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NPJ Parkinson's Disease Jun 2024The subthalamic nucleus (STN) is pivotal in basal ganglia function in health and disease. Micro-electrode recordings of >25,000 recording sites from 146 Parkinson's...
The subthalamic nucleus (STN) is pivotal in basal ganglia function in health and disease. Micro-electrode recordings of >25,000 recording sites from 146 Parkinson's patients undergoing deep brain stimulation (DBS) allowed differentiation between subthalamic input, represented by local field potential (LFP), and output, reflected in spike discharge rate (SPK). As with many natural systems, STN neuronal activity exhibits power-law dynamics characterized by the exponent α. We, therefore, dissected STN data into aperiodic and periodic components using the Fitting Oscillations & One Over F (FOOOF) tool. STN LFP showed significantly higher aperiodic exponents than SPK. Additionally, SPK beta oscillations demonstrated a downward frequency shift compared to LFP. Finally, the STN aperiodic and spiking parameters explained a significant fraction of the variance of the burden and treatment efficacy of Parkinson's disease. The unique STN input-output dynamics may clarify its role in Parkinson's physiology and can be utilized in closed-loop DBS therapy.
PubMed: 38879564
DOI: 10.1038/s41531-024-00737-8 -
Turkish Neurosurgery Aug 2023Apathy is a newly recognized non-motor symptom and has a high impact on the quality of life in Parkinson's Disease (PD). The effect of subthalamic deep brain stimulation...
AIM
Apathy is a newly recognized non-motor symptom and has a high impact on the quality of life in Parkinson's Disease (PD). The effect of subthalamic deep brain stimulation (STN DBS) on apathy is controversial. This study aimed to investigate the impact of STN DBS on apathy and the possible relationship between apathy, depression, and levodopa equivalent dosage (LED) in PD patients.
MATERIAL AND METHODS
A total of 26 patients have been evaluated via the Unified Parkinson Disease Rating Scale (UPDRS), Beck Depression Inventory (Beck D), and Beck Anxiety Inventory (Beck A), Montreal Cognitive Assessment (MoCA), Parkinson Disease Questionnaire (PDQ-39) just before and 6 months after DBS.
RESULTS
Apathy scores (AES) showed a slight decrease from 54.00±10.30 to 52.69±8.88 without any statistical significance (p= 0.502) after DBS therapy. No correlation was detected between the post-treatment changes in apathy and UPDRS scores, Beck D, Beck A. Although the direction of the correlation between changes in AES scores and LED values was negative, the results did not reach statistical significance.
CONCLUSION
STN DBS therapy does not have a negative effect on apathy in PD Patients. Despite the satisfactory motor improvement, conservative dopaminergic dose reduction after surgery seems to be the main point to prevent apathy increase in PD patients after STN DBS.
PubMed: 38874248
DOI: 10.5137/1019-5149.JTN.43415-23.3 -
Neurogastroenterology and Motility Jun 2024The gut microbiota has been implicated in Parkinson's disease (PD), with alterations observed in microbial composition and reduced microbial species richness, which may...
BACKGROUND
The gut microbiota has been implicated in Parkinson's disease (PD), with alterations observed in microbial composition and reduced microbial species richness, which may influence gastrointestinal symptoms in PD patients. It remains to be determined whether the severity of gastrointestinal symptoms correlates with microbiota variations in PD patients treated pharmacologically or with subthalamic nucleus deep brain stimulation (STN-DBS) therapy. This study aims to explore how these treatments affect gut microbiota and gastrointestinal symptoms in PD, identifying specific microbial differences associated with each treatment modality.
METHODS
A total of 42 individuals diagnosed with PD, along with 38 age-matched household control participants, contributed stool samples for microbiota characterization. Differences in the gut microbiota across various groups of PD patients and their households were identified through comprehensive sequencing of the 16S rRNA gene amplicon sequencing.
KEY RESULTS
Differences in microbial communities were observed between PD patients and controls, as well as between PD patients receiving pharmacological treatment and those with STN-DBS. Pharmacologically treated advanced PD patients have higher gastrointestinal dysfunctions. Gut microbiota profile linked to STN-DBS and reduced levodopa consumption, characterized by its anti-inflammatory properties, might play a role in diminishing gastrointestinal dysfunction relative to only pharmacological treatments.
