Giovanna Lagravinese

Attentional control of gait and falls: is cholinergic dysfunction a common substrate in the elderly and Parkinson's disease?

The aim of this study was to address whether deficits in the central cholinergic activity may contribute to the increased difficulty to allocate attention during gait in the elderly with heightened risk of falls. We recruited 50 participants with a history of two or more falls (33 patients with Parkinson’s Disease and 17 older adults) and 14 non-fallers age-matched adults. Cholinergic activity was estimated by means of short latency afferent inhibition (SAI), a transcranial magnetic stimulation (TMS) technique that assesses an inhibitory circuit in the sensorimotor cortex and is regarded as a global marker of cholinergic function in the brain. Increased difficulty to allocate attention during gait was evaluated by measuring gait performance under single and dual-task conditions. Global cognition was also assessed. Results showed that SAI was reduced in patients with PD than in the older adults (fallers and non-fallers) and in older adults fallers with respect to non-fallers. Reduction in SAI indicates less inhibition i.e., less cholinergic activity. Gait speed was reduced in the dual task gait compared to normal gait only in our faller population and changes in gait speed under dual task significantly correlated with the mean value of SAI. This association remained significant after adjusting for cognitive status. These findings suggest that central cholinergic activity may be a predictor of change in gait characteristics under dual tasking in older adults and PD fallers independently of cognitive status.

The cerebellum predicts the temporal consequences of observed motor acts.

It is increasingly clear that we extract patterns of temporal regularity between events to optimize information processing. The ability to extract temporal patterns and regularity of events is referred as temporal expectation. Temporal expectation activates the same cerebral network usually engaged in action selection, comprising cerebellum. However, it is unclear whether the cerebellum is directly involved in temporal expectation, when timing information is processed to make predictions on the outcome of a motor act. Healthy volunteers received one session of either active (inhibitory, 1Hz) or sham repetitive transcranial magnetic stimulation covering the right lateral cerebellum prior the execution of a temporal expectation task. Subjects were asked to predict the end of a visually perceived human body motion (right hand handwriting) and of an inanimate object motion (a moving circle reaching a target). Videos representing movements were shown in full; the actual tasks consisted of watching the same videos, but interrupted after a variable interval from its onset by a dark interval of variable duration. During the ‘dark’ interval, subjects were asked to indicate when the movement represented in the video reached its end by clicking on the spacebar of the keyboard. Performance on the timing task was analyzed measuring the absolute value of timing error, the coefficient of variability and the percentage of anticipation responses. The active group exhibited greater absolute timing error compared with the sham group only in the human body motion task. Our findings suggest that the cerebellum is engaged in cognitive and perceptual domains that are strictly connected to motor control.

Temporal processing of perceived body movement in cervical dystonia.

