of AD neuropathological changes were present at autopsy. There was right lateralization of α-synuclein and tau pathology ( T value = 3.1, P value = .007 and T value = 3.3, P value = .004 respectively)., Discussion: This case with overlapping tauopathy and synucleinopathy clinical features had in-depth biomarker characterization and rare bilateral post-mortem sampling showing lateralized tau and α-synuclein pathology suggesting possible synergistic relationships., Competing Interests: The authors have no competing interests or conflicts of interest to declare that are relevant to the content of this article., (© 2022 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Background: Phantom limb pain (PLP) is a common and in some cases debilitating consequence of upper- or lower-limb amputation for which current treatments are inadequate., Objective: This small clinical trial tested whether game-like interactions with immersive VR activities can reduce PLP in subjects with transtibial lower-limb amputation., Methods: Seven participants attended 5-7 sessions in which they engaged in a visually immersive virtual reality experience that did not require leg movements (Cool! TM ), followed by 10-12 sessions of targeted lower-limb VR treatment consisting of custom games requiring leg movement. In the latter condition, they controlled an avatar with 2 intact legs viewed in a head-mounted display (HTC Vive TM ). A motion-tracking system mounted on the intact and residual limbs controlled the movements of both virtual extremities independently., Results: All participants except one experienced a reduction of pain immediately after VR sessions, and their pre session pain levels also decreased over the course of the study. At a group level, PLP decreased by 28% after the treatment that did not include leg movements and 39.6% after the games requiring leg motions. Both treatments were successful in reducing PLP., Conclusions: This VR intervention appears to be an efficacious treatment for PLP in subjects with lower-limb amputation.

Unilateral spatial neglect (USN) is a syndrome characterized by inattention to or inaction in one side of space and affects between 23-46% of acute stroke survivors. The diagnosis and characterization of these symptoms in individual patients can be challenging and often requires skilled clinical staff. Virtual reality (VR) presents an opportunity to develop novel assessment tools for patients with USN. We aimed to design and build a VR tool to detect and characterize subtle USN symptoms, and to test the tool on subjects treated with inhibitory repetitive transcranial magnetic stimulation (TMS) of cortical regions associated with USN. We created three experimental conditions by applying TMS to two distinct regions of cortex associated with visuospatial processing- the superior temporal gyrus (STG) and the supramarginal gyrus (SMG) - and applied sham TMS as a control. We then placed subjects in a virtual reality environment in which they were asked to identify the flowers with lateral asymmetries of flowers distributed across bushes in both hemispaces, with dynamic difficulty adjustment based on each subject's performance. We found significant differences in average head yaw between subjects stimulated at the STG and those stimulated at the SMG and marginally significant effects in the average visual axis. VR technology is becoming more accessible, affordable, and robust, presenting an exciting opportunity to create useful and novel game-like tools. In conjunction with TMS, these tools could be used to study specific, isolated, artificial neurological deficits in healthy subjects, informing the creation of VR-based diagnostic tools for patients with deficits due to acquired brain injury. This study is the first to our knowledge in which artificially generated USN symptoms have been evaluated with a VR task.

