Optimizing home-based long-term intensive care for neurological patients with neurorehabilitation outreach teams - protocol of a multicenter, parallel-group randomized controlled trial (OptiNIV-Study).

BACKGROUND: Even with high standards of acute care and neurological early rehabilitation (NER) a substantial number of patients with neurological conditions still need mechanical ventilation and/or airway protection by tracheal cannulas when discharged and hence home-based specialised intensive care nursing (HSICN). It may be possible to improve the home care situation with structured specialized long-term neurorehabilitation support and following up patients with neurorehabilitation teams. Consequently, more people might recover over an extended period to a degree that they were no longer dependent on HSICN. METHODS: This healthcare project and clinical trial implements a new specialised neurorehabilitation outreach service for people being discharged from NER with the need for HSICN. The multicentre, open, parallel-group RCT compares the effects of one year post-discharge specialized outpatient follow-up to usual care in people receiving HSICN. Participants will randomly be assigned to receive the new form of healthcare (intervention) or the standard healthcare (control) on a 2:1 basis. Primary outcome is the rate of weaning from mechanical ventilation and/or decannulation (primary outcome) after one year, secondary outcomes include both clinical and economic measures. 173 participants are required to corroborate a difference of 30 vs. 10% weaning success rate statistically with 80% power at a 5% significance level allowing for 15% attrition. DISCUSSION: The OptiNIV-Study will implement a new specialised neurorehabilitation outreach service and will determine its weaning success rates, other clinical outcomes, and cost-effectiveness compared to usual care for people in need for mechanical ventilation and/or tracheal cannula and hence HSICN after discharge from NER. TRIAL REGISTRATION: The trial OptiNIV has been registered in the German Clinical Trials Register (DRKS) since 18.01.2022 with the ID DRKS00027326 .

Consensus Paper: Revisiting the Symptoms and Signs of Cerebellar Syndrome.

The cerebellum is involved in sensorimotor operations, cognitive tasks and affective processes. Here, we revisit the concept of the cerebellar syndrome in the light of recent advances in our understanding of cerebellar operations. The key symptoms and signs of cerebellar dysfunction, often grouped under the generic term of ataxia, are discussed. Vertigo, dizziness, and imbalance are associated with lesions of the vestibulo-cerebellar, vestibulo-spinal, or cerebellar ocular motor systems. The cerebellum plays a major role in the online to long-term control of eye movements (control of calibration, reduction of eye instability, maintenance of ocular alignment). Ocular instability, nystagmus, saccadic intrusions, impaired smooth pursuit, impaired vestibulo-ocular reflex (VOR), and ocular misalignment are at the core of oculomotor cerebellar deficits. As a motor speech disorder, ataxic dysarthria is highly suggestive of cerebellar pathology. Regarding motor control of limbs, hypotonia, a- or dysdiadochokinesia, dysmetria, grasping deficits and various tremor phenomenologies are observed in cerebellar disorders to varying degrees. There is clear evidence that the cerebellum participates in force perception and proprioceptive sense during active movements. Gait is staggering with a wide base, and tandem gait is very often impaired in cerebellar disorders. In terms of cognitive and affective operations, impairments are found in executive functions, visual-spatial processing, linguistic function, and affective regulation (Schmahmann's syndrome). Nonmotor linguistic deficits including disruption of articulatory and graphomotor planning, language dynamics, verbal fluency, phonological, and semantic word retrieval, expressive and receptive syntax, and various aspects of reading and writing may be impaired after cerebellar damage. The cerebellum is organized into (a) a primary sensorimotor region in the anterior lobe and adjacent part of lobule VI, (b) a second sensorimotor region in lobule VIII, and (c) cognitive and limbic regions located in the posterior lobe (lobule VI, lobule VIIA which includes crus I and crus II, and lobule VIIB). The limbic cerebellum is mainly represented in the posterior vermis. The cortico-ponto-cerebellar and cerebello-thalamo-cortical loops establish close functional connections between the cerebellum and the supratentorial motor, paralimbic and association cortices, and cerebellar symptoms are associated with a disruption of these loops.

