Transcranial direct current stimulation (tDCS) of left parietal cortex facilitates gesture processing in healthy subjects.

Gesture processing deficits constitute a key symptom of apraxia, a disorder of motor cognition frequently observed after left-hemispheric stroke. The clinical relevance of apraxia stands in stark contrast to the paucity of therapeutic options available. Transcranial direct current stimulation (tDCS) is a promising tool for modulating disturbed network function after stroke. Here, we investigate the effect of parietal tDCS on gesture processing in healthy human subjects. Neuropsychological and imaging studies suggest that the imitation and matching of hand gestures involve the left inferior parietal lobe (IPL). Using neuronavigation based on cytoarchitectonically defined anatomical probability maps, tDCS was applied over left IPL-areas PF, PFm, or PG in healthy participants (n = 26). Before and after tDCS, subjects performed a gesture matching task and a person discrimination task for control. Changes in error rates and reaction times were analyzed for the effects of anodal and cathodal tDCS (compared with sham tDCS). Matching of hand gestures was specifically facilitated by anodal tDCS applied over the cytoarchitectonically defined IPL-area PFm, whereas tDCS over IPL-areas PF and PG did not elucidate significant effects. Taking into account tDCS electrode size and the central position of area PFm within IPL, it can be assumed that the observed effect is rather the result of a combined stimulation of the supramarginal and angular gyrus than an isolated PFm stimulation. Our data confirm the pivotal role of the left IPL in gesture processing. Furthermore, anatomically guided tDCS of the left IPL may constitute a promising approach to neurorehabilitation of apraxic patients with gesture processing deficits.

Modulation of top-down control of visual attention by cathodal tDCS over right IPS.

The right intraparietal sulcus (rIPS) is a key region for the endogenous control of selective visual attention in the human brain. Previous studies suggest that the rIPS is especially involved in top-down control and spatial distribution of attention across both visual hemifields. We further explored these attentional functions using transcranial direct current stimulation (tDCS) of the rIPS to modulate behavioral performance in a partial report task. Performance was analyzed according to the theory of visual attention (TVA) (Bundesen, 1990), which provides a computational framework to investigate different parameters of visuo-attentional processing such as top-down control, attentional weighting, capacity of visual short term memory, and processing speed. We investigated the effects of different tDCS current strengths (1 mA and 2 mA) in two experiments: 1 mA tDCS (anodal, cathodal, sham) did not affect any of the TVA parameters, but cathodal 2 mA stimulation significantly enhanced top-down control as evidenced by a reduction of the α parameter of TVA, regardless of hemifield. This differential impact on the top-down control component of attentional processing suggests that the horizontal rIPS is mainly involved in attentional selection as none of the spatial or resource variables of TVA were altered. Furthermore, the data add evidence to previous work highlighting (1) the importance of using appropriate current strength in stimulation protocols, and (2) that the often reported inhibitory effect of cathodal stimulation in e.g., motor tasks might not extend to cognitive paradigms.

Functional localization in the human brain: Gradient-Echo, Spin-Echo, and arterial spin-labeling fMRI compared with neuronavigated TMS.

