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DBS has been shown to be an effective intervention for neurological disorders. However, the intervention is complex and many aspects have not been understood. Various clinical situations have no solution and follow trial and error approaches. Dystonia is a movement disorder characterized by involuntary muscle contractions, which gives rise to abnormal movements and postures. Status dystonicus (SD) represents a life-threatening condition that requires urgent assessment and management. Electrophysiological markers for risk of symptom worsening and SD related patterns of evolution in patients treated with long-term deep brain stimulation (DBS), and specially under the effect of withdrawal and renewals of simulation are needed. To this end, we study the variability of neural synchronization as a mechanism for symptom generation under successive perturbations to a system, i.e. withdrawals and renewals of neuromodulation, through computational simulation of clinical profiles under different plasticity conditions. The simulation shows that the neuroplasticity makeup influences the variability of oscillation synchronization patterns in virtual "patients". The difference between the effect of different electrophysiological signatures is remarkable and under a certain condition (equal medium long term potentiation and long term depression) the situation resembles that of a stable equilibrium, putatively making the sudden worsening or change less likely. Stability of variability can only be observed in this condition and is clearly distinct from other scenarios. Our results demonstrate that the neuroplasticity makeup affects the variability of the oscillatory synchrony. This i) informs the shaping of the electrophysiological makeup and ii) might serve as a marker for clinical behavior. • Variability of electrophysiological data is useful information for DBS patient management. • Modelling variability data sheds light on physiological signatures usually not accessible with in vivo data. • Risks associated with changes to neuromodulation can be elucidated via variability analysis. [ABSTRACT FROM AUTHOR]

Abstract: Background: Deep brain stimulation (DBS) of the internal globus pallidus (GPi) is an established therapy for primary generalized dystonia. However, the evolution of dystonia symptoms after DBS discontinuation after years of therapy has only rarely been reported. We therefore longitudinally studied the main physiological measurements known to be impaired in dystonia, with DBS ON and then again after termination of DBS, after at least five years of continuous DBS. Objective: We studied whether dystonia evolution after DBS discontinuation in patients benefiting from long-term GPi DBS is different from that observed in earlier stages of the therapy. Methods: In eleven DYT1 patients treated with bilateral GPi DBS for at least 5 years, dystonia was assessed ON-DBS, immediately after switch-off (OFF-DBS1) and 48 h after DBS termination (OFF-DBS2). We studied the influence of DBS intensity on dystonia when DBS was discontinued. Results: On average a significant difference in symptoms was measured only between ON-DBS and OFF-DBS1 conditions. Importantly, none of the patients returned to their preoperative dystonia severity, even 48 h after discontinuation. The amount of clinical deterioration in the OFF conditions positively correlated with higher stimulation current in the chronic ON-DBS condition. Conclusions: The duration of DBS application influences symptom evolution after DBS termination. DBS intensity seems to have a prominent role on evolution of dystonic symptoms when DBS is discontinued. In conclusion, DBS induces changing modulation of the motor network with less worsening of symptoms after long term stimulation, when DBS is stopped. [Copyright &y& Elsevier]

Abstract: This study aimed to investigate which cerebral cortices are involved in the central autonomic network and how they are linked to the peripheral (cardiac) autonomic network in Parkinson''s disease (PD) patients and normal controls. 26 PD patients with autonomic dysfunction and 23 age- and sex-matched controls were evaluated by simultaneous spectral analysis of electroencephalography (EEG) and electrocardiography (ECG) recording along with autonomic questionnaires. Although the PD group has significantly more symptoms of autonomic dysfunction, frequency-domain HRV can not differentiate these two groups. However, different patterns of central oscillation and their correlation with peripheral autonomic indices could be found for the two groups. While the power of specific EEG bands under electrodes F4, F7, Cz and Pz (parietal-lateral premotor cortex, which is considered as a compensatory area for the relative deficiency of mesial frontal-striatal circuits in PD) correlated significantly with the power of peripheral heart rate variability (HRV) indices in the PD group, those under electrodes C3, P3, P4 and F8 had significant correlation in the control group. In conclusion, functional connectivity between areas of cerebral cortex and peripheral autonomic system can be measured and differs between PD patients with autonomic dysfunction and healthy controls. The central autonomic network may play a role in brain re-organization in PD patients with autonomic dysfunction. [Copyright &y& Elsevier]

Abstract: Objective: To test whether inhibitory continuous Theta Burst (cTBS) transcranial magnetic stimulation (TMS) can alter neural activity involved in planning and execution of a self-paced movement. Methods: In seven subjects, cTBS was applied over either the left or right primary motor cortex (left M1 and right M1) and the left dorsal premotor cortex (left PMd) in different experimental sessions. Motor evoked potentials (MEP) at rest were measured as well as the two main components of the movement related cortical potential (MRCP), the Bereitschaftspotential (BP) and the negative slope (NS’), prior to self-paced right thumb opposition. Results: cTBS suppressed contralateral MEPs when it was applied over left M1, right M1 and left PMd. In addition, cTBS over left M1, but not at any other location, reduced the amplitude of the NS’ and tended to shorten the BP onset without changing EMG activity associated with voluntary muscular output. There was a significant correlation between the percent suppression of the MEP and the reduction in amplitude of the total MRCP (BP+NS’). Conclusions: cTBS can produce long-lasting effects on brain activity involved in the preparation and execution of a volitional movement. Significance: The fact that movement was not compromised while brain activity changed suggests that the motor system of healthy subjects operates with a safety factor that can adjust patterns of activation to compensate for the partial disruption caused by cTBS. [Copyright &y& Elsevier]

Abstract: Deep brain stimulation (DBS) is a powerful treatment option for movement disorders, including severe generalised dystonia. After several years of treatment, cases have been reported in which DBS has been stopped without any deterioration in clinical benefit. This might indicate that DBS can restore function in some cases. The mechanism of DBS induced clinical retention effects has been addressed before. Here, the question we asked was if such clinical stability is reflected at the underlying physiology level or whether there is indication to believe that a stand-still of symptoms might be at risk because of neurophysiological instability. We recorded patients with pre-intervention life-threatening or severe genetic dystonia with long lasting clinical benefit when turned off DBS. Despite clinical stability, our physiological studies revealed large changes in the excitability of excitatory and inhibitory motor circuits in the cortex, which exceed normal fluctuation. This discrepancy between instability in the motor network physiology caused by removal of DBS and clinical stability alerts as it potentially indicates a risk to fail and cause symptoms to return. [Copyright &y& Elsevier]