Higher Cognitive Dysfunction Research Articles

Subjective cognitive assessments and N-back are not correlated, and they are differentially affected by anxiety and depression

Cognitive function (CF) is a core feature related to all psychiatric disorders. However, self-report scales of CF (SRSC) may not always correlate with CF’s objective measures and may have different mediators. Tools to select for evaluating CF in diverse psychiatric populations and their determinants need to be studied. In this study, we aimed to assess the association of SRSC (Perceived Deficit Questionnaire-Depression (PDQ-D), and World Health Organization’s Adult Attention Deficit Hyperactivity Disorder Self-Report Scale (ASRS) and its inattentiveness subscale) with Letter-N-back as an objective measure of CF, and to analyze their association with psychopathology. Two hundred nine (131 nonclinical, and 78 clinical with a psychiatric diagnosis of ICD10 F31-39 [mood disorders excluding Bipolar I] or F40-F49 [neurotic, stress-related or psychosomatic disorder] categories) participants were evaluated with PDQ-D, ASRS, Beck Depression Inventory (BDI), and Beck’s Anxiety Inventory (BAI), and N-back. Both groups’ data were included in the analysis. PDQ-D showed a small correlation with N-back scores, whereas ASRS showed no correlation. PDQ-D and ASRS showed a large correlation. Age and BAI scores significantly predicted both PDQ-D and ASRS, whereas the cognitive subscale of BDI predicted PDQ-D, but not ASRS. Only BAI scores predicted N-back results. The mediation model revealed that 2-back scores of N-back task directly affects PDQ-D scores, independent of BDI scores. However, the cognitive subscale of BDI moderated 2-back and PDQ-D association. On the contrary, BAI scores significantly mediated the association of 2-back scores with PDQ-D. The direct effect of 2-back scores in PDQ-D was insignificant in the mediation of BAI scores. Our study validates the discordance between SRSC and an objective measurement of CF. Anxiety may affect both self-report and objective measurement of CF, whereas depressive thought content may lead to higher cognitive dysfunction reports in nondemented participants.

Action observation facilitates motor cortical activity in patients with stroke and hemiplegia

Motor imagery (MI) is a mental practice that reproduces the visual- and/or kinesthetic-modality brain activations accompanying movement. It is a useful rehabilitation technique as the affected motor cortex can be stimulated in patients with stroke and hemiplegia. However, most patients with stroke have difficulty with MI owing to advanced age and/or higher-cognitive dysfunction, thus impairing their ability to internally simulate the action. We therefore investigated whether action observation (AO), an alternative form of motor stimulation that works via the mirror-neuron system, could facilitate motor cortical activity in such patients. Combined AO and physical training of the observed actions has been reported to have a positive impact on motor deficits after stroke. Eleven patients with stroke and hemiplegia affecting the hand performed MI and AO with verbal and video instructions under 19 channels of electroencephalogram (EEG) recording. The event-related desynchronization (ERD) was measured as an electroencephalographic marker of motor cortical activity. The ERD power in the AO condition (30.0±5.0%) was significantly higher than that in the MI condition (12.2±3.9%). These results suggest that AO could be a good option for patients with stroke who have difficulty using MI to effectively stimulate and reestablish cortical-peripheral motor pathways.

Regulation of MET by FOXP2, Genes Implicated in Higher Cognitive Dysfunction and Autism Risk

Autism spectrum disorder (ASD) is a highly heritable, behaviorally defined, heterogeneous disorder of unknown pathogenesis. Several genetic risk genes have been identified, including the gene encoding the receptor tyrosine kinase MET, which regulates neuronal differentiation and growth. An ASD-associated polymorphism disrupts MET gene transcription, and there are reduced levels of MET protein expression in the mature temporal cortex of subjects with ASD. To address the possible neurodevelopmental contribution of MET to ASD pathogenesis, we examined the expression and transcriptional regulation of MET by a transcription factor, FOXP2, which is implicated in regulation of cognition and language, two functions altered in ASD. MET mRNA expression in the midgestation human fetal cerebral cortex is strikingly restricted, localized to portions of the temporal and occipital lobes. Within the cortical plate of the temporal lobe, the pattern of MET expression is highly complementary to the expression pattern of FOXP2, suggesting the latter may play a role in repression of gene expression. Consistent with this, MET and FOXP2 also are reciprocally expressed by differentiating normal human neuronal progenitor cells (NHNPs) in vitro, leading us to assess whether FOXP2 transcriptionally regulates MET. Indeed, FOXP2 binds directly to the 5' regulatory region of MET, and overexpression of FOXP2 results in transcriptional repression of MET. The expression of MET in restricted human neocortical regions, and its regulation in part by FOXP2, is consistent with genetic evidence for MET contributing to ASD risk.

Treatment response of high cognitive dysfunction depressed inpatients

A sample of depressed inpatients was subdivided according to their initial levels of cognitive dysfunction. These high cognitive dysfunction (HCD) patients and low cognitive dysfunction (LCD) patients received either pharmacotherapy or combined pharmacotherapy plus cognitive-behavioral psychotherapy. Treatments began in the hospital and continued for 20 weeks on an outpatient basis. Results indicated that HCD patients had significantly better treatment response to the combined treatment than pharmacotherapy alone, while LCD patients responded equally to pharmacotherapy alone and combined treatment.