Estimating changing contexts in schizophrenia.

SEE STEPHAN ET AL DOI101093/AWW120 FOR A SCIENTIFIC COMMENTARY ON THIS WORK: Real world information is often abstract, dynamic and imprecise. Deciding if changes represent random fluctuations, or alterations in underlying contexts involve challenging probability estimations. Dysfunction may contribute to erroneous beliefs, such as delusions. Here we examined brain function during inferences about context change from noisy information. We examined cortical-subcortical circuitry engaging anterior and dorsolateral prefrontal cortex, and midbrain. We hypothesized that schizophrenia-related deficits in prefrontal function might overestimate context change probabilities, and that this more chaotic worldview may subsequently gain familiarity and be over-reinforced, with implications for delusions. We then examined these opposing information processing biases against less expected versus familiar information patterns in relation to genetic risk for schizophrenia in unaffected siblings. In one experiment, 17 patients with schizophrenia and 24 normal control subjects were presented in 3 T magnetic resonance imaging with numerical information varying noisily about a context integer, which occasionally shifted up or down. Subjects were to indicate when the inferred numerical context had changed. We fitted Bayesian models to estimate probabilities associated with change inferences. Dynamic causal models examined cortical-subcortical circuitry interactions at context change inference, and at subsequent reduced uncertainty. In a second experiment, genetic risk for schizophrenia associated with similar cortical-subcortical findings were explored in an independent sample of 36 normal control subjects and 35 unaffected siblings during processing of intuitive number sequences along the number line, or during the inverse, less familiar, sequence. In the first experiment, reduced Bayesian models fitting subject behaviour suggest that patients with schizophrenia overestimated context change probabilities. Here, patients engaged anterior prefrontal cortex relatively less than healthy controls, in part driven by reduced effective connectivity from dorsolateral prefrontal cortex to anterior prefrontal cortex. In processing subsequent information indicating reduced uncertainty of their predictions, patients engaged relatively increased mid-brain activation, driven in part by increased dorsolateral prefrontal cortex to midbrain connectivity. These dissociable reduced and exaggerated prefrontal and subcortical circuit functions were accentuated in patients with delusions. In the second experiment, analogous dissociable reduced anterior prefrontal cortex and exaggerated midbrain engagement occurred in unaffected siblings when processing less expected versus more familiar number sequences. In conclusion, patients overestimated ambiguous context change probabilities with relatively reduced anterior frontal engagement. Subsequent reduced uncertainty about contextual state appeared over-reinforced, potentially contributing to confirmation bias and a cascade of aberrant belief processing about a more chaotic world relevant to delusions. These opposing cortical-subcortical effects relate in part to genetic risk for schizophrenia, with analogous imbalances in neural processing of less expected versus familiar information patterns.

Morphometric differences in planum temporale in schizophrenia and bipolar disorder revealed by statistical analysis of labeled cortical depth maps.

Differences in cortical thickness in the lateral temporal lobe, including the planum temporale (PT), have been reported in MRI studies of schizophrenia (SCZ) and bipolar disorder (BPD) patients. Most of these studies have used a single-valued global or local measure for thickness. However, additional and complementary information can be obtained by generating labeled cortical distance maps (LCDMs), which are distances of labeled gray matter (GM) voxels from the nearest point on the GM/white matter (WM) (inner) cortical surface. Statistical analyses of pooled and censored LCDM distances reveal subtle differences in PT between SCZ and BPD groups from data generated by Ratnanather et al. (Schizophrenia Research, http://dx.doi.org/10.1016/j.schres.2013.08.014). These results confirm that the left planum temporale (LPT) is more sensitive than the right PT in distinguishing between SCZ, BPD, and healthy controls. Also confirmed is a strong gender effect, with a thicker PT seen in males than in females. The differences between groups at smaller distances in the LPT revealed by pooled and censored LCDM analysis suggest that SCZ and BPD have different effects on the cortical mantle close to the GM/WM surface. This is consistent with reported subtle changes in the cortical mantle observed in post-mortem studies.

The diffeomorphometry of temporal lobe structures in preclinical Alzheimer's disease.

This paper examines morphometry of MRI biomarkers derived from the network of temporal lobe structures including the amygdala, entorhinal cortex and hippocampus in subjects with preclinical Alzheimer's disease (AD). Based on template-centered population analysis, it is demonstrated that the structural markers of the amygdala, hippocampus and entorhinal cortex are statistically significantly different between controls and those with preclinical AD. Entorhinal cortex is the most strongly significant based on the linear effects model (p < .0001) for the high-dimensional vertex- and Laplacian-based markers corresponding to localized atrophy. The hippocampus also shows significant localized high-dimensional change (p < .0025) and the amygdala demonstrates more global change signaled by the strength of the low-dimensional volume markers. The analysis of the three structures also demonstrates that the volume measures are only weakly discriminating between preclinical and control groups, with the average atrophy rates of the volume of the entorhinal cortex higher than amygdala and hippocampus. The entorhinal cortex thickness also exhibits an atrophy rate nearly a factor of two higher in the ApoE4 positive group relative to the ApoE4 negative group providing weak discrimination between the two groups.

Morphometry of superior temporal gyrus and planum temporale in schizophrenia and psychotic bipolar disorder.

Structural abnormalities in temporal lobe, including the superior temporal gyrus (STG) and planum temporale (PT), have been reported in schizophrenia (SCZ) and bipolar disorder (BPD) patients. While most MRI studies have suggested gray matter volume and surface area reduction in temporal lobe regions, few have explored changes in laminar thickness in PT and STG in SCZ and BPD. ROI subvolumes of the STG from 94 subjects were used to yield gray matter volume, gray/white surface area and laminar thickness for STG and PT cortical regions. Morphometric analysis suggests that there may be gender and laterality effects on the size and shape of the PT in BPD (n=36) and SCZ (n=31) with reduced laterality in PT in subjects with SCZ but not in BPD. In addition, PT surface area was seen to be larger in males, and asymmetry in PT surface area was larger in BPD. Subjects with SCZ had reduced thickness and smaller asymmetry in PT volume. Thus, the PT probably plays a more sensitive role than the STG in structural abnormalities seen in SCZ.

An MRI study of amygdala in schizophrenia and psychotic bipolar disorder.

Meta-analyses report larger amygdala in subjects with bipolar disorder compared to schizophrenia. However, few studies have compared the size of amygdala in psychotic bipolar disorder with schizophrenia. Here we examine size of amygdala in a sample of 36 patients with psychotic bipolar disorder, 31 patients with schizophrenia and 27 healthy comparison subjects. Patients with schizophrenia had smaller amygdala compared with patients with psychotic bipolar disorder (p=0.014). These results suggest that change in volume of amygdala may represent a morphologic feature distinguishing psychotic bipolar disorder from schizophrenia.