Clusters Of Significant Differences Research Articles

Hippocampal functional connectivity is related to self-reported cognitive concerns in breast cancer patients undergoing adjuvant therapy.

Nearly three out of four survivors experience Cancer-Related Cognitive Impairment (CRCI) for months or years following treatment. Both clinical and animal studies point to the hippocampus as a likely brain region affected in CRCI, however no previous study has investigated the functional connectivity of the hippocampus in CRCI. We compared hippocampal connectivity in cancer survivors and healthy controls and tested the relationship between functional connectivity differences and measures of objective and subjective cognition. Exploratory analysis of inflammatory markers was conducted in a small subset of participants as well. FMRI data were acquired during a memory task from 16 breast cancer survivors and 17 controls. The NIH Toolbox was used to assess cognitive performance and Neuro-QoL was used to measure self-reported cognitive concerns. Whole-brain group-level comparisons identified clusters with different connectivity to the hippocampus in survivors versus controls during task. Average connectivity was extracted from clusters of significant difference between the groups and correlated with cognitive performance and subjective report. Survivors performed worse on a test of episodic memory and reported greater cognitive concern than controls. Exploratory analysis found higher IL6 in cancer survivors compared to controls. Cancer survivors demonstrated higher connectivity of hippocampus with left cuneus, left lingual, left precuneus, and right middle prefrontal gyrus compared with controls. In survivors, higher task-related hippocampal-cortical connectivity was related to worse subjective measures of cognitive concern. Of the four significant clusters, higher connectivity of the precuneus with hippocampus was significantly associated with worse cognitive concern in survivors. The observed greater hippocampal-cortical connectivity in survivors compared to controls is the first reported fMRI biomarker of subjective concern, and may represent a compensatory response to cancer and its treatments. This compensation could explain, in part, the subjective feelings of cognitive impairment that were reported by survivors.

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

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.

EPA-0448 – Failure of de-activation in the default mode network: a trait marker for schizophrenia?

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 (SD) (Range) SCZ 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) Download : Download full-size image 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. Download : Download full-size image 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.