This module outlines the history of the development of surgical interventions for treating spasticity and discusses when surgical intervention is most appropriate for managing spasticity. A range of surgical techniques are considered; intrathecal baclofen, neurotomy, and muscle or tendon lengthening and transfer procedures. The implications and limitations of the surgical techniques are considered. The need for a multidisciplinary team to deliver optimal surgical treatment is also considered.

This module outlines the history of the development of surgical interventions for treating spasticity and discusses when surgical intervention is most appropriate for managing spasticity. A range of surgical techniques are considered; intrathecal baclofen, neurotomy, and muscle or tendon lengthening and transfer procedures. The implications and limitations of the surgical techniques are considered. The need for a multidisciplinary team to deliver optimal surgical treatment is also considered.

Impairments of action semantics (a cognitive domain that critically engages motor brain networks) are pervasive in early Parkinson’s disease (PD). However, no study has examined whether action semantic skills in persons with this disease can be influenced by non-invasive neuromodulation. Here, we recruited 22 PD patients and performed a five-day randomized, blinded, sham-controlled study to assess whether anodal transcranial direct current stimulation (atDCS) over the primary motor cortex, combined with cognitive training, can boost action–concept processing. On day 1, participants completed a picture–word association (PWA) task involving action-verb and object-noun conditions. They were then randomly assigned to either an atDCS (n = 11, 2 mA for 20 m) or a sham tDCS (n = 11, 2 mA for 30 s) group and performed an online PWA practice over three days. On day 5, they repeated the initial protocol. Relative to sham tDCS, the atDCS group exhibited faster reaction times for action (as opposed to object) concepts in the post-stimulation test. This result was exclusive to the atDCS group and held irrespective of the subjects’ cognitive, executive, and motor skills, further attesting to its specificity. Our findings suggest that action-concept deficits in PD are distinctively grounded in motor networks and might be countered by direct neuromodulation of such circuits. Moreover, they provide new evidence for neurosemantic models and inform a thriving agenda in the embodied cognition framework.

Non-invasive stimulation of the primary motor cortex (M1) modulates processing of decontextualized action words and sentences (i.e., verbal units denoting bodily motion). This suggests that language comprehension hinges on brain circuits mediating the bodily experiences evoked by verbal material. Yet, despite its relevance to constrain mechanistic language models, such a finding fails to reveal whether and how relevant circuits operate in the face of full-blown, everyday texts. Using a novel naturalistic discourse paradigm, we examined whether direct modulation of M1 excitability influences the grasping of narrated actions. Following random group assignment, participants received anodal transcranial direct current stimulation over the left M1, or sham stimulation of the same area, or anodal stimulation of the left ventrolateral prefrontal cortex. Immediately afterwards, they listened to action-laden and neutral stories and answered questions on information realized by verbs (denoting action and non-action processes) and circumstances (conveying locative or temporal details). Anodal stimulation of the left M1 selectively decreased outcomes on action-relative to non-action information -a pattern that discriminated between stimulated and sham participants with 74% accuracy. This result was particular to M1 and held irrespective of the subjects' working memory and vocabulary skills, further attesting to its specificity. Our findings suggest that offline modulation of motor-network excitability might lead to transient unavailability of putative resources needed to evoke actions in naturalistic texts, opening promising avenues for the language embodiment framework.

Cognitive deficits are increasingly being recognized as a common trait in Parkinson's disease (PD). Recently, transcranial direct current stimulation (tDCS) has been shown to exert positive effects as an adjunctive therapy on motor and non-motor symptoms in PD. This systematic review and meta-analysis aims to provide an overview of reported evidence on the efficacy of tDCS interventions in the treatment of cognitive impairments in PD. A systematic literature review was conducted to examine articles that were published in the past 10 years and that study the effects of tDCS on cognitive deficits in PD patients. The PubMed, Scopus and Scielo databases were searched. Eight tDCS studies involving 168 participants were included for the analysis. Our meta-analysis results showed that anodal tDCS (atDCS) had various levels or no evidence of effectiveness. In the pre-post stimulation analysis, a strong effect was reported for executive functions (pre-post: g = 1.51, Z = 2.41, p = 0.016); non-significant effects were reported for visuospatial skills (pre-post: g = 0.27, Z = 0.69, p = 0.490); attention (pre-post: g = 0.02, Z = 0.08, p = 0.934), memory (pre-post: g = 0.01, Z = 0.03, p = 0.972) and language (pre-post: g = 0.07, Z = 0.21, p = 0.832). However, in the pre-follow-up stimulation analysis, the duration of the effect was not clear. This study highlights the potential effectiveness of atDCS to improve cognitive performance in PD patients but failed to establish a cause-effect relationship between tDCS intervention and cognitive improvement in PD. Future directions and recommendations for methodological improvements are outlined.