CONCLUSIONS & INFERENCES
Advanced PD patients on medication exhibit more gastrointestinal issues, despite relatively stable microbial diversity, indicating a complex interaction between gut microbiota, PD progression, and treatment effects. An imbalanced gut-brain axis, particularly due to reduced butyrate production, may lead to constipation by affecting the enteric nervous system, which emphasizes the need to incorporate gut microbiome insights into treatment strategies.
PubMed: 38873926
DOI: 10.1111/nmo.14846 -
Brain : a Journal of Neurology Jun 2024Control of actions allows adaptive, goal-directed behaviour. The basal ganglia, including the subthalamic nucleus, are thought to play a central role in dynamically...
Control of actions allows adaptive, goal-directed behaviour. The basal ganglia, including the subthalamic nucleus, are thought to play a central role in dynamically controlling actions through recurrent negative feedback loops with the cerebral cortex. Here, we summarize recent translational studies that used deep brain stimulation to record neural activity from and apply electrical stimulation to the subthalamic nucleus in people with Parkinson's disease. These studies have elucidated spatial, spectral and temporal features of the neural mechanisms underlying the controlled delay of actions in cortico-subthalamic networks and demonstrated their causal effects on behaviour in distinct processing windows. While these mechanisms have been conceptualized as control signals for suppressing impulsive response tendencies in conflict tasks and as decision threshold adjustments in value-based and perceptual decisions, we propose a common framework linking decision-making, cognition and movement. Within this framework subthalamic deep brain stimulation can lead to suboptimal choices by reducing the time that patients take for deliberation before committing to an action. However, clinical studies have consistently shown that the occurrence of impulse control disorders is reduced, not increased, after subthalamic deep brain stimulation surgery. This apparent contradiction can be reconciled when recognizing the multifaceted nature of impulsivity, its underlying mechanisms and modulation by treatment. While subthalamic deep brain stimulation renders patients susceptible to making decisions without proper forethought, this can be disentangled from effects related to dopamine comprising sensitivity to benefits vs. costs, reward delay aversion and learning from outcomes. Alterations in these dopamine-mediated mechanisms are thought to underlie the development of impulse control disorders, and can be relatively spared with reduced dopaminergic medication after subthalamic deep brain stimulation. Together, results from studies using deep brain stimulation as an experimental tool have improved our understanding of action control in the human brain and have important implications for treatment of patients with Neurological disorders.
PubMed: 38869168
DOI: 10.1093/brain/awae184 -
The Journal of Neuroscience : the... Jun 2024During natural behavior, an action often needs to be suddenly stopped in response to unexpected sensory input - referred to as reactive stopping. Reactive stopping has...
During natural behavior, an action often needs to be suddenly stopped in response to unexpected sensory input - referred to as reactive stopping. Reactive stopping has been mostly investigated in humans, which led to hypotheses about the involvement of different brain structures, in particular the hyperdirect pathway. Here, we directly investigate the contribution and interaction of two key regions of the hyperdirect pathway, the orbitofrontal cortex (OFC) and subthalamic nucleus (STN), using dual-area, multi-electrode recordings in male rats performing a stop-signal task. In this task rats have to initiate movement to a go-signal, and occasionally stop their movement to the go-signal side after a stop-signal, presented at various stop-signal delays.Both the OFC and STN show near-simultaneous field potential reductions in the beta frequency range (12-30 Hz) compared to the period preceding the go-signal and the movement period. These transient reductions (∼200 ms) only happen during reactive stopping, which is when the stop-signal was received after action initiation, and are well-timed after stop-signal onset and before the estimated time of stopping. Phase synchronization analysis also showed a transient attenuation of synchronization between the OFC and STN in the beta range during reactive stopping.The present results provide the first direct quantification of local neural oscillatory activity in the OFC and STN and interareal synchronization specifically timed during reactive stopping. Different studies observed increases in oscillatory beta activity and suggested increased synchronization between the orbitofrontal cortex (OFC) and subthalamic nucleus (STN) during reactive stopping. However, there has been inconsistency in the timing of beta modulations, and no study has yet investigated phase synchronization during stopping in both the OFC and STN with anatomical and temporal precision. Using dual-area recordings during a stopping task, we observed substantial decreases in beta power in both the OFC and STN at the time of stopping, alongside a decrease in beta phase synchronization. Rather than increased beta-band activity, the OFC and STN appear to facilitate stopping through local and inter-areal desynchronization. This may enable functionally specific neuronal activity to selectively inhibit motor behavior downstream.
