Neuronavigated Transcranial Magnetic Stimulation Research Articles

The left posterior cerebellum is involved in orienting attention along the mental number line: An online-TMS study

Although converging evidence suggests that the posterior cerebellum is involved in visuospatial functions and in the orienting of attention, a clear topography of cerebellar regions causally involved in the control of spatial attention is still missing. In this study, we aimed to shed light on this issue by using online neuronavigated transcranial magnetic stimulation (TMS) to temporarily interfere with posterior medial (Vermis lobule VII) and left lateral (Crus I/II) cerebellar activity during a task measuring visuospatial (landmark task, Experiment 1 and 2) and representational (number bisection task, Experiment 2) asymmetries in the orienting of attention. At baseline, participants showed attentional biases consistent with the literature, that is a leftward and upward bias with horizontal and vertical lines, respectively, and a leftward bias in number bisection. Critically, TMS over the left cerebellar hemisphere significantly counteracted pseudoneglect in the number bisection task, whilst not affecting attentional biases in the landmark task. In turn, TMS over the posterior vermis did not affect performance in either task. Taken together, our findings suggest that the left posterior cerebellar hemisphere (but not the posterior vermis) is a critical node of an extended brain network subtending the control of spatial attention, at least when attention needs to be allocated to an internal representational space and a certain degree of mental manipulation is required (as in the number bisection task).

A feasibility study for somatomotor cortical mapping in Tourette syndrome using neuronavigated transcranial magnetic stimulation

Tourette syndrome (TS) is a hyperkinetic movement disorder characterised by the occurrence of chronic motor and vocal tics, and is associated with alterations in the balance of excitatory and inhibitory signalling within key brain networks; in particular the cortical-striatal-thalamic-cortical (CSTC) brain circuits that are implicated in movement selection and habit learning. Converging evidence indicates abnormal brain network function in TS may be largely due to the impaired operation of GABA signalling within the striatum and within cortical motor areas, leading to the occurrence of tics. TS has been linked to a heightened sensitivity to somatic stimulation and altered processing of somatosensory information, and there is evidence to indicate that alterations in GABAergic function is likely to contribute to altered somatomotor function. Based upon this evidence, we hypothesised that the specificity of somatomotor representations in primary motor cortex would likely be reduced in individuals with TS. To test this, we used a rapid acquisition method together with neuronavigated transcranial magnetic stimulation (nTMS) to measure the cortical representation of a several different muscles in a group of young adults with TS and a matched group of typically developing individuals.

Anterior and Posterior Left Inferior Frontal Gyrus Contribute to the Implementation of Grammatical Determiners During Language Production

The left inferior frontal gyrus (IFG) is a key region for language comprehension and production. Previous studies point to a preferential involvement of left anterior IFG (aIFG) in lexical and semantic processes, while the posterior IFG (pIFG) has been implicated in supporting syntactic and phonological processes. Here we used focal neuronavigated transcranial magnetic stimulation (TMS) to probe the functional involvement of left IFG in lexical and grammatical processing at the sentence level. We applied 10 Hz TMS effective or sham bursts to left aIFG and pIFG, while healthy volunteers performed an adjective-noun production task contrasting grammatical and lexical determiners. For each trial, we measured the time from the stimulus onset to the moment of articulation (response time) and the time from articulation onset to the end of articulation (duration). Focal TMS of IFG generally delayed response times. The TMS-induced delay in response times was relatively stronger for the grammatical condition compared to the lexical condition, when TMS targeted aIFG. Articulation of the determiner was generally shorter in trials presenting grammatical determiners relative to lexical determiners. The shorter articulation time for grammar determiners was facilitated by effective TMS to pIFG. Together, the effects of TMS on task performance provide novel evidence for a joint involvement of anterior and posterior parts of left IFG in implementing grammatical determiners during language production, suggesting an involvement of aIFG in the initiation and pIFG in the production of grammatically appropriate verbal responses at the sentence level.

Intranetwork and Internetwork Effects of Navigated Transcranial Magnetic Stimulation Using Low- and High-Frequency Pulse Application to the Dorsolateral Prefrontal Cortex: A Combined rTMS-fMRI Approach.