The frontal lobes are one of the most complex brain structures involved in both domain-general and specific functions. The goal of this work was to assess the anatomical and cognitive affectations from a unique case with massive bilateral frontal affectation. We report the case of GC, an eight-year old child with nearly complete affectation of bilateral frontal structures and spared temporal, parietal, occipital, and cerebellar regions. We performed behavioral, neuropsychological, and imaging (MRI, DTI, fMRI) evaluations. Neurological and neuropsychological examinations revealed a mixed pattern of affected (executive control/abstraction capacity) and considerably preserved (consciousness, language, memory, spatial orientation, and socio-emotional) functions. Both structural (DTI) and functional (fMRI) connectivity evidenced abnormal anterior connections of the amygdala and parietal networks. In addition, brain structural connectivity analysis revealed almost complete loss of frontal connections, with atypical temporo-posterior pathways. Similarly, functional connectivity showed an aberrant frontoparietal network and relative preservation of the posterior part of the default mode network and the visual network. We discuss this multilevel pattern of behavioral, structural, and functional connectivity results. With its unique pattern of compromised and preserved structures and functions, this exceptional case offers new constraints and challenges for neurocognitive theories.

Previous studies have shown that the application of non-invasive brain stimulation can potentially improve aspects of language training in patients with aphasia. The aim of the present study is to determine whether the application of transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) combined with intensive individualized language training can improve lexical retrieval in patients with logopenic primary progressive aphasia (lvPPA). In the present double-blind, placebo-controlled crossover study, two patients (a 52-year-old woman and a 68-year-old-man) with diagnosis of lvPPA were included. Sham tDCS was applied for 6 consecutive days and then excitatory tDCS (AtDCS) was applied for another 6 days during of 20 minutes/day over left DLPFC. During the stimulation the patient received a semantic language training. The main outcome was the production of nouns and verbs in the picture description task and during spontaneous speech. Furthermore, naming in treated and untreated categories was analyzed. None of the patients was able to recognize real or sham stimulation. A statistically significant increase was obtained by comparing the number of verbs and nouns produced by both patients after training+AtDCS vs training+sham. Furthermore, we observed in one of the patients a statistically significant improvement in trained categories naming. These results demonstrate an improvement in the lexical activation of the trained categories and in verbs and nouns production, through the combination of AtDCS and semantic language therapy. Taking into account the lack of effective therapeutic alternatives, the present proof- of-principle study could be considered for a future randomized multicenter trial with a bigger design.

Recent works evince the critical role of visual short-term memory (STM) binding deficits as a clinical and preclinical marker of Alzheimer's disease (AD). These studies suggest a potential role of posterior brain regions in both the neurocognitive deficits of Alzheimer's patients and STM binding in general. Thereupon, we surmised that stimulation of the posterior parietal cortex (PPC) might be a successful approach to tackle working memory deficits in this condition, especially at early stages. To date, no causal evidence exists of the role of the parietal cortex in STM binding. A unique approach to assess this issue is afforded by single-subject direct intracranial electrical stimulation of specific brain regions during a relevant cognitive task. Electrical stimulation has been used both for clinical purposes and to causally probe brain mechanisms. Previous evidence of electrical currents spreading through white matter along well defined functional circuits indicates that visual working memory mechanisms are subserved by a specific widely distributed network. Here, we stimulated the parietal cortex of a subject with intracranial electrodes as he performed the visual STM task. We compared the ensuing results to those from a non-stimulated condition and to the performance of a matched control group. In brief, direct stimulation of the parietal cortex induced a selective improvement in STM. These results, together with previous studies, provide very preliminary but promising ground to examine behavioral changes upon parietal stimulation in AD. We discuss our results regarding: (a) the usefulness of the task to target prodromal stages of AD; (b) the role of a posterior network in STM binding and in AD; and (c) the potential opportunity to improve STM binding through brain stimulation.

