Multimodal agility-based exercise training (MAT) versus strength and endurance training (SET) to improve multiple sclerosis-related fatigue and fatigability during inpatient rehabilitation: a randomized controlled pilot and feasibility study [ReFEx].

BACKGROUND: Multimodal agility-based exercise training (MAT) is a group-based exercise training framework for persons with multiple sclerosis (pwMS) with a potential to impact fatigue and fatigability. In a mixed-methods design, this study evaluated the feasibility of implementing MAT in an inpatient rehabilitation setting and the feasibility of a randomized controlled trial (RCT) study protocol with 'traditional' strength and endurance training (SET) as an active control condition. Secondarily, preliminary outcome data was acquired. METHODS: PwMS with low to moderate disability and self-reported fatigue were randomly allocated to either MAT or SET when starting inpatient rehabilitation (4-6 weeks). The MAT-participants exercised in a group following a MAT-manual (sessions were gym- (5x/week) and pool-based (3x/week)). SET-participants exercised individually 5x/week on a cycle ergometer, and 3x/week on strength training machines. Feasibility assessments focused on processes, resources, management, time, and scientific domains. Assessed clinical outcomes at admission and discharge included perceived fatigue, motor and cognitive fatigability, cognitive performance, motor function, and balance confidence. Perceived fatigue was reassessed 1, 4, and 12 weeks after discharge. Feasibility was determined regarding predetermined progression criteria. RESULTS: Twenty-two participants were randomized. Both groups performed the minimum number of sessions (> 18), and retention was adequate (73-91%). SET-participants performed more sessions than MAT-participants (30.8 vs. 22.7) and stayed longer in the facility (34.2 vs. 31.6 days). Non-eligibility of admitted pwMS was high (74% non-eligible), mainly due to high EDSS and inability to attend pool-based sessions. Consequently, recruitment (1.8/month) was slower than the predetermined progression criterium. Baseline assessments took longer than required (only 50% completed within 3 days). Short-term fatigue reduction was similar for both groups. Motor fatigability also improved in both groups, whereas cognitive fatigability deteriorated. In MAT, average improvement in walking endurance (43.9 m) exceeded minimal important change values for individuals (> 26.9 m). CONCLUSIONS: Progressing to a definitive RCT necessitates adaptation of eligibility criteria. In the present design it will also be difficult to attain similar dosing of interventions. A multicenter RCT focused only on gym-based MAT might be another option to assess the effect of MAT. The primary outcome measure should be able to measure change in perceived fatigue more robustly. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00023943, date of registration: 23 September 2021.

The Relationship between Diurnal Measures of Tonic Alertness and Self-Reported Fatigue in Persons with Multiple Sclerosis-A Retrospective Data Analysis.

OBJECTIVE: Fatigue in multiple sclerosis (MS) is common, burdensome, and usually assessed by self-report measures. This retrospective data analysis of the twice-daily Alertness test (Test battery of Attentional Performance) examined the extent to which this assessment procedure is associated with MS-related fatigue. METHOD: Two-hundred and thirteen German inpatients (136 women) aged 18-69 years with predominantly relapsing MS (72.8%) were included. Based on reaction time (RT) differences between morning tonic alertness (8:30-11:00 a.m.) and afternoon tonic alertness (3:00-4:30 p.m.), patients were divided into an "improver," "maintainer," or "decliner" group. Multinomial logistic regression (MLR) was calculated to predict the likelihood of belonging to one of these performance groups, taking into account cognitive fatigue (Fatigue Scale of Motor and Cognition, FSMCcog), disease severity (Expanded Disability Status Scale, EDSS), depression (Center for Epidemiologic Studies Depression Scale, CES-D), gender, and tonic alertness (a.m.). RESULTS: The final MLR model (R2 = .30) included tonic alertness (a.m.) (<.001), FSMCcog (.008), EDSS (.038), CES-D (.161), and gender (.057). Using this model, correct assignment to alertness performance groups was 56.8%. Tonic alertness (p.m.) demonstrated the greatest potential for differentiation among the three performance groups (<.001). CONCLUSIONS: These results show a relationship between subjective fatigue and tonic alertness. However, other variables also contribute to this association, suggesting that the RT differences between twice-daily measures of tonic alertness is not related to increased subjective fatigue in a substantial number of pwMS, which diminishes the diagnostic value. Further studies including relevant variables such as sleepiness are urgently needed.

