RESUMEN
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.
RESUMEN
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.