Generalized sleep decoding with basal ganglia signals in multiple movement disorders.

Sleep disturbances profoundly affect the quality of life in individuals with neurological disorders. Closed-loop deep brain stimulation (DBS) holds promise for alleviating sleep symptoms, however, this technique necessitates automated sleep stage decoding from intracranial signals. We leveraged overnight data from 121 patients with movement disorders (Parkinson's disease, Essential Tremor, Dystonia, Essential Tremor, Huntington's disease, and Tourette's syndrome) in whom synchronized polysomnograms and basal ganglia local field potentials were recorded, to develop a generalized, multi-class, sleep specific decoder - BGOOSE. This generalized model achieved 85% average accuracy across patients and across disease conditions, even in the presence of recordings from different basal ganglia targets. Furthermore, we also investigated the role of electrocorticography on decoding performances and proposed an optimal decoding map, which was shown to facilitate channel selection for optimal model performances. BGOOSE emerges as a powerful tool for generalized sleep decoding, offering exciting potentials for the precision stimulation delivery of DBS and better management of sleep disturbances in movement disorders.

Deep brain stimulation of the subthalamic nucleus for primary Meige syndrome: clinical outcomes and predictive factors.

OBJECTIVE: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has demonstrated efficacy against multiple types of dystonia, but only a few case reports and small-sample studies have investigated the clinical utility of STN-DBS for Meige syndrome, a rare but distressing form of craniofacial dystonia. Furthermore, the effects of DBS on critical neuropsychological sequelae, such as depression and anxiety, are rarely examined. In this study, the authors investigated the therapeutic efficacy of STN-DBS for both motor and psychiatric symptoms of Meige syndrome. METHODS: The authors retrospectively reviewed consecutive patients with Meige syndrome receiving bilateral STN-DBS at their institution from January 2016 to June 2023. Motor performance and nonmotor features including mood, cognitive function, and quality of life (QOL) were evaluated using standardized rating scales at baseline and at final postoperative follow-up. Clinical and demographic factors influencing postoperative motor outcome were evaluated by uni- and multivariable linear regression models. RESULTS: Fifty-one patients were ultimately included, with a mean ± SD follow-up duration of 27.3 ± 18.0 months. The mean Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) movement score improved from 12.9 ± 5.2 before surgery to 5.3 ± 4.2 at the last follow-up (mean improvement 58.9%, p < 0.001) and the mean BFMDRS disability score improved from 5.6 ± 3.3 to 2.9 ± 2.9 (mean improvement 44.6%, p < 0.001). Hamilton Depression and Anxiety Rating Scale scores also improved by 35.3% and 34.2%, respectively, and the postoperative 36-item Short-Form Health Survey score indicated substantial QOL enhancement. Global cognition remained stable after treatment. Multiple linear regression analysis identified disease duration (ß = -0.241, p = 0.027), preoperative anxiety severity (ß = -0.386, p = 0.001), and volume of activated tissue within the dorsolateral (sensorimotor) STN (ß = 0.483, p < 0.001) as independent predictors of motor outcome. CONCLUSIONS: These findings support STN-DBS as an effective and promising therapy for both motor and nonmotor symptoms of Meige syndrome. Timely diagnosis, treatment of preoperative anxiety, and precise electrode placement within the dorsolateral STN are essential for optimal clinical outcome.

Unlocking potential: low frequency subthalamic nucleus stimulation enhances executive function in Parkinson's disease patients with postural instability/gait disturbance.

