Giorgio Leodori

Somatosensory temporal discrimination threshold may help to differentiate patients with multiple system atrophy from patients with Parkinson's disease.

Somatosensory temporal discrimination threshold (STDT) is defined as the threshold at which two tactile stimuli applied to the skin are perceived as clearly distinct.

Primary somatosensory cortical plasticity and tactile temporal discrimination in focal hand dystonia

OBJECTIVE To investigate whether theta burst stimulation (TBS) applied over primary somatosensory cortex (S1) modulates somatosensory temporal discrimination threshold (STDT) and writing performances in patients with focal hand dystonia (FHD). METHODS Twelve patients with FHD underwent STDT testing and writing tasks before and after intermittent, continuous, or sham TBS (iTBS, cTBS, sham TBS) over S1 contralateral to the affected hand. Twelve healthy subjects underwent iTBS and cTBS over S1 and STDT values were tested on the right hand before and after TBS. RESULTS Baseline STDT values were higher in patients than in healthy subjects on both the affected and unaffected hand. In patients and healthy subjects iTBS decreased, whereas cTBS increased STDT values and did so to a similar extent in both groups. In patients, although STDT values decreased after iTBS, they did not normalize. S1 modulation did not improve the writing performance. CONCLUSIONS In patients, S1 responds normally to protocols inducing homotopic synaptic plasticity. The inhibitory interneuron activity responsible for STDT is altered. SIGNIFICANCE The pathophysiological mechanisms underlying abnormal temporal discrimination differ from those responsible for motor symptoms in FHD.

Cerebellar continuous theta-burst stimulation affects motor learning of voluntary arm movements in humans

In this study we investigated in healthy subjects whether continuous theta‐burst stimulation (cTBS) over the lateral cerebellum alters motor practice and retention phases during ipsilateral index finger and arm reaching movements. In 12 healthy subjects we delivered cTBS before repeated index finger abductions or arm reaching movements differing in complexity (reaching‐to‐grasp and reaching‐to‐point). We evaluated kinematic variables for index finger and arm reaching movements and changes in primary motor cortex (M1) activity tested with transcranial magnetic stimulation. Peak acceleration increased during motor practice for index finger abductions and reaching‐to‐grasp movements and persisted during motor retention. Peak acceleration decreased during motor practice for reaching‐to‐point movements and the decrease remained during motor retention. Cerebellar cTBS left the changes in peak acceleration during motor practice for index finger abductions and reaching‐to‐grasp arm movements unchanged but reduced peak acceleration at motor retention. Cerebellar cTBS prevented the decrease in peak acceleration for reaching‐to‐point movements during motor practice and at motor retention. Index finger abductions and arm reaching movements increased M1 excitability. Cerebellar cTBS decreased the motor evoked potential (MEP) facilitation induced by index finger movements, but increased the MEP facilitation after reaching‐to‐grasp and reaching‐to‐point movements. Cerebellar stimulation prevents motor retention for index finger abductions, reaching‐to‐grasp and reaching‐to‐point movements and degrades motor practice only for reaching‐to‐point movements. Cerebellar cTBS alters practice‐related changes in M1 excitability depending on how intensely the cerebellum contributes to the task. Changes in M1 excitability reflect mechanisms of homeostatic plasticity elicited by the interaction of an ‘exogenous’ (cTBS‐induced) and an ‘endogenous’ (motor practice‐induced) plasticity‐inducing protocol.

Effects of cerebellar theta-burst stimulation on arm and neck movement kinematics in patients with focal dystonia

OBJECTIVE To investigate the cerebellar inhibitory influence on the primary motor cortex in patients with focal dystonia using a cerebellar continuous theta-burst stimulation protocol (cTBS) and to evaluate any relationship with movement abnormalities. METHODS Thirteen patients with focal hand dystonia, 13 patients with cervical dystonia and 13 healthy subjects underwent two sessions: (i) cTBS over the cerebellar hemisphere (real cTBS) and (ii) cTBS over the neck muscles (sham cTBS). The effects of cerebellar cTBS were quantified as excitability changes in the contralateral primary motor cortex, as well as possible changes in arm and neck movements in patients. RESULTS Real cerebellar cTBS reduced the excitability in the contralateral primary motor cortex in healthy subjects and in patients with cervical dystonia, though not in patients with focal hand dystonia. There was no correlation between changes in primary motor cortex excitability and arm and neck movement kinematics in patients. There were no changes in clinical scores or in kinematic measures, after either real or sham cerebellar cTBS in patients. CONCLUSIONS The reduced cerebellar inhibitory modulation of primary motor cortex excitability in focal dystonia may be related to the body areas affected by dystonia as opposed to being a widespread pathophysiological abnormality. SIGNIFICANCE The present study yields information on the differential role played by the cerebellum in the pathophysiology of different focal dystonias.

