a-standardized-protocol-for-functional-motor-mapping-using-navigated

A Standardized Protocol for Functional Motor Mapping Using Navigated Transcranial Magnetic Stimulation

Navigated transcranial magnetic stimulation (nTMS) is based on the integration of individual brain imaging data to determine the precise positioning of ...

Paris Est Créteil University

Henri Mondor University Hospital, APHP

 Maximum safe resection of infiltrative brain tumors in eloquent area is the primary objective in surgical neuro-oncology. This goal can be achieved with direct electrical stimulation (DES) to perform a functional mapping of the brain in patients awake intraoperatively. When awake surgery is not possible, we propose a pipeline procedure that combines advanced techniques aiming at performing a dissection that respects the anatomo-functional connectivity of the peritumoral region. This procedure can benefit from intraoperative monitoring with computerized tomography scan (iCT-scan) and brain shift correction. Associated with this intraoperative monitoring, the additional value of preoperative investigation combining brain mapping by navigated transcranial magnetic stimulation (nTMS) with various neuroimaging modalities (tractography and resting state functional MRI) has not yet been reported.  A 42-year-old left-handed man had increased intracranial pressure (IICP), left hand muscle deficit, and dysarthria, related to an infiltrative tumor of the right frontal lobe with large mass effect and circumscribed contrast enhancement in motor and premotor cortical areas. Spectroscopy profile and intratumoral calcifications on CT-scan suggested an WHO grade III glioma, later confirmed by histology. The aforementioned surgical procedure was considered, since standard awake surgery was not appropriate for this patient. In preoperative time, nTMS mapping of motor function (deltoid, first interosseous, and tibialis anterior muscles) was performed, combined with magnetic resonance imaging (MRI)-based tractography reconstruction of 6 neural tracts (arcuate, corticospinal, inferior fronto-occipital, uncinate and superior and inferior longitudinal fasciculi) and resting-state functional MRI connectivity (rs-fMRI) of sensorimotor and language networks. In intraoperative time, DES mapping was performed with motor evoked response recording and tumor resection was optimized using non-rigid image transformation of the preoperative data (nTMS, tractography, and rs-fMRI) to iCT data. Image guidance was updated with correction for brain shift and tissue deformation using biomechanical modeling taking into account brain elastic properties. This correction was done at crucial surgical steps, i.e., when tumor bulged through the craniotomy after dura mater opening and when approaching the presumed eloquent brain regions. This procedure allowed a total resection of the tumor region with contrast enhancement as well as a complete regression of IICP and dysarthria. Hand paresis remained stable with no additional deficit. Postoperative nTMS mapping confirmed the good functional outcome.  This case report and technical note highlights the value of preoperative functional evaluation by nTMS updated intraoperatively with correction of brain deformation by iCT. This multimodal approach may become the optimized technique of reference for patients with brain tumors in eloquent areas that are unsuitable for awake brain surgery.

Case Report: Multimodal Functional and Structural Evaluation Combining Pre-operative nTMS Mapping and Neuroimaging With Intraoperative CT-Scan and Brain Shift Correction for Brain Tumor Surgical Resection.

Mild encephalopathy/encephalitis with reversible splenial lesion (MERS) is a transient clinico-radiological syndrome characterized by non-specific encephalopathy and specific magnetic resonance imaging (MRI) pattern. MRI shows an ovoid lesion in the mid-splenium of the corpus callosum (SCC), with signal-intensity anomaly similar to stroke but vanishing within few weeks. Although there are a lot of child MERS cases descriptions, there are just a few adult-onset reported. Our goal is to provide a better clinical and radiological description of this entity. We reported nine adult-onset cases of MERS managed in our stroke unit between 2017 and 2019. The study of our adult series suggests that epilepsy and the context of an infection are very common in MERS. Adult cases show frequent focal neurological deficits and few encephalopathies compared to children. The measurement of very low ADC values in SCC lesion is a new radiological feature of MERS that should be systematically assessed in suspected cases to differentiate this complex syndrome from SCC strokes.

Mild encephalopathy with reversible splenial lesion: Description of nine cases and review of the literature.

