Search

Spatial neglect is a strong and negative predictor of general functional outcome after stroke, and its therapy remains a challenge. Whereas inhibitory non-invasive brain stimulation over the contralesional, intact hemisphere has generally been shown to ameliorate neglect on a group level, a conspicuous variability of the effects at the individual level is typically observed. We aimed to assess the characteristics and determinants of the effects of inhibitory non-invasive brain stimulation in neglect, identifying which patients would respond to this therapeutic approach and which not. To this end, we prospectively included 60 patients with a subacute right-hemispheric stroke. In 30 patients with spatial neglect, continuous theta burst stimulation (cTBS) was applied over the left posterior parietal cortex in a randomized clinical trial, either in eight or 16 trains, or as sham stimulation. Thirty patients without neglect served as a control group. Neglect severity was measured with a neuropsychological test battery and the Catherine Bergego Scale, at admission to and at discharge from inpatient neurorehabilitation, as well as at 3 months follow-up. General functional outcome was assessed by means of the Functional Independence Measure and the Lucerne ICF-based Multidisciplinary Observation Scale. The impact of clinical and demographic factors was evaluated, and the influence of lesion location and extension was assessed by means of voxel-based lesion-symptom mapping. On a group level, both cTBS protocols (i.e. eight and 16 trains) significantly reduced neglect severity in both the Catherine Bergego Scale and the neuropsychological tests, at discharge and 3 months later. Furthermore, cTBS significantly improved general functional outcome. On an individual level, hierarchical cluster and voxel-based lesion-symptom mapping analyses revealed that the variability in the responses to cTBS is determined by the integrity of interhemispheric connections within the corpus callosum, in particular parieto-parietal connections. In cTBS responders, in whom neglect and general functional outcome were significantly improved, the corpus callosum was intact, whereas this was not the case in cTBS non-responders. Moreover, analyses based on the proportional recovery rule and the Maugeri predictive stroke recovery model showed that the recovery of neglect and of the activities of daily living was accelerated only in cTBS responders. Furthermore, the level of activities of daily living recovery of these neglect patients was brought close to the one of right-hemispheric control patients without neglect. Hence, in neglect patients with intact interhemispheric connectivity, cTBS over the contralesional posterior parietal cortex significantly improves and accelerates neglect recovery and, associated with it, general functional outcome., (© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The role of nonverbal communication in patients with post-stroke language impairment (aphasia) is not yet fully understood. This study investigated how aphasic patients perceive and produce co-speech gestures during face-to-face interaction, and whether distinct brain lesions would predict the frequency of spontaneous co-speech gesturing. For this purpose, we recorded samples of conversations in patients with aphasia and healthy participants. Gesture perception was assessed by means of a head-mounted eye-tracking system, and the produced co-speech gestures were coded according to a linguistic classification system. The main results are that meaning-laden gestures (e.g., iconic gestures representing object shapes) are more likely to attract visual attention than meaningless hand movements, and that patients with aphasia are more likely to fixate co-speech gestures overall than healthy participants. This implies that patients with aphasia may benefit from the multimodal information provided by co-speech gestures. On the level of co-speech gesture production, we found that patients with damage to the anterior part of the arcuate fasciculus showed a higher frequency of meaning-laden gestures. This area lies in close vicinity to the premotor cortex and is considered to be important for speech production. This may suggest that the use of meaning-laden gestures depends on the integrity of patients' speech production abilities.

Objective: Common sequelae of subarachnoid hemorrhage (SAH) include somatic and/or cognitive impairment. This can cause emotional stress, social tensions, and difficulties in relationships. To test our hypothesis that more severe somatic and cognitive impairments increased the likelihood of disruption of a relationship after SAH, we assessed the integrity of marriage or partnership status in a well-evaluated subset of SAH patients., Methods: Our sample comprised 50 SAH patients who were discharged to a neurologic, in-house rehabilitation center between 2005 and 2010. Deficits on admission to the rehabilitation center were divided into 18 categories and grouped into minor and major somatic deficits, as well as cognitive deficits. Clinical outcome scores, marital/partnership status, and duration of partnership before ictus were recorded. A follow-up questionnaire after 4.3 (2012) and 8.8 (2017) years was used to assess changes in marital/partnership status. Possible predictor parameters were estimated and included in a stepdown regression analysis., Results: In 2012, after a mean follow-up of 4.3 years, 8 of the 50 SAH patients were divorced or separated, whereas after 8.8 years only 1 additional relationship had ended. In our regression model analysis, a "short duration of relationship" before SAH and the presence of a "few minor somatic deficits" were associated with a higher likelihood of divorce or separation in the near future and remained unchanged at long-term follow-up., Conclusion: Contrary to our hypothesis, neither the presence of severe somatic or cognitive deficits nor clinical evaluation scores reliably predicted divorce or separation after SAH., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Cross-modal spatial cueing can affect performance in a visual search task. For example, search performance improves if a visual target and an auditory cue originate from the same spatial location, and it deteriorates if they originate from different locations. Moreover, it has recently been postulated that multisensory settings, i.e., experimental settings, in which critical stimuli are concurrently presented in different sensory modalities (e.g., visual and auditory), may trigger asymmetries in visuospatial attention. Thereby, a facilitation has been observed for visual stimuli presented in the right compared to the left visual space. However, it remains unclear whether auditory cueing of attention differentially affects search performance in the left and the right hemifields in audio-visual search tasks. The present study investigated whether spatial asymmetries would occur in a search task with cross-modal spatial cueing. Participants completed a visual search task that contained no auditory cues (i.e., unimodal visual condition), spatially congruent, spatially incongruent, and spatially non-informative auditory cues. To further assess participants' accuracy in localising the auditory cues, a unimodal auditory spatial localisation task was also administered. The results demonstrated no left/right asymmetries in the unimodal visual search condition. Both an additional incongruent, as well as a spatially non-informative, auditory cue resulted in lateral asymmetries. Thereby, search times were increased for targets presented in the left compared to the right hemifield. No such spatial asymmetry was observed in the congruent condition. However, participants' performance in the congruent condition was modulated by their tone localisation accuracy. The findings of the present study demonstrate that spatial asymmetries in multisensory processing depend on the validity of the cross-modal cues, and occur under specific attentional conditions, i.e., when visual attention has to be reoriented towards the left hemifield.

