Reorganization of brain connectivity across the spectrum of clinical cognitive decline.

Clinical cognitive decline, leading to Alzheimer's Disease Dementia (ADD), has long been interpreted as a disconnection syndrome, hindering the information flow capacity of the brain, hence leading to the well-known symptoms of ADD. The structural and functional brain connectome analyses play a central role in studies of brain from this perspective. However, most current research implicitly assumes that the changes accompanying the progression of cognitive decline are monotonous in time, whether measured across the entire brain or in fixed cortical regions. We investigate the structural and functional connectivity-wise reorganization of the brain without such assumptions across the entire spectrum. We utilize nodal assortativity as a local topological measure of connectivity and follow a data-centric approach to identify and verify relevant local regions, as well as to understand the nature of underlying reorganization. The analysis of our preliminary experimental data points to statistically significant, hyper and hypo-assortativity regions that depend on the disease's stage, and differ for structural and functional connectomes. Our results suggest a new perspective into the dynamic, potentially a mix of degenerative and compensatory, topological alterations that occur in the brain as cognitive decline progresses.

Changes in Brain Structure and Function in a Multisport Cohort of Retired Female and Male Athletes, Many Years after Suffering a Concussion: Implications for Neuroplasticity and Neurodegenerative Disease Pathogenesis.

Background: Cumulative effects of traumatic brain injury is of increasing concern, especially with respect to its role in the etiology and pathogenesis of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Objective: Compare regional brain volume and connectivity between athletes with a history of concussion and controls. Methods: We evaluated whole-brain volumetric effects with Bayesian regression models and functional connectivity with network-based statistics, in 125 retired athletes (a mean of 11 reported concussions) and 36 matched controls. Results: Brain regions significantly lower in volume in the concussed group included the middle frontal gyrus, hippocampus, supramarginal gyrus, temporal pole, and inferior frontal gyrus. Conversely, brain regions significantly larger included the hippocampal and collateral sulcus, middle occipital gyrus, medial orbital gyrus, caudate nucleus, lateral orbital gyrus, and medial postcentral gyrus. Functional connectivity analyses revealed increased edge strength, most marked in motor domains. Numerous edges of this network strengthened in athletes were significantly weakened with concussion. Aligned to meta-analytic neuroimaging data, the observed changes suggest functional enhancement within the motor, sensory, coordination, balance, and visual processing domains in athletes, attenuated by concussive head injury with a negative impact on memory and language. Conclusions: These findings suggest that engagement in sport may benefit the brain across numerous domains, but also highlights the potentially damaging effects of concussive head injury. Future studies with longitudinal cohorts including autopsy examination are needed to determine whether the latter reflects tissue loss from brain shearing, or the onset of a progressive Alzheimer's disease like proteinopathy.

Sex differences in the pleiotropy of hearing difficulty with imaging-derived phenotypes: a brain-wide investigation.

Hearing difficulty (HD) is one of the major health burdens in older adults. While aging-related changes in the peripheral auditory system play an important role, genetic variation associated with brain structure and function could also be involved in HD predisposition. We analyzed a large-scale HD genome-wide association study (GWAS; Ntotal = 501,825, 56% females) and GWAS data related to 3,935 brain imaging-derived phenotypes (IDPs) assessed in up to 33,224 individuals (52% females) using multiple magnetic resonance imaging modalities. To investigate HD pleiotropy with brain structure and function, we conducted genetic correlation, latent causal variable, Mendelian randomization, and multivariable generalized linear regression analyses. Additionally, we performed local genetic correlation and multi-trait colocalization analyses to identify genomic regions and loci implicated in the pleiotropic mechanisms shared between HD and brain IDPs. We observed a widespread genetic correlation of HD with 120 IDPs in females, 89 IDPs in males, and 171 IDPs in the sex-combined analysis. The latent causal variable analysis showed that some of these genetic correlations could be due to cause-effect relationships. For seven correlations, the causal effects were also confirmed by the Mendelian randomization approach: vessel volume→HD in the sex-combined analysis; hippocampus volume→HD, cerebellum grey matter volume→HD, primary visual cortex volume→HD, and HD→fluctuation amplitudes of node 46 in resting-state functional MRI dimensionality 100 in females; global mean thickness→HD and HD→mean orientation dispersion index in superior corona radiata in males. The local genetic correlation analysis identified 13 pleiotropic regions between HD and these seven IDPs. We also observed a colocalization signal for the rs13026575 variant between HD, primary visual cortex volume, and SPTBN1 transcriptomic regulation in females. Brain structure and function may have a role in the sex differences in HD predisposition via possible cause-effect relationships and shared regulatory mechanisms.

Brain Structural and Functional Damage Network Localization of Suicide.

BACKGROUND: Extensive neuroimaging research on brain structural and functional correlates of suicide has produced inconsistent results. Despite increasing recognition that damage in multiple different brain locations that causes the same symptom can map to a common brain network, there is still a paucity of research investigating network localization of suicide. METHODS: To clarify this issue, we initially identified brain structural and functional damage locations in relation to suicide from 63 published studies with 2135 suicidal and 2606 nonsuicidal individuals. By applying novel functional connectivity network mapping to large-scale discovery and validation resting-state functional magnetic resonance imaging datasets, we mapped these affected brain locations to 3 suicide brain damage networks corresponding to different imaging modalities. RESULTS: The suicide gray matter volume damage network comprised widely distributed brain areas primarily involving the dorsal default mode, basal ganglia, and anterior salience networks. The suicide task-induced activation damage network was similar to but less extensive than the gray matter volume damage network, predominantly implicating the same canonical networks. The suicide resting-state activity damage network manifested as a localized set of brain regions encompassing the orbitofrontal cortex and middle cingulate cortex. CONCLUSIONS: Our findings not only may help reconcile prior heterogeneous neuroimaging results, but also may provide insights into the neurobiological mechanisms of suicide from a network perspective, which may ultimately inform more targeted and effective strategies to prevent suicide.

Pleiotropic action of genetic variation rs1344706 in ZNF804A on brain structure and function in pa-tients with schizophrenia / 中华行为医学与脑科学杂志

Objective To explore the association between the ZNF804A gene genetic variation poly-morphism rs1344706 and brain structure and function in patients with schizophrenia. Methods Literature search was conducted in Pubmed and other databases,the processes were performed in strict accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines,then the Comprehensive Meta-Analysis software was used for meta-analysis. Results Schizophrenia patients with rs1344706 risk al-lele had lager gray matter in the amount of brain regions including frontal lobe (z＝3.445,P＝0.001),tempo-ral lobe (z＝2.140,P＝0.032) and other brain regions; healthy controls with the risk allele had smaller gray matter and regional activity in the frontal lobe ( gray matter: z＝－2.008, P＝0.045, regional activity: z＝－4.036,P＜0.01) and other regions. Sensitivity analysis was stable,but publication bias existed in a few ana-lyses of indexes. Conclusion The risk allele in ZNF804A gene rs1344706 has positive effects on the brain structure in patients with schizophrenia,but negative effects on the brain structure and function in the healthy individuals.