PubMed: 38866485
DOI: 10.1523/JNEUROSCI.0463-24.2024 -
Journal of Psychiatric Research Jun 2024Deep brain stimulation (DBS) has been reported as a therapy option for the motor dysfunction of severe tardive dystonia (TD). The major psychiatric diseases, however,...
BACKGROUND
Deep brain stimulation (DBS) has been reported as a therapy option for the motor dysfunction of severe tardive dystonia (TD). The major psychiatric diseases, however, are contraindications to DBS treatment in TD patients.
METHODS
Six severe, medically refractory TD patients undergoing bilateral anterior capsulotomy combined with bilateral subthalamic nucleus (STN)-DBS treatment were studied retrospectively at two time points: pre-operation, and 1-3 years post-operation. Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) was used to assess the dystonia and disability. Depressive, anxiety, psychiatric symptoms, and Quality of Life (QoL) were evaluated using the 17-item Hamilton Depression Scale (HAMD-17), the 14-item Hamilton Anxiety Scale (HAMA-14), the Positive and Negative Syndrome Scale (PANSS), and 36-item Short-Form Health Survey (SF-36), respectively.
RESULTS
After receiving the combination treatment for 25 ± 11.6 months (range, 12-41 months), significant clinical symptom improvements were reported in TD patients. BFMDRS motor and disability scores were ameliorated by 78.5 ± 32.0% (p = 0.031) and 76.5 ± 38.6% (p = 0.031), respectively. The HAMD-17 and HAMA-14 scores were reduced by 60.3 ± 27.9% (p = 0.007) and 60.0 ± 24.6% (p = 0.009), respectively. Furthermore, the PANSS scores of the comorbidity schizophrenia TD patients decreased by 58.1 ± 6.0% (p = 0.022), and the QoL improved by 59.7 ± 14.1% (SF-36, p = 0.0001). During the research, there were no notable adverse effects or problems.
CONCLUSION
Bilateral anterior capsulotomy combined with bilateral STN-DBS may be an effective and relatively safe treatment option for severe TD comorbid with major psychiatric disorders.
PubMed: 38865864
DOI: 10.1016/j.jpsychires.2024.06.011 -
Journal of Neurophysiology Jun 2024Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for Parkinson's disease, but its mechanisms of action remain unclear. Detailed...
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for Parkinson's disease, but its mechanisms of action remain unclear. Detailed multi-compartment computational models of STN neurons are often used to study how DBS electric fields modulate the neurons. However, currently available STN neuron models have some limitations in their biophysical realism. In turn, the goal of this study was to update a detailed rodent STN neuron model originally developed by Gillies & Willshaw [2006]. Our design requirements consisted of explicitly representing an axon connected to the neuron and updating the ion channel distributions based on the experimental literature to match established electrophysiological features of rodent STN neurons. We found that adding an axon to the STN neuron model substantially altered its firing characteristics. We then used a genetic algorithm to optimize the biophysical parameters of the model. The optimized model exhibited spontaneous firing, action potential shape, hyperpolarization response, and frequency-current curve that aligned well with experimental recordings from STN neurons. Subsequently, we evaluated the general compatibility of the updated biophysics by applying them to 26 different STN neuron morphologies derived from 3D anatomical reconstructions. The different morphologies affected the firing behavior of the model, but the updated biophysics were robustly capable of maintaining the desired electrophysiological features. The new STN neuron model developed in this work offers a valuable tool for studying STN neuron firing properties, and may find application in simulating STN local field potentials or analysis of the effects of STN DBS.
PubMed: 38863430
DOI: 10.1152/jn.00287.2023 -
Translational Neuroscience Jan 2024Motor commands are transmitted from the motor cortical areas to effectors mostly via the corticospinal (CS) projection. Several subcortical motor nuclei also play an... (Review)
Review
Adaptation of the layer V supraspinal motor corticofugal projections from the primary (M1) and premotor (PM) cortices after CNS motor disorders in non-human primates: A survey.
