BackgroundMinor hallucinations (MH) affect 30-60% of patients with Parkinson's disease (PD), and are considered precursors to structured visual hallucinations and cognitive decline. While the link between structured visual hallucinations and dementia is well established, the neuropsychological correlates of MH in PD remain unclear; most studies finding no significant cognitive differences between patients with MH and those without any hallucinations.ObjectivesPresence hallucinations (PH) being among the most prevalent MH in PD, we used a robotic procedure delivering somatomotor conflicts inducing PH experimentally to investigate whether sensitivity to such robot-induced PH aids in detecting cognitive differences between patients with MH and without hallucinations.Methods31 PD patients with MH (PD-MH) and 37 without hallucinations (PD-nH) underwent neuropsychological assessment and the robotic procedure inducing PH. The sensitivity to report robot-induced PH was analyzed in relation to cognitive performance in neuropsychological tests.ResultsPD-MH patients reported more robot-induced PH than PD-nH patients, supporting previous findings. While both groups showed comparable performance in neuropsychological testing, we found a significant association between increased sensitivity to the PH-induction and poorer performance in frontal subcortical cognitive functions, in PD-MH patients, but not in PD-nH patients.ConclusionsThese findings demonstrate that sensitivity to robot-induced PH reveals a previously undetected link between MH and frontal subcortical cognitive deficits in PD, pointing to shared underlying mechanisms between executive dysfunction and somatomotor processes involved in MH. This approach offers a novel and clinically valuable means of identifying early cognitive vulnerability that assessments relying only on standard testing may overlook.

Abstract Dopamine replacement therapy (DRT) alleviates motor symptoms in Parkinson’s disease (PD) but can trigger hallucinations in a subset of patients, yet the neural basis of this selective vulnerability is unknown. Hallucinations are among the most disabling non-motor symptoms of PD, linked to social isolation, dementia and institutionalization. Using a validated robotic paradigm to induce and quantify hallucinations in real-time, combined with resting-state fMRI in a crossover On/Off DRT design, we studied patients with PD with (PD-H) and without (PD-nH) hallucinations. DRT selectively amplified sensitivity to robot-induced hallucinations in patients with pre-existing hallucinatory phenotype (PD-H, but not PD-nH) and was accompanied by cortico-striatal and large-scale network hyperconnectivity. Rather than supporting a uniform hallucinogenic effect of dopamine in PD, these findings indicate that DRT interacts with an intrinsic neural vulnerability that varies in patients. Prospective studies will establish whether this pharmacological–behavioural signature identifies patients at risk before clinical hallucinations emerge.

INTRODUCTION:Deep brain stimulation (DBS) targeting the posterior subthalamic area (PSA) is a more recent target to manage medication-refractory essential tremor (ET), with some studies suggesting enhanced tremor control and more favorable side-effects profile compared to traditional ventral intermediate nucleus (Vim). This study aims to assess the long-term efficacy and side effect profile of PSA-DBS in ET patients. METHODS:Fourteen ET patients who underwent bilateral PSA-DBS were evaluated using the Fahn-Tolosa-Marin Tremor Rating Scale preoperatively, at 12 months, and at the last follow-up (range 10-63 months). Within the first 6 months postoperatively, systematic monopolar contact testing was performed to determine individual thresholds for tremor suppression and adverse effects. Standardized neurological examinations and blinded video assessments were used to document stimulation-induced side effects. RESULTS:Tremor was significantly reduced postoperatively, allowing a 59% reduction at 12 months and 39% at last follow-up. Common side effects at last follow-up included dysarthria (93%), ataxia (57%), and gait disturbances (79%), mainly mild to moderate in severity. Additionally, stimulation-induced dyskinesia occurred in 21% of patients. Patient satisfaction remained high, with 85.7% reporting significant improvements. CONCLUSIONS:Bilateral PSA-DBS demonstrates sustained tremor reduction but can frequently present stimulation-induced side-effects, highlighting the importance of careful long-term monitoring and programming adjustments.

