Subcortical structures, which include the basal ganglia and parts of the limbic system, have key roles in learning, motor control and emotion, but also contribute to higher-order executive functions. Prior studies have reported volumetric alterations in subcortical regions in schizophrenia. Reported results have sometimes been heterogeneous, and few large-scale investigations have been conducted. Moreover, few large-scale studies have assessed asymmetries of subcortical volumes in schizophrenia. Here, as a work completely independent of a study performed by the ENIGMA consortium, we conducted a large-scale multisite study of subcortical volumetric differences between patients with schizophrenia and controls. We also explored the laterality of subcortical regions to identify characteristic similarities and differences between them. T1-weighted images from 1680 healthy individuals and 884 patients with schizophrenia, obtained with 15 imaging protocols at 11 sites, were processed with FreeSurfer. Group differences were calculated for each protocol and meta-analyzed. Compared with controls, patients with schizophrenia demonstrated smaller bilateral hippocampus, amygdala, thalamus and accumbens volumes as well as intracranial volume, but larger bilateral caudate, putamen, pallidum and lateral ventricle volumes. We replicated the rank order of effect sizes for subcortical volumetric changes in schizophrenia reported by the ENIGMA consortium. Further, we revealed leftward asymmetry for thalamus, lateral ventricle, caudate and putamen volumes, and rightward asymmetry for amygdala and hippocampal volumes in both controls and patients with schizophrenia. Also, we demonstrated a schizophrenia-specific leftward asymmetry for pallidum volume. These findings suggest the possibility of aberrant laterality in neural pathways and connectivity patterns related to the pallidum in schizophrenia.
Because awareness of emotional states in the self is a prerequisite to recognizing such states in others, alexithymia (ALEX), difficulty in identifying and expressing one's own emotional states, should involve impairment in empathy. Using functional magnetic resonance imaging (fMRI), we compared an ALEX group (n = 16) and a non-alexithymia (non-ALEX) group (n = 14) for their regional hemodynamic responses to the visual perception of pictures depicting human hands and feet in painful situations. Subjective pain ratings of the pictures and empathy-related psychological scores were also compared between the 2 groups. The ALEX group showed less cerebral activation in the left dorsolateral prefrontal cortex (DLPFC), the dorsal pons, the cerebellum, and the left caudal anterior cingulate cortex (ACC) within the pain matrix. The ALEX group showed greater activation in the right insula and inferior frontal gyrus. Furthermore, alexithymic participants scored lower on the pain ratings and on the scores related to mature empathy. In conclusion, the hypofunction in the DLPFC, brain stem, cerebellum, and ACC and the lower pain-rating and empathy-related scores in ALEX are related to cognitive impairments, particularly executive and regulatory aspects, of emotional processing and support the importance of self-awareness in empathy.
Impulsivity is a personality trait exhibited by healthy individuals, but excessive impulsivity is associated with some mental disorders. Lesion and functional neuroimaging studies indicate that the ventromedial prefrontal region (VMPFC), including the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC) and medial prefrontal cortex, and the amygdala may modulate impulsivity and aggression. However, no morphometric study has examined the association between VMPFC and impulsivity. We hypothesized that healthy subjects with high impulsivity would have smaller volumes in these brain regions compared with those with low impulsivity. Sixty-two healthy subjects were studied (age 35.4 +/- 12.1 years) using a 1.5-T MRI system. The Barratt impulsiveness scale (BIS) was used to assess impulsivity. Images were processed using an optimized voxel-based morphometry (VBM) protocol. We calculated the correlations between BIS scale scores and the gray matter (GM) and white matter (WM) volumes of VMPFC and amygdala. GM volumes of the left and right OFC were inversely correlated with the BIS total score (P = 0.04 and 0.02, respectively). Left ACC GM volumes had a tendency to be inversely correlated with the BIS total score (P = 0.05). Right OFC GM volumes were inversely correlated with BIS nonplanning impulsivity, and left OFC GM volumes were inversely correlated with motor impulsivity. There were no significant WM volume correlations with impulsivity. The results of this morphometry study indicate that small OFC volume relate to high impulsivity and extend the prior finding that the VMPFC is involved in the circuit modulating impulsivity.
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