Apraxia is a motor-cognitive disorder that primary sensorimotor deficits cannot solely explain. Previous research in stroke patients has focused on damage to the fronto-parietal praxis networks in the left hemisphere (LH) as the cause of apraxic deficits. In contrast, the potential role of the (left) primary motor cortex (M1) has largely been neglected. However, recent brain stimulation and lesion-mapping studies suggest an involvement of left M1 in motor cognitive processes-over and above its role in motor execution. Therefore, this study explored whether the left M1 plays a specific role in apraxia.

We identified 157 right-handed patients with first-ever unilateral LH stroke in the sub-acute phase (< 90 days post-stroke), for whom apraxia assessments performed with the ipsilesional left hand and lesion maps were available. Utilizing the maximum probability map of Brodmann area 4 (representing M1) provided by the JuBrain Anatomy Toolbox in SPM, patients were subdivided into two groups depending on whether their lesions involved (n = 40) or spared (n = 117) left M1. We applied a mixed model ANCOVA with repeated measures to compare apraxic deficits between the two patient groups, considering the factors "body part" and "gesture meaning". Furthermore, we explored potential differential effects of the anterior (4a) and posterior (4p) parts of Brodmann area 4 by correlation analyses.

Patients with and without M1 involvement did not differ in age and time post-stroke but in lesion size. When controlling for lesion size, the total apraxia scores did not differ significantly between groups. However, the mixed model ANCOVA showed that LH stroke patients with lesions involving left M1 performed differentially worse when imitating meaningless finger gestures. This effect was primarily driven by lesions affecting Brodmann area 4p.

Even though many current definitions of apraxia disregard a relevant role of (left) M1, the observed differential effect of M1 lesions, specifically involving subarea 4p, on the imitation of meaningless finger gestures in the current sample of LH stroke patients suggests a specific role of left M1 in imitation when high amounts of (motor) attention and sensorimotor integration are required.

Brain imaging and electrophysiology have significantly enhanced our current understanding of stroke-related changes in brain structure and function and their implications for recovery processes. In the motor domain, most studies have focused on key motor areas of the frontal lobe including the primary and secondary motor cortices. Time- and recovery-dependent alterations in regional anatomy, brain activity and inter-regional connectivity have been related to recovery. In contrast, the involvement of posterior parietal cortical areas in stroke recovery is poorly understood although these regions are similarly important for important aspects of motor functioning in the healthy brain. Just in recent years, the field has increasingly started to explore to what extent posterior parietal cortical areas might undergo equivalent changes in task-related activation, regional brain structure and inter-regional functional and structural connectivity after stroke. The aim of this scoping review is to give an update on available data covering these aspects and thereby providing novel insights into parieto-frontal interactions for systems neuroscience stroke recovery research in the upper limb motor domain.

Previous studies on left hemisphere (LH) stroke patients reported effector-specific (hand, fingers, bucco-facial) differences in imitation performance. Furthermore, imitation performance differed between meaningless (ML) and meaningful (MF) gestures. Recent work suggests that a gesture's meaning impacts the body-part specificity of gesture imitation.

We tested the hypothesis that the gesture's meaning (ML vs MF) affects the lesion correlates of effector-specific imitation deficits (here: bucco-facial vs arm/hand gestures) using behavioural data and support vector regression-based lesion-symptom mapping (SVR-LSM) in a large sample of 194 sub-acute LH stroke patients.

Behavioural data revealed a significant interaction between the effector used for imitation and the meaning of the imitated gesture. SVR-LSM analyses revealed shared lesion correlates for impaired imitation independent of effector or gesture meaning in the left supramarginal (SMG) and superior temporal gyri (STG). Besides, within the territory of the left middle cerebral artery, impaired imitation of bucco-facial gestures was associated with more anterior lesions, while arm/hand imitation deficits were associated with more posterior lesions. MF gestures were specifically associated with lesions in the left inferior frontal gyrus and the left insular region. Notably, an interaction of effector-specificity and gesture meaning was also present at the lesion level: A more pronounced difference in imitation performance between the effectors for ML (versus MF) gestures was associated with left-hemispheric lesions in the STG, SMG, putamen, precentral gyrus and white matter tracts.

The current behavioural data show that ML gestures are particularly sensitive in assessing effector-specific imitation deficits in LH stroke patients. Moreover, a gesture's meaning modulated the effector-specific lesion correlates of bucco-facial and arm/hand gesture imitation. Hence, it is crucial to consider gesture meaning in apraxia assessments.

