Cortical inefficiency in patients with unipolar depression: an event-related FMRI study with the Stroop task.

BACKGROUND: The present study is aimed to examine the neuronal correlates of Stroop interference in medication-free patients with major depressive disorder. METHODS: Sixteen patients fulfilling Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for unipolar depression and 16 healthy control subjects matched for age, gender, and education were included. All subjects underwent an event-related functional magnetic resonance imaging (fMRI) design with an adapted version of the Stroop task including congruent and incongruent task conditions. The fMRI experiment was conducted on a 1.5 T magnetic resonance (MR) scanner, and item responses were given manually by the subjects. RESULTS: With regard to behavioral performance, patients revealed no differences in both reaction time and accuracy relative to control subjects. With regard to brain activations, direct comparison of patients with control subjects in the interference condition revealed hyperactivity in rostral anterior cingulate gyrus (rACG) and left dorsolateral prefrontal cortex (DLPFC) in depressive patients, which correlated strongly with the Stroop interference. CONCLUSIONS: The study provides new evidence for the functioning and dissociation of the anterior cingulate in depressed patients. The greater prefrontal activation may reflect a cortical inefficiency due to hyperactivity in rACG enhancing the cognitive interferences from the emotional state.

Effects of lorazepam on the neuromagnetic mismatch negativity (MMNm) and auditory evoked field component N100m.

The mismatch negativity (MMN) as an auditory evoked potential is thought to reflect an early, preconscious attention process. While this component has gained great importance in studies on clinical populations and in basic research on auditory information processing, the involvement of different neurotransmitters in the generation of this component is less well understood. We investigated the impact of the benzodiazepine lorazepam as a GABA agonist on the neuromagnetic MMN (MMNm) and auditory evoked field component N100m. A group of 12 healthy subjects was studied in single blind trials under the following three conditions: after the intake of 1.25 mg lorazepam, 100 mg caffeine or placebo. Neuromagnetic recordings were obtained before drug intake and three times after it. Controlled visual attention was tested additionally using a version of the Continuous Performance Test (CPT). The neuromagnetic activity was reconstructed by a single moving dipole, and the dipole moment and its latency were compared between conditions and time points of measurement. Lorazepam diminished the signal detection performance in the CPT 25 min after drug intake. The source of the field component N100m was attenuated, most significantly in the recording 105 min after lorazepam intake. The attenuation of the MMNm under lorazepam became significant at 105 min, but was visually less apparent, because in all conditions a decrease of the MMNm dipole moment within the course of a session was observed. Besides the already known effects of benzodiazepines on controlled attention functions, preconscious attention functions as reflected in the MMN are impaired by acute benzodiazepine intake. MMN studies on clinical populations have to be controlled for the recording time because of the strong habituation of this component.