Carla Ogliastro

1-Hz repetitive TMS over ipsilateral motor cortex influences the performance of sequential finger movements of different complexity

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.

Training based on mirror visual feedback influences transcallosal communication

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.

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.

Electroretinographic assessment in major depressed patients receiving duloxetine: might differences between responders and non-responders indicate a differential biological background?

INTRODUCTION Despite intense research efforts, still too little is known about the biological determinants of depression, thus soliciting diverse study approaches. Among others, the electroretinography (ERG) has been proposed even as a putative proxy (retinal) measurement of central dopaminergic activity for Major Depressive Disorder (MDD) both in drug-naïve patients and subjects receiving antidepressant treatments. Nonetheless, current evidences are merely preliminary, essentially considering just older classes of antidepressants, thus requiring confirmation studies even with newer agents as duloxetine. METHOD Twenty MDD subjects and 20 matched controls received duloxetine 60 mg/day for 12 weeks, being monitored both by standard ERG recording and by administration of the Hamilton scales for Depression and Anxiety and the Young Mania Rating Scale at baseline and week 12 (end of the study). RESULTS ERG mean rod b-wave amplitude significantly reduced from baseline to week 12 in those depressed subjects achieving final response (p=.024), decreasing from the highest rank values to the ones, substantially unmodified, seen among non-responders and controls. LIMITATIONS Small sample size and lack of multiple assessments. CONCLUSIONS At least some MDD patients responding to duloxetine might exhibit a peculiar ERG pattern, hypothetically indicating a specific biological background. If confirmed by larger-sampled studies, these results might shed further light in the understanding of the biological determinants of different subtypes of depression, ideally showing alternative patterns of response upon different treatment interventions.

Interaction Between Finger Opposition Movements and Aftereffects of 1Hz-rTMS on Ipsilateral Motor Cortex

One-hertz repetitive transcranial magnetic stimulation (1Hz-rTMS) over ipsilateral motor cortex is able to modify up to 30 min the motor performance of repetitive finger opposition movements paced with a metronome at 2 Hz. We investigated whether the long-lasting rTMS effect on motor behavior can be modulated by subsequent engagement of the contralateral sensorimotor system. Motor task was performed in different experimental conditions: immediately after rTMS, 30 min after rTMS, or when real rTMS was substituted with sham rTMS. Subjects performing the motor task immediately after rTMS showed modifications in motor behavior < or =30 min after rTMS. On the other hand, when real rTMS was substituted with sham stimulation or when subjects performed the motor task 30 min after the rTMS session, the effect was no longer present. These findings suggest that the combination of ipsilateral 1Hz-rTMS and voluntary movement is crucial to endure the effect of rTMS on the movement itself, probably acting on synaptic plasticity-like mechanism. This finding might provide some useful hints for neurorehabilitation protocols.

Mirror Visual Feedback to Improve Bradykinesia in Parkinson’s Disease

Mirror visual feedback (MVF) therapy has been applied to improve upper limb function in stroke. When combined with motor training, MVF improves the performance of the trained and untrained hand by enhancing the excitability of both primary motor cortices (M1s). Bradykinesia is a typical feature of Parkinsons disease (PD), characterized by slowness in the execution of movement. This condition is often asymmetrical and possibly supported by a volitional hypoactivation of M1. MVF therapy could tentatively treat bradykinesia since the untrained hand, which benefits from the exercise, is generally more severely impaired in undertaking sequential movements. Aim of the study was to evaluate whether MVF therapy may improve bradykinesia of the more affected hand in PD patients. Twelve PD patients and twelve healthy controls performed for 10 minutes a finger sequence, receiving MVF of the more affected/nondominant hand. Before and after MVF training, participants performed a finger sequence at their spontaneous pace with both hands. M1 excitability was assessed in the trained and untrained hemispheres by means of transcranial magnetic stimulation. Movement speed increased after MVF training in either hand of both groups. MVF therapy enhanced cortical excitability of M1s in both groups. Our preliminary data support the use of MVF therapy to improve bradykinesia in PD patients.

