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2023 Acuerdos transformativos CRUE, Aim: Impulse‐control disorder is a common neuropsychiatric complication in Parkinson's disease (PD) under dopamine replacement therapy. Prior studies tested the balance between enhanced desire towards reward and cognitive control deficits, hypothesized to be biased towards the former in impulse control disorders. We provide evidence for this hypothesis by measuring behavioral and neural patterns behind the influence of sexual desire over response inhibition and tools towards functional restoration using repetitive transcranial stimulation in patients with hypersexuality as predominant impulsive disorder. Methods: The effect of sexual cues on inhibition was measured with a novel erotic stop‐signal task under on and off dopaminergic medication. Task‐related functional and anatomical connectivity models were estimated in 16 hypersexual and 17 nonhypersexual patients with PD as well as in 17 healthy controls. Additionally, excitatory neuromodulation using intermittent theta‐burst stimulation (sham‐controlled) was applied over the pre‐supplementary motor area in 20 additional hypersexual patients with PD aiming to improve response inhibition. Results: Compared with their nonhypersexual peers, patients with hypersexuality recruited caudate, pre‐supplementary motor area, ventral tegmental area, and anterior cingulate cortex while on medication. Reduced connectivity was found between pre‐supplementary motor area and caudate nucleus in hypersexual compared with nonhypersexual patients (while medicated), a result paralleled by compensatory enhanced anatomical connectivity. Furthermore, stimulation over the pre‐supplementary motor area improved response inhibition in hypersexual patients with PD when exposed to sexual cues. Conclusion: This study, therefore, has identified a specific fronto‐striatal and mesolimbic circuitry underlying uncontrolled sexual responses in medicated patients with PD where cortical neuromodulation halts its expression., Ministerio de Ciencia, Innovación y Universidades, Instituto de Salud Carlos III, Fundación Jesús de Gangoiti Barrera, Depto. de Psicobiología y Metodología en Ciencias del Comportamiento, Fac. de Psicología, TRUE, pub, APC financiada por la UCM

[Background] Unilateral focused ultrasound subthalamotomy (FUS-STN) improves motor features of Parkinson’s disease (PD) in moderately advanced patients. The less invasive nature of FUS makes its early application in PD feasible. We aim to assess the safety and efficacy of unilateral FUS-STN in patients with PD of less than 5 years from diagnosis (early PD)., [Methods] Prospective, open-label study. Eligible patients with early PD had highly asymmetrical cardinal features. The primary outcome was safety, defined as treatment-related adverse events at 6 months. Secondary outcomes included efficacy, assessed as motor improvement in the Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), motor fluctuations, non-motor symptoms, daily living activities, quality of life, medication and patients’ impression of change., [Results] Twelve patients with PD (median age 52.0 (IQR 49.8–55.3) years, median time from diagnosis 3.0 (2.1–3.9) years) underwent unilateral FUS-STN. Within 2 weeks after treatment, five patients developed dyskinesia on the treated side, all resolved after levodopa dose adjustment. One patient developed mild contralateral motor weakness which fully resolved in 4 weeks. One patient developed dystonic foot and another hand and foot dystonia. The latter impaired gait and became functionally disabling initially. Both cases were well controlled with botulinum toxin injections. The off-medication motor MDS-UPDRS score for the treated side improved at 12 months by 68.7% (from 14.5 to 4.0, p=0.002), and the total motor MDS-UPDRS improved by 49.0% (from 26.5 to 13.0, p=0.002). Eleven patients (92%) reported global improvement 12 months after treatment., [Conclusion] Unilateral FUS-STN may be safe and effective to treat motor manifestations in patients with early PD. A larger confirmatory trial is warranted., [Trial registration number] NCT04692116.

