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1.
J Neurosci Methods ; 407: 110156, 2024 Jul.
Article En | MEDLINE | ID: mdl-38703796

BACKGROUND: DBS entails the insertion of an electrode into the patient brain, enabling Subthalamic nucleus (STN) stimulation. Accurate delineation of STN borders is a critical but time-consuming task, traditionally reliant on the neurosurgeon experience in deciphering the intricacies of microelectrode recording (MER). While clinical outcomes of MER have been satisfactory, they involve certain risks to patient safety. Recently, there has been a growing interest in exploring the potential of local field potentials (LFP) due to their correlation with the STN motor territory. METHOD: A novel STN detection system, integrating LFP and wavelet packet transform (WPT) with stacking ensemble learning, is developed. Initial steps involve the inclusion of soft thresholding to increase robustness to LFP variability. Subsequently, non-linear WPT features are extracted. Finally, a unique ensemble model, comprising a dual-layer structure, is developed for STN localization. We harnessed the capabilities of support vector machine, Decision tree and k-Nearest Neighbor in conjunction with long short-term memory (LSTM) network. LSTM is pivotal for assigning adequate weights to every base model. RESULTS: Results reveal that the proposed model achieved a remarkable accuracy and F1-score of 89.49% and 91.63%. COMPARISON WITH EXISTING METHODS: Ensemble model demonstrated superior performance when compared to standalone base models and existing meta techniques. CONCLUSION: This framework is envisioned to enhance the efficiency of DBS surgery and reduce the reliance on clinician experience for precise STN detection. This achievement is strategically significant to serve as an invaluable tool for refining the electrode trajectory, potentially replacing the current methodology based on MER.


Deep Brain Stimulation , Subthalamic Nucleus , Wavelet Analysis , Subthalamic Nucleus/physiology , Humans , Deep Brain Stimulation/methods , Deep Brain Stimulation/instrumentation , Support Vector Machine , Machine Learning , Signal Processing, Computer-Assisted , Microelectrodes
2.
Nat Commun ; 15(1): 4602, 2024 May 30.
Article En | MEDLINE | ID: mdl-38816390

Circadian rhythms have been shown in the subthalamic nucleus (STN) in Parkinson's disease (PD), but only a few studies have focused on the globus pallidus internus (GPi). This retrospective study investigates GPi circadian rhythms in a large cohort of subjects with PD (130 recordings from 93 subjects) with GPi activity chronically recorded in their home environment. We found a significant change in GPi activity between daytime and nighttime in most subjects (82.4%), with a reduction in GPi activity at nighttime in 56.2% of recordings and an increase in activity in 26.2%. GPi activity in higher frequency bands ( > 20 Hz) was more likely to decrease at night and in patients taking extended-release levodopa medication. Our results suggest that circadian fluctuations in the GPi vary across individuals and that increased power at night might be due to the reemergence of pathological neural activity. These findings should be considered to ensure successful implementation of adaptive neurostimulation paradigms in the real-world.


Circadian Rhythm , Deep Brain Stimulation , Globus Pallidus , Levodopa , Parkinson Disease , Humans , Globus Pallidus/physiopathology , Parkinson Disease/physiopathology , Circadian Rhythm/physiology , Male , Female , Middle Aged , Retrospective Studies , Aged , Levodopa/therapeutic use , Subthalamic Nucleus/physiopathology
3.
Proc Natl Acad Sci U S A ; 121(22): e2316149121, 2024 May 28.
Article En | MEDLINE | ID: mdl-38768342

Speech impediments are a prominent yet understudied symptom of Parkinson's disease (PD). While the subthalamic nucleus (STN) is an established clinical target for treating motor symptoms, these interventions can lead to further worsening of speech. The interplay between dopaminergic medication, STN circuitry, and their downstream effects on speech in PD is not yet fully understood. Here, we investigate the effect of dopaminergic medication on STN circuitry and probe its association with speech and cognitive functions in PD patients. We found that changes in intrinsic functional connectivity of the STN were associated with alterations in speech functions in PD. Interestingly, this relationship was characterized by altered functional connectivity of the dorsolateral and ventromedial subdivisions of the STN with the language network. Crucially, medication-induced changes in functional connectivity between the STN's dorsolateral subdivision and key regions in the language network, including the left inferior frontal cortex and the left superior temporal gyrus, correlated with alterations on a standardized neuropsychological test requiring oral responses. This relation was not observed in the written version of the same test. Furthermore, changes in functional connectivity between STN and language regions predicted the medication's downstream effects on speech-related cognitive performance. These findings reveal a previously unidentified brain mechanism through which dopaminergic medication influences speech function in PD. Our study sheds light into the subcortical-cortical circuit mechanisms underlying impaired speech control in PD. The insights gained here could inform treatment strategies aimed at mitigating speech deficits in PD and enhancing the quality of life for affected individuals.


