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Gait and balance disorders are common signs in several neurodegenerative diseases such as Parkinson's disease, atypical parkinsonism, idiopathic normal pressure hydrocephalus, cerebrovascular disease, dementing disorders and multiple sclerosis. According to each condition, patients present with different gait and balance alterations depending on the structural and functional brain changes through the disease course. In this review, we will summarize the main clinical characteristics of gait and balance disorders in the major neurodegenerative conditions, providing an overview of the significant structural and functional MRI brain alterations underlying these deficits. We also will discuss the role of neurorehabilitation strategies in promoting brain plasticity and gait/balance improvements in these 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).

Handwriting abnormalities in people with Parkinson’s disease include several dynamic and kinematic features such as increased writing stroke duration, reduced velocity and altered fluency of the writing strokes. “Dysgraphia” is a term that includes all the possible handwriting alterations and the “micrographia”, that defines an impairment of a fine motor skill manifesting mainly as a progressive or stable reduction in amplitude during a writing task, is only one of the characteristics of parkinsonian handwriting. Few studies investigated the effects of a rehabilitative training on handwriting or used measures of handwriting as an outcome in people with PD. We aim to conduct a scoping review to answer the following question: “What are the effects of a rehabilitative program on handwriting in people with PD?”

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.

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.

Background White matter hyperintensities (WMHs) have a role in cognitive impairment in normal brain aging, while the effect on Parkinson's disease (PD) progression is still controversial. Objective To investigate the longitudinal evolution of micro- and macrostructural damage of cerebral white matter (WM) and its relationship with the clinical picture in PD. Methods A total of 154 PD patients underwent clinical, cognitive, and magnetic resonance imaging (MRI) assessment once a year for up to 4 years. Sixty healthy controls underwent the same protocol at baseline. WMHs were identified and total WMH volume was measured. WMHs were also used as exclusion masks to define normal-appearing white matter (NAWM). Using tract-based spatial statistics, diffusion tensor (DT) MRI metrics of whole-brain WM and NAWM were obtained. Linear mixed-effects models defined the longitudinal evolution and association between variables. WM alterations were tested as risk factors of disease progression using linear regression and Cox proportional hazards models. Results At baseline, PD patients showed alterations of all DT MRI measures compared to controls. Longitudinally, DT MRI measures did not vary significantly and no association with clinical variables was found. WMH volume changed over time and was associated with impairment in global cognition, executive functions, and language. Baseline WMH volume was a moderate risk factor for progression to mild cognitive impairment. Conclusions Our study suggests an association between WMHs and cognitive deterioration in PD, whereas WM microstructural damage is a negligible contributor to clinical deterioration. WMHs assessed by MRI can provide an important tool for monitoring the development of cognitive impairment in PD patients. © 2021 International Parkinson and Movement Disorder Society.

Background: In the last few years, virtual reality (VR) has been increasingly used to strengthen the effect of balance training (BT) in Parkinson’s disease (PD). Objective: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the effects of VR-BT relative to BT alone for improving balance and mobility PD subjects with balance/mobility difficulties. Methods: Four electronic databases were searched: two reviewers independently selected RCTs, extracted data, and applied the Cochrane risk-of-bias tool for randomized trials (version 2) and the GRADE framework for assessing the certainty of evidence. Primary outcomes were balanced (Berg Balance Scale-BBS), mobility (Timed Up and Go-TUG) and walking speed. Secondary outcomes were falls, walking distance and stability, spatial gait parameters, balance confidence, sensory integration ability, motor signs and quality of life. Results: We included 22 studies (901 patients). Meta-analysis on fourteen trials (430 patients) showed a mean difference (MD) of 2.09 points (95% confidence interval [CI] 0.86–3.33) on BBS favoring VR-BT compared to BT (low certainty evidence). Subgroup analyses showed higher balance improvement in most affected subjects (moderate certainty evidence) and using VR rehabilitation-specific systems vs. VR non-specific systems. Eight trials (236 patients) assessing mobility showed a MD of 1.55s (95% CI 0.04–3.06) on TUG favoring VR-BT (very low certainty evidence). No differences were observed in walking speed. Estimated effects were not maintained for any outcome at follow-up. Conclusions: This review suggests that VR-BT is more effective than BT to improve balance in PD subjects immediately after training, particularly in individuals with higher postural instability at baseline.