Modulation of excitability in the motor system can be observed before overt movements but also in response to covert invitations to act. We asked whether such changes can be induced in the absence of even covert motor instructions, namely, as a function of the location of the hand with reference to the body. Participants received single-pulse TMS over the motor cortex while they placed their contralateral hand (right hand in Experiment 1, left hand in Experiment 2) to the right or left of their body midline, and looked either at or away from their hand. In both experiments, greater excitability was observed when gaze was directed to the right. This finding is interpreted as a consequence of left brain lateralization of motor attention. Contrary to our expectations, we furthermore consistently observed greater excitability when gaze was directed away from the hand. To account for this finding, we introduce the concept of "surveillance attention" which, we speculate, modulates cortical gain, and thereby cortical excitability. Its function is to increase readiness to act in non-foveated regions of space. Such a process confers an advantage in environments, like those in which humans evolved, in which threatening stimuli may appear unexpectedly, and at any time., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

We examined visually-guided reaching and perception in an individual who underwent resection of a small tumor in right intraparietal sulcus (pIPS). In the first experiment, she reached to targets presented on a touch screen. Vision was occluded from reach onset on half of the trials, whereas on the other half she had vision during the entire reach. For visually-guided reaching, she demonstrated significantly more reach errors for targets left of fixation versus right of fixation. However, there were no hemispatial differences when reaching without vision. Furthermore, her performance was consistent for reaches with either hand, providing evidence that pIPS encodes location based on an eye-centered reference frame. Second, previous studies reported that optic ataxics are more accurate when reaching to remembered versus visible target locations. We repeated the first experiment, adding a five second delay between stimulus presentation and reach initiation. In contrast to prior reports, she was less accurate in delayed versus immediate reaching. Finally, we examined whether a small pIPS resection would disrupt visuospatial processing in a simple perceptual task. We presented two small circles in succession in either the same location or offset at varying distances, and asked whether the two circles were presented in the same or different position. She was significantly more impaired left of fixation compared to right of fixation, providing evidence for a perceptual deficit after a dorsal stream lesion., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Increasing perceived hand size with magnifying lenses improves tactile discrimination and induces changes in action performance. We previously demonstrated that motor skills (tested with grip force, finger tapping, and a reach to grasp tasks) improved when actions were performed with magnified compared to normal vision; twenty-eight percent of 25 participants with stroke exhibited significant improvement on a composite measure of motor performance with magnification as compared to a session without magnification., Methods: To investigate the potential implications of magnification of vision for motor rehabilitation, we recruited individuals with stroke from the original cohort who exhibited an improvement of at least 10% in grip force and/or finger tapping for a home training protocol. Six individuals with stroke completed a two-week home-based training program in which they performed a range of activities while looking at their hand magnified. Motor skills were measured before, immediately after, and two weeks after the training., Results: Five of the six participants showed an improvement on motor tasks when tested after the training. In two participants the improvement was evident immediately after the training and persisted in time, while it occurred at two-weeks post-training in the other participants. These results suggest that the magnification of vision is a potential tool for the rehabilitation of post-stroke motor deficits., Competing Interests: The authors declare there are no competing interests.

The mechanisms and brain regions underlying error monitoring in complex action are poorly understood, yet errors and impaired error correction in these tasks are hallmarks of apraxia, a common disorder associated with left hemisphere stroke. Accounts of monitoring of language posit an internal route by which production planning or competition between candidate representations provide predictive signals that monitoring is required to prevent error, and an external route in which output is monitored using the comprehension system. Abnormal reliance on the external route has been associated with damage to brain regions critical for sensory-motor transformation and a pattern of gradual error 'clean-up' called conduite d'approche (CD). Action pantomime data from 67 participants with left hemisphere stroke were consistent with versions of internal route theories positing that competition signals monitoring requirements. Support Vector Regression Lesion Symptom Mapping (SVR-LSM) showed that lesions in the inferior parietal, posterior temporal, and arcuate fasciculus/superior longitudinal fasciculus predicted action conduite d'approche, overlapping the regions previously observed in the language