Spatiotemporal Gait Differences before and after Botulinum Toxin in People with Focal Dystonia: A Pilot Study.

BACKGROUND: The impact of focal dystonia on gait has attracted little attention and remains elusive. Considering the importance of both visual and head control in gait, blepharospasm and cervical dystonia should affect gait. Improvement of cervical/eyelid control following botulinum toxin (BTX) injections would translate into gait changes. OBJECTIVES: To assess gait differences in people with focal dystonia before and after BTX treatment. METHODS: Ten patients with blepharospasm, 10 patients with cervical dystonia, and 20 healthy age- and gender-matched controls were included. Gait was assessed before and 1-month after BTX injections using Biodex Gait Trainer™ 3. Gait velocity, cadence, step length, step asymmetry, and variability of step length were compared between patients and controls, and between the two time-points using non-parametric statistics. RESULTS: At baseline, compared to controls, cervical dystonia patients showed reduced gait velocity, step length, and cadence. After BTX injections, while gait velocity and step length were significantly increased and step length variability reduced, gait parameters still differed between patients and controls. In blepharospasm patients, baseline gait velocity and step length were significantly smaller than in controls. After BTX injections, these gait parameters were significantly increased and variability decreased, so that patients no longer differed from controls. CONCLUSION: Gait differences exist between patients with focal dystonia not directly affecting the lower limbs and healthy controls. These gait abnormalities were improved differently by BTX treatment according to the type of dystonia. These disparities suggest different pathophysiological mechanisms and support the need for changes in rehabilitation routines in cervical dystonia.

Fluctuations in Parkinson's disease and personalized medicine: bridging the gap with the neuropsychiatric fluctuation scale.

Background: Neuropsychiatric fluctuations (NpsyF) are frequent and disabling in people with Parkinson's disease (PD). In OFF-medication, NpsyF entail minus neuropsychiatric symptoms (NPS) like anxiety, apathy, sadness, and fatigue. In ON-medication, NpsyF consist in plus NPS, such as high mood, hypomania, and hyperactivity. Accurate identification of these NpsyF is essential to optimize the overall PD management. Due to lack of punctual scales, the neuropsychiatric fluctuation scale (NFS) has been recently designed to assess NpsyF in real time. The NFS comprises 20 items with two subscores for plus and minus NPS, and a total score. Objective: To evaluate the psychometric properties of the NFS in PD. Methods: PD patients with motor fluctuations and healthy controls (HC) were assessed. In PD patients, the NFS was administrated in both the ON-and OFF-medication conditions, together with the movement disorders society-unified Parkinson disease rating scale parts I-IV. Depression (Beck depression scale II), apathy (Starkstein apathy scale) and non-motor fluctuations items of the Ardouin scale of behaviour in PD (ASBPD OFF and ON items) were also assessed. NFS internal structure was evaluated with principal component analysis consistency (PCA) in both medication conditions in PD patients and before emotional induction in HC. NFS internal consistency was assessed using Cronbach's alpha coefficient. NFS convergent and divergent validity was measured through correlations with BDI-II, Starktein, and ASBPD OFF and ON non motor items. Specificity was assessed comparing NFS global score between the HC and PD populations. Sensitivity was evaluated with t-student test comparing the ON-and the OFF-medication conditions for NFS global score and for minus and plus subscores. Results: In total, 101 consecutive PD patients and 181 HC were included. In PD patients and HC, PCA highlighted one component that explained 32-35 and 42% of the variance, respectively. Internal consistency was good for both the NFS-plus (alpha =0.88) and NFS-minus items (alpha =0.8). The NFS showed a good specifity for PD (p < 0.0001) and a good sensitivity to the medication condition (p < 0.0001). Conclusion: The satisfactory properties of the NFS support its use to assess acute neuropsychiatric fluctuations in PD patients, adding to available tools.

Long-term independence and quality of life after subthalamic stimulation in Parkinson disease.