Language , Parkinson Disease , Speech , Subthalamic Nucleus , Humans , Parkinson Disease/physiopathology , Parkinson Disease/drug therapy , Subthalamic Nucleus/physiopathology , Subthalamic Nucleus/drug effects , Male , Speech/physiology , Speech/drug effects , Female , Middle Aged , Aged , Magnetic Resonance Imaging , Dopamine/metabolism , Nerve Net/drug effects , Nerve Net/physiopathology , Cognition/drug effects , Dopamine Agents/pharmacology , Dopamine Agents/therapeutic use
4.
Mov Disord Clin Pract ; 11(6): 698-703, 2024 Jun.
Article En | MEDLINE | ID: mdl-38698586

BACKGROUND: Blood pressure control in Parkinson's disease (PD) under subthalamic deep brain stimulation (STN-DBS) is influenced by several intertwined aspects, including autonomic failure and levodopa treatment. OBJECTIVE: To evaluate the effect of chronic STN-DBS, levodopa, and their combination on cardiovascular autonomic functions in PD. METHODS: We performed cardiovascular reflex tests (CRTs) before and 6-months after STN-DBS surgery in 20 PD patients (pre-DBS vs. post-DBS). CRTs were executed without and with medication (med-OFF vs. med-ON). RESULTS: CRT results and occurrence of neurogenic orthostatic hypotension (OH) did not differ between pre- and post-DBS studies in med-OFF condition. After levodopa intake, the BP decrease during HUTT was significantly greater compared to med-OFF, both at pre-DBS and post-DBS evaluation. Levodopa-induced OH was documented in 25% and 5% of patients in pre-DBS/med-ON and post-DBS/med-ON study. CONCLUSION: Chronic stimulation did not influence cardiovascular responses, while levodopa exerts a relevant hypotensive effect. The proportion of patients presenting levodopa-induced OH decreases after STN-DBS surgery.


Antiparkinson Agents , Autonomic Nervous System , Deep Brain Stimulation , Levodopa , Parkinson Disease , Humans , Parkinson Disease/therapy , Parkinson Disease/physiopathology , Deep Brain Stimulation/methods , Male , Female , Middle Aged , Aged , Levodopa/therapeutic use , Levodopa/adverse effects , Levodopa/administration & dosage , Autonomic Nervous System/physiopathology , Autonomic Nervous System/drug effects , Antiparkinson Agents/therapeutic use , Antiparkinson Agents/adverse effects , Blood Pressure/physiology , Blood Pressure/drug effects , Subthalamic Nucleus/physiopathology , Hypotension, Orthostatic/therapy , Hypotension, Orthostatic/etiology , Hypotension, Orthostatic/physiopathology
5.
Neurobiol Dis ; 197: 106529, 2024 Jul.
Article En | MEDLINE | ID: mdl-38740349

