Parkinson's disease is characterized by exaggerated beta activity (13–35 Hz) in cortico‐basal ganglia motor loops. Beta activity includes both periodic fluctuations (i.e. oscillatory activity) and ...aperiodic fluctuations reflecting spiking activity and excitation/inhibition balance (i.e. non‐oscillatory activity). However, the relative contribution, dopamine dependency and clinical correlations of oscillatory vs. non‐oscillatory beta activity remain unclear. We recorded, modelled and analysed subthalamic local field potentials in parkinsonian patients at rest while off or on medication. Autoregressive modelling with additive 1/f noise clarified the relationships between measures of beta activity in the time domain (i.e. amplitude and duration of beta bursts) or in the frequency domain (i.e. power and sharpness of the spectral peak) and oscillatory vs. non‐oscillatory activity: burst duration and spectral sharpness are specifically sensitive to oscillatory activity, whereas burst amplitude and spectral power are ambiguously sensitive to both oscillatory and non‐oscillatory activity. Our experimental data confirmed the model predictions and assumptions. We subsequently analysed the effect of levodopa, obtaining strong‐to‐extreme Bayesian evidence that oscillatory beta activity is reduced in patients on vs. off medication, with moderate evidence for absence of modulation of the non‐oscillatory component. Finally, specifically the oscillatory component of beta activity correlated with the rate of motor progression of the disease. Methodologically, these results provide an integrative understanding of beta‐based biomarkers relevant for adaptive deep brain stimulation. Biologically, they suggest that primarily the oscillatory component of subthalamic beta activity is dopamine dependent and may play a role not only in the pathophysiology but also in the progression of Parkinson's disease.
Key points
Beta activity in Parkinson's disease includes both true periodic fluctuations (i.e. oscillatory activity) and aperiodic fluctuations reflecting spiking activity and synaptic balance (i.e. non‐oscillatory activity).
The relative contribution, dopamine dependency and clinical correlations of oscillatory vs. non‐oscillatory beta activity remain unclear.
Burst duration and spectral sharpness are specifically sensitive to oscillatory activity, while burst amplitude and spectral power are ambiguously sensitive to both oscillatory and non‐oscillatory activity.
Only the oscillatory component of subthalamic beta activity is dopamine‐dependent.
Stronger beta oscillatory activity correlates with faster motor progression of the disease.
figure legend Oscillatory and non‐oscillatory components of beta activity in Parkinson's disease. At least under stationary conditions, subthalamic beta burst dynamics in the time domain (i.e. average burst amplitude and duration) correspond to spectral measures in the frequency domain (i.e. power and sharpness of the spectral peak, respectively). Sharpness and burst duration are specific to the oscillatory activity, whereas peak power and burst amplitude ambiguously reflect both oscillatory and non‐oscillatory activity. Only the oscillatory beta activity is dopamine dependent and, consequently, primarily relevant for adaptive deep brain stimulation (aDBS) in Parkinson's disease. Furthermore, oscillatory beta activity correlates with the rate of motor progression of the disease, and may thus play a role not only in the pathophysiology but also in the progression of Parkinson's disease.
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.
Expanding the Phenotypic Variability of PMPCA‐Related Ataxia Sanesteban‐Beceiro, Esteban; Fenollar‐Cortés, María; Herrero‐Forte, Clara ...
Movement disorders clinical practice (Hoboken, N.J.),
July 2024, Letnik:
11, Številka:
7
Journal Article
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.
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.
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 in 1 at 4 months; and gait disturbance in 13 patients, which persisted in 2 at 4 months. In 6 patients in the active-treatment group, some of these deficits were present at 12 months.
Focused ultrasound subthalamotomy in one hemisphere improved motor features of Parkinson's disease in selected patients with asymmetric signs. Adverse events included speech and gait disturbances, weakness on the treated side, and dyskinesia. (Funded by Insightec and others; ClinicalTrials.gov number, NCT03454425.).
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