Although transcranial magnetic stimulation (TMS) is routinely applied in neuroscience and clinical settings, not much is known about its effects on brain networks. Therefore, this pilot study was set up using repetitive navigated transcranial magnetic stimulation (rTMS) combined with resting-state functional MRI (rs-fMRI) to explore frequency-dependent stimulation effects on an intranetwork and internetwork level. Six healthy subjects (median age: 23.5 years) underwent two rTMS sessions (1 and 10 Hz), 7 days apart, and prestimulation and poststimulation rs-fMRI. Repetitive navigated transcranial magnetic stimulation was delivered to the left dorsolateral prefrontal cortex, with the exact stimulation target being determined by independent component analysis. Alterations of functional connectivity strength were evaluated using seed-based correlation analyses within and between the salience network, central executive network, and posterior and anterior default mode network. Low-frequency rTMS resulted in significant intranetwork alterations only for the anterior default mode network and primarily within the left hemisphere. In contrast, high-frequency rTMS led to changes within all four networks of interest. Moreover, the posterior and anterior default mode network largely showed opposite effects to rTMS, and the anterior default mode network was rather isolated from the other networks, which was especially true for low-frequency rTMS. Changes in functional connectivity strength because of low-frequency rTMS were even detectable 7 days after stimulation. This is one of the first studies using neuronavigated TMS with independent component analysis-based target selection to explore frequency-dependent stimulation effects in a combined rTMS-fMRI approach. Future studies including higher subject numbers may define the underlying mechanisms for the different responses to low- and high-frequency rTMS.

Enhancement of behavioral and linguistic outcome measures in autism spectrum disorder through neuro-navigated transcranial magnetic stimulation: A pilot study

Enhancement of behavioral and linguistic outcome measures in autism spectrum disorder through neuro-navigated transcranial magnetic stimulation: A pilot study

Transcranial Magnetic Stimulation of the Medial Prefrontal Cortex Decreases Emotional Memory Schemas.

Mood-congruent memory bias is a critical characteristic of depression, but the underlying neural mechanism is largely unknown. Negative memory schemas might enhance encoding and consolidation of negative experiences, thereby contributing to the genesis and perpetuation of depressive pathology. To investigate this relationship, we aimed to perturb medial prefrontal cortex (mPFC) processing, using neuronavigated transcranial magnetic stimulation (TMS) targeting the mPFC. Forty healthy volunteers first underwent a negative mood induction to activate negative schema processing after which they received either active inhibitory (N = 20) or control (N = 20) stimulation to the mPFC. Then, all participants performed the encoding of an emotional false memory task. Recall and recognition performance was tested the following morning. Polysomnographic data were recorded continuously during the night before and after encoding. We observed a significantly lower false recognition of negative critical lures following mPFC inhibition, but no differences in veridical memory. These findings were supported by reaction time data, showing a relative slower response to negative compared with positive critical lures. The current findings support previous causal evidence for a role of the mPFC in schema memory processing and further suggest a role of the mPFC in memory bias.

Neuronavigated TMS of early visual cortex eliminates unconscious processing of chromatic stimuli

Some neurological patients with primary visual cortex (V1) lesions can guide their behavior based on stimuli presented to their blind visual field. One example of this phenomenon is the ability to discriminate colors in the absence of awareness. These so-called patients with blindsight must have a neural pathway that bypasses V1, explaining their ability to unconsciously process stimuli. The pathways that have been most often hypothesized to be the cause of blindsight connect lateral geniculate nucleus (LGN) or superior colliculus (SC) to extrastriate cortex, most likely V5, and parietal areas. To test if similar pathways function in neurologically healthy individuals or if unconscious processing depends on early visual cortex, we disturbed the visibility of a chromatic stimulus with metacontrast masking (Experiment 1) or neuronavigated transcranial magnetic stimulation (TMS) of early visual cortex, exact target being retinotopically mapped V1 (Experiment 2). We measured unconscious processing using the redundant target effect (RTE), which is the speeding up of reaction times in response to dual stimuli compared with one stimulus, when the task is to respond to any number of stimuli. An unconscious chromatic RTE was found when the visibility of the redundant chromatic stimulus was suppressed with a visual mask. When TMS was targeted to the correct retinotopic location of V1, and conscious perception of the redundant chromatic stimulus suppressed, the RTE was eliminated. Whether the elimination of unconscious RTE during TMS was exclusively due to disruption of V1 activity, or whether it was due to the possible interference with processing in V2 or even V3, is discussed. Based on our results and converging evidence from previous studies, we conclude that unconscious processing of chromatic information depends on the early visual cortex, in neurologically healthy participants.

