Mirta Fiorio

The influence of hands posture on mental rotation of hands and feet

Behavioural and functional neuroanatomy studies demonstrate that mental rotation of body parts is carried out through a sort of inner motor simulation. Here we examined whether changes of hands posture influence the mental rotation of hands and feet. Twenty healthy subjects were asked to verbally judge the laterality of hands and feet pictures in two different postural conditions. In one condition, subjects kept hands on their knees in anatomical position; in the other, their hands were kept in an unusual posture with intertwined fingers, behind the back. Results show that mental rotation of hands but not of feet was influenced by changes in hands posture. Indeed, while mental rotation of hands was faster in the front than in the back hands position, no similar effect was found when mentally rotating feet. Thus, sensory-motor and postural information coming from the body may influence mental rotation of body parts according to specific, somatotopic rules.

Temporal processing of visuotactile and tactile stimuli in writer's cramp

Neurophysiological studies in animals show that basal ganglia are involved not only in motor and nonmotor timing functions but also in integrating tactile and visual signals delivered in the peripersonal space. We tested temporal discrimination of cross‐modal and unimodal stimuli in 13 controls and 14 patients with writers cramp, a disorder supposedly linked to dysfunction of basal ganglia. Subjects were asked to discriminate whether pairs of visual, tactile, or visuotactile stimuli were simultaneous or sequential (temporal discrimination threshold) and which stimulus preceded the other (temporal order judgment). Patients were impaired in temporal processing of tactile and cross‐modal stimuli. A significant positive correlation between temporal deficits and the severity of disability was detected for both affected and unaffected sides. Findings suggest that multimodal and not only modality‐specific temporal processing is defective in focal hand dystonia. Deficits of temporal processing of stimuli delivered to the unaffected side may represent a behavioral index of the susceptibility to develop dystonia and thus have remarkable practical and theoretical implications. Ann Neurol 2003

Somatosensory temporal discrimination in patients with primary focal dystonia

Purposes: To determine whether somatosensory temporal discrimination will reliably detect subclinical sensory impairment in patients with various forms of primary focal dystonia. Methods: The somatosensory temporal discrimination threshold (STDT) was tested in 82 outpatients affected by cranial, cervical, laryngeal and hand dystonia. Results were compared with those for 61 healthy subjects and 26 patients with hemifacial spasm, a non-dystonic disorder. STDT was tested by delivering paired stimuli starting with an interstimulus interval of 0 ms followed by a progressively increasing interstimulus interval. Results: STDT was abnormal in all the different forms of primary focal dystonias in all three body regions (eye, hand and neck), regardless of the distribution and severity of motor symptoms. Receiver operating characteristic curve analysis calculated in the three body regions yielded high diagnostic sensitivity and specificity for STDT abnormalities. Conclusions: These results provide definitive evidence that STDT abnormalities are a generalised feature of patients with primary focal dystonias and are a valid tool for screening subclinical sensory abnormalities.

Sensory functions in dystonia: Insights from behavioral studies†‡

The pathophysiology of primary dystonia is thought to involve dysfunction of the basal ganglia cortico‐striatal‐thalamo‐cortical motor circuits. In the past, emphasis was placed on the role of the basal ganglia in controlling movements; in more recent times, however, it has also become clear that they play an important part in sensory as well as cognitive functions. Here, we review evidence for dysfunction of sensory processing in patients with dystonia, and speculate that this may lead to abnormalities in a crucial role of the basal ganglia that links sensory information to appropriate motor output. Sensory function, particularly in the somatosensory domain, has been shown to be compromised in patients with primary dystonia, both in adult onset focal dystonia and in genetically characterized DYT1 dystonia. Given that nonaffected DYT1 gene carriers may show similar abnormalities to clinically affected individuals, sensory deficits could constitute a subclinical endophenotypic trait of disease that precedes overt clinical manifestations. Whether they can trigger primary dystonia or are an epiphenomenon is an issue warranting further study, but the fact that a number of different neurorehabilitative approaches explicitly manipulate somatosensory inputs to improve motor function suggests there may be a causal link between them. We believe that in future, randomized, blind and controlled studies in large patient populations should address this issue, providing efficient strategies to aid functional recovery, particularly in focal hand dystonia, where the available medical treatments offer little benefit.