Somatosensory temporal discrimination in essential tremor and isolated head and voice tremors

The aim of this study was to investigate the somatosensory temporal discrimination threshold in patients with essential tremor (sporadic and familial) and to evaluate whether somatosensory temporal discrimination threshold values differ depending on the body parts involved by tremor. We also investigated the somatosensory temporal discrimination in patients with isolated voice tremor. We enrolled 61 patients with tremor: 48 patients with essential tremor (31 patients with upper limb tremor alone, nine patients with head tremor alone, and eight patients with upper limb plus head tremor; 22 patients with familial vs. 26 sporadic essential tremor), 13 patients with isolated voice tremor, and 45 healthy subjects. Somatosensory temporal discrimination threshold values were normal in patients with familial essential tremor, whereas they were higher in patients with sporadic essential tremor. When we classified patients according to tremor distribution, somatosensory temporal discrimination threshold values were normal in patients with upper limb tremor and abnormal only in patients with isolated head tremor. Temporal discrimination threshold values were also abnormal in patients with isolated voice tremor. Somatosensory temporal discrimination processing is normal in patients with familial as well as in patients with sporadic essential tremor involving the upper limbs. By contrast, somatosensory temporal discrimination is altered in patients with isolated head tremor and voice tremor. This study with somatosensory temporal discrimination suggests that isolated head and voice tremors might possibly be considered as separate clinical entities from essential tremor.

Bradykinesia in early and advanced Parkinson's disease

BACKGROUND Motor impairment in Parkinsons disease (PD) includes slowness (bradykinesia), decreased amplitude (hypokinesia), impaired rhythm and a progressive reduction in speed and amplitude during movement repetition (sequence effect). In the present study we aimed to analyse bradykinesia features in newly-diagnosed and drug-näive patients with PD. Kinematic data were compared with PD patients in the advanced stages of the disease and with healthy controls. We also investigated the effect of selegiline on motor impairment in early PD. METHODS Fourteen newly-diagnosed and drug-näive PD patients in the early stage of the disease, 11 patients with advanced PD and 20 healthy controls performed a repetitive finger tapping task. Early PD patients were assessed in two separate sessions at baseline and four weeks after treatment with selegiline (10 mg taken daily). The repetitive finger movement was analysed using kinematic techniques. RESULTS The speed and amplitude of repetitive finger movement were lower in early PD patients than in healthy controls. Early PD patients also had a progressive decrement of movement amplitude (sequence effect). Patients with advanced PD had lower speed, amplitude and movement regularity during finger tapping in comparison to early PD and healthy controls but no sequence effect. In early PD, selegiline improved both the movement speed and amplitude though it did not influence the sequence effect. CONCLUSIONS The study yields an objective characterization of motor impairment in early and advanced PD. The kinematic assessment of the effects of selegiline on movement abnormalities in early PD provides a better understanding and interpretation of their pathophysiological mechanisms.

Somatosensory temporal discrimination threshold in Parkinson’s disease parallels disease severity and duration

OBJECTIVE To investigate whether the somatosensory temporal discrimination threshold (STDT) is already altered at the clinical onset of Parkinsons disease (PD) and whether STDT abnormalities correlate with disease progression we tested STDT values in patients with different severity of disease. METHODS We prospectively and consecutively enrolled 63 PD patients: 26 drug-naive PD patients with symptom onset no longer than two years prior to inclusion in the study (early-phase), 37 PD patients with varying degrees of disease severity and 51 age-matched healthy subjects. The STDT was tested on the index finger of both hands, and on both sides of the face. Twelve out of 26 early phase PD patients were re-tested two years after the initial diagnosis. RESULTS PD patients as a whole displayed higher STDT values than healthy subjects. STDT values did not significantly differ between early-phase PD patients and healthy subjects, whereas they were significantly higher in patients with mild/moderate and advanced PD. In early-phase PD patients STDT values at the two years-follow up assessment did not statistically differ from those obtained at baseline. Considering the whole group of PD patients STDT abnormalities significantly correlated with duration and severity of the disease. CONCLUSIONS STDT increases as disease progresses. In early-phase PD patients STDT values are still statistically similar to those of healthy subjects, thus implying that dopaminergic depletion alone may not be sufficient to cause STDT abnormalities. SIGNIFICANCE Our study gives new insight into the sensory abnormalities in PD.

