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Psychiatry and Clinical... Dec 2023The aim of the study was to investigatie apathy and cognitive functions in Parkinson's disease patients who underwent deep brain stimulation surgery on bilateral...
BACKGROUND
The aim of the study was to investigatie apathy and cognitive functions in Parkinson's disease patients who underwent deep brain stimulation surgery on bilateral subthalamic nuclei.
METHODS
This study included 18 patients with Parkinson's disease who were accommodated in the Parkinson's and Movement Disorders Center of Adana City Training and Research Hospital for treatment in 2022. Patients were evaluated by psychiatry, neurology and neurosurgery specialists with a multidisciplinary approach and found to be surgically appropriate. Standardized Mini-Mental Test and Montreal Cognitive Assessment Scale, Apathy Evaluation Scale, and Hamilton Anxiety and Depression Scale were administered to each patient before the operation and at 6 months after effective stimulation parameters were reached.
RESULTS
The mean apathy score at the preoperative zeroth month was 47.77 ± 15.83 in patients having deep brain stimulation surgery and 30.83 ± 13.59 in the postoperative sixth month. Statistically that reduction was significant ( = .003) and showed clinical development. The average Hamilton Anxiety Scale scores at the preoperative zeroth month was 11.50 ± 5.14 and 10.22 ± 5.57 at the postoperative sixth month, with no clinical significance ( = .280). The determined value for the Unified Parkinson's Disease Rating Scale, on treatment, was 22.55 ± 7.53 in the preoperative zeroth month and 14.50 ± 6.99 in the postoperative sixth month, with statistical significance (). The Unified Parkinson's Disease Rating Scale, off treatment, score was revealed to be significant in the preoperative zeroth month (37.44 ± 9.85) in comparison to that of the postoperative sixth month (23.44 ± 7.86; < .001).
CONCLUSION
This study showed that bilateral subthalamic stimulation improves nonmotor and motor symptoms in patients having Parkinson's disease. The mechanism is complex, and we believe that future studies focusing on pharmacological and nonpharmacological treatments involving more patient groups will be useful for clinicians.
PubMed: 38765847
DOI: 10.5152/pcp.2023.23621 -
NPJ Parkinson's Disease May 2024Deep brain stimulation of the subthalamic nucleus (STN-DBS) effectively treats motor and non-motor symptoms in advanced Parkinson's disease (PD). As considerable...
Deep brain stimulation of the subthalamic nucleus (STN-DBS) effectively treats motor and non-motor symptoms in advanced Parkinson's disease (PD). As considerable interindividual variability of outcomes exists, neuroimaging-based biomarkers, including microstructural metrics, have been proposed to anticipate treatment response. In this prospective open-label study, we sought to detect microstructural properties of brain areas associated with short-term non-motor outcomes following STN-DBS. Thirty-seven PD patients underwent diffusion MRI and clinical assessments at preoperative baseline and 6-month follow-up. Whole brain voxel-wise analysis assessed associations between microstructural metrics and non-motor outcomes. Intact microstructure within specific areas, including the right insular cortex, right putamen, right cingulum, and bilateral corticospinal tract were associated with greater postoperative improvement of non-motor symptom burden. Furthermore, microstructural properties of distinct brain regions were associated with postoperative changes in sleep, attention/memory, urinary symptoms, and apathy. In conclusion, diffusion MRI could support preoperative patient counselling by identifying patients with above- or below-average non-motor responses.
PubMed: 38762510
DOI: 10.1038/s41531-024-00717-y -
NeuroImage Jul 2024Mental representation is a key concept in cognitive science; nevertheless, its neural foundations remain elusive. We employed non-invasive electrical brain stimulation...
Mental representation is a key concept in cognitive science; nevertheless, its neural foundations remain elusive. We employed non-invasive electrical brain stimulation and functional magnetic resonance imaging to address this. During this process, participants perceived flickering red and green visual stimuli, discerning them either as distinct, non-fused colours or as a mentally generated, fused colour (orange). The application of transcranial alternating current stimulation to the medial prefrontal region (a key node of the default-mode network) suppressed haemodynamic activation in higher-order subthalamic and central executive networks associated with the perception of fused colours. This implies that higher-order thalamocortical and default-mode networks are crucial in humans' conscious perception of mental representation.
Topics: Humans; Male; Magnetic Resonance Imaging; Female; Adult; Transcranial Direct Current Stimulation; Consciousness; Young Adult; Prefrontal Cortex; Color Perception; Brain Mapping; Brain; Default Mode Network; Photic Stimulation
PubMed: 38761552
DOI: 10.1016/j.neuroimage.2024.120647 -
Cell Reports. Medicine Jun 2024Levodopa-induced dyskinesia (LID) is an intractable motor complication arising in Parkinson's disease with the progression of disease and chronic treatment of levodopa....