Addiction is a chronic relapsing condition characterized by compulsive reward seeking and impaired behavioral control, associated with major individual and societal burden. Mechanistic investigation in humans remains constrained by ethical limitations, uncontrolled exposure histories, and ecological confounds. Parkinson's disease treated with dopamine replacement therapy provides a human framework for investigating addiction-relevant mechanisms under controlled dopaminergic modulation. We performed a narrative synthesis of clinical, neuropsychological, pharmacological, neuroimaging, and electrophysiological evidence linking impulse control disorders and dopamine dysregulation syndrome in Parkinson's disease to dimensional and circuit-based models of addiction. We examined phenotypic and neurobiological convergences, experimental opportunities, and translational relevance while outlining its boundary conditions. A subset of Parkinson's disease patients exposed to dopamine replacement treatment develops impulse control disorders and dopamine dysregulation syndrome. Impulse control disorders comprise heterogeneous behavioral phenotypes that share selected dimensions with behavioral addictions, whereas dopamine dysregulation syndrome most closely approximates pharmacological substance use disorders. These phenotypes share selected addiction-related dimensions, including craving, impaired control, compulsive reward-seeking, and persistence despite harm, while showing partial clinical and neurobiological convergence with behavioral addictions and substance use disorders. Parkinson's disease patients with neuropsychiatric fluctuations may represent a sensitized vulnerability state in which dopaminergic modulation dynamically influences reward processing, motivation, and compulsive behaviors. Parkinson's disease under dopamine replacement therapy enables within-subject dopaminergic manipulation, longitudinal observation, prospective assessment of vulnerability traits, multimodal neurobiological investigation, and reduced environmental confounding. It therefore provides a unique human window for investigating addiction-relevant mechanisms under controlled dopaminergic modulation, complementing animal models while remaining constrained by disease-specific boundary conditions.

Deep brain stimulation (DBS) effectively treats motor symptoms in movement disorders but often compromises speech through incompletely defined mechanisms. We conducted a PROSPERO-registered systematic review and meta-analysis of publications through August 2024 (CRD42024527738). Among 2726 screened records, we included 184 studies: 131 in Parkinson's disease (PD), 32 in essential tremor (ET), and 21 in dystonia, assessing perceptual, acoustic, and patient-reported speech outcomes. Meta-analyses showed that subthalamic nucleus DBS in PD resulted in poorer speech intelligibility compared with best medical treatment (effect size -0.24; 95% confidence interval: -0.46 to -0.03; P = 0.027), with state-dependent decline under active stimulation on longitudinal analysis (Unified Parkinson's Disease Rating Scale Part III item 18 monthly change: medication on +0.016, P < 0.001; medication off +0.002, P = 0.50). In ET, DBS consistently suppressed vocal tremor but increased the risk of dysarthria, particularly with bilateral stimulation. Dystonia outcomes showed greater heterogeneity. Across disorders, sustained phonation measures improved, whereas connected speech performance worsened, indicating selective vulnerability of complex motor tasks. Neuroanatomical mapping identified two nonexclusive mechanisms: current spread to corticobulbar fibers producing spastic speech features and to the cerebellothalamocortical pathway producing ataxic features. Hypokinetic and stuttering-like phenotypes also occurred but likely reflect network-level interactions rather than tract-specific spread. These tract-mediated and network-level alterations appear to interact with hemispheric lateralization, medication state, and longer-term plasticity to produce complex clinical phenotypes. We outline a clinical framework integrating systematic screening, phenotype identification, and targeted programming adjustments. Enhanced speech assessment, precise field mapping, and adaptive DBS paradigms may promote individualized care that optimizes speech and motor function in precision DBS therapy. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Sensing-guided deep brain stimulation (DBS) offers potential to further optimize symptom control in Parkinson’s disease (PD) patients. Emerging evidence suggests that basal ganglia signals reflect not only motor, but also chronic neuropsychiatric symptoms. However, it remains unclear whether local field potentials (LFPs) can inform about acute neuropsychiatric states in PD, which we address in this work. Fourteen PD patients implanted with a brain-sense-enabled neurostimulator underwent an acute levodopa challenge OFF/ON stimulation one year after surgery. In each condition, resting state STN-LFPs were recorded, and the acute neuropsychiatric state was evaluated using the Neuropsychiatric Fluctuation Scale. The relationship between neuropsychiatric state and fluctuation scores with STN low-frequency activity (4–12 Hz) was assessed. An acute low neuropsychiatric state in the OFF-medication condition was associated with elevated theta/low-alpha power. Moreover, the 6–8 Hz activity was indicative of the neuropsychiatric state change following medication intake. Those results were most evident in recordings from the ventral contacts closer to the limbic STN, while chronic stimulation settings covering the dorsal associative and motor STN captured a similar trend. STN low-frequency activity may serve as a biomarker for the acute neuropsychiatric state and neuropsychiatric responsiveness to dopamine and may inform future sensing-guided DBS strategies.