Motor commands are transmitted from the motor cortical areas to effectors mostly via the corticospinal (CS) projection. Several subcortical motor nuclei also play an important role in motor control, the subthalamic nucleus, the red nucleus, the reticular nucleus and the superior colliculus. These nuclei are influenced by motor cortical areas via respective corticofugal projections, which undergo complex adaptations after motor trauma (spinal cord/motor cortex injury) or motor disease (Parkinson), both in the absence or presence of putative treatments, as observed in adult macaque monkeys. A dominant effect was a nearly complete suppression of the corticorubral projection density and a strong downregulation of the corticoreticular projection density, with the noticeable exception in the latter case of a considerable increase of projection density following spinal cord injury, even enhanced when an anti-NogoA antibody treatment was administered. The effects were diverse and less prominent on the corticotectal and corticosubthalamic projections. The CS projection may still be the major efferent pathway through which motor adaptations can take place after motor trauma or disease. However, the parallel supraspinal motor corticofugal projections may also participate in connectional adaptations supporting the functional recovery of motor abilities, representing potential targets for future clinical strategies, such as selective electrical neurostimulations.
PubMed: 38860225
DOI: 10.1515/tnsci-2022-0342 -
Cureus May 2024Background Deep brain stimulation (DBS) is a well-recognised treatment for advanced Parkinson's disease (PD) patients. Structural brain alterations of the white matter...
Background Deep brain stimulation (DBS) is a well-recognised treatment for advanced Parkinson's disease (PD) patients. Structural brain alterations of the white matter can correlate with disease progression and act as a biomarker for DBS therapy outcomes. This study aims to develop a machine learning-driven predictive model for DBS patient selection using whole-brain white matter radiomics and common clinical variables. Methodology A total of 120 PD patients underwent DBS of the subthalamic nucleus. Their therapy effect was assessed at the one-year follow-up with the Unified Parkinson's Disease Rating Scale-part III (UPDRSIII) motor component. Radiomics analysis of whole-brain white matter was performed with PyRadiomics. The following machine learning methods were used: logistic regression (LR), support vector machine, naïve Bayes, K-nearest neighbours, and random forest (RF) to allow prediction of clinically meaningful UPRDSIII motor response before and after. Clinical variables were also added to the model to improve accuracy. Results The RF model showed the best performance on the final whole dataset with an area under the curve (AUC) of 0.99, accuracy of 0.95, sensitivity of 0.93, and specificity of 0.97. At the same time, the LR model showed an AUC of 0.93, accuracy of 0.88, sensitivity of 0.84, and specificity of 0.91. Conclusions Machine learning models can be used in clinical decision support tools which can deliver true personalised therapy recommendations for PD patients. Clinicians and engineers should choose between best-performing, less interpretable models vs. most interpretable, lesser-performing models. Larger clinical trials would allow to build trust among clinicians and patients to widely use these AI tools in the future.
PubMed: 38854362
DOI: 10.7759/cureus.59915 -
Movement Disorders Clinical Practice Jun 2024In our early experience programming directional deep brain stimulation (d-DBS) in PD, we found the optimal directional segment changed over time in some patients. To...
BACKGROUND
In our early experience programming directional deep brain stimulation (d-DBS) in PD, we found the optimal directional segment changed over time in some patients. To determine the frequency/reasons for this we examined whether (1) different programmers would identify the same segment as "optimal"; and (2) the same programmer would select the same "optimal" segment over time. We hypothesized there would be a moderately high level of agreement on optimal electrode selection between different assessors and repeated assessments by the same evaluator.
METHODS
This was a prospective, double-blind investigation evaluating the reliability and stability of programming d-DBS. Each patient underwent a mono-polar survey four times (2 time points by 2 separate assessors). The primary aim was the inter-rater agreement of selecting the optimal electrode at 1 and 6 months. The secondary aim was to determine the intra-rater agreement of selecting the optimal electrode from 1 to 6 months.
RESULTS
Twenty-one patients were enrolled. There was fair inter-rater agreement at 1 month and moderate at 6 months. There was minimal intra-rater agreement between 1 and 6 months.
DISCUSSION
The data refuted our hypothesis. Potential reasons for low agreement include (1) the arduous/subjective nature of identifying the optimal electrode in d-DBS systems, especially in well-placed electrodes; and/or (2) acute changes to the location of stimulation delivery offering temporary improvement in symptoms. Key takeaways gathered were it may, (1) behoove the programmer to explore different electrode montages after a period of time; and (2) be more efficient to review the directional electrode montage only when dictated by clinical symptoms/disease progression.
PubMed: 38853400
DOI: 10.1002/mdc3.14120