Altered domain-specific striatal functional connectivity in patients with Parkinson's disease and urinary symptoms.

BACKGROUND: In this study, we aimed at investigating the possible association of urinary symptoms with whole-brain MRI resting-state functional connectivity (FC) alterations from distinct striatal subregions in a large cohort of early PD patients. METHODS: Seventy-nine drug-naive PD patients (45 PD-urinary+/34 PD-urinary-) and 38 healthy controls (HCs) were consecutively enrolled. Presence/absence of urinary symptoms were assessed by means of the Nonmotor Symptom Scale - domain 7. Using an a priori connectivity-based domain-specific parcellation, we defined three ROIs (per each hemisphere) for different striatal functional subregions (sensorimotor, limbic and cognitive) from which seed-based FC voxel-wise analyses were conducted over the whole brain. RESULTS: Compared to PD-urinary-, PD-urinary+ patients showed increased FC between striatal regions and motor and premotor/supplementary motor areas as well as insula/anterior dorsolateral PFC. Compared to HC, PD-urinary+ patients presented decreased FC between striatal regions and parietal, insular and cingulate cortices. CONCLUSIONS: Our findings revealed a specific pattern of striatal FC alteration in PD patients with urinary symptoms, potentially associated to altered stimuli perception and sensorimotor integration even in the early stages. These results may potentially help clinicians to design more effective and tailored rehabilitation and neuromodulation protocols for PD patients.

Resting-State Functional MRI Approaches to Parkinsonisms and Related Dementia.

PURPOSE OF THE REVIEW: In this review, we attempt to summarize the most updated studies that applied resting-state functional magnetic resonance imaging (rs-fMRI) in the field of Parkinsonisms and related dementia. RECENT FINDINGS: Over the past decades, increasing interest has emerged on investigating the presence and pathophysiology of cognitive symptoms in Parkinsonisms and their possible role as predictive biomarkers of neurodegenerative brain processes. In recent years, evidence has been provided, applying mainly three methodological approaches (i.e. seed-based, network-based and graph-analysis) on rs-fMRI data, with promising results. Neural correlates of cognitive impairment and dementia have been detected in patients with Parkinsonisms along the diseases course. Interestingly, early functional connectivity signatures were proposed to track and predict future progression of neurodegenerative processes. However, longitudinal studies are still sparce and further investigations are needed to overcome this knowledge gap.

Resting-state network connectivity changes in drug-naive Parkinson's disease patients with probable REM sleep behavior disorder.

Epidemiological studies have shown that Parkinson's disease (PD) patients with probable REM sleep behavior disorder (pRBD) present an increased risk of worse cognitive progression over the disease course. The aim of this study was to investigate, using resting-state functional MRI (RS-fMRI), the functional connectivity (FC) changes associated with the presence of pRBD in a cohort of newly diagnosed, drug-naive and cognitively unimpaired PD patients compared to healthy controls (HC). Fifty-six drug-naïve patients (25 PD-pRBD+ and 31 PD-pRBD-) and 23 HC underwent both RS-fMRI and clinical assessment. Single-subject and group-level independent component analysis was used to analyze intra- and inter-network FC differences within the major large-scale neurocognitive networks, namely the default mode (DMN), frontoparietal (FPN), salience (SN) and executive-control (ECN) networks. Widespread FC changes were found within the most relevant neurocognitive networks in PD patients compared to HC. Moreover, PD-pRBD+ patients showed abnormal intrinsic FC within the DMN, ECN and SN compared to PD-pRBD-. Finally, PD-pRBD+ patients showed functional decoupling between left and right FPN. In the present study, we revealed that FC changes within the most relevant neurocognitive networks are already detectable in early drug-naïve PD patients, even in the absence of clinical overt cognitive impairment. These changes are even more evident in PD patients with RBD, potentially leading to profound impairment in cognitive processing and cognitive/behavioral integration, as well as to fronto-striatal maladaptive compensatory mechanisms.

Longitudinal brain connectivity changes and clinical evolution in Parkinson's disease.