BACKGROUND:Sleep architecture and circadian rhythms are frequently disrupted in Parkinson's disease (PD). BrainSense-enabled neurostimulators combined with wearable technology enable chronic assessment of nocturnal brain activity, with potential for future diagnostics and personalized treatments. OBJECTIVES:To neurophysiologically characterize and decode sleep architecture and circadian rhythmicity from ambulatory subthalamic nucleus (STN) recordings in PD and to evaluate the influence of clinical factors. METHODS:Eighteen PD patients implanted with the Medtronic Percept system underwent 4-8 weeks of ambulatory STN local field potential recordings, alongside wearable-based sleep monitoring. Spectral dynamics of three biomarkers (low-frequency-, beta-, and finely-tuned-gamma [FTG]-activity) were characterized across circadian cycles and sleep stages (Awake, Core, Deep, REM [rapid eye movement]). Machine-learning classifiers were developed for state decoding. RESULTS:A total of 3140 hr of representative sleep data were analyzed. All biomarkers exhibited circadian modulation, most evident in beta and FTG activity. REM sleep and nocturnal wakefulness were associated with increased beta/FTG, whereas Deep sleep showed increased low-frequency and reduced beta/FTG. Classifiers showed that beta and FTG decoded circadian states, while low-frequency identified Deep sleep. Bilateral biomarker combination improved prediction. Clinically, greater motor impairment correlated with reduced REM beta power. Levodopa dosage and electrocardiogram artefacts influenced beta-based predictions, whereas age and sleep quality affected FTG-related predictions. CONCLUSIONS:This proof-of-concept study demonstrates that ambulatory basal ganglia recordings from implantable neurostimulators can capture key aspects of sleep stage architecture in PD. Distinct spectral biomarkers show differential sleep insights and practical utility, supporting the development of diagnostic tools and sleep-informed adaptive deep brain stimulation. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

OBJECTIVE:Dysarthria is one of the most common and disabling side effects of subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD). Stimulation often exacerbates speech dysfunction beyond the effects of PD progression, likely because of current spread to structures surrounding the STN. This study aimed to develop speech biomarkers sensitive to DBS-induced dysarthria by isolating stimulation side effects and mapping their emergence across incrementally increased amplitudes. METHODS:Twenty-four PD patients with bilateral STN-DBS completed a standardized speech assessment in each hemisphere separately, including sustained phonations, rapid syllable repetitions, and reading passages across 7 increasing stimulation amplitudes defined relative to a clinically determined stimulation-induced dysarthria threshold. A composite dysarthria index based on 7 key acoustic features, patient perceptual self-ratings, and intelligibility scores were extracted. RESULTS:More than 2,500 speech task recordings were analyzed. Both the composite dysarthria index and subjective self-ratings worsened rapidly with increasing stimulation amplitude above a threshold (p < 0.001), whereas intelligibility scores varied markedly and did not reach significance. Among individual acoustic features, phonation duration, voice quality, and monopitch exhibited significant sensitivity to increasing stimulation amplitudes. Left-sided stimulation induced greater speech deterioration than right-sided stimulation. INTERPRETATION:We systematically identified speech biomarkers that capture DBS-induced dysarthria, characterized the progressive deterioration of speech with increasing amplitude, and highlighted the pivotal role of left basal ganglia circuitry in speech production. Our objective metric holds promise as safety outcome measure for surgical therapies, guidepost for initial and troubleshooting DBS programming, and input for adaptive, closed-loop stimulation control. ANN NEUROL 2026;100:628-640.