Background: Approximately 70-80% of stroke survivors have limited activities of daily living, mainly due to dexterous problems. Videogame-based training (VBT) along with virtual reality seems to be beneficial to train upper limb function., Objective: To evaluate the usability of VBT using the Leap Motion Controller (LMC) to train fine manual dexterity in the early rehabilitation phase of stroke patients as an add-on to conventional therapy. Additionally, this study aimed to estimate the feasibility and potential efficacy of the VBT., Methods: During 3 months, 64 stroke patients were screened for eligibility, 13 stroke patients were included (4 women and 9 men; age range: 24-91 years; mean time post stroke: 28.2 days)., Intervention: Nine sessions of 30 min VBT, three times per week as an add-on to conventional therapy with stroke inpatients., Outcome Measures: Primary outcome was the usability of the system measured with the System Usability Scale. Secondary outcomes concerning feasibility were the compliance rate calculated from the total time spent on the intervention (TT) compared to planned time, the opinion of participants via open-end questions, and the level of active participation measured with the Pittsburgh Rehabilitation Participation Scale. Regarding the potential efficacy secondary outcomes were: functional dexterity measured with the Nine Hole Peg Test (NHPT), subjective dexterity measured with the Dexterity Questionnaire 24, grip strength measured with the Jamar dynamometer, and motor impairment of the upper limb measured with the Fugl-Meyer Upper Extremity (FM-UE) scale., Results: Primarily, the usability of the system was good to excellent. The patient's perception of usability remained stable over a mean period of 3 weeks of VBT. Secondly, the compliance rate was good, and the level of active participation varied between good and very good. The opinion of the participants revealed that despite individual differences, the overall impression of the therapy and device was good. Patients showed significant improvements in hand dexterity. No changes were found in motor impairment of the upper limb (FM-UE) during intervention., Conclusion: VBT using LMC is a usable rehabilitation tool to train dexterity in the early rehabilitation phase of stroke inpatients.

In stroke patients, the clinical presentation of visual field defects (VFDs) is frequently accompanied by visual neglect, i.e., the inability to attend and respond to the contralesional space. However, the diagnostic discrimination between the lack of reactions to contralesional stimuli due to VFDs or visual neglect is challenging during clinical examination. This discrimination is particularly relevant, since both clinical pictures are associated with different therapeutic approaches and outcomes. The aim of this study was to systematically investigate the effectiveness of trunk rotation toward the contralesional side-a manipulation dissociating the coordinate system of the trunk from that of the head and eyes-in disentangling real VFDs from "pseudo-VFDs" that occur due to visual neglect. Twenty patients with a left-sided VFD after a right-hemispheric stroke (10 additionally showing visual neglect in neuropsychological testing, VFD + neglect; 10 without neglect, VFD) were tested with Goldmann perimetry in both standard and trunk rotation conditions. In the standard condition, both VFD and VFD + neglect patients showed a conspicuous narrowing of the left visual field. However, trunk rotation triggered strikingly different patterns of change in the two groups: it elicited a significant increase in visual field extension in the VFD + neglect group, but left visual field extension virtually unchanged in the VFD group. Our results highlight contralesional trunk rotation as a simple, viable manipulation to effectively and rapidly disentangle real VFDs from "pseudo-VFDs" (i.e., due to visual neglect) during clinical examination.

Background: Patients with Parkinson's disease exhibit disturbed manual dexterity. This impairment leads to difficulties in activities of daily living, such as buttoning a shirt or hand-writing. The aim of the present study was to investigate the effectiveness of a home-based dexterity program on fine motor skills in a single-blinded, randomized controlled trial, in patients with Parkinson's disease., Methods: One hundred and three patients with Parkinson's disease (aged between 48 and 80 years, Hoehn & Yahr stage I-IV) were randomized to either a home-based dexterity program (HOMEDEXT) or Thera-band program. All patients trained over a period of 4 weeks, 5 times/week, 30 min for each session. A baseline, post-intervention, and follow-up assessment (12 weeks later, time period without intervention) were done. The primary outcome measure was dexterity as measured with the Nine Hole peg test (9-HPT). Secondary outcome measures included strength, motor parkinsonian symptoms, dexterity-related activities of daily living (ADL) and Health-related Quality of Life (HrQoL)., Results: There was a significant difference in favor of the HOMEDEXT group as compared to the Thera-band group on the primary outcome 9-HPT (p = 0.006) and dexterity-related ADL (p = 0.02) at post intervention. No significant differences were found for the other outcomes, nor at follow-up., Conclusion: This is the first randomized controlled trial showing that an intensive, task specific home-based dexterity program significantly improved fine motor skills in Parkinson's disease. The effect generalized to dexterity-related ADL functions. As these improvements did not sustain, the finding suggest that continuous training is required to maintain the benefit., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background and Purpose: Motor tests performed at stroke onset have been shown to predict the recovery of upper limb motor impairment. Less is known about upper limb recovery at the level of functional activity or of participation and how spatial neglect may influence the integration of the upper limb in the activities of daily living (ADL). Our objective was to investigate whether the initial severity of spatial neglect may predict upper limb use in ADL., Methods: Eighty-two patients with a right-hemispheric stroke (RHS) were prospectively included in the study. They were assessed twice in the acute/subacute and in the subacute/chronic phases (mean time interval of 45 days) after stroke. The Catherine Bergego Scale (CBS) was used to quantify the influence of spatial neglect on the ADL. Contralesional upper limb use in the ADL was evaluated with the Lucerne international classification of function, disability and health-based Multidisciplinary Observation Scale. Hand strength was measured using the Jamar, dexterity with the Nine Hole Peg test, and tactile perception using the stereognosis subtest of the Nottingham Sensory Assessment. Cognitive functions were assessed with the Montreal Cognitive Assessment., Results: Regression analyses revealed that spatial neglect is an independent and a significant predictor of upper limb outcome. A CBS score of ≤5 at the time of admission to neurorehabilitation care was highly predictive for good upper limb use in the ADL 45 days later., Conclusions: This study demonstrates that spatial neglect severity, as observed in the ADL, is a significant and an independent predictor of upper limb outcome. Neglect therapy is thus needed to further improve contralesional upper limb use in the ADL in RHS patients., (© 2017 S. Karger AG, Basel.)

With a reduced level of alertness, healthy individuals typically show a rightward shift when deploying visual attention in space. The impact of alertness on the neural networks governing visuospatial attention is, however, poorly understood. By using a transcranial magnetic stimulation twin-coil approach, the present study aimed at investigating the effects of an alertness manipulation on the excitability of the left and the right posterior parietal cortices (PPCs), crucial nodes of the visuospatial attentional network. Participants' visuospatial attentional deployment was assessed with a free visual exploration task and concurrent eye tracking. Their alertness level was manipulated through the time of the day, that is, by testing chronotypically defined evening types both during their circadian on- and off-peak times. The results revealed an increased excitability of the left compared with the right PPC during low alertness. On the horizontal dimension, these results were accompanied by a significant rightward shift in the center and a bilateral narrowing in the periphery of the visual exploration field, as well as a central upward shift on the vertical dimension. The findings show that the manipulation of non-spatial attentional aspects (i.e., alertness) can affect visuospatial attentional deployment and modulate the excitability of areas subtending spatial attentional control., (© The Author 2016. Published by Oxford University Press.)