Tactile temporal discrimination in patients with blepharospasm

Background: Blepharospasm is an adult-onset focal dystonia that causes involuntary blinking and eyelid spasms. Studies have shown the presence of sensory deficits associated with dystonia. Aim: To rule out any confounding effect of muscle spasms on sensory performance in affected and unaffected body regions of patients with blepharospasm and with hemifacial spasm. Methods: Participants (19 patients with blepharospasm, 19 patients with hemifacial spasm and 19 control subjects) were asked to discriminate between two stimuli that were either simultaneous or sequential (temporal discrimination threshold, TDT). Pairs of tactile stimuli were delivered with increasing or decreasing inter-stimulus intervals from 0 to 400 ms (in 10-ms steps) to the hands or on the skin over the orbicularis oculi muscle. Results: Tactile stimuli elicited similar TDTs in control subjects and patients with hemifacial spasm, but significantly higher TDTs in patients with blepharospasm, regardless of whether stimuli were applied to the orbicularis muscle or the hand. Conclusions: As TDT was abnormal in unaffected body regions of patients with blepharospasm, and patients with hemifacial spasm processed tactile stimuli normally, TDT deficits in blepharospasm depend on central rather than peripheral factors. This study further supports the link between focal dystonia and impaired temporal processing of somatosensory inputs.

Modulation of beta oscillations in the subthalamic area during action observation in Parkinson's disease.

Mapping observed actions into the onlookers motor system seems to provide the neurofunctional mechanisms for action understanding. Subthalamic nucleus (STN) local field potential (LFP) recordings in patients with movement disorders disclosed that network oscillations in the beta range are involved in conveying motor and non-motor information across the cortico-basal ganglia-thalamo-cortical loop. This evidence, together with the existence of connections between the STN and cortical areas active during observation of actions performed by other people, suggests that the STN oscillatory activity in specific frequency bands could encode not only motor information, but also information related to action observation. To test this hypothesis we directly recorded STN oscillations through electrodes for deep brain stimulation in patients with Parkinsons disease during observation of actions and of static objects. We found selective action-related oscillatory modulations in two functionally distinct beta bands: whereas low-beta oscillations (10-18 Hz) selectively desynchronized only during action-observation, high-beta oscillations (20-30 Hz) synchronized both during the observation of action and action-related objects. Low-beta modulations are therefore specific to action observation and high-beta modulations are related to the action scene. Our findings show that in the basal ganglia there are functional changes spreading to the action environment, probably presetting the motor system in relation to the motor context and suggesting that the dynamics of beta oscillations can contribute to action understanding mechanisms.

Deficits of temporal discrimination in dystonia are independent from the spatial distance between the loci of tactile stimulation.

To assess whether spatial variables influence deficits of temporal somesthetic discrimination in dystonic patients, 10 patients with idiopathic dystonia and 12 healthy controls were tested with pairs of non‐noxious electrical stimuli separated by different time intervals. Stimuli were delivered: (1) to the pad of the index finger (same‐point condition), (2) to the pad and to the base of the index finger (same‐finger condition), and (3) to the pad of the index and ring fingers (different‐finger condition). Subjects were asked to report whether they perceived single or double stimuli in the first condition and synchronous or asynchronous stimuli in the second and third conditions. Somesthetic temporal discrimination thresholds (STDTs) were obtained by computing the shortest time interval at which stimuli, applied to the left or the right hand, were perceived as separate in the first condition or asynchronous in the second and third conditions. STDTs were significantly higher in dystonic patients than controls in all three conditions. In both dystonia patients and controls, STDTs resulted highest in conditions whereby stimuli were maximally separated in space. Results extend current knowledge of deficits of somesthetic temporal discrimination in dystonia by showing that temporal deficits are not influenced by spatial variables.

Timing of tactile and visuo-tactile events is impaired in patients with cervical dystonia.