Movement-related gamma activity (> 60 Hz) in cortico-basal ganglia networks reflects pro-kinetic synchronization dynamics. While in the cortex these temporal dynamics are known to unfold spatially across topographically distributed networks, it remains unclear whether a similar spatial propagation occurs within the basal ganglia, and how such spatial encoding may contribute to both physiological and disease-related mechanisms. The subthalamic nucleus (STN) is a key integrative hub for motor processing within the basal ganglia-cortical circuitry. At rest, STN activity is topographically distributed according to its spectral frequency components. To assess whether this spectral topography is dynamic and underlies movement encoding, we dissected the spatiotemporal properties of STN local field potentials recorded intraoperatively at rest and during movement across 63 hemispheres from patients with Parkinson's disease. Using multi-contact deep brain stimulation leads, we captured high-resolution anatomical signal dynamics and contrasted a broad frequency spectrum (60-400 Hz), including high-gamma, fast-gamma, slow high-frequency oscillations and fast high-frequency oscillations. Moreover, we compared these signals to upper limb muscle activity and movement-related beta desynchronization, and examined their association with clinical impairment and levodopa responsiveness. All sub-bands exhibited significant movement-related synchronization in both the contralateral and ipsilateral STN, however, with distinct magnitude and temporal dynamics. The presence and degree of temporal locking to muscle activity and inverse relationship to movement-related beta desynchronization also varied by sub-band. Importantly, each sub-band exhibited spatially segregated hotspots located within the STN that propagate primarily along the inferior-superior axis, yet in band-specific directions. This spatial propagation evolved throughout the movement period but temporally decoupled from synchronization magnitude, indicating that spatial dynamics reflect a distinct property relevant for motor encoding. Notably, propagation of frequencies above 110 Hz inversely correlated with dopamine-related motor improvement, suggesting that exaggerated spatial dynamics may reflect compensatory mechanisms secondary to neurodegeneration. These findings demonstrated that synchronization within the basal ganglia is not a spatially static phenomenon but rather unfolds in space which expands on the current understanding of the basal ganglia mechanism. Propagation of movement-related activity may serve as a potential marker for motor impairment in Parkinson's disease, opening new avenues for spectro-behavioural research and spatially informed neuromodulation strategies.