Randomised controlled pilot and feasibility study of multimodal agility-based exercise training (MAT) versus strength and endurance training (SET) to improve multiple sclerosis-related fatigue and fatigability during inpatient rehabilitation (ReFEx): study protocol.

INTRODUCTION: Subjective fatigue and objectively assessed fatigability are common symptoms in persons with multiple sclerosis (pwMS). Recent work has suggested a positive effect of balance and motor control training (BMCT) in reducing fatigue. It is unclear whether this effect can also be attained during inpatient rehabilitation. Multimodal agility-based exercise training (MAT) has been developed as a framework that incorporates BMCT with added agility components but has not been applied to pwMS. Therefore, this study will evaluate the feasibility of a randomised controlled trial comparing MAT against strength and endurance training (SET) for the improvement of MS-related fatigue and fatigability in a German neurological rehabilitation centre. METHODS AND ANALYSIS: A total of 24 pwMS (Expanded Disability Status Scale ≤5.0, Fatigue Scale for Motor and Cognitive Functions ≥53) will be randomly assigned to either SET or land and water-based MAT for 4-6 weeks during inpatient rehabilitation. Assessments of subjective fatigue, motor and cognitive fatigability, cognitive and cardiorespiratory performance, and balance confidence will be performed at admission and discharge. Subjective fatigue will also be assessed at 1, 4 and 12 weeks after discharge. Feasibility outcomes will include patients' acceptance of study procedures and interventions, recruitment rate, retention rate, time needed to complete baseline assessments, intervention adherence and fidelity. All quantitative outcomes will be reported descriptively. A total of 12 pwMS (6 per group) will be interviewed to gain insights into participants' experiences during study participation. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Ethics Committee of the University of Bonn (reference number: 543/20). Dissemination of findings is planned via peer-reviewed journals, conferences and media releases. TRIAL REGISTRATION NUMBER: DRKS00023943.

Fear of Progression is Determined by Anxiety and Self-Efficacy but not Disease-Specific Parameters in Patients with Parkinson's Disease: Preliminary Data from a Multicenter Cross-Sectional Study.

BACKGROUND: Fear of progression (FoP) is a reactive, conscious concern about chronic disease progression and its consequences which may limit quality of life substantially. Only one study has examined FoP in Parkinson's disease (PD), showing the second highest FoP scores among chronic diseases. OBJECTIVE: To examine FoP prevalence and to exploratorily analyze determinants of FoP in PD. METHODS: Within a multicenter cross-sectional study, 120 PD inpatients (age: 64.45±9.20; 60.8% male; UPDRS-III: 28.86±16.12) were examined with the FoP questionnaire (FoP-Q; max. 20 points). Stepwise multiple linear regression analysis examined sociodemographic, clinical, and (neuro-) psychological determinants of FoP. RESULTS: With a mean FoP-Q score of 8.08±2.17, 63.0% of the patients were classified with moderate FoP and 17.6% with dysfunctional (i.e., severe) FoP. The highest scores were shown for the subscale 'loss of autonomy'. Increased levels of anxiety, less self-efficacy, female gender, current employment, and lower health literacy were identified as significant determinants associated with FoP. CONCLUSION: With more than 80% of patients showing moderate to dysfunctional FoP, it must be regarded as a frequent symptom in PD, which needs to be further understood and addressed in clinical practice. Clinical parameters like PD duration and severity were no determinants for FoP, indicating that FoP awareness must be considered by professionals at all disease stages.

Cognitive Fatigue Predicts Cognitive Failure in Multiple Sclerosis Patients and Healthy Controls: A Case-Control Study.