BACKGROUND AND PURPOSE: Studies on long-term nonmotor outcomes of subthalamic nucleus stimulation in Parkinson disease (PD) are scarce. This study reports on very long-term non-motor and motor outcomes in one of the largest cohorts of people with advanced PD, treated for >10 years with subthalamic nucleus stimulation. The main outcome was to document the evolution of independence in activities of daily living. The secondary outcomes were to measure the change in quality of life, as well as non-motor and motor outcomes. METHODS: Patients were studied preoperatively, at 1 year, and beyond 10 years after subthalamic stimulation with an established protocol including motor, non-motor, and neuropsychological assessments. RESULTS: Eighty-five people with PD were included. Independence scores in the off-medication condition (measured with the Schwab & England Activities of Daily Living Scale) as well as quality of life (measured with the Parkinson's Disease Questionnaire [PDQ]-37) remained improved at longest follow-up compared to preoperatively (respectively, p < 0.001, p = 0.015). Cognitive scores, measured with the Mattis Dementia Rating Scale, significantly worsened compared to before and 1 year after surgery (p < 0.001), without significant change in depression, measured with the Beck Depression Inventory. Motor fluctuations, dyskinesias, and off dystonia remained improved at longest follow-up (p < 0.001), with a significant reduction in dopaminergic treatment (45%, p < 0.001). CONCLUSIONS: This study highlights the long-term improvement of subthalamic stimulation on independence and quality of life, despite the progression of disease and the occurrence of levodopa-resistant symptoms.

Contribution of Basal Ganglia to the Sense of Upright: A Double-Blind Within-Person Randomized Trial of Subthalamic Stimulation in Parkinson's Disease with Pisa Syndrome.

BACKGROUND: Verticality perception is frequently altered in Parkinson's disease (PD) with Pisa syndrome (PS). Is it the cause or the consequence of the PS? OBJECTIVE: We tested the hypothesis that both scenarios coexist. METHODS: We performed a double-blind within-person randomized trial (NCT02704910) in 18 individuals (median age 63.5 years) with PD evolving for a median of 17.5 years and PS for 2.5 years and treated with bilateral stimulation of the subthalamus nuclei (STN-DBS) for 6.5 years. We analyzed whether head and trunk orientations were congruent with the visual (VV) and postural (PV) vertical, and whether switching on one or both sides of the STN-DBS could modulate trunk orientation via verticality representation. RESULTS: The tilted verticality perception could explain the PS in 6/18 (33%) patients, overall in three right-handers (17%) who showed net and congruent leftward trunk and PV tilts. Two of the 18 (11%) had an outstanding clinical picture associating leftward: predominant parkinsonian symptoms, whole-body tilt (head -11°, trunk -8°) and transmodal tilt in verticality perception (PV -10°, VV -8.9°). Trunk orientation or VV were not modulated by STN-DBS, whereas PV tilts were attenuated by unilateral or bilateral stimulations if it was applied on the opposite STN. CONCLUSION: In most cases of PS, verticality perception is altered by the body deformity. In some cases, PS seems secondary to a biased internal model of verticality, and DBS on the side of the most denervated STN attenuated PV tilts with a quasi-immediate effect. This is an interesting track for further clinical studies.

Deep Brain Stimulation for Freezing of Gait in Parkinson's Disease With Early Motor Complications.

BACKGROUND: Effects of DBS on freezing of gait and other axial signs in PD patients are unclear. OBJECTIVE: Secondary analysis to assess whether DBS affects these symptoms within a large randomized controlled trial comparing DBS of the STN combined with best medical treatment and best medical treatment alone in patients with early motor complications (EARLYSTIM-trial). METHODS: One hundred twenty-four patients were randomized in the stimulation group and 127 patients in the best medical treatment group. Presence of freezing of gait was assessed in the worst condition based on item-14 of the UPDRS-II at baseline and follow-up. The posture, instability, and gait-difficulty subscore of the UPDRS-III, and a gait test including quantification of freezing of gait and number of steps, were performed in both medication-off and medication-on conditions. RESULTS: Fifty-two percent in both groups had freezing of gait at baseline based on UPDRS-II. This proportion decreased in the stimulation group to 34%, but did not change in the best medical treatment group at 24 months (P = 0.018). The steps needed to complete the gait test decreased in the stimulation group and was superior to the best medical treatment group (P = 0.016). The axial signs improved in the stimulation group compared to the best medical treatment group (P < 0.01) in both medication-off and medication-on conditions. CONCLUSIONS: Within the first 2 years of DBS, freezing of gait and other axial signs improved in the medication-off condition compared to best medical treatment in these patients. © 2019 International Parkinson and Movement Disorder Society.

Deep Brain Stimulation of the Pedunculopontine Nucleus Area in Parkinson Disease: MRI-Based Anatomoclinical Correlations and Optimal Target.