Emotional information prioritizes human behavior. How much emotions influence ongoing behavior critically depends on the extent of executive control functions in a given context. One form of executive control is based on stimulus-stop associations (i.e., habitual inhibition) that rapidly and effortlessly elicits control over the interruption of ongoing behavior. So far, no behavioral accounts have explored the emotional impact on habitual inhibition. We aimed to examine the emotional modulation on habitual inhibition and associated psycho-physiological changes. A go/no-go association task asked participants to learn stimulus-stop and stimulus-response associations during 10-day training to form habitual inhibition (without emotional interference). Probabilistic feedback guided learning with varying probabilities of congruent feedback, generating stronger versus weaker pairings. A reversal test measured habitual inhibition strength counteracted by emotional cues (high-arousal positive and negative stimuli compared with neutral ones). Our training protocol induced stable behavioral and psycho-physiological responses compatible with habitual behavior. At reversal, habitual inhibition was evident as marked by significant speed costs of reversed no-go trials for strongly associated stimuli. Positive and negative emotional cues produced larger impact on habitual inhibition. We report first evidence on a cognitive control mechanism that is vulnerable to emotional stimuli and suggest alternative explanations on how emotions may boost or counteract certain behavioral abnormalities mediated by habitual inhibition.

2023 Acuerdos transformativos CRUE, Aim: Impulse‐control disorder is a common neuropsychiatric complication in Parkinson's disease (PD) under dopamine replacement therapy. Prior studies tested the balance between enhanced desire towards reward and cognitive control deficits, hypothesized to be biased towards the former in impulse control disorders. We provide evidence for this hypothesis by measuring behavioral and neural patterns behind the influence of sexual desire over response inhibition and tools towards functional restoration using repetitive transcranial stimulation in patients with hypersexuality as predominant impulsive disorder. Methods: The effect of sexual cues on inhibition was measured with a novel erotic stop‐signal task under on and off dopaminergic medication. Task‐related functional and anatomical connectivity models were estimated in 16 hypersexual and 17 nonhypersexual patients with PD as well as in 17 healthy controls. Additionally, excitatory neuromodulation using intermittent theta‐burst stimulation (sham‐controlled) was applied over the pre‐supplementary motor area in 20 additional hypersexual patients with PD aiming to improve response inhibition. Results: Compared with their nonhypersexual peers, patients with hypersexuality recruited caudate, pre‐supplementary motor area, ventral tegmental area, and anterior cingulate cortex while on medication. Reduced connectivity was found between pre‐supplementary motor area and caudate nucleus in hypersexual compared with nonhypersexual patients (while medicated), a result paralleled by compensatory enhanced anatomical connectivity. Furthermore, stimulation over the pre‐supplementary motor area improved response inhibition in hypersexual patients with PD when exposed to sexual cues. Conclusion: This study, therefore, has identified a specific fronto‐striatal and mesolimbic circuitry underlying uncontrolled sexual responses in medicated patients with PD where cortical neuromodulation halts its expression., Ministerio de Ciencia, Innovación y Universidades, Instituto de Salud Carlos III, Fundación Jesús de Gangoiti Barrera, Depto. de Psicobiología y Metodología en Ciencias del Comportamiento, Fac. de Psicología, TRUE, pub, APC financiada por la UCM

Social Cognition (SC) has been scarcely studied in Parkinson's disease (PD), and findings in early disease are controversial. SC encompasses different capacities such as facial emotion recognition (FER); Theory of Mind (ToM), the ability to understand other people's intentions (cognitive-ToM) and emotions (affective-ToM); and self-monitoring, the ability to regulate one's own behavior in social contexts. A relationship between dopaminergic deficit and SC in PD has been suggested.

Impulse-control disorder is a common neuropsychiatric complication in Parkinson's disease (PD) under dopamine replacement therapy. Prior studies tested the balance between enhanced desire towards reward and cognitive control deficits, hypothesized to be biased towards the former in impulse control disorders. We provide evidence for this hypothesis by measuring behavioral and neural patterns behind the influence of sexual desire over response inhibition and tools towards functional restoration using repetitive transcranial stimulation in patients with hypersexuality as predominant impulsive disorder.

