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The pulvinar and the mediodorsal (MDN) nuclei of the thalamus are higher order nuclei which have been implicated in directed effort and corollary discharge systems. We used seed-based resting fMRI to examine functional connectivity to bilateral pulvinar and MDN in 24 schizophrenic patients (SZ), 24 major depressive disorder patients (MDD), and 24 age-matched healthy controls. SZ had less connectivity than controls between the left pulvinar and precuneus, left ventral-lateral prefrontal cortex (vlPFC), and superior and medial-frontal regions, between the right pulvinar and right frontal pole, and greater connectivity between the right MDN and left dorsolateral prefrontal cortex (dlPFC). SZ had less connectivity than MDD between the left pulvinar and ventral anterior cingulate (vACC), left vlPFC, anterior insula, posterior cingulate cortex (PCC), and right hippocampus, between the right pulvinar and right PCC, and between the right MDN and right dorsal anterior cingulate (dACC). This is the first study to measure the functional connectivity to the higher order nuclei of the thalamus in both SZ and MDD. We observed less connectivity in SZ than MDD between pulvinar and emotional encoding regions, a directed effort region, and a region involved in representation and salience, and between MDN and a directed effort region., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Thalamic glutamine loss and grey matter reduction suggest neurodegeneration in first-episode schizophrenia, but the duration is unknown., Aims: To observe glutamine and glutamate levels, grey matter volumes and social functioning in patients with schizophrenia followed to 80 months after diagnosis., Method: Grey matter volumes and proton magnetic resonance spectroscopy metabolites in left anterior cingulate and left thalamus were measured in 17 patients with schizophrenia before medication and 10 and 80 months after diagnosis. Social functioning was assessed with the Life Skills Profile Rating Scale (LSPRS) at 80 months., Results: The sum of thalamic glutamate and glutamine levels decreased over 80 months, and correlated inversely with the LSPRS. Thalamic glutamine and grey matter loss were significantly correlated in frontal, parietal, temporal and limbic regions., Conclusions: Brain metabolite loss is correlated with deteriorated social functioning and grey matter losses in schizophrenia, consistent with neurodegeneration.

Background: Progressive volumetric changes in the brains of people with schizophrenia have been attributed to a number of factors., Aims: To determine whether glutamatergic changes in patients with schizophrenia correlated with grey-matter losses during the first years of illness., Method: Left anterior cingulate and thalamic glutamatergic metabolite levels and grey-matter volumes were examined in 16 patients with first-episode schizophrenia before and after 10 months and 30 months of antipsychotic treatment and in 16 healthy participants on two occasions 30 months apart., Results: Higher than normal glutamine levels were found in the anterior cingulate and thalamus of never-treated patients. Thalamic levels of glutamine were significantly reduced after 30 months. Limited grey-matter reductions were seen in patients at 10 months followed by widespread grey-matter loss at 30 months. Parietal and temporal lobe grey-matter loss was correlated with thalamic glutamine loss., Conclusions: Elevated glutamine levels in never-treated patients followed by decreased thalamic glutamine and grey-matter loss in connected regions could indicate either neurodegeneration or a plastic response to reduced subcortical activity.

