Focused ultrasound therapy in movement disorders: management roadmap toward optimal pathway organization.

MRI-guided focused ultrasound (MRgFUS) lesioning is an innovative, safe and effective treatment which provides an innovative development in the field of minimally invasive stereotactic neurosurgery. Based on the application of focused ultrasound energy under full MR planning and thermal imaging control, unilateral lesioning of the thalamus, subthalamic nucleus, and globus pallidus is indicated for the treatment of movement disorders, including essential tremor, Parkinson's disease, and dystonia. We started to apply this technique in February 2019 for the treatment of patients with movement disorders. The authors developed a diagnostic therapeutic care pathway, which is herewith proposed and applied as an explication of standard clinical practice in use. The project was the result of the application of different methods such as Health Technology Assessment (HTA), Strengths, Weaknesses, Opportunities and Threats analysis (SWOT) and Demin -Plan, Do, Check, Act (PDCA) cycle. The aim of this project was to standardize the MRgFUS diagnostic-therapeutic pathway (DTP), describe its application and the appropriateness of different phases (patient selection, intervention phase and follow-up). Here, we described in detail our experience in the DTP application from 2019 up to now in 610 patients with movement disorders.

Frontal cortex BOLD signal changes in premanifest Huntington disease: a possible fMRI biomarker.

OBJECTIVE: To identify a possible functional imaging biomarker sensitive to the earliest neural changes in premanifest Huntington disease (preHD), allowing early therapeutic approaches aimed at preventing or delaying clinical onset. METHODS: Sixteen preHD and 18 healthy participants were submitted to anatomical acquisitions and functional MRI (fMRI) acquisitions during the execution of the exogenous covert orienting of attention task. Due to strong a priori hypothesis, all fMRI correlation analyses were restricted to the following: (1) the frontal oculomotor cortex identified by the means of a prosaccadic task, comprising frontal eye fields and supplementary frontal eye fields; and (2) the data collected during inhibition of return, a phenomenon occurring during the executed task. In preHD, multiple regression analysis was performed between fMRI data and the probability to develop the disease in the next 5 years (p5HD). Moreover, mean blood oxygen level-dependent (BOLD) signal changes in the frontal oculomotor cortex and striatal volumes were linearly correlated with p5HD. RESULTS: In preHD, multiple regression analysis showed that clusters of activity strongly correlated with p5HD in the right frontal oculomotor cortex. Importantly, mean BOLD signal changes of this region correlated with p5HD (r(2) = 0.52). Among the considered striatal volumes, a modest correlation (r(2) = 0.29) was observed in the right putamen and p5HD. CONCLUSION: fMRI activations in the right-frontal oculomotor cortex during inhibition of return can be considered a possible functional imaging biomarker in preHD.

In medication-overuse headache, fMRI shows long-lasting dysfunction in midbrain areas.

OBJECTIVE: The primary aim of our study was to evaluate if a group of medication-overuse headache (MOH) patients present dysfunctions in the mesocorticolimbic dopamine circuit. The secondary aim was to disentangle the role of the medication overuse and of the acute/chronic headache in determining these alterations and to investigate their persistence. BACKGROUND: Several researches have suggested that MOH may belong to the spectrum of addictive behavior. Preclinical models and neuroimaging studies have consistently demonstrated that in addiction, critical long-lasting alterations occur in the mesocorticolimbic dopamine circuit. If MOH shares some neurophysiological features with addiction, long-lasting functional alterations of the mesocorticolimbic dopamine system related to medication overuse should be present. METHODS: We collected functional magnetic resonance imaging data during the execution of a decision-making under risk paradigm in 8 MOH patients immediately after beginning medication withdrawal, in 8 detoxified MOH patients at 6 months after beginning medication withdrawal, in 8 chronic migraine patients, and in 8 control subjects. RESULTS: Our results revealed that MOH patients present: (1) reduced task-related activity in the substantia nigra/ventral tegmental area complex and increased activity in the ventromedial prefrontal cortex, when compared with controls; (2) reduced activity in the substantia nigra/ventral tegmental area complex, when compared with chronic migraine patients; (3) increased activity in the ventromedial prefrontal cortex, when compared with detoxified MOH patients. CONCLUSION: Our study showed that MOH patients present dysfunctions in the mesocorticolimbic dopamine circuit, in particular in the ventromedial prefrontal cortex and in the substantia nigra/ventral tegmental area complex. The ventromedial prefrontal cortex dysfunctions seem to be reversible and attributable to the acute/chronic headache, whereas the substantia nigra/ventral tegmental area complex dysfunctions are persistent and possibly related to medication overuse. These dysfunctions might be the expression of long-lasting neuroadaptations related to the overuse of medications and/or a pre-existing neurophysiological condition leading to vulnerability to medication overuse. The observed persistent dysfunctions in the midbrain dopamine suggest that MOH may share some neurophysiological features with addiction.

Neural signatures of economic parameters during decision-making: a functional MRI (FMRI), electroencephalography (EEG) and autonomic monitoring study.

Adaptive behaviour requires an ability to obtain rewards by choosing between different risky options. Financial gambles can be used to study effective decision-making experimentally, and to distinguish processes involved in choice option evaluation from outcome feedback and other contextual factors. Here, we used a paradigm where participants evaluated 'mixed' gambles, each presenting a potential gain and a potential loss and an associated variable outcome probability. We recorded neural responses using autonomic monitoring, electroencephalography (EEG) and functional neuroimaging (fMRI), and used a univariate, parametric design to test for correlations with the eleven economic parameters that varied across gambles, including expected value (EV) and amount magnitude. Consistent with behavioural economic theory, participants were risk-averse. Gamble evaluation generated detectable autonomic responses, but only weak correlations with outcome uncertainty were found, suggesting that peripheral autonomic feedback does not play a major role in this task. Long-latency stimulus-evoked EEG potentials were sensitive to expected gain and expected value, while alpha-band power reflected expected loss and amount magnitude, suggesting parallel representations of distinct economic qualities in cortical activation and central arousal. Neural correlates of expected value representation were localized using fMRI to ventromedial prefrontal cortex, while the processing of other economic parameters was associated with distinct patterns across lateral prefrontal, cingulate, insula and occipital cortices including default-mode network and early visual areas. These multimodal data provide complementary evidence for distributed substrates of choice evaluation across multiple, predominantly cortical, brain systems wherein distinct regions are preferentially attuned to specific economic features. Our findings extend biologically-plausible models of risky decision-making while providing potential biomarkers of economic representations that can be applied to the study of deficits in motivational behaviour in neurological and psychiatric patients.