Stroke is a leading cause of disability worldwide. Limb apraxia is a group of higher order motor disorders associated with greater disability and dependence after stroke. Original neuropsychology studies distinguished separate brain pathways involved in perception and action, known as the dual stream hypothesis. This framework has allowed a better understanding of the deficits identified in Limb Apraxia. In this review, we propose a hierarchical organization of this disorder, in which a distinction can be made between several visuomotor pathways that lead to purposeful actions. Based on this, executive apraxias (such as limb kinetic apraxia) cause deficits in executing fine motor hand skills, and intermediate apraxias (such as optic ataxia and tactile apraxia) cause deficits in reaching to grasp and manipulating objects in space. These disorders usually affect the contralesional limb. A further set of disorders collectively known as limb apraxias include deficits in gesture imitation, pantomime, gesture recognition, and object use. These deficits are due to deficits in integrating perceptual and semantic information to generate complex movements. Limb apraxias are usually caused by left-hemisphere lesions in right-handed stroke patients, affecting both limbs. The anterior- to posterior-axis of brain areas are disrupted depending on the increasing involvement of perceptual and semantic processes with each condition. Lower-level executive apraxias are linked to lesions in the frontal lobe and the basal ganglia, while intermediate apraxias are linked to lesions in dorso-dorsal subdivisions of the dorsal fronto-parietal networks. Limb apraxias can be caused by lesions in both dorsal and ventral subdivisions including the ventro-dorsal stream and a third visuomotor pathway, involved in body schema and social cognition. Rehabilitation of these disorders with behavioral therapies has aimed to either restore perceptuo-semantic deficits or compensate to overcome these deficits. Further studies are required to better stratify patients, using modern neurophysiology and neuroimaging techniques, to provide targeted and personalized therapies for these disorders in the future.

Apraxia is a common syndrome of left hemispheric stroke. A parieto-premotor-prefrontal network has been associated with apraxia, in which the left inferior parietal lobe (IPL-L) plays a major role. We hypothesized that transcranial continuous theta burst stimulation (cTBS) over the right inferior parietal lobe (IPL-R) improves gesturing by reducing its inhibition on the contralateral IPL in left hemispheric stroke patients. It was assumed that this effect is independent of lesion volume and that transcallosal connectivity is predictive for gestural effect after stimulation.

Nineteen stroke patients were recruited. Lesion volume and fractional anisotropy of the corpus callosum were acquired with structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Each patient had pseudorandomised sessions with sham or with stimulation over the IPL-R or over the right inferior frontal gyrus IFG-R. Gesturing was assessed in a double-blinded manner before and after each session. We tested the effects of stimulation on gesture performance using a linear mixed-effects model.

Pairwise treatment contrasts showed, that, compared to sham, the behavioral effect was higher after stimulation over IPL-R (12.08, 95% CI 6.04 - 18.13, p < 0.001). This treatment effect was approximately twice as high as the contrasts for IFG-R vs. sham (6.25, 95% CI -0.20 - 12.70, p = 0.058) and IPL-R vs. IFG-R vs. sham (5.83, 95% CI -0.49 - 12.15, p = 0.071). Furthermore, higher fractional anisotropy in the splenium (connecting the left and right IPL) were associated with higher behavioral effect. Relative lesion volume did not affect the changes after sham or stimulation over IPL-R or IFG-R.

One single session of cTBS over the IPL-R improved gesturing after left hemispheric stroke. Denser microstructure in the corpus callosum correlated with favorable gestural response. We therefore propose the indirect transcallosal modulation of the IPL-L as a promising model of restoring interhemispheric balance, which may be useful in rehabilitation of apraxia.

Apraxia is characterised by multiple deficits of higher motor functions, primarily caused by left hemisphere (LH) lesions to parietal-frontal praxis networks. While previous neuropsychological and lesion studies tried to relate the various apraxic deficits to specific lesion sites, a comprehensive analysis of the different apraxia profiles and the related (impaired) motor-cognitive processes as well as their differential neural substrates in LH stroke is lacking. To reveal the cognitive mechanisms that underlie the different patterns of praxis and (related) language deficits, we applied principal component analysis (PCA) to the scores of sub-acute LH stroke patients (n = 91) in several tests of apraxia and aphasia. Voxel-based lesion-symptom mapping (VLSM) analyses were then used to investigate the neural substrates of the identified components. The PCA yielded a first component related to language functions and three components related to praxis functions, with each component associated with specific lesion patterns. Regarding praxis functions, performance in imitating arm/hand gestures was accounted for by a second component related to the left precentral gyrus and the inferior parietal lobule. Imitating finger configurations, pantomiming the use of objects related to the face, and actually using objects loaded on component 3, related to the left anterior intraparietal sulcus and angular gyrus. The last component represented the imitation of bucco-facial gestures and was linked to the basal ganglia and LH white matter tracts. The results further revealed that pantomime of (limb-related) object use depended on both the component 2 and 3, which were shared with gesture imitation and actual object use. Data support and extend the notion that apraxia represents a multi-componential syndrome comprising different (impaired) motor-cognitive processes, which dissociate - at least partially - from language processes. The distinct components might be disturbed to a varying degree following LH stroke since they are associated with specific lesion patterns within the LH.