Altered high energy and membrane metabolism, measured with phosphorus magnetic resonance spectroscopy (31P-MRS), has been inconsistently reported in schizophrenic patients in several anatomical brain regions implicated in the pathophysiology of this illness, with little attention to the effects of brain tissue type on the results. Tissue regression analysis correlates brain tissue type to measured metabolite levels, allowing for the extraction of "pure" estimated grey and white matter compartment metabolite levels. We use this tissue analysis technique on a clinical dataset of first episode schizophrenic patients and matched controls to investigate the effect of brain tissue specificity on altered energy and membrane metabolism. In vivo brain spectra from two regions, (a) the fronto-temporal-striatal region and (b) the frontal-lobes, were analyzed from 12 first episode schizophrenic patients and 11 matched controls from a (31)P chemical shift imaging (CSI) study at 4 Tesla (T) field strength. Tissue regression analyses using voxels from each region were performed relating metabolite levels to tissue content, examining phosphorus metabolite levels in grey and white matter compartments. Compared with controls, the first episode schizophrenic patient group showed significantly increased adenosine triphosphate levels (B-ATP) in white matter and decreased B-ATP levels in grey matter in the fronto-temporal-striatal region. No significant metabolite level differences were found in grey or white matter compartments in the frontal cortex. Tissue regression analysis reveals grey and white matter specific aberrations in high-energy phosphates in first episode schizophrenia. Although past studies report inconsistent regional differences in high-energy phosphate levels in schizophrenia, the present analysis suggests more widespread differences that seem to be strongly related to tissue type. Our data suggest that differences in grey and white matter tissue content between past studies may account for some of the variance in the literature.

Objective: To use functional magnetic resonance imaging (fMRI) to investigate functional connectivity, and hence, underlying neural networks, in never-treated, first-episode patients with schizophrenia using a word fluency paradigm known to activate prefrontal, anterior cingulate, and thalamic regions. Abnormal connectivity between the prefrontal cortex (PFC) and other brain regions has been demonstrated in chronic, medicated patients in previous positron emission tomography (PET) studies, but has not to our knowledge, previously been demonstrated using both first-episode, drug-naïve patients and fMRI technology., Methods: A 4.0-Tesla (T) fMRI was used to examine activation and functional connectivity [psychophysiological interactions (PPIs)] during a word fluency task compared to silent reading in 10 never-treated, first-episode patients with schizophrenia and 10 healthy volunteers of comparable age, sex, handedness, and parental education., Results: Compared to healthy volunteers, the schizophrenia patient group exhibited less activation during the word fluency task, mostly in the right anterior cingulate and prefrontal regions. Psychophysiological interactions between right anterior cingulate and other parts of the brain revealed a localized interaction with the left temporal lobe in healthy volunteers during the task and a widespread unfocussed interaction in patients., Conclusion: These findings suggest anterior cingulate involvement in the neuronal circuitry underlying schizophrenia.

This study used high-field magnetic resonance spectroscopy to examine the correlation of 1H and 31P metabolite levels in patients with schizophrenia and normal controls. 1H and 31P in vivo spectra were acquired successively from the left anterior cingulate and left thalamus of nine chronic schizophrenic patients and eight comparable healthy controls. A significant positive correlation between glutamine (Gln) and phosphoethanolamine (PEtn) was found in the left anterior cingulate of patients. In the left thalamus of patients, a significant negative correlation between N-acetylaspartate (NAA) and glycerophosphocholine (GroPCho) was found. No significant correlations were found in controls. The correlation between glutamine and phosphoethanolamine may reflect a link between neurotransmission alterations and membrane phospholipid metabolism alterations. The negative correlation between N-acetylaspartate and glycerophosphocholine may reflect the presence of neurodegeneration.

Background: Membrane phospholipid and high-energy abnormalities measured with phosphorus magnetic resonance spectroscopy ((31)P-MRS) have been reported in patients with schizophrenia in several brain regions., Aims: Using improved imaging techniques, previously inaccessible brain regions were examined in patients with first-episode schizophrenia and healthy volunteers with 4.0 T (31)P-MRS., Method: Brain spectra were collected in vivo from 15 patients with first-episode schizophrenia and 15 healthy volunteers from 15 cm(3) effective voxels in the thalamus, cerebellum, hippocampus, anterior/posterior cingulate, prefrontal cortex and parieto-occipital cortex., Results: People with first-episode schizophrenia showed increased levels of glycerophosphocholine in the anterior cingulate. Inorganic phosphate, phosphocreatine and adenosine triphosphate concentrations were also increased in the anterior cingulate in this group., Conclusions: The increased phosphodiester and high-energy phosphate levels in the anterior cingulate of brains of people with first-episode schizophrenia may indicate neural overactivity in this region during the early stages of the illness, resulting in increased excitotoxic neural membrane breakdown.