OBJECTIVE: Fatigue and cognitive deficits are frequent symptoms of multiple sclerosis (MS). However, the exact nature of their co-occurrence is not fully understood. We sought to determine the impact of cognitive and physical fatigue on subjective cognitive deficits in MS patients and healthy controls. METHODS: Self-reports of fatigue (FSMC), depression (CES-D), cognitive deficits (CFQ), and personality traits (NEO-FFI, ANPS) among 30 MS inpatients and 30 healthy controls were analyzed using hierarchical regression models. The frequency of cognitive mistakes was used as the dependent variable and the extent of cognitive and physical fatigue as the independent variable. RESULTS: Cognitive fatigue was the only unique and significant predictor of cognitive mistakes in both groups, explaining 13.3% of additional variance in the MS group after correcting for age, mood, and physical fatigue. Physical fatigue had no significant impact on cognitive mistakes. While age had an impact on cognitive mistakes and depression in healthy controls, this association was not significant in MS patients. Depression was significantly correlated with cognitive mistakes and cognitive fatigue in MS patients. CONCLUSIONS: The interplay of cognitive fatigue and subjective cognitive impairment can be generalized, with the exception of the variables of age and depression, which were shown to have differing impacts on cognitive mistakes in MS patients and healthy controls, respectively. Cognitive fatigue was linked to cognitive mistakes even after correcting for overlapping items in MS patients only. Future research should further investigate the link between cognitive fatigue and attention lapses in daily life by using various objective assessments.

Feasibility of Music-Assisted Treadmill Training in Parkinson's Disease Patients With and Without Deep Brain Stimulation: Insights From an Ongoing Pilot Randomized Controlled Trial.

Background: Music-assisted treadmill training (MATT) is a new therapeutic approach for Parkinson's disease (PD) patients, combining treadmill training with rhythmic auditory cueing and visual feedback. PD studies have shown larger positive effects on motor outcomes than usual treadmill training. However, effects on cognition, in contrast, are less clear. Existing studies provided intensive training protocols and included only stable medicated patients. Thus, a pilot randomized controlled trial was designed to analyze the feasibility of a shorter training protocol as well as preliminary effects on cognition, motor function, and patient-centered outcomes in a rehabilitation setting where PD patients with and without deep brain stimulation (DBS) undergo adaptation of medication and DBS settings. Here, we present the results from the feasibility analysis of the still ongoing trial. Methods: Non-demented PD patients with and without DBS were recruited during their inpatient rehabilitation and randomized to an experimental group (EG; 20 min MATT) or an active control group (CG; 20 min bike ergometer training). The trainings took place for 8 consecutive days and were added to the usual rehabilitation. Feasibility was assessed with the following parameters: patients' study protocol acceptance, study protocol transferability into clinical routine, training-induced adverse events, and patients' training perception. Results: Thirty-two patients (EG: n = 15; CG: n = 17; 72% DBS) were included. The study protocol was well-accepted (inclusion rate: 84%). It was transferable into clinical routines; dropout rates of 40% (EG) and 18% (CG) were observed. However, an in-depth analysis of the dropout cohort did not reveal intervention-related dropout reasons. The MATT and the standard ergometer training showed no adverse events and were positively perceived by PD patients with and without DBS. Conclusion: MATT was shown to be a feasible, safe, and enjoyable treatment option in PD patients with and without DBS. Furthermore, the dropout cohort analysis revealed some exciting first insights into possible dropout reasons that go beyond the form of intervention. Therefore, research would benefit from a common practice of dropout analyses, as this would enhance our understanding of patients' therapy adherence and expectations.

Preserved performance monitoring and error detection in left hemisphere stroke.

Depending on the lesion site, a stroke typically affects various aspects of cognitive control. While executing a task, the performance monitoring system constantly compares an intended action plan with the executed action and thereby registers inaccurate actions in case of any mismatch. When errors occur, the performance monitoring system signals the need for more cognitive control, which is most efficient when the subject notices errors rather than processing them subconsciously. The current study aimed to investigate performance monitoring and error detection in a large sample of patients with left hemisphere (LH) stroke. In addition to clinical and neuropsychological tests, 24 LH stroke patients and 32 healthy age-matched controls performed a Go/Nogo task with simultaneous electroencephalography (EEG) measurements. This set-up enabled us to compare performance monitoring at the behavioral and the neural level. EEG data were analyzed using event-related potentials [ERPs; e.g., the error-related negativity (Ne/ERN) and error positivity (Pe)] and additionally more sensitive whole-brain multivariate pattern classification analyses (MVPA). We hypothesized that LH stroke patients would show behavioural deficits in error detection when compared to healthy controls, mirrored by differences in neural signals, in particular reflected in the Pe component. Interestingly, despite clinically relevant cognitive deficits (e.g., aphasia and apraxia) including executive dysfunction (trail making test), we did not observe any behavioral impairments related to performance monitoring and error processing in the current LH stroke patients. Patients also showed similar results for Ne/ERN and Pe components, compared to the control group, and a highly similar prediction of errors from multivariate signals. ERP abnormalities during stimulus processing (i.e., N2 and P3) demonstrated the specificity of these findings in the current LH stroke patients. In contrast to previous studies, by employing a relatively large patient sample, a well-controlled experimental paradigm with a standardized error signaling procedure, and advanced data analysis, we were able to show that performance monitoring (of simple actions) is a preserved cognitive control function in LH stroke patients that might constitute a useful resource in rehabilitative therapies for re-learning impeded functions.