Parkinson's disease (PD) is characterized by the disruption of repetitive, concurrent and sequential motor actions due to compromised timing-functions principally located in cortex-basal ganglia (BG) circuits. Increasing evidence suggests that motor impairments in untreated PD patients are linked to an excessive synchronization of cortex-BG activity at beta frequencies (13-30 Hz). Levodopa and subthalamic nucleus deep brain stimulation (STN-DBS) suppress pathological beta-band reverberation and improve the motor symptoms in PD. Yet a dynamic tuning of beta oscillations in BG-cortical loops is fundamental for movement-timing and synchronization, and the impact of PD therapies on sensorimotor functions relying on neural transmission in the beta frequency-range remains controversial. Here, we set out to determine the differential effects of network neuromodulation through dopaminergic medication (ON and OFF levodopa) and STN-DBS (ON-DBS, OFF-DBS) on tapping synchronization and accompanying cortical activities. To this end, we conducted a rhythmic finger-tapping study with high-density EEG-recordings in 12 PD patients before and after surgery for STN-DBS and in 12 healthy controls. STN-DBS significantly ameliorated tapping parameters as frequency, amplitude and synchrony to the given auditory rhythms. Aberrant neurophysiologic signatures of sensorimotor feedback in the beta-range were found in PD patients: their neural modulation was weaker, temporally sluggish and less distributed over the right cortex in comparison to controls. Levodopa and STN-DBS boosted the dynamics of beta-band modulation over the right hemisphere, hinting to an improved timing of movements relying on tactile feedback. The strength of the post-event beta rebound over the supplementary motor area correlated significantly with the tapping asynchrony in patients, thus indexing the sensorimotor match between the external auditory pacing signals and the performed taps. PD patients showed an excessive interhemispheric coherence in the beta-frequency range during the finger-tapping task, while under DBS-ON the cortico-cortical connectivity in the beta-band was normalized. Ultimately, therapeutic DBS significantly ameliorated the auditory-motor coupling of PD patients, enhancing the electrophysiological processing of sensorimotor feedback-information related to beta-band activity, and thus allowing a more precise cued-tapping performance.


Beta Rhythm , Cortical Synchronization , Deep Brain Stimulation , Fingers , Levodopa , Motor Cortex , Parkinson Disease , Subthalamic Nucleus , Humans , Parkinson Disease/therapy , Parkinson Disease/physiopathology , Male , Female , Middle Aged , Deep Brain Stimulation/methods , Aged , Beta Rhythm/physiology , Motor Cortex/physiopathology , Motor Cortex/physiology , Cortical Synchronization/physiology , Levodopa/therapeutic use , Subthalamic Nucleus/physiopathology , Antiparkinson Agents/therapeutic use , Electroencephalography
6.
Neuroimage Clin ; 42: 103617, 2024.
Article En | MEDLINE | ID: mdl-38749145

BACKGROUND AND OBJECTIVES: The intricate relationship between deep brain stimulation (DBS) in Parkinson's disease (PD) and cognitive impairment has lately garnered substantial attention. The presented study evaluated pre-DBS structural and microstructural cerebral patterns as possible predictors of future cognitive decline in PD DBS patients. METHODS: Pre-DBS MRI data in 72 PD patients were combined with neuropsychological examinations and follow-up for an average of 2.3 years after DBS implantation procedure using a screening cognitive test validated for diagnosis of mild cognitive impairment in PD in a Czech population - Dementia Rating Scale 2. RESULTS: PD patients who would exhibit post-DBS cognitive decline were found to have, already at the pre-DBS stage, significantly lower cortical thickness and lower microstructural complexity than cognitively stable PD patients. Differences in the regions directly related to cognition as bilateral parietal, insular and cingulate cortices, but also occipital and sensorimotor cortex were detected. Furthermore, hippocampi, putamina, cerebellum and upper brainstem were implicated as well, all despite the absence of pre-DBS differences in cognitive performance and in the position of DBS leads or stimulation parameters between the two groups. CONCLUSIONS: Our findings indicate that the cognitive decline in the presented PD cohort was not attributable primarily to DBS of the subthalamic nucleus but was associated with a clinically silent structural and microstructural predisposition to future cognitive deterioration present already before the DBS system implantation.


Cognitive Dysfunction , Deep Brain Stimulation , Magnetic Resonance Imaging , Parkinson Disease , Subthalamic Nucleus , Humans , Deep Brain Stimulation/adverse effects , Parkinson Disease/therapy , Parkinson Disease/diagnostic imaging , Parkinson Disease/pathology , Male , Female , Subthalamic Nucleus/diagnostic imaging , Middle Aged , Cognitive Dysfunction/etiology , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/physiopathology , Cognitive Dysfunction/pathology , Aged , Magnetic Resonance Imaging/methods , Neuropsychological Tests
7.
Physiol Rep ; 12(9): e16001, 2024 May.
Article En | MEDLINE | ID: mdl-38697943

Local field potential (LFP) oscillations in the beta band (13-30 Hz) in the subthalamic nucleus (STN) of Parkinson's disease patients have been implicated in disease severity and treatment response. The relationship between single-neuron activity in the STN and regional beta power changes remains unclear. We used spike-triggered average (STA) to assess beta synchronization in STN. Beta power and STA magnitude at the beta frequency range were compared in three conditions: STN versus other subcortical structures, dorsal versus ventral STN, and high versus low beta power STN recordings. Magnitude of STA-LFP was greater within the STN compared to extra-STN structures along the trajectory path, despite no difference in percentage of the total power. Within the STN, there was a higher percent beta power in dorsal compared to ventral STN but no difference in STA-LFP magnitude. Further refining the comparison to high versus low beta peak power recordings inside the STN to evaluate if single-unit activity synchronized more strongly with beta band activity in areas of high beta power resulted in a significantly higher STA magnitude for areas of high beta power. Overall, these results suggest that STN single units strongly synchronize to beta activity, particularly units in areas of high beta power.


