A longitudinal functional magnetic resonance imaging study of verbal working memory in depression after antidepressant therapy

Nicholas D Walsh, Steven C R Williams, Michael J Brammer, Edward T Bullmore, Jieun Kim, John Suckling, Martina T Mitterschiffthaler, Anthony J Cleare, Emilio Merlo Pich, Mitul A Mehta, Cynthia H Y Fu

Research output: Contribution to journalArticlepeer-review

118 Citations (Scopus)


BACKGROUND: Impairments in the neural circuitry of verbal working memory are evident in depression. Factors of task demand and depressive state might have significant effects on its functional neuroanatomy.

METHODS: Two groups underwent functional magnetic resonance imaging while performing a verbal working memory task of varying cognitive load (n-back). The patient group comprised 20 medication-free individuals in an acute episode of unipolar major depression and the control group comprised 20 healthy individuals. Scans were acquired at weeks 0 (baseline), 2, and 8. Patients received treatment with fluoxetine after the baseline scan. Cerebral activations were measured for mean overall activation as well as the linear and quadratic load-response activity with increasing task demand (1-, 2-, 3-back).

RESULTS: There were no significant differences in performance accuracy between groups. However, a main effect of group was observed in the load-response activity in frontal and posterior cortical regions within the verbal working memory network in which patients showed a greater load-response relative to control subjects. Group by time effects were revealed in the load-response activity in the caudate and thalamus. As a marker of treatment response, a lower linear load-response at baseline in the dorsal anterior cingulate, left middle frontal, and lateral temporal cortices was associated with an improved clinical outcome.

CONCLUSIONS: Maintenance of performance accuracy in patients was accompanied by a significant increase in the load-response activity in frontal and posterior cortical regions within the verbal working memory network. These data also provide further support for resilience of activity in the anterior cingulate as a predictor of treatment response in depression.

Original languageEnglish
Pages (from-to)1236-43
Number of pages8
JournalBiological Psychiatry
Issue number11
Publication statusPublished - 1 Dec 2007


  • Adult
  • Antidepressive Agents
  • Antidepressive Agents, Second-Generation
  • Caudate Nucleus
  • Cerebral Cortex
  • Cognition
  • Depressive Disorder, Major
  • Echo-Planar Imaging
  • Female
  • Fluoxetine
  • Humans
  • Image Processing, Computer-Assisted
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Memory, Short-Term
  • Middle Aged
  • Psychiatric Status Rating Scales
  • Psychomotor Performance
  • Thalamus
  • Verbal Behavior

Cite this