Patients with idiopathic dystonia exhibit changes in the cognitive processing of movement. We showed that patients with writer’s cramp are less accurate than normal subjects in temporally predicting perceived handwriting. Whether this is selectively linked to the body area affected by dystonia or is a generalized cognitive feature of dystonia remains unclear. We addressed this issue by applying the same experimental paradigm to patients with focal cervical dystonia (CD). Fifteen patients with focal CD, aged 56.2 6 13.9 y and treatment-free for at least 6 mo, and 15 age-matched healthy subjects were recruited in the Department of Neuroscience, University of Genoa. Patients’ disease duration was 9 6 6.5 y, and mean 6 standard deviation score on the Toronto Western Spasmodic Torticollis Rating Scale was 14.3 6 4.8. The experimental paradigm, previously published in Avanzino et al., consisted of the perception on a screen of two videos, one showing a right hand writing a sentence (target task), and another showing a ball reaching a target (control task). After a variable interval from its onset (6, 9, and 12 seconds), videos were darkened. Subjects were asked to indicate when the perceived movement reached its end by clicking on the keyboard space-bar (Supplemental Data). The timing error (Reproduced Interval – Dark Interval), the normalized absolute timing error ([Timing Error/Dark Interval] 3 100), and the coefficient of variability (standard deviation/mean of Reproduced Intervals) were measured and analyzed with a repeated-measures analysis of variance with the factors GROUP, TASK, and DARK INTERVAL. Repeated-measures analysis of variance showed a significant GROUP*TASK interaction only for the normalized absolute timing error (F[1,28] 5 5.85; P 5 0.022; Fig. 1). On post hoc, this parameter was greater at all dark intervals only in CD patients (P 5 0.006) and exclusively for the target task (P 5 0.024). In both groups of subjects, consistently with what was observed in our previous work, the ability to temporally predict the end of the perceived movement was influenced by the duration of the target interval and the type of motion. Shorter dark intervals were associated with a tendency to overestimate the duration of movement (F[2,56] 5 136.61; P< 0.001), greater variability (F[2,56] 5 50.60, P< 0.001), and greater absolute timing error (F[2,56] 5 26.06; P< 0.001). Finally, a tendency to overestimate the duration of movement was observed for the target task compared with the control task (F[1,28] 5 6.38, P 5 0.017). Absolute timing error did not correlate with disease severity (Spearman’s rho 5 –0.161; P 5 0.58) or duration (Spearman’s rho 5 0.040; P 5 0.89). Our findings suggest that the abnormal timing of visually perceived human body motion is not exclusive to movements topographically related to dystonia. Brain regions relevant to the pathophysiology of dystonia, for example, sensorimotor regions of premotor and parietal cortices and cerebellum, modulate the spatiotemporal prediction of dynamic visual stimuli, and could be involved in the detected abnormality. Despite the relatively small sample size, the lack of correlation between timing performance and severity/duration of CD suggests that the observed abnormality may not be a direct expression of the dystonia. The selectivity of the timing abnormality might depend in part on the difference in complexity between handwriting and the inanimate object motion. However, if motion complexity is the main determinant of implicit timing performance, timing error should decrease at the increase of task complexity also in control subjects, but this was not observed. This notwithstanding, future studies should explore temporal processing of motion in dystonia, using

Time Processing and Motor Control in Movement Disorders

The subjective representation of “time” is critical for cognitive tasks but also for several motor activities. The neural network supporting motor timing comprises: lateral cerebellum, basal ganglia, sensorimotor and prefrontal cortical areas. Basal ganglia and associated cortical areas act as a hypothetical “internal clock” that beats the rhythm when the movement is internally generated. When timing information is processed to make predictions on the outcome of a subjective or externally perceived motor act, cerebellar processing and outflow pathways appear to be primarily involved. Clinical and experimental evidence on time processing and motor control points to a dysfunction of the neural networks involving basal ganglia and cerebellum in movement disorders. In some cases, temporal processing deficits could directly contribute to core motor features of the movement disorder, as in the case of bradykinesia in Parkinsons disease. For other movement disorders, the relationship between abnormal time processing and motor performance is less obvious and requires further investigation, as in the reduced accuracy in predicting the temporal outcome of a motor act in dystonia. We aim to review the literature on time processing and motor control in Parkinsons disease, dystonia, Huntingtons disease, and Tourette syndrome, integrating the available findings with current pathophysiological models; we will highlight the areas in which future explorations are warranted, as well as the aspects of time processing in motor control that present translational aspects in future rehabilitation strategies. The subjective representation of “time” is critical for cognitive tasks but also for motor activities. Recently, greater attention has been devoted to improve our understanding of how temporal information becomes integrated within the mechanisms of motor control. Experimental evidence recognizes time processing in motor control as a complex neural function supported by diffuse cerebral networks including cortical areas, cerebellum, and other subcortical structures (Ivry and Spencer, 2004; Coull and Nobre, 2008). Timing is an essential component of motor control primarily within two types of motor tasks: (i) when producing sequential rhythmic movements or sustained movements of a definite duration (explicit timing); (ii) when the temporal information is used implicitly, such as when coordinating our movements to those of moving objects or individuals within the external environment (implicit timing). In this review, we will provide a brief description of the neural network supporting motor timing focusing only on instrumental information to explain the link between timing and motor control in movement disorders. Then we will review available data on motor timing in Parkinsons disease, dystonia, Huntingtons disease, and Tourette syndrome, and discuss how this body of evidence integrates with the available information on the pathophysiology of these movement disorders. Finally, we will discuss the translational aspects of the explored neural mechanisms with respect to future rehabilitation strategies.