A spatial mismatch of up to 14 mm between optimal transcranial magnetic stimulation (TMS) site and functional magnetic resonance imaging (fMRI) signal has consistently been reported for the primary motor cortex. The underlying cause might be the effect of magnetic susceptibility around large draining veins in Gradient-Echo blood oxygenation level-dependent (GRE-BOLD) fMRI. We tested whether alternative fMRI sequences such as Spin-Echo (SE-BOLD) or Arterial Spin-Labeling (ASL) assessing cerebral blood flow (ASL-CBF) may localize neural activity closer to optimal TMS positions and primary motor cortex than GRE-BOLD. GRE-BOLD, SE-BOLD, and ASL-CBF signal changes during right thumb abductions were obtained from 15 healthy subjects at 3 Tesla. In 12 subjects, tissue at fMRI maxima was stimulated with neuronavigated TMS to compare motor-evoked potentials (MEPs). Euclidean distances between the fMRI center-of-gravity (CoG) and the TMS motor mapping CoG were calculated. Highest SE-BOLD and ASL-CBF signal changes were located in the anterior wall of the central sulcus [Brodmann Area 4 (BA4)], whereas highest GRE-BOLD signal changes were significantly closer to the gyral surface. TMS at GRE-BOLD maxima resulted in higher MEPs which might be attributed to significantly higher electric field strengths. TMS-CoGs were significantly anterior to fMRI-CoGs but distances were not statistically different across sequences. Our findings imply that spatial differences between fMRI and TMS are unlikely to be caused by spatial unspecificity of GRE-BOLD fMRI but might be attributed to other factors, e.g., interactions between TMS-induced electric field and neural tissue. Differences between techniques should be kept in mind when using fMRI coordinates as TMS (intervention) targets.

Diagnosis and treatment of neurogenic dysphagia - S1 guideline of the German Society of Neurology.

INTRODUCTION: Neurogenic dysphagia defines swallowing disorders caused by diseases of the central and peripheral nervous system, neuromuscular transmission, or muscles. Neurogenic dysphagia is one of the most common and at the same time most dangerous symptoms of many neurological diseases. Its most important sequelae include aspiration pneumonia, malnutrition and dehydration, and affected patients more often require long-term care and are exposed to an increased mortality. Based on a systematic pubmed research of related original papers, review articles, international guidelines and surveys about the diagnostics and treatment of neurogenic dysphagia, a consensus process was initiated, which included dysphagia experts from 27 medical societies. RECOMMENDATIONS: This guideline consists of 53 recommendations covering in its first part the whole diagnostic spectrum from the dysphagia specific medical history, initial dysphagia screening and clinical assessment, to more refined instrumental procedures, such as flexible endoscopic evaluation of swallowing, the videofluoroscopic swallowing study and high-resolution manometry. In addition, specific clinical scenarios are captured, among others the management of patients with nasogastric and tracheotomy tubes. The second part of this guideline is dedicated to the treatment of neurogenic dysphagia. Apart from dietary interventions and behavioral swallowing treatment, interventions to improve oral hygiene, pharmacological treatment options, different modalities of neurostimulation as well as minimally invasive and surgical therapies are dealt with. CONCLUSIONS: The diagnosis and treatment of neurogenic dysphagia is challenging and requires a joined effort of different medical professions. While the evidence supporting the implementation of dysphagia screening is rather convincing, further trials are needed to improve the quality of evidence for more refined methods of dysphagia diagnostics and, in particular, the different treatment options of neurogenic dysphagia. The present article is an abridged and translated version of the guideline recently published online ( https://www.awmf.org/uploads/tx_szleitlinien/030-111l_Neurogene-Dysphagie_2020-05.pdf ).

The dorsal premotor cortex orchestrates concurrent speech and fingertapping movements.

Human speech and hand use both involve highly specialized complex movement patterns. Whereas previous studies in detail characterized the cortical motor systems mediating speech and finger movements, the network that provides coordination of concurrent speech and hand movements so far is unknown. Using functional magnetic resonance imaging (fMRI), the present study investigated differential cortical networks devoted to speech or fingertapping, and regions mediating integration of these complex movement patterns involving different effectors. The conjunction contrasts revealing regions activated both during sole fingertapping and sole repetitive articulation or reading aloud showed contralateral regions at the border of ventral and dorsal motor cortex. In contrast, the analyses revealing regions showing a higher level of fMRI activation for concurrent movements of both effectors compared with sole hand movements or repetitive articulation or reading aloud showed distinct premotor activations, which were situated dorsal and caudal to the areas activated across speech and fingertapping tasks. These results indicate that the premotor cortex (PMC) subserves coordination of concurrent speech with hand movements. This integrative motor region is not identical with the area that shows overlapping activations for speech and fingertapping. Thus, concurrent performance of these complex movement patterns involving different effectors requires, in addition to somatotopic motor cortex activation, orchestration subserved by a distinct PMC area.