Cognitive Enhancement via Network-Targeted Cortico-cortical Associative Brain Stimulation.

Fluid intelligence (gf) represents a crucial component of human cognition, as it correlates with academic achievement, successful aging, and longevity. However, it has strong resilience against enhancement interventions, making the identification of gf enhancement approaches a key unmet goal of cognitive neuroscience. Here, we applied a spike-timing-dependent plasticity (STDP)-inducing brain stimulation protocol, named cortico-cortical paired associative stimulation (cc-PAS), to modulate gf in 29 healthy young subjects (13 females-mean ±standard deviation, 25.43years ± 3.69), based on dual-coil transcranial magnetic stimulation (TMS). Pairs of neuronavigated TMS pulses (10-ms interval) were delivered over two frontoparietal nodes of the gf network, based on individual functional magnetic resonance imaging data and in accordance with cognitive models of information processing across the prefrontal and parietal lobe. cc-PAS enhanced accuracy at gf tasks, with parieto-frontal and fronto-parietal stimulation significantly increasing logical and relational reasoning, respectively. Results suggest the possibility of using SPTD-inducing TMS protocols to causally validate cognitive models by selectively engaging relevant networks and manipulating inter-regional temporal dynamics supporting specific cognitive functions.

Phonological picture-word interference in language mapping with transcranial magnetic stimulation: an objective approach for functional parcellation of Broca's region.

Functional imaging data suggest different regions for semantic, syntactic, and phonological processing in an anterior-to-posterior direction along the inferior frontal gyrus. Language mapping by use of neuro-navigated transcranial magnetic stimulation (TMS) is frequently applied in clinical research to identify language-related cortical regions. Recently, we proposed a high spatial resolution approach for more detailed language mapping of cortical sub-areas such as Broca's region. Here, we employed a phonological picture-word interference paradigm in healthy subjects to reveal functional specialization in Broca's region for phonological processing. The behavioral phonological priming effect is characterized by accelerated naming responses to target pictures accompanied by phonologically related auditory distractor words. We hypothesized that the inhibitory effects of TMS on language processing would reduce phonological priming only at stimulation sites involved in phonological processing. In active as compared to sham TMS, we found reduced phonological facilitation specifically at sites overlapping with the probabilistic cytoarchitectonic area 44. Our findings complemented functional imaging data by revealing structure-function relationship in Broca's region. The introduction of a reactiontime based interference paradigm into TMS language mapping increases the objectivity of the method and allows to explore functional specificity with high temporal resolution. Findings may help to interpret results in clinical applications.

NeuroMeasure: A Software Package for Quantification of Cortical Motor Maps Using Frameless Stereotaxic Transcranial Magnetic Stimulation.

The recent enhanced sophistication of non-invasive mapping of the human motor cortex using MRI-guided Transcranial Magnetic Stimulation (TMS) techniques, has not been matched by refinement of methods for generating maps from motor evoked potential (MEP) data, or in quantifying map features. This is despite continued interest in understanding cortical reorganization for natural adaptive processes such as skill learning, or in the case of motor recovery, such as after lesion affecting the corticospinal system. With the observation that TMS-MEP map calculation and quantification methods vary, and that no readily available commercial or free software exists, we sought to establish and make freely available a comprehensive software package that advances existing methods, and could be helpful to scientists and clinician-researchers. Therefore, we developed NeuroMeasure, an open source interactive software application for the analysis of TMS motor cortex mapping data collected from Nexstim® and BrainSight®, two commonly used neuronavigation platforms. NeuroMeasure features four key innovations designed to improve motor mapping analysis: de-dimensionalization of the mapping data, fitting a predictive model, reporting measurements to characterize the motor map, and comparing those measurements between datasets. This software provides a powerful and easy to use workflow for characterizing and comparing motor maps generated with neuronavigated TMS. The software can be downloaded on our github page: https://github.com/EdwardsLabNeuroSci/NeuroMeasureAimThis paper aims to describe a software platform for quantifying and comparing maps of the human primary motor cortex, using neuronavigated transcranial magnetic stimulation, for the purpose of studying brain plasticity in health and disease.