Dysphagia--a common, transient symptom in critical illness polyneuropathy: a fiberoptic endoscopic evaluation of swallowing study*.

OBJECTIVES: Critical illness polyneuropathy is a common disorder in the neurological ICU. Dysphagia is well known to deteriorate outcome in the ICU. The prevalence of dysphagia in critical illness polyneuropathy is not known. The aim of this study was to evaluate the prevalence of dysphagia in critical illness polyneuropathy using fiberoptic endoscopic evaluation of swallowing. DESIGN: Prospective, cohort study. SETTING: Neurological rehabilitation ICU. PATIENTS: Twenty-two patients with critical illness polyneuropathy. INTERVENTIONS: Clinical swallowing examination and serial fiberoptic endoscopic evaluation of swallowing (days 3, 14, and 28 after admission). MEASUREMENTS AND MAIN RESULTS: Swallowing of saliva, pureed consistencies, and liquids was tested using fiberoptic endoscopic evaluation of swallowing at three different time points. The penetration-aspiration scale by Rosenbek et al and the secretion severity rating scale by Murray et al were used for grading. Functional outcome after rehabilitation was assessed using the functional independence measure.: Pathologic swallowing was found in 20 of 22 patients (91%). Hypesthesia of laryngeal structures was found in 17 of 22 patients (77%) during the first fiberoptic endoscopic evaluation of swallowing. Over the 4-week follow-up period, laryngeal hypesthesia resolved in 75% of affected cases. Pureed consistencies were swallowed safely in 18 of 22 cases (82%), whereas liquids and saliva showed high aspiration rates (13 of 17 [78%] and 10 of 22 [45%], respectively). Swallowing function recovered completely in 21 of 22 (95%) within 4 weeks. CONCLUSIONS: Dysphagia is frequent among patients with critical illness polyneuropathy treated in the ICU. Old age, chronic obstructive pulmonary disease, the mode of mechanical ventilation, the prevalence of tracheal tubes, and behavioral "learned nonuse" may all be contributing factors for the development of dysphagia in critical illness polyneuropathy. Complete recovery occurs in a high percentage of affected individuals within 4 weeks.

Diagnosis and decision making for patients with disorders of consciousness: a survey among family members.

OBJECTIVES: To examine the perceptions of family members of patients with disorders of consciousness (DOC) in regard to the patients' level of consciousness, communicative status, and prognosis as compared with the objective medical categories, and to elicit the family members' self-reported practice of treatment decision-making. DESIGN: Cross-sectional semiquantitative survey. SETTING: Five specialized neurologic rehabilitation facilities. PARTICIPANTS: Consecutive sample of primary family members (N=44) of patients with DOC as determined by the Coma Recovery Scale-Revised, surveyed 6 months after the patient's brain injury. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Perception of level of consciousness as compared with the medical diagnosis; assessment of communicative status and prognosis; and practice of treatment decision-making. RESULTS: The study included 44 family members of patients, most of whom had sustained global cerebral ischemia. Six months after brain injury, 36% were in a vegetative state (VS), 20% were in a minimally conscious state (MCS), and 39% had emerged from an MCS. In 76% of cases, the relatives assumed the same level of consciousness that diagnostic tests showed. In the other cases, consciousness was mostly underestimated. While relatives of patients in a VS, and to a lesser extent of those in an MCS, were more skeptical about the patients' chances to advance to an independent life, all had high hopes that the patients would regain the ability to communicate. Yet, 59% of family members had thought about limiting life-sustaining treatment. Most of them base treatment decisions on the patient's well-being; very few relied on previously expressed patient wishes. CONCLUSIONS: According to our sample, family members of patients with DOC largely assess the level of consciousness correctly and express high hopes to reestablish communication with the patient.

