Similarly to brain-mapping studies of patients with schizophrenia, regional deficits of neural activity (indexed by cerebral blood flow or glucose utilization) can be detected in the 'resting' brains of depressed patients.(2 25) Many resting-state studies have shown a reduction of regional brain functional activity, most frequently reported in the prefrontal cortex, compared with normal controls. However, the exact location of prefrontal change (dorsolateral, ventrolateral, orbitofrontal, and medial frontal areas) has been variably emphasized by different authors.(2 25 and 26)
As demonstrated in schizophrenia, significant associations between cortical activity and cognitive function, symptom clusters, including mood, and response to treatments are apparent.*25' Similarly to schizophrenia, the resting-state functional brain abnormalities may represent the physiological correlates of aspects of the depressed state such as depressed mood, retardation, or cognitive impairment rather than trait markers of the illness itself.
Psychological challenge paradigms have been applied in a few studies in depressed cohorts to test whether specific brain regions, subserving select cognitive processes, are impaired in depressed patients. For example, the Tower of London planning task has been used to investigate a 'planning network' in depressed patients/27) Patients in this study showed reduced activity throughout the network with complete loss of functional activity in the anterior cingulate cortex; a cortical region involved in attentional processing and highly connected with other prefrontal areas. Using a different activation strategy, mood induction paradigms have mapped the neural correlates of subjective mood. In one of the first of these studies, recall of sad situations resulted in increased activity in inferior orbitofrontal cortex. In more recent studies, increased flow in limbic and paralimbic structures including the left prefrontal, bilateral anterior cingulate, hypothalamus, and inferomedial prefrontal cortex have been observed. (27>
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