Both dorsal and ventral attention network nodes are implicated in exogenously driven visuospatial anticipation

Neuroimaging and transcranial magnetic stimulation (TMS) studies have implicated a dorsal fronto-parietal network in endogenous attention control and a more ventral set of areas in exogenous attention shifts. However, the extent and circumstances under which these cortical networks overlap and/or interact remain unclear. Crucially, whereas previous studies employed experimental designs that tend to confound exogenous with endogenous attentional engagement, we used a cued target discrimination paradigm that behaviourally dissociates exogenous from endogenous attention processes. Participants engaged with endogenous attention cues, while simultaneous apparent motion cues were driving exogenous attention along the motion path towards or away from the target position. To interfere with dorsal or ventral attention networks, we delivered neuronavigated double-pulse TMS over either right intraparietal sulcus (rIPS) or right temporo-parietal junction (rTPJ) towards the end of the cue target interval, and compared the effects to a sham-TMS condition. For sham-TMS, endogenous and exogenous cueing both benefitted discrimination accuracy. Target discrimination was enhanced at validly versus invalidly cued locations (endogenous cueing benefit) as well as when targets appeared in versus out of the motion path (exogenous cueing benefit), despite motion being uninformative and task-irrelevant, replicating previous findings. Interestingly, both rIPS- and rTPJ-TMS abolished attention benefits from exogenous cueing, while endogenous cueing benefits were unaffected. Our findings provide evidence against independent involvement of the dorsal and ventral attention network nodes in exogenous attention processes.

Use-Dependent Plasticity in Human Primary Motor Hand Area: Synergistic Interplay Between Training and Immobilization.

Training and immobilization are powerful drivers of use-dependent plasticity in human primary motor hand area (M1HAND). In young right-handed volunteers, corticomotor representations of the left first dorsal interosseus and abductor digiti minimi muscles were mapped with neuronavigated transcranial magnetic stimulation (TMS) to elucidate how finger-specific training and immobilization interact within M1HAND. A first group of volunteers trained to track a moving target on a smartphone with the left index or little finger for one week. Linear sulcus shape-informed TMS mapping revealed that the tracking skill acquired with the trained finger was transferred to the nontrained finger of the same hand. The cortical representations of the trained and nontrained finger muscle converged in proportion with skill transfer. In a second group, the index or little finger were immobilized for one week. Immobilization alone attenuated the corticomotor representation and pre-existing tracking skill of the immobilized finger. In a third group, the detrimental effects of finger immobilization were blocked by concurrent training of the nonimmobilized finger. Conversely, immobilization of the nontrained fingers accelerated learning in the adjacent trained finger during the first 2 days of training. Together, the results provide novel insight into use-dependent cortical plasticity, revealing synergistic rather than competitive interaction patterns within M1HAND.

The temporal involvement of the left supramarginal gyrus in planning functional grasps: A neuronavigated TMS study