Outcome of Intensive Care Unit-Dependent, Tracheotomized Patients with Cerebrovascular Diseases.

BACKGROUND: Outcome studies in intensive care unit -dependent, tracheotomized, and mechanical ventilated patients with cerebrovascular disease (CVD) are scarce. METHODS: In a retrospective approach, we analyzed the outcome of 143 patients with ischemic stroke (IS), primary intracerebral hemorrhage (PICH), and subarachnoid hemorrhage (SAH). To measure the potential benefit of in-patient rehabilitation, we used the Functional Independence Measure (FIM). In addition, weaning and rehabilitation duration, duration of mechanical ventilation (MV) in the acute care hospital (preweaning), and mortality rates were assessed. RESULTS: Approximately 50% of all patients were transferred home. These patients were fully independent or under nursing support. We found no differences regarding weaning and rehabilitation durations, or FIM scores in between each entity. Log-regression analyses showed that every day on MV generates a 3.2% reduction of the possibility to achieve a beneficial outcome (FIM ≥ 50 points [only moderate assistance necessary]), whereas every day in-patient rehabilitation without MV increases the chance for favorable outcome by 1.9%. Mortality rates were 5% for IS and 10% for PICH and SAH, respectively. CONCLUSIONS: This study shows that even severely affected, tracheotomized patients with CVD benefit from early in-patient rehabilitation, irrespective of the etiology of vascular brain injury. Mortality rates of early rehabilitation in CVD are low. Until no validated outcome predictors are available, all efforts should be undertaken to enable in-patient rehabilitation, even in severe cases of CVD to improve outcome and to prevent accommodation in long-time-care facilities.

The effects of 1 Hz rTMS preconditioned by tDCS on gait kinematics in Parkinson's disease.

Hypokinetic gait is a common and very disabling symptom of Parkinson's disease (PD). Repetitive transcranial magnetic stimulation (rTMS) over the motor cortex has been used with variable effectiveness to treat hypokinesia in PD. Preconditioning rTMS by transcranial direct current stimulation (tDCS) may enhance its effectiveness to treat hypokinetic gait in PD. Three-dimensional kinematic gait analysis was performed (1) prior to, (2) immediately after and (3) 30 min after low-frequency rTMS (1 Hz, 900 pulses, 80% of resting motor threshold) over M1 contralateral to the more affected body side preconditioned by (1) cathodal, (2) anodal or (3) sham tDCS (amperage: 1 mA, duration: 10 min) in ten subjects with PD (7 females, mean age 63 ± 9 years) and ten healthy subjects (four females, mean age 50 ± 11 years). The effects of tDCS-preconditioned rTMS on gait kinematics were assessed by the following parameters: number of steps, step length, stride length, double support time, cadence, swing and stance phases. Our data suggest a bilateral improvement of hypokinetic gait in PD after 1 Hz rTMS over M1 of the more affected body side preceded by anodal tDCS. In contrast, 1 Hz rTMS alone (preceded by sham tDCS) and 1 Hz rTMS preceded by cathodal tDCS were ineffective to improve gait kinematics in PD. In healthy subjects, gait kinematics was unaffected by either intervention. Preconditioning motor cortex rTMS by tDCS is a promising approach to treat hypokinetic gait in PD.

Consensus paper: roles of the cerebellum in motor control--the diversity of ideas on cerebellar involvement in movement.

Considerable progress has been made in developing models of cerebellar function in sensorimotor control, as well as in identifying key problems that are the focus of current investigation. In this consensus paper, we discuss the literature on the role of the cerebellar circuitry in motor control, bringing together a range of different viewpoints. The following topics are covered: oculomotor control, classical conditioning (evidence in animals and in humans), cerebellar control of motor speech, control of grip forces, control of voluntary limb movements, timing, sensorimotor synchronization, control of corticomotor excitability, control of movement-related sensory data acquisition, cerebro-cerebellar interaction in visuokinesthetic perception of hand movement, functional neuroimaging studies, and magnetoencephalographic mapping of cortico-cerebellar dynamics. While the field has yet to reach a consensus on the precise role played by the cerebellum in movement control, the literature has witnessed the emergence of broad proposals that address cerebellar function at multiple levels of analysis. This paper highlights the diversity of current opinion, providing a framework for debate and discussion on the role of this quintessential vertebrate structure.