BACKGROUND: Experimental studies led to testing of deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) as a new therapy to treat freezing of gait (FOG) in Parkinson disease (PD). Despite promising initial results fueling a growing interest toward that approach, several clinical studies reported heterogeneity in patient responses. Variation in the position of electrode contacts within the rostral brainstem likely contributes to such heterogeneity. OBJECTIVE: To provide anatomoclinical correlations of the effect of DBS of the caudal mesencephalic reticular formation (cMRF) including the PPN to treat FOG by comparing the normalized positions of the active contacts among a series of 11 patients at 1- and 2-yr follow-up and to provide an optimal target through an open-label study. METHODS: We defined a brainstem normalized coordinate system in relation to the pontomesencephalic junction. Clinical evaluations were based on a composite score using objective motor measurements and questionnaires allowing classification of patients as "bad responders" (2 patients), "mild responders" (1 patient) and "good responders" (6 patients). Two patients, whose long-term evaluation could not be completed, were excluded from the analysis. RESULTS: Most effective DBS electrode contacts to treat FOG in PD patients were located in the posterior part of the cMRF (encompassing the posterior PPN and cuneiform nucleus) at the level of the pontomesencephalic junction. CONCLUSION: In the present exploratory study, we performed an anatomoclinical analysis using a new coordinate system adapted to the brainstem in 9 patients who underwent PPN area DBS. We propose an optimal DBS target that allows a safe and efficient electrode implantation in the cMRF.

Managing Gait, Balance, and Posture in Parkinson's Disease.

PURPOSE OF REVIEW: Postural instability and gait difficulties inexorably worsen with Parkinson's disease (PD) progression and become treatment resistant, with a severe impact on autonomy and quality of life. We review the main characteristics of balance instability, gait disabilities, and static postural alterations in advanced PD, and the available treatment strategies. RECENT FINDINGS: It remains very difficult to satisfactorily alleviate gait and postural disturbances in advanced PD. Medical and surgical interventions often fail to provide satisfactory or durable alleviation of these axial symptoms, that may actually call for differential treatments. Exercise and adapted physical activity programs can contribute to improving the patients' condition. Gait, balance, and postural disabilities are often lumped together under the Postural Instability and Gait Difficulties umbrella term. This may lead to sub-optimal patients' management as data suggest that postural, balance, and gait problems might depend on distinct underlying mechanisms. We advocate for a multidisciplinary approach from the day of diagnosis.

Pedunculopontine nucleus deep brain stimulation in Parkinson's disease: A clinical review.

Pedunculopontine nucleus region deep brain stimulation (DBS) is a promising but experimental therapy for axial motor deficits in Parkinson's disease (PD), particularly gait freezing and falls. Here, we summarise the clinical application and outcomes reported during the past 10 years. The published dataset is limited, comprising fewer than 100 cases. Furthermore, there is great variability in clinical methodology between and within surgical centers. The most common indication has been severe medication refractory gait freezing (often associated with postural instability). Some patients received lone pedunculopontine nucleus DBS (unilateral or bilateral) and some received costimulation of the subthalamic nucleus or internal pallidum. Both rostral and caudal pedunculopontine nucleus subregions have been targeted. However, the spread of stimulation and variance in targeting means that neighboring brain stem regions may be implicated in any response. Low stimulation frequencies are typically employed (20-80 Hertz). The fluctuating nature of gait freezing can confound programming and outcome assessments. Although firm conclusions cannot be drawn on therapeutic efficacy, the literature suggests that medication refractory gait freezing and falls can improve. The impact on postural instability is unclear. Most groups report a lack of benefit on gait or limb akinesia or dopaminergic medication requirements. The key question is whether pedunculopontine nucleus DBS can improve quality of life in PD. So far, the evidence supporting such an effect is minimal. Development of pedunculopontine nucleus DBS to become a reliable, established therapy would likely require a collaborative effort between experienced centres to clarify biomarkers predictive of response and the optimal clinical methodology. © 2017 International Parkinson and Movement Disorder Society.

The laser shoes: A new ambulatory device to alleviate freezing of gait in Parkinson disease.

