Failure of deactivation in the default mode network: a trait marker for schizophrenia?

BACKGROUND: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

Structural abnormalities in schizophrenia: further evidence on the key role of the anterior cingulate cortex.

OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSION: Our results replicate typical brain-structural abnormalities with new findings in the medial prefrontal cortex, suggested to be a key region in this disorder.

Correlated structural and functional brain abnormalities in the default mode network in schizophrenia patients.

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.

Schizophrenia and frontal cortex: where does it fail?

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.

Cerebral correlates of declarative memory dysfunctions in early traumatic brain injury.

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.

Apolipoproteins E and C1 and brain morphology in memory impaired elders.

Previous research has shown that polymorphisms of the apolipoproteins E ( APOE) and APOC1 represent genetic risk factors for dementia and for cognitive impairment in the elderly. The brain mechanisms by which these genetic variations affect behavior or clinical severity are poorly understood. We studied the effect of APOE and APOC1 genes on magnetic resonance imaging measures in a sample of 50 subjects with age-associated memory impairment. The APOE E4 allele was associated with reduced left hippocampal volumes and APOE*E3 status was associated with greater frontal lobe white matter volumes. However, no APOE effects were observed when analyses accounted for other potential confounding variables. The effects of APOC1 on hippocampal volumes appeared to be more robust than those of the APOE polymorphism. However, no modulatory effects on brain morphology outside the medial temporal lobe region were observed when demographic variables, clinical status, and other anatomical brain measurements were taken into consideration. Our results suggest that the role of the APOC1 polymorphism in brain morphology of the cognitively impaired elderly should be examined in further studies.

[Evaluation of diffuse cerebral atrophy in patients with a history of traumatic brain injury and its relation to cognitive deterioration]. / Evaluación de la atrofia cerebral difusa en pacientes con antecedentes de traumatismo craneoencefálico y su relación con el deterioro cognitivo.

INTRODUCTION: Diffuse damage secondary to traumatic brain injury (TBI) can be studied through volumetric analysis of several structures that are sensible to this kind of injury, such as corpus callosum, ventricular system, hippocampus, basal ganglia and the volume of cerebrospinal fluid spaces. OBJECTIVE: Our aim is to describe how closed head injury (CHI) occurred in early years produce diffuse damage, and how this damage affects general cognitive functioning at long term. PATIENTS AND METHODS: Initially the group of subjects was composed of 27 head injured children and adolescents following paediatric moderate to severe TBI. From this initial group we selected 15 patients without focal lesion, or in case of having suffered focal lesion, this was smaller than 2,600 mm3. These subjects were assessed by means of volumetric analysis of cerebrospinal fluid spaces, corpus callosum, hippocampus and caudate nucleus, comparing the results with a matched control group. We calculated the degree of general cognitive ability of these subjects through tests of intellectual, memory, frontal lobe and motor speed functioning. RESULTS: This study demonstrates that early CHI produce a volume decrease in all measured structures. Corpus callosum atrophy is the factor that better explains general cognitive impairment. CONCLUSIONS: Diffuse damage secondary to moderate to severe peadiatric TBI has long term effects on several cerebral structures and on cognitive performance. Corpus callosum atrophy is the best predictor for general cognitive impairment, compared with other affected structures.

[Cerebral activation during Stroop's test in a case of early focal brain injury]. / Activación cerebral durante el test de Stroop en un caso de lesión cerebral focal temprana.

INTRODUCTION: Functional magnetic resonance imaging (fMRI) offers an important advantage over other functional neuroimaging techniques used with children because of its harmlessness. Previous studies conducted with adults with alexia suggested two ways the brain can reorganise reading after a brain injury affecting the left hemisphere, one contralateral and the other ipsilateral. CASE REPORT: We describe a study carried out using fMRI of a 10 year old girl with an injury to the left hemisphere caused by a fishing harpoon when she was 6 years old. As a result of the accident the girl presented a right hemiparesia. The girl s parents and teachers also reported difficulties in the acquisition of reading writing and arithmetic, as well as a certain degree of attentional deficit. An fMRI exploration was performed while the girl was doing the Stroop test. The structural MR images showed left hemisphere cortical lesions in the orbital and angular gyrus regions, in addition to the caudate and putamen nuclei, and in the inferior longitudinal bundle. The fRMI revealed a strong overactivation of the right dorsolateral frontal cortex, in the evaluation of interference, and activations of the right angular and bilateral supramarginal gyri, in the evaluation of word reading. CONCLUSION: The functional study suggests the existence of a reorganisation of reading that is both intra and inter hemispheric.

[Functional magnetic resonance in the evaluation of the activity of the anterior cingulate cortex using Stroop's paradigm]. / Resonancia magnética funcional en la evaluación de la actividad del cingulado anterior mediante el paradigma de Stroop.

INTRODUCTION: Stroop s paradigm has been used to evaluate the anterior attention system which regulates the inhibitory capacity of automatic responses. Functional neuroimaging techniques have shown a preponderant role for the anterior cingulate cortex in carrying out this paradigm. OBJECTIVE: To evaluate the activity of the anterior cingulate cortex in view of its clinical importance in the study of neurological and psychiatric disorders. PATIENTS AND METHODS: Eleven healthy volunteers took part in the study. The functional images were analyzed using the software SPM99 and by second order individual and group analysis. RESULTS: Initial local analysis showed activation in the right anterior cingulated cortex (Brodmann s area 32) and left central (areas 31 and 23); caudate nucleus (right body and left tail) and thalamus (bilateral). Overall there was significant activation of the left hemisphere, in areas 44 (Broca s area), 7, 40 (supra marginal gyrus and insular cortex, and in the right hemisphere in area 19. In spite of this there was great individual variation. CONCLUSIONS: The overall results are concordant with complex functional connections for attention and the control of automatic responses. In our study the anterior cingulated cortex was not selectively activated. The activation of the thalamus and caudate nucleus may be explained by their involvement in the frontostriatal circuits. The lack of individual consistency may be due to different personal cognitive styles of resolving conflicts. According to our results, Stroop s paradigm would not be clinically useful for showing good or bad functioning of the anterior cingulated cortex.