100 years after Liepmann-Lesion correlates of diminished selection and application of familiar versus novel tools.

100 years ago, Liepmann highlighted the role of left ventro-dorsal lesions for impairments in conceptual (rather ventral) and motor (more dorsal) related aspects of apraxia. Many studies thereafter attributed to an extended left fronto-temporo-parietal network. Yet, to date there are only few studies that looked at apraxic performance in the selection and application of familiar versus novel tools. In the current study we applied modern voxel-based lesion-symptom mapping (VLSM) to analyze neural correlates of impaired selection and application of familiar versus novel tools. 58 left (LBD) and 51 right brain damaged (RBD) stroke patients participated in the Novel Tools Test (NTT) and the Familiar Tools Test (FTT) of the Diagnostic Instrument for Limb Apraxia (DILA-S). We further assessed performance in control tasks, namely semantic knowledge (BOSU), visuo-spatial working memory (Corsi Block Tapping) and meaningless imitation of gestures (IML). Impaired tool use was most pronounced after LBD. Our VLSM results in the LBD group suggested that selection- versus application-related aspects of praxis and semantics of familiar versus novel tool use can be behaviorally and neuro-anatomically differentiated. For impairments in familiar tool tasks, the major focus of lesion maps was rather ventral while deficiencies in novel tool tasks went along with rather dorsal lesions. Affected selection processes were linked to rather anterior lesions, while impacted application processes went along with rather posterior lesion maps. In our study, particular tool selection processes were rather specific for familiar versus novel tools. Foci for lesion overlaps of experimental and control tasks were noticed ventrally for semantic knowledge and FTT, in fronto-parietal regions for working memory and NTT, and ventro-dorsally for imitation of meaningless gestures and the application of NTT and FTT. We visualized our current interpretation within a neuroanatomical model for apraxia of tool use.

Increased Amygdala Activity Associated With Cognitive Reappraisal Strategy in Functional Neurologic Disorder.

Cognitive reappraisal is an emotion regulation strategy to reduce the impact of affective stimuli. This regulation could be incomplete in patients with functional neurologic disorder (FND) resulting in an overflowing emotional stimulation perpetuating symptoms in FND patients. Here we employed functional MRI to study cognitive reappraisal in FND. A total of 24 FND patients and 24 healthy controls employed cognitive reappraisal while seeing emotional visual stimuli in the scanner. The Symptom Checklist-90-R (SCL-90-R) was used to evaluate concomitant psychopathologies of the patients. During cognitive reappraisal of negative IAPS images FND patients show an increased activation of the right amygdala compared to normal controls. We found no evidence of downregulation in the amygdala during reappraisal neither in the patients nor in the control group. The valence and arousal ratings of the IAPS images were similar across groups. However, a subgroup of patients showed a significant higher account of extreme low ratings for arousal for negative images. These low ratings correlated inversely with the item "anxiety" of the SCL-90-R. The increased activation of the amygdala during cognitive reappraisal suggests altered processing of emotional stimuli in this region in FND patients.

Behavioral and neurophysiological effects of an intensified robot-assisted therapy in subacute stroke: a case control study.

BACKGROUND: Physical training is able to induce changes at neurophysiological and behavioral level associated with performance changes for the trained movements. The current study explores the effects of an additional intense robot-assisted upper extremity training on functional outcome and motor excitability in subacute stroke patients. METHODS: Thirty moderately to severely affected patients < 3 months after stroke received a conventional inpatient rehabilitation. Based on a case-control principle 15 patients were assigned to receive additional 45 min of robot-assisted therapy (Armeo®Spring) 5 times per week (n = 15, intervention group, IG). The Fugl-Meyer Assessment for the Upper Extremity (FMA-UE) was chosen as primary outcome parameter. Patients were tested before and after a 3-week treatment period as well as after a follow-up period of 2 weeks. Using transcranial magnetic stimulation motor evoked potentials (MEPs) and cortical silent periods were recorded from the deltoid muscle on both sides before and after the intervention period to study effects at neurophysiological level. Statistical analysis was performed with non-parametric tests. Correlation analysis was done with Spearman´s rank correlation co-efficient. RESULTS: Both groups showed a significant improvement in FMA-UE from pre to post (IG: + 10.6 points, control group (CG): + 7.3 points) and from post to follow-up (IG: + 3.9 points, CG: + 3.3 points) without a significant difference between them. However, at neurophysiological level post-intervention MEP amplitudes were significantly larger in the IG but not in the CG. The observed MEP amplitudes changes were positively correlated with FMA-UE changes and with the total amount of robot-assisted therapy. CONCLUSION: The additional robot-assisted therapy induced stronger excitability increases in the intervention group. However, this effect did not transduce to motor performance improvements at behavioral level. Trial registration The trial was registered in German Clinical Trials Register. CLINICAL TRIAL REGISTRATION NUMBER: DRKS00015083. Registration date: September 4th, 2018. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00015083 . Registration was done retrospectively.

