T. Bocci

Transcutaneous spinal direct current stimulation modulates human corticospinal system excitability

This study aimed to assess the effects of thoracic anodal and cathodal transcutaneous spinal direct current stimulation (tsDCS) on upper and lower limb corticospinal excitability. Although there have been studies assessing how thoracic tsDCS influences the spinal ascending tract and reflexes, none has assessed the effects of this technique over upper and lower limb corticomotor neuronal connections. In 14 healthy subjects we recorded motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) from abductor hallucis (AH) and hand abductor digiti minimi (ADM) muscles before (baseline) and at different time points (0 and 30 min) after anodal or cathodal tsDCS (2.5 mA, 20 min, T9-T11 level). In 8 of the 14 subjects we also tested the soleus H reflex and the F waves from AH and ADM before and after tsDCS. Both anodal and cathodal tsDCS left the upper limb MEPs and F wave unchanged. Conversely, while leaving lower limb H reflex unchanged, they oppositely affected lower limb MEPs: whereas anodal tsDCS increased resting motor threshold [(mean ± SE) 107.33 ± 3.3% increase immediately after tsDCS and 108.37 ± 3.2% increase 30 min after tsDCS compared with baseline] and had no effects on MEP area and latency, cathodal tsDCS increased MEP area (139.71 ± 12.9% increase immediately after tsDCS and 132.74 ± 22.0% increase 30 min after tsDCS compared with baseline) without affecting resting motor threshold and MEP latency. Our results show that tsDCS induces polarity-specific changes in corticospinal excitability that last for >30 min after tsDCS offset and selectively affect responses in lower limb muscles innervated by lumbar and sacral motor neurons.

Transcallosal inhibition dampens neural responses to high contrast stimuli in human visual cortex

Visual cortical areas in the two hemispheres interact via the corpus callosum, but the precise role of the callosal pathway in visual processing remains controversial. Here we have investigated the function of transcallosal projections in human primary visual cortex (V1). Visual evoked potentials (VEPs) triggered by grating stimuli of different contrasts were recorded before and after functional inactivation of the occipital cortex of one hemisphere via off-line low-frequency repetitive transcranial magnetic stimulation (rTMS; 0.5 Hz stimulation for 20 min). VEPs were recorded in V1 before (T0), immediately after (T1) and 45 following the completion of rTMS (T2). We found that low-frequency rTMS had an inhibitory effect on VEPs amplitudes at all contrasts in the treated side. Remarkably, reduction of VEP amplitudes in the inhibited hemisphere at T1 was accompanied by an increase in VEP amplitudes in the contralateral side only at mid-high contrasts (50-90%). This disinhibitory effect was observed with both central and hemifield stimulation. No changes in VEP amplitudes were observed when rTMS was applied to a cortical site more anterior with respect to V1. These data provide the first evidence that a mechanism of transcallosal inhibition dampens neural responses at high contrasts in human visual cortex.

14. Cerebellar direct current stimulation modulates hand blink reflex: Implications for defensive behavior in humans

The cerebellum is involved in a wide number of integrative functions. We evaluated the role of cerebellum in peripersonal defensive behavior, as assessed by the so-called hand blink reflex (HBR). Twenty subjects underwent to cerebellar (sham, anodal, cathodal) and motor cortex (anodal or cathodal) tDCS (20′, 2xa0mA). For the recording of HBR, electrical stimuli were delivered using a surface bipolar electrode placed on the median nerve at the wrist and EMG activity recorded from the orbicularis oculi muscle bilaterally. HBR was assessed in four different conditions: “hand far”, “hand near” (eyes open), “side hand” and “hand patched” (eyes closed). While sham and cathodal cerebellar stimulation had no significant effect, anodal tcDCS dramatically dampened the magnitude of the HBR, as measured by the area under the curve (AUC), in the hand-patched and side hand conditions only, for ipsilateral (pxa0 Our results support a role of the cerebellum in the defensive responses within the peripersonal space surrounding the face and suggesting a cerebellar involvement in visual-independent learning of defensive behavior.