Postural instability/gait disturbance (PIGD) is very common in advanced Parkinson's disease, and associated with cognitive dysfunction. Research suggests that low frequency (5-12 Hz) subthalamic nucleus-deep brain stimulation (STN-DBS) could improve cognition in patients with Parkinson's disease (PD). However, the clinical effectiveness of low frequency stimulation in PIGD patients has not been explored. This study was designed in a double-blinded randomized cross-over manner, aimed to verify the effect of low frequency STN-DBS on cognition of PIGD patients. Twenty-nine PIGD patients with STN-DBS were tested for cognitive at off (no stimulation), low frequency (5 Hz), and high frequency (130 Hz) stimulation. Neuropsychological tests included the Stroop Color-Word Test (SCWT), Verbal fluency test, Symbol Digital Switch Test, Digital Span Test, and Benton Judgment of Line Orientation test. For conflict resolution of executive function, low frequency stimulation significantly decreased the completion time of SCWT-C (p = 0.001) and Stroop interference effect (p < 0.001) compared to high frequency stimulation. However, no significant differences among stimulation states were found for other cognitive tests. Here we show, low frequency STN-DBS improved conflict resolution of executive function compared to high frequency. Our results demonstrated the possibility of expanding the treatment coverage of DBS to cognitive function in PIGD, which will facilitate integration of low frequency stimulation into future DBS programming.

Pallidal activities during sleep and sleep decoding in dystonia, Huntington's, and Parkinson's disease.

BACKGROUND: Sleep disturbances are highly prevalent in movement disorders, potentially due to the malfunctioning of basal ganglia structures. Pallidal deep brain stimulation (DBS) has been widely used for multiple movement disorders and been reported to improve sleep. We aimed to investigate the oscillatory pattern of pallidum during sleep and explore whether pallidal activities can be utilized to differentiate sleep stages, which could pave the way for sleep-aware adaptive DBS. METHODS: We directly recorded over 500 h of pallidal local field potentials during sleep from 39 subjects with movement disorders (20 dystonia, 8 Huntington's disease, and 11 Parkinson's disease). Pallidal spectrum and cortical-pallidal coherence were computed and compared across sleep stages. Machine learning approaches were utilized to build sleep decoders for different diseases to classify sleep stages through pallidal oscillatory features. Decoding accuracy was further associated with the spatial localization of the pallidum. RESULTS: Pallidal power spectra and cortical-pallidal coherence were significantly modulated by sleep-stage transitions in three movement disorders. Differences in sleep-related activities between diseases were identified in non-rapid eye movement (NREM) and REM sleep. Machine learning models using pallidal oscillatory features can decode sleep-wake states with over 90% accuracy. Decoding accuracies were higher in recording sites within the internus-pallidum than the external-pallidum, and can be precited using structural (P < 0.0001) and functional (P < 0.0001) whole-brain neuroimaging connectomics. CONCLUSION: Our findings revealed strong sleep-stage dependent distinctions in pallidal oscillations in multiple movement disorders. Pallidal oscillatory features were sufficient for sleep stage decoding. These data may facilitate the development of adaptive DBS systems targeting sleep problems that have broad translational prospects.

Association between Cognitive Impairment and Freezing of Gait in Patients with Parkinson's Disease.

Background: Freezing of gait (FOG) is a common disabling symptom in Parkinson's disease (PD). Cognitive impairment may contribute to FOG. Nevertheless, their correlations remain controversial. We aimed to investigate cognitive differences between PD patients with and without FOG (nFOG), explore correlations between FOG severity and cognitive performance and assess cognitive heterogeneity within the FOG patients. Methods: Seventy-four PD patients (41 FOG, 33 nFOG) and 32 healthy controls (HCs) were included. Comprehensive neuropsychological assessments testing cognitive domains of global cognition, executive function/attention, working memory, and visuospatial function were performed. Cognitive performance was compared between groups using independent t-test and ANCOVA adjusting for age, sex, education, disease duration and motor symptoms. The k-means cluster analysis was used to explore cognitive heterogeneity within the FOG group. Correlation between FOG severity and cognition were analyzed using partial correlations. Results: FOG patients showed significantly poorer performance in global cognition (MoCA, p < 0.001), frontal lobe function (FAB, p = 0.015), attention and working memory (SDMT, p < 0.001) and executive function (SIE, p = 0.038) than nFOG patients. The FOG group was divided into two clusters using the cluster analysis, of which cluster 1 exhibited worse cognition, and with older age, lower improvement rate, higher FOGQ3 score, and higher proportion of levodopa-unresponsive FOG than cluster 2. Further, in the FOG group, cognition was significantly correlated with FOG severity in MoCA (r = -0.382, p = 0.021), Stroop-C (r = 0.362, p = 0.030) and SIE (r = 0.369, p = 0.027). Conclusions: This study demonstrated that the cognitive impairments of FOG were mainly reflected by global cognition, frontal lobe function, executive function, attention and working memory. There may be heterogeneity in the cognitive impairment of FOG patients. Additionally, executive function was significantly correlated with FOG severity.