Transdermal dopaminergic stimulation with rotigotine in Parkinsonian akinetic crisis.

Akinetic crisis (AC) is a much-feared complication of Parkinson's disease (PD) which may appear upon abrupt cessation or malabsorption of dopaminergic medication due to gastrointestinal tract disorders or acute surgery. Intravenous infusion of amantadine sulphate or subcutaneous administration of apomorphine are established treatment strategies for AC. We speculate whether the use of a non-invasive transdermal application form (patch) of a dopaminergic drug (rotigotine) may represent a useful alternative treatment option. We describe the successful treatment of severe AC using rotigotine in a PD patient with gastro-oesophageal ulcers which precluded administration of any oral medication. This case demonstrates that a rotigotine patch might be effective in the treatment of AC. We suggest that rotigotine may represent a useful treatment option due to its favourable receptor profile and unique application form. In particular, it may be helpful in situations that might provoke AC, such as acute surgery. However, experience of the use of the rotigotine patch in this clinical setting is rather sparse and the patch is currently not approved for this indication.

Action verbs and the primary motor cortex: a comparative TMS study of silent reading, frequency judgments, and motor imagery.

Single pulse transcranial magnetic stimulation (TMS) was applied to the hand area of the left primary motor cortex or, as a control, to the vertex (STIMULATION: TMS(M1) vs. TMS(vertex)) while right-handed volunteers silently read verbs related to hand actions. We examined three different tasks and time points for stimulation within the same experiment: subjects indicated with their left foot when they (i) had finished reading, (ii) had judged whether the corresponding movement involved a hand rotation after simulating the hand movement, and (iii) had judged whether they would frequently encounter the action verb in a newspaper (TASK: silent reading, motor imagery, and frequency judgment). Response times were compared between TMS(M1) and TMS(vertex), both applied at different time points after stimulus onset (DELAY: 150, 300, 450, 600, and 750 ms). TMS(M1) differentially modulated task performance: there was a significant facilitatory effect of TMS(M1) for the imagery task only (about 88 ms), with subjects responding about 10% faster (compared to TMS(vertex)). In contrast, response times for silent reading and frequency judgments were unaffected by TMS(M1). No differential effect of the time point of TMS(M1) was observed. The differential effect of TMS(M1) when subjects performed a motor imagery task (relative to performing silent reading or frequency judgments with the same set of verbs) suggests that the primary motor cortex is critically involved in processing action verbs only when subjects are simulating the corresponding movement. This task-dependent effect of hand motor cortex TMS on the processing of hand-related action verbs is discussed with respect to the notion of embodied cognition and the associationist theory.

Enhancing language performance with non-invasive brain stimulation--a transcranial direct current stimulation study in healthy humans.

In humans, transcranial direct current stimulation (tDCS) can be used to induce, depending on polarity, increases or decreases of cortical excitability by polarization of the underlying brain tissue. Cognitive enhancement as a result of tDCS has been reported. The purpose of this study was to test whether weak tDCS (current density, 57 microA/cm(2)) can be used to modify language processing. Fifteen healthy subjects performed a visual picture naming task before, during and after tDCS applied over the posterior perisylvian region (PPR), i.e. an area which includes Wernicke's area [BA 22]. Four different sessions were carried out: (1) anodal and (2) cathodal stimulation of left PPR and, for control, (3) anodal stimulation of the homologous region of the right hemisphere and (4) sham stimulation. We found that subjects responded significantly faster following anodal tDCS to the left PPR (p<0.01). No decreases in performance were detected. Our finding of a transient improvement in a language task following the application of tDCS together with previous studies which investigated the modulation of picture naming latency by transcranial magnetic stimulation (TMS) and repetitive TMS (rTMS) suggest that tDCS applied to the left PPR (including Wernicke's area [BA 22]) can be used to enhance language processing in healthy subjects. Whether this safe, low cost, and easy to use brain stimulation technique can be used to ameliorate deficits of picture naming in aphasic patients needs further investigations.