domain. A second experiment with 12 patients who produced substantial action CD assessed whether factors impacting the internal route (action production ability, competition) versus external route (vision of produced actions, action comprehension) influenced correction attempts. In these 'high CD' patients, vision of produced actions and integrity of gesture comprehension interacted to determine successful error correction, supporting external route theories. Viewed together, these and other data suggest that skilled actions are monitored both by an internal route in which conflict aids in detection and correction of errors during production planning, and an external route that detects mismatches between produced actions and stored knowledge of action appearance. The parallels between language and action monitoring mechanisms and neuroanatomical networks pave the way for further exploration of common and distinct processes across these domains., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Increasing perceived hand size using magnifying lenses improves tactile discrimination and motor performance in neurologically-intact individuals. We tested whether magnification of the hand can improve motor function in individuals with chronic stroke. Twenty-five individuals with a history of stroke more than 6 months prior to testing underwent a series of tasks exploring different aspects of motor performance (grip force, finger tapping, reaching and grasping, and finger matching) under two visual conditions: magnified or normal vision. Performance was also assessed shortly after visual manipulation to test if these effects persisted. Twenty-eight percent of individuals showed an immediate significant improvement averaged across all tasks with magnification; similar beneficial responses were also observed in 32% of individuals after a short delay. These results suggest that magnification of the image of the hand may be of utility in rehabilitation of individuals with stroke., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Closing-in behavior (CIB) is observed in copying tasks (graphic or gestural) when the copy is performed near or on the top of the model. This symptom has been classically considered to be a manifestation of constructional apraxia and is often associated with a visuospatial impairment. More recent work emphasizes the attentional and/or executive nature of the behavior and its association with frontal lobe dysfunction. We describe three patients in whom CIB was associated with posterior parietal deficits of different etiologies (stroke in Patient 1 and dementia in Patients 2 and 3). In copying figures, Patient 1 produced the shape with high accuracy but the rendering overlapped the model, while for Patients 2 and 3 the copies were distorted but overlapping or in close proximity to the target. In gesture imitation, Patient 2 performed the gestures toward the examiner's space, while Patient 1 showed a peculiar form of CIB: when he was asked to place the ipsilesional arm in a position that mirrored the contralesional hand, Patient 1 moved his hand toward his contralesional hand. Patient 3 did not present gestural CIB. While CIB in Patient 1 was associated with selective deficits in executive functions and attention, additional visuospatial deficits were observed in Patients 2 and 3. The latter two patients showed a general visuoconstructional deficit. These case studies support a primary attentional account of CIB but also suggest that visuoconstructional impairments may contribute to the emergence of CIB, in some subjects. This evidence argues for different types of CIB with different cognitive and neural underpinnings. Furthermore, the data support the hypothesis of a differential involvement of fronto-parietal network in CIB.

Changes in the perceived size of a body part using magnifying lenses influence tactile perception and pain. We investigated whether the visual magnification of one's hand also influences the motor system, as indexed by transcranial magnetic stimulation (TMS)-induced motor evoked potentials (MEPs). In Experiment 1, MEPs were measured while participants gazed at their hand with and without magnification of the hand. MEPs were significantly larger when participants gazed at a magnified image of their hand. In Experiment 2, we demonstrated that this effect is specific to the hand that is visually magnified. TMS of the left motor cortex did not induce an increase of MEPs when participants looked at their magnified left hand. Experiment 3 was performed to determine if magnification altered the topography of the cortical representation of the hand. To that end, a 3 × 5 grid centered on the cortical hot spot (cortical location at which a motor threshold is obtained with the lowest level of stimulation) was overlaid on the participant's MRI image, and all 15 sites in the grid were stimulated with and without magnification of the hand. We confirmed the increase in the MEPs at the hot spot with magnification and demonstrated that MEPs significantly increased with magnification at sites up to 16.5 mm from the cortical hot spot. In Experiment 4, we used paired-pulse TMS to measure short-interval intracortical inhibition and intracortical facilitation. Magnification was associated with an increase in short-interval intracortical inhibition. These experiments demonstrate that the visual magnification of one's hand induces changes in motor cortex excitability and generates a rapid remapping of the cortical representation of the hand that may, at least in part, be mediated by changes in short-interval intracortical inhibition.