Fronto-parieto-subthalamic activity decodes motor status in Parkinson's disease.

AIMS: Patients with Parkinson's disease (PD) have various motor difficulties, including standing up, gait initiation and freezing of gait. These abnormalities are associated with cortico-subthalamic dysfunction. We aimed to reveal the characteristics of cortico-subthalamic activity in PD patients during different motor statuses. METHODS: Potentials were recorded in the superior parietal lobule (SPL), the primary motor cortex (M1), premotor cortex (PMC), and the bilateral subthalamic nucleus (STN) in 18 freely walking patients while sitting, standing, walking, dual-task walking, and freezing in medication "off" (Moff) and "on" (Mon) states. Different motor status activities were compared in band power, and a machine learning classifier was used to differentiate the motor statuses. RESULTS: SPL beta power was specifically inhibited from standing to walking, and negatively correlated with walking speed; M1 beta power reflected the degree of rigidity and was reversed by medication; XGBoost algorithm classified the five motor statuses with acceptable accuracy (68.77% in Moff, 60.58% in Mon). SPL beta power ranked highest in feature importance in both Moff and Mon states. CONCLUSION: SPL beta power plays an essential role in walking status classification and could be a physiological biomarker for walking speed, which would aid the development of adaptive DBS.

Deep Brain Stimulation Electrode Reconstruction: Comparison between Lead-DBS and Surgical Planning System.

BACKGROUND: Electrode reconstruction for postoperative deep brain simulation (DBS) can be achieved manually using a surgical planning system such as Surgiplan, or in a semi-automated manner using software such as the Lead-DBS toolbox. However, the accuracy of Lead-DBS has not been thoroughly addressed. METHODS: In our study, we compared the DBS reconstruction results of Lead-DBS and Surgiplan. We included 26 patients (21 with Parkinson's disease and 5 with dystonia) who underwent subthalamic nucleus (STN)-DBS, and reconstructed the DBS electrodes using the Lead-DBS toolbox and Surgiplan. The electrode contact coordinates were compared between Lead-DBS and Surgiplan with postoperative CT and MRI. The relative positions of the electrode and STN were also compared between the methods. Finally, the optimal contact during follow-up was mapped onto the Lead-DBS reconstruction results to check for overlap between the contacts and the STN. RESULTS: We found significant differences in all axes between Lead-DBS and Surgiplan with postoperative CT, with the mean variance for the X, Y, and Z coordinates being -0.13, -1.16, and 0.59 mm, respectively. Y and Z coordinates showed significant differences between Lead-DBS and Surgiplan with either postoperative CT or MRI. However, no significant difference in the relative distance of the electrode and the STN was found between the methods. All optimal contacts were located in the STN, with 70% of them located within the dorsolateral region of the STN in the Lead-DBS results. CONCLUSIONS: Although significant differences in electrode coordinates existed between Lead-DBS and Surgiplan, our results suggest that the coordinate difference was around 1 mm, and Lead-DBS can capture the relative distance between the electrode and the DBS target, suggesting it is reasonably accurate for postoperative DBS reconstruction.

Low-frequency oscillations link frontal and parietal cortex with subthalamic nucleus in conflicts.