On the role of the ventral premotor cortex and anterior intraparietal area for predictive and reactive scaling of grip force.

When lifting objects of different mass but identical visual appearance, we apply grip forces that match the expected mass of the object. Here we study the role of the primary motor cortex (M1), the ventral premotor cortex (PMv) and the anterior intraparietal area (AIP) for predictive and reactive scaling of grip forces. Participants performed a precision grip between the index finger and thumb of the right hand to lift two different masses of identical visual appearance in random order. Neuronavigated single pulse transcranial magnetic stimulation (TMS) over (i) left M1, (ii) left PMv, (iii) left AIP and (iv) the vertex (for control) was applied at two time points of the grasping movement after an unexpected change in mass had occurred: (a) at the time of movement onset and (b) at the time of peak grasp aperture. TMS over the PMv, but not over the vertex, M1 or the AIP, interfered with the predictive scaling of grip forces according to the most recent lift when applied at the time of peak grasp aperture. In contrast, TMS over AIP, but not over the vertex, M1 or PMv, disrupted the reactive adjustment of grip force to the novel mass of the object at hand. The findings highlight the differential involvement of PMv in the predictive scaling of grip force and of AIP in the reactive online adjustment of grip force during object manipulation.

The role of the anterior intraparietal sulcus in crossmodal processing of object features in humans: an rTMS study.

Investigations in macaques and humans have shown that the anterior intraparietal sulcus (IPS) has an important function in the integration of information from tactile and visual object manipulation. The goal of this study was to investigate the special functional role of the anterior IPS in visuo-tactile matching in humans. We used the "virtual-lesion" technique of repetitive transcranial magnetic stimulation (rTMS) to test the functional relevance of anterior IPS for visuo-tactile crossmodal matching. Two crossmodal (visual encoding and tactile recognition and vice versa) and two unimodal delayed matching-to-sample tests with geometrical patterns were performed by 12 healthy subjects. We determined error rates before and after focal low-frequency rTMS applied over the left anterior IPS, right anterior IPS and vertex. During the manipulation of objects with the right hand, rTMS over the left anterior IPS induced a significant deterioration for visual encoding and tactile recognition, but not for tactile encoding and visual recognition. For the visual and tactile unimodal conditions, no significant alterations in task performance were found. rTMS application over right IPS when manipulating objects with the left hand did not affect crossmodal task performance. In conclusion, we have demonstrated an essential functional role of the left anterior IPS for visuo-tactile matching when manipulating objects with the right hand. However, we found no clear evidence for left IPS involvement in tactile encoding and visual recognition. The differential effect of rTMS on tactile and visual encoding and recognition are not consistently explained by previous concepts of visuo-tactile integration.

Excitability of human motor and visual cortex before, during, and after hyperventilation.

In humans, hyperventilation (HV) has various effects on systemic physiology and, in particular, on neuronal excitability and synaptic transmission. However, it is far from clear how the effects of HV are mediated at the cortical level. In this study we investigated the effects of HV-induced hypocapnia on primary motor (M1) and visual cortex (V1) excitability. We used 1) motor threshold (MT) and phosphene threshold (PT) and 2) stimulus-response (S-R) curves (i.e., recruitment curves) as measures of excitability. In the motor cortex, we additionally investigated 3) the intrinsic inhibitory and facilitatory neuronal circuits using a short-interval paired-pulse paradigm. Measurements were performed before, during, and after 10 min of HV (resulting in a minimum end-tidal Pco(2) of 15 Torr). HV significantly increased motor-evoked potential (MEP) amplitudes, particularly at lower transcranial magnetic stimulation (TMS) intensities. Paired-pulse stimulation indicated that HV decreases intracortical inhibition (ICI) without changing intracortical facilitation. The results suggestthat low Pco(2) levels modulate, in particular, the intrinsic neuronal circuits of ICI, which are largely mediated by neurons containing gamma-aminobutyric acid. Modulation of MT probably resulted from alterations of Na(+) channel conductances. A significant decrease of PT, together with higher intensity of phosphenes at low stimulus intensities, furthermore suggested that HV acts on the excitability of M1 and V1 in a comparable fashion. This finding implies that HV also affects other brain structures besides the corticospinal motor system. The further exploration of these physiological mechanisms may contribute to the understanding of the various HV-related clinical phenomenona.