Beta Rhythm , Parkinson Disease , Subthalamic Nucleus , Subthalamic Nucleus/physiopathology , Parkinson Disease/physiopathology , Humans , Male , Beta Rhythm/physiology , Middle Aged , Female , Aged , Action Potentials/physiology , Neurons/physiology , Deep Brain Stimulation/methods
8.
Nat Commun ; 15(1): 3130, 2024 Apr 11.
Article En | MEDLINE | ID: mdl-38605039

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) produces an electrophysiological signature called evoked resonant neural activity (ERNA); a high-frequency oscillation that has been linked to treatment efficacy. However, the single-neuron and synaptic bases of ERNA are unsubstantiated. This study proposes that ERNA is a subcortical neuronal circuit signature of DBS-mediated engagement of the basal ganglia indirect pathway network. In people with Parkinson's disease, we: (i) showed that each peak of the ERNA waveform is associated with temporally-locked neuronal inhibition in the STN; (ii) characterized the temporal dynamics of ERNA; (iii) identified a putative mesocircuit architecture, embedded with empirically-derived synaptic dynamics, that is necessary for the emergence of ERNA in silico; (iv) localized ERNA to the dorsal STN in electrophysiological and normative anatomical space; (v) used patient-wise hotspot locations to assess spatial relevance of ERNA with respect to DBS outcome; and (vi) characterized the local fiber activation profile associated with the derived group-level ERNA hotspot.


Deep Brain Stimulation , Parkinson Disease , Subthalamic Nucleus , Humans , Parkinson Disease/therapy , Deep Brain Stimulation/methods , Subthalamic Nucleus/physiology , Basal Ganglia/physiology , Neurons/physiology
9.
Nat Commun ; 15(1): 3166, 2024 Apr 12.
Article En | MEDLINE | ID: mdl-38605062

Increasing evidence suggests a considerable role of pre-movement beta bursts for motor control and its impairment in Parkinson's disease. However, whether beta bursts occur during precise and prolonged movements and if they affect fine motor control remains unclear. To investigate the role of within-movement beta bursts for fine motor control, we here combine invasive electrophysiological recordings and clinical deep brain stimulation in the subthalamic nucleus in 19 patients with Parkinson's disease performing a context-varying task that comprised template-guided and free spiral drawing. We determined beta bursts in narrow frequency bands around patient-specific peaks and assessed burst amplitude, duration, and their immediate impact on drawing speed. We reveal that beta bursts occur during the execution of drawing movements with reduced duration and amplitude in comparison to rest. Exclusively when drawing freely, they parallel reductions in acceleration. Deep brain stimulation increases the acceleration around beta bursts in addition to a general increase in drawing velocity and improvements of clinical function. These results provide evidence for a diverse and task-specific role of subthalamic beta bursts for fine motor control in Parkinson's disease; suggesting that pathological beta bursts act in a context dependent manner, which can be targeted by clinical deep brain stimulation.


Deep Brain Stimulation , Parkinson Disease , Subthalamic Nucleus , Humans , Parkinson Disease/therapy , Beta Rhythm/physiology , Movement/physiology
11.
J Integr Neurosci ; 23(4): 84, 2024 Apr 19.
Article En | MEDLINE | ID: mdl-38682230

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established treatment for the motor symptoms of Parkinson's disease (PD). While PD is primarily characterized by motor symptoms such as tremor, rigidity, and bradykinesia, it also involves a range of non-motor symptoms, and anxiety is one of the most common. The relationship between PD and anxiety is complex and can be a result of both pathological neural changes and the psychological and emotional impacts of living with a chronic progressive condition. Managing anxiety in PD is critical for improving the patients' quality of life. However, patients undergoing STN DBS can occasionally experience increased anxiety. METHODS: This study investigates changes in risk-avoidant behavior following STN DBS in a pre-motor animal model of PD under chronic and acute unilateral high frequency stimulation. RESULTS: No significant changes in risk-avoidant behaviors were observed in rats who underwent STN DBS compared with sham stimulation controls. Chronic stimulation prevented sensitization in the elevated zero maze. CONCLUSIONS: These results suggest that unilateral stimulation of the STN may have minimal effects on risk-avoidant behaviors in PD. However, additional research is required to fully understand the mechanisms responsible for changes in anxiety during STN DBS for PD.