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.

This study aimed to identify functional neuroimaging patterns anticipating the clinical indication for deep brain stimulation (DBS) in patients with Parkinson’s disease (PD). A cohort of prospectively recruited patients with PD underwent neurological evaluations and resting-state functional MRI (RS-fMRI) at baseline and annually for 4 years. Patients were divided into two groups: 19 patients eligible for DBS over the follow-up and 41 patients who did not meet the criteria to undergo DBS. Patients selected as candidates for DBS did not undergo surgery at this stage. Sixty age- and sex-matched healthy controls performed baseline evaluations. Graph analysis and connectomics assessed global and local topological network properties and regional functional connectivity at baseline and at each time point. At baseline, network analysis showed a higher mean nodal strength, local efficiency, and clustering coefficient of the occipital areas in candidates for DBS over time relative to controls and patients not eligible for DBS. The occipital hyperconnectivity pattern was confirmed by regional analysis. At baseline, a decreased functional connectivity between basal ganglia and sensorimotor/frontal networks was found in candidates for DBS compared to patients not eligible for surgery. In the longitudinal analysis, patient candidate for DBS showed a progressively decreased topological brain organization and functional connectivity, mainly in the posterior brain networks, and a progressively increased connectivity of basal ganglia network compared to non-candidates for DBS. RS-fMRI may support the clinical indication to DBS and could be useful in predicting which patients would be eligible for DBS in the earlier stages of PD.

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.

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.

GCH1 gene encodes the guanosine-5'-triphosphate (GTP) cyclohydrolase 1 (GTP-CH1), which is the enzyme involved in the first and rate-limiting step of the de novo biosynthesis of tetrahydrobiopterin and an essential cofactor for the synthesis of dopamine in nigrostriatal neurons. GCH1 mutation is the most common cause of the DOPA-responsive dystonia (DRD).1 This rare autosomal-dominant movement disorder is characterised predominantly by limb dystonia during childhood, although parkinsonian features may also be present.1 The hallmark of the disease is an excellent and sustained response to small doses of levodopa, generally without the occurrence of motor complications.1 Lack of changes in neuropathological and in majority of dopaminergic imaging studies in patients with GCH1 -related DRD suggest that this is a neurotransmitter rather than a neurodegenerative disorder.1 However, case reports showed a nigrostriatal dopaminergic denervation (abnormal DaTSCAN) in some individuals carrying GCH1 mutation with adult-onset dystonia-parkinsonism.2 Residual symptoms might partially result from a lack of timely therapy, possibly suggesting underlying neurodegeneration. It has been hypothesised that, after a period of compensation, chronic reduction of dopamine levels resulting from GTP-CH1 deficiency could predispose to nigral cell damage by making them more vulnerable to environmental or other genetic factors.2 To the best of our knowledge, no MRI studies have been performed to assess the presence of structural damage supporting the possible neurodegenerative process underlying DRD. In order to fill the gap in line with previous suggestions, in this study we used structural MRI (1.5 T) to evaluate patterns of cortical thickness, basal ganglia volumes, and white matter (WM) microstructural alterations …

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.

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 1year of follow up and a widespread cortical thinning over 3–6years 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.