Anodal tDCS over left parietal cortex expedites recovery from stroke-induced apraxic imitation deficits: a pilot study.

BACKGROUND: To date, specific therapeutic approaches to expedite recovery from apraxic deficits after left hemisphere (LH) stroke remain sparse. Thus, in this pilot study we evaluated the effect of anodal transcranial direct current stimulation (tDCS) in addition to a standardized motor training on apraxic imitation deficits. METHODS: In a rehabilitation hospital, we assessed apraxic, aphasic, and motor deficits in 30 LH stroke patients before and after a five-day standard programme of motor training combined with either anodal (10 min, 2 mA; n = 14) or sham (10 min, 0 mA, n = 16) tDCS applied in a double-blind fashion over left posterior parietal cortex (PPC). Where appropriate, data were analyzed with either t-test, Fisher's exact test, or univariate/ repeated measures ANOVA. RESULTS: Compared to sham tDCS, five sessions of anodal tDCS expedited recovery from apraxic imitation deficits (p < 0.05): Already after 5 days, the anodal tDCS group showed levels of imitation performance that were achieved in the sham tDCS group after 3 months. However, the primary outcome of the study (i.e., anodal tDCS induced improvement of the total apraxia score) failed significance, and there was no significant tDCS effect on apraxia after 3 months. Anodal tDCS improved grip force (of the contra-lesional, i.e., right hand), but had no effect on aphasia. CONCLUSIONS: Data from this pilot study show that repetitive, anodal tDCS over left PPC combined with a standardized motor training expedites recovery from imitation deficits in LH stroke patients with apraxia (relative to sham stimulation). Results suggest that in patients suffering from apraxic imitation deficits a randomized controlled trial (RCT) is warranted that investigates the effects of tDCS applied over PPC in addition to a standardized motor training.

Preserved but Less Efficient Control of Response Interference After Unilateral Lesions of the Striatum.

Previous research on the neural basis of cognitive control processes has mainly focused on cortical areas, while the role of subcortical structures in cognitive control is less clear. Models of basal ganglia function as well as clinical studies in neurodegenerative diseases suggest that the striatum (putamen and caudate nucleus) modulates the inhibition of interfering responses and thereby contributes to an important aspect of cognitive control, namely response interference control. To further investigate the putative role of the striatum in the control of response interference, 23 patients with stroke-induced lesions of the striatum and 32 age-matched neurologically healthy controls performed a unimanual version of the Simon task. In the Simon task, the correspondence between stimulus location and response location is manipulated so that control over response interference can be inferred from the reaction time costs in incongruent trials. Results showed that stroke patients responded overall slower and more erroneous than controls. The difference in response times (RTs) between incongruent and congruent trials (known as the Simon effect) was smaller in the ipsilesional/-lateral hemifield, but did not differ significantly between groups. However, in contrast to controls, stroke patients exhibited an abnormally stable Simon effect across the reaction time distribution indicating a reduced efficiency of the inhibition process. Thus, in stroke patients unilateral lesions of the striatum did not significantly impair the general ability to control response interference, but led to less efficient selective inhibition of interfering responses.

DBS Electrodes With Single Disconnected Contacts: Long-Term Observation and Implications for the Management.

