Deep brain stimulation (DBS) is an established treatment for patients with Parkinson’s disease (PD). Sleep disorders are common complications of PD and affected by subthalamic DBS treatment. To achieve more precise neuromodulation, chronic sleep monitoring and closed-loop DBS toward sleep-wake cycles could potentially be utilized. Local field potential (LFP) signals that are sensed by the DBS electrode could be processed as primary feedback signals. This is the first study to systematically investigate the sleep-stage classification based on LFPs in subthalamic nucleus (STN). With our newly developed recording and transmission system, STN-LFPs were collected from 12 PD patients during wakefulness and nocturnal polysomnography sleep monitoring at one month after DBS implantation. Automatic sleep-stage classification models were built with robust and interpretable machine learning methods (support vector machine and decision tree). The accuracy, sensitivity, selectivity, and specificity of the classification reached high values (above 90% at most measures) at group and individual levels. Features extracted in alpha (8–13 Hz), beta (13–35 Hz), and gamma (35–50 Hz) bands were found to contribute the most to the classification. These results will directly guide the engineering development of implantable sleep monitoring and closed-loop DBS and pave the way for a better understanding of the STN-LFP sleep patterns.

Freezing of gait is a debilitating symptom in advanced Parkinson’s disease and responds heterogeneously to treatments such as deep brain stimulation. Recent studies indicated that cortical dysfunction is involved in the development of freezing, while evidence depicting the specific role of the primary motor cortex in the multi-circuit pathology of freezing is lacking. Since abnormal beta-gamma phase-amplitude coupling recorded from the primary motor cortex in patients with Parkinson’s disease indicates parkinsonian state and responses to therapeutic deep brain stimulation, we hypothesized this metric might reveal unique information on understanding and improving therapy on freezing of gait. Here we directly recorded potentials in the primary motor cortex using subdural electrocorticography and synchronously captured gait freezing using optoelectronic motion-tracking systems in 16 freely-walking patients with Parkinson’s disease who received subthalamic nucleus deep brain stimulation surgery. Overall, we recorded 451 timed up-and-go walking trials, and quantified 7,073 s of stable walking and 3,384 s of gait freezing in conditions of ON/OFF-stimulation and with/without dual-tasking. We found that (i) high beta-gamma phase-amplitude coupling in the primary motor cortex was detected in freezing trials (i.e., walking trials that contained freezing), but not nonfreezing trials, and the high coupling in freezing trials was not caused by dual-tasking or the lack of movement; (ii) nonfreezing episodes within freezing trials also demonstrated abnormally high couplings, which predicted freezing severity; (iii) deep brain stimulation of subthalamic nucleus reduced these abnormal couplings and simultaneously improved freezing; and (iv) in trials that were at similar coupling levels, stimulation trials still demonstrated lower freezing severity than no-stimulation trials. These findings suggest that elevated phase-amplitude coupling in the primary motor cortex indicates higher probabilities of freezing. Therapeutic deep brain stimulation alleviates freezing by both decoupling cortical oscillations and enhancing cortical resistance to abnormal coupling. We formalized these findings to a novel “bandwidth model,” which specifies the role of cortical dysfunction, cognitive burden, and therapeutic stimulation on the emergence of freezing. By targeting key elements in the model, we may develop next-generation deep brain stimulation approaches for freezing of gait.

ABSTRACT.Purpose: To examine frequency and associated factors of glaucoma-like appearance of the optic nerve head in patients with intrasellar, suprasellar or parasellar tumours. Methods: This retrospective clinical observational study included patients who were consecutively treated for intrasellar tumours (n = 143), suprasellar tumours (n = 321), parasellar tumours (n = 36) or retrosellar tumour (n = 1), and all of whom had undergone fundus photography and full-threshold visual field examination. The tumour spectrum included 336 pituitary gland tumours, 32 meningiomas, 89 craniopharyngiomas, 9 chiasmal gliomas and 35 other types of tumours or lesions. An age-matched control group was formed from the population-based Beijing Eye Study. Using fundus photographs and visual field examinations, glaucoma was defined by a neuroretinal rim shape not following the ISNT rule (Disc glaucoma group) and by an abnormal rim shape plus glaucoma-like visual field defects (Field glaucoma group). Type and size of the tumours were assessed on neuroradiological images. Results: Five-hundred and one patients fulfilled the inclusion criteria. Disc glaucoma and Field glaucoma were detected significantly more frequently in the study population [34 (6.8%) patients and 31 (6.3%) patients, respectively] than in the population-based control group of the same ethnicity (1.3% ± 0.5%; p < 0.001). In multivariate analysis, presence of Disc glaucoma [odds ratio (OR) = 2.64; p = 0.016] and presence of Field glaucoma (OR = 3.01; p = 0.027) were significantly associated with tumour location [suprasellar > parasellar > intrasellar]. The same held true for tumour width (OR = 1.08; p = 0.002; and OR = 1.08; p = 0.003, respectively). Conclusions: Large perisellar tumours were associated with a glaucoma-like appearance of the optic nerve head in eyes. It may diagnostically and pathogenetically be of importance.