Longitudinal connectivity studies might guide our understanding of the underlying neurodegenerative processes. We report the results of a longitudinal study in patients at different stages of Parkinson's disease (PD), who performed motor and non-motor evaluations and serial resting state (RS) functional MRI (fMRI). Cluster analysis was applied to demographic and clinical data of 146 PD patients to define disease subtypes. Brain network functional alterations were assessed at baseline in PD relative to 60 healthy controls and every year for a maximum of 4 years in PD groups. Progression of brain network changes were compared between patient clusters using RS fMRI. The contribution of network changes in predicting clinical deterioration was explored. Two main PD clusters were identified: mild PD (86 patients) and moderate-to-severe PD (60 patients), with the latter group being older and having earlier onset, longer PD duration, more severe motor, non-motor and cognitive deficits. Within the mild patient cluster, two clinical subtypes were further identified: mild motor-predominant (43) and mild-diffuse (43), with the latter being older and having more frequent non-motor symptoms. Longitudinal functional connectivity changes vary across patients in different disease stages with the coexistence of hypo- and hyper-connectivity in all subtypes. RS fMRI changes were associated with motor, cognitive and non-motor evolution in PD patients. Baseline RS fMRI presaged clinical and cognitive evolution. Our network perspective was able to define trajectories of functional architecture changes according to PD stages and prognosis. RS fMRI may be an early biomarker of PD motor and non-motor progression.

Action Observation and Motor Imagery Improve Dual Task in Parkinson's Disease: A Clinical/fMRI Study.

BACKGROUND: Action observation training and motor imagery may improve motor learning in Parkinson's disease (PD). OBJECTIVES: The objectives of this study were to assess mobility and balance (performing motor and dual tasks) and brain functional reorganization following 6 weeks of action observation training and motor imagery associated with dual-task gait/balance exercises in PD patients with postural instability and gait disorders relative to dual-task training alone. METHODS: Twenty-five PD-postural instability and gait disorder patients were randomized into 2 groups: the DUAL-TASK+AOT-MI group performed a 6-week gait/balance training consisting of action observation training-motor imagery combined with practicing the observed-imagined exercises; the DUAL-TASK group performed the same exercises combined with watching landscape videos. Exercises were increasingly difficult to include the dual task. At baseline and at 6 weeks, patients underwent: mobility, gait, and balance evaluations (also repeated 2 months after training), cognitive assessment, and functional MRI, including motor and dual tasks. RESULTS: Dual-task gait/balance training enhanced mobility, during both single- and dual-task conditions, and executive functions in PD-postural instability and gait disorders, with a long-lasting effect at 14 weeks. When exercises were preceded by action observation training-motor imagery, PD-postural instability and gait disorders showed greater improvement of balance and gait velocity both with and without the dual task, particularly during the turning phase. After training, the DUAL-TASK+AOT-MI group showed reduced recruitment of frontal areas and increased activity of cerebellum during functional-MRI motor and dual task, correlating with balance/turning velocity and executive improvements, respectively. The DUAL-TASK group showed reduced activity of supplementary motor area and increased recruitment of temporo-parietal areas during the dual task and decreased cerebellar activity during the motor task correlating with faster turning velocity. Functional MRI results were not corrected for multiple comparisons and should be interpreted carefully. CONCLUSIONS: Adding action observation training-motor imagery to dual-task gait/balance training promotes specific functional reorganization of brain areas involved in motor control and executive-attentive abilities and more long-lasting effects on dual-task mobility and balance in PD-postural instability and gait disorders. © 2021 International Parkinson and Movement Disorder Society.

Breakdown of the affective-cognitive network in functional dystonia.

