Resting-state functional connectivity correlates of brain structural aging in schizophrenia.

A large body of research has shown that schizophrenia patients demonstrate increased brain structural aging. Although this process may be coupled with aberrant changes in intrinsic functional architecture of the brain, they remain understudied. We hypothesized that there are brain regions whose whole-brain functional connectivity at rest is differently associated with brain structural aging in schizophrenia patients compared to healthy controls. Eighty-four male schizophrenia patients and eighty-six male healthy controls underwent structural MRI and resting-state fMRI. The brain-predicted age difference (b-PAD) was a measure of brain structural aging. Resting-state fMRI was applied to obtain global correlation (GCOR) maps comprising voxelwise values of the strength and sign of functional connectivity of a given voxel with the rest of the brain. Schizophrenia patients had higher b-PAD compared to controls (mean between-group difference + 2.9 years). Greater b-PAD in schizophrenia patients, compared to controls, was associated with lower whole-brain functional connectivity of a region in frontal orbital cortex, inferior frontal gyrus, Heschl's Gyrus, plana temporale and polare, insula, and opercular cortices of the right hemisphere (rFTI). According to post hoc seed-based correlation analysis, decrease of functional connectivity with the posterior cingulate gyrus, left superior temporal cortices, as well as right angular gyrus/superior lateral occipital cortex has mainly driven the results. Lower functional connectivity of the rFTI was related to worse verbal working memory and language production. Our findings demonstrate that well-established frontotemporal functional abnormalities in schizophrenia are related to increased brain structural aging.

Executive control of language in schizophrenia patients with history of auditory verbal hallucinations: A neuropsychological and resting-state fMRI study.

BACKGROUND: As demonstrated by a plethora of studies, compromised executive functions (EF) and language are implicated in mechanisms of auditory verbal hallucinations (AVH), but the contribution of their interaction to AVH remains unclear. We hypothesized that schizophrenia patients with history of AVH (AVHh+) vs. without history of AVH (AVHh-) have a specific deficit of executive control of language and alterations in functional connectivity (FC) between the brain regions involved in EF and language, and these neuropsychological and neurophysiological traits are associated with each other. METHODS: To explore the executive control of language and its contribution to AVH, we used an integrative approach involving analysis of neuropsychological and resting-state fMRI data of 34 AVHh+, 16 AVHh-, and 40 healthy controls. We identified the neuropsychological and FC measures that differentiated between AVHh+, AVHh-, and HC, and tested the associations between them. RESULTS: AVHh+ were characterized by decreased category and phonological verbal fluency, utterance length, productivity in the planning tasks, and poorer retelling. AVHh+ had decreased FC between the left inferior frontal gyrus and the anterior cingulate cortex. Productivity in category verbal fluency was associated with the FC between these regions. CONCLUSIONS: Poor executive control of word retrieval and deficient programming of sentence and narrative related to more general deficits of planning may be the neuropsychological traits specific for AVHh+. A neurophysiological trait specific for AVHh+ may be a decreased FC between regions involved in language production and differentiation between alien- vs. self-generated speech and between language production vs. comprehension.

Systematic Review and Meta-analysis of Language Symptoms due to Cerebellar Injury.

To date, cerebellar contribution to language is well established via clinical and neuroimaging studies. However, the particular functional role of the cerebellum in language remains to be clarified. In this study, we present the first systematic review of the diverse language symptoms in spoken language after cerebellar lesion that were reported in case studies for the last 30 years (18 clinical cases from 13 papers), and meta-analysis using cluster analysis with bootstrap and symptom co-occurrence analysis. Seven clusters of patients with similar language symptoms after cerebellar lesions were found. Co-occurrence analysis revealed pairs of symptoms that tend to be comorbid. Our results imply that the "linguistic cerebellum" has a multiform contribution to language function. The most possible mechanism of such contribution is the cerebellar reciprocal connectivity with supratentorial brain regions, where the cerebellar level of the language network has a general modulation function and the supratentorial level is more functionally specified. Based on cerebellar connectivity with supratentorial components of the language network, the "linguistic cerebellum" might be further functionally segregated.

Functional connectivity of the dorsolateral prefrontal cortex contributes to different components of executive functions.

OBJECTIVE: The dorsolateral prefrontal cortex (DLPFC) orchestrates other brain regions and plays a vital role for "the most uniquely human" executive functions (EFs), which are divided into distinct components. Components of EFs have been localized to different brain regions and at the same time the DLPFC was found to be involved in a majority of EF components. The possible mechanism of the DLPFC's contribution to EF components might be found in DLPFC functional connectivity (FC): this FC of the DLPFC with other brain regions contributes to different EF components. METHOD: To explore the DLPFC FC contribution to different EFs, we used an integrative approach involving analysis of fMRI and neuropsychological assessment of EFs. Fifty healthy adults (27 females and 23 males, mean age 34.5 ± 16.6 years) underwent neuropsychological assessment of EFs as well as task-based and resting-state fMRI. Task-based fMRI was applied as a functional localizer for individually defined DLPFC ROIs that were further used for the FC seed-based correlation analysis of the resting-state data. Then we looked for associations between individual scores of different EF components and the whole-brain resting-state FC of the DLPFC. RESULTS: Resting-state correlates of DLPFC FC were revealed for three out of the seven EF components derived from an extensive neuropsychological assessment: inhibition, switching, and the verbal EF component. CONCLUSIONS: Our study is the first to reveal the contribution of the DLPFC FC to several distinct EF components. The obtained results give insight into the brain mechanisms of EFs.