Deep Brain Stimulation , Disease Models, Animal , Oxidopamine , Subthalamic Nucleus , Animals , Oxidopamine/pharmacology , Male , Behavior, Animal/physiology , Parkinsonian Disorders/therapy , Parkinsonian Disorders/physiopathology , Anxiety/etiology , Anxiety/physiopathology , Rats , Rats, Sprague-Dawley , Avoidance Learning/physiology , Parkinson Disease/therapy , Parkinson Disease/physiopathology
12.
Neurobiol Dis ; 195: 106490, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38561111

The auditory oddball is a mainstay in research on attention, novelty, and sensory prediction. How this task engages subcortical structures like the subthalamic nucleus and substantia nigra pars reticulata is unclear. We administered an auditory OB task while recording single unit activity (35 units) and local field potentials (57 recordings) from the subthalamic nucleus and substantia nigra pars reticulata of 30 patients with Parkinson's disease undergoing deep brain stimulation surgery. We found tone modulated and oddball modulated units in both regions. Population activity differentiated oddball from standard trials from 200 ms to 1000 ms after the tone in both regions. In the substantia nigra, beta band activity in the local field potential was decreased following oddball tones. The oddball related activity we observe may underlie attention, sensory prediction, or surprise-induced motor suppression.


Acoustic Stimulation , Deep Brain Stimulation , Parkinson Disease , Pars Reticulata , Subthalamic Nucleus , Humans , Subthalamic Nucleus/physiology , Male , Middle Aged , Female , Parkinson Disease/physiopathology , Parkinson Disease/therapy , Aged , Pars Reticulata/physiology , Deep Brain Stimulation/methods , Acoustic Stimulation/methods , Auditory Perception/physiology , Evoked Potentials, Auditory/physiology , Substantia Nigra/physiology , Adult
13.
Medicine (Baltimore) ; 103(17): e37955, 2024 Apr 26.
Article En | MEDLINE | ID: mdl-38669414

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN-DBS) is a viable therapeutic for advanced Parkinson's disease. However, the efficacy and safety of STN-DBS under local anesthesia (LA) versus general anesthesia (GA) remain controversial. This meta-analysis aims to compare them using an expanded sample size. METHODS: The databases of Embase, Cochrane Library and Medline were systematically searched for eligible cohort studies published between 1967 and 2023. Clinical efficacy was assessed using either Unified Parkinson's Disease Rating Scale (UPDRS) section III scores or levodopa equivalent dosage requirements. Subgroup analyses were performed to assess complications (adverse effects related to stimulation, general neurological and surgical complications, and hardware-related complications). RESULTS: Fifteen studies, comprising of 13 retrospective cohort studies and 2 prospective cohort studies, involving a total of 943 patients were included in this meta-analysis. The results indicate that there were no significant differences between the 2 groups with regards to improvement in UPDRS III score or postoperative levodopa equivalent dosage requirement. However, subgroup analysis revealed that patients who underwent GA with intraoperative imaging had higher UPDRS III score improvement compared to those who received LA with microelectrode recording (MER) (P = .03). No significant difference was found in the improvement of UPDRS III scores between the GA group and LA group with MER. Additionally, there were no notable differences in the incidence rates of complications between these 2 groups. CONCLUSIONS: Our meta-analysis indicates that STN-DBS performed under GA or LA have similar clinical outcomes and complications. Therefore, GA may be a suitable option for patients with severe symptoms who cannot tolerate the procedure under LA. Additionally, the GA group with intraoperative imaging showed better clinical outcomes than the LA group with MER. A more compelling conclusion would require larger prospective cohort studies with a substantial patient population and extended long follow-up to validate.