Levodopa-induced dyskinesia (LID) is an intractable motor complication arising in Parkinson's disease with the progression of disease and chronic treatment of levodopa. However, the specific cell assemblies mediating dyskinesia have not been fully elucidated. Here, we utilize the activity-dependent tool to identify three brain regions (globus pallidus external segment [GPe], parafascicular thalamic nucleus, and subthalamic nucleus) that specifically contain dyskinesia-activated ensembles. An intensity-dependent hyperactivity in the dyskinesia-activated subpopulation in GPe (GPe) is observed during dyskinesia. Optogenetic inhibition of GPe significantly ameliorates LID, whereas reactivation of GPe evokes dyskinetic behavior in the levodopa-off state. Simultaneous chemogenetic reactivation of GPe and another previously reported ensemble in striatum fully reproduces the dyskinesia induced by high-dose levodopa. Finally, we characterize GPe as a subset of prototypic neurons in GPe. These findings provide theoretical foundations for precision medication and modulation of LID in the future.
Topics: Levodopa; Globus Pallidus; Dyskinesia, Drug-Induced; Animals; Neurons; Male; Optogenetics; Mice; Parkinson Disease; Humans; Subthalamic Nucleus
PubMed: 38759649
DOI: 10.1016/j.xcrm.2024.101566 -
NeuroImage. Clinical 2024The intricate relationship between deep brain stimulation (DBS) in Parkinson's disease (PD) and cognitive impairment has lately garnered substantial attention. The...
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.
Topics: Humans; Deep Brain Stimulation; Parkinson Disease; Male; Female; Subthalamic Nucleus; Middle Aged; Cognitive Dysfunction; Aged; Magnetic Resonance Imaging; Neuropsychological Tests
PubMed: 38749145
DOI: 10.1016/j.nicl.2024.103617 -
BioRxiv : the Preprint Server For... May 2024Reactive inhibitory control is crucial for survival. Traditionally, this control in mammals was attributed solely to the hyperdirect pathway, with cortical control...
Reactive inhibitory control is crucial for survival. Traditionally, this control in mammals was attributed solely to the hyperdirect pathway, with cortical control signals flowing unidirectionally from the subthalamic nucleus (STN) to basal ganglia output regions. Yet recent findings have put this model into question, suggesting that the STN is assisted in stopping actions through ascending control signals to the striatum mediated by the external globus pallidus (GPe). Here we investigate this suggestion by harnessing a biologically-constrained spiking model of the corticobasal ganglia-thalamic (CBGT) circuit that includes pallidostriatal pathways originating from arkypallidal neurons. Through a series of experiments probing the interaction between three critical inhibitory nodes (the STN, arkypallidal cells, and indirect path-way spiny projection neurons), we find that the GPe acts as a critical mediator of both ascending and descending inhibitory signals in the CBGT circuit. In particular, pallidostriatal pathways regulate this process by weakening the direct pathway dominance of the evidence accumulation process driving decisions, which increases the relative suppressive influence of the indirect pathway on basal ganglia output. These findings delineate how pallidostriatal pathways can facilitate action cancellation by managing the bidirectional flow of information within CBGT circuits.
PubMed: 38746308
DOI: 10.1101/2024.05.03.592321 -
MedRxiv : the Preprint Server For... May 2024Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD); however, there is limited understanding of which subthalamic pathways are recruited...
Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD); however, there is limited understanding of which subthalamic pathways are recruited in response to stimulation. Here, by focusing on the polarity of the stimulus waveform (cathodic vs. anodic), our goal was to elucidate biophysical mechanisms that underlie electrical stimulation in the human brain. In clinical studies, cathodic stimulation more easily triggers behavioral responses, but anodic DBS broadens the therapeutic window. This suggests that neural pathways involved respond preferentially depending on stimulus polarity. To experimentally compare the activation of therapeutically relevant pathways during cathodic and anodic subthalamic nucleus (STN) DBS, pathway activation was quantified by measuring evoked potentials resulting from antidromic or orthodromic activation in 15 PD patients undergoing DBS implantation. Cortical evoked potentials (cEP) were recorded using subdural electrocorticography, DBS local evoked potentials (DLEP) were recorded from non-stimulating contacts and EMG activity was recorded from arm and face muscles. We measured: 1) the amplitude of short-latency cEP, previously demonstrated to reflect activation of the cortico-STN hyperdirect pathway, 2) DLEP amplitude thought to reflect activation of STN-globus pallidus (GP) pathway, and 3) amplitudes of very short-latency cEP and motor evoked potentials (mEP) for activation of cortico-spinal/bulbar tract (CSBT). We constructed recruitment and strength-duration curves for each EP/pathway to compare the excitability for different stimulation polarities. We compared experimental data with the most advanced DBS computational models. Our results provide experimental evidence that subcortical cathodic and anodic stimulation activate the same pathways in the STN region and that cathodic stimulation is in general more efficient. However, relative efficiency varies for different pathways so that anodic stimulation is the least efficient in activating CSBT, more efficient in activating the HDP and as efficient as cathodic in activating STN-GP pathway. Our experiments confirm biophysical model predictions regarding neural activations in the central nervous system and provide evidence that stimulus polarity has differential effects on passing axons, terminal synapses, and local neurons. Comparison of experimental results with clinical DBS studies provides further evidence that the hyperdirect pathway may be involved in the therapeutic mechanisms of DBS.