Non-invasive brain stimulation (NIBS) techniques can significantly modulate cognitive functions in healthy subjects and patients with neuropsychiatric disorders. Recently, they have been applied in patients with mild cognitive impairment (MCI) and subjective cognitive impairment (SCI) to prevent or delay the development of Alzheimer's disease (AD). Here we review this emerging empirical corpus and discuss therapeutic effects of NIBS on several target functions (e.g., memory for face-name associations and non-verbal recognition, attention, psychomotor speed, everyday memory). Available studies have yielded mixed results, possibly due to differences among their tasks, designs, and samples, let alone the latter's small sizes. Thus, the impact of NIBS on cognitive performance in MCI and SCI remains to be determined. To foster progress in this direction, we outline methodological approaches that could improve the efficacy and specificity of NIBS in both conditions. Furthermore, we discuss the need for multicenter studies, accurate diagnosis, and longitudinal approaches combining NIBS with specific training regimes. These tenets could cement biomedical developments supporting new treatments for MCI and preventive therapies for AD.

* Postervortrag auf der 59. Jahrestagung der Deutschen Gesellschaft für Klinische Neurophysiologie und Funktionelle Bildgebung, 18.–21.03.2015, Tübingen; international publiziert [1]

Physiological aging is paralleled by a decline of fine motor skills accompanied by structural and functional alterations of the underlying brain network. Here, we aim to investigate age-related changes in the spectral distribution of neuronal oscillations during fine skilled motor function. We employ the concept of spectral entropy in order to describe the flatness and peaked-ness of a frequency spectrum to quantify changes in the spectral distribution of the oscillatory motor response in the aged brain. Electroencephalogram was recorded in elderly (n = 32) and young (n = 34) participants who performed either a cued finger movement or a pinch or a whole hand grip task with their dominant right hand. Whereas young participant showed distinct, well-defined movement-related power decreases in the alpha and upper beta band, elderly participants exhibited a flat broadband, frequency-unspecific power desynchronization. This broadband response was reflected by an increase of spectral entropy over sensorimotor and frontal areas in the aged brain. Neuronal activation patterns differed between motor tasks in the young brain, while the aged brain showed a similar activation pattern in all tasks. Moreover, we found a wider recruitment of the cortical motor network in the aged brain. The present study adds to the understanding of age-related changes of neural coding during skilled motor behavior, revealing a less predictable signal with great variability across frequencies in a wide cortical motor network in the aged brain. The increase in entropy in the aged brain could be a reflection of random noise-like activity or could represent a compensatory mechanism that serves a functional role.

Cerebellar transcranial direct current stimulation (tDCS) has the potential to modulate cerebellar outputs and visuomotor adaptation. The cerebellum plays a pivotal role in the acquisition and control of skilled hand movements, especially its temporal aspects. We applied cerebellar anodal tDCS concurrently with training of a synchronization-continuation motor task. We hypothesized that anodal cerebellar tDCS will enhance motor skill acquisition. Cerebellar tDCS was applied to the right cerebellum in 31 healthy subjects in a double-blind, sham-controlled, parallel design. During synchronization, the subjects tapped the sequence in line with auditory cues. Subsequently, in continuation, the learned sequence was reproduced without auditory cuing. Motor task performance was evaluated before, during, 90 min, and 24 h after training. Anodal cerebellar tDCS, compared with sham, improved the task performance in the follow-up tests (F1,28 = 5.107, P = 0.032) of the synchronization part. This effect on retention of the skill was most likely mediated by enhanced motor consolidation. We provided first evidence that cerebellar tDCS can enhance the retention of a fine motor skill. This finding supports the promising approach of using noninvasive brain stimulation techniques to restore impaired motor functions in neurological patients, such after a stroke.

Functional imaging studies have argued that interactions between cortical motor areas and the cerebellum are relevant for motor output and recovery processes after stroke. However, the impact of the underlying structural connections is poorly understood. To investigate this, diffusion-weighted brain imaging was conducted in 26 well-characterized chronic stroke patients (aged 63 +/- 1.9 years, 18 males) with supratentorial ischemic lesions and 26 healthy participants. Probabilistic tractography was used to reconstruct reciprocal cortico-cerebellar tracts and to relate their microstructural integrity to residual motor functioning applying linear regression modeling. The main finding was a significant association between cortico-erebellar structural connectivity and residual motor function, independent fromthe level of damage to the cortico-spinal tract. Specifically, white matter integrity of the cerebellar outflow tract, the dentato-thalamo-cortical tract, was positively related to both general motor output and fine motor skills. Additionally, the integrity of the descending cortico-ponto-cerebellar tract contributed to rather fine motor skills. A comparable structure-function relationship was not evident in the controls. The present study provides first tract-related structural data demonstrating a critical importance of distinct cortico-cerebellar connections for motor output after stroke.

