Abstract Background There is increasing evidence of default mode network (DMN) dysfunction in schizophrenia. It has also been suggested that brain structural changes are maximal in a medial frontal ...area which overlaps with the anterior midline node of this network. Methods Brain deactivations were examined in 14 schizophrenic patients and 14 controls during performance of two tasks requiring identification or labelling of facial emotions. Grey matter and white matter volumes were compared using voxel-based morphometry. Results Relative to the controls, the schizophrenic patients showed failure to deactivate in the anterior and posterior midline nodes of the default mode network, as well as other areas considered to be part of the network. Grey matter volume reductions in the patients were found in medial cortical regions which overlapped with the same parts of the network. The functional and structural changes showed significant correlations in a number of medial cortical areas. Conclusions Failure of deactivation in the default mode network is seen in schizophrenic patients when they perform facial emotion tasks. This failure is more extensive than that seen during performance of working memory tasks. The study also supports recent findings of brain structural changes in schizophrenia in the territory of the default mode network.
Functional imaging studies in relatives of schizophrenic patients have had inconsistent findings, particularly with respect to altered dorsolateral prefrontal cortex activation. Some recent studies ...have also suggested that failure of deactivation may be seen.
A total of 28 patients with schizophrenia, 28 of their siblings and 56 healthy controls underwent functional magnetic resonance imaging during performance of the n-back working memory task. An analysis of variance was fitted to individual whole-brain maps from each set of patient-relative-matched pair of controls. Clusters of significant difference among the groups were then used as regions of interest to compare mean activations and deactivations among the groups.
In all, five clusters of significant differences were found. The schizophrenic patients, but not the relatives, showed reduced activation compared with the controls in the lateral frontal cortex bilaterally, the left basal ganglia and the cerebellum. In contrast, both the patients and the relatives showed significant failure of deactivation compared with the healthy controls in the medial frontal cortex, with the relatives also showing less failure than the patients. Failure of deactivation was not associated with schizotypy scores or presence of psychotic-like experiences in the relatives.
Both schizophrenic patients and their relatives show altered task-related deactivation in the medial frontal cortex. This in turn suggests that default mode network dysfunction may function as a trait marker for schizophrenia.
The present study examined whole-brain structural abnormalities in schizophrenia, with a special focus on the anterior and posterior cingulate cortex (ACC, PCC) as this is an understudied issue in ...schizophrenia.
Whole-brain voxel-based morphometry analyses of gray matter (GM) and white matter (WM) were performed to detect volumetric differences between 14 patients with schizophrenia and 14 healthy controls matched for age, sex, educational level and parents' educational level. We examined within-group GM and WM correlations and completed the analysis with measurements of sulci in medial cortical areas.
Compared with the healthy controls, the schizophrenic patients showed significant decreases in GM volumes in the ACC and PCC, and in neighboring WM regions such as the corpus callosum and the fimbriae of the fornix. Moreover, the patient group also displayed a negative correlation between volumes of GM and WM in the ACC. Finally, the patients showed significantly reduced volumes in the right cingulate sulci and left inferior frontal sulci.
Our results replicate typical brain-structural abnormalities with new findings in the medial prefrontal cortex, suggested to be a key region in this disorder.
Dopamine (DA) acts as a key neurotransmitter in the brain. Numerous studies have shown its regulatory role in motor and cognitive function. However, the impairment of emotional processes in ...neurologic and psychiatric pathologies involving the dopaminergic system (Parkinson disease, schizophrenia, autism, Attention Deficit Hyperactivity Disorder, Huntington disease, frontal lobe lesions), as well as the influence that administration of dopaminergic agonists/antagonists exert on the processing of emotion, suggest a role for DA in emotional processes. Moreover, emotional processes are dependent upon a variety of structures, the majority of which form part of the limbic system and are subject to DA innervation. In reviewing the literature, the amygdala emerges as a brain structure critical for emotional processing. It may also be implicated in deficits in emotional recognition found in two major disorders where DA's implication is clear: Parkinson disease and schizophrenia. In addition, the amygdala's response to emotional tasks is likely to be altered by the administration of both agonist and antagonist dopaminergic drugs. Experimental studies reinforce the idea of a dopaminergic contribution to emotional response, as suggested by biochemical, pharmacologic, and lesion experiments. Although the implication of the dopaminergic system in emotional processing appears to be clearly documented, the contribution of specific DA receptor subtypes, or of the DA cotransmitters cholecystokinin and neurotensin, or even glutamate, is, however, still unclear. Altogether, these observations suggest that DA has, undoubtedly, a direct and/or indirect role in the full emotional process.