Anesthesia, General , Anesthesia, Local , Deep Brain Stimulation , Parkinson Disease , Subthalamic Nucleus , Humans , Deep Brain Stimulation/methods , Deep Brain Stimulation/adverse effects , Parkinson Disease/therapy , Anesthesia, General/methods , Anesthesia, Local/methods , Treatment Outcome
14.
Neurotherapeutics ; 21(3): e00356, 2024 Apr.
Article En | MEDLINE | ID: mdl-38608373

Deep brain stimulation (DBS) is an established therapeutic tool for the treatment of Parkinson's disease (PD). The mechanisms of DBS for PD are likely rooted in modulation of the subthalamo-pallidal network. However, it can be difficult to electrophysiologically interrogate that network in human patients. The recent identification of large amplitude evoked potential (EP) oscillations from DBS in the subthalamic nucleus (STN) or globus pallidus internus (GPi) are providing new scientific opportunities to expand understanding of human basal ganglia network activity. In turn, the goal of this review is to provide a summary of DBS-induced EPs in the basal ganglia and attempt to explain various components of the EP waveforms from their likely network origins. Our analyses suggest that DBS-induced antidromic activation of globus pallidus externus (GPe) is a key driver of these oscillatory EPs, independent of stimulation location (i.e. STN or GPi). This suggests a potentially more important role for GPe in the mechanisms of DBS for PD than typically assumed. And from a practical perspective, DBS EPs are poised to become clinically useful electrophysiological biomarker signals for verification of DBS target engagement.


Basal Ganglia , Deep Brain Stimulation , Evoked Potentials , Parkinson Disease , Deep Brain Stimulation/methods , Humans , Basal Ganglia/physiology , Basal Ganglia/physiopathology , Evoked Potentials/physiology , Parkinson Disease/therapy , Parkinson Disease/physiopathology , Animals , Globus Pallidus/physiology , Subthalamic Nucleus/physiology
15.
J Clin Neurosci ; 124: 81-86, 2024 Jun.
Article En | MEDLINE | ID: mdl-38669906

BACKGROUND: Delayed-onset seizures after deep brain stimulation (DBS) surgery were seldom reported. This study summarized the clinical characteristics of delayed-onset seizures after subthalamic nucleus (STN) DBS surgery for Parkinson's disease (PD) and analyzed risk factors. METHODS: A single-center retrospective study containing consecutive STN-DBS PD patients from 2006 to 2021 was performed. Seizures occurred during the DBS surgery or within one month after DBS surgery were identified based on routine clinical records. Patients with postoperative magnetic resonance imaging (MRI) were included to further analyze the risk factors for postoperative seizures with univariate and multivariate statistical methods. RESULTS: 341 consecutive PD patients treated with bilateral STN-DBS surgery wereidentified, and five patients experienced seizures after DBS surgery with an incidence of 1.47 %. All seizures of the five cases were characterized as delayed onset with average 12 days post-operatively. All seizures presented as generalized tonic-clonic seizures and didn't recur after the first onset. In those seizures cases, peri-electrode edema was found in both hemispheres without hemorrhage and infarction. The average diameter of peri-electrode edema of patients with seizures was larger than those without seizures (3.15 ± 1.00 cm vs 1.57 ± 1.02 cm, p = 0.005). Multivariate risk factor analysis indicated that seizures were only associated with the diameter of peri-electrode edema (OR 4.144, 95 % CI 1.269-13.530, p = 0.019). CONCLUSIONS: Delayed-onset seizures after STN-DBS surgery in PD patients were uncommon with an incidence of 1.47 % in this study. The seizures were transient and self-limiting, with no developing into chronic epilepsy. Peri-electrode edema was a risk factor for delayed-onset seizures after DBS surgery. Patients with an average peri-electrode edema diameter > 2.70 cm had a higher risk to develop seizures.