The third-stimulus temporal discrimination threshold: focusing on the temporal processing of sensory input within primary somatosensory cortex

The somatosensory temporal discrimination threshold (STDT) has been used in recent years to investigate time processing of sensory information, but little is known about the physiological correlates of somatosensory temporal discrimination. The objective of this study was to investigate whether the time interval required to discriminate between two stimuli varies according to the number of stimuli in the task. We used the third-stimulus temporal discrimination threshold (ThirdDT), defined as the shortest time interval at which an individual distinguishes a third stimulus following a pair of stimuli delivered at the STDT. The STDT and ThirdDT were assessed in 31 healthy subjects. In a subgroup of 10 subjects, we evaluated the effects of the stimuli intensity on the ThirdDT. In a subgroup of 16 subjects, we evaluated the effects of S1 continuous theta-burst stimulation (S1-cTBS) on the STDT and ThirdDT. Results show that ThirdDT is shorter than STDT. We found a positive correlation between STDT and ThirdDT values. As long as the stimulus intensity was within the perceivable and painless range, it did not affect ThirdDT values. S1-cTBS significantly affected both STDT and ThirdDT, although the latter was affected to a greater extent and for a longer period of time. We conclude that the interval needed to discriminate between time-separated tactile stimuli is related to the number of stimuli used in the task. STDT and ThirdDT are encoded in S1, probably by a shared tactile temporal encoding mechanism whose performance rapidly changes during the perception process. ThirdDT is a new method to measure somatosensory temporal discrimination.NEW & NOTEWORTHY To investigate whether the time interval required to discriminate between stimuli varies according to changes in the stimulation pattern, we used the third-stimulus temporal discrimination threshold (ThirdDT). We found that the somatosensory temporal discrimination acuity varies according to the number of stimuli in the task. The ThirdDT is a new method to measure somatosensory temporal discrimination and a possible index of inhibitory activity at the S1 level.

Freezing of gait in Parkinson’s disease: gray and white matter abnormalities

Freezing of gait (FOG) is a disabling disorder that often affects Parkinson’s disease (PD) patients in advanced stages of the disease. To study structural gray matter (GM) and white matter (WM) changes in PD patients with and without FOG, twenty-one PD patients with FOG (PD-FOG), 16 PD patients without FOG (PD-nFOG) and 19 healthy subjects (HS) underwent a standardized MRI protocol. For the gray matter evaluation, cortical volume (CV), cortical thickness (CTh), and surface area (SA) were analyzed using the FreeSurfer pipeline. For the white matter evaluation, DTI images were analyzed using tracts constrained by underlying anatomy (TRACULA) toolbox in FreeSurfer. PD-FOG patients exhibited lower CTh than HS in the mesial surface of both cerebral hemispheres, including the superior frontal gyrus, paracentral lobule, posterior cingulate cortex, precuneus and pericalcarine cortex, and in the right dorsolateral prefrontal cortex. Moreover, significant WM changes were observed in PD-FOG patients in comparison with HS in the superior longitudinal fasciculus, uncinate fasciculus, cingulum cingulate gyrus and inferior longitudinal fasciculus (prevalently in the right hemisphere) and in the frontal radiations of the corpus callosum. DTI abnormalities in specific WM bundles correlated significantly with cognitive measures. The damage of multiple cortical areas involved in high-level gait control together with WM disruption between motor, cognitive and limbic structures may represent the anatomical correlate of FOG.

l-DOPA and Freezing of Gait in Parkinson’s Disease: Objective Assessment through a Wearable Wireless System

Freezing of gait (FOG) is a leading cause of falls and fractures in Parkinson’s disease (PD). The episodic and rather unpredictable occurrence of FOG, coupled with the variable response to l-DOPA of this gait disorder, makes the objective evaluation of FOG severity a major clinical challenge in the therapeutic management of patients with PD. The aim of this study was to examine and compare gait, clinically and objectively, in patients with PD, with and without FOG, by means of a new wearable system. We also assessed the effect of l-DOPA on FOG severity and specific spatiotemporal gait parameters in patients with and without FOG. To this purpose, we recruited 28 patients with FOG, 16 patients without FOG, and 16 healthy subjects. In all participants, gait was evaluated clinically by video recordings and objectively by means of the wearable wireless system, during a modified 3-m Timed Up and Go (TUG) test. All patients performed the modified TUG test under and not under dopaminergic therapy (ON and OFF therapy). By comparing instrumental data with the clinical identification of FOG based on offline video-recordings, we also assessed the performance of the wearable system to detect FOG automatically in terms of sensitivity, specificity, positive and negative predictive values, and finally accuracy. TUG duration was longer in patients than in controls, and the amount of gait abnormalities was prominent in patients with FOG compared with those without FOG. l-DOPA improved gait significantly in patients with PD and particularly in patients with FOG mainly by reducing FOG duration and increasing specific spatiotemporal gait parameters. Finally, the overall wireless system performance in automatic FOG detection was characterized by excellent sensitivity (93.41%), specificity (98.51%), positive predictive value (89.55%), negative predictive value (97.31%), and finally accuracy (98.51%). Our study overall provides new information on the beneficial effect of l-DOPA on FOG severity and specific spatiotemporal gait parameters as objectively measured by a wearable sensory system. The algorithm here reported potentially opens to objective long-time sensing of FOG episodes in patients with PD.