Efficient cognitive tasks sensitive to longitudinal deterioration in small cohorts of Huntington's disease (HD) patients are lacking in HD research. We thus developed and assessed the digitized arithmetic task (DAT), which combines inner language and executive functions in approximately 4 minutes.

Cognitive decline in Huntington's disease in the Digitalized Arithmetic Task (DAT).

Time processing over intervals of hundreds of milliseconds to minutes, also known as interval timing, is associated with the striatum. Huntington's disease patients (HD) with striatal degeneration have impaired interval timing, but the extent and specificity of these deficits remain unclear. Are they specific to the temporal domain, or do they extend to the spatial domain too? Do they extend to both the perception and production of interval timing? Do they appear before motor symptoms in Huntington's disease (Pre-HD)? We addressed these issues by assessing both temporal abilities (in the seconds range) and spatial abilities (in the cm range) in 20 Pre-HD, 25 HD patients, and 25 healthy Controls, in discrimination, bisection and production paradigms. In addition, all participants completed a questionnaire assessing temporal and spatial disorientation in daily life, and the gene carriers (i.e., HD and Pre-HD participants) underwent structural brain MRI. Overall, HD patients were more impaired in the temporal than in the spatial domain in the behavioral tasks, and expressed a greater disorientation in the temporal domain in the daily life questionnaire. In contrast, Pre-HD participants showed no sign of a specific temporal deficit. Furthermore, MRI analyses indicated that performances in the temporal discrimination task were associated with a larger striatal grey matter volume in the striatum in gene carriers. Altogether, behavioral, brain imaging and questionnaire data support the hypothesis that the striatum is a specific component of interval timing processes. Evaluations of temporal disorientation and interval timing processing could be used as clinical tools for HD patients.

The specific role of the striatum in interval timing: The Huntington's disease model.

Cognitive deficits represent a hallmark of neurodegenerative diseases, but evaluating their progression is complex. Most current evaluations involve lengthy paper-and-pencil tasks which are subject to learning effects dependent on the mode of response (motor or verbal), the countries' language or the examiners. To address these limitations, we hypothesized that applying neuroscience principles may offer a fruitful alternative. We thus developed the SelfCog, a digitized battery that tests motor, executive, visuospatial, language and memory functions in 15 min. All cognitive functions are tested according to the same paradigm, and a randomization algorithm provides a new test at each assessment with a constant level of difficulty. Here, we assessed its validity, reliability and sensitivity to detect decline in early-stage Huntington's disease in a prospective and international multilingual study (France, the UK and Germany). Fifty-one out of 85 participants with Huntington's disease and 40 of 52 healthy controls included at baseline were followed up for 1 year. Assessments included a comprehensive clinical assessment battery including currently standard cognitive assessments alongside the SelfCog. We estimated associations between each of the clinical assessments and SelfCog using Spearman's correlation and proneness to retest effects and sensitivity to decline through linear mixed models. Longitudinal effect sizes were estimated for each cognitive score. Voxel-based morphometry and tract-based spatial statistics analyses were conducted to assess the consistency between performance on the SelfCog and MRI 3D-T1 and diffusion-weighted imaging in a subgroup that underwent MRI at baseline and after 12 months. The SelfCog detected the decline of patients with Huntington's disease in a 1-year follow-up period with satisfactory psychometric properties. Huntington's disease patients are correctly differentiated from controls. The SelfCog showed larger effect sizes than the classical cognitive assessments. Its scores were associated with grey and white matter damage at baseline and over 1 year. Given its good performance in longitudinal analyses of the Huntington's disease cohort, it should likely become a very useful tool for measuring cognition in Huntington's disease in the future. It highlights the value of moving the field along the neuroscience principles and eventually applying them to the evaluation of all neurodegenerative diseases.

A new approach to digitized cognitive monitoring: validity of the SelfCog in Huntington's disease.

The purpose of this study was to compare a highly-accelerated double inversion recovery (fast-DIR) sequence using a recent parallel imaging technique (CAIPIRINHA) with a conventional DIR (conv-DIR) sequence for image quality and the detection of juxtacortical and infratentorial multiple sclerosis (MS) lesions.