Background: Patients with Parkinson's disease exhibit disturbed dexterity. Validated self-reported outcomes for dexterity in Parkinson's disease are lacking. The aim of this study was to investigate the reliability, content and construct validity of a new Dexterity Questionnaire 24., Methods: One hundred and three patients with Parkinson's disease completed the Dexterity Questionnaire 24 (score range 24-96), at baseline and four weeks later. The internal consistency was determined. Test-retest reliability was assessed in a subgroup (N = 44). Standard error of measurements and the minimal detectable change were defined. The construct validity was examined in the whole group (N = 103). Floor and ceiling effects were investigated., Results: The internal consistency of the Dexterity Questionnaire 24 was high (α = 0.91). High test-retest reliability was found (Intra Class Correlation Coefficient = 0.91, Confidence interval: 0.84-0.95). Standard error of measurement was 2.9 and minimal detectable change was 8 points. (i.e., 11%). Good structural, convergent and divergent validity of the Dexterity questionnaire 24 was found (r = 0.73 with Activities of Daily Living-subscale of the Parkinson's Disease Questionnaire-39, and r = 0.66, and r = 0.50, p-values all < 0.0001, respectively with the subscales II and III of the Movement Disorders Society-Unified Parkinson Disease Rating Scale). Low not significant correlations were found between the Dexterity Questionnaire 24 and the subscales stigma and social support (r = 0.20, and r = 0.14 respectively). No floor or ceiling effects were found for the total Dexterity Questionnaire 24., Conclusion: The Dexterity Questionnaire 24 is valid and reliable for evaluating dexterity in patients with Parkinson's disease., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Dorsal pre-motor cortex (PMd) is thought to play a role in fine motor control. The aim of the present study was to investigate whether inhibitory or excitatory stimulation of PMd would have an impact on manual dexterity in Parkinson's disease (PD). Fifteen patients with PD participated in this study. High resolution structural MRI was used for neuro-navigated TBS. Participants were targeted with one train of TBS in three experimental sessions: sham stimulation over vertex, continuous TBS (cTBS) over PMd and intermittent TBS (iTBS) over PMd, respectively. Dexterity was measured by a coin rotation task (CRT), which is a valid measure to detect limb kinetic apraxia (LKA). Neither cTBS or iTBS significantly interfered with CRT. Post hoc sub-analysis in a group of PD patients (n = 5) with stronger baseline impairment, indicating LKA, revealed further deterioration of dexterous performance for the cTBS condition (p = 0.04). This sham controlled pilot study demonstrates that TBS over PMd does not significantly interfere with dexterity in PD. However, patients with dexterous impairment qualifying for LKA may be more susceptible to TBS.

An impairment of the spatial deployment of visual attention during exploration of static (i.e., motionless) stimuli is a common finding after an acute, right-hemispheric stroke. However, less is known about how these deficits: (a) are modulated through naturalistic motion (i.e., without directional, specific spatial features); and, (b) evolve in the subacute/chronic post-stroke phase. In the present study, we investigated free visual exploration in three patient groups with subacute/chronic right-hemispheric stroke and in healthy subjects. The first group included patients with left visual neglect and a left visual field defect (VFD), the second patients with a left VFD but no neglect, and the third patients without neglect or VFD. Eye movements were measured in all participants while they freely explored a traffic scene without (static condition) and with (dynamic condition) naturalistic motion, i.e., cars moving from the right or left. In the static condition, all patient groups showed similar deployment of visual exploration (i.e., as measured by the cumulative fixation duration) as compared to healthy subjects, suggesting that recovery processes took place, with normal spatial allocation of attention. However, the more demanding dynamic condition with moving cars elicited different re-distribution patterns of visual attention, quite similar to those typically observed in acute stroke. Neglect patients with VFD showed a significant decrease of visual exploration in the contralesional space, whereas patients with VFD but no neglect showed a significant increase of visual exploration in the contralesional space. No differences, as compared to healthy subjects, were found in patients without neglect or VFD. These results suggest that naturalistic motion, without directional, specific spatial features, may critically influence the spatial distribution of visual attention in subacute/chronic stroke patients., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Increasing time-on-task leads to fatigue and, as shown by previous research, differentially affects the deployment of visual attention towards the left and the right visual space. In healthy participants, an increasing rightward bias is commonly observed with increasing time-on-task. Yet, it is unclear whether specific mechanisms involved in the spatial deployment of visual attention are differentially affected by increasing time-on-task. The aim of the present study was to investigate whether prolonged time-on-task would affect a specific mechanism of visuospatial attentional deployment, namely attentional disengagement, in an asymmetrical fashion. For this purpose, we administered to healthy participants a prolonged gap/overlap saccadic paradigm, with left- and right-sided target stimuli. This oculomotor paradigm allowed to quantify disengagement costs according to the direction of the subsequent attentional shifts, and to evaluate the temporal development of disengagement costs with increasing time-on-task. Our results show that, with increasing time-on-task, participants demonstrated significantly lower disengagement costs for rightward compared to leftward saccades. These effects were specific, since concurring side differences of saccadic latencies were found for overlap trials (requiring attentional disengagement), but not for gap trials (requiring no or less attentional disengagement). Moreover, the results were paralleled by a non-lateralised decrease in saccadic peak velocity with increasing time-on-task, a common finding indicating an increasing level of fatigue. Our findings support the idea that non-spatial attentional aspects, such as fatigue due to increasing time-on-task, can have a substantial influence on the spatial deployment of visual attention, in particular on its disengagement, depending on the direction of the subsequent attentional shift., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The human turn-taking system regulates the smooth and precise exchange of speaking turns during face-to-face interaction. Recent studies investigated the processing of ongoing turns during conversation by measuring the eye movements of noninvolved observers. The findings suggest that humans shift their gaze in anticipation to the next speaker before the start of the next turn. Moreover, there is evidence that the ability to timely detect turn transitions mainly relies on the lexico-syntactic content provided by the conversation. Consequently, patients with aphasia, who often experience deficits in both semantic and syntactic processing, might encounter difficulties to detect and timely shift their gaze at turn transitions. To test this assumption, we presented video vignettes of natural conversations to aphasic patients and healthy controls, while their eye movements were measured. The frequency and latency of event-related gaze shifts, with respect to the end of the current turn in the videos, were compared between the two groups. Our results suggest that, compared with healthy controls, aphasic patients have a reduced probability to shift their gaze at turn transitions but do not show significantly increased gaze shift latencies. In healthy controls, but not in aphasic patients, the probability to shift the gaze at turn transition was increased when the video content of the current turn had a higher lexico-syntactic complexity. Furthermore, the results from voxel-based lesion symptom mapping indicate that the association between lexico-syntactic complexity and gaze shift latency in aphasic patients is predicted by brain lesions located in the posterior branch of the left arcuate fasciculus. Higher lexico-syntactic processing demands seem to lead to a reduced gaze shift probability in aphasic patients. This finding may represent missed opportunities for patients to place their contributions during everyday conversation.

Background: Good responsive functional outcome measures are important to measure change in stroke patients. The aim of study was to compare the internal and external responsiveness, floor and ceiling effects of the motor, cognition, and communication subscales of the Lucerne ICF-based Multidisciplinary Observation Scale (LIMOS) with the motor and cognition subscales of the Functional Independence Measure (FIM), and the Barthel Index (BI), in a large cohort of stroke patients., Methods: One hundred eighteen stroke patients participated in this study. Admission and discharge score distributions of the LIMOS motor, LIMOS cognition and communication, FIM motor and FIM cognition, and BI were analyzed based on skewness and kurtosis. Floor and ceiling effects of the scales were determined. Internal responsiveness was assessed with t -tests, effect sizes (ESs), and standardized response means (SRMs). External responsiveness was investigated with linear regression analyses., Results: The LIMOS motor and LIMOS cognition and communication subscales were more responsive, expressed by higher ESs (ES = 0.65, SRM = 1.17 and ES = 0.52, SRM = 1.17, respectively) as compared with FIM motor (ES = 0.54, SRM = 0.96) and FIM cognition (ES = 0.41, SRM = 0.88) and the BI (ES = 0.41, SRM = 0.65). The LIMOS subscales showed neither floor nor ceiling effects at admission and discharge (all <15%). In contrast, ceiling effects were found for the FIM motor (16%), FIM cognition (15%) at discharge and the BI at admission (22%) and discharge (43%). LIMOS motor and LIMOS cognition and communication subscales significantly correlated ( p  < 0.0001) with a change in the FIM motor and FIM cognition subscales, suggesting good external responsiveness., Conclusion: We found that the LIMOS motor and LIMOS cognition and communication, which are ICF-based multidisciplinary standardized observation scales, might have the potential to better detect changes in functional outcome of stroke patients, compared with the FIM motor and FIM cognition and the BI.