Cortical, subcortical and spinal neural correlates of slackline training-induced balance performance improvements.

Humans develop posture and balance control during childhood. Interestingly, adults can also learn to master new complex balance tasks, but the underlying neural mechanisms are not fully understood yet. Here, we combined broad scale brain connectivity fMRI at rest and spinal excitability measurements during movement. Six weeks of slackline training improved the capability to walk on a slackline which was paralleled by functional connectivity changes in brain regions associated with posture and balance control and by task-specific changes of spinal excitability. Importantly, the performance of trainees was not better than control participants in a different, untrained balance task. In conclusion, slackline training induced large-scale neuroplasticity which solely transferred into highly task specific performance improvements.

Neural correlates of effort-dependent and effort-independent cognitive fatigue components in patients with multiple sclerosis.

BACKGROUND: Among patients with multiple sclerosis (MS), fatigue is the most commonly reported symptom. It can be subdivided into an effort-dependent (fatigability) and an effort-independent component (trait-fatigue). OBJECTIVE: The objective was to disentangle activity changes associated with effort-independent "trait-fatigue" from those associated with effort-dependent fatigability in MS patients. METHODS: This study employed behavioral measures and functional magnetic imaging to investigate neural changes in MS patients associated with fatigue. A total of 40 MS patients and 22 age-matched healthy controls performed in a fatigue-inducing N-back task. Effort-independent fatigue was assessed using the Fatigue Scale of Motor and Cognition (FSMC) questionnaire. RESULTS: Effort-independent fatigue was observed to be reflected by activity increases in fronto-striatal-subcortical networks primarily involved in the maintenance of homeostatic processes and in motor and cognitive control. Effort-dependent fatigue (fatigability) leads to activity decreases in attention-related cortical and subcortical networks. CONCLUSION: These results indicate that effort-independent (fatigue) and effort-dependent fatigue (fatigability) in MS patients have functionally related but fundamentally different neural correlates. Fatigue in MS as a general phenomenon is reflected by complex interactions of activity increases in control networks (effort-independent component) and activity reductions in executive networks (effort-dependent component) of brain areas.

Induction of cognitive fatigue in MS patients through cognitive and physical load.

The objective of the study was to investigate whether cognitive fatigue in patients with multiple sclerosis (MS) is a spontaneous phenomenon or whether it can be provoked or exacerbated through cognitive effort and motor exercise. Thirty two patients with definite MS and cognitive fatigue according to the Fatigue Scale for Motor and Cognitive Functions (FSMC ≥ 22) performed attention tests (alertness, selective, and divided attention subtests from the TAP test battery for attention performance) twice during rest (baseline), and before and after treadmill training and cognitive load (a standardised battery of neuropsychological tests lasting 2.5 hours). Subjective exhaustion was assessed with a 10-point rating scale. Tonic alertness turned out to be the most sensitive test and showed significantly increased reaction times after treadmill training and after cognitive load. Patients' subjective assessment of exhaustion (10-point rating scale) and the objective test results were discrepant. In contrast, healthy control subjects (N = 20) did not show any decline of performance in the subtest alertness after cognitive or physical load. Data favour the concept that fatigue is induced by physical and mental load. Discrepancies between subjective and objective assessment offer therapeutic options. The common notion of a purely "subjective" lack of physical and/or mental energy should be reconsidered.