To investigate the pattern of brain atrophy across time in a sample of Parkinson's disease (PD) patients with and without dementia using voxelbased morphometry (VBM) analysis.
The initial sample ...comprised thirteen non-demented PD patients and sixteen demented patients. Longitudinal cognitive assessment and structural MRI were performed. The mean follow-up period was 25 months (SD=5.2). From this initial group, eight PD patients with dementia (5 men and 3 women) and eleven PD patients without dementia (7 men and 4 women) were reevaluated. MRI 3D structural images were acquired and analyzed by means of the optimized VBM procedure with Statistical Parametric Mapping (SPM2).
VBM analysis showed a progressive grey matter volume decrease in patients with PD without dementia in limbic, paralimbic and neocortical associative temporooccipital regions. In patients with dementia the loss mainly involved neocortical regions.
VBM revealed a significant loss of grey matter volume in PD patients with and without dementia with disease progression. The decrease in limbic and paralimbic regions is widespread in non-demented patients. Neocortical volume reduction is the most relevant finding in patients with dementia. This suggests that the neocortex is a substrate for dementia in Parkinson disease.
We investigated residual brain damage in subjects who suffered severe traumatic brain injury (TBI) in childhood, and its relationship with declarative memory impairment. Magnetic resonance imaging ...(MRI) volumetric data and memory performance were compared between 16 adolescents with antecedents of severe TBI and 16 matched normal controls. Volumes of grey matter, white matter, cerebrospinal fluid (CSF), hippocampus, and caudate nuclei were measured. Verbal memory was assessed by the Rey’s Auditory Verbal Learning test and visual memory by the Rey’s Complex Figure. TBI patients performed significantly worse than controls in both verbal and visual memory. Patients presented decreased white matter volume and increased CSF. The hippocampus was reduced, but not the caudate nuclei. Memory performance correlated with CSF. Plasticity is incomplete for structural and functional deficits in children with TBI. Hippocampal atrophy, white matter loss, and memory impairment remain until adolescence. Memory sequelae are related more to diffuse brain injury, as reflected by MRI findings of increased CSF, than to hippocampal injury.
A leading theory of the negative symptoms of schizophrenia is that they reflect reduced responsiveness to rewarding stimuli. This proposal has been linked to abnormal (reduced) dopamine function in ...the disorder, because phasic release of dopamine is known to code for reward prediction error (RPE). Nevertheless, few functional imaging studies have examined if patients with negative symptoms show reduced RPE-associated activations.
Matched groups of DSM-5 schizophrenia patients with high negative symptom scores (HNS,
= 27) or absent negative symptoms (ANS,
= 27) and healthy controls (HC,
= 30) underwent fMRI scanning while they performed a probabilistic monetary reward task designed to generate a measure of RPE.
In the HC, whole-brain analysis revealed that RPE was positively associated with activation in the ventral striatum, the putamen, and areas of the lateral prefrontal cortex and orbitofrontal cortex, among other regions. Group comparison revealed no activation differences between the healthy controls and the ANS patients. However, compared to the ANS patients, the HNS patients showed regions of significantly reduced activation in the left ventrolateral and dorsolateral prefrontal cortex, and in the right lingual and fusiform gyrus. HNS and ANS patients showed no activation differences in ventral striatal or midbrain regions-of-interest (ROIs), but the HNS patients showed reduced activation in a left orbitofrontal cortex ROI.
The findings do not suggest that a generalized reduction of RPE signalling underlies negative symptoms. Instead, they point to a more circumscribed dysfunction in the lateral frontal and possibly the orbitofrontal cortex.