Objective: This in vivo (1)H magnetic resonance spectroscopy study examined levels of glutamate, glutamine, and N-acetylaspartate in medicated patients with chronic schizophrenia., Method: Localized in vivo (1)H spectra were acquired at 4.0 T from the left anterior cingulate and thalamus of 21 patients with schizophrenia and 21 comparable healthy volunteers., Results: Significantly lower levels of glutamine and glutamate were found in the left anterior cingulate cortex of patients with schizophrenia than in the healthy volunteers. For the schizophrenia patients, the glutamine level in the left thalamus was found to be higher than normal, and there was a significant negative correlation between N-acetylaspartate level and duration of positive symptoms., Conclusions: Since previous studies have found higher than normal levels of glutamine in the left anterior cingulate of never-treated patients, decreased levels of these metabolites in chronic patients could be related to neurodegeneration or the effects of chronic medication.

Objective: This in vivo (1)H magnetic resonance spectroscopy study examined levels of glutamate, glutamine, and N-acetylaspartate in patients experiencing their first episode of schizophrenia., Method: Localized in vivo (1)H spectra were acquired at 4.0 T from the left anterior cingulate and thalamus of 21 never-treated patients with schizophrenia and 21 comparable healthy volunteers., Results: The level of glutamine was significantly higher in the left anterior cingulate cortex and thalamus of the patients with schizophrenia than in the healthy subjects. No differences were found between groups in the levels of other metabolites in the anterior cingulate or thalamus., Conclusions: Higher than normal glutamine levels in the left anterior cingulate and thalamus provide in vivo evidence of greater than normal glutamatergic activity proposed by glutamatergic models of schizophrenia. In contrast to other studies in chronically ill patients, no differences were seen in the levels of N-acetylaspartate in either location, suggesting that the findings in patients with chronic schizophrenia may be related to the effect of medication or the progression of the illness.

Background: Membrane phospholipid abnormalities in people with schizophrenia, measured with (31)P magnetic resonance spectroscopy ((31)P-MRS), have been previously reported in brain regions involved in this disorder., Aims: In this 4.0 Tesla (31)P-MRS study of people with schizophrenia, membrane phospholipid metabolism was examined in brain regions previously inaccessible due to their small volumes., Method: Three-dimensional chemical-shift imaging (3D-CSI) examined 15 cc volumes in 12 brain regions in 11 people with chronic schizophrenia and 11 healthy control volunteers., Results: Glycerophosphoethanolamine was decreased in the anterior cingulate, right prefrontal cortex and left thalamus, but increased in the left hippocampus and cerebellum in those with schizophrenia. Phosphoethanolamine and glycerophosphocholine were decreased in the right prefrontal region and phosphocholine was decreased in the anterior cingulate. No significant difference in membrane phospholipid levels existed between groups in the parieto-occipital and posterior cingulate regions., Conclusions: Altered membrane phospholipid metabolism was demonstrated in all regions implicated in schizophrenia.

Anomalies in the medial prefrontal cortex, anterior insulae, and large-scale brain networks associated with them have been proposed to underlie the pathophysiology of schizophrenia and major depressive disorder (MDD). In this study, we examined the connectivity of the medial prefrontal cortices and anterior insulae in 24 healthy controls, 24 patients with schizophrenia, and 24 patients with MDD early in illness with seed-based resting state functional magnetic resonance imaging analysis using Statistical Probability Mapping. As hypothesized, reduced connectivity was found between the medial prefrontal cortex and the dorsal anterior cingulate cortex and other nodes associated with directed effort in patients with schizophrenia compared to controls while patients with MDD had reduced connectivity between the medial prefrontal cortex and ventral prefrontal emotional encoding regions compared to controls. Reduced connectivity was found between the anterior insulae and the medial prefrontal cortex in schizophrenia compared to controls, but contrary to some models emotion processing regions failed to demonstrate increased connectivity with the medial prefrontal cortex in MDD compared to controls. Although, not statistically significant after correction for multiple comparisons, patients with schizophrenia tended to demonstrate decreased connectivity between basal ganglia-thalamocortical regions and the medial prefrontal cortex compared to patients with MDD, which might be expected as these regions effect action. Results were interpreted to support anomalies in nodes associated with directed effort in schizophrenia and nodes associated with emotional encoding network in MDD compared to healthy controls. [ABSTRACT FROM AUTHOR]

