Striatal hypoactivation and cognitive slowing in patients with partially remitted and remitted major depression

Abstract

The present pilot study investigated neuronal correlates of executive functioning in patients previously diagnosed with recurrent Major Depressive Disorder (MDD). The aim of the study was to examine a partial remitted and remitted MDD patient group with functional magnetic resonance imaging (fMRI) using a cognitive activation paradigm in order to probe aspects of response inhibition, attention shift and working memory. Twenty MDD patients and 19 healthy controls, matched for age and gender, participated in the study. A working memory n-back task with single presentations of incongruent Stroop words was used, with the instruction to either remember the colour of the ink the word was written in, or the colour word itself, presented 2 or 3 words back in the presentation series. MR images were acquired on a 1.5T GE Signa HD MR scanner. In addition to MR data, response time (RT) and response accuracy (RA) behavioural data were recorded. The behavioural results showed longer RT and lower RA in the MDD group compared to the control group across instruction conditions and working memory load. Based on previous studies of executive function, a composite ROI mask of the anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), caudate and putamen was used in statistical analysis. Significant activation was observed in controls throughout this corticostriatal network. When compared to controls, patients showed no significant difference in the level of activation in the ACC and the DLPFC. However, in the putamen and caudate, hypoactivation in the patient group was observed. It was concluded that these effects could be due to a scar effect as a result of previous episodes of MDD.

Mapping the physiological and molecular markers of stress and SSRI antidepressant treatment in S100a10 corticostriatal neurons

“…Loss of excitatory serotonergic modulation through exposure to chronic social isolation stress would be expected to perturb corticostriatal signaling and the integration of sensory and emotional processing and goal-directed behavior. Of note, this predicted pattern of reduced functional corticostriatal connectivity has been seen in human imaging studies of depression [59,60]. Interestingly, S100a10 neurons of the motor and somatosensory cortices appear to share similar serotonergic modulation to their counterparts in the prefrontal cortex [61,62], raising the question of whether chronic social isolation stress affects the modulation of emotional and cognitive corticostriatal circuits in a manner similar to that observed in our study.…”

Neuronal underpinnings of cognitive impairment and - improvement in mood disorders

“…48,60,73,108 However, this association between direction of dlPFC activity and performance was not uniform; 3 studies reported no increase in dlPFC in remitted patients with intact working memory performance, 34,78,94 and 1 study found no dlPFC hypo-activation in cognitively impaired patients. 59 Notably, 2 of the 3 studies showing intact working memory performance and normal dlPFC activity were conducted in remitted patients, suggesting that cognitive and neural functioning is normalized after remission in some UD patients 34,94 . Finally, symptomatic and remitted UD patients were found to display altered FC within PFC regions and between PFC and parietal nodes of the cognitive control network.…”

Dynamic switching between intrinsic and extrinsic mode networks as demands change from passive to active processing

“…The ROIs were chosen because these regions have shown significant activations during resting-and task-absent periods 4,5,32,49 . Similarly, they have shown ROI-activations during active processing and task-presence 15,19,28,29,50 including tasks and processes covered by the current three tasks.…”

“…This task adds an executive function process to the working memory process, making it cognitively more demanding. It has previously been shown to discriminate between healthy and depressed patients 28 , and reliably elicits demands for working memory processing. Each presentation lasted for 300 ms, with 20 presentations in total, and with five (40%) pseudo-randomly interspersed target trials where the two displays matched.…”

“…A mental rotation task 24 was chosen because this task is shown to provide significant fronto-parietal activations [25][26][27] . A working memory task was chosen because working memory is a central cognitive concept, which includes attention and executive control in addition to short-term memory 28,29 , and would thus be a valid proxy for the varying processing demands during an ordinary work-day in life. Arithmetics with adding numbers was chosen because it draws on a common cognitive ability encountered every day, the ability for mental arithmetic and to manipulate numbers.…”