Working memory dysfunction in major depression: an event-related potential study

Objectives: To study working memory function in untreated major depression using a digit probe identification and matching task. Methods: We compared behavioural performance and event-related potentials during processing of the Sternberg working memory task in 14 depressed patients and 14 healthy matched control subjects. Results: Patients made more mistakes than controls as the memory load was increased from one to 5 digits and had significantly slower reaction times at all levels of memory load. The patientsʹ event-related potentials (ERPs) differed significantly from controls. Pathological changes were similar for auditory and visual presentation. Surface negative activity in the 157–210 ms section of the waveform was reduced for all levels of memory load, suggesting abnormal sensory/perceptual processing in the modality-specific association cortices, possibly due to a failure of selective attention mechanisms. In the 375–840 ms epoch, the patientsʹ responses showed large amplitude sustained negative activity, maximal at Cz and a reduced late positive wave. The large prolonged negativity in the patientsʹ ERPs suggests activation of additional neuronal assemblies than those normally participating in the task. This could reflect either compensatory mechanism or dysfunction of inhibitory systems. These changes were sensitive to memory load, suggesting that they reflect alterations of memory-related processes. Conclusions: This study provides objective evidence that major depression significantly affects working memory. The ERP changes in depression could be accounted for by dysfunction of the central executive control of working memory.