Lesion to symptom mapping (LSM) is a crucial tool for understanding the causality of brain-behavior relationships. The analyses are typically performed by applying statistical methods on individual brain voxels (VLSM), a method called the mass-univariate approach. Several authors have shown that VLSM suffers from limitations that may decrease the accuracy and reliability of the findings, and have proposed the use of multivariate methods to overcome these limitations. In this study, we propose a multivariate optimization technique known as sparse canonical correlation analysis for neuroimaging (SCCAN) for lesion to symptom mapping. To validate the method and compare it with mass-univariate results, we used data from 131 patients with chronic stroke lesions in the territory of the middle cerebral artery, and created synthetic behavioral scores based on the lesion load of 93 brain regions (putative functional units). LSM analyses were performed with univariate VLSM or SCCAN, and the accuracy of the two methods was compared in terms of both overlap and displacement from the simulated functional areas. Overall, SCCAN produced more accurate results - higher dice overlap and smaller average displacement - compared to VLSM. This advantage persisted at different sample sizes (N = 20-131) and different multiple comparison corrections (false discovery rate, FDR; Bonferroni; permutation-based family wise error rate, FWER). These findings were replicated with a fully automated SCCAN routine that relied on cross-validated predictive accuracy to find the optimal sparseness value. Simulations of one, two, and three brain regions showed a systematic advantage of SCCAN over VLSM; under no circumstance could VLSM exceed the accuracy obtained with SCCAN. When considering functional units composed of multiple brain areas VLSM identified fewer areas than SCCAN. The investigation of real scores of aphasia severity (aphasia quotient and picture naming) showed that SCCAN could accurately identify known language-critical areas, while VLSM either produced diffuse maps (FDR correction) or few scattered voxels (FWER correction). Overall, this study shows that a multivariate method, such as, SCCAN, outperforms VLSM in a number of scenarios, including functional dependency on single or multiple areas, different sample sizes, different multi-area combinations, and different thresholding mechanisms (FWER, Bonferroni, FDR). These results support previous claims that multivariate methods are in general more accurate than mass-univariate approaches, and should be preferred over traditional VLSM approaches. All the methods described in this study are available in the newly developed LESYMAP package for R., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose of Review: In part because of their striking clinical presentations, disorders of higher nervous system function figured prominently in the early history of neurology. These disorders are not merely historical curiosities, however. As apraxia, neglect, and agnosia have important clinical implications, it is important to possess a working knowledge of the conditions and how to identify them., Recent Findings: Apraxia is a disorder of skilled action that is frequently observed in the setting of dominant hemisphere pathology, whether from stroke or neurodegenerative disorders. In contrast to some previous teaching, apraxia has clear clinical relevance as it is associated with poor recovery from stroke. Neglect is a complex disorder with many different manifestations that may have different underlying mechanisms. Neglect is, in the author's view, a multicomponent disorder in which impairment in attention and arousal is a major contributor. Finally, agnosias come in a wide variety of forms, reflecting impairments ranging from low-level sensory processing to access to stored knowledge of the world (semantics)., Summary: The classic behavioral disorders reviewed here were of immense interest to early neurologists because of their arresting clinical phenomenology; more recent investigations have done much to advance the neuroscientific understanding of the disorders and to reveal their clinical relevance.

The neural mechanisms underlying time perception are of vital importance to a comprehensive understanding of behavior and cognition. Recent work has suggested a supramodal role for beta oscillations in measuring temporal intervals. However, the precise function of beta oscillations and whether their manipulation alters timing has yet to be determined. To accomplish this, we first re-analyzed two, separate EEG datasets and demonstrate that beta oscillations are associated with the retention and comparison of a memory standard for duration. We next conducted a study of 20 human participants using transcranial alternating current stimulation (tACS), over frontocentral cortex, at alpha and beta frequencies, during a visual temporal bisection task, finding that beta stimulation exclusively shifts the perception of time such that stimuli are reported as longer in duration. Finally, we decomposed trialwise choice data with a drift diffusion model of timing, revealing that the shift in timing is caused by a change in the starting point of accumulation, rather than the drift rate or threshold. Our results provide evidence for the intrinsic involvement of beta oscillations in the perception of time, and point to a specific role for beta oscillations in the encoding and retention of memory for temporal intervals.

Up to 90% of amputees experience sensations in their phantom limb, often including strong, persistent phantom limb pain (PLP). Standard treatments do not provide relief for the majority of people who experience PLP, but virtual reality (VR) has shown promise. This study provides additional evidence that game-like training with low-cost immersive VR activities can reduce PLP in lower-limb amputees. The user of our system views a real-time rendering of two intact legs in a head-mounted display while playing a set of custom games. The movements of both virtual extremities are controlled by measurements from inertial sensors mounted on the intact and residual limbs. Two individuals with unilateral transtibial amputation underwent multiple sessions of the VR treatment over several weeks. Both participants experienced a significant reduction of pain immediately after each VR session, and their pre-session pain levels also decreased greatly over the course of the study. Although preliminary, these data support the idea that VR interventions like ours may be an effective low-cost treatment of PLP in lower-limb amputees.