The aging population is facing important challenges associated to impairments in cognitive abilities including sensorimotor functions. In our daily life the acquisition and long-term retention of motor skills play a crucial role for the appropriate implementation of motor acts, such as practicing sport or the use of modern communication tools. Notably, motor cortical plasticity is altered in older adults (OA) due to changes in neurotransmission and synaptic functioning. Changes in GABAergic activity and its modulatory capacity has been described, as well as diminished LTP-like mechanisms contributing to associative plasticity and motor memory formation. Strong interest lies in the understanding of age-associated mechanisms underlying impairment of motor performance and motor learning in old and in possible ways of ameliorating age-related deficits in these domains. Experiment 1: We investigated the process of learning of sequential finger tapping in a group of 15 healthy OA (73.9 ± 5.9 years ± standard deviation [SD]) and compared to 15 healthy young subjects (24.4 ± 3.5 SD). The learning process was accompanied by double-pulse transcranial magnetic stimulation (dp-TMS) in order to investigate intracortical effects during the learning process reflecting activity of GABAergic neurotransmission. The task was performed during 5 consecutive training days, with 3 follow-up time points on day 10, 20 and 60. Experiment 2: In a subsequent experiment, we investigated the effects of transcranial direct current stimulation (tDCS) in a group of 28 healthy OA aged 72.0 ± 5.4 SD. tDCS provides the possibility to modulate cortical excitability and neuroplasticity. We tested the hypothesis that tDCS in combination with training will enhance the effect of skill acquisition in OA. In our double-blind, placebo controlled study tDCS was applied to the motor cortex, contralateral to the training performing hand. Either anodal or placebo/sham stimulation was applied for 20 min while subjects underwent the same training as mentioned above. Experiment 1: Analyses revealed impaired skill acquisition in the OA group in relation to the young group during training period (pMOVE). The group of young healthy subjects showed learning related changes of SICIMOVE towards an enhanced event-related disinhibition. This was not the case for OA. Experiment 2: The group receiving real stimulation showed a different learning curve in the 5 days of training with significantly enhanced skill acquisition compared to the sham group (p = 0.044), a behavioral effect still apparent 60 days after interventions. Motor skill acquisition was impaired in healthy older subjects, this effect was mainly driven by a reduction in offline effects. Furthermore, tDCS can ameliorate age-related deficits in the acquisition of a novel motor skill, offering a promising interventional strategy to address age-related cognitive deficits.

PURPOSE:Recovery of hand function after stroke has been associated with transient overactivation of the cerebral sensorimotor network. One open question has been as to how much this transient overactivation is related to 'true' reorganisation of the network or reflecting the fact that a simple motor task is difficult to perform for a patient with a motor deficit, i.e. reflecting 'effort'. METHODS:To address this, we combined a constant-output (varying effort) and constant-effort (varying output) task in a longitudinal (T1 = 3-5 days, T2 = 6 weeks, T3 = 3 months after stroke) multimodal (functional magnetic resonance imaging (FMRI), electroencephalography (EEG)) study of 12 (EEG)/8 (FMRI) patients (7 male, age 67 ± 9 years) showing significant recovery from a hand motor deficit. RESULTS:The reduction of sensorimotor activation from T1 to T3 was significant (p = 0.012). But task effort did not exhibit any significant impact on the evolution of task-related brain activation over time. This proved to be equally applicable to FMRI and EEG data. CONCLUSION:We conclude that initial up-regulation of brain activity after stroke is not simply a consequence of enhanced effort early after stroke but rather reflects neural processes involved in reorganisation and recovery of function.

BACKGROUND:Cognitive difficulties are the most common neurological complications in neurofibromatosis type 1 (NF1) patients. Recent animal models proposed increased GABA-mediated inhibition as one underlying mechanism directly affecting the induction of long-term potentiation (LTP) and learning. In most adult NF1 patients, apparent cognitive and attentional deficits, tumors affecting the nervous system and other confounding factors for neuroscientific studies are difficult to control for. Here we used a highly specific group of adult NF1 patients without cognitive or nervous system impairments. Such selected NF1 patients allowed us to address the following open questions: Is the learning process of acquiring a challenging motor skill impaired in NF1 patients? And is such an impairment in relation to differences in intracortical inhibition?METHODS:We used an established non-invasive, double-pulse transcranial magnetic stimulation (dp-TMS) paradigm to assess practice-related modulation of intracortical inhibition, possibly mediated by gamma-minobutyric acid (GABA)ergic-neurotransmission. This was done during an extended learning paradigm in a group of NF1 patients without any neuropsychological deficits, functioning normally in daily life and compared them to healthy age-matched controls.FINDINGS:NF1 patients experienced substantial decline in motor skill acquisition (F = 9.2, p = 0.008) over five-consecutives training days mediated through a selective reduction in the early acquisition (online) and the consolidation (offline) phase. Furthermore, there was a consistent decrease in task-related intracortical inhibition as a function of the magnitude of learning (T = 2.8, p = 0.014), especially evident after the early acquisition phase.INTERPRETATIONS:Collectively, the present results provide evidence that learning of a motor skill is impaired even in clinically intact NF1 patients based, at least partially, on a GABAergic-cortical dysfunctioning as suggested in previous animal work.

