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Brain stimulation of attention networks: examining old principles and developing new clinical applications

Periodic Reporting for period 1 - TMS_ATT (Brain stimulation of attention networks: examining old principles and developing new clinical applications)

Reporting period: 2016-06-01 to 2018-05-31

The main goals of the action were to investigate the functional organization of the brain networks underlying attentional control using neuroimaging and brain stimulation, and to explore a novel brain-based treatment approach for attention deficits after stroke. Combining the fellow’s expertise in brain stimulation and the expertise at the host institute in translational neuroscience enabled the fellow to conduct a series of experiments illuminating various aspects of attentional control in healthy volunteers and patients.
While the work in healthy volunteers has been completed already, and is all ready to be submitted for publication, the work in stroke patients will continue beyond the end of the project because of the challenging nature of the project and specific recruitment criteria required for the patient sample (requiring a short term window of plasticity after the stroke event, which implies that patients are assessed a few days after acute stroke, imposing careful assessment of stabilization of the clinical event and non rare exclusions). This was discussed during the monitoring visit. Nevertheless, planned original publications in healthy volunteers and stroke patients submitted to EEG and TMS are already being prepared (data collection and analysis are finished). One paper is already under review in PLOS One, as well as a review article in the Journal Cerebrovascular Disease. We would like also to emphasize the unique multimodal nature of the data set being generated in stroke patients, which is involving the collaboration of a the University Hospital of the University of Coimbra and a National Rehabilitation Hospital. The results attained so far suggest that we achieved promising biological markers for assessing the results of neurostimulation
To provide a general overview, the following work has been completed:
• Completion of a neuroimaging experiment (fMRI) in healthy volunteers to reveal hemispheric asymmetries in the dorsal attention network.
• Completion of a brain stimulation experiment (TMS) with eye tracking in healthy volunteers to reveal the functional role of frontal nodes of the dorsal attention network.
• Completion of a brain stimulation experiment (TMS) with electroencephalography (EEG) in healthy volunteers and in stroke patients to obtain neurophysiological evidence for inhibition/disinhibition mechanisms between hemispheres. The analysis of the 1st dataset led to a first submission.
• Completion of a brain stimulation experiment (TMS) with neuroimaging (fMRI) in healthy volunteers to strengthen connectivity within the attention network to boost attentional performance.
• Establishing a collaboration between the host institute and the stroke unit at the University Hospital of Coimbra to study attention deficits in stroke patients in the acute phase (1 week after stroke). Detailed multimodal data were obtained in a series of patients.
• Establishing a collaboration between the host institute and a Rehabilitation Centre of National Scope to study attention deficits in stroke patients in the sub-acute phase. A multimodal dataset is being acquired. These data are of paramount importance to ensure the long term implications of the project.
• Development and implementation of a protocol to conduct brain stimulation, neuroimaging, and neuropsychological testing in stroke patients in the acute and sub-acute phase.
• Acquisition and implementation of analysis pipeline for neuroimaging data obtained in stroke patients.
• Presentations at international conferences.
• Preparation of manuscripts for publication in international peer-reviewed journals.
• Dissemination of obtained expertise in certification courses for clinical applications of brain stimulation.
• Participation in host academic activities to share knowledge and advanced skills during lab meetings, project presentations, scientific talks, and consultations. Training of master, PhD and postdoctoral fellows, locally and in international courses was achieved, with substantial impact. The Host Institution took advantage of this action to implement additional translational research projects, some of which achieved prizes and additional funding to probe neurostimulation techniques in neurological disorders.

The action has greatly contributed to the fellow’s academic development and career, leading to a position as assistant professor at Maastricht University. The action has strengthened the link between the University of Coimbra and Maastric
The project had the expected impact on the fellow’s career and academic development, advanced the scientific understanding of the brain mechanisms underlying attention, made these insights available to the scientific community and clinicians, and strengthened the collaboration between various institutes in Portugal and the Netherlands dedicated to translational neuroscience.

Personal impact
The aim of the fellow was to establish himself as a translational researcher that develops, tests, and applies new TMS treatment options based on both methodological developments and state-of-the-art neurocognitive models. The action greatly contributed to this goal by further advancing the fellow’s neuroimaging and brain stimulation expertise and gaining critical clinical experience and knowledge. The fellow is now equipped with the broad skill set required to further pursue innovative research at the forefront of translational neuroscience. These academic developments have already advanced the fellow’s career, who recently obtained a tenure-track position as assistant professor at Maastricht University where he will build on the foundation laid by this MSC fellowship.

Scientific and clinical impact
As outline in previous sections, several experiments in healthy volunteers have been complete during the fellowship period and pioneering work in stroke patients is still ongoing. The insights obtained during the action have been disseminated at conferences, and workshops, and results have been submitted to international peer-reviewed journal for publication. In particular the clinical impact of the action has to be emphasized. During the fellowship period, the fellow has contributed to eight workshops organized in various European cities to share his expertise in brain stimulation as a novel treatment approach for brain-based disorders. More than 200 clinicians from all continents have attended these courses and the resulting network will be of great value in the future.

European impact
The action has strengthened the collaboration between the University of Coimbra, the local university hospital, the rehabilitation center in the Coimbra region, and Maastricht University. Combining expertise across European research institutes is a necessity for cutting-edge multidisciplinary research and a strong foundation for large-scale studies aiming at establishing the efficacy of novel brain-based treatment approached. In that sense, the action certainly contributed to the strengthening of the European position in translational neuroscience.
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