Abstract Schizophrenia is characterized by cognitive, social, and emotional impairments and by psychotic symptoms. Neuroimaging studies have reported abnormalities within the prefrontal cortex and it ...has been hypothesized that schizophrenia results from poor or miswired anatomical/functional connections. We have compared the functional connectivity within the frontal cortex in control and schizophrenic subjects during the realization of a Continuous Performance Task. The connectivity pattern within the frontal cortex was uncovered by the analysis of the correlation matrix computed from the fMRI time series in frontal areas for 14 schizophrenic patients and 14 control subjects. In control subjects, the right dorsolateral prefrontal cortex (DLFCr) activity correlated i) positively with the left dorsolateral prefrontal cortex and the posterior part of the supplementary motor area, ii) negatively with the medial and anterior/inferior part of the frontal cortex. In the schizophrenic group, these relations were abolished or strongly lowered. The negative relation between the DLFCr and the medial frontal cortex has been proposed to play a key role in setting a harmonious balance between the direction of attention to the external world and the expression of the individual believes and self-referential activities, and therefore, the impaired relation of right DLFCr with other frontal areas could explain a distorted perception of external world in relation with internal motivations.
Background Functional imaging abnormality has been proposed as a trait marker or endophenotype for schizophrenia. Although studies examining dorsolateral prefrontal cortex activation in relatives of ...schizophrenic patients have not had consistent findings, failure of de-activation in the medial frontal cortex may be a promising alternative candidate. Method Twenty-nine patients with schizophrenia, 29 of their siblings and 58 healthy controls underwent fMRI during performance of the n-back working memory task. An ANOVA was fitted to individual whole-brain maps from each set of patient-relative-matched pair of controls. Clusters of significant difference among the groups were used as regions-of-interest to compare mean activations/de-activations between them. Results Four clusters of significant difference were found. The schizophrenic patients, but not the relatives, showed reduced activation compared to the controls in the left lateral frontal cortex, the left basal ganglia and the cerebellum. In contrast, both the patients and the relatives showed significantly reduced de-activation compared to the healthy controls in the medial frontal cortex, with evidence of an intermediate pattern in the relatives. Failure of de-activation was not associated with schizotypy scores or presence of psychotic experiences in the relatives. Conclusions Both schizophrenic patients and their relatives show altered task-related de-activation in the medial frontal cortex. This in turn suggests that default mode dysfunction may function as a trait marker or endophenotype for schizophrenia. Table. 1 Demographic characteristics of the patinents ( n = 29), healthy relatives ( n = 29) and controls ( n = 58) Schizophrenic patients (n = 29) Healthy relatives (n = 29) Controls (n = 58) p value Sex (male/female) 7/22 12/17 19/39 p = 0.38 Age (SD) (Range) 35.79 (9.55) (19-57) 37-31 (9.03) (19-52) 36.86 (9.91) (19-60) p = 0.82 Pre-morbid IQ (TAP) (SD) (Range) 94.92 (9.56) (77-110) 101.96 (7.80) (83-112) 100.05 (8.09) (81-114) p = 0.03 Current IQ score (WAIS-III score) 92.08 (14.17) (63-121) 108.76 (11.29) (81-122) 104.27 (12.47) (72-128) SCZ < CTRL, REL p < 0.01 (SD) (Range) SCZ < CTRL, REL GAF score (SD) (Range) 52.41 (12.07) (35-75) - - PANSS score (SD) (Range) 66.55 (14.79) (35-96) - - Positives symptoms 15.44 (4.53) (8-26) Negative symptoms 20.88 (7.33) (7-30) General symptoms 30.92 (8.08) (17-50) Fig. 1 Brain regions showing a significant effect in the 2-back versus baseline contrast in controls (a), healthy first-degree relatives (b) and in schizophrenic patients (c) Yellow indicates a positive association (activation) with the task. Blue indicates areas where the task led to a decrease in the blood oxygenation level-dependent (BOLD) response (deactivation). Numbers refer to Montreal Neurological Institute (MNI) z coordinates of the slice shown. The right side of each image represents the right side of the brain. Results are thresholdedd at z = 3.5 and corrected for multiple comparisons across space using Gaussian random field methods. Fig. 2 Clusters of difference between schizophrenic patients (SCZ, n = 29), their first-degree healthy relatives (REL, n = 29) and healthy controls (CTRL, n = 58) (a) Left caudate gryus, globus pallidus and putamen activation, (b) bilateral cerebellar activation, (c) left dorsolateral activation and (d) anterior cingulate deactivation. The right side of each image represents the right side of the brain. Whole brain results are corrected for multiple comparisons across space using Gaussian random field methods. Analyses within ROIs were FDR-corrected for multiple comparisons.
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