OBJECTIVE: To assess, in a cross-sectional study, the feasibility and immediate efficacy of laser shoes, a new ambulatory visual cueing device with practical applicability for use in daily life, on freezing of gait (FOG) and gait measures in Parkinson disease (PD). METHODS: We tested 21 patients with PD and FOG, both "off" and "on" medication. In a controlled gait laboratory, we measured the number of FOG episodes and the percent time frozen occurring during a standardized walking protocol that included FOG provoking circumstances. Participants performed 10 trials with and 10 trials without cueing. FOG was assessed using offline video analysis by an independent rater. Gait measures were recorded in between FOG episodes with the use of accelerometry. RESULTS: Cueing using laser shoes was associated with a significant reduction in the number of FOG episodes, both "off" (45.9%) and "on" (37.7%) medication. Moreover, laser shoes significantly reduced the percent time frozen by 56.5% (95% confidence interval [CI] 32.5-85.8; p = 0.004) when "off" medication. The reduction while "on" medication was slightly smaller (51.4%, 95% CI -41.8 to 91.5; p = 0.075). These effects were paralleled by patients' positive subjective experience on laser shoes' efficacy. There were no clinically meaningful changes in the gait measures. CONCLUSIONS: These findings demonstrate the immediate efficacy of laser shoes in a controlled gait laboratory, and offer a promising intervention with potential to deliver in-home cueing for patients with FOG. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with PD, laser shoes significantly reduce FOG severity (both number and duration of FOG episodes).

The Practicalities of Assessing Freezing of Gait.

BACKGROUND: Freezing of gait (FOG) is a mysterious, complex and debilitating phenomenon in Parkinson's disease. Adequate assessment is a pre-requisite for managing FOG, as well as for assigning participants in FOG research. The episodic nature of FOG, as well as its multiple clinical expressions make its assessment challenging. OBJECTIVE: To highlight the available assessment tools and to provide practical, experience-based recommendations for reliable assessment of FOG. METHODS: We reviewed FOG assessment from history taking, questionnaires, lab and home-based measurements and examined how these methods account for presence and severity of FOG, their limits and advantages. The practicalities for their use in clinical and research practice are highlighted. RESULTS: According to the available assessment tools severity of FOG is marked by one or a combination of multiple clinical expressions including frequency, duration, triggering circumstances, response to levodopa, association with falls and fear of falling, or need for assistance to avoid falls. CONCLUSIONS: To date, a unique methodological tool that encompasses the entire complexity of FOG is lacking. Combining methods should give a better picture of FOG severity, in accordance with the precise clinical or research context. Further development of any future assessment tool requires understanding and thorough analysis of the specific clinical expressions of FOG.

Physiology of freezing of gait.

Freezing of gait (FOG) is a common and debilitating, but largely mysterious, symptom of Parkinson disease. In this review, we will discuss the cerebral substrate of FOG focusing on brain physiology and animal models. Walking is a combination of automatic movement processes, afferent information processing, and intentional adjustments. Thus, normal gait requires a delicate balance between various interacting neuronal systems. To further understand gait control and specifically FOG, we will discuss the basic physiology of gait, animal models of gait disturbance including FOG, alternative etiologies of FOG, and functional magnetic resonance studies investigating FOG. The outcomes of these studies point to a dynamic network of cortical areas such as the supplementary motor area, as well as subcortical areas such as the striatum and the mesencephalic locomotor region including the pedunculopontine nucleus (PPN). Additionally, we will review PPN (area) stimulation as a possible treatment for FOG, and ponder whether PPN stimulation truly is the right step forward. Ann Neurol 2016;80:644-659.

Polymorphism of the dopamine transporter type 1 gene modifies the treatment response in Parkinson's disease.