OBJECTIVES: To evaluate the long-term course of quadripolar DBS electrodes with disconnected single contacts that cannot be used for DBS. MATERIALS AND METHODS: Quadripolar electrodes with open circuits of single contacts or monopolar impedances >6500 Ω were identified from a cohort of 2082 electrodes from 1044 patients with variable movement disorders. The long-term course was analyzed from follow-up data. RESULTS: Disconnected contacts were found in 58 electrodes (2.8%) from 49 patients (4.7%). The dysfunction was restricted to one contact in 51 electrodes (87.9%), two contacts in 5 electrodes (8.6%), three contacts in 2 electrodes (3.4%). Onset was related to surgery (implantation, impulse generator replacement, or other surgical revision) in 34 electrodes (58.6%), trauma in 2 electrodes, undetermined in 11 electrodes, and occurred spontaneously after previous normal measurements in 11 electrodes (19.0%). Repeated measurements at follow-ups of ≥3 months were available in 39 electrodes. In 16 electrodes (41.0%) abnormal impedances persisted constantly during observations up to 11½ years (47 ± 35 months, median 41 months). In 21 electrodes (53.8%) abnormal impedances remained restricted to the initial contact(s) but varied considerably between measurements during up to six years (39 ± 18 months, median 38 months). Only two electrodes (5.1%) with initially one disconnected contact developed a disconnection of a second contact. CONCLUSIONS: Disconnections of single contacts occur with increasing cumulative incidence during long-term DBS. Surgery is the main causative risk factor. In the majority of electrodes, the dysfunction remains restricted to the initial contact(s).

Reduced awareness for apraxic deficits in left hemisphere stroke.

OBJECTIVE: Reduced awareness for motor or cognitive impairments has mainly been studied in relation to right-hemispheric deficits such as left-sided hemiparesis. However, recent studies suggest that also left hemisphere (LH) stroke can lead to reduced awareness for neurological/neuropsychological deficits, for example, aphasia. The aim of the current study was to characterize reduced awareness for apraxic as well as aphasic deficits in patients suffering from LH stroke. METHOD: After the assessment of apraxia and aphasia, patients (n = 32) were asked to rate their performance on a 1- to 5-point rating scale. An unawareness score (UAS) was computed as the difference between the examiners' ratings and self-ratings, resulting in negative scores for patients who overestimated their performance in a given assessment, that is, exhibited reduced awareness for their stroke-related deficits. RESULTS: Patients with apraxia (n = 14) and aphasia (n = 16) significantly overestimated their performance in the respective assessment. However, the level of awareness was not generally related to the severity of apraxia, and there were no group differences in other variables between patients with full (n = 7) and reduced awareness (n = 7) for apraxic deficits. The reduction of awareness for apraxic deficits did not differ significantly for buccofacial versus limb gestures. CONCLUSION: Data show that LH stroke can lead to reduced awareness not only for aphasic deficits but also for buccofacial and limb apraxia. (PsycINFO Database Record

Personality and Primary Emotional Traits: Disentangling Multiple Sclerosis Related Fatigue and Depression.

OBJECTIVE: It remains an unresolved research objective to clarify the overlap/association between fatigue (especially its cognitive facet) and depression in People with MS (PwMS). Therefore, in this study the patterns of personality and primary emotional traits (PETs) associated with each (motoric/cognitive fatigue and depression in PwMS) were investigated and compared in order to disentangle the three constructs in PwMS. Additionally, differences in personality and PETs between PwMS and healthy controls (HC) were examined. METHOD: Associations between motoric/cognitive fatigue, depression, personality and PETs were investigated in 52 PwMS. Personality and PETs were also assessed in a gender matched HC sample (N = 52) and results regarding these were compared between PwMS and HC. RESULTS: Low extraversion was the only significant predictor of MS related motoric fatigue (ß = -.341, p = .013). High neuroticism was a predictor of both MS related cognitive fatigue (ß = .426, p = .002) and depression (ß = .443, p < .001). Whereas neuroticism was the only significant predictor for MS related cognitive fatigue, the cluster of (high) neuroticism, (high) SADNESS (ß = .273, p = .023), and (low) extraversion (ß = -.237, p = .025) predicted MS related depression. PwMS showed significantly higher scores in neuroticism and FEAR compared to HC. CONCLUSIONS: MS related motoric/cognitive fatigue and depression in PwMS share variance. But the substantial amount of non-shared variance (motoric fatigue, depression: 72%; cognitive fatigue, depression: 66%) together with additional predictors for depression (SADNESS being a predictor of depression only), indicate that MS related motoric/cognitive fatigue and depression are distinguishable. Consequently, we recommend assessing especially SADNESS scores to distinguish between MS related fatigue and depression.

