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Mapping mania symptoms based on focal brain damage.

ABSTRACT: BACKGROUNDAlthough mania is characteristic of bipolar disorder, it can also occur following focal brain damage. Such cases may provide unique insight into brain regions responsible for mania symptoms and identify therapeutic targets.METHODSLesion locations associated with mania were identified using a systematic literature search (n = 41) and mapped onto a common brain atlas. The network of brain regions functionally connected to each lesion location was computed using normative human connectome data (resting-state functional MRI, n = 1000) and contrasted with those obtained from lesion locations not associated with mania (n = 79). Reproducibility was assessed using independent cohorts of mania lesions derived from clinical chart review (n = 15) and of control lesions (n = 490). Results were compared with brain stimulation sites previously reported to induce or relieve mania symptoms.RESULTSLesion locations associated with mania were heterogeneous and no single brain region was lesioned in all, or even most, cases. However, these lesion locations showed a unique pattern of functional connectivity to the right orbitofrontal cortex, right inferior temporal gyrus, and right frontal pole. This connectivity profile was reproducible across independent lesion cohorts and aligned with the effects of therapeutic brain stimulation on mania symptoms.CONCLUSIONBrain lesions associated with mania are characterized by a specific pattern of brain connectivity that lends insight into localization of mania symptoms and potential therapeutic targets.FUNDINGFundação para a Ciência e Tecnologia (FCT), Harvard Medical School DuPont-Warren Fellowship, Portuguese national funds from FCT and Fundo Europeu de Desenvolvimento Regional, Child Neurology Foundation Shields Research, Sidney R. Baer, Jr. Foundation, Nancy Lurie Marks Foundation, Mather's Foundation, and the NIH.

SUBMITTER: Cotovio G

PROVIDER: S-EPMC7524493 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Mapping mania symptoms based on focal brain damage.

Cotovio Gonçalo G Talmasov Daniel D Barahona-Corrêa J Bernardo JB Hsu Joey J Senova Suhan S Ribeiro Ricardo R Soussand Louis L Velosa Ana A Silva Vera Cruz E VCE Rost Natalia N Wu Ona O Cohen Alexander L AL Oliveira-Maia Albino J AJ Fox Michael D MD

The Journal of clinical investigation 20201001 10

BACKGROUNDAlthough mania is characteristic of bipolar disorder, it can also occur following focal brain damage. Such cases may provide unique insight into brain regions responsible for mania symptoms and identify therapeutic targets.METHODSLesion locations associated with mania were identified using a systematic literature search (n = 41) and mapped onto a common brain atlas. The network of brain regions functionally connected to each lesion location was computed using normative human connectome ...[more]

PMID: 32831292

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Project description:A traditional and widely used approach for linking neurological symptoms to specific brain regions involves identifying overlap in lesion location across patients with similar symptoms, termed lesion mapping. This approach is powerful and broadly applicable, but has limitations when symptoms do not localize to a single region or stem from dysfunction in regions connected to the lesion site rather than the site itself. A newer approach sensitive to such network effects involves functional neuroimaging of patients, but this requires specialized brain scans beyond routine clinical data, making it less versatile and difficult to apply when symptoms are rare or transient. In this article we show that the traditional approach to lesion mapping can be expanded to incorporate network effects into symptom localization without the need for specialized neuroimaging of patients. Our approach involves three steps: (i) transferring the three-dimensional volume of a brain lesion onto a reference brain; (ii) assessing the intrinsic functional connectivity of the lesion volume with the rest of the brain using normative connectome data; and (iii) overlapping lesion-associated networks to identify regions common to a clinical syndrome. We first tested our approach in peduncular hallucinosis, a syndrome of visual hallucinations following subcortical lesions long hypothesized to be due to network effects on extrastriate visual cortex. While the lesions themselves were heterogeneously distributed with little overlap in lesion location, 22 of 23 lesions were negatively correlated with extrastriate visual cortex. This network overlap was specific compared to other subcortical lesions (P < 10(-5)) and relative to other cortical regions (P < 0.01). Next, we tested for generalizability of our technique by applying it to three additional lesion syndromes: central post-stroke pain, auditory hallucinosis, and subcortical aphasia. In each syndrome, heterogeneous lesions that themselves had little overlap showed significant network overlap in cortical areas previously implicated in symptom expression (P < 10(-4)). These results suggest that (i) heterogeneous lesions producing similar symptoms share functional connectivity to specific brain regions involved in symptom expression; and (ii) publically available human connectome data can be used to incorporate these network effects into traditional lesion mapping approaches. Because the current technique requires no specialized imaging of patients it may prove a versatile and broadly applicable approach for localizing neurological symptoms in the setting of brain lesions.

Project description:Background and objectivesQuantitative MRI (qMRI) permits the quantification of brain changes compatible with inflammation, degeneration and repair in multiple sclerosis (MS) patients. In this study, we propose a new method to provide personalized maps of tissue alterations and longitudinal brain changes based on different qMRI metrics, which provide complementary information about brain pathology.MethodsWe performed baseline and two-years follow-up on (i) 13 relapsing-remitting MS patients and (ii) four healthy controls. A group consisting of up to 65 healthy controls was used to compute the reference distribution of qMRI metrics in healthy tissue. All subjects underwent 3T MRI examinations including T1, T2, T2* relaxation and Magnetization Transfer Ratio (MTR) imaging. We used a recent partial volume estimation algorithm to estimate the concentration of different brain tissue types on T1 maps; then, we computed a deviation map (z-score map) for each contrast at both time-points. Finally, we subtracted those deviation maps only for voxels showing a significant difference with healthy tissue in one of the time points, to obtain a difference map for each subject.Results and conclusionControl subjects did not show any significant z-score deviations or longitudinal z-score changes. On the other hand, MS patients showed brain regions with cross-sectional and longitudinal concomitant increase in T1, T2, T2* z-scores and decrease of MTR z-scores, suggesting brain tissue degeneration/loss. In the lesion periphery, we observed areas with cross-sectional and longitudinal decreased T1/T2 and slight decrease in T2* most likely related to iron accumulation. Moreover, we measured longitudinal decrease in T1, T2 - and to a lesser extent in T2* - as well as a concomitant increase in MTR, suggesting remyelination/repair. In summary, we have developed a method that provides whole-brain personalized maps of cross-sectional and longitudinal changes in MS patients, which are computed in patient space. These maps may open new perspectives to complement and support radiological evaluation of brain damage for a given patient.

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Mapping mania symptoms based on focal brain damage.

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Mapping mania symptoms based on focal brain damage.

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