On the functional role of human parietal cortex in number processing: How gender mediates the impact of a 'virtual lesion' induced by rTMS.

Areas around the horizontal part of the intraparietal sulcus (hIPS) have repeatedly been reported to participate in processing numerical magnitude. Using transcranial magnetic stimulation (TMS), we investigated the functional role of the hIPS by examining two effects from the domain of numerical cognition: in magnitude comparison tasks response latencies are inversely related to the numerical distance between two numbers. This distance effect indexes access to the mental number representation. In magnitude comparison tasks responses are faster when decade and unit comparison would lead to the same decision (e.g. 42_57, 4 < 5 and 2 < 7) than when they would not (e.g. 47_62, 4 < 6 but 7 > 2). This compatibility effect reflects unit-decade integration processes. Differential susceptibility of (fe)male participants to TMS was examined. We applied repetitive TMS (rTMS; 1Hz for 10 min) over the left hIPS in 12 participants (6 female). No stimulation and vertex stimulation served as control conditions. The effect of rTMS was mediated by gender: in male participants, the distance effect decreased after TMS over hIPS. For female participants distance and compatibility effect both increased. This modulation of the compatibility effect was limited in duration to no more than 4 min. The hIPS seems to be functionally involved both in number magnitude processing and in integrating unit-decade magnitude information of two-digit numbers. Relative hemispheric specialization of the hIPS with respect to two-digit magnitude comparison is discussed.

Interhemispheric imbalance during visuospatial attention investigated by unilateral and bilateral TMS over human parietal cortices.

We used single-pulse transcranial magnetic stimulation (TMS) to study visuospatial attention. TMS was applied over one hemisphere, or simultaneously over both the right and left posterior parietal cortex (PPC), at two different interstimulus intervals (ISI) during a visual detection task. Unilateral TMS over the right and left PPC, respectively, impaired detection of contralateral presented visual stimuli at an ISI of 150 ms. By contrast, simultaneous biparietal TMS induced no significant changes in correct stimulus detection. TMS at an ISI of 250 ms evoked no changes for magnetic stimulation over either the right or the left parietal cortex. These results suggest that both PPC play a crucial role at a relatively early stage in the widely distributed brain network of visuospatial attention. The abolition of behavioral deficits during simultaneous biparietal TMS underlines the common hypothesis that an interhemispheric imbalance might underlie the disorders of neglect and extinction seen following unilateral brain damage.

Enhancing picture naming with transcranial magnetic stimulation.

The enhancement of cognitive function in healthy subjects by medication, training or intervention yields increasing political, social and ethical attention. In this paper facilitatory effects of single-pulse TMS and repetitive TMS on a simple picture naming task are presented. A significant shortening of picture naming latencies was observed after single-pulse TMS over Wernicke's area. The accuracy of the response was not affected by this speed effect. After TMS over the dominant motor cortex or over the non-dominant temporal lobe, however, no facilitation of picture naming was observed. In the rTMS experiments only rTMS of Wernicke's area had an impact on picture naming latencies resulting in a shortening of naming latencies without affecting the accuracy of the response. rTMS over the visual cortex, Broca's area or over the corresponding sites in the non-dominant hemisphere had no effect. Single-pulse TMS is able to facilitate lexical processes due to a general preactivation of language-related neuronal networks when delivered over Wernicke's area. Repetitive transcranial magnetic stimulation over Wernicke's area also leads to a brief facilitation of picture naming possibly by shortening linguistic processing time. Whether TMS or rTMS can be used to aid linguistic therapy in the rehabilitation phase of aphasic patients should be subject of further investigations.