Background: Hallucinations, ranging from minor (MH) to structured, are a common non-motor symptom in Parkinson's disease (PD). Structured hallucinations have been associated with altered functional connectivity (FC) between dorsal/ventral attention (DAN, VAN) and default mode (DMN) networks. As structured hallucinations are linked to rapid cognitive decline and MH are often viewed as their precursor, it is imperative to understand the neural basis of MH, and its relationship with cognitive alterations. Objectives: We aimed to identify a whole-brain FC pattern associated with MH and alterations in attention-executive functioning in PD, leveraging a robotic procedure inducing presence hallucinations (riPH) experimentally, to which patients with hallucinations previously showed increased sensitivity. Methods: Non-demented PD patients (N = 53) were categorized into three subgroups based on their hallucination symptoms: no hallucinations (nH; n = 19), MH (n = 18), and structured hallucinations, with or without MH (SMH; n = 16). We combined results from the riPH procedure and neuropsychological tests and applied multivariate methods capturing their shared variance in resting-state fMRI data across the three subgroups. Results: We identified a distributed FC pattern more strongly expressed in patients with hallucinations (MH, SMH), and equally so across both groups, significantly associated with alterations in attention-executive functions and differences in riPH sensitivity. The pattern was primarily driven by FC between subcortical areas and visual network, DAN and DMN, and within-cerebellar and within-subcortical FC. Conclusions: Our results highlight the role of subcortical-cortical connectivity in PD hallucinations, associated with cognitive alterations and already present in less advanced MH patients. ### Competing Interest Statement OB is one of the inventors on patent US 10,286,555 B2 (Title: Robot-controlled induction of the feeling of a presence) held by the Swiss Federal Institute of Technology (EPFL) that covers the robot-induction of the presence hallucinations (riPH). O.B. is one of the inventors on patent US 10,349,899 B2 (Title: System and method for predicting hallucinations) held by the Swiss Federal Institute of Technology (EPFL) that covers a robotic system for the prediction of hallucinations for diagnostic purposes. OB, JP and FB are inventors on patent n. EP4407627A1 (Title: Numerosity estimation impairment measurement system) held by the Swiss Federal Institute of Technology (EPFL) that covers the implicit measure of presence hallucinations. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Cantonal Ethics Committee of Geneva gave ethical approval for this work (protocol reference 2019-02275), in accordance with the Declaration of Helsinki. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data sharing will require a formal data use agreement. Requests will be evaluated based on institutional and departmental policies to determine whether the data requested is subject to intellectual property or patient privacy obligations. Swiss National Science Foundation, https://ror.org/00yjd3n13 Fondazione Teofilo Rossi di Montelera e di Premuda Fondation Bertarelli, https://ror.org/04h7fev25 Parkinson Schweiz Fondation Leenaards, https://ror.org/004h88r69 Empiris foundation Synapsis Foundation, https://ror.org/03jrr8f73

BACKGROUND:Novel commercial brain-sense neurostimulators enable us to contextualize brain activity with symptom and medication states in real-life ambulatory settings in Parkinson's disease (PD). Although various candidate biomarkers have been proposed for adaptive deep brain stimulation (DBS), a comprehensive comparison of their ambulatory profiles is lacking. OBJECTIVES:To systematically compare the ambulatory neurophysiological dynamics and clinical properties of three candidate biomarkers-low-frequency, beta (β), and finely tuned γ (FTG) activity. METHODS:We investigated 14 PD patients implanted with the Medtronic Percept PC, who underwent up to two 4-week ambulatory multimodal recording periods on their regular medication and stimulation. Subthalamic nucleus local field potentials (LFPs) of low-frequency, β, and FTG activity were recorded. Additionally, objective motor symptom states, physical activity and heart rate using wearables, as well as medication-intake times, sleep-awake times, and subjective symptom states using diaries were co-registered. LFP dynamics were also compared to high-resolution in-hospital recordings under off/on dopaminergic medication and stimulation conditions. RESULTS:FTG reliably indexed off to on medication states in the ambulatory setting at the group and individual levels, and these spectral dynamics could be anticipated by high-resolution in-hospital recordings. Both FTG and low-frequency correlated with wearable-based dyskinesia scores, whereas diary-based dyskinesia events were only linked to FTG. Importantly, FTG indicated on-medication states regardless of the presence of dyskinesia and despite potential motion and heart rate artifacts. The 24-hour profile revealed large circadian power shifts that may overdrive medication-intake dynamics. CONCLUSION:Despite the limitations of low-temporal resolution recordings, this work provides valuable insights into the real-life dynamics of biomarkers. Specifically, it highlights the utility of FTG as a primary and reliable indicator of medication states for adaptive DBS. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Effects of subthalamic nucleus deep brain stimulation (STN-DBS) on neuropsychiatric symptoms of Parkinson’s disease (PD) remain debated. Sensor technology might help to objectively assess behavioural changes after STN-DBS. 5 PD patients were assessed 1 before and 5 months after STN-DBS with the Movement Disorders Society Unified Parkinson’s Disease Rating Scale part III in the medication ON (plus postoperatively stimulation ON) condition, the Montreal Cognitive Assessment, the Questionnaire for Impulsive-Compulsive Behaviors in Parkinson’s Disease Rating Scale present version, the Hospital Anxiety and Depression Scale and the Starkstein Apathy Scale. Steps taken per hour, nighttime spent in bed and time spent outside were monitored with a smartwatch and ambient sensors placed in patient homes for an average of 20 days pre- and postoperatively. Postoperative improvement in ICDs and concomitant anxious-depressive symptoms was observed in 3 patients and was accompanied by a decrease in steps taken per hour, as well as an increase in nighttime spent in bed. In the two patients without baseline ICDs, mild anxiety and apathy improved postoperatively, and no new neuropsychiatric symptoms occurred. Steps taken per hour did not decrease in these cases and nighttime spent in bed improved in one of the patients, but decreased in the other, who had experienced pain during OFF-phases at night before STN-DBS. Changes in neuropsychiatric symptoms are associated with distinct activity patterns after STN-DBS, and wearable and ambient sensors may aid to capture those gradual shifts in behavior.