The microtubule-associated protein tau (MAPT) H1 homozygosity (H1/H1 haplotype) is a genetic risk factor for neurodegenerative diseases, such as Parkinson's disease (PD). MAPT H1 homozygosity has been associated with conversion to PD; however, results are conflicting since some studies did not find a strong influence. Cortical hypometabolism is associated with cognitive impairment in PD. In this study, we aimed to evaluate the metabolic pattern in nondemented PD patients MAPT H1/H1 carriers in comparison with MAPT H1/H2 haplotype. In addition, we evaluated domain-specific cognitive differences according to MAPT haplotype.

Unilateral magnetic resonance-guided focused ultrasound subthalamotomy (FUS-STN) has been shown to improve the cardinal motor features of Parkinson disease (PD). Whether this effect is sustained is not known. This study aims to report the long-term outcome of patients with PD treated with unilateral FUS-STN.

Parkinson's disease (PD) exhibits a high prevalence of dementia as disease severity and duration progress. Focused ultrasound (FUS) has been applied for transient blood-brain barrier (BBB) opening of cortical regions in neurodegenerative disorders. The striatum is a primary target for delivery of putative therapeutic agents in PD.

Introduction: Impulse control disorders (ICDs) represent a side effect of dopaminergic medication in Parkinson's disease (PD). Patients experience an excessive desire toward natural rewards paired with uncontrolled actions. Yet, the precise neural and behavioral mechanisms associated with ICDs and, importantly, each specific subdomain remain unclear. We aim to decipher resting-state and corticolimbic functional connectivity in PD patients with and without hypersexual ICD. Materials and Methods: Seventeen PD patients with hypersexuality (PD+HS) and 15 PD patients without hypersexuality (PD-HS) underwent two sessions (with and without medication) of resting-state functional magnetic resonance imaging and were compared with 17 healthy controls. Dual-regression independent component analyses extracted salience, sensorimotor, default-mode, and central executive networks. Seed-based functional connectivity with three striatal subdivisions (motor, associative, and limbic) was obtained and significant changes were correlated with key impulsivity and inhibitory measures. Results: Enhanced salience network (SN) activity represented by a significant rise in the right inferior frontal gyrus was found in PD+HS compared with PD-HS. Connectivity analyses revealed a functional disconnection between associative and limbic striatum with precuneus and superior parietal lobe in PD+HS, some connections explained by abnormal sexual behavior and inhibition in PD+HS. Conclusions: Hypersexual ICD is associated with enhanced SN signaling and corticolimbic disconnections, including striatal associative and limbic loops that contribute to altered control of sexually driven behavior and overall severity in PD and ICD. Impact statement We enlarge the neurobiological basis to one specific Parkinson's disease (PD) and impulse control disorder (ICD) (PD+ICD) subtype-that is, hypersexuality-and reveal its associated resting-state functional connectivity linked to altered behavior. We report enhanced

In Parkinson’s disease, striatal dopamine depletion produces profound alterations in the neural activity of the cortico-basal ganglia motor loop, leading to dysfunctional motor output and parkinsonism. A key regulator of motor output is the balance between excitation and inhibition in the primary motor cortex, which can be assessed in humans with transcranial magnetic stimulation techniques. Despite decades of research, the functional state of cortical inhibition in Parkinson’s disease remains uncertain. Towards resolving this issue, we applied paired-pulse transcranial magnetic stimulation protocols in 166 patients with Parkinson’s disease (57 levodopa-naı¨ve, 50 non-dyskinetic, 59 dyskinetic) and 40 healthy controls (age-matched with the levodopa-naı¨ve group). All patients were studied OFF medication. All analyses were performed with fully automatic procedures to avoid confirmation bias, and we systematically considered and excluded several potential confounding factors such as age, gender, resting motor threshold, EMG background activity and amplitude of the motor evoked potential elicited by the single-pulse test stimuli. Our results show that short-interval intracortical inhibition is decreased in Parkinson’s disease compared to controls. This reduction of intracortical inhibition was obtained with relatively low-intensity conditioning stimuli (80% of the resting motor threshold) and was not associated with any significant increase in short-interval intracortical facilitation or intracortical facilitation with the same low-intensity conditioning stimuli, supporting the involvement of cortical inhibitory circuits. Short-interval intracortical inhibition was similarly reduced in levodopa-naı¨ve, non-dyskinetic and dyskinetic patients. Importantly, intracortical inhibition was reduced compared to control subjects also on the less affected side (n = 145), even in de novo drug-naı¨ve patients in whom the less affected side was minimally symptomatic (lateralized Uni