Investigation of the primary visual cortex using short-interval paired-pulse transcranial magnetic stimulation (TMS).

Previous studies using short-interval paired-pulse TMS have provided valuable insights into physiology of human motor cortex. Depending on the interstimulus interval (ISI) between the two pulses intra-cortical facilitation (ICF) or intra-cortical inhibition (ICI) can be observed. Similar patterns of inhibition and facilitation have also been demonstrated in prefrontal and parietal cortices. In order to prove whether principles that govern cortical excitability in the motor system also extend to the visual system and to further characterize possible neural correlates of phosphene generation, we applied short-interval paired-pulse TMS to the occipital cortex. In addition, we examined the effect of different coil orientations on perception of phosphenes induced by paired-pulse TMS. In all of 10 healthy subjects, a general facilitation of phosphene perception could be observed for interstimulus intervals of 2-12 ms (conditioning stimulus (CS) 90% and test stimulus (TS) 100% of subject's phosphene threshold) compared to TS alone. With CS intensity decreasing to 80% or less, the effect diminished. No significant changes occurred when TS intensity was increased to 110%. Phosphene perception was enhanced with an induced current direction from lateral to medial at an ISI of 12 ms. Inhibition was not observed in any condition. Our results indicate that the mechanisms underlying phosphene induction in the visual cortex are different from those underlying intracortical inhibition and facilitation in the motor cortex.

Modulation of attention functions by anodal tDCS on right PPC.

Attention is a complex construct that comprises at least three major subcomponents: alerting, spatial (re-)orienting, and executive functions, all of which have specific neural correlates along frontoparietal networks. Attention deficits are a common consequence of brain damage. Transcranial direct current stimulation (tDCS) has been shown to modulate spatial attention. We investigated whether tDCS of different stimulation targets differentially modulates alerting, spatial (re-)orienting, and executive functions. Twenty-four healthy participants were included in this randomized, double-blinded study, which employed a within-subject design. On four different days, the effects of 1.5 mA anodal tDCS (real and sham) on the left dorsolateral (EEG 10-20 point F3), left parietal (P3) and right parietal cortex (P4) were assessed using a modified attention network test. tDCS of the right parietal cortex enhanced spatial re-orienting, while tDCS of the other cortical targets did not modulate the assessed attention functions. With regard to visual field asymmetries in attentional processing, right parietal tDCS selectively enhanced mean network efficiency for targets presented in the contralateral left visual field. The observed visual field specific tDCS effects on reorienting suggest that systematic investigations into novel approaches for the treatment of patients suffering from spatial neglect patients are warranted.

Motor cortex hand area and speech: implications for the development of language.

Recently a growing body of evidence has suggested that a functional link exists between the hand motor area of the language dominant hemisphere and the regions subserving language processing. We examined the excitability of the hand motor area and the leg motor area during reading aloud and during non-verbal oral movements using transcranial magnetic stimulation (TMS). During reading aloud, but not before or afterwards, excitability was increased in the hand motor area of the dominant hemisphere. This reading effect was found to be independent of the duration of speech. No such effect could be found in the contralateral hemisphere. The excitability of the leg area of the motor cortex remained unchanged during reading aloud. The excitability during non-verbal oral movements was slightly increased in both hemispheres. Our results are consistent with previous findings and may indicate a specific functional connection between the hand motor area and the cortical language network.

Visual cortex excitability increases during visual mental imagery--a TMS study in healthy human subjects.

