BACKGROUND: Falls are frequent in Parkinson's disease and ageing. Impairments in the cholinergic-mediated attentional supervision of gait may contribute to increased fall risk, especially when obstacles challenge gait. Interventions combining motor-cognitive approaches have been shown to improve motor performance, cognitive skills and falls number. Here, we hypothesized that an intervention simulating an attention-demanding walking condition could impact not only complex gait performance and fall risk but also short-latency afferent inhibition (SAI), as a marker of cholinergic activity. METHODS: Thirty-nine participants at falls risk (24 Parkinson's disease subjects and 15 older adults) were recruited in a randomized controlled trial. Participants were assigned to treadmill training or treadmill training with non-immersive virtual reality intervention and trained 3 times a week for 6 weeks. SAI, a transcranial magnetic stimulation paradigm, was used to assess cholinergic activity. Gait kinematics was measured during usual walking and while negotiating physical obstacles. Transcranial magnetic stimulation and gait assessments were performed pre, post, and 6 months post intervention. RESULTS: Treadmill training combined with non-immersive virtual reality induced an increase in inhibition of the SAI protocol on cortical excitability, improved obstacle negotiation performance and induced a reduction of the number of falls compared to treadmill training. Furthermore, the more SAI increased after training, the more the obstacle negotiation performance improved and fall rate decreased.

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.

To elucidate the role of ipsilateral motor cortex (M1) in the control of unilateral finger movements (UFMs) in humans we used a conditioning protocol of 1-Hz repetitive transcranial magnetic stimulation (1-Hz rTMS) over M1 in 11 right-handed healthy subjects. We analysed the effects of conditioning rTMS on UFMs of different complexity (simple vs sequential finger movements), and performed with a different modality (internally vs externally paced movements). UFMs were monitored with a sensor-engineered glove, and a quantitative evaluation of the following parameters was performed: touch duration (TD); inter-tapping interval (ITI); timing error (TE); and number of errors (NE). 1-Hz rTMS over ipsilateral M1 was able to affect the performance of a sequence of finger opposition movements in a metronome-paced condition, significantly increasing TD and reducing ITI without TE changes. The effects on motor behaviour had a different magnitude as a function of the sequence complexity. Further, we found a different effect of the ipsilateral 1-Hz rTMS on externally paced movements with respect to an internally paced condition. All these findings indicate that ipsilateral M1 plays an important role in the execution of sequential UFMs. Interestingly, NE did not change in any experimental condition, suggesting that ipsilateral M1 influences only the temporal and not the spatial accuracy of UFMs. Finally, the duration (up to 30 min) of 1-Hz rTMS effects on ipsilateral M1 can indicate its direct action on the mechanisms of cortical plasticity, suggesting that rTMS can be used to modulate the communication between the two hemispheres in rehabilitative protocols.

Mirror visual feedback (MVF) therapy has been demonstrated to be successful in neurorehabilitation, probably inducing neuroplasticity changes in the primary motor cortex (M1). However, it is not known whether MVF training influences the hemispheric balance between the M1s. This topic is of extreme relevance when MVF training is applied to stroke rehabilitation, as the competitive interaction between the two hemispheres induces abnormal interhemispheric inhibition (IHI) that weakens motor function in stroke patients. In the present study, we evaluated, in a group of healthy subjects, the effect of motor training and MVF training on the excitability of the two M1s and the IHI between M1s. The IHI from the 'active' M1 to the opposite M1 (where 'active' means the M1 contralateral to the moving hand in the motor training and the M1 of the seen hand in the MVF training) increased, after training, in both the experimental conditions. Only after motor training did we observe an increase in the excitability of the active M1. Our findings show that training based on MVF may influence the excitability of the transcallosal pathway and support its use in disorders where abnormal IHI is a potential target, such as stroke, where an imbalance between the affected and unaffected M1s has been documented.

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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.

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