BACKGROUND The subthalamic nucleus is the preferred neurosurgical target for deep-brain stimulation to treat cardinal motor features of Parkinson’s disease. Focused ultrasound is an imaging-guided method for creating therapeutic lesions in deep-brain structures, including the subthalamic nucleus. METHODS We randomly assigned, in a 2:1 ratio, patients with markedly asymmetric Parkinson’s disease who had motor signs not fully controlled by medication or who were ineligible for deep-brain stimulation surgery to undergo focused ultrasound subthalamotomy on the side opposite their main motor signs or a sham procedure. The primary efficacy outcome was the between-group difference in the change from baseline to 4 months in the Movement Disorder Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) motor score (i.e., part III) for the more affected body side (range, 0 to 44, with higher scores indicating worse parkinsonism) in the off-medication state. The primary safety outcome (procedure-related complications) was assessed at 4 months. RESULTS Among 40 enrolled patients, 27 were assigned to focused ultrasound subthalamotomy (active treatment) and 13 to the sham procedure (control). The mean MDS-UPDRS III score for the more affected side decreased from 19.9 at baseline to 9.9 at 4 months in the active-treatment group (least-squares mean difference, 9.8 points; 95% confidence interval [CI], 8.6 to 11.1) and from 18.7 to 17.1 in the control group (least-squares mean difference, 1.7 points; 95% CI, 0.0 to 3.5); the between-group difference was 8.1 points (95% CI, 6.0 to 10.3; P<0.001). Adverse events in the active-treatment group were dyskinesia in the off-medication state in 6 patients and in the on-medication state in 6, which persisted in 3 and 1, respectively, at 4 months; weakness on the treated side in 5 patients, which persisted in 2 at 4 months; speech disturbance in 15 patients, which persisted in 3 at 4 months; facial weakness in 3 patients, which persisted i

The subthalamic nucleus is the preferred neurosurgical target for deep-brain stimulation to treat cardinal motor features of Parkinson's disease. Focused ultrasound is an imaging-guided method for creating therapeutic lesions in deep-brain structures, including the subthalamic nucleus.

Essential tremor (ET) is the most common movement disorder, affecting 1% of the population worldwide. There is sound evidence that medically refractory tremor improves with thalamotomy and deep brain stimulation (DBS) targeting the thalamic ventralis intermedius nucleus (VIM). In the last few years, the incisionless technique of magnetic resonance- guided focused ultrasound (MRgFUS) has been demonstrated to be an effective procedure for unilateral thalamotomy,1 with a positive profile with regard to side effects. The thalamus is involved in cognitive functions such as attention/executive control, memory and language. Focal ablation of the thalamus, even when targeting a sensorimotor region as the VIM, raises question about potential cognitive side effects. After unilateral VIM-DBS in 40 patients with ET, Fields et al2 showed statistically significant improvements in visuoperceptual function and verbal memory. There was no significant decline in any measure, but four patients with preoperative low verbal fluency showed a further decline. Most studies have shown reduced verbal fluency under active VIM-DBS.2–4 Since focused ultrasound thalamotomy is a less invasive procedure, we hypothesised that the risk of procedure-related cognitive decline is further reduced.