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Brain stimulation and brain lesions converge on common causal circuits in neuropsychiatric disease.

ABSTRACT: Damage to specific brain circuits can cause specific neuropsychiatric symptoms. Therapeutic stimulation to these same circuits may modulate these symptoms. To determine whether these circuits converge, we studied depression severity after brain lesions (n = 461, five datasets), transcranial magnetic stimulation (n = 151, four datasets) and deep brain stimulation (n = 101, five datasets). Lesions and stimulation sites most associated with depression severity were connected to a similar brain circuit across all 14 datasets (P < 0.001). Circuits derived from lesions, deep brain stimulation and transcranial magnetic stimulation were similar (P < 0.0005), as were circuits derived from patients with major depression versus other diagnoses (P < 0.001). Connectivity to this circuit predicted out-of-sample antidepressant efficacy of transcranial magnetic stimulation and deep brain stimulation sites (P < 0.0001). In an independent analysis, 29 lesions and 95 stimulation sites converged on a distinct circuit for motor symptoms of Parkinson's disease (P < 0.05). We conclude that lesions, transcranial magnetic stimulation and DBS converge on common brain circuitry that may represent improved neurostimulation targets for depression and other disorders.

SUBMITTER: Siddiqi SH

PROVIDER: S-EPMC8688172 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Brain stimulation and brain lesions converge on common causal circuits in neuropsychiatric disease.

Siddiqi Shan H SH Schaper Frederic L W V J FLWVJ Horn Andreas A Hsu Joey J Padmanabhan Jaya L JL Brodtmann Amy A Cash Robin F H RFH Corbetta Maurizio M Choi Ki Sueng KS Dougherty Darin D DD Egorova Natalia N Fitzgerald Paul B PB George Mark S MS Gozzi Sophia A SA Irmen Frederike F Kuhn Andrea A AA Johnson Kevin A KA Naidech Andrew M AM Pascual-Leone Alvaro A Phan Thanh G TG Rouhl Rob P W RPW Taylor Stephan F SF Voss Joel L JL Zalesky Andrew A Grafman Jordan H JH Mayberg Helen S HS Fox Michael D MD

Nature human behaviour 20210708 12

Damage to specific brain circuits can cause specific neuropsychiatric symptoms. Therapeutic stimulation to these same circuits may modulate these symptoms. To determine whether these circuits converge, we studied depression severity after brain lesions (n = 461, five datasets), transcranial magnetic stimulation (n = 151, four datasets) and deep brain stimulation (n = 101, five datasets). Lesions and stimulation sites most associated with depression severity were connected to a similar brain circ ...[more]

PMID: 34239076

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Project description:Deep brain stimulation of the subthalamic nucleus for Parkinson's disease is an established advanced therapy that addresses motor symptoms and improves quality of life. However, it has also been associated with neuropsychiatric symptoms such as impulsivity and hypomania. When significant, these symptoms can be distressing, necessitating psychiatric intervention. However, a comprehensive analysis of neurocognitive and neuropsychiatric outcomes with reference to the site of subthalamic stimulation has not been undertaken. We examined this matter in a consecutive sample of 64 persons with Parkinson's disease undertaking subthalamic deep brain stimulation. Participants were assessed with a battery of neuropsychiatric instruments at baseline and at repeated postoperative intervals. A psychiatrist identified patients with emergent, clinically-significant symptoms due to stimulation. The site of the active electrode contact and a simulated volume of activated tissue were evaluated with reference to putative limbic, associative and motor subregions of the subthalamic nucleus. We studied anatomical correlates of longitudinal neuropsychiatric change and delineated specific subthalamic regions associated with neuropsychiatric impairment. We tested the ability of these data to predict clinically-significant symptoms. Subthalamic stimulation within the right associative subregion was associated with inhibitory errors on the Excluded Letter Fluency task at 6-weeks (p = 0.023) and 13-weeks postoperatively (p = 0.0017). A cluster of subthalamic voxels associated with inhibitory errors was identified in the right associative and motor subregions. At 6-weeks, clinically-significant neuropsychiatric symptoms were associated with the distance of the active contact to the right associative subregion (p = 0.0026) and stimulation within the right associative subregion (p = 0.0009). At 13-weeks, clinically-significant symptoms were associated with the distance to the right (p = 0.0027) and left (p = 0.0084) associative subregions and stimulation within the right associative subregion (p = 0.0026). Discrete clusters of subthalamic voxels associated with high and low likelihood of postoperative neuropsychiatric symptoms were identified in ventromedial and dorsolateral zones, respectively. When a classifier was trained on these data, clinically-significant symptoms were predicted with an accuracy of 79%. These data underscore the importance of accurate electrode targeting, contact selection and device programming to reduce postoperative neuropsychiatric impairment. The ability to predict neuropsychiatric symptoms based on subthalamic data may permit anticipation and prevention of these occurrences, improving safety and tolerability.