Previous neuroimaging studies provided evidence that visual mental imagery relies, in part, on the primary visual cortex. We hypothesized that, analogous to the finding that motor imagery increases the excitability of motor cortex, visual imagery should increase visual cortex excitability, as indexed by a decrease in the phosphene threshold (PT). In order to test visual cortex excitability, the primary visual cortex was stimulated with transcranial magnetic stimulation (TMS), so as to elicit phosphenes in the right lower visual quadrant. Subjects performed a visual imagery task and an auditory control task. We applied TMS with increasing intensity to determine the PT for each subject. Independent of the quadrant in which subjects placed their visual images, imagery decreased PT compared to baseline PT; in contrast, the auditory task did not change PT. These findings demonstrate for the first time a short-term, task-dependent modulation of PT. These results constitute evidence that early visual areas participate in visual imagery processing.

Repetitive transcranial magnetic stimulation of the parietal cortex transiently ameliorates phantom limb pain-like syndrome.

OBJECTIVE: Phantom pain is linked to a reorganization of the partially deafferented sensory cortex. In this study we have investigated whether the pain syndrome can be influenced by repetitive transcranial magnetic stimulation (rTMS). METHODS: Two patients with a longstanding unilateral avulsion of the lower cervical roots and chronic pain in the arm were studied. As a control the acute effects of rTMS (15 Hz, 2 s duration) on pain were studied in 4 healthy subjects. Pain intensity was assessed with the Visual Analogue Scale. RESULTS: Stimulation of the contralateral parietal cortex led to a reproducible reduction in pain intensity lasting up to 10 min. Stimulation of other cortical areas produced only minor alterations in the severity of the pain. Both 1 and 10 Hz rTMS trains applied to the contralateral parietal cortex on weekdays for 3 consecutive weeks did, however, not lead to permanent changes in the pain intensity. Experimentally induced pain (cold water immersion of the right hand) in normal subjects was not influenced by rTMS. CONCLUSIONS: These results do not favor the use of rTMS in the treatment of phantom limb pain. The results, however, support the concept that phantom pain is due to a dysfunctional activity in the parietal cortex. The transient rTMS-induced analgesic effect may be due to a temporary interference with the cerebral representation of the deafferented limb.

Motor representation in patients rapidly recovering after stroke: a functional magnetic resonance imaging and transcranial magnetic stimulation study.

OBJECTIVE: Neuroimaging studies have suggested an evolution of the brain activation pattern in the course of motor recovery after stroke. Initially poor motor performance is correlated with an recruitment of the uninjured hemisphere that continuously vanished until a nearly normal (contralateral) activation pattern is achieved and motor performance is good. Here we were interested in the early brain activation pattern in patients who showed a good and rapid recovery after stroke. METHODS: Ten patients with first-ever ischemic stroke affecting motor areas had to perform self-paced simple or more complex movements with the affected or the unaffected hand during functional magnetic resonance imaging (fMRI). The location and number of activated voxels above threshold were determined. To study possible changes in the cortical motor output map the amplitude of the motor evoked potentials (MEP) and the extent of the excitable area were determined using transcranial magnetic stimulation (TMS). RESULTS: The pattern of activation observed with movements of the affected and the unaffected hand was similar. In the simple motor task significant (P<0.05) increases were found in the primary motor cortex ipsilateral to the movement, the supplementary motor area and the cerebellar hemisphere contralateral to the movement during performance with the affected hand compared to movements with the unaffected hand. When comparing simple with more complex movements performed with either the affected or the unaffected hand, a further tendency to increased activation in motor areas was observed. The amplitude of MEPs obtained from the affected hemisphere was smaller and the extent of cortical output maps was decreased compared to the unaffected hemisphere; but none of the patients showed MEPs at the affected hand when the ipsilateral unaffected motor cortex was stimulated. CONCLUSIONS: Despite a rapid and nearly complete motor recovery the brain activation pattern was associated with increased activity in (bilateral) motor areas as revealed with fMRI. TMS revealed impaired motor output properties, but failed to demonstrate ipsilateral motor pathways. Successful recovery in our patients may therefore rely on the increased bilateral activation of existing motor networks spared by the injury.