After more than 50 years of treating Parkinson's disease with l-DOPA, there are still no guidelines on setting the optimal dose for a given patient. The dopamine transporter type 1, now known as solute carrier family 6 (neurotransmitter transporter), member 3 (SLC6A3) is the most powerful determinant of dopamine neurotransmission and might therefore influence the treatment response. We recently demonstrated that methylphenidate (a dopamine transporter inhibitor) is effective in patients with Parkinson's disease with motor and gait disorders. The objective of the present study was to determine whether genetic variants of the dopamine transporter type 1-encoding gene (SLC6A3) are associated with differences in the response to treatment of motor symptoms and gait disorders with l-DOPA and methylphenidate (with respect to the demographic, the disease and the treatment parameters and the other genes involved in the dopaminergic neurotransmission). This analysis was part of a multicentre, parallel-group, double-blind, placebo-controlled, randomized clinical trial of methylphenidate in Parkinson's disease (Protocol ID:2008-005801-20; ClinicalTrials.gov:NCT00914095). We scored the motor Unified Parkinson's Disease Rating Scale and the Stand-Walk-Sit Test before and after a standardized acute l-DOPA challenge before randomization and then after 3 months of methylphenidate treatment. Patients were screened for variants of genes involved in dopamine metabolism: rs28363170 and rs3836790 polymorphisms in the SLC6A3 gene, rs921451 and rs3837091 in the DDC gene (encoding the aromatic L-amino acid decarboxylase involved in the synthesis of dopamine from l-DOPA), rs1799836 in the MAOB gene (coding for monoamine oxidase B) and rs4680 in the COMT gene (coding for catechol-O-methyltransferase). Investigators and patients were blinded to the genotyping data throughout the study. Eighty-one subjects were genotyped and 61 were analysed for their acute motor response to l-DOPA. The SLC6A3 variants were significantly associated with greater efficacy of l-DOPA for motor symptoms. The SLC6A3 variants were also associated with greater efficacy of methylphenidate for motor symptoms and gait disorders in the ON l-DOPA condition. The difference between motor Unified Parkinson's Disease Rating Scale scores for patients with different SLC6A3 genotypes was statistically significant in a multivariate analysis that took account of other disease-related, treatment-related and pharmacogenetic parameters. Our preliminary results suggest that variants of SLC6A3 are genetic modifiers of the treatment response to l-DOPA and methylphenidate in Parkinson's disease. Further studies are required to assess the possible value of these genotypes for (i) guiding l-DOPA dose adaptations over the long term; and (ii) establishing the risk/benefit balance associated with methylphenidate treatment for gait disorders.

Neural substrates of levodopa-responsive gait disorders and freezing in advanced Parkinson's disease: a kinesthetic imagery approach.

Gait disturbances, including freezing of gait, are frequent and disabling symptoms of Parkinson's disease. They often respond poorly to dopaminergic treatments. Although recent studies have shed some light on their neural correlates, their modulation by dopaminergic treatment remains quite unknown. Specifically, the influence of levodopa on the networks involved in motor imagery (MI) of parkinsonian gait has not been directly studied, comparing the off and on medication states in the same patients. We therefore conducted an [H2 (15) 0] Positron emission tomography study in eight advanced parkinsonian patients (mean disease duration: 12.3 ± 3.8 years) presenting with levodopa-responsive gait disorders and FoG, and eight age-matched healthy subjects. All participants performed three tasks (MI of gait, visual imagery and a control task). Patients were tested off, after an overnight withdrawal of all antiparkinsonian treatment, and on medication, during consecutive mornings. The order of conditions was counterbalanced between subjects and sessions. Results showed that imagined gait elicited activations within motor and frontal associative areas, thalamus, basal ganglia and cerebellum in controls. Off medication, patients mainly activated premotor-parietal and pontomesencephalic regions. Levodopa increased activation in motor regions, putamen, thalamus, and cerebellum, and reduced premotor-parietal and brainstem involvement. Areas activated when patients are off medication may represent compensatory mechanisms. The recruitment of these accessory circuits has also been reported for upper-limb movements in Parkinson's disease, suggesting a partly overlapping pathophysiology between imagined levodopa-responsive gait disorders and appendicular signs. Our results also highlight a possible cerebellar contribution in the pathophysiology of parkinsonian gait disorders through kinesthetic imagery.

Iowa gambling task impairment in Parkinson's disease can be normalised by reduction of dopaminergic medication after subthalamic stimulation.

BACKGROUND: Impulse control disorders (ICD), including pathological gambling, are common in Parkinson's disease (PD) and tend to improve after subthalamic (STN) stimulation after a marked reduction of dopaminergic medication. In order to investigate the effect of STN stimulation on impulsive decision making, we used the Iowa Gambling task (IGT). METHODS: We investigated IGT performance in 20 patients with PD before STN surgery with and without dopaminergic treatment and in 24 age-matched controls. All patients underwent an extensive neuropsychological interview screening for behavioural disorders. Assessment in patients was repeated 3 months after surgery without dopaminergic treatment with and without stimulation. RESULTS: Chronic antiparkinsonian treatment was drastically reduced after surgery (-74%). At baseline, on high chronic dopaminergic treatment 8/20 patients with PD presented with pathological hyperdopaminergic behaviours, which had resolved in 7/8 patients 3 months after surgery on low chronic dopaminergic treatment. Preoperative performance on the IGT was significantly impaired compared to after surgery. CONCLUSIONS: Dopaminergic medication likely contributes to the impairment in decision making underlying ICDs. Deep brain stimulation allows drastic reduction of dopaminergic medication and, thus, concomitant remediation of medication-induced impairment in decision making.