Spontaneous movement tempo can be influenced by combining action observation and somatosensory stimulation

Spontaneous movement tempo (SMT) was a popular field of study of the Gestalt psychologists It can be determined from subjects freely tapping out a rhythm with their finger, and it has been found to average about 2 Hz. A previous study showed that SMT changed after the observation of rhythmical movements performed at frequency different from the SMT. This effect was long-lasting only when movement execution immediately followed action observation (AO). We recently demonstrated that only when AO was combined with peripheral nerve stimulation (AO-PNS) was it possible to induce plastic changes in the excitability of the motor cortex, whereas AO and PNS alone did not evoke any changes. Here we investigated whether the observation of rhythmical actions at a frequency higher than the SMT combined with PNS induced lasting changes in SMT even in absence of immediate movement execution. Forty-eight participants were assigned to four groups. In AO-PNS group they observed a video showing a right hand performing a finger opposition movement sequence at 3 Hz and contemporarily received an electrical stimulation at the median nerve; in AO group and PNS group participants either observed the same video or received the same electrical stimulation of the AO-PNS group, respectively; in LANDSCAPE group subjects observed a neutral video. Participants performed a finger opposition movement sequence at spontaneous movement rate before and 30 min after the conditioning protocols. Results showed that SMT significantly changed only after AO-PNS. This result suggested that the AO-PNS protocol was able to induce lasting changes in SMT due to neuroplasticity mechanisms, indicating possible application of AO-PNS in rehabilitative treatments.

Action observation: mirroring across our spontaneous movement tempo

During action observation (AO), the activity of the “mirror system” is influenced by the viewer’s expertise in the observed action. A question that remains open is whether the temporal aspects of the subjective motor repertoire can influence the “mirror system” activation.

Learning by observing: the effect of multiple sessions of action-observation training on the spontaneous movement tempo and motor resonance

ABSTRACT The present study was designed to explore the changes in motor performance and motor resonance after multiple sessions of action observation (AO) training. Subjects were exposed to the observation of a video showing finger tapping movements executed at 3 Hz, a frequency higher than the spontaneous one (2 Hz) for four consecutive days. Motor performance and motor resonance were tested before the AO training on the first day, and on the last day. Results showed that multiple sessions of AO training induced a shift of the speed of execution of finger tapping movements toward the observed one and a change in motor resonance. Before the 3 Hz‐AO training cortical excitability was highest during the observation of the 2 Hz video. This motor resonance effect was lost after one single session of 3 Hz‐AO training whereas after multiple sessions of 3 Hz‐AO training cortical excitability was highest during the observation of the 3 Hz video. Our study shows for the first time that multiple sessions of AO training are able not only to induce performance gains but also to change the way by which the observers motor system recognizes a certain movement as belonging to the individual motor repertoire. These results may encourage the development of novel rehabilitative protocols based on multiple sessions of action observation aimed to regain a correct movement when its spontaneous speed is modified by pathologies or to modify the innate temporal properties of certain movements. HIGHLIGHTSM1 excitability resonated with the spontaneous tempo (SMT) of the observed movement.Multiple sessions of action observation (AO‐training) induced SMT changes.After AO‐training M1 excitability resonated with the tempo of the trained motor act.This work adds new evidence on the neurophysiological basis of AO‐training.

Adaptation of feedforward movement control is abnormal in patients with cervical dystonia and tremor

OBJECTIVE It is under debate whether the cerebellum plays a role in dystonia pathophysiology and in the expression of clinical phenotypes. We investigated a typical cerebellar function (anticipatory movement control) in patients with cervical dystonia (CD) with and without tremor. METHODS Twenty patients with CD, with and without tremor, and 17 healthy controls were required to catch balls of different load: 15 trials with a light ball, 25 trials with a heavy ball (adaptation) and 15 trials with a light ball (post-adaptation). Arm movements were recorded using a motion capture system. We evaluated: (i) the anticipatory adjustment (just before the impact); (ii) the extent and rate of the adaptation (at the impact) and (iii) the aftereffect in the post-adaptation phase. RESULTS The anticipatory adjustment was reduced during adaptation in CD patients with tremor respect to CD patients without tremor and controls. The extent and rate of adaptation and the aftereffect in the post-adaptation phase were smaller in CD with tremor than in controls and CD without tremor. CONCLUSION Patients with cervical dystonia and tremor display an abnormal predictive movement control. SIGNIFICANCE Our findings point to a possible role of cerebellum in the expression of a clinical phenotype in dystonia.