Reading strategies vary across languages according to orthographic depth - the complexity of the grapheme in relation to phoneme conversion rules - notably at the level of eye movement patterns. We recently demonstrated that a group of early bilinguals, who learned both languages equally under the age of seven, presented a first fixation location (FFL) closer to the beginning of words when reading in German as compared with French. Since German is known to be orthographically more transparent than French, this suggested that different strategies were being engaged depending on the orthographic depth of the used language. Opaque languages induce a global reading strategy, and transparent languages force a local/serial strategy. Thus, pseudo-words were processed using a local strategy in both languages, suggesting that the link between word forms and their lexical representation may also play a role in selecting a specific strategy. In order to test whether corresponding effects appear in late bilinguals with low proficiency in their second language (L2), we present a new study in which we recorded eye movements while two groups of late German-French and French-German bilinguals read aloud isolated French and German words and pseudo-words. Since, a transparent reading strategy is local and serial, with a high number of fixations per stimuli, and the level of the bilingual participants' L2 is low, the impact of language opacity should be observed in L1. We therefore predicted a global reading strategy if the bilinguals' L1 was French (FFL close to the middle of the stimuli with fewer fixations per stimuli) and a local and serial reading strategy if it was German. Thus, the L2 of each group, as well as pseudo-words, should also require a local and serial reading strategy. Our results confirmed these hypotheses, suggesting that global word processing is only achieved by bilinguals with an opaque L1 when reading in an opaque language; the low level in the L2 gives way to a local and serial reading strategy. These findings stress the fact that reading behavior is influenced not only by the linguistic mode but also by top-down factors, such as readers' proficiency.

Cognitive impairment is found in up to 70% of patients with multiple sclerosis (MS). Once thought of as a variant of subcortical dementia with a characteristic set of deficits, we now know that MS-related cognitive impairment can have many faces. This conceptual change in neuropsychology is embedded in a paradigm shift in the neuroscientific understanding of MS over the past 25 years: Partly based on modern neuroimaging techniques, the classical view of MS as an inflammatory demyelinating disease affecting the white matter of the central nervous system has been extended. In particular, many studies have shown that the MS pathology also includes neurodegeneration, and that gray matter structures such as the cerebral cortex can also show focal lesions, atrophy, or both. The authors present an updated summary of the clinical manifestation and neuroimaging correlates of cognitive impairment in MS, and discuss the relatively few treatment options available to date., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

One of the leading approaches to non-invasively treat a variety of brain disorders is transcranial magnetic stimulation (TMS). However, despite its clinical prevalence, very little is known about the action of TMS at the cellular level let alone what effect it might have at the subcellular level (e.g. dendrites). Here, we examine the effect of single-pulse TMS on dendritic activity in layer 5 pyramidal neurons of the somatosensory cortex using an optical fiber imaging approach. We find that TMS causes GABAB-mediated inhibition of sensory-evoked dendritic Ca(2+) activity. We conclude that TMS directly activates fibers within the upper cortical layers that leads to the activation of dendrite-targeting inhibitory neurons which in turn suppress dendritic Ca(2+) activity. This result implies a specificity of TMS at the dendritic level that could in principle be exploited for investigating these structures non-invasively.

Background: Co-speech gestures are omnipresent and a crucial element of human interaction by facilitating language comprehension. However, it is unclear whether gestures also support language comprehension in aphasic patients. Using visual exploration behavior analysis, the present study aimed to investigate the influence of congruence between speech and co-speech gestures on comprehension in terms of accuracy in a decision task., Method: Twenty aphasic patients and 30 healthy controls watched videos in which speech was either combined with meaningless (baseline condition), congruent, or incongruent gestures. Comprehension was assessed with a decision task, while remote eye-tracking allowed analysis of visual exploration., Results: In aphasic patients, the incongruent condition resulted in a significant decrease of accuracy, while the congruent condition led to a significant increase in accuracy compared to baseline accuracy. In the control group, the incongruent condition resulted in a decrease in accuracy, while the congruent condition did not significantly increase the accuracy. Visual exploration analysis showed that patients fixated significantly less on the face and tended to fixate more on the gesturing hands compared to controls., Conclusion: Co-speech gestures play an important role for aphasic patients as they modulate comprehension. Incongruent gestures evoke significant interference and deteriorate patients' comprehension. In contrast, congruent gestures enhance comprehension in aphasic patients, which might be valuable for clinical and therapeutic purposes.

Visual neglect is considerably exacerbated by increases in visual attentional load. These detrimental effects of attentional load are hypothesised to be dependent on an interplay between dysfunctional inter-hemispheric inhibitory dynamics and load-related modulation of activity in cortical areas such as the posterior parietal cortex (PPC). Continuous Theta Burst Stimulation (cTBS) over the contralesional PPC reduces neglect severity. It is unknown, however, whether such positive effects also operate in the presence of the detrimental effects of heightened attentional load. Here, we examined the effects of cTBS on neglect severity in overt visual search (i.e., with eye movements), as a function of high and low visual attentional load conditions. Performance was assessed on the basis of target detection rates and eye movements, in a computerised visual search task and in two paper-pencil tasks. cTBS significantly ameliorated target detection performance, independently of attentional load. These ameliorative effects were significantly larger in the high than the low load condition, thereby equating target detection across both conditions. Eye movement analyses revealed that the improvements were mediated by a redeployment of visual fixations to the contralesional visual field. These findings represent a substantive advance, because cTBS led to an unprecedented amelioration of overt search efficiency that was independent of visual attentional load., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: We aimed at further elucidating whether aphasic patients' difficulties in understanding non-canonical sentence structures, such as Passive or Object-Verb-Subject sentences, can be attributed to impaired morphosyntactic cue recognition, and to problems in integrating competing interpretations., Methods: A sentence-picture matching task with canonical and non-canonical spoken sentences was performed using concurrent eye tracking. Accuracy, reaction time, and eye tracking data (fixations) of 50 healthy subjects and 12 aphasic patients were analysed., Results: Patients showed increased error rates and reaction times, as well as delayed fixation preferences for target pictures in non-canonical sentences. Patients' fixation patterns differed from healthy controls and revealed deficits in recognizing and immediately integrating morphosyntactic cues., Conclusion: Our study corroborates the notion that difficulties in understanding syntactically complex sentences are attributable to a processing deficit encompassing delayed and therefore impaired recognition and integration of cues, as well as increased competition between interpretations.