The left supramarginal gyrus (SMG) is a critical structure in tool use actions, including such simple acts as selection of appropriate grasps and, if necessary, their on-line corrections. Yet, its temporal contribution to initial planning of functional grasps of tools is largely unknown. We used MRI-guided, event-related transcranial magnetic stimulation (TMS) to determine the time point when SMG involvement in processing of tools for functional grasp decision was affected most. In Exp. 1, with 15 participants, triple-pulse (10 Hz) TMS was applied to either the left anterior-to-mid SMG (amSMG; subdivisions PFt/PF) or vertex at three different time points: starting from 17 ms (i.e., delivered at 17/117/217 ms), 117 ms (117/217/317 ms) or 217 ms (217/317/417 ms) after stimulus onset. In Exp. 2, with 12 participants, we applied single-pulse TMS to either left amSMG or the left rostral middle frontal gurus (rMFG; area 46) at these same time points relative to stimulus onset. Subject- and item-based analyses of response times (RTs) were performed. Whereas the amSMG and vertex stimulation with triple pulse has revealed differential effects on RTs in general, as well as on tool orientation processing, it gave only vague pointers as to their temporal contributions to the task. Yet, amSMG and rMFG stimulation with single pulse demonstrated that, while the processing in both of these areas can be enhanced at 17 ms and no doubt at 117 ms (as compared to 217 ms), the earliest stimulation facilitated amSMG (vs. rMFG) contribution, and the latest stimulation had the opposite effect, facilitating rMFG (vs. amSMG) contribution to planning functional grasps. These outcomes demonstrate that the critical role of SMG in tool-related actions can be invoked substantially earlier than previously thought.

The Impact of Repetitive Transcranial Magnetic Stimulation on Affected and Unaffected Sides of a Child with Hemiplegic Cerebral Palsy.

The purpose of this study was to investigate the therapeutic effects of neuro-navigated repetitive transcranial magnetic stimulation (rTMS) combined with occupational therapy (OT) on gait impairment of a child (male, age: 13.2) with spastic hemiplegic cerebral palsy (CP). The treatment included 4 days a week of rTMS sessions for 3 weeks and 4 days of rTMS and OT sessions per week for 3 weeks. Transcranial magnetic stimulation (TMS) was used to evaluate corticospinal tract (CST) activities and H-reflex test was used to assess reflex hyper-excitability. Common clinical tests demonstrate the clinical status of the patient. Evaluations were performed in 4 time steps: baseline, 3 weeks after the beginning of the treatment, at the end of the treatment, and 1 month after the end of the treatment. The patient did not receive any specific treatment after the end of the treatment up to the follow up evaluations. The tests' results were compared between the affected and unaffected legs of the patient. Four parameters of the TMS test were calculated (motor evoked potential (MEP) latency, MEP peak-to-peak amplitude, cortical silent period (cSP), and stimulation intensity). These parameters were all improved for the affected side and cSP improved for the unaffected side, but MEP p-p amplitude and intensity got worse slightly for the unaffected side. Recruitment curves of H response and M-wave of the H-reflex test for both sides were obtained. Improvements could be seen after the treatment for both sides. Max H response on max M-wave (H/M) and H response latency got better after the treatment for both sides. Walking speed for self and fast velocity, timed up and go, and walking endurance improved during and after the treatment. All the improvements persisted after one month of the end of the treatment in the follow up evaluations. These findings indicate that rTMS combined with OT can have effective and long-lasting impact on neuromuscular impairments in spastic CP children.

F193. What remains as transcranial cortical response after accounting for the contribution of somatosensory and auditory evoked responses?

Focal transcranial magnetic stimulation (TMS) induces somatosensory input due to excitation of peripheral trigeminal nerve branches as well as auditory input caused by the loud click produced during stimulus discharge. In a recent study, we have demonstrated that these peripheral sources of cortical activation make a strong contribution to the transcranial evoked potentials (TEPs) that can be recorded with EEG at the scalp. Here we investigated the components of the TEP after removal of multisensory contributions. In 10 healthy young volunteers, we applied single-pulse neuronavigated TMS using two coil orientations (perpendicular and parallel to the target gyrus) and two positions (superior frontal gyrus and superior parietal lobule) and recorded the TEPs. We also recorded the evoked EEG response in a sham condition during which the TMS click was given simultaneously with bipolar electrical skin stimulation at the site corresponding to the centre of the coil during real TMS. We applied a fitting procedure to the sham and real-TMS conditions to exclude the signal related to somatosensory and auditory processing from the transcranially evoked TMS response. Some of the standard peaks commonly reported in the TMS/EEG literature were reduced or modified, suggesting that they were also caused by multisensory peripheral stimulation. For example, this was the case for the negative deflection that appears at around 100 ms after single-pulse TMS. We also identified TEP components which were not changed after accounting for somatosensory and auditory EEG response. This uncovered TEP signal was sensitive to the direction of the coil orientation, showing statistical difference in time intervals that were not present in the original TEP. This study confirms the need to exclude the somatosensory and auditory confounds in order to have a deeper insight into the TMS/EEG results. The appropriate approach is to include a sham procedure that controls for the contribution of peripheral sensory stimulation to the TEPs. Our novel procedure renders it possible to study the brain response to direct magnetic stimulation of the cortex also in time intervals affected or covered by unwanted sensory inputs.