Background The neural basis of task specificity in dystonia is still poorly understood. This study investigated gray and white matter (WM) brain alterations in patients with task-specific dystonia (TSD) and non-task-specific dystonia (NTSD). Methods Thirty-six patients with TSD (spasmodic dysphonia, writer's cramp), 61 patients with NTSD (blepharospasm, cervical dystonia), and 83 healthy controls underwent 3D T1-weighted and diffusion tensor magnetic resonance imaging (MRI). Whole brain cortical thickness and voxel-based morphometry; volumes of basal ganglia, thalamus, nucleus accumbens, amygdala, and hippocampus; and WM damage were assessed. Analysis of variance models were used to compare MRI measures between groups, adjusting for age and botulinum toxin (BoNT) treatment. Results The comparison between focal dystonia patients showed cortical thickness and gray matter (GM) volume differences (ie, decreased in NTSD, increased in TSD) in frontal, parietal, temporal, and occipital cortical regions; basal ganglia; thalamus; hippocampus; and amygdala. Cerebellar atrophy was found in NTSD patients relative to controls. WM damage was more severe and widespread in task-specific relative to NTSD patients. TSD patients receiving BoNT, relative to nontreated patients, had cortical thickening and increased GM volume in frontoparietal, temporal, and occipital regions. NTSD patients experiencing pain showed cortical thickening of areas involved in pain-inhibitory mechanisms. Conclusions TSD and NTSD are characterized by opposite alterations of the main cortical and subcortical sensorimotor and cognitive-controlling brain structures, suggesting the possible presence of different pathophysiological and/or compensatory mechanisms underlying the complexity of the two clinical phenotypes of focal dystonia. © 2020 International Parkinson and Movement Disorder Society.

Highlights • Cortical and subcortical atrophy is accelerated early after the onset of PD. • Brain atrophy in PD progressed with cognitive, non-motor and mood deficits. • Structural MRI may be useful for predicting disease progression in PD., 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.

This study assessed brain structural alterations in two diverse clinical forms of functional (psychogenic) dystonia (FD) – the typical fixed dystonia (FixFD) phenotype and the “mobile” dystonia (MobFD) phenotype, which has been recently described in one study. Forty-four FD patients (13 FixFD and 31 MobFD) and 43 healthy controls were recruited. All subjects underwent 3D T1-weighted and diffusion tensor (DT) magnetic resonance imaging (MRI). Cortical thickness, volumes of gray matter (GM) structures, and white matter (WM) tract integrity were assessed. Normal cortical thickness in both FD patient groups compared with age-matched healthy controls were found. When compared with FixFD, MobFD patients showed cortical thinning of the left orbitofrontal cortex, and medial and lateral parietal and cingulate regions bilaterally. Additionally, compared with controls, MobFD patients showed reduced volumes of the left nucleus accumbens, putamen, thalamus, and bilateral caudate nuclei, whereas MobFD patients compared with FixFD demonstrated atrophy of the right hippocampus and globus pallidus. Compared with both controls and MobFD cases, FixFD patients showed a severe disruption of WM architecture along the corpus callous, corticospinal tract, anterior thalamic radiations, and major long-range tracts bilaterally. This study showed different MRI patterns in two variants of FD. MobFD had alterations in GM structures crucial for sensorimotor processing, emotional, and cognitive control. On the other hand, FixFD patients were characterized by a global WM disconnection affecting main sensorimotor and emotional control circuits. These findings may have important implications in understanding the neural substrates underlying different phenotypic FD expression levels.

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.

