Executive function network's white matter alterations relate to Parkinson's disease motor phenotype.

Parkinson's disease (PD) patients with postural instability and gait disorder phenotype (PIGD) are at high risk of cognitive deficits compared to those with tremor dominant phenotype (TD). Alterations of white matter (WM) integrity can occur in patients with normal cognitive functions (PD-N). However, the alterations of WM integrity related to cognitive functions in PD-N, especially in these two motor phenotypes, remain unclear. Diffusion tensor imaging (DTI) is a non-invasive neuroimaging method to evaluate WM properties and by applying DTI tractography, one can identify WM tracts connecting functional regions. Here, we 1) compared the executive function (EF) in PIGD phenotype with normal cognitive functions (PIGD-N) and TD phenotype with normal cognitive functions (TD-N) phenotypes; 2) used DTI tractography to evaluated differences in WM alterations between these two phenotypes within a task-based functional network; and 3) examined the WM integrity alterations related to EF in a whole brain network for PD-N patients regardless of phenotypes. Thirty-four idiopathic PD-N patients were classified into two groups based on phenotypes: TD-N and PIGD-N, using an algorithm based on UPDRS part III. Neuropsychological tests were used to evaluate patients' EF, including the Trail making test part A and B, the Stroop color naming, the Stroop word naming, the Stroop color-word interference task, as well as the FAS verbal fluency task and the animal category fluency tasks. DTI measures were calculated among WM regions associated with the verbal fluency network defined from previous task fMRI studies and compared between PIGD-N and TD-N groups. In addition, the relationship of DTI measures and verbal fluency scores were evaluated for our full cohort of PD-N patients within the whole brain network. These values were also correlated with the scores of the FAS verbal fluency task. Only the FAS verbal fluency test showed significant group differences, having lower scores in PIGD-N when compared to TD-N phenotype (p < 0.05). Compared to the TD-N, PIGD-N group exhibited significantly higher MD and RD in the tracts connecting the left superior temporal gyrus and left insula, and those connecting the right pars opercularis and right insula. Moreover, compared to TD-N, PIGD-N group had significantly higher RD in the tracts connecting right pars opercularis and right pars triangularis, and the tracts connecting right inferior temporal gyrus and right middle temporal gyrus. For the entire PD-N cohort, FAS verbal fluency scores positively correlated with MD in the superior longitudinal fasciculus (SLF). This study confirmed that PIGD-N phenotype has more deficits in verbal fluency task than TD-N phenotype. Additionally, our findings suggest: (1) PIGD-N shows more microstructural changes related to FAS verbal fluency task when compared to TD-N phenotype; (2) SLF plays an important role in FAS verbal fluency task in PD-N patients regardless of motor phenotypes.

Assessment of Emergency Department and Inpatient Use and Costs in Adult and Pediatric Functional Neurological Disorders.

Importance: There is limited information about health care use and costs in patients with functional neurological disorders (FNDs). Objective: To assess US emergency department (ED) and inpatient use and charges for FNDs. Design, Setting, and Participants: This economic evaluation used Healthcare Cost and Utilization Project data to assess all-payer (1) adult (age, ≥18 years) hospitalizations (2008-2017), (2) pediatric (age, 5-17 years) hospitalizations (2003, 2006, 2009, 2012, and 2016), and (3) adult and pediatric ED evaluations (2008-2017). International Classification of Diseases, Ninth Revision, Clinical Modification code 300.11 (conversion disorder) or 306.0 (musculoskeletal malfunction arising from mental factors) and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Clinical Modification codes for conversion disorder/functional neurological symptom disorder (F44.4 to F44.7) were used to conservatively define FNDs and to compare them with other neurological disorders that are associated with high levels of health care use. Analysis was performed between January 2019 and July 2020. Main Outcomes and Measures: Admission traits (eg, demographic characteristics of patients, length of stay, and discharge disposition) and hospital charges. Results: Compared with other neurological disorders in 2017, emergency FND evaluations of 36 359 adults (25 807 women [71.0%] and 3800 children (2733 girls [71.9%]) more frequently resulted in inpatient admissions (22 895 adult admissions [69.2% female] and 1264 pediatric admissions [73.4% ]). These FND admissions had a shorter mean (SEM) hospital length of stay (5.21 [0.15] days vs 6.03 [0.03] days, P < .001) but higher workup rates than admissions for comparable neurological diagnoses. Admissions for FNDs had low rates of inpatient physical therapy, occupational therapy, speech and language pathology, and psychiatric consultation. The total annual costs (a proxy for total costs in 2017 US dollars) were $1066 million (95% CI, $971-$1160 million) for adult FND inpatient charges in 2017 compared with $1241 million (95% CI, $1132-$1351 million) for anterior horn cell disease; $75 million (95% CI, $57-$92 million) for pediatric FND inpatient charges in 2012 compared with $86 million (95% CI, $63-$108 million) for demyelinating diseases; and $163 million (95% CI, $144-$182 million) for adult and pediatric ED visits in 2017 compared with $135 million (95% CI $111-$159 million) for refractory epilepsy. Total charges per admission for ED care of FNDs were higher than the other comparison groups in adults. Total costs and costs per admission for FNDs increased from 2008 to 2017 at a higher rate than that of other neurological disorders. Conclusions and Relevance: This economic evaluation found that the more than $1.2 billion and increasing annual costs for ED and inpatient care of FNDs were similar to other investigation-intensive and pharmacologically demanding neurological disorders. Unnecessary investigations and iatrogenic harm inflate costs at the expense of necessary but neglected psychiatric and rehabilitative treatments.

Cognitive control involves theta power within trials and beta power across trials in the prefrontal-subthalamic network.

There is increasing evidence that the medial prefrontal cortex participates in conflict and feedback monitoring while the subthalamic nucleus adjusts actions. Yet how these two structures coordinate their activity during cognitive control remains poorly understood. We recorded from the human prefrontal cortex and the subthalamic nucleus simultaneously while participants (n = 22) performed a novel task involving high conflict trials, complete response inhibition trials, and trial-to-trial behavioural adaptations to conflict and errors. Overall, we found that within-trial adaptions to both conflict and complete response inhibition involved changes in the theta band while across-trial behavioural adaptations to both conflict and errors involved changes in the beta band (P < 0.05). Yet the role each region's theta and beta oscillations played during the task differed significantly between the two sites. Trials that involved either within-trial conflict or complete response inhibition were associated with increased theta phase synchrony between the medial prefrontal cortex and the subthalamic nucleus (P < 0.05). Despite increased synchrony, however, increases in prefrontal theta power were associated with response inhibition, while increases in subthalamic theta power were associated with response execution (P < 0.05). In the beta band, post-response increases in prefrontal beta power were suppressed when the completed trial contained either conflict or an erroneous response (P < 0.05). Subthalamic beta power, on the other hand, was only modified during the subsequent trial that followed a conflict or error trial. Notably, these adaptation trials exhibited slower response times (P < 0.05), suggesting that both brain regions contribute to across-trial adaptations but do so at different stages of the adaptation process. Taken together, our data shed light on the mechanisms underlying within-trial and across-trial cognitive control and how disruption of this network can negatively impact cognition. More broadly, however, our data also demonstrate that the specific role of a brain region, rather than the frequency being utilized, governs the behavioural correlates of oscillatory activity.