Search

Although described as non-progressive, alternating hemiplegia of childhood (AHC) can display a sudden deterioration, anecdotally reported mainly in childhood. Outcome in adulthood is uncertain.Aim of this study is to describe the long-term follow-up of neurological function in adults with AHC.Seven adults with AHC were included in this retrospective single-center study. Clinical history and previous investigation data were gathered from the review of medical records. Video-documented neurological examination was performed at the last follow-up visit in four out of the seven reported indivisuals.Over a median follow-up of 16 years, neurological outcome and trajectories were heterogeneous. All individuals showed new neurological signs or symptoms. Three experienced a serious irreversible neurological deterioration after prolonged quadriplegic episodes and/or status epilepticus in their second or third decade. One patient died at age 29.This video-series suggests that AHC in adulthood is not stationary; larger cohorts are needed to identify genotype-phenotype correlations and clinically useful outcome predictors.

Progressive myoclonic epilepsy type 1 (EPM1) is caused by biallelic alterations in the CSTB gene, most commonly dodecamer repeat expansions. Although transcranial magnetic stimulation (TMS)-induced long-interval intracortical inhibition (LICI) was previously reported to be normal in EPM1, short-interval intracortical inhibition (SICI) was reduced. We explored the association between these measures and the clinical and genetic features in a separate group of patients with EPM1.TMS combined with electromyography was performed under neuronavigation. LICI was induced with an inter-stimulus interval (ISI) of 100 ms, and SICI with ISIs of 2 and 3 ms, and their means (mSICIs) were expressed as the ratio of conditioned to unconditioned stimuli. LICI and mSICI were compared between patients and controls. Nonparametric correlation was used to study the association between inhibition and parameters of clinical severity, including the Unified Myoclonus Rating Scale (UMRS); among patients with EPM1 due to biallelic expansion repeats, also the association with the number of repeats was assessed.The study protocol was completed in 19 patients (15 with biallelic expansion repeats and 4 compound heterozygotes), and 7 healthy, age- and sex-matched control participants. Compared to controls, patients demonstrated significantly less SICI (median mSICI ratio 1.18 vs 0.38; p .001). Neither LICI nor SICI was associated with parameters of clinical severity. In participants with biallelic repeat expansions, the number of repeats in the more affected allele (greater repeat number [GRN]) correlated with LICI (rho = 0.872; p .001) and SICI (rho = 0.689; p = .006).Our results strengthen the finding of deranged γ-aminobutyric acid (GABA)ergic inhibition in EPM1. LICI and SICI may have use as markers of GABAergic impairment in future trials of disease-modifying treatment in this condition. Whether a higher number of expansion repeats leads to greater GABAergic impairment warrants further study.

Transcranial magnetic stimulation (TMS)-evoked EEG potentials (TEPs) have been used to study the excitability of different cortical areas (CAs) in humans. Characterising the interhemispheric symmetry of TMS-EEG may provide further understanding of structure-function association in physiological and pathological conditions. We hypothesise that, in keeping with the underlying cytoarchitectonics, TEPs in contralateral homologous CAs share similar, symmetric spectral features, whilst ipsilateral TEPs from different CAs diverge in their waveshape and frequency content. We performed single-pulse (1 Hz) navigated monophasic TMS, combined with high-density EEG with active electrodes, in 10 healthy participants. We targeted two bilateral CAs: premotor and motor. We compared frequency power bands, computed Pearson correlation coefficient (R) and Correlated Component Analysis (CorrCA) to detect divergences, as well as common components across TEPs. The main frequency of TEPs was faster in premotor than in motor CAs (p .05) across all participants. Frequencies were not different between contralateral homologous CAs, whilst, despite closer proximity, there was a significant difference between ipsilateral premotor and motor CAs (p .5), with frequency decreasing from anterior to posterior CAs. Correlation was high between contralateral homologous CAs and low between ipsilateral CAs. When applying CorrCA, specific components were shared by contralateral homologous TEPs. We show physiological symmetry of TEP spectral features between contralateral homologous CAs, whilst ipsilateral premotor and motor TEPs differ despite lower geometrical distance. Our findings support the role of TEPs as biomarker of local cortical properties and provide a first reference dataset for TMS-EEG studies in asymmetric brain disorders.