Long-Term Stability of Short Circuits in Deep Brain Stimulation.

OBJECTIVES: To evaluate the long-term course of DBS electrodes with short-circuited contacts. MATERIALS AND METHODS: Electrodes with bipolar impedances below 150 Ω were identified from a cohort of 1044 patients with 2082 electrodes for variable movement disorders. The long-term course was analyzed from follow-up data. RESULTS: Short circuits were found in 62 electrodes (3.0%) from 60 patients (5.7%). They were restricted to two contacts in 57 electrodes (91.9%) and included more than two contacts in five electrodes. Onset was related to surgery (implantation, impulse generator replacements, or other surgical revisions) in 42 electrodes (67.7%). The onset was undetermined in 11 electrodes. In eight electrodes (12.9%) with previously normal impedances, the short circuit occurred spontaneously during long-term DBS and in one electrode after a fall. Repeated impedance checks at follow-ups of ≥3 months were available in 41 electrodes with short circuits. Twenty-six electrodes (63.4%) showed stable low impedances during observation up to nine years and two months (median 29 months). In four electrodes low impedances were stable until surgical revisions. In eight electrodes (19.5%) with observation up to nine years and seven months (median 54 months), short circuits were only detected intermittently but remained restricted to two contacts. In three electrodes (7.3%) intermittent short circuits between more than two contacts were found during long-term DBS. CONCLUSIONS: An increasing cumulative incidence demonstrates the clinical importance of short circuits. In the majority of electrodes, short circuits are restricted and remain restricted to two contacts during long-term stimulation.

Timing independent spatial motor sequence learning is preserved in left hemisphere stroke.

During neurorehabilitation, the re-learning of motor sequences is crucial for patients with motor deficits, enabling them to master again complex movements. A recent study showed that patients with left hemisphere (LH) stroke exhibited preserved motor sequence learning (as assessed by the serial reaction time (SRT) task) when the timing of the stimuli was comparable in the training and later test phase. However, patients showed significantly smaller learning scores as compared to healthy controls when the temporal delay between the patient's motor response and the following stimulus was randomized in the test phase. We here investigated whether LH stroke patients were able to learn spatial motor sequences even if no predictable temporal information was provided (i.e., adopting random response-stimulus intervals, RSIs) already during the training phase. Twelve right-handed LH stroke patients and 18 right-handed healthy controls performed a SRT task with random RSIs to test incidental learning of a complex spatial motor sequence. Results indicate that, although the learning condition with random RSIs was more difficult than learning with predictable RSIs, LH stroke patients performed as well as healthy controls regarding sequence specific learning. Thus, data show for the first time that LH stroke patients are able to incidentally learn a spatial sequence even when no predictable temporal information is available.

Lesion evidence for a human mirror neuron system.

More than two decades ago, the mirror neuron system (MNS) was discovered in non-human primates: Single-cell recordings detected visuo-motor neurons that discharged not only when the monkey performed an action, but also when it observed conspecifics performing the same action. It has been proposed that a fronto-parietal circuitry constitutes the human homolog of the MNS. However, the functional role of a human MNS (i.e., whether it is functionally necessary for imitation or action understanding) to date remains controversial. We here examined how patients with left hemisphere (LH) stroke imitate, recognize, and comprehend intransitive meaningful limb actions. In particular, we investigated whether apraxic patients with lesions affecting key nodes of the putative human MNS show deficits in action imitation, action recognition, and action comprehension to a similar degree - as predicted by the MNS hypothesis. Behavioral results showed that patients with apraxia (n = 18) indeed performed significantly worse in all three motor cognitive tasks compared to non-apraxic patients (n = 26) and healthy controls (n = 19), whose performance did not differ significantly. Lesions of the apraxic (compared to non-apraxic) patients with LH stroke affected more frequently key regions of the putative human MNS, i.e., the left inferior frontal, superior temporal, and supramarginal gyri as well as the inferior parietal lobe (p < .01, false discovery rate - FDR-corrected). Albeit largely overlapping, voxel-based lesion-symptom mapping (VLSM) revealed that deficits in gesture comprehension were mainly associated with lesions of more anterior parts of the MNS, whereas lesions located more posteriorly mainly resulted in gesture imitation deficits (p < .05, FDR-corrected). Our clinical data support key hypotheses derived from the notion of a human MNS: LH lesions to the MNS core regions affected - critically and to a similar extent - the imitation, recognition, and comprehension of meaningful actions.