Deep Brain Stimulation , Parkinson Disease , Postoperative Complications , Seizures , Subthalamic Nucleus , Humans , Deep Brain Stimulation/adverse effects , Parkinson Disease/therapy , Parkinson Disease/surgery , Male , Female , Middle Aged , Subthalamic Nucleus/surgery , Retrospective Studies , Seizures/etiology , Seizures/epidemiology , Aged , Postoperative Complications/etiology , Postoperative Complications/epidemiology , Risk Factors , Magnetic Resonance Imaging
16.
Prog Neurobiol ; 236: 102613, 2024 May.
Article En | MEDLINE | ID: mdl-38631480

While medial frontal cortex (MFC) and subthalamic nucleus (STN) have been implicated in conflict monitoring and action inhibition, respectively, an integrated understanding of the spatiotemporal and spectral interaction of these nodes and how they interact with motor cortex (M1) to definitively modify motor behavior during conflict is lacking. We recorded neural signals intracranially across presupplementary motor area (preSMA), M1, STN, and globus pallidus internus (GPi), during a flanker task in 20 patients undergoing deep brain stimulation implantation surgery for Parkinson disease or dystonia. Conflict is associated with sequential and causal increases in local theta power from preSMA to STN to M1 with movement delays directly correlated with increased STN theta power, indicating preSMA is the MFC locus that monitors conflict and signals STN to implement a 'break.' Transmission of theta from STN-to-M1 subsequently results in a transient increase in M1-to-GPi beta flow immediately prior to movement, modulating the motor network to actuate the conflict-related action inhibition (i.e., delayed response). Action regulation during conflict relies on two distinct circuits, the conflict-related theta and movement-related beta networks, that are separated spatially, spectrally, and temporally, but which interact dynamically to mediate motor performance, highlighting complex parallel yet interacting networks regulating movement.


Conflict, Psychological , Deep Brain Stimulation , Motor Cortex , Parkinson Disease , Prefrontal Cortex , Subthalamic Nucleus , Theta Rhythm , Humans , Theta Rhythm/physiology , Subthalamic Nucleus/physiology , Male , Female , Middle Aged , Adult , Prefrontal Cortex/physiology , Motor Cortex/physiology , Parkinson Disease/physiopathology , Aged , Neural Pathways/physiology , Dystonia/physiopathology
17.
Neurobiol Dis ; 197: 106519, 2024 Jul.
Article En | MEDLINE | ID: mdl-38685358

Neural oscillations are critical to understanding the synchronisation of neural activities and their relevance to neurological disorders. For instance, the amplitude of beta oscillations in the subthalamic nucleus has gained extensive attention, as it has been found to correlate with medication status and the therapeutic effects of continuous deep brain stimulation in people with Parkinson's disease. However, the frequency stability of subthalamic nucleus beta oscillations, which has been suggested to be associated with dopaminergic information in brain states, has not been well explored. Moreover, the administration of medicine can have inverse effects on changes in frequency and amplitude. In this study, we proposed a method based on the stationary wavelet transform to quantify the amplitude and frequency stability of subthalamic nucleus beta oscillations and evaluated the method using simulation and real data for Parkinson's disease patients. The results suggest that the amplitude and frequency stability quantification has enhanced sensitivity in distinguishing pathological conditions in Parkinson's disease patients. Our quantification shows the benefit of combining frequency stability information with amplitude and provides a new potential feedback signal for adaptive deep brain stimulation.


Deep Brain Stimulation , Parkinson Disease , Subthalamic Nucleus , Parkinson Disease/drug therapy , Parkinson Disease/therapy , Parkinson Disease/physiopathology , Humans , Deep Brain Stimulation/methods , Male , Female , Middle Aged , Aged , Beta Rhythm/physiology , Beta Rhythm/drug effects , Antiparkinson Agents/therapeutic use , Wavelet Analysis
18.
Neuroimage Clin ; 42: 103607, 2024.
Article En | MEDLINE | ID: mdl-38643635

BACKGROUND: Nigrostriatal microstructural integrity has been suggested as a biomarker for levodopa response in Parkinson's disease (PD), which is a strong predictor for motor response to deep brain stimulation (DBS) of the subthalamic nucleus (STN). This study aimed to explore the impact of microstructural integrity of the substantia nigra (SN), STN, and putamen on motor response to STN-DBS using diffusion microstructure imaging. METHODS: Data was collected from 23 PD patients (mean age 63 ± 7, 6 females) who underwent STN-DBS, had preoperative 3 T diffusion magnetic resonance imaging including multishell diffusion-weighted MRI with b-values of 1000 and 2000 s/mm2 and records of motor improvement available. RESULTS: The association between a poorer DBS-response and increased free interstitial fluid showed notable effect sizes (rho > |0.4|) in SN and STN, but not in putamen. However, this did not reach significance after Bonferroni correction and controlling for sex and age. CONCLUSION: Microstructural integrity of SN and STN are potential biomarkers for the prediction of therapy efficacy following STN-DBS, but further studies are required to confirm these associations.