Case report: A complicated course of Collet-Sicard syndrome after internal carotid artery dissection and lenticulo-striatal artery infarction.

A 40-year-old Caucasian man presented with sudden onset of left-sided hemiparesis associated with dysphonia, dysphagia, and right-sided weakness on shoulder elevation and head rotation. The clinical examination revealed deviation of the tongue to the right, absence of right-sided gag reflex, right-sided palatal and vocal cord paresis, and weakness of the right trapezius and sternocleidomastoid muscles; all were in addition to left-sided brachiocephalic-accentuated hemiparesis. The diagnostic examination revealed dissection of the right carotid artery with occlusion of the middle cerebral artery and infarction in the lenticular-striatal artery territory. Mechanical thrombectomy with stent angioplasty of the right internal carotid artery was performed. The paresis of the left side of the body completely regressed within a week after symptom onset, but the dysphonia, weakness of the right trapezius and sternocleidomastoid muscles, and especially dysphagia persisted and regressed slowly but gradually. The patient required percutaneous gastric tube feeding for the next 12 weeks, possibly because of involvement of subcortical white matter tracts. The constellation of symptoms and clinical findings were consistent with Collet-Sicard syndrome, an extremely rare disorder caused by direct compression of the caudal cranial nerves at the base of the skull.

The thumb rolling test: a novel variant of the forearm rolling test.

BACKGROUND: Neurologists use a variety of tests to detect subtle upper motor neuron lesion causing a mild motor impairment of the upper limb. The forearm and index finger rolling tests are some of these. Their sensitivity varies, but in general these tests appear to be more likely to be abnormal in mild motor impairment of the arm and hand due to a cortico-spinal tract lesion than tests of power, muscle tone or reflexes. Thumb rolling involves more distal limb segments than forearm rolling and distal limb segments are typically more affected than proximal limb segments after cerebral lesions to the cortico-spinal tract. METHODS: Thumb rolling was tested, in comparison to pronator drift, forearm rolling and index finger rolling, for its sensitivity to detect a cerebral lesion of the cortico-spinal tract in 17 consecutive patients with mild pure motor stroke affecting only one arm and hand. RESULTS: Thumb rolling is more sensitive (88%) than pronator drift (47%), forearm rolling (65%) and index finger rolling (65%) to detect a cerebral lesion of the cortico-spinal tract in mild pure motor stroke of the upper limb. CONCLUSION: The thumb rolling test may be a valuable adjunct clinical test to detect a subtle lesion of the cortico-spinal tract causing mild pure motor stroke of the arm and hand when the remainder of routine neurological examination is unremarkable.

Modulating cortical connectivity in stroke patients by rTMS assessed with fMRI and dynamic causal modeling.

Data derived from transcranial magnetic stimulation (TMS) studies suggest that transcallosal inhibition mechanisms between the primary motor cortex of both hemispheres may contribute to the reduced motor performance of stroke patients. We here investigated the potential of modulating pathological interactions between cortical motor areas by means of repetitive TMS using functional magnetic resonance imaging (fMRI) and dynamic causal modeling (DCM). Eleven subacute stroke patients were scanned 1-3 months after symptom onset while performing whole hand fist closure movements. After a baseline scan, patients were stimulated with inhibitory 1-Hz rTMS applied over two different locations: (i) vertex (control stimulation) and (ii) primary motor cortex (M1) of the unaffected (contralesional) hemisphere. Changes in the endogenous and task-dependent effective connectivity were assessed by DCM of a bilateral network comprising M1, lateral premotor cortex, and the supplementary motor area (SMA). The results showed that rTMS applied over contralesional M1 significantly improved the motor performance of the paretic hand. The connectivity analysis revealed that the behavioral improvements were significantly correlated with a reduction of the negative influences originating from contralesional M1 during paretic hand movements. Concurrently, endogenous coupling between ipsilesional SMA and M1 was significantly enhanced only after rTMS applied over contralesional M1. Therefore, rTMS applied over contralesional M1 may be used to transiently remodel the disturbed functional network architecture of the motor system. The connectivity analyses suggest that both a reduction of pathological transcallosal influences (originating from contralesional M1) and a restitution of ipsilesional effective connectivity between SMA and M1 underlie improved motor performance.