Project description:Abstract Vertigo is a common neurological complaint, which can result in significant morbidity and decreased quality of life. While pathology to peripheral and subtentorial brain structures is a well-established cause of vertigo, cortical lesions have also been linked to vertigo and may lend insight into relevant neuroanatomy. Here, we investigate the supratentorial lesion locations associated with vertigo and test whether they map to a common brain network. We performed a systematic literature search and identified 23 cases of supratentorial brain lesions associated with vertigo. We mapped the lesion locations to a standard brain template and computed the network of brain regions functionally connected to each lesion location, using a ‘wiring diagram’ of the human brain termed the human connectome (n = 1000). Sensitivity was assessed by identifying the most common connection to lesion locations associated with vertigo, and specificity was assessed through comparison with control lesions associated with symptoms other than vertigo (n = 68). We found that functional connectivity between lesion locations and the bilateral ventral posterior insula was both sensitive (22/23 lesions) and specific (voxel-wise family-wise error-corrected P < 0.05) for lesion-induced vertigo. We computed connectivity with this hub region to define a lesion-based vertigo network, which included regions in the bilateral insula, somatosensory cortex, higher-level visual areas, cingulate sulcus, thalamus and multiple cerebellar regions in the territory of the posterior inferior cerebellar artery. Next, we used stereo-electroencephalography (80 stimulation sites across 17 patients) to test whether stimulation sites associated with vertigo mapped to this same network. We found that 36/42 (86%) of stimulation sites eliciting vertigo fell within the lesion-based vertigo network in contrast to 16/39 (41%) of stimulation sites that did not elicit vertigo. Connectivity between stimulation sites and our lesion-based hub in the ventral posterior insula was also significantly associated with vertigo (P < 0.0001). We conclude that cortical lesions and direct electrical stimulation sites associated with vertigo map to a common brain network, offering insights into the causal neuroanatomical substrate of vertigo. Vertigo is a common neurological complaint, affecting almost all people at some point during their life span. Li et al. showed a cortical vertigo network derived from brain lesions and the intracranial direct electrical stimulation sites, which offers new insights into the neuroanatomical substrate of vertigo. Graphical Abstract Graphical Abstract

Project description:Cervical dystonia is a neurological disorder characterized by sustained, involuntary movements of the head and neck. Most cases of cervical dystonia are idiopathic, with no obvious cause, yet some cases are acquired, secondary to focal brain lesions. These latter cases are valuable as they establish a causal link between neuroanatomy and resultant symptoms, lending insight into the brain regions causing cervical dystonia and possible treatment targets. However, lesions causing cervical dystonia can occur in multiple different brain locations, leaving localization unclear. Here, we use a technique termed 'lesion network mapping', which uses connectome data from a large cohort of healthy subjects (resting state functional MRI, n = 1000) to test whether lesion locations causing cervical dystonia map to a common brain network. We then test whether this network, derived from brain lesions, is abnormal in patients with idiopathic cervical dystonia (n = 39) versus matched controls (n = 37). A systematic literature search identified 25 cases of lesion-induced cervical dystonia. Lesion locations were heterogeneous, with lesions scattered throughout the cerebellum, brainstem, and basal ganglia. However, these heterogeneous lesion locations were all part of a single functionally connected brain network. Positive connectivity to the cerebellum and negative connectivity to the somatosensory cortex were specific markers for cervical dystonia compared to lesions causing other neurological symptoms. Connectivity with these two regions defined a single brain network that encompassed the heterogeneous lesion locations causing cervical dystonia. These cerebellar and somatosensory regions also showed abnormal connectivity in patients with idiopathic cervical dystonia. Finally, the most effective deep brain stimulation sites for treating dystonia were connected to these same cerebellar and somatosensory regions identified using lesion network mapping. These results lend insight into the causal neuroanatomical substrate of cervical dystonia, demonstrate convergence across idiopathic and acquired dystonia, and identify a network target for dystonia treatment.

Dataset Information

Brain stimulation and brain lesions converge on common causal circuits in neuropsychiatric disease.

Publications

Brain stimulation and brain lesions converge on common causal circuits in neuropsychiatric disease.

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