Previous studies suggested that brain regions subtending affective-cognitive processes can be implicated in the pathophysiology of functional dystonia (FD). In this study, the role of the affective-cognitive network was explored in two phenotypes of FD: fixed (FixFD) and mobile dystonia (MobFD). We hypothesized that each of these phenotypes would show peculiar functional connectivity (FC) alterations in line with their divergent disease clinical expressions. Resting state fMRI (RS-fMRI) was obtained in 40 FD patients (12 FixFD; 28 MobFD) and 43 controls (14 young FixFD-age-matched [yHC]; 29 old MobFD-age-matched [oHC]). FC of brain regions of interest, known to be involved in affective-cognitive processes, and independent component analysis of RS-fMRI data to explore brain networks were employed. Compared to HC, all FD patients showed reduced FC between the majority of affective-cognitive seeds of interest and the fronto-subcortical and limbic circuits; enhanced FC between the right affective-cognitive part of the cerebellum and the bilateral associative parietal cortex; enhanced FC of the bilateral amygdala with the subcortical and posterior cortical brain regions; and altered FC between the left medial dorsal nucleus and the sensorimotor and associative brain regions (enhanced in MobFD and reduced in FixFD). Compared with yHC and MobFD patients, FixFD patients had an extensive pattern of reduced FC within the cerebellar network, and between the majority of affective-cognitive seeds of interest and the sensorimotor and high-order function ("cognitive") areas with a unique involvement of dorsal anterior cingulate cortex connectivity. Brain FC within the affective-cognitive network is altered in FD and presented specific features associated with each FD phenotype, suggesting an interaction between brain connectivity and clinical expression of the disease.

Telerehabilitation: A Solution for Patients After Hip Fracture?

- Hip fracture is the most common cause of hospitalization in frail geriatric subjects due to osteoporosis and recurrent falls. The clinical practice guidelines for rehabilitation after surgery in patients with hip fractures recommend to start treatment early. However, the outbreak of SARS-CoV-2 pandemic between December 2019 and January 2020 forced to lockdown. Thus, telerehabilitation seemed the best solution to remote assistance. In this scenario, the aim of our study is to assess the effects of telerehabilitation and to clarify and rearrange the knowledge about its usability and feasibility in patients after hip fracture in emergency conditions, such as the pandemic of SARS-CoV-2. Three databases were systematically searched from caption to December 2023, considering only articles published in peer-reviewed journals, with the use of three macro-areas: 'telerehabilitation', 'remote rehabilitation' and 'hip fracture'. In the present review, 26 articles were considered eligible and 10 were included. Heterogeneous results were found due to the different characteristics of the patients recruited in the studies, designs and type of the studies, and reporting/conducting of the research. Also, the typologies of telerehabilitation provided were various. In conclusion, this review demonstrated that telerehabilitation is safe, effective and well tolerated from patients and seems to be not inferior to the conventional physiotherapy. It also plays a positive role in psychological rehabilitation, in the prevention of complications and in the maintenance of achieved goals. However, further studies are needed to guide the clinical practice in providing the better posology and typology of telerehabilitation.

MRI biomarkers of freezing of gait development in Parkinson's disease.

This study investigated longitudinal clinical, structural and functional brain alterations in Parkinson's disease patients with freezing of gait (PD-FoG) and in those developing (PD-FoG-converters) and not developing FoG (PD-non-converters) over two years. Moreover, this study explored if any clinical and/or MRI metric predicts FoG development. Thirty PD-FoG, 11 PD-FoG-converters and 11 PD-non-converters were followed for two years. Thirty healthy controls were included at baseline. Participants underwent clinical and MRI visits. Cortical thickness, basal ganglia volumes and functional network graph metrics were evaluated at baseline and over time. In PD groups, correlations between baseline MRI and clinical worsening were tested. A ROC curve analysis investigated if baseline clinical and MRI measures, selected using a stepwise model procedure, could differentiate PD-FoG-converters from PD-non-converters. At baseline, PD-FoG patients had widespread cortical/subcortical atrophy, while PD-FoG-converters and non-converters showed atrophy in sensorimotor areas and basal ganglia relative to controls. Over time, PD-non-converters accumulated cortical thinning of left temporal pole and pallidum without significant clinical changes. PD-FoG-converters showed worsening of disease severity, executive functions, and mood together with an accumulation of occipital atrophy, similarly to PD-FoG. At baseline, PD-FoG-converters relative to controls and PD-FoG showed higher global and parietal clustering coefficient and global local efficiency. Over time, PD-FoG-converters showed reduced parietal clustering coefficient and sensorimotor local efficiency, PD-non-converters showed increased sensorimotor path length, while PD-FoG patients showed stable graph metrics. Stepwise prediction model including dyskinesia, postural instability and gait disorders scores and parietal clustering coefficient was the best predictor of FoG conversion. Combining clinical and MRI data, ROC curves provided the highest classification power to predict the conversion (AUC = 0.95, 95%CI: 0.86-1). Structural MRI is a useful tool to monitor PD progression, while functional MRI together with clinical features may be helpful to identify FoG conversion early.