Differential effects of high-frequency repetitive transcranial magnetic stimulation over ipsilesional primary motor cortex in cortical and subcortical middle cerebral artery stroke.

OBJECTIVE: Facilitation of cortical excitability of the ipsilesional primary motor cortex (M1) may improve dexterity of the affected hand after stroke. The effects of 10 Hz repetitive transcranial magnetic stimulation (rTMS) over ipsilesional M1 on movement kinematics and neural activity were examined in patients with subcortical or cortical stroke. METHODS: Twenty-nine patients with impaired dexterity after stroke (16 subcortical middle cerebral artery [MCA] strokes, 13 MCA strokes involving subcortical tissue and primary or secondary cortical sensorimotor areas) received 1 session of 10 Hz rTMS (5-second stimulation, 25-second break, 1,000 pulses, 80% of the resting motor threshold) applied over: 1) ipsilesional M1 and 2) vertex (control stimulation). For behavioral testing, 29 patients performed index finger and hand tapping movements with the affected and unaffected hand prior to and following each rTMS application. For functional magnetic resonance imaging, 18 patients performed index finger tapping movements with the affected and unaffected hand before and after each rTMS application. RESULTS: Ten-Hz rTMS over ipsilesional M1, but not over vertex, improved movement kinematics in 14 of 16 patients with subcortical stroke, but not in patients with additional cortical stroke. Ten-Hz rTMS slightly deteriorated dexterity of the affected hand in 7 of 13 cortical stroke patients. At a neural level, rTMS over ipsilesional M1 reduced neural activity of the contralesional M1 in 11 patients with subcortical stroke, but caused a widespread bilateral recruitment of primary and secondary motor areas in 7 patients with cortical stroke. Activity in ipsilesional M1 at baseline correlated with improvement of index finger tapping frequency induced by rTMS. INTERPRETATION: The beneficial effects of 10 Hz rTMS over ipsilesional M1 on motor function of the affected hand depend on the extension of MCA stroke. Neural activity in ipsilesional M1 may serve as a surrogate marker for the effectiveness of facilitatory rTMS.

Mechanisms and applications of theta-burst rTMS on the human motor cortex.

Theta-burst Stimulation (TBS) is a novel form of repetitive transcranial magnetic stimulation (rTMS). Applied over the primary motor cortex it has been successfully used to induce changes in cortical excitability. The advantage of this stimulation paradigm is that it is able to induce strong and long lasting effects using a lower stimulation intensity and a shorter time of stimulation compared to conventional rTMS protocols. Since its first description, TBS has been used in both basic and clinical research in the last years and more recently it has been expanded to other domains than the motor system. Its capacity to induce synaptic plasticity could lead to therapeutic implications for neuropsychiatric disorders. The neurobiological mechanisms of TBS are not fully understood at present; they may involve long-term potentiation (LTP)- and depression (LTD)-like processes, as well as inhibitory mechanisms modulated by GABAergic activity. This article highlights current hypotheses regarding the mechanisms of action of TBS and some central factors which may influence cortical responses to TBS. Furthermore, previous and ongoing research performed in the field of TBS on the motor cortex is summarized.

Alien limb phenomenon following posterior cerebral artery stroke: a distinct clinical entity.