Stimulation of the pedunculopontine nucleus area in Parkinson's disease: effects on speech and intelligibility.

Improvement of gait disorders following pedunculopontine nucleus area stimulation in patients with Parkinson's disease has previously been reported and led us to propose this surgical treatment to patients who progressively developed severe gait disorders and freezing despite optimal dopaminergic drug treatment and subthalamic nucleus stimulation. The outcome of our prospective study on the first six patients was somewhat mitigated, as freezing of gait and falls related to freezing were improved by low frequency electrical stimulation of the pedunculopontine nucleus area in some, but not all, patients. Here, we report the speech data prospectively collected in these patients with Parkinson's disease. Indeed, because subthalamic nucleus surgery may lead to speech impairment and a worsening of dysarthria in some patients with Parkinson's disease, we felt it was important to precisely examine any possible modulations of speech for a novel target for deep brain stimulation. Our results suggested a trend towards speech degradation related to the pedunculopontine nucleus area surgery (off stimulation) for aero-phonatory control (maximum phonation time), phono-articulatory coordination (oral diadochokinesis) and speech intelligibility. Possibly, the observed speech degradation may also be linked to the clinical characteristics of the group of patients. The influence of pedunculopontine nucleus area stimulation per se was more complex, depending on the nature of the task: it had a deleterious effect on maximum phonation time and oral diadochokinesis, and mixed effects on speech intelligibility. Whereas levodopa intake and subthalamic nucleus stimulation alone had no and positive effects on speech dimensions, respectively, a negative interaction between the two treatments was observed both before and after pedunculopontine nucleus area surgery. This combination effect did not seem to be modulated by pedunculopontine nucleus area stimulation. Although limited in our group of patients, speech impairment following pedunculopontine nucleus area stimulation is a possible outcome that should be considered before undertaking such surgery. Deleterious effects could be dependent on electrode insertion in this brainstem structure, more than on current spread to nearby structures involved in speech control. The effect of deep brain stimulation on speech in patients with Parkinson's disease remains a challenging and exploratory research area.

The pathogenesis of Pisa syndrome in Parkinson's disease.

Postural abnormalities such as postural deviations affect nearly all patients with advanced Parkinson's disease and represent an important source of disability. Although their existence has long been known, their management remains a challenge as they respond poorly to medication, brain surgery, or physiotherapy. Improving management strategies will require better understanding of the mechanisms underlying such postural deformities. In this review on the pathophysiology of Pisa syndrome, we examine the data supporting the central and peripheral hypotheses that attempt to explain these lateral trunk deviations. Although the pathophysiology is very probably multifactorial, the bulk of the data supports central, rather than peripheral, hypotheses. The central hypotheses that are best supported by both animal studies and clinical data include asymmetry of basal ganglia output and abnormalities in the central integration of sensory information. Further studies are needed to elucidate the pathophysiology underlying Pisa syndrome.

Using motor imagery to study the neural substrates of dynamic balance.

This study examines the cerebral structures involved in dynamic balance using a motor imagery (MI) protocol. We recorded cerebral activity with functional magnetic resonance imaging while subjects imagined swaying on a balance board along the sagittal plane to point a laser at target pairs of different sizes (small, large). We used a matched visual imagery (VI) control task and recorded imagery durations during scanning. MI and VI durations were differentially influenced by the sway accuracy requirement, indicating that MI of balance is sensitive to the increased motor control necessary to point at a smaller target. Compared to VI, MI of dynamic balance recruited additional cortical and subcortical portions of the motor system, including frontal cortex, basal ganglia, cerebellum and mesencephalic locomotor region, the latter showing increased effective connectivity with the supplementary motor area. The regions involved in MI of dynamic balance were spatially distinct but contiguous to those involved in MI of gait (Bakker et al., 2008; Snijders et al., 2011; Crémers et al., 2012), in a pattern consistent with existing somatotopic maps of the trunk (for balance) and legs (for gait). These findings validate a novel, quantitative approach for studying the neural control of balance in humans. This approach extends previous reports on MI of static stance (Jahn et al., 2004, 2008), and opens the way for studying gait and balance impairments in patients with neurodegenerative disorders.