Short-term plasticity of the motor cortex compensates for bradykinesia in Parkinson's disease.

Patients with Parkinson's disease (PD) show impaired short-term potentiation (STP) mechanisms in the primary motor cortex (M1). However, the role played by this neurophysiological abnormality in bradykinesia pathophysiology is unknown. In this study, we used a multimodal neuromodulation approach to test whether defective STP contributes to bradykinesia. We evaluated STP by measuring motor-evoked potential facilitation during 5 Hz-repetitive transcranial magnetic stimulation (rTMS) and assessed repetitive finger tapping movements through kinematic techniques. Also, we used transcranial alternating current stimulation (tACS) to drive M1 oscillations and experimentally modulate bradykinesia. STP was assessed during tACS delivered at beta (ß) and gamma (γ) frequency, and during sham-tACS. Data were compared to those recorded in a group of healthy subjects. In PD, we found that STP was impaired during sham- and γ-tACS, while it was restored during ß-tACS. Importantly, the degree of STP impairment was associated with the severity of movement slowness and amplitude reduction. Moreover, ß-tACS-related improvements in STP were linked to changes in movement slowness and intracortical GABA-A-ergic inhibition during stimulation, as assessed by short-interval intracortical inhibition (SICI). Patients with prominent STP amelioration had greater SICI reduction (cortical disinhibition) and less slowness worsening during ß-tACS. Dopaminergic medications did not modify ß-tACS effects. These data demonstrate that abnormal STP processes are involved in bradykinesia pathophysiology and return to normal levels when ß oscillations increase. STP changes are likely mediated by modifications in GABA-A-ergic intracortical circuits and may represent a compensatory mechanism against ß-induced bradykinesia in PD.

Driving motor cortex oscillations modulates bradykinesia in Parkinson's disease.

In patients with Parkinson's disease, beta (ß) and gamma (γ) oscillations are altered in the basal ganglia, and this abnormality contributes to the pathophysiology of bradykinesia. However, it is unclear whether ß and γ rhythms at the primary motor cortex (M1) level influence bradykinesia. Transcranial alternating current stimulation (tACS) can modulate cortical rhythms by entraining endogenous oscillations. We tested whether ß- and γ-tACS on M1 modulate bradykinesia in patients with Parkinson's disease by analysing the kinematic features of repetitive finger tapping, including movement amplitude, velocity and sequence effect, recorded during ß-, γ- and sham tACS. We also verified whether possible tACS-induced bradykinesia changes depended on modifications in specific M1 circuits, as assessed by short-interval intracortical inhibition and short-latency afferent inhibition. Patients were studied OFF and ON dopaminergic therapy. Results were compared to those obtained in a group of healthy subjects. In patients, movement velocity significantly worsened during ß-tACS and movement amplitude improved during γ-tACS, while the sequence effect did not change. In addition, short-latency afferent inhibition decreased (reduced inhibition) during ß-tACS and short-interval intracortical inhibition decreased during both γ- and ß-tACS in Parkinson's disease. The effects of tACS were comparable between OFF and ON sessions. In patients OFF therapy, the degree of short-interval intracortical inhibition modulation during ß- and γ-tACS correlated with movement velocity and amplitude changes. Moreover, there was a positive correlation between the effect of γ-tACS on movement amplitude and motor symptoms severity. Our results show that cortical ß and γ oscillations are relevant in the pathophysiology of bradykinesia in Parkinson's disease and that changes in inhibitory GABA-A-ergic interneuronal activity may reflect compensatory M1 mechanisms to counteract bradykinesia. In conclusion, abnormal oscillations at the M1 level of the basal ganglia-thalamo-cortical network play a relevant role in the pathophysiology of bradykinesia in Parkinson's disease.

Transcranial alternating current stimulation modulates cortical processing of somatosensory information in a frequency- and time-specific manner.

Neural oscillations can be modulated by non-invasive brain stimulation techniques, including transcranial alternating current stimulation (tACS). However, direct evidence of tACS effects at the cortical level in humans is still limited. In a tACS-electroencephalography co-registration setup, we investigated the ability of tACS to modulate cortical somatosensory information processing as assessed by somatosensory-evoked potentials (SEPs). To better elucidate the neural substrates of possible tACS effects we also recorded peripheral and spinal SEPs components, high-frequency oscillations (HFOs), and long-latency reflexes (LLRs). Finally, we studied whether changes were limited to the stimulation period or persisted thereafter. SEPs, HFOs, and LLRs were recorded during tACS applied at individual mu and beta frequencies and at the theta frequency over the primary somatosensory cortex (S1). Sham-tACS was used as a control condition. In a separate experiment, we assessed the time course of mu-tACS effects by recording SEPs before (T0), during (T1), and 1 min (T2) and 10 min (T3) after stimulation. Mu-tACS increased the amplitude of the N20 component of SEPs compared to both sham and theta-tACS. No differences were found between sham, beta-, and theta-tACS conditions. Also, peripheral and spinal SEPs, P25, HFOs, and LLRs did not change during tACS. Finally, mu-tACS-induced modulation of N20 amplitude specifically occurred during stimulation (T1) and vanished afterwards (i.e., at T2 and T3). Our findings suggest that TACS applied at the individual mu frequency is able to modulate early somatosensory information processing at the S1 level and the effect is limited to the stimulation period.