Functional MRI connectivity of the primary motor cortex in functional dystonia patients.

BACKGROUND: Functional movement disorders include a wide spectrum of clinically documented movement disorders without an apparent organic substrate. OBJECTIVE: To explore the functional connectivity (FC) of the primary motor (M1) cortex in functional dystonia (FD) patients relative to healthy controls, with a focus on different clinical phenotypes. METHODS: Forty FD patients (12 fixed [FixFD]; 28 mobile [MobFD]) and 43 healthy controls (14 young FixFD-age-matched [yHC]; 29 old MobFD-age-matched [oHC]) underwent resting state fMRI. A seed-based FC analysis was performed using bilateral M1 as regions of interest. RESULTS: Compared to controls, FD patients showed reduced FC between left M1 and left dorsal anterior cingulate cortex, and between right M1 and left M1, premotor/supplementary motor area (SMA), dorsal posterior cingulate cortex (PCC), and bilateral precuneus. Relative to yHC, FixFD patients showed reduced FC between M1 and precuneus bilaterally. Compared to oHC, MobFD patients revealed reduced FC between right M1 and left M1, premotor/SMA, dorsal-PCC, bilateral primary sensory cortices and parieto-occipital areas, and increased FC of right M1 with right associative visual cortex and bilateral ventral-PCC. FixFD patients, relative to MobFD, showed lower FC between the right M1 and right associative visual area, and bilateral precuneus and ventral-PCC. CONCLUSIONS: This study suggests an altered brain FC of the motor circuit with areas involved in emotional processes and sense of agency in FD. FixFD patients showed FC abnormalities mainly in areas related to sense of agency, while MobFD in regions involved in sensorimotor functions (reduced FC) and emotional processing (increased FC).

Longitudinal clinical, cognitive, and neuroanatomical changes over 5 years in GBA-positive Parkinson's disease patients.

OBJECTIVE: To study the longitudinal disease course of Parkinson's disease (PD) patients with glucocerebrosidase (GBA) mutation (GBA-positive) compared to PD non-carriers (GBA-negative) along a 5-year follow-up, evaluating changes in clinical and cognitive outcomes, cortical thickness, and gray-matter (GM) volumes. METHODS: Ten GBA-positive and 20 GBA-negative PD patients underwent clinical, neuropsychological, and MRI assessments (cortical thickness and subcortical, hippocampal, and amygdala volumes) at study entry and once a year for 5 years. At baseline and at the last visit, each group of patients was compared with 22 age-matched healthy controls. Clinical, cognitive, and MRI features were compared between groups at baseline and over time. RESULTS: At baseline, GBA-positive and GBA-negative PD patients had similar clinical and cognitive profiles. Compared to GBA-negative and controls, GBA-positive patients showed cortical thinning of left temporal, parietal, and occipital gyri. Over time, compared to GBA-negative, GBA-positive PD patients progressed significantly in motor and cognitive symptoms, and showed a greater pattern of cortical thinning of posterior regions, and frontal and orbito-frontal cortices. After 5 years, compared to controls, GBA-negative PD patients showed a pattern of cortical thinning similar to that showed by GBA-positive cases at baseline. The two groups of patients showed similar patterns of subcortical, hippocampal, and amygdala volume loss over time. CONCLUSIONS: Compared to GBA-negative PD, GBA-positive patients experienced a more rapid motor and cognitive decline together with a greater, earlier and faster cortical thinning. Cortical thickness measures may be a useful tool for monitoring and predicting PD progression in accordance with the genetic background.