Over the past decade, neuropsychiatric fluctuations in Parkinson’s disease (PD) have been increasingly recognized for their impact on patients’ quality of life. Speech, a complex function carrying motor, emotional, and cognitive information, offers potential insights into these fluctuations. While previous studies have focused on acoustic analysis to assess motor speech disorders reliably, the potential of linguistic patterns associated with neuropsychiatric fluctuations in PD remains unexplored. This study analyzed the content of spontaneous speech from 33 PD patients in ON and OFF medication states, using machine learning and large language models (LLMs) to predict medication states and a neuropsychiatric state score. The top-performing model, the LLM Gemma-2 (9B), achieved 98% accuracy in differentiating ON and OFF states and its predicted scores were highly correlated with actual scores (Spearman’s ρ = 0.81). These methods could provide a more comprehensive assessment of PD treatment effects, allowing remote neuropsychiatric symptom monitoring via mobile devices.

Parkinson’s disease (PD) is characterized by hypokinetic motor symptoms, tremor, and various non-motor symptoms with frequent fluctuations of symptoms in advanced disease stages. Invasive therapies, such as deep brain stimulation (DBS), ablative therapies, and continuous subcutaneous or intrajejunal delivery of dopaminergic drugs via pump therapies are available for the management of this complex motor symptomatology and may also impact non-motor symptoms. The recent update of the clinical guideline on PD by the German Neurological Society (Deutsche Gesellschaft für Neurologie e.V.; DGN) offers clear guidance on the indications and applications of these treatment options. The guideline committee formulated diagnostic questions for invasive therapies and structured them according to the PICOS framework (Population–Intervention–Comparisons–Outcome–Studies). A systematic literature review was conducted. Questions were addressed using the findings from the literature review and consented by the guideline committee. Specific recommendations are given regarding (i) the optimal timing for starting invasive therapies, (ii) the application of DBS, (iii) the use of pump therapies in advanced PD, (iv) the indications for ablative procedures, and (iv) selecting the most appropriate therapy according to individual patient characteristics. This review is an adapted excerpt of the chapters on the use of invasive therapies in PD of the novel German guideline on PD. Clear recommendations on the use of treatment options for advanced PD are provided.