BackgroundThe impact of transcranial magnetic stimulation (TMS) on cortical neurons is currently hard to predict based on a priori biophysical and anatomical knowledge alone. This problem can hamper the reliability and reproducibility of protocols aimed at measuring electroencephalographic (EEG) responses to TMS.New MethodWe introduce and release a novel software tool to facilitate and standardize the acquisition of TMS-evoked potentials (TEPs). The tool, rt-TEP (real-time TEP), interfaces with different EEG amplifiers and offers a series of informative visualization modes to assess in real time the immediate impact of TMS on the underlying neuronal circuits.ResultsWe show that rt-TEP can be used to abolish or minimize magnetic and muscle artifacts contaminating the post-stimulus period thus affording a clear visualization and quantification of the amplitude of the early (Comparison with Existing MethodsThe ensemble of real-time visualization modes of rt-TEP are not implemented in any current commercial software and provide a key readout to titrate TMS parameters beyond the a priori information provided by anatomical models.ConclusionsReal-time optimization of stimulation parameters with rt-TEP can facilitate the acquisition of reliable TEPs with a high signal-to-noise ratio and improve the standardization and reproducibility of data collection across laboratories.Highlightsrt-TEP provides an immediate EEG readout to assess the quality of TEPs in real timert-TEP interfaces with most commercial EEG systemsInformative, real time visualization allows maximising the cortical impact of TMS while minimizing artifactsrt-TEP facilitates the acquisition of reliable TEPs with a high signal-to-noise ratio

To elucidate the effects of single and paired-pulse TMS on seizure activity at electrographic and clinical levels in people with and without epilepsy.A cohort of 35 people with epilepsy, two people with alternating hemiplegia of childhood (AHC) with no epilepsy, and 16 healthy individuals underwent single or paired-pulse TMS combined with EEG. Clinical records and subject interviews were used to examine seizure frequency four weeks before and after TMS.There were no significant differences in seizure frequency in any subject after TMS exposure. There was no occurrence of seizures in healthy individuals, and no worsening of hemiplegic attacks in people with AHC.No significant changes in seizure activity were found before or after TMS.This study adds evidence on the safety of TMS in people with and without epilepsy with follow-up of four weeks after TMS.

BackgroundCoupling transcranial magnetic stimulation with electroencephalography (TMS-EEG) allows recording the EEG response to a direct, non-invasive cortical perturbation. However, obtaining a genuine TMS-evoked EEG potential requires controlling for several confounds, among which a main source is represented by the auditory evoked potentials (AEPs) associated to the TMS discharge noise (TMS click). This contaminating factor can be in principle prevented by playing a masking noise through earphones.New methodHere we release TMS Adaptable Auditory Control (TAAC), a highly flexible, open-source, Matlab®-based interface that generates in real-time customized masking noises. TAAC creates noises starting from the stimulator-specific TMS click and tailors them to fit the individual, subject-specific click perception by mixing and manipulating the standard noises in both time and frequency domains.ResultsWe showed that TAAC allows us to provide standard as well as customized noises able to effectively and safely mask the TMS click.Comparison with existing methodsHere, we showcased two customized noises by comparing them to two standard noises previously used in the TMS literature (i.e., a white noise and a noise generated from the stimulator-specific TMS click only). For each, we quantified the Sound Pressure Level (SPL; measured by a Head and Torso Simulator - HATS) required to mask the TMS click in a population of 20 healthy subjects. Both customized noises were effective at safe (according to OSHA and NIOSH safety guidelines), lower SPLs with respect to standard noises.ConclusionsAt odds with previous methods, TAAC allows creating effective and safe masking noises specifically tailored on each TMS device and subject. The combination of TAAC with tools for the real-time visualization of TEPs can help control the influence of auditory confounds also in non-compliant patients. Finally, TAAC is a highly flexible and open-source tool, so it can be further extended to meet different experimental requirements.

Electroencephalographic (EEG) signals evoked by transcranial magnetic stimulation (TMS) are usually recorded with passive electrodes (PE). Active electrode (AE) systems have recently become widely available, compared to PE, they allow for easier electrode preparation and a higher-quality signal, due to the preamplification at the electrode stage, which reduces electrical line noise. The performance between the AE and PE can differ, especially with fast EEG voltage changes, which can easily occur with TMS-EEG, however, a systematic comparison in the TMS-EEG setting has not been made. Therefore, we recorded TMS-evoked EEG potentials (TEPs) in a group of healthy subjects in two sessions, one using PE and the other using AE. We stimulated the left primary motor cortex and right medial prefrontal cortex and used two different approaches to remove early TMS artefacts, Independent Component Analysis and Signal Space Projection&mdash, Source Informed Recovery. We assessed statistical differences in amplitude and topography of TEPs, and their similarity, by means of the concordance correlation coefficient (CCC). We also tested the capability of each system to approximate the final TEP waveform with a reduced number of trials. The results showed that TEPs recorded with AE and PE do not differ in amplitude and topography, and only few electrodes showed a lower-than-expected CCC between the two methods of amplification. We conclude that AE are a viable solution for TMS-EEG recording.