Progression of grey and white matter brain damage in Parkinson's disease: a critical review of structural MRI literature.

The current review summarizes the current knowledge on longitudinal cortical and subcortical grey and white matter MRI findings assessed using T1-weighted and one-tensor diffusion-weighted MRI in Parkinson's disease (PD) patients. Results were reviewed according to disease duration, disease severity and cognitive impairment. The most consistent findings are those showing a progressive cortical atrophy accumulation in caudate, putamen, temporal/hippocampal, frontal and parietal areas in de novo PD cases and in the early/middle phase of the disease, with the achievement of a plateau in the later stage. Analyzing results according to the patient cognitive status, only a few studies used longitudinal MRI metrics to predict mild cognitive impairment or dementia conversion in PD patients, suggesting that atrophy of the hippocampus, fronto-temporal areas, caudate, thalamus and accumbens might play a role in this process. Stratifying patients according to disease severity, findings appear partially controversial, although showing a progressive atrophy of basal ganglia over 1 year of follow up and a widespread cortical thinning over 3-6 years in mild to moderate PD patients. Finally, microstructural damage of the main motor and associative WM tracts seems to be present, and rapidly progress, even in the early phase of PD. The utility of structural MRI metrics as biomarkers of PD progression and their role in improving the accuracy of disease progression prediction is still debated.

Brain activity of the emotional circuit in Parkinson's disease patients with freezing of gait.

OBJECTIVE: Emotional processes might influence freezing of gait (FoG) in Parkinson's disease (PD) patients. We assessed brain functional MRI (fMRI) activity during a "FoG-observation-task" in PD-FoG patients relative to healthy controls. METHODS: Twenty-four PD-FoG patients and 18 age- and sex-matched healthy controls performed clinical and neuropsychological evaluations, and fMRI experiments including: i) "FoG-observation-task" consisting of watching a patient experiencing FoG during a walking task (usually evoking FoG); ii) "gait-observation-task" consisting of watching a healthy subject performing similar walking tasks without experiencing FoG. RESULTS: During both tasks, PD-FoG patients showed reduced activity of the fronto-parietal mirror neuron system (MNS) relative to controls. In the "FoG-observation-task" relative to the "gait-observation-task", PD-FoG patients revealed an increased recruitment of the anterior medial prefrontal cortex and a reduced recruitment of the dorsomedial prefrontal cortex and hippocampus relative to controls. Healthy controls in the "FoG-observation-task" relative to the "gait-observation-task" showed increased recruitment of cognitive empathy areas and decreased activity of the fronto-parietal MNS. CONCLUSION: Our results suggest that when PD-FoG patients observe a subject experiencing FoG, there is an increased activity of brain areas involved in self-reflection emotional processes and a reduced activity of areas related to motor programming, executive functions and cognitive empathy. These findings support previous evidence on the critical role of the emotional circuit in the mechanisms underlying FoG.

The Burden of Cardio-Cerebrovascular Risk Factors: Differences Between Individual Risk and Population Risk.

INTRODUCTION: Cardio-cerebrovascular (CCV) disease contributes significantly to the global burden of disease, with dramatic consequences in terms of mortality and general health. Mitigate CCV risk factors is the key to reduce individual and population risk of CCV events. Evidence-based medicine and epidemiological investigations of risk factors are essential to optimize actions. AIM: To contribute to the knowledge of the burden of risk factors in determining CCV events in the individual patient and in the community. METHODS: Clinical data and risk factors were collected through a longitudinal survey (1999) as part of a larger epidemiology and cardiovascular prevention project, namely the "VIP (Valle dell'Irno Prevention) Project". We assessed the incidence of major cardiovascular events (MACE) and for each risk factor we calculated: prevalence, absolute risk, odds ratio (OR), additional risk (AR) = risk of exposed to the risk factor - risk of non-exposed, population attributable risk (PAR) = additional risk * prevalence, population attributable risk fraction (PAF) = PAR/total incidence of the disease. RESULTS: Comparing the MACE group with the non-MACE group, a statistically significant difference was found for the following: glomerular filtration rate (GFR), glucose and systolic blood pressure (SBP), BMI, diastolic blood pressure (DBP), cholesterol, triglycerides, creatinine and uric acid. GFR, glucose and SBP showed the highest OR. Age, creatinine, glycemia, SBP and uric acid were independent predictor of MACE. When calculating the PAF, the CCV risk factors with the greatest impact on MACE were: SBP (29.6%), triglyceridemia (19.4%) and metabolic syndrome (18.3%). CONCLUSION: The burden of risk factors on MACE changes substantially according to whether it is calculated in the single patient or in the population. It is crucial for physicians to take these differences into account when applying their own intervention to reduce CCV events.