Does TMS on V3 block conscious visual perception?

Primary visual cortex (V1) and extrastriate V2 are necessary for the emergence of visual consciousness, but the effects of involvement of extrastriate V3 on visual consciousness is unclear. The objective of this study was to examine the causal role of V3 in visual consciousness in humans. We combined neuronavigated transcranial magnetic stimulation (TMS) with a computational model of the TMS-induced electric field to test whether or not the intact processing of visual input in V3, like in V1 and V2, is necessary for conscious visual perception. We targeted the stimulation both to V2 and to V3. If TMS of V3 blocks conscious visual perception of stimuli, then activation in V3 is a causally necessary prerequisite for conscious perception of stimuli. According to the alternative hypothesis, TMS of V3 will not block the conscious visual perception of stimuli, because the pathways from V1 to the higher cortical areas that go around V3 provide sufficient visual input for the emergence of conscious visual perception. The results showed that TMS interfered with conscious perception of features, detection of stimulus presence and the ability to discriminate the letter stimuli both when TMS was targeted either to V3 or to V2. For the conscious detection of stimulus presence, the effect was significantly stronger when V2 was stimulated than when V3 was stimulated. The results of the present study suggest that in addition to the primary visual cortex and V2, also V3 causally contributes to the generation of the most basic form of visual consciousness. Importantly, the results also indicate that V3 is necessary for visual perception in general, not only for visual consciousness.

High-resolution language mapping of Broca's region with transcranial magnetic stimulation.

Broca's region, corresponding roughly to cytoarchitectonic areas 44 and 45 in the inferior frontal cortex, holds a multifunctional role in language processing, as shown, e.g., by functional imaging data. Neuro-navigated transcranial magnetic stimulation (TMS) enables complementary non-invasive mapping of cortical functions with high spatial resolution. Here, we report on detailed TMS language mapping of Broca's region in 12 healthy participants. The test protocol with an object naming task was adapted for high-resolution and semi-quantitative mapping of TMS-induced effects on speech and language performance. Hierarchical cluster analysis of normalized ratings of error frequency and severity revealed a clear focus of TMS impact at dorso-posterior target sites, close to the inferior frontal junction. Adjacent clusters of moderate and slightly affected stimulation sites yielded a posterosuperior-to-anteroinferior gradient of TMS susceptibility. Our findings indicate that the part of Broca's region most susceptible to TMS-induced language inhibition in object naming is located in the dorsal area 44.

