Cognitive impairment (CI) is the most frequent non-motor symptom in Parkinson’s disease and is associated with deficits in a number of cognitive functions including working memory. However, the pathophysiology of Parkinson’s disease CI is poorly understood. Beta oscillations have previously been shown to play an important role in cognitive functions including working memory encoding. Decreased dopamine in motor cortico-striato-thalamo-cortical (CSTC) circuits increases the spectral power of beta oscillations and results in Parkinson’s disease motor symptoms. Analogous changes in parallel cognitive CSTC circuits involving the caudate and dorsolateral prefrontal cortex (DLPFC) may contribute to Parkinson’s disease CI. The objective of our study is to evaluate whether changes in beta oscillations in the caudate and DLPFC contribute to CI in Parkinson’s disease patients. To investigate this, we used local field potential recordings during deep brain stimulation surgery in 15 Parkinson’s disease patients. Local field potentials were recorded from DLPFC and caudate at rest and during a working memory task. We examined changes in beta oscillatory power during the working memory task as well as the relationship of beta oscillatory activity to preoperative cognitive status, as determined from neuropsychological testing results. We additionally conducted exploratory analyses on the relationship between cognitive impairment and task-based changes in spectral power in additional frequency bands. Spectral power of beta oscillations decreased in both DLPFC and caudate during working memory encoding and increased in these structures during feedback. Subjects with cognitive impairment had smaller decreases in caudate and DLPFC beta oscillatory power during encoding. In our exploratory analysis, we found that similar differences occurred in alpha frequencies in caudate and theta and alpha in DLPFC. Our findings suggest that oscillatory power changes in cognitive CSTC circuits may contribute to cognitive symptoms in Parkinson’s disease patients. These findings may inform the future development of novel neuromodulatory treatments for Parkinson’s disease CI.

Cognitive impairment (CI) is the most frequent nonmotor symptom in Parkinsons Disease (PD) and is associated with deficits in executive functions such as working memory. Previous studies have demonstrated that caudate beta power underlies learning and working memory. Decreased dopamine in motor cortico-striato-thalamo-cortical (CSTC) circuits results in increased beta power and PD motor symptoms. Analogous changes in cognitive CSTC circuits, including the caudate and dorsolateral prefrontal cortex (DLPFC), may contribute to PD CI. A better understanding of anatomic structures and neurophysiologic changes associated with working memory deficits is needed to develop potential neuromodulatory treatment strategies for PD CI. The objective of our study is to evaluate neurophysiologic changes underlying cognitive dysfunction in PD patients via direct local field potential recordings during deep brain stimulation surgery. Fifteen patients were included, one of which completed 2 minutes of resting state data collection while the other fourteen completed resting state collection and task based data collection with a verbal working memory 2-back task with feedback. LFP signals from DLPFC (50 channels) and caudate (25 channels) were sampled at 1000Hz, demeaned by channel and aligned to task events of encoding and feedback. Correlations of resting state beta power and pre-operative neuropsychological testing as well as caudate volumes were performed. Beta power decreased in both DLPFC and caudate during encoding and was significantly different for correct and incorrect trials, whereas beta power increased in DLPFC and caudate during feedback and was significantly different for correct and incorrect trials. Beta power during encoding was inversely correlated with memory scores on pre-operative neuropsychological testing. Understanding neurophysiologic correlates of cognitive dysfunction within cognitive CSTC circuits will aid in development of novel neuromodulatory therapies for patients with PD CI and other cognitive disorders.

We report an institutional experience of UCSF500 results from peripheral nerve tumor samples.METHODS: The UCSF 500 Cancer Gene Test uses capture-based next-generation sequencing to target and analyze the coding regions (exons) of 529 cancer genes, as well as select introns of 47 genes. This test can be ordered on solid tumors, hematopoietic malignancies, or lesional tissue specimens. A retrospective analysis of patients with schwannoma, malignant peripheral nerve sheath tumors (MPNST), neurofibroma, and other types of peripheral nerve tumors was performed.RESULTS: 178 samples from 163 patients with peripheral nerve tumors undergoing genetic testing met inclusion criteria. The top 5 mutated genes and their frequency for Neuroblastoma includes PIK3C2G (1.0), IGF1R (0.2), NOTCH2 (0.2), CIC (0.2), ATR (0.2). The 5 genes with the highest frequency copy number alteration (CNA) include SOX9, SRSF2, PRKAR1A, PRKCA, PPM1D. Schwannoma: NF2 (0.58), LZTR1 (0.21), MSH2 (0.14), FAT3 (.13), SMARCB1 (0.1). The top 5 CNA genes were all deletions on chromosome 22. MPNST: TYK2 (1.0), MRE11 (1.0), NF1 (0.65), SUZ12 (0.33), TP53 (0.32). Neurofibroma: TNFAIP3 (1.0), ADGRA2 (1.0), FLT4 (1.0), NF1 (0.61), PRKCH (0.11). Other: TERT (0.39), DDR1 (0.25), KMT2C (0.25), FAT1 (0.15), NRG1 (0.13).CONCLUSIONS: We describe an institutional experience with UCSF500 genetic test results on all peripheral nerve tumors sent for analysis from 2015 to 2022. Using these data to guide the development of understudied genes of interest could lead to increased understanding of the genetic mechanism of these tumors.