Dual-task clinical and functional MRI correlates in Parkinson's disease with postural instability and gait disorders.

BACKGROUND: Dual-task is a challenge for Parkinson's disease patients with postural instability and gait disorders (PD-PIGD). OBJECTIVE: This study investigated clinical, cognitive and functional brain correlates of dual-task deficits in PD-PIGD patients using quantitative gait analysis, neuropsychological evaluations and functional MRI (fMRI). METHODS: Twenty-three PD-PIGD patients performed a clinical assessment of gait/balance abilities. Single and dual-task Timed-Up-and-Go tests were monitored using an optoelectronic system to study turning velocity. Patients underwent executive-attentive function evaluation and two fMRI tasks: motor-task (foot anti-phase movements), and dual-task (foot anti-phase movements while counting backwards by threes starting from 100). Twenty-three healthy subjects underwent neuropsychological and fMRI assessments. RESULTS: Dual-task in PD-PIGD patients resulted in worse gait performance, particularly during turning. Performing the dual-task relative to the motor-fMRI task, healthy subjects showed widespread increased recruitment of sensorimotor, cognitive and cerebellar areas and reduced activity of inferior frontal and supramarginal gyri, while PD-PIGD patients showed increased recruitment of inferior frontal gyrus and supplementary motor area and reduced activity of primary motor, supramarginal and caudate areas. Dual-task gait alterations in patients correlated with balance and executive deficits and with altered dual-task fMRI brain activity of frontal areas. CONCLUSIONS: This study suggested the correlation between dual-task gait difficulties, postural instability and executive dysfunction in PD-PIGD patients. FMRI results suggest that an optimized recruitment of motor and cognitive networks is associated with a better dual-task performance in PD-PIGD. Future studies should evaluate the effect of specific gait/balance and dual-task trainings to improve gait parameters and optimize brain functional activity during dual-tasks.

Brain activity during lower limb movements in Parkinson's disease patients with and without freezing of gait.

In this study, we assessed brain functional MRI (fMRI) activity during a foot movement task in Parkinson's disease patients with (PD-FoG) and without freezing of gait (PD-noFoG). Twenty-seven PD patients (17 PD-FoG) and 18 healthy controls (HC) were recruited. PD-FoG cases were divided into nine with mild and eight with moderate FoG according to the FoG questionnaire. Patients underwent motor and neuropsychological evaluations. Both patients and controls performed an fMRI task consisting of alternate dorsal/plantar foot flexion movements according to an auditory stimulus of 0.5 Hz. PD-FoG and PD-noFoG patients were similar for all motor variables (except for the presence of FoG). PD-FoG patients performed worse in executive, attention and working memory, visuospatial, language and memory cognitive tests relative to HC and in executive and language functions compared with PD-noFoG patients. While PD-noFoG patients showed an increased recruitment of the fronto-striatal circuit relative to HC during the fMRI task, PD-FoG subjects showed an increased activity of the parieto-occipital and cerebellar areas compared with HC and a reduced basal ganglia activity when compared with PD-noFoG patients. Within the PD-FoG group, patients with more severe FoG scores showed a decreased recruitment of fronto-parietal areas relative to less severe cases. fMRI modifications correlated with FoG severity and with executive-attentive and visuospatial deficits in PD-FoG patients. This study revealed the presence of two different patterns of brain activity during a foot movement task in PD-FoG and PD-noFoG patients, suggesting a possible compensatory role of parieto-occipital networks to overcome the fronto-striatal failure in PD-FoG cases.

