Effects of electroconvulsive therapy on cerebellar-cerebral functional connectivity in patients with treatment-resistant depression and their correlations with gene expression profiles.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment for patients with advanced Parkinson's disease and motor response fluctuations. However, with regards to the cognitive adverse effects, controversy remains. Meta-analyses showed that the most pronounced and consistently reported cognitive side-effect is verbal fluency (VF) decline after STN-DBS with noteworthy effect sizes ( = .51,  = −.49, Hedges’  = −.56). The cause of this decline in VF remains unclear. Previous studies sought to explore the stimulation itself, microlesions, electrode positions, and changes in dopaminergic medication as possible explanations, although these remain inconclusive. A previous study found that the postoperative VF decline was accompanied by prolonged lexical decision latencies, while there were no lexical dysfunctions, and suggested that these findings point to a reduction of cognitive speed following STN-DBS in Parkinson's patients. Another study also implied a possible general cognitive slowdown after STN-DBS, after finding a significant correlation of phonemic VF decline with increased time needed on two mental speed tasks; i.e., the Trail Making Test (TMT) part A and the word card of the Stroop color-word test. Other studies found that the VF decline after STN-DBS was accompanied by decline in performance on executive processes, such as selective attention measured by Stroop color-word card and mental flexibility measured by TMT part B. Moreover, the phonemic VF task itself is also commonly interpreted as a test for executive control, aside from measuring verbal ability. Successful performance on the task not only requires access to the mental lexicon to retrieve words, but also executive control processes that are needed to focus on the selection of words that meet the criteria given in the instruction of the task, while avoiding repetition and rule-breaks. Thus, given the partly executive nature of the phonemic VF task itself, as well as the co-occurrence of decline in performance of other executive functioning tests after STN-DBS, it is possible that an executive dysfunction is an underlying mechanism responsible for the postoperative phonemic VF decline. Besides studies of reduction of cognitive speed and executive dysfunctions, some previous studies analyzed the content of the phonemic VF. However, the relation of the content analysis of phonemic VF (consisting of clusters and switches) to the TMT or Stroop test in a sample size like the current study is relatively new. The content profile, formed by the verbal fluency scoring system, (i.e., phonemic and/or semantic subcategories (clusters) and their transitions (switches)) offers additional information about underlying cognitive processes. Clusters are in succession produced words that belong to a described semantic or phonemic subcategory. A switch is the transition from one cluster to another cluster, or to no cluster at all. It is assumed switching relies on the frontal lobe and executive functions, such as strategy use in search processes, shifting and cognitive flexibility. Fewer switches are proposed to reflect an executive dysfunction. Thus, TMT and Stroop test, as well as the number of switches in the phonemic VF test could serve as a marker for executive (dys)function.