Although the parietal lobe was considered by many of the earliest investigators of disordered language to be a major component of the neural systems instantiating language, most views of the anatomic substrate of language emphasize the role of temporal and frontal lobes in language processing. We review evidence from lesion studies as well as functional neuroimaging, demonstrating that the left parietal lobe is also crucial for several aspects of language. First, we argue that the parietal lobe plays a major role in semantic processing, particularly for "thematic" relationships in which information from multiple sensory and motor domains is integrated. Additionally, we review a number of accounts that emphasize the role of the left parietal lobe in phonologic processing. Although the accounts differ somewhat with respect to the nature of the linguistic computations subserved by the parietal lobe, they share the view that the parietal lobe is essential for the processes by which sound-based representations are transcoded into a format that can drive action systems. We suggest that investigations of the linguistic capacities of the parietal lobe constrained by the understanding of the parietal lobe in action and multimodal sensory integration may serve to enhance not only our understanding of language, but also the relationship between language and more basic brain functions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Antemortem behavioural and anatomic abnormalities have largely been associated with right hemisphere disease in behavioural-variant frontotemporal dementia, but post-mortem neuropathological examination of bilateral hemispheres remains to be defined. Here we measured the severity of post-mortem pathology in both grey and white matter using a validated digital image analysis method in four cortical regions sampled from each hemisphere in 26 patients with behavioural-variant frontotemporal dementia, including those with frontotemporal degeneration (i.e. tau = 9, TDP-43 = 14, or FUS = 1 proteinopathy) or Alzheimer's pathology (n = 2). We calculated an asymmetry index based on the difference in measured pathology from each left-right sample pair. Analysis of the absolute value of the asymmetry index (i.e. degree of asymmetry independent of direction) revealed asymmetric pathology for both grey and white matter in all four regions sampled in frontototemporal degeneration patients with tau or TDP-43 pathology (P ≤ 0.01). Direct interhemispheric comparisons of regional pathology measurements within-subjects in the combined tauopathy and TDP-43 proteinopathy group found higher pathology in the right orbitofrontal grey matter compared to the left (P < 0.01) and increased pathology in ventrolateral temporal lobe grey matter of the left hemisphere compared to the right (P < 0.02). Preliminary group-wise comparisons between tauopathy and TDP-43 proteinopathy groups found differences in patterns of interhemispheric burden of grey and white matter regional pathology, with greater relative white matter pathology in tauopathies. To test the association of pathology measurement with ante-mortem observations, we performed exploratory analyses in the subset of patients with imaging data (n = 15) and found a direct association for increasing pathologic burden with decreasing cortical thickness in frontotemporal regions on ante-mortem imaging in tauopathy (P = 0.001) and a trend for TDP-43 proteinopathy (P = 0.06). Exploratory clinicopathological correlations demonstrated an association of socially-inappropriate behaviours with asymmetric right orbitofrontal grey matter pathology, and reduced semantically-guided category naming fluency was associated asymmetric white matter pathology in the left ventrolateral temporal region. We conclude that pathologic disease burden is distributed asymmetrically in behavioural-variant frontotemporal dementia, although not universally in the right hemisphere, and this asymmetry contributes to the clinical heterogeneity of the disorder. The basis for this asymmetric profile is enigmatic but may reflect distinct species or strains of tau and TDP-43 pathologies with propensities to spread by distinct cell- and region-specific mechanisms. Patterns of region-specific pathology in the right hemisphere as well as the left hemisphere may play a role in antemortem clinical observations, and these observations may contribute to antemortem identification of molecular pathology in frontotemporal degeneration., (© The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background and Objective: While noninvasive brain stimulation techniques show promise for language recovery after stroke, the underlying mechanisms remain unclear. We applied inhibitory repetitive transcranial magnetic stimulation (rTMS) to regions of interest in the right inferior frontal gyrus of patients with chronic poststroke aphasia and examined changes in picture naming performance and cortical activation., Methods: Nine