Sensory trick phenomenon in cervical dystonia: a functional MRI study.

Sensory trick may relieve dystonic symptoms in patients with idiopathic cervical dystonia (CD). We investigated the patterns of brain functional MRI (fMRI) during resting state, sensory trick simulation and sensory trick imagination in CD patients both with and without an effective sensory trick. We recruited 17 CD patients and 15 healthy controls. Nine patients (CD-trick) had an effective sensory trick, while 8 patients (CD-no-trick) did not. Cervical range of motion validated instrument assessed dystonic posture and sensory trick effect. Participants underwent resting state fMRI, which was repeated by patients while executing the sensory trick. Patients also performed an fMRI task in which they were asked to imagine a sensory trick execution. CD-trick and CD-no-trick patients were comparable in terms of CD severity. Applying the sensory trick, CD-trick patients significantly improved dystonic posture. CD-no-trick patients showed an increased functional connectivity of sensorimotor network relative to controls during classic resting state fMRI. During resting state fMRI with sensory trick, CD-trick patients showed a decrease of sensorimotor network connectivity. During the sensory trick imagination fMRI task, CD-trick relative to CD-no-trick patients increased the recruitment of cerebellum bilaterally. This study suggests a hyper-connectivity of sensorimotor areas during resting state in CD-no-trick subjects. In CD-trick patients, the sensory trick performance was associated with a decreased connectivity of the sensorimotor network. The increased activation of cerebellum in CD-trick patients during the sensory trick imagination suggests a possible role of this area in modulating cortical activity.

Progressive brain atrophy and clinical evolution in Parkinson's disease.

Clinical manifestations and evolution are very heterogeneous among individuals with Parkinson's disease (PD). The aims of this study were to investigate the pattern of progressive brain atrophy in PD according to disease stage and to elucidate to what extent cortical thinning and subcortical atrophy are related to clinical motor and non-motor evolution. 154 patients at different PD stages were assessed over time using motor, non-motor and structural MRI evaluations for a maximum of 4 years. Cluster analysis defined clinical subtypes. Cortical thinning and subcortical atrophy were assessed at baseline in patients relative to 60 healthy controls. Longitudinal trends of brain atrophy progression were compared between PD clusters. The contribution of brain atrophy in predicting motor, non-motor, cognitive and mood deterioration was explored. Two main PD clusters were defined: mild (N = 87) and moderate-to-severe (N = 67). Two mild subtypes were further identified: mild motor-predominant (N = 43) and mild-diffuse (N = 44), with the latter group being older and having more severe non-motor and cognitive symptoms. The initial pattern of brain atrophy was more severe in patients with moderate-to-severe PD. Over time, mild-diffuse PD patients had the greatest brain atrophy accumulation in the cortex and the left hippocampus, while less distributed atrophy progression was observed in moderate-to-severe and mild motor-predominant patients. Baseline and 1-year cortical thinning was associated with long-term progression of motor, cognitive, non-motor and mood symptoms. Cortical and subcortical atrophy is accelerated early after the onset of PD and becomes prominent in later stages of disease according to the development of cognitive, non-motor and mood dysfunctions. Structural MRI may be useful for monitoring and predicting disease progression in PD.

Functional MRI in Idiopathic Parkinson's Disease.

Functional MRI (fMRI) has been widely used to study abnormal patterns of brain connectivity at rest and activation during a variety of tasks in patients with idiopathic Parkinson's disease (PD). fMRI studies in PD have led to a better understanding of many aspects of the disease including both motor and non-motor symptoms. Although its translation into clinical practice is still at an early stage, fMRI measures hold promise for multiple clinical applications in PD, including the early detection, predicting future change in clinical status, and as a marker of alterations in brain physiology related to neurotherapeutic agents and neurorehabilitative strategies.