Factor structure and ammonia-related modulation of the human retinal oscillatory potentials

OBJECTIVE To investigate in man the factor structure of retinal oscillatory potentials (OPs) to full-field luminance stimulation (0.9-9.5 cd.s.m(-2)) and the correlation with the spontaneous fluctuations of plasma ammonia. METHODS Six male healthy volunteers were studied. Five OP recordings and ammonia determinations (GLDH method) were obtained for each subject at 2 h interval during an 8 h experimental session. A standard factor analysis was applied on the OP latency (time from stimulus to peak) and amplitudes values. RESULTS Two consecutive factors on latencies and two factors on amplitudes were identified, consistent with reported differences between the earlier and later OP waves. The model explained a large portion of the OP variance. Both factors on latencies and factor 1 on amplitudes were directly correlated to the stimulus intensity and the ammonia plasma concentration in the 15.8-39.5 micromol/l range. Factors 1 and 2 on latencies decreased and factor 1 on amplitude increased at increasing stimulus intensities. The latency factors decreased and the amplitude factor increased with increasing ammonia concentration. Factor 2 on amplitudes did not correlate with the stimulus intensity or ammonia concentration. CONCLUSIONS The factor structure further supports the evidence of functional differences between early and late OP waves. The observed correlation conceivably reflects a role of ammonia in the modulation of retinal electrophysiology in physiological conditions and potentially accounts for spontaneous variability in otherwise controlled electrophysiological studies.

Electroretinographic modifications induced by agomelatine: a novel avenue to the understanding of the claimed antidepressant effect of the drug?

Background Agomelatine, the first melatonergic antidepressant, has been postulated to enhance the dopaminergic activity at the central nervous system by 5-hydroxytryptamine receptor type 2C (5-HT2C) antagonism, yet the impact of melatonergic agonism on this pathway is unclear. Previous studies employing simplified, yet reliable, proxy (retinal) measures of the central nervous system dopaminergic activity, namely the standard electroretinogram (ERG) technique, suggested a reduction of the dopaminergic activity of the main ERG parameter, the b-wave, by pure melatonin, notably a hormone devoid of any antidepressant activity. Therefore, the antidepressant effects of the melatonergic antidepressant drug agomelatine should be reflected by a differential b-wave trend at ERG versus the effect exerted by pure melatonin, which was eventually found to be due to a contrasting effect on central dopaminergic transmission between the two drugs. Objective and methods The aim of the present preliminary ERG study carried out on healthy volunteers (n=23) receiving agomelatine was to explore the impact of this antidepressant drug on b-wave amplitude and latency of cones in daylight conditions using standard ERG. Results As postulated, agomelatine induced an enhancement of retinal dopaminergic activity, in contrast to what has been previously documented for melatonin. Conclusion Given the limits of this explorative study, especially the lack of a control group and that of a luminance response function to measure retinal sensitivity, further studies in clinical samples are recommended to allow more tenable conclusions about the potential role of ERG in discriminating between 5-HT antagonism and melatonergic (MT) agonism in relationship to the claimed antidepressant effect of agomelatine.

Real-time artifact filtering in continuous VEPs/fMRI recording

Continuous recording of Visual Evoked Potentials (VEPs) and functional Magnetic Resonance Imaging (fMRI) exploits the VEPs high temporal resolution and the fMRI high spatial resolution. In this work, we present a new method of continuous VEPs/fMRI recording to study visual function in seven normal subjects. Our real-time artifact filtering is characterized by a procedure based on an analytical study of echo-planar imaging (EPI) sequence parameters related electro-encephalogram (EEG)-artifact shapes. The magnetic field artifacts were minimized by using a dedicated amagnetic device and by a subtraction algorithm that takes into account the EPI sequence parameters. No significant decrease in signal-to-noise ratio was observed in case of EEG recording simultaneously with MR acquisition; similarly, transient and steady-state VEPs parameters were comparable during fMRI acquisition and in the off-phase of fMRI recording. We also applied this method to one patient with optic neuritis, and, compared with controls, found different results. We suggest that our technique can be reliably used to investigate the function of human visual cortex and properly correlate the electrophysiological and functional neuroimaging related changes.