Alien limb syndrome following stroke within the territory of the posterior cerebral artery is exceedingly rare. A right-handed female experienced left homonymous hemianopia, visuospatial neglect, and proprioceptive loss of her left hemi-body. She experienced unintended, involuntary movements of her left arm and hand, which interfered with and disturbed motor actions of daily life performed with her right upper limb. There was no denial of ownership, but she interpreted movements of her left upper limb to be annoying, out of her will and unwanted. The alien limb phenomenon improved in parallel with improvement of proprioceptive loss over a 12-week of in-patient rehabilitation. A recently proposed theoretical concept of the alien limb phenomenon after posterior artery stroke is discussed.

Psychogenic movement disorders: aetiology, phenomenology, neuroanatomical correlates and therapeutic approaches.

Paralysis and movement disorders unexplained by identifiable neurological disease are common clinical presentations in neurological outpatient clinics. Despite their frequency and potential importance from a neuroscientific viewpoint these disorders have received surprisingly little attention in clinically oriented neuroscientific research. In this review we summarize the available literature that specifically relates to the functional neuroanatomy of psychogenic movement disorders. We discuss the aetiology, clinical phenomenology, the current concepts of the dynamic neuroanatomical networks underlying psychogenic neurological syndromes as elucidated by neuroimaging and their potential implications for novel therapeutic approaches.

Cortical connectivity after subcortical stroke assessed with functional magnetic resonance imaging.

OBJECTIVE: This study aimed at identifying the impact of subcortical stroke on the interaction of cortical motor areas within and across hemispheres during the generation of voluntary hand movements. METHODS: Twelve subacute stroke patients with a subcortical ischemic lesion and 12 age-matched control subjects were scanned using 3-Tesla functional magnetic resonance imaging. Subjects performed visually paced hand movements with their left, right, or both hands. Changes of effective connectivity among a bilateral network of core motor regions comprising M1, lateral premotor cortex, and the supplementary motor area (SMA) were assessed using dynamic causal modeling. RESULTS: The data showed significant disturbances in the effective connectivity of motor areas in the patients group: Independently from hand movements, the intrinsic neural coupling between ipsilesional SMA and M1, and the interhemispheric coupling of both SMAs was significantly reduced. Furthermore, movements of the stroke-affected hand showed additional inhibitory influences from contralesional to ipsilesional M1 that correlated with the degree of motor impairment. For bimanual movements, interhemispheric communication between ipsilesional SMA and contralesional M1 was significantly reduced, which also correlated with impaired bimanual performance. INTERPRETATION: The motor deficit of patients with a single subcortical lesion is associated with pathological interhemispheric interactions among key motor areas. The data suggest that a dysfunction between ipsilesional and contralesional M1, and between ipsilesional SMA and contralesional M1 underlies hand motor disability after stroke. Assessing effective connectivity by means of functional magnetic resonance imaging and dynamic causal modeling might be used in the future for the evaluation of interventions promoting recovery of function.

Arbitrary visuomotor mapping during object manipulation in Parkinson's disease.

The objective of this study is to investigate whether subjects with Parkinson's disease are able to use arbitrary color cues linked to the mass of an object to be lifted allowing for the predictive selection of appropriate grip forces. Fourteen patients with Parkinson's disease used a precision grip to lift two objects of different masses (400 and 600 g) in random order. In a "no cue" condition, a noninformative neutral visual stimulus was presented before each lift, thereby not allowing any judgement about which mass to be lifted. In a "cue" condition an arbitrary color cue provided advance information about which of the two masses patients would have to lift in the subsequent trial. Patients performed the conditions with either hand and by both on and off drugs. In the "no cue" trials patients scaled the predictive grip force output according to the perceived mass of the preceding lift. In the "cue" experiment patients scaled grip force in a predictive manner to mass based on the provided color cues. The ability of arbitrary visuomotor mapping was evident at either hand and not influenced by medication on/off. The precision of arbitrary visuomotor mapping correlated negatively with age, but not with disease duration, severity of motor disability on and off drug, severity of cognitive impairment on and off drug, or the amount of levodopa equivalent daily dosage of dopaminergic drugs. These data imply that Parkinson's disease does not preclude the ability of visuomotor mapping in the grip-lift task.