An Emotion-Enriched Context Influences the Effect of Action Observation on Cortical Excitability

Observing other people in action activates the “mirror neuron system” that serves for action comprehension and prediction. Recent evidence suggests that this function requires a high level codification triggered not only by components of motor behavior, but also by the environment where the action is embedded. An overlooked component of action perceiving is the one related to the emotional information provided by the context where the observed action takes place. Indeed, whether valence and arousal associated to an emotion might exert an influence on motor system activation during action observation has not been assessed so far. Here, cortico-spinal excitability of the left motor cortex was recorded in three groups of subjects. In the first condition, motor-evoked potential (MEPs) were recorded from a muscle involved in the grasping movement (i.e., abductor pollicis brevis, APB) while participants were watching the same reach-to-grasp movement embedded in contexts with negative emotional valence, but different levels of arousal: sadness (low arousal), and disgust (high arousal) (“Context plus Movement-APB” condition). In the second condition, MEPs were recorded from APB muscle while participants were observing static images representing the contexts in which the movement observed by participants in “Context plus Movement-APB” condition took place (“Context Only-APB” condition). Finally, in the third condition, MEPS were recorded from a muscle not involved in the grasping action, i.e., abductor digiti minimi, ADM, while participants were watching the same videos shown during the “Context plus Movement-APB” condition (“Context plus Movement-ADM” condition). Results showed a greater increase of cortical excitability only during the observation of the hand moving in the context eliciting disgust, and these changes were specific for the muscle involved in the observed action. Our findings show that the emotional context in which a movement occurs modulates motor resonance and that the combination of negative valence/high arousal drives the greater response in the observer’s mirror neuron system in a strictly muscle specific fashion.

Relationships between gait and emotion in Parkinson’s disease: A narrative review

BACKGROUND Disturbance of gait is a key feature of Parkinsons disease (PD) and has a negative impact on quality of life. Deficits in cognition and sensorimotor processing impair the ability of people with PD to walk quickly, efficiently and safely. Recent evidence suggests that emotional disturbances may also affect gait in PD. RESEARCH QUESTION We explored if there were relationships between walking ability, emotion and cognitive impairment in people with PD. METHODS The literature was firstly reviewed for unimpaired individuals. The recent experimental evidence for the influence of emotion on gait in people with PD was then explored. The contribution of affective disorders to continuous gait disorders was investigated, particularly for bradykinetic and hypokinetic gait. In addition, we investigated the influence of emotional processing on episodic gait disturbances, such as freezing of gait. Potential effects of pharmacological, surgical and physical therapy interventions were also considered. RESULTS Emerging evidence showed that emotional disturbances arising from affective disorders such as anxiety and depression, in addition to cognitive impairment, could contribute to gait disorders in some people with PD. An analysis of the literature indicated mixed evidence that improvements in affective disorders induced by physical therapy, pharmacological management or surgery improve locomotion in PD. SIGNIFICANCE When assessing and treating gait disorders in people with PD, it is important to take into the account non-motor symptoms such as anxiety, depression and cognitive impairment, in addition to the motor sequalae of this progressive neurological condition.BACKGROUND Disturbance of gait is a key feature of Parkinsons disease (PD) and has a negative impact on quality of life. Deficits in cognition and sensorimotor processing impair the ability of people with PD to walk quickly, efficiently and safely. Recent evidence suggests that emotional disturbances may also affect gait in PD. RESEARCH QUESTION We explored if there were relationships between walking ability, emotion and cognitive impairment in people with PD. METHODS The literature was firstly reviewed for unimpaired individuals. The recent experimental evidence for the influence of emotion on gait in people with PD was then explored. The contribution of affective disorders to continuous gait disorders was investigated, particularly for bradykinetic and hypokinetic gait. In addition, we investigated the influence of emotional processing on episodic gait disturbances, such as freezing of gait. Potential effects of pharmacological, surgical and physical therapy interventions were also considered. RESULTS Emerging evidence showed that emotional disturbances arising from affective disorders such as anxiety and depression, in addition to cognitive impairment, could contribute to gait disorders in some people with PD. An analysis of the literature indicated mixed evidence that improvements in affective disorders induced by physical therapy, pharmacological management or surgery improve locomotion in PD. SIGNIFICANCE When assessing and treating gait disorders in people with PD, it is important to take into the account non-motor symptoms such as anxiety, depression and cognitive impairment, in addition to the motor sequalae of this progressive neurological condition.