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The brain regions responsible for hallucinations remain unclear. We studied 89 brain lesions causing hallucinations using a recently validated technique termed lesion network mapping. We found that hallucinations occurred following lesions to a variety of different brain regions, but these lesion locations fell within a single functionally connected brain network. This network was defined by connectivity to the cerebellar vermis, inferior cerebellum (bilateral lobule X), and the right superior temporal sulcus. Within this single hallucination network, additional connections with the lesion location dictated the sensory modality of the hallucination: lesions causing visual hallucinations were connected to the lateral geniculate nucleus in the thalamus while lesions causing auditory hallucinations were connected to the dentate nucleus in the cerebellum. Our results suggest that lesions causing hallucinations localize to a single common brain network, but additional connections within this network dictate the sensory modality, lending insight into the causal neuroanatomical substrate of hallucinations.

Psychiatric disorders share neurobiology and frequently co-occur. This neurobiological and clinical overlap highlights opportunities for transdiagnostic treatments. In this study, we used coordinate and lesion network mapping to test for a shared brain network across psychiatric disorders. In our meta-analysis of 193 studies, atrophy coordinates across six psychiatric disorders mapped to a common brain network defined by positive connectivity to anterior cingulate and insula, and by negative connectivity to posterior parietal and lateral occipital cortex. This network was robust to leave-one-diagnosis-out cross-validation and specific to atrophy coordinates from psychiatric versus neurodegenerative disorders (72 studies). In 194 patients with penetrating head trauma, lesion damage to this network correlated with the number of post-lesion psychiatric diagnoses. Neurosurgical ablation targets for psychiatric illness (four targets) also aligned with the network. This convergent brain network for psychiatric illness may partially explain high rates of psychiatric comorbidity and could highlight neuromodulation targets for patients with more than one psychiatric disorder. The authors use morphometric and brain lesion data to identify a convergent brain network shared by psychiatric disorders.

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.

Background We hypothesized that TSPO PET, which measures microglia density, would be elevated in the presence of amyloid and impairment across different clinical variants in a pattern that follows their characteristic tau distribution. Method Participants (n = 17 amyloid‐negative control, 3 amyloid‐positive AD, 2 amyloid‐positive PCA, 6 amyloid‐negative with impairment (1 aMCI, 1 MCI, 3 AD, 1 LATE); age = 69±7, 43% women) from the Longitudinal Imaging of Microglial Activation in Different Clinical Variants of Alzheimer’s Disease study underwent amyloid PET (Florbetaben), tau PET (MK6240), and TSPO PET (ER176). Amyloid positivity was determined by visual read. Clinical groups were determined at ADRC consensus. Partial volume corrected TSPO and tau SUVR was compared across amyloid positivity and clinical variants (amyloid‐negative controls as reference group). Result The amyloid‐positive AD group had elevated TSPO in amygdala (0.34, p = 0.01), prefrontal cortex (0.31, p = 0.0004), middle inferior temporal gyrus (0.29, p = 0.0003), inferior parietal lobe (0.28, p = 0.001), superior temporal lobe (0.23, p = 0.001), cingulate gyrus (0.19, p = 0.01), superior parietal lobe (0.19, 0.04), insula (0.14, p = 0.02), and lingual gyrus (0.13, p = 0.02), while the amyloid‐positive PCA group had elevated TSPO in amygdala (0.50, p = 0.001), superior parietal lobe (0.38, p = 0.04), inferior parietal lobe (0.29, p = 0.001), middle inferior temporal gyrus (0.20, p = 0.0003), prefrontal cortex (0.15, p = 0.0004), superior temporal lobe (0.14, p = 0.001), cingulate gyrus (0.13, p = 0.01), and insula (0.06, p = 0.02). The impaired amyloid‐negative group had elevated TPSO in the amygdala (0.31, p = 0.04), fusiform gyrus (0.15, p = 0.05), cingulate gyrus (0.14, p = 0.02), middle inferior temporal gyrus (0.12, p = 0.02), superior temporal lobe (0.12, p = 0.02), prefrontal cortex (0.12, p = 0.02), and inferior parietal lobe (0.11, p = 0.02). These elevations in TSPO spatially coincide with elevations in tau burden (Figure 1). Conclusion Microglia may respond to amyloid pathology and follow a spatial pattern similar to that of tau pathology for a given clinical variant. Interestingly, microglia were elevated to the greatest extent in key limbic regions for amyloid‐negative impaired participants. Non‐AD pathologies may be driving this limbic neuroinflammation or limbic neuroinflammation itself may be sufficient for clinical impairment in the context of low amyloid and tau burden.

BACKGROUND. Although 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. METHODS. Lesion 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. RESULTS. Lesion 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. CONCLUSION. Brain 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. FUNDING. Fundaçâo para a Ciencia e Tecnología (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.