tDCS modulates cortical plasticity and has shown potential to improve cognitive/motor functions in healthy young humans. However, age-related alterations of brain structure and functions might require an adaptation of tDCS-parameters to achieve a targeted plasticity effect in older humans and conclusions obtained from young adults might not be directly transferable to older adults. Thus, our study aimed to systematically explore the association between tDCS-parameters and induced aftereffects on motor cortical excitability to determine optimal stimulation protocols for older individuals, as well as to investigate age-related differences of motor cortex plasticity in two different age groups of older adults.

32 healthy, volunteers from two different age groups of Young-Old (50-65 years, n = 16) and Old-Old (66-80 years, n = 16) participated in this study. Anodal tDCS was applied over the primary motor cortex, with respective combinations of three intensities (1, 2, and 3 mA) and durations (15, 20, and 30 min), in a sham-controlled cross-over design. Cortical excitability alterations were monitored by single-pulse TMS-induced MEPs until the next day morning after stimulation.

All active stimulation conditions resulted in a significant enhancement of motor cortical excitability in both age groups. The facilitatory aftereffects of anodal tDCS did not significantly differ between age groups. We observed prolonged plasticity in the late-phase range for two protocols with the highest stimulation intensity (i.e., 3 mA-20 min, 3 mA-30 min).

Our study highlights the role of stimulation dosage in tDCS-induced neuroplastic aftereffects in the motor cortex of healthy older adults and delivers crucial information about optimized tDCS protocols in the domain of the primary motor cortex. Our findings might set the grounds for the development of optimal stimulation protocols to reinstate neuroplasticity in different cortical areas and induce long-lasting, functionally relevant plasticity in normal aging and in pathological conditions, which would require however systematic tDCS titration studies over respective target areas.

Stroke is the leading cause of acquired disability in western societies. (Motor) cognitive deficits like apraxia significantly contribute to disability after stroke, harming activities of daily living and rehabilitation outcome. To date, efficient therapeutic options for apraxia remain sparse. Thus, randomized controlled trials (RCTs) are warranted.

Based on promising results of a pilot study, the on-going RAdiCS (Rehabilitating stroke-induced Apraxia with direct Current Stimulation) study is a randomized controlled trial, which follows a double-blinded (investigator and patient), two-arm parallel interventional model. It is designed to include 110 apraxic patients (as diagnosed by the Cologne Apraxia Screening, KAS) in the subacute phase after a left hemisphere (LH) stroke. The University of Cologne initiated the trial, which is conducted in two German Neurorehabilitation Centers.The study aims to evaluate the effect of anodal (versus sham) transcranial direct current stimulation (tDCS) applied over the left posterior parietal cortex (PPC) with an intensity of 2 mA for 10 min on five consecutive days on apraxic deficits. In addition to anodal or sham tDCS, all LH stroke patients undergo a motor (cognitive) training that is performed before and after the stimulation (off-line stimulation).The primary outcome measure is the (differential) change in the overall KAS score after five daily sessions of anodal versus sham tDCS when compared to the baseline assessment before tDCS. Secondary study outcomes include further apraxia scores, aphasia severity, and measures of motor performance and disability after stroke. All outcome measures are obtained in the post-stimulation assessment as well as during follow-up (3-4 months after tDCS).

The RCT RAdiCS shall evaluate in a large number of LH stroke patients whether anodal tDCS (compared to sham tDCS) expedites the rehabilitation of apraxia - over and above additional motor (cognitive) training and standard care. A positive study outcome would provide a new strategy for the treatment of apraxia, which hopefully ameliorates the negative impact of apraxia on daily living and long-term outcome.

Clinical Trials Gov: NCT03185234, registered 14 June 2017 ; Deutsches Register für Klinische Studien: DRKS00012292, registered 01 June 2017.

Participant enrollment began on 22 June 2017. The trial is expected to be completed on 30 June 2022.