ABSTRACT
BACKGROUND: Bipolar depression has been found to be associated with changes in prefrontal cortex activity during performance of cognitive tasks. However, the role of task-related de-activations has been little investigated. METHOD: Forty-one bipolar depressed patients and 41 matched normal controls underwent fMRI scanning while performing baseline, 1-back and 2-back versions of the n-back task. Linear models were used to obtain maps of within-group activations and areas of differential activation between the groups. RESULTS: The bipolar depressed patients showed reduced activation in the dorsolateral prefrontal cortex (DLPFC) bilaterally and several other regions. After controlling for differences in task performance only differences in the DLPFC and cerebellum remained. Left DLPFC activation was inversely correlated with Hamilton and MADRS scores. The patients showed failure to de-activate in the medial prefrontal cortex, an area corresponding to the anterior medial node of the default mode network. LIMITATIONS: To confirm default mode network dysfunction demonstration of resting-state connectivity abnormalities would also be required. The study was carried out on treated patients, and did not assess for presence of depressive symptoms in the healthy controls. CONCLUSIONS: Both prefrontal cortical and default mode network dysfunction appear to characterise bipolar depression. The former, but not the latter, is associated with symptom severity.
Subject(s)
Bipolar Disorder/physiopathology , Memory, Short-Term/physiology , Task Performance and Analysis , Adult , Case-Control Studies , Cerebellum/physiopathology , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Prefrontal Cortex/physiopathologyABSTRACT
OBJECTIVES: Manic patients have been found to show reduced activation in the prefrontal cortex and other regions during performance of cognitive tasks. However, little is known about de-activations associated with the disorder. This study aimed to examine, at the whole-brain level, abnormal patterns of task-related activation and de-activation during performance of a working memory task. METHODS: Twenty-nine DSM-IV bipolar patients and 46 healthy controls underwent fMRI during performance of the n-back task. The patients were scanned while they were in a manic episode. Linear models were used to obtain maps of within-group activations and areas of differential activation between the groups. RESULTS: The manic patients showed reduced activation compared to the controls in the bilateral dorsolateral prefrontal cortex and the right parietal cortex. They also showed failure of de-activation in the medial frontal cortex, extending to the temporal poles and parts of the limbic system bilaterally. The failure of activation in the dorsolateral prefrontal cortex disappeared when differences in task performance were controlled for in the analysis. However, the medial frontal failure of de-activation survived controlling for this. CONCLUSIONS: This study suggests that, in addition to reduced prefrontal activation, failure of de-activation is an important functional imaging abnormality in mania. This, together with its location in the medial prefrontal cortex, implies default mode network dysfunction in the disorder.
Subject(s)
Bipolar Disorder/physiopathology , Nerve Net/physiopathology , Prefrontal Cortex/physiopathology , Adult , Discrimination, Psychological/physiology , Female , Humans , Magnetic Resonance Imaging/instrumentation , Magnetic Resonance Imaging/methods , Male , Middle Aged , Neuropsychological Tests , Young AdultABSTRACT
BACKGROUND: Cognitive impairment is an established feature of schizophrenia. However, little is known about its relationship to the structural and functional brain abnormalities that characterise the disorder. Aims To identify structural and/or functional brain abnormalities associated with schizophrenic cognitive impairment. METHOD: We carried out structural magnetic resonance imaging (MRI) and voxel-based morphometry in 26 participants who were cognitively impaired and 23 who were cognitively preserved, all with schizophrenia, plus 39 matched controls. Nineteen of those who were cognitively impaired and 18 of those who were cognitively preserved plus 34 controls also underwent functional MRI during performance of a working memory task. RESULTS: No differences were found between the participants who were cognitively intact and those who were cognitively impaired in lateral ventricular volume or whole brain volume. Voxel-based morphometry also failed to reveal clusters of significant difference in grey and white matter volume between these two groups. However, during performance of the n-back task, the participants who were cognitively impaired showed hypoactivation compared with those who were cognitively intact in the dorsolateral prefrontal cortex among other brain regions. CONCLUSIONS: Cognitive impairment in schizophrenia is not a function of the structural brain abnormality that accompanies the disorder but has correlates in altered brain function.