Interhemispheric transfer of predictive force control during grasping in cerebellar disorders.

When an object is repeatedly grasped and lifted, the balance between grip force (normal to the object's surface) and lift force (tangential to the object's surface) is programmed according to the mechanical object features within a few lifts. Information related to the mechanical object properties is easily transferred in between both hands, and the cerebellum may play an essential role for the integration and generalization of this information. Recently, we have shown that the transfer of weight-related information in between both hands is impaired in cerebellar degeneration (Nowak et al., Neuropsychologia, 43:20-27, 2005). Here, we investigated the role of the cerebellum for the inter-manual transfer of friction-related information. Healthy subjects and patients with either focal or generalized cerebellar disorders first repeatedly lifted an object with one hand followed by a series of lifts of the same object with the opposite hand. The experiments were performed with the object's grip surfaces covered with either silk or sandpaper. Patients and healthy subjects scaled grip force differentially to surface friction within a few lifts. However, the ability to transfer friction-related information from one hand to the other was disturbed in cerebellar patients. We interpret these data within the recent concept that the cerebellum is essential for the rapid integration and generalization of mechanical object features in between both hemispheres when handling objects in the environment.

Interhemispheric competition after stroke: brain stimulation to enhance recovery of function of the affected hand.

BACKGROUND AND PURPOSE: Within the concept of interhemispheric competition, technical modulation of the excitability of motor areas in the contralesional and ipsilesional hemisphere has been applied in an attempt to enhance recovery of hand function following stroke. This review critically summarizes the data supporting the use of novel electrophysiological concepts in the rehabilitation of hand function after stroke. SUMMARY OF REVIEW: Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are powerful tools to inhibit or facilitate cortical excitability. Modulation of cortical excitability may instantaneously induce plastic changes within the cortical network of sensorimotor areas, thereby improving motor function of the affected hand after stroke. No significant adverse effects have been noted when applying brain stimulation in stroke patients. To date, however, the clinical effects are small to moderate and short lived. Future work should elucidate whether repetitive administration of rTMS or tDCS over several days and the combination of these techniques with behavioral training (ie, physiotherapy) could result in an enhanced effectiveness. CONCLUSION: Brain stimulation is a safe and promising tool to induce plastic changes in the cortical sensorimotor network to improve motor behavior after stroke. However, several methodological issues remain to be answered to further improve the effectiveness of these new approaches.

Continuous theta-burst stimulation over the dorsal premotor cortex interferes with associative learning during object lifting.

When lifting objects of different mass, humans scale grip force according to the expected mass. In this context, humans are able to associate a sensory cue, such as a colour, to a particular mass of an object and link this association to the grip forces necessary for lifting. Here, we study the role of the dorsal premotor cortex (PMd) in setting-up an association between a colour cue and a particular mass to be lifted. Healthy right-handed subjects used a precision grip between the index finger and thumb to lift two different masses. Colour cues provided information about which of the two masses subjects would have to lift. Subjects first performed a series of lifts with the right hand to establish a stable association between a colour cue and a mass, followed by 20sec of continuous high frequency repetitive trancranial magnetic stimulation using a recently developed protocol (continuous theta-burst stimulation, cTBS) over (i) the left primary motor cortex, (ii) the left PMd and (iii) the left occipital cortex to be commenced by another series of lifts with either the right or left hand. cTBS over the PMd, but not over the primary motor cortex or O1, disrupted the predictive scaling of isometric finger forces based on colour cues, irrespective of whether the right or left hand performed the lifts after the stimulation. Our data highlight the role of the PMd to generalize and maintain associative memory processes relevant for predictive control of grip forces during object manipulation.