Background Action observation activates brain motor networks and, if followed by action imitation, it facilitates motor learning and functional recovery in patients with both neurological and musculoskeletal disorders. To date, few studies suggested that action observation plus imitation can improve balance skills; however, it is still unclear whether the simple repetitive observation of challenging balance tasks is enough to modify postural control. Thus, the primary aim of this study was to investigate whether repetitive action observation of balance exercises without imitation has the potential to improve balance performance; the secondary aim was to estimate the different training effects of action observation, action observation plus imitation and balance training relative to a control condition in healthy subjects. Methods Seventy-nine healthy young adults were randomly assigned to 4 groups: action observation, action observation plus imitation, balance training and control. The first three groups were trained for about 30 minutes every day for three weeks, whereas the control group received no training. Center of pressure path length and sway area were evaluated on a force platform at baseline and after training using posturographic tests with eyes open and closed. Results As expected, both action observation plus imitation and balance training groups compared to the control group showed balance improvements, with a medium to large effect size performing balance tasks with eyes open. Action observation without imitation group showed a balance improvement with eyes open, but without a significant difference relative to the control group. Conclusions Both action observation plus imitation and balance training have similar effects in improving postural control in healthy young subjects. Future studies on patients with postural instability are necessary to clarify whether AOT can induce longer lasting effects. Action observation alone showed a trend toward improving postural control in healthy subjects, suggesting the possibility to study its effects in temporarily immobilized diseased subjects.

Gait disorders represent a therapeutic challenge in Parkinson’s disease (PD). This study investigated the efficacy of 4-week action observation training (AOT) on disease severity, freezing of gait and motor abilities in PD, and evaluated treatment-related brain functional changes. 25 PD patients with freezing of gait were randomized into two groups: AOT (action observation combined with practicing the observed actions) and “Landscape” (same physical training combined with landscape-videos observation). At baseline and 4-week, patients underwent clinical evaluation and fMRI. Clinical assessment was repeated at 8-week. At 4-week, both groups showed reduced freezing of gait severity, improved walking speed and quality of life. Moreover, AOT was associated with reduced motor disability and improved balance. AOT group showed a sustained positive effect on motor disability, walking speed, balance and quality of life at 8-week, with a trend toward a persisting reduced freezing of gait severity. At 4-week vs. baseline, AOT group showed increased recruitment of fronto-parietal areas during fMRI tasks, while the Landscape group showed a reduced fMRI activity of the left postcentral and inferior parietal gyri and right rolandic operculum and supramarginal gyrus. In AOT group, functional brain changes were associated with clinical improvements at 4-week and predicted clinical evolution at 8-week. AOT has a more lasting effect in improving motor function, gait and quality of life in PD patients relative to physical therapy alone. AOT-related performance gains are associated with an increased recruitment of motor regions and fronto-parietal mirror neuron and attentional control areas.

The present chapter reports the current knowledge on the use of functional MRI (fMRI) in patients with atypical parkinsonisms, including Multiple System Atrophy, Corticobasal Syndrome and Progressive Supranuclear Palsy syndrome. Both resting state functional connectivity and task-based brain activity abnormalities are reported in atypical parkinsonisms relative to healthy controls and Parkinson's disease patients. Functional alterations were observed earlier than structural damage and may help to make early diagnosis. The chapter also examines the few longitudinal evidence on fMRI changes in patients with these conditions. The potential use of fMRI techniques in aiding the differential diagnosis, accurately measuring disease progression and assessing the effectiveness of therapeutic interventions is discussed.

BACKGROUND: Functional MRI (fMRI) has been widely used to study abnormal patterns of functional connectivity at rest in patients with movement disorders such as idiopathic Parkinson's disease (PD) and atypical parkinsonisms. METHODS: This manuscript provides an educational review of the current use of resting‐state fMRI in the field of parkinsonian syndromes. RESULTS: Resting‐state fMRI studies have improved the current knowledge about the mechanisms underlying motor and non‐motor symptom development and progression in movement disorders. Even if its inclusion in clinical practice is still far away, resting‐state fMRI has the potential to be a promising biomarker for early disease detection and prediction. It may also aid in differential diagnosis and monitoring brain responses to therapeutic agents and neurorehabilitation strategies in different movement disorders. CONCLUSIONS: There is urgent need to identify and validate prodromal biomarkers in PD patients, to perform further studies assessing both overlapping and disease‐specific fMRI abnormalities among parkinsonian syndromes, and to continue technical advances to fully realize the potential of fMRI as a tool to monitor the efficacy of chronic therapies.