No abstract

Background: Following a stroke event, patients often are severely affected by disabilities that hinder their quality-of-life. There are currently several rehabilitative options and strategies, and it is crucial to find the most effective interventions. The applicability of transcranial magnetic stimulation (TMS) to the recovery of nonmotor functions such as communication skills, swallowing ability and spatial attention after stroke remains important clinical questions. Summary: We searched PubMed and ISI Web of Science for articles that used repetitive TMS protocols to rehabilitate post-stroke deficits. We analysed qualitatively 38 articles that met the eligibility criteria; of these, 21 dealt with aphasia, 8 with dysphagia, 8 with neglect and 1 with visual extinction. The efficacy of TMS as an intervention for post-stroke rehabilitation of these nonmotor deficits was studied as well as the current limitations were assessed. Key Messages: Most part of the included studies reported statistically significant functional improvements, supporting the use of TMS for the rehabilitation of aphasia, dysphagia and neglect. Future research, with larger sample sizes, is mandatory to confirm its efficacy, determine the optimal stimulation parameters and investigate inter-subject variability.

People interested in the research are advised to contact the author for the final version of the publication, or visit the DOI to the publisher's website.• The final author version and the galley proof are versions of the publication after peer review.• The final published version features the final layout of the paper including the volume, issue and page numbers. Link to publication General rightsCopyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal.If the publication is distributed under the terms of Article 25fa of the Dutch Copyright Act, indicated by the "Taverne" license above, please follow below link for the End User Agreement:

Excitatory/inhibitory imbalance has been suggested as a neurobiological substrate of the cognitive symptomatology in Autism Spectrum Disorder (ASD). Studies using magnetic resonance spectroscopy (MRS) attempted to characterize GABA and Glutamate brain levels in ASD. However mixed findings have been reported. Here, we characterize both neurochemical and physiological aspects of GABA system in ASD by implementing a more comprehensive approach combining MRS and transcranial magnetic stimulation (TMS). A group of 16 young ASD adults and a group of 17 controls participated in this study. We employed one MRS session to assess motor cortex GABA+ and Glutamate+Glutamine (Glx) levels using MEGAPRESS and PRESS sequences, respectively. Additionally, a TMS experiment was implemented including paired-pulse (SICI, ICF and LICI), input-output curve and cortical silent period to probe cortical excitability. Our results showed a significantly increased Glx, with unchanged GABA+ levels in the ASD group compared with controls. Single TMS measures did not differ between groups, although exploratory within-group analysis showed impaired inhibition in SICI5ms, in ASD. Importantly, we observed a correlation between GABA levels and measures of the input-output TMS recruitment curve (slope and MEP amplitude) in the control group but not in ASD, as further demonstrated by direct between group comparisons. In this exploratory study, we found evidence of increased Glx levels which may contribute to ASD excitatory/inhibitory imbalance while highlighting the relevance of conducting further larger-scale studies to investigate the GABA system from complementary perspectives, using both MRS and TMS techniques.

Neurofibromatosis type 1 (NF1) is associated with GABAergic dysfunction which has been suggested as the underlying cause of cognitive impairments. Previous intervention trials investigated the statins’ effects using cognitive outcome measures. However, available outcome measures have led to inconclusive results and there is a need to identify other options. Here, we aimed at investigating alternative outcome measures in a feasibility trial targeting cortical inhibition mechanisms known to be altered in NF1. We explored the neurochemical and physiological changes elicited by lovastatin, with magnetic resonance spectroscopy and transcranial magnetic stimulation (TMS). Fifteen NF1 adults participated in this randomized, triple-blind, placebo-controlled crossover trial (Clinicaltrials.gov NCT03826940) composed of one baseline and two reassessment visits after lovastatin/placebo intake (60 mg/day, 3-days). Motor cortex GABA+ and Glx concentrations were measured using HERMES and PRESS sequences, respectively. Cortical inhibition was investigated by paired-pulse, input–output curve, and cortical silent period (CSP) TMS protocols. CSP ratios were significantly increased by lovastatin (relative: p = 0.027; absolute: p = 0.034) but not by placebo. CSP durations showed a negative correlation with the LICI 50 ms amplitude ratio. Lovastatin was able to modulate cortical inhibition in NF1, as assessed by TMS CSP ratios. The link between this modulation of cortical inhibition and clinical improvements should be addressed by future large-scale studies.