Low-frequency oscillations (LFOs, 28 Hz) in the subthalamic nucleus(STN) are known to reflect cognitive conflict. However, it is unclear if LFOs mediate communication and functional interactions among regions implicated in conflict processing, such as the motor cortex (M1), premotor cortex (PMC), and superior parietal lobule (SPL). To investigate the potential contribution of LFOs to cognitive conflict mediation, we recorded M1, PMC, and SPL activities by right subdural electrocorticography (ECoG) simultaneously with bilateral STN local field potentials (LFPs) by deep brain stimulation electrodes in 13 patients with Parkinson's disease who performed the arrow version of the Eriksen flanker task. Elevated cue-related LFO activity was observed across patients during task trials, with the earliest onset in PMC and SPL. At cue onset, LFO power exhibited a significantly greater increase or a trend of a greater increase in the PMC, M1, and STN, and less increase in the SPL during high-conflict (incongruent) trials than in low-conflict (congruent) trials. The local LFO power increases in PMC, SPL, and right STN were correlated with response time, supporting the notion that these structures are critical hubs for cognitive conflict processing. This power increase was accompanied by increased functional connectivity between the PMC and right STN, which was correlated with response time across subjects. Finally, ipsilateral PMC-STN Granger causality was enhanced during high-conflict trials, with direction from STN to PMC. Our study indicates that LFOs link the frontal and parietal cortex with STN during conflicts, and the ipsilateral PMC-STN connection is specifically involved in this cognitive conflict processing.

Comparison of cognitive performance between patients with Parkinson's disease and dystonia using an intraoperative recognition memory test.

Neuroscientific studies on the function of the basal ganglia often examine the behavioral performance of patients with movement disorders, such as Parkinson's disease (PD) and dystonia (DT), while simultaneously examining the underlying electrophysiological activity during deep brain stimulation surgery. Nevertheless, to date, there have been no studies comparing the cognitive performance of PD and DT patients during surgery. In this study, we assessed the memory function of PD and DT patients with the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE). We also tested their cognitive performance during the surgery using a continuous recognition memory test. The results of the MoCA and MMSE failed to reveal significant differences between the PD and DT patients. Additionally, no significant difference was detected by the intraoperative memory test between the PD and DT patients. The intraoperative memory test scores were highly correlated with the MMSE scores and MoCA scores. Our data suggest that DT patients perform similarly to PD patients in cognitive tests during surgery, and intraoperative memory tests can be used as a quick memory assessment tool during surgery.

Balance response to levodopa predicts balance improvement after bilateral subthalamic nucleus deep brain stimulation in Parkinson's disease.

The effect of subthalamic nucleus deep brain stimulation (STN-DBS) on balance function in patients with Parkinson's disease (PD) and the potential outcome predictive factors remains unclear. We retrospectively included 261 PD patients who underwent STN-DBS and finished the 1-month follow-up (M1) assessment in the explorative set for identifying postoperative balance change predictors, and 111 patients who finished both the M1 and 12-month follow-up (M12) assessment in the validation set for verifying the identified factors. Motor and balance improvement were evaluated through the UPDRS-III and the Berg balance scale (BBS) and pull test (PT), respectively. Candidate predictors of balance improvement included age, disease duration, motor subtypes, baseline severity of PD, cognitive status, motor and balance response to levodopa, and stimulation parameters. In the off-medication condition, STN-DBS significantly improved BBS and PT performance in both the M1 and M12, in both datasets. While in the on-medication condition, no significant balance improvement was observed. Higher preoperative BBS response to levodopa was significantly associated with larger postoperative off-medication, but not on-medication, BBS (p < 0.001) and PT (p < 0.001) improvement in both the M1 and M12. BBS subitems 8, 9, 11, 13, and 14 were the major contributors to the prediction of balance improvement after STN-DBS. STN-DBS improves short-term off-medication, but not on-medication, balance function assessed through BBS and PT. Preoperative BBS response to levodopa best predicts postoperative off-medication balance improvement. For patients who manifested severe balance problems, a levodopa challenge test on BBS or the short version of BBS is recommended.