Referred to as orthographic depth, the degree of consistency of grapheme/phoneme correspondences varies across languages from high in shallow orthographies to low in deep orthographies. The present study investigates the impact of orthographic depth on reading route by analyzing evoked potentials to words in a deep (French) and shallow (German) language presented to highly proficient bilinguals. ERP analyses to German and French words revealed significant topographic modulations 240-280 ms post-stimulus onset, indicative of distinct brain networks engaged in reading over this time window. Source estimations revealed that these effects stemmed from modulations of left insular, inferior frontal and dorsolateral regions (German>French) previously associated to phonological processing. Our results show that reading in a shallow language was associated to a stronger engagement of phonological pathways than reading in a deep language. Thus, the lexical pathways favored in word reading are reinforced by phonological networks more strongly in the shallow than deep orthography., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Brain lesions in the visual associative cortex are known to impair visual perception, i.e., the capacity to correctly perceive different aspects of the visual world, such as motion, color, or shapes. Visual perception can be influenced by non-invasive brain stimulation such as transcranial direct current stimulation (tDCS). In a recently developed technique called high definition (HD) tDCS, small HD-electrodes are used instead of the sponge electrodes in the conventional approach. This is believed to achieve high focality and precision over the target area. In this paper we tested the effects of cathodal and anodal HD-tDCS over the right V5 on motion and shape perception in a single blind, within-subject, sham controlled, cross-over trial. The purpose of the study was to prove the high focality of the stimulation only over the target area. Twenty one healthy volunteers received 20 min of 2 mA cathodal, anodal and sham stimulation over the right V5 and their performance on a visual test was recorded. The results showed significant improvement in motion perception in the left hemifield after cathodal HD-tDCS, but not in shape perception. Sham and anodal HD-tDCS did not affect performance. The specific effect of influencing performance of visual tasks by modulating the excitability of the neurons in the visual cortex might be explained by the complexity of perceptual information needed for the tasks. This provokes a "noisy" activation state of the encoding neuronal patterns. We speculate that in this case cathodal HD-tDCS may focus the correct perception by decreasing global excitation and thus diminishing the "noise" below threshold.

Background and Purpose: In stroke patients, neglect diagnostic is often performed by means of paper-pencil cancellation tasks. These tasks entail static stimuli, and provide no information concerning possible changes in the severity of neglect symptoms when patients are confronted with motion. We therefore aimed to directly contrast the cancellation behaviour of neglect patients under static and dynamic conditions. Since visual field deficits often occur in neglect patients, we analysed whether the integrity of the optic radiation would influence cancellation behaviour., Methods: Twenty-five patients with left spatial neglect after right-hemispheric stroke were tested with a touchscreen cancellation task, once when the evenly distributed targets were stationary, and once when the identic targets moved with constant speed on a random path. The integrity of the right optic radiation was analysed by means of a hodologic probabilistic approach., Results: Motion influenced the cancellation behaviour of neglect patients, and the direction of this influence (i.e., an increase or decrease of neglect severity) was modulated by the integrity of the right optic radiation. In patients with an intact optic radiation, the severity of neglect significantly decreased in the dynamic condition. Conversely, in patients with damage to the optic radiation, the severity of neglect significantly increased in the dynamic condition., Conclusion: Motion may influence neglect in stroke patients. The integrity of the optic radiation may be a predictor of whether motion increases or decreases the severity of neglect symptoms.

Continuous theta burst stimulation (cTBS) represents a promising approach in the treatment of neglect syndrome. However, it is not known whether cTBS in conjunction with another technique may enhance the therapeutic effects. In the present sham-controlled study, we aimed to combine cTBS with smooth pursuit training (SPT), another method known to effectively improve neglect symptoms, and to evaluate whether this combination would result in a stronger effect than SPT alone. Eighteen patients with left spatial neglect after right-hemispheric stroke were included in the study and performed a cancellation task on a large 54.6″ touchscreen monitor. A sequential application of cTBS and SPT induced a significantly greater improvement of neglect than SPT alone. After the combined application of these two methods, patients detected significantly more targets and their cancellation behaviour presented a significantly greater shift towards the contralesional hemispace. We suggest that a combined, sequential application of cTBS and SPT is a promising new approach to treat neglect., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The frontal eye field (FEF) is known to be involved in saccade generation and visual attention control. Studies applying covert attentional orienting paradigms have shown that the right FEF is involved in attentional shifts to both the left and the right hemifield. In the current study, we aimed at examining the effects of inhibitory continuous theta burst (cTBS) transcranial magnetic stimulation over the right FEF on overt attentional orienting, as measured by a free visual exploration paradigm. In forty-two healthy subjects, free visual exploration of naturalistic pictures was tested in three conditions: (1) after cTBS over the right FEF; (2) after cTBS over a control site (vertex); and, (3) without any stimulation. The results showed that cTBS over the right FEF-but not cTBS over the vertex-triggered significant changes in the spatial distribution of the cumulative fixation duration. Compared to the group without stimulation and the group with cTBS over the vertex, cTBS over the right FEF decreased cumulative fixation duration in the left and in the right peripheral regions, and increased cumulative fixation duration in the central region. The present study supports the view that the right FEF is involved in the bilateral control of not only covert, but also of overt, peripheral visual attention., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Valid and multidisciplinary assessment of a stroke patient's ability to perform activities of daily living is very important to define individual goals and to plan targeted rehabilitation. Until today, there is no observation scale that relies on International Classification of Functioning, Disability and Health (ICF). The aim of the present study was to develop and evaluate the reliability and validity of a new multidisciplinary observation scale for stroke patients, shortly called LIMOS, which is based on ICF., Methods: In a first phase, LIMOS was defined, using a Delphi approach, by an expert panel and a pilot testing was conducted in a small group of stroke patients (n =10) to investigate feasibility and practicability. In a second phase, LIMOS was assessed for its reliability (internal consistency and test-retest reliability) and validity in a large cohort of stroke patients (n = 102). For convergent validity, the correlation between total scores of the LIMOS and the Functional Independence Measure (FIM) was assessed., Results: LIMOS consisted of seven ICF chapters incorporating 45 domains. A high internal consistency (=0.98) of LIMOS was found. Furthermore, good test-retest reliability at item and subscale level was found. Principal component analysis revealed that among the seven ICF chapters, four components could be found: (1) interpersonal activities, mobility and self-care, (2) communication, (3) knowledge and general tasks, and (4) domestic life. Significant associations were found between LIMOS and the FIM indicating good convergent validity., Conclusions: The new LIMOS is a reliable and valid observation scale for stroke patients based on ICF, which can be used by a multidisciplinary team working in a neurorehabilitation setting.