Deep Brain Stimulation , Parkinson Disease , Substantia Nigra , Subthalamic Nucleus , Humans , Deep Brain Stimulation/methods , Subthalamic Nucleus/diagnostic imaging , Subthalamic Nucleus/pathology , Female , Male , Parkinson Disease/therapy , Parkinson Disease/diagnostic imaging , Parkinson Disease/pathology , Middle Aged , Substantia Nigra/diagnostic imaging , Substantia Nigra/pathology , Aged , Diffusion Magnetic Resonance Imaging/methods , Treatment Outcome
19.
Neurotherapeutics ; 21(3): e00348, 2024 Apr.
Article En | MEDLINE | ID: mdl-38579455

Deep Brain Stimulation (DBS) has become a pivotal therapeutic approach for Parkinson's Disease (PD) and various neuropsychiatric conditions, impacting over 200,000 patients. Despite its widespread application, the intricate mechanisms behind DBS remain a subject of ongoing investigation. This article provides an overview of the current knowledge surrounding the local, circuit, and neurobiochemical effects of DBS, focusing on the subthalamic nucleus (STN) as a key target in PD management. The local effects of DBS, once thought to mimic a reversible lesion, now reveal a more nuanced interplay with myelinated axons, neurotransmitter release, and the surrounding microenvironment. Circuit effects illuminate the modulation of oscillatory activities within the basal ganglia and emphasize communication between the STN and the primary motor cortex. Neurobiochemical effects, encompassing changes in dopamine levels and epigenetic modifications, add further complexity to the DBS landscape. Finally, within the context of understanding the mechanisms of DBS in PD, the article highlights the controversial question of whether DBS exerts disease-modifying effects in PD. While preclinical evidence suggests neuroprotective potential, clinical trials such as EARLYSTIM face challenges in assessing long-term disease modification due to enrollment timing and methodology limitations. The discussion underscores the need for robust biomarkers and large-scale prospective trials to conclusively determine DBS's potential as a disease-modifying therapy in PD.


Deep Brain Stimulation , Parkinson Disease , Subthalamic Nucleus , Humans , Deep Brain Stimulation/methods , Parkinson Disease/therapy , Parkinson Disease/physiopathology , Subthalamic Nucleus/physiology , Animals , Neurosciences/methods
20.
Article En | MEDLINE | ID: mdl-38656860

In neurodegenerative disorders, neuronal firing patterns and oscillatory activity are remarkably altered in specific brain regions, which can serve as valuable biomarkers for the identification of deep brain regions. The subthalamic nucleus (STN) has been the primary target for DBS in patients with Parkinson's disease (PD). In this study, changes in the spike firing patterns and spectral power of local field potentials (LFPs) in the pre-STN (zona incerta, ZI) and post-STN (cerebral peduncle, cp) regions were investigated in PD rats, providing crucial evidence for the functional localization of the STN. Sixteen-channel microelectrode arrays (MEAs) with sites distributed at different depths and widths were utilized to record neuronal activities. The spikes in the STN exhibited higher firing rates than those in the ZI and cp. Furthermore, the LFP power in the delta band in the STN was the greatest, followed by that in the ZI, and was greater than that in the cp. Additionally, increased LFP power was observed in the beta bands in the STN. To identify the best performing classification model, we applied various convolutional neural networks (CNNs) based on transfer learning to analyze the recorded raw data, which were processed using the Gram matrix of the spikes and the fast Fourier transform of the LFPs. The best transfer learning model achieved an accuracy of 95.16%. After fusing the spike and LFP classification results, the time precision for processing the raw data reached 500 ms. The pretrained model, utilizing raw data, demonstrated the feasibility of employing transfer learning for training models on neural activity. This approach highlights the potential for functional localization within deep brain regions.


Deep Brain Stimulation , Microelectrodes , Rats, Sprague-Dawley , Subthalamic Nucleus , Subthalamic Nucleus/physiopathology , Animals , Rats , Male , Disease Models, Animal , Parkinson Disease/physiopathology , Parkinson Disease/rehabilitation , Action Potentials/physiology , Algorithms , Computer Systems , Parkinsonian Disorders/physiopathology , Parkinsonian Disorders/rehabilitation , Machine Learning
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