Changes in neural circuitry of language before and after treatment of major depression

Language tasks requiring semantic analysis of word meaning activate distinct brain areas including the anterior cingulate gyrus at about 200 msec after the stimulus onset, the left lateral prefrontal cortex at about 250 msec, and the left temporo-parietal (Wernicke's) area at 500-600 msec. Reading the same words activate the insula around 800 msec and left occipital cortex around 200 msec stronger than the semantic analysis in normal subjects. Many of these brain areas also show abnormal activity in resting state in patients with major unipolar depression. We measured 128-channel event-related brain potentials (ERPs) and statistical probability mapping in the use generation task carried out with single visual nouns to explore the topography and time course of these cortical activations related to semantic processing in 11 patients with major unipolar depression before and 8 weeks after treatment with the selective serotonin reuptake inhibitor (SSRI) citalopram. Before treatment in depressed state, the time course for the left prefrontal cortex activation did not show slowing, but was accompanied by the right prefrontal activation with a similar time course. The left posterior temporo-parietal activation appeared later than in normals. Treatment was accompanied by the complete elimination of the right prefrontal activation in the same use generation task. Time course of the posterior left temporo-parietal area showed a trend toward normalization. Insula-related activation in reading task was not seen in depressed state, but was evident in the same patient group after the depression has lifted, presumably as a result of treatment with citalopram.