patients received 10 days of 1-Hz rTMS (Monday through Friday for 2 weeks). We assessed naming performance before and immediately after stimulation on the first and last days of rTMS therapy, and then again at 2 and 6 months post-rTMS. A subset of six of these patients underwent functional magnetic resonance imaging pre-rTMS (baseline) and at 2 and 6 months post-rTMS., Results: Naming accuracy increased from pre- to post-rTMS on both the first and last days of treatment. We also found naming improvements long after rTMS, with the greatest improvements at 6 months post-rTMS. Long-lasting effects were associated with a posterior shift in the recruitment of the right inferior frontal gyrus: from the more anterior Brodmann area 45 to the more posterior Brodmann areas 6, 44, and 46. The number of left hemispheric regions recruited for naming also increased., Conclusions: This study found that rTMS to the right hemisphere Broca area homologue confers long-lasting improvements in picture naming performance. The mechanism involves dynamic bilateral neural network changes in language processing, which take place within the right prefrontal cortex and the left hemisphere more generally., Clinical Trial Registration: ClinicalTrials.gov (Identifier NCT00608582).

The severity of post-stroke aphasia and the potential for recovery are highly variable and difficult to predict. Evidence suggests that optimal estimation of aphasia severity requires the integration of multiple neuroimaging modalities and the adoption of new methods that can detect multivariate brain-behavior relationships. We created and tested a multimodal framework that relies on three information sources (lesion maps, structural connectivity, and functional connectivity) to create an array of unimodal predictions which are then fed into a final model that creates "stacked multimodal predictions" (STAMP). Crossvalidated predictions of four aphasia scores (picture naming, sentence repetition, sentence comprehension, and overall aphasia severity) were obtained from 53 left hemispheric chronic stroke patients (age: 57.1 ± 12.3 yrs, post-stroke interval: 20 months, 25 female). Results showed accurate predictions for all four aphasia scores (correlation true vs. predicted: r = 0.79-0.88). The accuracy was slightly smaller but yet significant (r = 0.66) in a full split crossvalidation with each patient considered as new. Critically, multimodal predictions produced more accurate results that any single modality alone. Topological maps of the brain regions involved in the prediction were recovered and compared with traditional voxel-based lesion-to-symptom maps, revealing high spatial congruency. These results suggest that neuroimaging modalities carry complementary information potentially useful for the prediction of aphasia scores. More broadly, this study shows that the translation of neuroimaging findings into clinically useful tools calls for a shift in perspective from unimodal to multimodal neuroimaging, from univariate to multivariate methods, from linear to nonlinear models, and, conceptually, from inferential to predictive brain mapping. Hum Brain Mapp 38:5603-5615, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Reaching and grasping movements rely on visual information regarding the target characteristics (e.g. size) and the hand position during the action execution. Changes in the visual representation of the body (e.g. increase in the perceived size of the hand) can modify action performance, but it is still unclear how these modifications interact with changes in the external environment. We investigated this topic by manipulating the perceived size of both hand and target objects and the degree of visual feedback available during the movement execution. Ten young adults were asked to reach and grasp geometrical objects in four different conditions: (i) with normal vision with the light on, (ii) with normal vision in the dark, (iii) using magnifying lenses in the light and (iv) using magnifying lenses in the dark. In contrast with previous works, our results show that movement execution is longer in magnified vision compared to normal when the action is executed in the light, but the grasping component was not affected by changes in size in this condition. On the contrary, when the visual feedback of the hand was removed and participants performed the action in the dark, movements were faster and the distances across fingers larger in the magnified than normal vision. This pattern of data suggests that grasping movements adapt rapidly and compensate for changes in vision when this process depends on the degree of visual feedback and/or environmental cues available. In the debate regarding the dissociation between action and perception, our data suggest that action may overcome changes in perception when visual feedback is available, but perception may trick action in situations of reduced visual information., (Copyright © 2017 Elsevier B.V. All rights reserved.)