Abstract.Psychophysical studies show alterations of cross-modal integration and timing processes in patients with generalized and focal hand dystonia. Here we assess the capability of 10 cervical dystonia patients, 5 patients with cervical pain but no dystonia, and 10 healthy controls to determine whether pairs of visual, tactile or visuo-tactile stimuli were simultaneous or sequential (TD threshold) and which stimulus preceded the other (temporal order judgement, TOJ). Visual stimuli consisted of light emitting diodes and tactile stimuli of non-noxious electrical shocks delivered to the hands. Intervals between stimuli were increased from 0 to 400 ms in steps of 10 ms. Cervical dystonia patients had a clear impairment of tactile and visuo-tactile temporal discrimination compared with patients with cervical pain but no dystonia who performed as well as healthy subjects. This suggests that deficits of temporal discrimination in cervical dystonia patients are not due to the possible distracting effect of unpleasant sensations or pain. Comparisons with previous studies show that deficits in cervical dystonia were more severe than in focal hand dystonia and less severe than in generalized dystonia. Thus, impairment of sensory timing may be a marker of disease, which varies along a continuum in the different forms of dystonia.

Genotype–phenotype interactions in primary dystonias revealed by differential changes in brain structure

Our understanding of how genotype determines phenotype in primary dystonia is limited. Familial young-onset primary dystonia is commonly due to the DYT1 gene mutation. A critical question, given the 30% penetrance of clinical symptoms in DYT1 mutation carriers, is why the same genotype leads to differential clinical expression and whether non-DYT1 adult-onset primary dystonia, with and without family history share pathophysiological mechanisms with DYT1 dystonia. This study examines the relationship between dystonic phenotype and the DYT1 gene mutation by monitoring whole-brain structure using voxel-based morphometry. We acquired magnetic resonance imaging data of symptomatic and asymptomatic DYT1 mutation carriers, of non-DYT1 primary dystonia patients, with and without family history and control subjects with normal DYT1 alleles. By crossing the factors genotype and phenotype we demonstrate a significant interaction in terms of brain anatomy confined to the basal ganglia bilaterally. The explanation for this effect differs according to both gene and dystonia status: non-DYT1 adult-onset dystonia patients and asymptomatic DYT1 carriers have significantly larger basal ganglia compared to healthy subjects and symptomatic DYT1 mutation carriers. There is a significant negative correlation between severity of dystonia and basal ganglia size in DYT1 mutation carriers. We propose that differential pathophysiological and compensatory mechanisms lead to brain structure changes in non-DYT1 primary adult-onset dystonias and DYT1 gene carriers. Given the range of age of onset, there may be differential genetic modulation of brain development that in turn determines clinical expression. Alternatively, a DYT1 gene dependent primary defect of motor circuit development may lead to stress-induced remodelling of the basal ganglia and hence dystonia.

Temporal discrimination of cross-modal and unimodal stimuli in generalized dystonia.

Background: Motor and nonmotor timing functions and cross-modal processing of visual–tactile signals may be linked to basal ganglia. These neural structures are thought to be dysfunctional in dystonia. Objective: To test whether cross-modal stimulation influences deficits of temporal discrimination in dystonia. Methods: Eight patients with generalized dystonia and 10 control subjects were asked to discriminate whether pairs of unimodal (tactile or visual) and cross-modal (visual and tactile) stimuli were simultaneous or sequential and, in the latter case, which stimulus preceded the other. Visual stimuli consisted of red lights and tactile stimuli of non-noxious electrical shocks. Intervals between stimuli in each pair were increased from 0 to 400 msec (in steps of 10 msec). Results: Patients with dystonia recognized the asynchrony between the experimental stimuli and judged correctly which stimulus in a pair came first, at significantly longer intervals than did controls. Moreover, differences in performance between patients and controls were maximal for cross-modal stimuli. The defective performance of patients with dystonia in the cross-modal combinations showed a high positive correlation with the severity of symptoms. Conclusion: Patients with generalized dystonia present with difficulties both in timing functions and in cross-modal processing of visual–tactile stimuli.