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Functional connectome alterations, including modular network organization, have been related to the experience of hallucinations. It remains to be determined whether individuals with hallucinations across the psychosis continuum exhibit similar alterations in modular brain network organization. This study assessed functional connectivity matrices of 465 individuals with and without hallucinations, including patients with schizophrenia and bipolar disorder, nonclinical individuals with hallucinations, and healthy controls. Modular brain network organization was examined at different scales of network resolution, including (1) global modularity measured as Qmax and Normalised Mutual Information (NMI) scores, and (2) within- and between-module connectivity. Global modular organization was not significantly altered across groups. However, alterations in within- and between-module connectivity were observed for higher-order cognitive (e.g., central-executive salience, memory, default mode), and sensory modules in patients with schizophrenia and nonclinical individuals with hallucinations relative to controls. Dissimilar patterns of altered within- and between-module connectivity were found bipolar disorder patients with hallucinations relative to controls, including the visual, default mode, and memory network, while connectivity patterns between visual, salience, and cognitive control modules were unaltered. Bipolar disorder patients without hallucinations did not show significant alterations relative to controls. This study provides evidence for alterations in the modular organization of the functional connectome in individuals prone to hallucinations, with schizophrenia patients and nonclinical individuals showing similar alterations in sensory and higher-order cognitive modules. Other higher-order cognitive modules were found to relate to hallucinations in bipolar disorder patients, suggesting differential neural mechanisms may underlie hallucinations across the psychosis continuum.

Cerebral white matter (WM) aberrations in schizophrenia have been linked to multiple neurobiological substrates but the underlying mechanisms remain unknown. Moreover, antipsychotic treatment and substance use constitute potential confounders. Multimodal studies using diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI) may provide deeper insight into the whole brain WM pathophysiology in schizophrenia. We combined DTI and MTI to investigate WM integrity in 51 antipsychotic-naïve, first-episode schizophrenia patients and 55 matched healthy controls, using 3 T magnetic resonance imaging (MRI). Psychopathology was assessed with the positive and negative syndrome scale (PANSS). A whole brain partial least squares correlation (PLSC) method was used to conjointly analyze DTI-derived measures (fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), mode of anisotropy (MO)) and the magnetization transfer ratio (MTR) to identify group differences, and associations with psychopathology. In secondary analyses, we excluded recreational substance users from both groups resulting in 34 patients and 51 healthy controls. The primary PLSC group difference analysis identified a significant pattern of lower FA, AD, MO and higher RD in patients (p = 0.04). This pattern suggests disorganized WM microstructure in patients. The secondary PLSC group difference analysis without recreational substance users revealed a significant pattern of lower FA and higher AD, RD, MO, MTR in patients (p = 0.04). This pattern in the substance free patients is consistent with higher extracellular free-water concentrations, which may reflect neuroinflammation. No significant associations with psychopathology were observed. Recreational substance use appears to be a confounding issue, which calls for attention in future WM studies.

Electroconvulsive therapy (ECT) is the most effective treatment for depression, yet its working mechanism remains unclear. In the animal analog of ECT, neurogenesis in the dentate gyrus (DG) of the hippocampus is observed. In humans, volume increase of the hippocampus has been reported, but accurately measuring the volume of subfields is limited with common MRI protocols. If the volume increase of the hippocampus in humans is attributable to neurogenesis, it is expected to be exclusively present in the DG, whereas other processes (angiogenesis, synaptogenesis) also affect other subfields. Therefore, we acquired an optimized MRI scan at 7-tesla field strength allowing sensitive investigation of hippocampal subfields. A further increase in sensitivity of the within-subjects measurements is gained by automatic placement of the field of view. Patients receive two MRI scans: at baseline and after ten bilateral ECT sessions (corresponding to a 5-week interval). Matched controls are also scanned twice, with a similar 5-week interval. A total of 31 participants (23 patients, 8 controls) completed the study. A large and significant increase in DG volume was observed after ECT (M = 75.44 mm

Schizophrenia is characterized by loss of brain volume, which may represent an ongoing pathophysiological process. This loss of brain volume may be explained by reduced neuropil rather than neuronal loss, suggesting abnormal synaptic plasticity and cortical microcircuitry. A possible mechanism is hypofunction of the NMDA-type of glutamate receptor, which reduces the excitation of inhibitory GABAergic interneurons, resulting in a disinhibition of glutamatergic pyramidal neurons. Disinhibition of pyramidal cells may result in excessive stimulation by glutamate, which in turn could cause neuronal damage or death through excitotoxicity. In this study, GABA/creatine ratios, and glutamate, NAA, creatine and choline concentrations in the prefrontal and parieto-occipital cortices were measured in 17 patients with schizophrenia and 23 healthy controls using proton magnetic resonance spectroscopy at an ultra-high magnetic field strength of 7 T. Significantly lower GABA/Cr ratios were found in patients with schizophrenia in the prefrontal cortex as compared to healthy controls, with GABA/Cr ratios inversely correlated with cognitive functioning in the patients. No significant change in the GABA/Cr ratio was found between patients and controls in the parieto-occipital cortex, nor were levels of glutamate, NAA, creatine, and choline differed in patients and controls in the prefrontal and parieto-occipital cortices. Our findings support a mechanism involving altered GABA levels distinguished from glutamate levels in the medial prefrontal cortex in schizophrenia, particularly in high functioning patients. A (compensatory) role for GABA through altered inhibitory neurotransmission in the prefrontal cortex may be ongoing in (higher functioning) patients with schizophrenia., Highlights • GABA and glutamate were measured in schizophrenia patients and healthy controls using 1H-MRS at 7 T. • Patients showed significantly lower prefrontal GABA levels, and no changes were found for glutamate. • Prefrontal GABA levels were inversely correlated with total IQ in patients. • This suggests a mechanism involving GABA distinguished from glutamate in the prefrontal cortex. • GABA may have a compensatory role in the prefrontal cortex in (higher functioning) patients.

It has been shown that brain volume and general intellectual ability are to a significant extent influenced by the same genetic factors. Several cortical regions of the brain also show a genetic correlation with intellectual ability, demonstrating that intellectual functioning is probably represented in a heritable distributed network of cortical regions throughout the brain. This study is the first to investigate a genetic association between subcortical volumes and intellectual ability, taking into account the thalamus, caudate nucleus, putamen, globus pallidus, hippocampus, amygdala, and nucleus accumbens using an extended twin design. Genetic modeling was performed on a healthy adult twin sample consisting of 106 twin pairs and 30 of their siblings, IQ data was obtained from 132 subjects. Our results demonstrate that of all subcortical volumes measured, only thalamus volume is significantly correlated with intellectual functioning. Importantly, the association found between thalamus volume and intellectual ability is significantly influenced by a common genetic factor. This genetic factor is also implicated in cerebral brain volume. The thalamus, with its widespread cortical connections, may thus play a key role in human intelligence. Hum Brain Mapp 35:2632–2642, 2014. © 2013 Wiley Periodicals, Inc.