See Krone and Vyazovskiy (doi:10.1093/brain/awaa396) for a scientific commentary on this article. Using TMS and EEG in awake patients with focal cortical injuries, Sarasso et al. reveal the presence of sleep-like dynamics in perilesional areas, coexisting with typical wakefulness cortical reactivity in control areas. Reversing perilesional sleep-like dynamics could represent a novel strategy for rehabilitation., The functional consequences of focal brain injury are thought to be contingent on neuronal alterations extending beyond the area of structural damage. This phenomenon, also known as diaschisis, has clinical and metabolic correlates but lacks a clear electrophysiological counterpart, except for the long-standing evidence of a relative EEG slowing over the injured hemisphere. Here, we aim at testing whether this EEG slowing is linked to the pathological intrusion of sleep-like cortical dynamics within an awake brain. We used a combination of transcranial magnetic stimulation and electroencephalography (TMS/EEG) to study cortical reactivity in a cohort of 30 conscious awake patients with chronic focal and multifocal brain injuries of ischaemic, haemorrhagic and traumatic aetiology. We found that different patterns of cortical reactivity typically associated with different brain states (coma, sleep, wakefulness) can coexist within the same brain. Specifically, we detected the occurrence of prominent sleep-like TMS-evoked slow waves and off-periods—reflecting transient suppressions of neuronal activity—in the area surrounding focal cortical injuries. These perilesional sleep-like responses were associated with a local disruption of signal complexity whereas complex responses typical of the awake brain were present when stimulating the contralesional hemisphere. These results shed light on the electrophysiological properties of the tissue surrounding focal brain injuries in humans. Perilesional sleep-like off-periods can disrupt network activity but are potentially reversible, thus representing a principled read-out for the neurophysiological assessment of stroke patients, as well as an interesting target for rehabilitation.

The Brain Imaging Data Structure (BIDS) is a community-driven specification for organizing neuroscience data and metadata with the aim to make datasets more transparent, reusable, and reproducible. Intracranial electroencephalography (iEEG) data offer a unique combination of high spatial and temporal resolution measurements of the living human brain. To improve internal (re)use and external sharing of these unique data, we present a specification for storing and sharing iEEG data: iEEG-BIDS.

Our own experiences with disturbances to sleep demonstrate its crucial role in the recovery of cognitive functions. This importance is likely enhanced in the recovery from stroke; both in terms of its physiology and cognitive abilities. Decades of experimental research have highlighted which aspects and mechanisms of sleep are likely to underlie these forms of recovery. Conversely, damage to certain areas of the brain, as well as the indirect effects of stroke, may disrupt sleep. However, only limited research has been conducted which seeks to directly explore this bidirectional link between both the macro and micro-architecture of sleep and stroke. Here we describe a series of semi-independent approaches that aim to establish this link through observational, perturbational, and interventional experiments. Our primary aim is to describe the methodology for future clinical and translational research needed to delineate competing accounts of the current data. At the observational level we suggest the use of high-density EEG recording, combined analysis of macro and micro-architecture of sleep, detailed analysis of the stroke lesion, and sensitive measures of functional recovery. The perturbational approach attempts to find the causal links between sleep and stroke. We promote the use of transcranial magnetic stimulation combined with EEG to examine the cortical dynamics of the peri-infarct stroke area. Translational research should take this a step further using optogenetic techniques targeting more specific cell populations. The interventional approach focuses on how the same clinical and translational perturbational techniques can be adapted to influence long-term recovery of function.

Intracranial electroencephalography (iEEG) data offer a unique combination of high spatial and temporal resolution measures of the living human brain. However, data collection is limited to highly specialized clinical environments. To improve internal (re)use and external sharing of these unique data, we present a structure for storing and sharing iEEG data: BIDS-iEEG, an extension of the Brain Imaging Data Structure (BIDS) specification, along with freely available examples and a bids-starter-kit. BIDS is a framework for organizing and documenting data and metadata with the aim to make datasets more transparent and reusable and to improve reproducibility of research. It is a community-driven specification with an inclusive decision-making process. As an extension of the BIDS specification, BIDS-iEEG facilitates integration with other modalities such as fMRI, MEG, and EEG. As the BIDS-iEEG extension has received input from many iEEG researchers, it provides a common ground for data transfer within labs, between labs, and in open-data repositories. It will facilitate reproducible analyses across datasets, experiments, and recording sites, allowing scientists to answer more complex questions about the human brain. Finally, the cross-modal nature of BIDS will enable efficient consolidation of data from multiple sites for addressing questions about generalized brain function.

Introduction Peripheral as well as direct cortical stimulations have been classically used to probe the reactivity of thalamocortical circuits across brain states, showing consistent state-dependent modifications. Methods Here we aim at directly comparing state-dependent changes across the wake/sleep cycle of the electroencephalographic (EEG) responses to transcranial magnetic stimulation (TMS – applied over premotor and parietal areas) and to electrical median nerve stimulation (EMNS - applied at an intensity able to reproducibly elicit thumb movements) in two groups of 8 healthy individuals each. Results By tuning stimulation parameters, we roughly equalized the strength of brain activation elicited by TMS and EMNS during wakefulness and achieved a similar (p = 0.8) overall (0–600 ms) global mean field power (GMFP). The time-course of wakefulness GMFP significantly peaked (p Conclusions Despite a common reduction of complexity during sleep, brain activation elicited by the two stimulation approaches reveals different state-dependent changes, highlighting the presence of cortical bistability in the case of TMS and of subcortical gating in the case of EMNS.