According to the direct matching hypothesis, perceived movements automatically activate existing motor components through matching of the perceived gesture and its execution. The aim of the present study was to test the direct matching hypothesis by assessing whether visual exploration behavior correlate with deficits in gestural imitation in left hemisphere damaged (LHD) patients. Eighteen LHD patients and twenty healthy control subjects took part in the study. Gesture imitation performance was measured by the test for upper limb apraxia (TULIA). Visual exploration behavior was measured by an infrared eye-tracking system. Short videos including forty gestures (20 meaningless and 20 communicative gestures) were presented. Cumulative fixation duration was measured in different regions of interest (ROIs), namely the face, the gesturing hand, the body, and the surrounding environment. Compared to healthy subjects, patients fixated significantly less the ROIs comprising the face and the gesturing hand during the exploration of emblematic and tool-related gestures. Moreover, visual exploration of tool-related gestures significantly correlated with tool-related imitation as measured by TULIA in LHD patients. Patients and controls did not differ in the visual exploration of meaningless gestures, and no significant relationships were found between visual exploration behavior and the imitation of emblematic and meaningless gestures in TULIA. The present study thus suggests that altered visual exploration may lead to disturbed imitation of tool related gestures, however not of emblematic and meaningless gestures. Consequently, our findings partially support the direct matching hypothesis., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The dorsolateral prefrontal cortex (DLPFC) plays a key role in working memory. Evidence indicates that transcranial magnetic stimulation (TMS) over the DLPFC can interfere with working memory performance. Here we investigated for how long continuous theta-burst stimulation (cTBS) over the DLPFC decreases working memory performance and whether the effect of cTBS on performance depends on working memory load. Forty healthy young subjects received either cTBS over the left DLPFC or sham stimulation before performing a 2-, and 3-back working memory letter task. An additional 0-back condition served as a non-memory-related control, measuring general attention. cTBS over the left DLPFC significantly impaired 2-back working memory performance for about 15 min, whereas 3-back and 0-back performances were not significantly affected. Our results indicate that the effect of left DLPFC cTBS on working memory performance lasts for roughly 15 min and depends on working memory load.

Background: Co-speech gestures are part of nonverbal communication during conversations. They either support the verbal message or provide the interlocutor with additional information. Furthermore, they prompt as nonverbal cues the cooperative process of turn taking. In the present study, we investigated the influence of co-speech gestures on the perception of dyadic dialogue in aphasic patients. In particular, we analysed the impact of co-speech gestures on gaze direction (towards speaker or listener) and fixation of body parts. We hypothesized that aphasic patients, who are restricted in verbal comprehension, adapt their visual exploration strategies., Methods: Sixteen aphasic patients and 23 healthy control subjects participated in the study. Visual exploration behaviour was measured by means of a contact-free infrared eye-tracker while subjects were watching videos depicting spontaneous dialogues between two individuals. Cumulative fixation duration and mean fixation duration were calculated for the factors co-speech gesture (present and absent), gaze direction (to the speaker or to the listener), and region of interest (ROI), including hands, face, and body., Results: Both aphasic patients and healthy controls mainly fixated the speaker's face. We found a significant co-speech gesture × ROI interaction, indicating that the presence of a co-speech gesture encouraged subjects to look at the speaker. Further, there was a significant gaze direction × ROI × group interaction revealing that aphasic patients showed reduced cumulative fixation duration on the speaker's face compared to healthy controls., Conclusion: Co-speech gestures guide the observer's attention towards the speaker, the source of semantic input. It is discussed whether an underlying semantic processing deficit or a deficit to integrate audio-visual information may cause aphasic patients to explore less the speaker's face., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Central and peripheral vision is needed for object detection. Previous research has shown that visual target detection is affected by age. In addition, light conditions also influence visual exploration. The aim of the study was to investigate the effects of age and different light conditions on visual exploration behavior and on driving performance during simulated driving., Methods: A fixed-base simulator with 180 degree field of view was used to simulate a motorway route under daylight and night conditions to test 29 young subjects (25-40 years) and 27 older subjects (65-78 years). Drivers' eye fixations were analyzed and assigned to regions of interests (ROI) such as street, road signs, car ahead, environment, rear view mirror, side mirror left, side mirror right, incoming car, parked car, road repair. In addition, lane-keeping and driving speed were analyzed as a measure of driving performance., Results: Older drivers had longer fixations on the task relevant ROI, but had a lower frequency of checking mirrors when compared to younger drivers. In both age groups, night driving led to a less fixations on the mirror. At the performance level, older drivers showed more variation in driving speed and lane-keeping behavior, which was especially prominent at night. In younger drivers, night driving had no impact on driving speed or lane-keeping behavior., Conclusions: Older drivers' visual exploration behavior are more fixed on the task relevant ROI, especially at night, when driving performance becomes more heterogeneous than in younger drivers.

Background. Freezing of Gait (FOG) is a disabling parkinsonian symptom. The Freezing of Gait Questionnaire (FOG-Q) reliably detects FOG in patients with Parkinson's disease (PD). Objectives. The aim of this study was to develop a German translated version of the FOG-Q and to assess its validity. Methods. The translation was accomplished using forward-backward-translation. The construct validity of the FOG-Q was examined in twenty-seven German native speaking PD patients. Convergent validity was assessed by correlating the FOG-Q with the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) II-III, the Parkinson Disease Questionnaire 39 (PDQ-39), and the Timed Up and Go Test (TUG). Divergent validity was assessed by correlating the FOG-Q with the MDS-UPDRS I. The internal consistency was measured using Cronbach's alpha (Cα). Results. A good internal structure of the FOG-Q was found (Cα = 0.83). Significant moderate correlations between the FOG-Q and the MDS-UPDRS item 2.13 (freezing) (r s = 0.568, P = 0.002) and between the FOG-Q and the PDQ-39 subscale mobility (r s = 0.516, P = 0.006) were found. The lack of correlation with the MDS-UPDRS I demonstrated good divergent validity. Conclusion. The German FOG-Q is a valid tool to assess FOG in German native speaking PD patients.

Visual perception is not identical in the upper and lower visual hemifields. The mechanisms behind this difference can be found at the retinal, cortical, or higher attentional level. In this study, a new visual test battery, that involves real-time comparisons of complex visual stimuli, such as shape of objects, and speed of moving dot patterns, in the upper and lower visual hemifields, is presented. This study represents, to our knowledge, the first to implement such a visual test battery in an immersive environment composed of a hemisphere, in order to present visual stimuli in precise regions of the visual field. Ten healthy volunteers were tested in this pilot study. The results showed a higher accuracy in the image matching when the visual test was performed in the lower visual hemifield.