Timing Matters? Learning of Complex Spatiotemporal Sequences in Left-hemisphere Stroke Patients.

During rehabilitation after stroke motor sequence learning is of particular importance because considerable effort is devoted to (re)acquiring lost motor skills. Previous studies suggest that implicit motor sequence learning is preserved in stroke patients but were restricted to the spatial dimension, although the timing of single action components is as important as their spatial order. As the left parietal cortex is known to play a critical role in implicit timing and spatiotemporal integration, in this study we applied an adapted version of the SRT task designed to assess both spatial (different stimulus locations) and temporal (different response-stimulus intervals) aspects of motor learning to 24 right-handed patients with a single left-hemisphere (LH) stroke and 24 age-matched healthy controls. Implicit retrieval of sequence knowledge was tested both at Day 1 and after 24 hr (Day 2). Additionally, voxel-based lesion symptom mapping was used to investigate the neurobiological substrates of the behavioral effects. Although LH stroke patients showed a combined spatiotemporal learning effect that was comparable to that observed in controls, LH stroke patients did not show learning effects for the learning probes in which only one type of sequence information was maintained whereas the other one was randomized. Particularly on Day 2, patients showed significantly smaller learning scores for these two learning probes than controls. Voxel-based lesion symptom mapping analyses revealed for all learning probes that diminished learning scores on Day 2 were associated with lesions of the striatum. This might be attributed to its role in motor chunking and offline consolidation as group differences occurred on Day 2 only. The current results suggest that LH stroke patients rely on multimodal information (here: temporal and spatial information) when retrieving motor sequence knowledge and are very sensitive to any disruption of the learnt sequence information as they seem to build very rigid chunks preventing them from forming independent spatial and temporal sequence representations.

Deficits of reach-to-grasp coordination following stroke: Comparison of instructed and natural movements.

The present work evaluates whether stroke-induced deficits of reach-to-grasp movements, established by typical laboratory paradigms, transfer unconditionally to more natural situations. Sixteen patients with a stroke to the motor-dominant left hemisphere and 16 age- and gender-matched healthy control subjects executed grasping movements with their left (ipsilesional, non-dominant) hand. All movements started in the same position, were aimed at the same object positioned in the same location, and were followed by forward displacement of that object along the same path. Twenty movements were performed as a repetitive, externally triggered task executed for their own sake (context L, as in typical laboratory tasks). Twenty movements were performed as part of a self-initiated action sequence aimed at winning a reward (context E, similar to many everyday situations). The kinematics and dynamics of the transport, grasp and manipulation component of each reach-to-grasp movement were quantified by 41 parameters. Analyses of variance yielded a significant effect of Context for 29 parameters, a significant effect of Group for 9 parameters (mostly related to the coupling of hand transport and grip aperture), and a significant interaction for 5 parameters (all related to the coupling of hand transport and grip aperture). The interaction reflected the fact that stroke patients' movement parameters were more abnormal in context E than in context L. Our data indicate that unilateral stroke degrades the grasp-transport coupling, and that stroke-related motor deficits may be more pronounced in a natural than in a laboratory context. Thus, for stroke patients, assessments and rehabilitation regimes should mainly use activities that are as natural as possible.

The neural basis of anosognosia for spatial neglect after stroke.

BACKGROUND AND PURPOSE: The present study investigated the lesion anatomy of anosognosia for visuospatial neglect resulting from right hemispheric stroke. METHODS: In 63 patients, self-ratings of performance in paper-and-pencil tests were contrasted with external performance ratings. Lesion analysis was conducted on patient subgroups with different degrees of anosognosia but comparable visuospatial impairment. RESULTS: Independent of the severity of visuospatial neglect per se, damage to the right angular and superior temporal gyrus was associated with higher levels of anosognosia. CONCLUSIONS: Using a novel assessment of anosognosia for spatial neglect, the present study relates stroke-induced self-awareness deficits to inferior parietal and superior temporal brain damage.