Prefrontal Physiomarkers of Anxiety and Depression in Parkinson’s Disease

Abstract

Objective: Anxiety and depression are prominent non-motor symptoms of Parkinson’s disease (PD), but their pathophysiology remains unclear. We sought to understand their neurophysiological correlates from chronic invasive recordings of the prefrontal cortex (PFC).Methods: We studied four patients undergoing deep brain stimulation (DBS) for their motor signs, who had comorbid mild to moderate anxiety and/or depressive symptoms. In addition to their basal ganglia leads, we placed a permanent prefrontal subdural 4-contact lead. These electrodes were attached to an investigational pulse generator with the capability to sense and store field potential signals, as well as deliver therapeutic neurostimulation. At regular intervals over 3–5 months, participants paired brief invasive neural recordings with self-ratings of symptoms related to depression and anxiety.Results: Mean age was 61 ± 7 years, mean disease duration was 11 ± 8 years and a mean Unified Parkinson’s Disease Rating Scale, with part III (UPDRS-III) off medication score of 37 ± 13. Mean Beck Depression Inventory (BDI) score was 14 ± 5 and Beck Anxiety Index was 16.5 ± 5. Prefrontal cortex spectral power in the beta band correlated with patient self-ratings of symptoms of depression and anxiety, with r-values between 0.31 and 0.48. Mood scores showed negative correlation with beta spectral power in lateral locations, and positive correlation with beta spectral power in a mesial recording location, consistent with the dichotomous organization of reward networks in PFC.Interpretation: These findings suggest a physiological basis for anxiety and depression in PD, which may be useful in the development of neurostimulation paradigms for these non-motor disease features.

Neural correlates of impulse control behaviors in Parkinson’s disease: Analysis of multimodal imaging data

“…Nevertheless, PD patients with depression and anxiety should be monitored closely for ICB symptoms since these patients seem to be more vulnerable ( Marín-Lahoz et al, 2019 ). In this study, correlation analysis within the PDICB+ group also revealed higher depression score related to reduced gray matter volume in the medial frontal cortex, a region which has been associated with ICB and depression ( de Hemptinne et al, 2021 , Imperiale et al, 2018 , Schmaal et al, 2017 , Voon et al, 2011 ). The medial frontal cortex is known to be involved in cognitive control, reward, and affective processes ( Putnam and Chang, 2021 , Ridderinkhof et al, 2004 ).…”

Stereotactic electroencephalography in epilepsy patients for mapping of neural circuits related to emotional and psychiatric behaviors: a systematic review

“…Sensing closed-loop devices implanted for psychiatric or nonpsychiatric indications may be leveraged to further our understanding of mood fluctuations, social interactions, and affective disorders in ambulatory settings. [55][56][57] Our review has a number of limitations. Using the RDoC framework, we limited our search to positive and negative valence domains given their relevance to psychiatric behaviors.…”

Artifact characterization and mitigation techniques during concurrent sensing and stimulation using bidirectional deep brain stimulation platforms

“…Two bipolar recording channels were also obtained from the two pairs of contacts (contact pairs 8–9 and 10–11) on both ECoG strips. The DBS electrode (Medtronic Model 3387) and 4-contact flexible ECoG paddle (Medtronic Model 5387A) in each hemisphere were connected to an implantable neural stimulator (INS), such that each DBS electrode was connected to an independent INS ( de Hemptinne et al, 2021 ). In total, there were three bipolar recording channels per hemisphere, one sensing VC/VS activity, and two sensing OFC activity.…”