A group of European experts was commissioned to establish guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS) from evidence published up until March 2014, regarding pain, movement disorders, stroke, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, consciousness disorders, tinnitus, depression, anxiety disorders, obsessive-compulsive disorder, schizophrenia, craving/addiction, and conversion. Despite unavoidable inhomogeneities, there is a sufficient body of evidence to accept with level A (definite efficacy) the analgesic effect of high-frequency (HF) rTMS of the primary motor cortex (M1) contralateral to the pain and the antidepressant effect of HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC). A Level B recommendation (probable efficacy) is proposed for the antidepressant effect of low-frequency (LF) rTMS of the right DLPFC, HF-rTMS of the left DLPFC for the negative symptoms of schizophrenia, and LF-rTMS of contralesional M1 in chronic motor stroke. The effects of rTMS in a number of indications reach level C (possible efficacy), including LF-rTMS of the left temporoparietal cortex in tinnitus and auditory hallucinations. It remains to determine how to optimize rTMS protocols and techniques to give them relevance in routine clinical practice. In addition, professionals carrying out rTMS protocols should undergo rigorous training to ensure the quality of the technical realization, guarantee the proper care of patients, and maximize the chances of success. Under these conditions, the therapeutic use of rTMS should be able to develop in the coming years., (Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: Higher visual functions can be defined as cognitive processes responsible for object recognition, color and shape perception, and motion detection. People with impaired higher visual functions after unilateral brain lesion are often tested with paper pencil tests, but such tests do not assess the degree of interaction between the healthy brain hemisphere and the impaired one. Hence, visual functions are not tested separately in the contralesional and ipsilesional visual hemifields., Methods: A new measurement setup, that involves real-time comparisons of shape and size of objects, orientation of lines, speed and direction of moving patterns, in the right or left visual hemifield, has been developed. The setup was implemented in an immersive environment like a hemisphere to take into account the effects of peripheral and central vision, and eventual visual field losses. Due to the non-flat screen of the hemisphere, a distortion algorithm was needed to adapt the projected images to the surface. Several approaches were studied and, based on a comparison between projected images and original ones, the best one was used for the implementation of the test. Fifty-seven healthy volunteers were then tested in a pilot study. A Satisfaction Questionnaire was used to assess the usability of the new measurement setup., Results: The results of the distortion algorithm showed a structural similarity between the warped images and the original ones higher than 97%. The results of the pilot study showed an accuracy in comparing images in the two visual hemifields of 0.18 visual degrees and 0.19 visual degrees for size and shape discrimination, respectively, 2.56° for line orientation, 0.33 visual degrees/s for speed perception and 7.41° for recognition of motion direction. The outcome of the Satisfaction Questionnaire showed a high acceptance of the battery by the participants., Conclusions: A new method to measure higher visual functions in an immersive environment was presented. The study focused on the usability of the developed battery rather than the performance at the visual tasks. A battery of five subtasks to study the perception of size, shape, orientation, speed and motion direction was developed. The test setup is now ready to be tested in neurological patients.

Background and Purpose: Lee Silverman Voice Treatment Big (LSVT BIG) is characterized by intensive exercising of high-amplitude movements to overcome bradykinesia and hypokinesia in patients with Parkinson disease (PD). The aim of the present case series was to explore possible beneficial effects of LSVT BIG training on gait, balance, bed mobility, and dexterity., Case Description: Three patients with mild to moderate PD (all male; aged 52, 54, and 70 years; Hoehn & Yahr stages I-III) completed a 4-week LSVT BIG training program (16 individual 1-hour sessions) and an intensive home training program in accordance with the LSVT BIG protocol. Two certified LSVT BIG physical therapists delivered the LSVT BIG training sessions., Outcomes: The outcome measures for gait and balance included the Functional Gait Assessment (FGA), Functional Reach Test (FRT), Timed "Up & Go" Test (TUG), Freezing of Gait Questionnaire (FOGQ), and motor score on part III of the Unified Parkinson's Disease Rating Scale (UPDRS III). Bed mobility was addressed using the Lindop Parkinson's Disease Mobility Assessment (LPA). The Nine-Hole Peg Test (9HPT) was used to measure dexterity. The 3 patients performed better on balance and gait assessments, as indicated by increased scores on the FRT and FGA (all 3 patients) and decreased scores on the TUG, FOGQ, and UPDRS III, of which scores of the FRT and UPDRS III achieved the minimal detectable change. Furthermore, the patients were quicker in tasks related to bed mobility (LPA). The patients' dexterity skills did not improve for their dominant (right) hand (9HPT)., Discussion: This case series suggests that the LSVT BIG may be beneficial for gait, balance, and bed mobility. Future work is needed to ascertain the effectiveness by means of randomized controlled trials., (© 2014 American Physical Therapy Association.)

Objective: Neuro-imaging studies have suggested that the ability to imitate meaningless and meaningful gestures may differentially depend on superior (SPL) and inferior (IPL) parietal lobule. Therefore, we hypothesized that imaging-guided neuro-navigated continuous theta burst stimulation (cTBS) over left SPL mainly affects meaningless and over left IPL predominantly meaningful gestures., Methods: Twelve healthy subjects participated in this study. High resolution structural MRI was used for imaging guided neuro-navigation cTBS. Participants were targeted with one train of cTBS in three experimental sessions: sham stimulation over vertex and real cTBS over left SPL and IPL, respectively. An imitation task, including 24 meaningless and 24 meaningful gestures, was performed 'offline'., Results: cTBS over both left IPL and SPL significantly interfered with gestural imitation. There was no differential effect of SPL and IPL cTBS on gesture type (meaningless versus meaningful)., Conclusions: Our findings confirm that left posterior parietal cortex plays a predominant role in gestural imitation. However, the hypothesis based on the dual route model suggesting a differential role of SPL and IPL in the processing of meaningless and meaningful gestures could not be confirmed., Significance: Left SPL and IPL play a common role within the posterior-parietal network in gestural imitation regardless of semantic content., (Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

This study investigated the roles of the right and left dorsolateral prefrontal (rDLPFC, lDLPFC) and the medial frontal cortex (MFC) in executive functioning using a theta burst transcranial magnetic stimulation (TMS) approach. Healthy subjects solved two visual search tasks: a number search task with low cognitive demands, and a number and letter search task with high cognitive demands. To observe how subjects solved the tasks, we assessed their behavior with and without TMS using eye movements when subjects were confronted with specific executive demands. To observe executive functions, we were particularly interested in TMS-induced changes in visual exploration strategies found to be associated with good or bad performance in a control condition without TMS stimulation. TMS left processing time unchanged in both tasks. Inhibition of the rDLPFC resulted in a decrease in anticipatory fixations in the number search task, i.e., a decrease in a good strategy in this low demand task. This was paired with a decrease in stimulus fixations. Together, these results point to a role of the rDLPFC in planning and response selection. Inhibition of the lDLPFC and the MFC resulted in an increase in anticipatory fixations in the number and letter search task, i.e., an increase in the application of a good strategy in this task. We interpret these results as a compensatory strategy to account for TMS-induced deficits in attentional switching when faced with high switching demands. After inhibition of the lDLPFC, an increase in regressive fixations was found in the number and letter search task. In the context of high working memory demands, this strategy appears to support TMS-induced working memory deficits. Combining an experimental TMS approach with the recording of eye movements proved sensitive to discrete decrements of executive functions and allows pinpointing the functional organization of the frontal lobes.

Systematic differences in circadian rhythmicity are thought to be a substantial factor determining inter-individual differences in fatigue and cognitive performance. The synchronicity effect (when time of testing coincides with the respective circadian peak period) seems to play an important role. Eye movements have been shown to be a reliable indicator of fatigue due to sleep deprivation or time spent on cognitive tasks. However, eye movements have not been used so far to investigate the circadian synchronicity effect and the resulting differences in fatigue. The aim of the present study was to assess how different oculomotor parameters in a free visual exploration task are influenced by: a) fatigue due to chronotypical factors (being a 'morning type' or an 'evening type'); b) fatigue due to the time spent on task. Eighteen healthy participants performed a free visual exploration task of naturalistic pictures while their eye movements were recorded. The task was performed twice, once at their optimal and once at their non-optimal time of the day. Moreover, participants rated their subjective fatigue. The non-optimal time of the day triggered a significant and stable increase in the mean visual fixation duration during the free visual exploration task for both chronotypes. The increase in the mean visual fixation duration correlated with the difference in subjectively perceived fatigue at optimal and non-optimal times of the day. Conversely, the mean saccadic speed significantly and progressively decreased throughout the duration of the task, but was not influenced by the optimal or non-optimal time of the day for both chronotypes. The results suggest that different oculomotor parameters are discriminative for fatigue due to different sources. A decrease in saccadic speed seems to reflect fatigue due to time spent on task, whereas an increase in mean fixation duration a lack of synchronicity between chronotype and time of the day.