Improved detection of juxtacortical lesions using highly accelerated double inversion-recovery MRI in patients with multiple sclerosis.

Patient-induced inhomogeneities in the static magnetic field cause distortions and blurring (off-resonance artifacts) during acquisitions with long readouts such as in SWI. Conventional versatile correction methods based on extended Fourier models are too slow for clinical practice in computationally demanding cases such as 3D high-resolution non-Cartesian multi-coil acquisitions.

Deep learning-assisted model-based off-resonance correction for non-Cartesian SWI.

The prevalent belief that individuals with Huntington's disease exhibit selfish behaviour, disregarding the thoughts, feelings and actions of others, has been challenged by patient organizations and clinical experts. To further investigate this issue and study whether participants with Huntington's disease can pay attention to others, a joint memory task was carried out in patients with Huntington's disease with and without a partner. This study involved 69 participants at an early stage of Huntington's disease and 56 healthy controls from the UK, France and Germany, who participated in the international Repair-HD multicentre study (NCT03119246). Participants completed a semantic categorization task across three categories: animals, fruits and vegetables and manufactured objects. They performed the task either alone (Alone condition) or with the examiner acting as a partner (Pair condition). In the Pair condition, the participant was assigned one category, their partner was assigned another and one category was left unassigned. Afterwards, participants engaged in a surprise free recall task to remember as many words as possible. Words not assigned to anyone were considered socially irrelevant in contrast to the ones assigned to the participant and to the partner. Both groups demonstrated the expected self-prioritization effect, recalling their assigned words better than their partner's or unassigned words in both conditions. Additionally, a joint memory effect was observed, with better recall for the partner's assigned words than the unassigned words in the Pair condition (controls: difference = 0.45,  < 0.001; participants with Huntington's disease: difference = 0.34,  < 0.001). Socially relevant words were thus better recalled than irrelevant words. The number of recalled words correlated with cognitive performance (all -values < 0.05) and MRI analysis revealed a negative correlation between the joint memory effect and right orbitofrontal grey matter density in participants with Huntington's disease. These findings challenge the notion that individuals with Huntington's disease display selfish behaviours because of disinterest in others. They show the ability to process information about their partners, implying that their social difficulties may arise from factors other than social cognition deficits. This opens the door for more ecological assessments of social cognition in patients with Huntington's disease.

The joint memory effect: challenging the selfish stigma in Huntington's disease?

The clinical utility of routine brain MRI in psychiatry is debated with heterogeneous practices.

Article	Year
Case Report: Multimodal Functional and Structural Evaluation Combining Pre-operative nTMS Mapping and Neuroimaging With Intraoperative CT-Scan and Brain Shift Correction for Brain Tumor Surg... Frontiers in human neuroscience\| PubMed ID: 33716700	2021
Mild encephalopathy with reversible splenial lesion: Description of nine cases and review of the literature. Seizure\| PubMed ID: 33839562	2021
Cognitive decline in Huntington's disease in the Digitalized Arithmetic Task (DAT). PloS one\| PubMed ID: 34424902	2021
The specific role of the striatum in interval timing: The Huntington's disease model. NeuroImage. Clinical\| PubMed ID: 34749287	2021
A new approach to digitized cognitive monitoring: validity of the SelfCog in Huntington's disease. Brain communications\| PubMed ID: 36938527	2023
Improved detection of juxtacortical lesions using highly accelerated double inversion-recovery MRI in patients with multiple sclerosis. Diagnostic and interventional imaging\| PubMed ID: 37156721	2023
Deep learning-assisted model-based off-resonance correction for non-Cartesian SWI. Magnetic resonance in medicine\| PubMed ID: 37345701	2023
The joint memory effect: challenging the selfish stigma in Huntington's disease? Brain communications\| PubMed ID: 39744082	2025
Brain MRI in patients with psychiatric disorders: A retrospective evaluation in routine clinical practice. Journal of neuroradiology = Journal de neuroradiologie\| PubMed ID: 41547332	2026

Blanche Bapst

Biography

JoVE Journal Publications

Other Publications