PubMed: 38746250
DOI: 10.1101/2024.05.01.24306044 -
Frontiers in Cellular Neuroscience 2024Deep brain stimulation (DBS) is a highly effective treatment option in Parkinson's disease. However, the underlying mechanisms of action, particularly effects on...
INTRODUCTION
Deep brain stimulation (DBS) is a highly effective treatment option in Parkinson's disease. However, the underlying mechanisms of action, particularly effects on neuronal plasticity, remain enigmatic. Adult neurogenesis in the subventricular zone-olfactory bulb (SVZ-OB) axis and in the dentate gyrus (DG) has been linked to various non-motor symptoms in PD, e.g., memory deficits and olfactory dysfunction. Since DBS affects several of these non-motor symptoms, we analyzed the effects of DBS in the subthalamic nucleus (STN) and the entopeduncular nucleus (EPN) on neurogenesis in 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian rats.
METHODS
In our study, we applied five weeks of continuous bilateral STN-DBS or EPN-DBS in 6-OHDA-lesioned rats with stable dopaminergic deficits compared to 6-OHDA-lesioned rats with corresponding sham stimulation. We injected two thymidine analogs to quantify newborn neurons early after DBS onset and three weeks later. Immunohistochemistry identified newborn cells co-labeled with NeuN, TH and GABA within the OB and DG. As a putative mechanism, we simulated the electric field distribution depending on the stimulation site to analyze direct electric effects on neural stem cell proliferation.
RESULTS
STN-DBS persistently increased the number of newborn dopaminergic and GABAergic neurons in the OB but not in the DG, while EPN-DBS does not impact neurogenesis. These effects do not seem to be mediated via direct electric stimulation of neural stem/progenitor cells within the neurogenic niches.
DISCUSSION
Our data support target-specific effects of STN-DBS on adult neurogenesis, a putative modulator of non-motor symptoms in Parkinson's disease.
PubMed: 38746080
DOI: 10.3389/fncel.2024.1396780 -
Neurological Sciences : Official... May 2024Drug-resistant juvenile myoclonic epilepsy (DR-JME) remains a significant challenge in neurology. Traditional management strategies often fail to achieve satisfactory...
BACKGROUND
Drug-resistant juvenile myoclonic epilepsy (DR-JME) remains a significant challenge in neurology. Traditional management strategies often fail to achieve satisfactory control, necessitating innovative treatments.
OBJECTIVE
This case report aims to evaluate the efficacy and safety of deep brain stimulation (DBS) targeting the subthalamic nucleus (STN-DBS) in a patient with DR-JME.
METHODS
We describe the treatment of a patient with DR-JME using STN-DBS. The patient underwent implantation and received high-frequency stimulation (HFS) at the STN.
RESULTS
One year post-implantation, the patient demonstrated a substantial reduction in motor seizure frequency by 87.5%, with improvements in quality of life and seizure severity by 52.0% and 46.7%, respectively. No adverse events were reported during the follow-up period.
CONCLUSIONS
This case represents the first report of favorable outcomes with STN-DBS in a patient with DR-JME, suggesting that long-term HFS of the STN may be a promising treatment option for patients suffering from this condition.
PubMed: 38740728
DOI: 10.1007/s10072-024-07553-1 -
Neurobiology of Disease Jul 2024Parkinson's disease (PD) is characterized by the disruption of repetitive, concurrent and sequential motor actions due to compromised timing-functions principally...
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.
Topics: Humans; Parkinson Disease; Male; Female; Middle Aged; Deep Brain Stimulation; Aged; Beta Rhythm; Motor Cortex; Cortical Synchronization; Levodopa; Fingers; Subthalamic Nucleus; Antiparkinson Agents; Electroencephalography
PubMed: 38740349
DOI: 10.1016/j.nbd.2024.106529