The aim of this study was to examine the effects of aging and target eccentricity on a visual search task comprising 30 images of everyday life projected into a hemisphere, realizing a ±90° visual field. The task performed binocularly allowed participants to freely move their eyes to scan images for an appearing target or distractor stimulus (presented at 10°; 30°, and 50° eccentricity). The distractor stimulus required no response, while the target stimulus required acknowledgment by pressing the response button. One hundred and seventeen healthy subjects (mean age = 49.63 years, SD = 17.40 years, age range 20-78 years) were studied. The results show that target detection performance decreases with age as well as with increasing eccentricity, especially for older subjects. Reaction time also increases with age and eccentricity, but in contrast to target detection, there is no interaction between age and eccentricity. Eye movement analysis showed that younger subjects exhibited a passive search strategy while older subjects exhibited an active search strategy probably as a compensation for their reduced peripheral detection performance.

Cognitive functions, such as working memory, depend on neuronal excitability in a distributed network of cortical regions. It is not known, however, if interindividual differences in cortical excitability are related to differences in working memory performance. In the present transcranial magnetic stimulation study, which included 188 healthy young subjects, we show that participants with lower resting motor threshold, which is related to higher corticospinal excitability, had increased 2-back working memory performance. The findings may help to better understand the link between cortical excitability and cognitive functions and may also have important clinical implications with regard to conditions of altered cortical excitability.

In the antisaccade task, subjects are requested to suppress a reflexive saccade towards a visual target and to perform a saccade towards the opposite side. In addition, in order to reproduce an accurate saccadic amplitude, the visual saccade vector (i.e., the distance between a central fixation point and the peripheral target) must be exactly inverted from one visual hemifield to the other. Results from recent studies using a correlational approach (i.e., fMRI, MEG) suggest that not only the posterior parietal cortex (PPC) but also the frontal eye field (FEF) might play an important role in such a visual vector inversion process. In order to assess whether the FEF contributes to visual vector inversion, we applied an interference approach with continuous theta burst stimulation (cTBS) during a memory-guided antisaccade task. In 10 healthy subjects, one train of cTBS was applied over the right FEF prior to a memory-guided antisaccade task. In comparison to the performance without stimulation or with sham stimulation, cTBS over the right FEF induced a hypometric gain for rightward but not leftward antisaccades. These results obtained with an interference approach confirm that the FEF is also involved in the process of visual vector inversion.

Mutations in the voltage-gated Cav2.1 P/Q-type calcium channel (CACNA1A) can cause a wide spectrum of phenotypes, including the episodic ataxia type 2. Beside the growing number of descriptions of novel CACNA1A mutations with episodic ataxia type 2 phenotype; there are only rare reports on interictal oculomotor signs other than nystagmus. We describe a novel CACNA1A mutation and an unclassified CACNA1A in-frame variant in a Swiss family presenting as the episodic ataxia type 2 phenotype associated with reduced saccade velocity. In this case series interictal clinical examination showed only minimal neurological findings as mild limb ataxia and nystagmus, but most interestingly saccade analysis of all three affected individuals demonstrated reduced mean saccade velocity. Genetic testing of CACNA1A revealed a de novo frame-shift mutation (c.2691dupC/p.Thyr898Leufs 170) in the index patient in addition to an unclassified in-frame variant (c.6657&#95;6659dupCCA/p.His2220dup) segregating in all three affected individuals. The de novo frame-shift CACNA1A mutation and the unclassified in-frame CACNA1A variant were associated with the episodic ataxia type 2 phenotype and reduced mean saccade velocity, which suggests involvement of brainstem or neural pathways connecting brainstem and the cerebellum in this disease.

Continuous theta-burst stimulation (cTBS) can modify behavior, but effects are inconsistent and their mechanisms insufficiently understood. As coherence in resting-state networks influences human behavior, we hypothesized that cTBS may act via modulation of neural oscillation coherence. This study used electroencephalography (EEG) to investigate whether behavioral effects of cTBS on visuospatial attention are associated with coherence changes in the attention network. In healthy human subjects, cTBS of the right posterior parietal cortex (PPC) and the right frontal eye field was compared with sham stimulation. Effects on visuospatial attention were quantified with a visual exploration task, and network effects were assessed from surface EEG with inverse solutions and source coherence analyses. Before stimulation, left visual exploration was linearly correlated with alpha-band coherence between the right temporo-parietal cortex and the rest of the brain. Posterior parietal cortex stimulation induced neglect-like visual exploration behavior in the majority, but not all, subjects. It reduced alpha-band coherence between the stimulation site and the rest of the brain but also enhanced it between the contralateral left parietal cortex and the rest of the brain. The contralateral increase correlated with the induced reduction in left visual attention. The behavioral response of individual participants to cTBS could be predicted by coherence in the right temporo-parietal junction before stimulation. Behavioral effects of cTBS therefore depend on network states before stimulation and are linearly associated with changes in network interactions. In particular, cTBS modulates an interhemispheric competition in alpha-band coherence. EEG network imaging might help to optimize therapeutic cTBS in the future., (© 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Here, we review the effects of non-invasive brain stimulation such as transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) in the rehabilitation of neglect. We found 12 studies including 172 patients (10 TMS studies and 2 tDCS studies) fulfilling our search criteria. Activity of daily living measures such as the Barthel Index or, more specifically for neglect, the Catherine Bergego Scale were the outcome measure in three studies. Five studies were randomized controlled trials with a follow-up time after intervention of up to 6 weeks. One TMS study fulfilled criteria for Class I and one for Class III evidence. The studies are heterogeneous concerning their methodology, outcome measures, and stimulation parameters making firm comparisons and conclusions difficult. Overall, there are however promising results for theta-burst stimulation, suggesting that TMS is a powerful add-on therapy in the rehabilitation of neglect patients.

The role of low-level stimulus-driven control in the guidance of overt visual attention has been difficult to establish because low- and high-level visual content are spatially correlated within natural visual stimuli. Here we show that impairment of parietal cortical areas, either permanently by a lesion or reversibly by repetitive transcranial magnetic stimulation (rTMS), leads to fixation of locations with higher values of low-level features as compared to control subjects or in a no-rTMS condition. Moreover, this unmasking of stimulus-driven control crucially depends on the intrahemispheric balance between top-down and bottom-up cortical areas. This result suggests that although in normal behavior high-level features might exert a strong influence, low-level features do contribute to guide visual selection during the exploration of complex natural stimuli., (Copyright © 2012 Elsevier Ltd. All rights reserved.)