BACKGROUND:Shame is frequent in Parkinson's disease (PD) and often overlooked. OBJECTIVE:The aim was to assess factors associated with PD-related shame. METHODS:PD-related shame was measured using the Shame and Embarrassment in PD (SPARK) scale in patients without cognitive impairment. Correlation between personal determinants (demographics, psychological traits [shame/guilt propensity, trait anxiety]), PD-related determinants (PD characteristics; motor, cognitive, and neuropsychiatric symptoms; medication; and health-related quality of life [QoL]), and SPARK was analyzed using multiple correlation analysis and generalized linear mixed models. To describe the cohort's response to shame, data-driven clustering based on SPARK was conducted, and clusters' associations with the determinants were analyzed. RESULTS:Forty-seven PD patients were included. PD-related shame correlated with psychological traits (trait anxiety, shame, and guilt propensity), clinical symptoms (dyskinesia, state anxiety, depression, and apathy), and QoL. These determinants explained 79.3% of the total variance in the subsequent linear model analysis, with QoL and anxiety as the strongest covariates of shame. Apathy positively covaried with SPARK self-esteem subscale. Cluster analysis identified 3 patient groups. Highest-intensity shame cluster demonstrated elevated scores on both motor and nonmotor symptom-related shame and was associated with higher levels in anxiety, depression, and apathy, and poorer QoL. The remaining clusters showed a dissociation, with motor symptom-related shame predominating in one and nonmotor symptom-related shame in the other. CONCLUSIONS:This study provides an in-depth understanding of shame, highlighting its multifactorial nature. Due to its impact on QoL, shame should be addressed in clinical practice through pharmacological/nonpharmacological interventions, targeting both shame and its modifiable determinants. Identifying distinct shame profiles underscores the need for tailored interventions.

BACKGROUND:Many centers perform Deep Brain Stimulation (DBS) surgery under general anesthesia (GA), known as asleep DBS. Local field potential (LFP) of the Subthalamic Nucleus (STN) recorded in awake Parkinson's disease (PD) patients revealed important insights into disease mechanism and DBS optimization-strategies. In contrast, the spectral characteristics of oscillations recorded in the GA-induced unconscious state remain only partially understood. OBJECTIVES:To contrast the spectral and topographical characteristics of STN-LFPs recorded in both awake and asleep states and assess the clinical DBS response prediction based on neurophysiological hotspot positions. METHODS:STN-LFPs were recorded intraoperatively from 69 PD patients (128 hemispheres) awake and 26 patients (51 hemispheres) under propofol-anesthesia using multi-contact DBS electrodes. Spectral power (4 to 400 Hz), topographical hotspot distributions and their clinical predictive values were compared. The relationship between LFPs and frontal-EEG, anesthetic depth and dopamine withdrawal were also evaluated. RESULTS:Asleep LFPs showed increased alpha (8-12 Hz), low-beta (13-20 Hz), and fast-gamma (110-140 Hz) activity, and decreased theta (4-7 Hz), high-beta (21-30 Hz), and low-gamma (35-45 Hz) power, while high-gamma (60-90 Hz), slow-HFO (205-295 Hz) and fast-HFO (305-495 Hz) activity remained unchanged compared to the awake state. Under asleep DBS the spectral topographical map shifted medially, posteriorly and inferiorly, hereby losing its clinical predictive value. STN-LFPs echo propofol-induced changes in frontal-EEG, while time of dopamine withdrawal did not impact asleep-LFP. CONCLUSIONS:Unconsciousness reshapes the spectral and spatial topography of the STN in PD patients, hereby losing its predictive values for motor DBS-response. Dynamical changes of spectral features in space may inform future sleep-tailored DBS.

Sensing-based deep brain stimulation should optimally consider both the motor and neuropsychiatric domain to maximize quality of life of Parkinson’s disease (PD) patients. Here we characterize the neurophysiological properties of the subthalamic nucleus (STN) in 69 PD patients using a newly established neurophysiological gradient metric and contextualize it with motor symptoms and apathy. We could evidence a STN power gradient that holds most of the spectral information between 5 and 30 Hz spanning along the dorsal-ventral axis. It shows elevated power in the sub-beta range (8-12 Hz) toward the ventral STN, and elevated dorsal beta power (16–24 Hz) indicative for the hemispheres contralateral to the more affected hemi-body side. The rigidity response to DBS was highest dorsally on the axis. Importantly, apathetic symptoms can be related to reduced ventral alpha power. In conclusion, the STN spectral gradient may inform about the motor and neuropsychiatric domain, supporting integrative closed-loop strategies.