The role of frailty in Parkinson's disease: a cross-sectional study.

BACKGROUND: Frailty is an age-related state of increased risk for health-related adverse outcomes that reflects multisystem physiological changes and likely influences the clinical expression and disease progression of neurodegenerative disorders. The aim of the present study was to assess the potential relationship between frailty, as assessed by a frailty index (FI), and motor symptom severity, motor subtypes, and non-motor domains in Parkinson's disease (PD). METHODS: We consecutively enrolled 150 PD patients. We administered an FI specifically designed for PD that included 50 age-related multidimensional biological deficits. Patients underwent a clinical assessment that evaluated motor and non-motor manifestations of PD. Using the FI score, we classified PD patients as relatively fit (FI ≤ 0.10), less fit (0.10 < FI ≤ 0.21), or frail (FI > 0.21). A linear regression model was designed to explore possible associations between frailty level and PD motor and non-motor manifestations. RESULTS: Frail patients showed greater motor symptom severity and motor complications than fitter patients. A trend towards a higher prevalence of the postural instability/gait disorder subtype was also observed in frail versus relatively fit and less fit patients. The global burden of non-motor symptoms was higher in frail patients. Increased frailty was associated with more severe motor and non-motor symptoms, as well as with more pronounced cognitive deficits. These associations remained significant even when "traditional" predictors of PD severity (age, disease duration, and levodopa equivalent daily dose) were considered. CONCLUSIONS: The present findings indicate that the FI is associated with both motor and non-motor features of PD.

Investigating the effects of transcranial alternating current stimulation on primary somatosensory cortex.

Near-threshold tactile stimuli perception and somatosensory temporal discrimination threshold (STDT) are encoded in the primary somatosensory cortex (S1) and largely depend on alpha and beta S1 rhythm. Transcranial alternating current stimulation (tACS) is a non-invasive neurophysiological technique that allows cortical rhythm modulation. We investigated the effects of tACS delivered over S1 at alpha, beta, and gamma frequencies on near-threshold tactile stimuli perception and STDT, as well as phase-dependent tACS effects on near-threshold tactile stimuli perception in healthy subjects. In separate sessions, we tested the effects of different tACS montages, and tACS at the individualised S1 µ-alpha frequency peak, on STDT and near-threshold tactile stimuli perception. We found that tACS applied over S1 at alpha, beta, and gamma frequencies did not modify STDT or near-threshold tactile stimuli perception. Moreover, we did not detect effects of tACS phase or montage. Finally, tACS did not modify near-threshold tactile stimuli perception and STDT even when delivered at the individualised µ-alpha frequency peak. Our study showed that tACS does not alter near-threshold tactile stimuli or STDT, possibly due to the inability of tACS to activate deep S1 layers. Future investigations may clarify tACS effects over S1 in patients with focal dystonia, whose pathophysiology implicates increased STDT.

Hair Mercury Levels Detection in Fishermen from Sicily (Italy) by ICP-MS Method after Microwave-Assisted Digestion.

A number of ninety-six hair samples from Sicilian fishermen were examined for total mercury detection by an Inductively Coupled Plasma Mass Spectrometry (ICP-MS) method. The mercury levels obtained were compared with mercury levels of 96 hair samples from a control group, in order to assess potential exposure to heavy metals of Sicilian fishermen due to fish consumption and closeness to industrial activities. Furthermore, the mercury levels obtained from hair samples were sorted by sampling area in order to verify the possible risks linked to the different locations. The overall mean concentration in the hair of the population of fishermen was 6.45 ± 7.03 µg g(-1), with a highest value in a fisherman of Sciacca (16.48 µg g(-1)). Hair mercury concentration in fishermen group was significantly higher than in control group (p < 0.01). There was no significant difference in hair total mercury concentrations between sampling areas (p > 0.05). The results of this study indicate a greater risk of exposure to mercury in Sicilian fishermen, in comparison to the control population, due to the high consumption of fish and the close relationship with sources of exposure (ports, dumps, etc.).