Background The temporoparietal junction (TPJ) has been linked to lower-level attentional and higher-level social processing, both of which are affected in schizophrenia (SZ) and major depressive disorder (MDD). We examined resting functional connectivity of bilateral anterior and posterior TPJ in SZ and MDD to evaluate potential anomalies in each disorder and differences between disorders. Methods Resting-state functional magnetic resonance imaging data were acquired from 24 patients with SZ, 24 patients with MDD, and 24 age-matched healthy controls. We performed seed-based functional connectivity analyses with seed regions in bilateral anterior and posterior TPJ, covarying for gender and smoking. Results SZ had reduced connectivity versus controls between left anterior TPJ and dorsolateral prefrontal cortex (dlPFC) and posterior cingulate cortex (PCC); between left posterior TPJ and middle cingulate cortex, left dorsal PFC, and right lateral PFC; between right anterior TPJ and bilateral PCC; and between right posterior TPJ and middle cingulate cortex, left posterior insula, and right insula. MDD had reduced connectivity versus controls between left posterior TPJ and right dlPFC and between right posterior TPJ and PCC and dlPFC. SZ had reduced connectivity versus MDD between right posterior TPJ and left fusiform gyrus and right superior-posterior temporal cortex. Conclusion Functional connectivity to the TPJ was demonstrated to be disrupted in both SZ and MDD. However, TPJ connectivity may differ in these disorders with reduced connectivity in SZ versus MDD between TPJ and posterior brain regions. [ABSTRACT FROM AUTHOR]

Abstract: Altered high energy and membrane metabolism, measured with phosphorus magnetic resonance spectroscopy (31P-MRS), has been inconsistently reported in schizophrenic patients in several anatomical brain regions implicated in the pathophysiology of this illness, with little attention to the effects of brain tissue type on the results. Tissue regression analysis correlates brain tissue type to measured metabolite levels, allowing for the extraction of “pure” estimated grey and white matter compartment metabolite levels. We use this tissue analysis technique on a clinical dataset of first episode schizophrenic patients and matched controls to investigate the effect of brain tissue specificity on altered energy and membrane metabolism. In vivo brain spectra from two regions, (a) the fronto-temporal-striatal region and (b) the frontal-lobes, were analyzed from 12 first episode schizophrenic patients and 11 matched controls from a 31P chemical shift imaging (CSI) study at 4 Tesla (T) field strength. Tissue regression analyses using voxels from each region were performed relating metabolite levels to tissue content, examining phosphorus metabolite levels in grey and white matter compartments. Compared with controls, the first episode schizophrenic patient group showed significantly increased adenosine triphosphate levels (B-ATP) in white matter and decreased B-ATP levels in grey matter in the fronto-temporal-striatal region. No significant metabolite level differences were found in grey or white matter compartments in the frontal cortex. Tissue regression analysis reveals grey and white matter specific aberrations in high-energy phosphates in first episode schizophrenia. Although past studies report inconsistent regional differences in high-energy phosphate levels in schizophrenia, the present analysis suggests more widespread differences that seem to be strongly related to tissue type. Our data suggest that differences in grey and white matter tissue content between past studies may account for some of the variance in the literature. [Copyright &y& Elsevier]