Background; Impulse control disorders (ICD) are common side effects of dopaminergic treatment in Parkinson's disease (PD). Whereas some studies show a reduction in ICD after subthalamic nucleus deep brain stimulation (STN-DBS), others report worsening of ICD or impulsivity. Objective: The aim was to study ICD in the context of STN-DBS using an objective measure of decision-making. Methods: Ten PD patients performed an effort-based decision-making task alongside neuropsychiatric and cognitive evaluation before and 4 months after STN-DBS. Further, 33 PD patients underwent the same experimental procedures just once after an average 40 months of chronic STN-DBS. Participants were examined preoperatively in the medication on state and postoperatively in the medication on/stimulation ON state. Mixed linear models were used to assess the impact of ICD and STN-DBS on acceptance rate and decision time in the task while controlling for motor symptom burden, cognitive measures, and dopaminergic medication. Results: Results revealed an increased willingness to exert high levels of effort in return for reward in patients with ICD, but acceptance rate was not modulated by chronic STN-DBS. Further, ICD, cognitive processing speed, and STN-DBS were all identified as positive predictors for faster decision speed. ICD scores showed a tendency to improve 4 months after STN-DBS, without an increase in apathy scores. Conclusions: Chronic STN-DBS and ICD facilitate effort-based decision-making by speeding up judgment. Furthermore, ICD enhances the willingness to exert high levels of effort for reward. Both STN-DBS and dopaminergic medication impact motivated behavior and should be titrated carefully to balance neuropsychiatric symptoms.

Parkinson’s disease (PD) encompasses motor (e.g., bradykinesia) and non-motor (e.g., apathy) symptoms. We aimed to use reflexive and voluntary saccades as a proxy for bradykinesia and apathy. Seventeen PD patients and thirteen controls (matched for age and educational level) were recruited. We assessed apathy using the Dimensional Apathy Scale (DAS) and bradykinesia using MDS-UPDRS III. Subjects were asked to fixate successively two green points (cues, 40° apart) alternating at 1 Hz. After 20 s, all stimuli disappeared, and participants were required to continue fixating on the previous locations of the cues at the same frequency for another 20 s. We measured the Maximal Amplitude (MA) (saccade amplitude from side to side) and its period. Linear mixed models assessed the effect of the group (patient/control), cue, DAS, and bradykinesia score. Overall, the DAS was similarly correlated to the period (p = 0.0157) and the MA (p = 0.0002) in the absence of a cue. However, this correlation was significant only in the patient subgroup for the MA (p = 0.0005). In the absence of cue, bradykinesia was similarly correlated to the period (p = .0001) and the MA (p = 0.0004). However, the period was better correlated to bradykinesia than the DAS. While the saccade period best correlates with bradykinesia, maximal amplitude in the absence of cue better reflects the severity of apathy. Our paradigm may be a promising objective biomarker for assessing bradykinesia and apathy in PD.

Creativity, the capacity and motivation to produce novel and personally meaningful ideas or behaviors, can be influenced by Parkinson’s disease (PD). Non-motor neuropsychological symptoms, such as apathy and negative schizotypy have been linked to reduced creativity, while dopaminergic treatments are associated with increased creative engagement. Building on epidemiological findings investigating changes in creativity, we examined possible drivers of increased and decreased creative activity. In a cross-sectional study, 360 participants with PD completed a questionnaire assessing self-reported creativity changes and associated factors, including personality (Big-Five, Multidimensional-Schizotypy-Scale), lifestyle (e.g., creative lifestyle, free time), and clinical (HY-scores, MoCA, dopaminergic treatments). Using machine learning (gradient-boosted decision-trees), we explained 23% of variance in creativity changes. Dopamine agonists, extraversion, free time, and a creative lifestyle since symptom onset predicted increased creativity, while disorganized schizotypy predicted decreases. The findings provide new insights for future research on creativity as part of PD’s neuropsychological spectrum and for person-centered treatment.