P 14 Motor component of speech errors in rTMS language mapping

Objective Using neuronavigated repetitive transcranial magnetic stimulation (rTMS) to disrupt language function during an online-task (e.g., picture naming) is a novel mapping technique which has recently been introduced for presurgical diagnostics in brain tumor patients. However, the method has some limitations due to its rather low specificity. Beyond its dependency on the task, the distinct error categories may have a major effect on the mapping results. We, here, studied the reliability and the spatial localization of rTMS-induced naming errors related to motor-speech function in contrast to semantic language errors. Methods 13 right-handed, healthy volunteers were investigated in 3 consecutive sessions (short-term: 2–5 days, long-term: 21–40 days) by 10 Hz-rTMS. First, the primary motor representation of the face (M1) was mapped by single-pulse TMS. Then, the minimal stimulation intensity which was required to disrupt rhythmic tongue movements by at least three out of five consecutive stimulations over the M1 hotspot was assessed by two independent observers. The “motor inhibition threshold” (MIT) determined the stimulation intensity for the following rTMS language mapping. Online-rTMS was then applied during a picture-naming task using black-and-white drawings of everyday objects which were presented simultaneously (triggered, delay = 0 ms) with the rTMS. The rTMS bursts lasted for 1.5 s (15 pulses). The continuous stimulated area of the left hemisphere had the following anatomical boundaries: middle temporal sulcus (caudal), angular gyrus/ middle parietal sulcus (mediodorsal), hand knob and middle frontal sulcus (medial), triangular part of the inferior frontal gyrus (rostral). Errors were rated by two independent raters by post hoc video analysis. The error frequency (number of errors per 100 TMS trains) as well as the spatial representation and the reliability of distinct motor-speech-related errors, i.e., speech arrest and dysarthria, were compared to language errors associated with semantic processing, i.e., anomia and semantic paraphasia. Test-retest-reliability was assessed by the average intraclass correlation coefficient for a fixed rater (ICC). Results Overall, speech/ language errors were rare events. Amongst the four analyzed error categories, dysarthria represented the most frequent error ( 4.0 ± 2.5 % ) whereas only very few semantic paraphasias were induced ( 0.5 ± 0.4 % ). Motor-speech errors were found significantly more often than semantic language errors ( p 0.01 ). In comparison to semantic errors, the test-retest-reliability of the error rates was lower for motor-speech errors (ICC = 0.45 vs. 0.64). By contrast, the spatial reliability was higher for motor speech errors and showed a strong clustering over M1 and the premotor cortex, especially for the category “arrest”. Conclusion RTMS language mapping is a promising novel technique but the results are still hard to interpret and highly variable. The great majority of errors seems to be at least partially due to motor network disruption rather than being induced by interference with language processing. Further studies, combining different neuroimaging techniques and online-EEG, are mandatory to gain further insight into the underlying mechanisms and the brain-state-dependency of rTMS during language tasks.

Persistent uncrossed corticospinal connections in patients with intractable focal epilepsy

Corticospinal connections may be bilateral at birth, but a predominantly unilateral and crossed pattern develops by the toddler years. Acquired injury can alter the normal development of laterality such that uncrossed corticospinal connections persist, particularly if the injury is early in life and involves the motor system. Whether other developmental insults, such as childhood epilepsy, affect the development of crossed laterality in the motor system is unknown, although this topic has relevance for understanding the broader impact of epilepsy on brain development. Accordingly, in a cohort of children with intractable focal epilepsy, we tested by neuronavigated transcranial magnetic stimulation (nTMS) whether childhood epilepsy is associated with persistent uncrossed corticospinal connections. Specifically, we hypothesized that in contrast to early-life neuroclastic corticospinal tract injury that induces preservation of uncrossed corticospinal connections in the contralesional hemisphere, uncrossed corticospinal connections will be preserved in the epileptic hemisphere where the corticospinal tract is intact, but overstimulated by ongoing seizures and epileptic interictal discharges. Motor cortex mapping was performed by nTMS as part of a clinical presurgical evaluation, and the analysis was limited to patients with radiographically intact motor cortices and corticospinal tracts. Given that foot motor cortex representation is often bilateral, we focused on the lateralization for the tibialis anterior muscle cortical motor representation and its relation to the seizure focus. We demonstrate preserved uncrossed corticospinal connections for the tibialis anterior region of the hemisphere affected by the epilepsy. These findings indicate a pathologically preserved immature motor lateralization in patients with epilepsy and suggest that developmental processes associated with hemispheric lateralization are affected by epilepsy.

Preliminary results from a randomized sham-controlled trial of augmentative Neuro-navigated right-dorsolateral prefrontal cortex low-frequency repetitive transcranial magnetic stimulation for antidepressant non-responding Bipolar depression

Preliminary results from a randomized sham-controlled trial of augmentative Neuro-navigated right-dorsolateral prefrontal cortex low-frequency repetitive transcranial magnetic stimulation for antidepressant non-responding Bipolar depression