Spontaneous recovery of motor deficits after stroke evolve at a rather unpredictable fashion regarding the time and extend of skill reacquisition (Langhorne et al., Lancet, 2011). Previous longitudinal studies investigating brain activity during recovery from hand motor deficits point to an early overactivation of the motor network with a decrease back to near normal patterns later after stroke (Rehme et al., Neuroimage, 2012). Since patients regain force and skill during recovery, changes in neural activation over time could be explained by a decreased relative task effort over time. Such a behavioral bias could affect neuroimaging findings and their interpretation in regard to recovery, a question not or not sufficiently accounted for in previous studies. The aim of the present study was to systematically investigate the influence of task effort on recovery-related brain activation. We addressed the question whether keeping either task effort or task output constant leads to differing patterns of recovery-related brain activation over time within a “constant output-constant effort” design. We speculated that due to the recovery-related increase in manual power, the two experimental conditions show different evolutions of brain activity patterns with constant output reflecting stronger changes over time. Since electroencephalography and functional magnetic resonance imaging measure different aspects of brain activation, we used a multimodal approach. We assessed brain activity with functional magnetic resonance imaging (FMRI, blood oxygenation level dependent signal (BOLD)) and EEG based task-related spectral-power within lower alpha, upper alpha, beta band, in a longitudinal design covering the acute (3–5 d post stroke), subacute (30 days) and early chronic (90 days) phase after an ischemic infarction causing a hand motor deficit. At every time point, patients (n = 12 (EEG)/8 (FMRI), m = 6, age 66.67 ± 9.03 (mean ± std), 4 left hemispheric lesions) performed whole hand grips with both 5 kg constant output and 20% of the current individual maximal force (constant effort). Patients showed significant recovery over time (increase in grip force over time, p < 0.001). In parallel, we found a significant reduction in task-related brain activity during recovery (p < 0.01). Relative task effort had no significant impact on the evolution of task-related brain activation over time (TASK × TIME, n.s.). This proved to be equally applicable to FMRI and EEG data (TASK × TIME × METHOD, n.s.; TASK × METHOD n.s.; TIME × METHOD, n.s.). This longitudinal study demonstrates in mildly affected patients that task-related brain activity significantly decreases over time as suggested previously. The main finding was that the dynamic change of brain activation over time did not relate to the effort necessary to perform the task at each measurement time point. In detail, this shows that the task effort had no significant effect on the slope of brain activity decrease in the course of recovery. These data suggest that the decline of motor task-related brain activity during recovery is largely reflecting adaptive processes in the course of neuronal reorganization and is not influenced significantly by behavioral/cognitive differences, such as effort, over time. Using multimodal imaging, two independent measures of neural activity (BOLD, EEG power) support this finding, mutually validating methodological assessment of brain activation and augmenting the explanatory power.

Stroke is the leading cause of disability among adults. Motor deficit is the most common impairment after stroke. Especially, deficits in fine motor skills impair numerous activities of daily life. Re-acquisition of motor skills resulting in improved or more accurate motor performance is paramount to regain function, and is the basis of behavioral motor therapy after stroke. Within the past years, there has been a rapid technological and methodological development in neuroimaging leading to a significant progress in the understanding of the neural substrates that underlie motor skill acquisition and functional recovery in stroke patients. Based on this and the development of novel non-invasive brain stimulation (NIBS) techniques, new adjuvant interventional approaches that augment the response to behavioral training have been proposed. Transcranial direct current, transcranial magnetic, and paired associative (PAS) stimulation are NIBS techniques that can modulate cortical excitability, neuronal plasticity and interact with learning and memory in both healthy individuals and stroke patients. These techniques can enhance the effect of practice and facilitate the retention of tasks that mimic daily life activities. The purpose of the present review is to provide a comprehensive overview of neuroplastic phenomena in the motor system during learning of a motor skill, recovery after brain injury, and of interventional strategies to enhance the beneficial effects of customarily used neurorehabilitation after stroke.