O201 Interhemispheric processing in hyperkinetic movement disorders

Objectives changes in interhemispheric connectivity have been recently studied in Huntington’s Disease (HD), although their significance and temporal relation with clinical features are still debated. We studied interhemispheric connectivity in healthy volunteers, early HD and in patients with idiopathic dystonia. Methods ipsilateral Silent Period (onset latency, iSPOL, and duration, iSPD) and Transcallosal Conduction Time (TCT) from the abductor pollicis brevis (APB) muscle were evaluated. In HD, we correlated TMS data with clinical (UHDRS-I, Disease Burden Index), genetic (CAG-length) and cognitive (UHDRS-II) scores. Results iSPD decreased in HD, paralleled by a significant lengthening of iSPOL and TCT (pxa0 Discussion Our results could have implications for the disruption of both sensorimotor integration and voluntary motor control in HD. Before voluntary movements, interhemispheric interactions are responsible for the temporary inhibition of ipsilateral primary motor cortex (M1) and the increased excitability of contralateral one. Concurrently, especially during non-dominant hand movements, enhanced interhemispheric inhibition from the ipsilateral hemisphere suppresses superfluous activation arising from the contralateral cortex. These mutual interactions may be lost in symptomatic HD, thus contributing to hyperkinesias. Significance This is the first study using TMS to assess interhemispheric connectivity in hyperkinetic movement disorders, possibly leading to a better knowledge of disease mechanisms.

O208 Evidence by direct current stimulation (tDCS) of cerebellum involvement in pain perception and modulation in humans

Objective cerebellum is involved in a wide number of integrative functions; its role in pain processing has been scarcely investigated. We tried to clarify this aspect using transcranial cerebellar direct current stimulation (tcDCS) and studying changes in perceptive threshold (PT), pain intensity (VAS) and laser evoked potentials (LEPs) responses (N1 and N2/P2). Materials and methods Fifteen subjects were studied before and after anodal, cathodal and sham tcDCS. LEPs were obtained using a Nd:YAP laser; signals were amplified, band pass filtered. The left hand dorsum was stimulated by laser pulses with short duration (5xa0ms) and small diameter spots (5xa0mm). VAS was evaluated by delivering laser pulses at two different intensities, respectively two and three times the pain threshold (PT). Results Cathodal polarization dampened the PT and increased the VAS score, while the anodal one had opposite effects ( p p Discussion tcDCS modulates pain perception and its cortical correlates. As it is effective on N1 and N2/P2 components and these responses are generated by parallel and partially segregated spinal pathways reaching different cortical targets, we speculate that the cerebellum modulates the activity of both somatosensory and cingulate cortices, interfering with the sensory-discriminative as well as emotional dimensions of pain. Conclusions Present findings prove Cerebellum involvement in pain processing and prompt further investigations on tcDCS employments as novel therapeutic tool in chronic pain patients.

79. Laser-evoked potentials in non-organic origin pain

Laser-evoked potentials (LEPs) represent the most reliable method to diagnose and follow over time painful small fiber neuropathies. Here, we investigated LEPs in patients with pain of non-organic origin. LEPs were recorded with a Nd:Yag Laser in 4 subjects with pain of non-organic origin, stimulating the dorsum of the hand and the dorsum of the foot bilaterally. We measured the perceptive threshold, latency and amplitude of N1 wave and N2/P2 complex within the painful territory and at contralateral site. We then compared these responses with those obtained in five sex- and age-matched healthy volunterees. We observed a significant increase in amplitude of N1 (pxa0=xa00.023) and N2/P2 (pxa0=xa00.015) responses in the painful territory compared both with contralateral side and healthy subjects. In patients, an additional positive wave at about 300xa0ms was detected only when the painfulside was stimulated; this response became more pronounced during stimulus expectation. Our data suggest that increased laser responses characterize subjects with pain of non-organic origin and likely reflect a strong emotional component in the nociceptive experience; the P3 component is probably related to cognitive modulation and anticipation phenomena, thus suggesting a functional (psychogenic) origin of the pain.

P179 Suprasegmental effects of dorsal transcutaneous spinal Direct Current Stimulation (tsDCS) on the Ia-motoneuron connections

Introduction tsDCS is a novel non-invasive tool to modulate human spinal cord function (Cogiamanian et al., 2008). Anodal tsDCS is known to reduce the post activaction depression of the H reflex in the lower limb (Winkler et al., 2010), and to induce a leftward shift of the stimulus–response curve of the H reflex, with no effect on H max/M max ratio (Lamy et al., 2012). No data are available about the effects of tsDCS on the upper limb H reflex. Objectives To assess whether dorsal tsDCS modulates the cervical Ia-motoneuron connections, we tested the influence of tsDCS on the H reflex in the human upper limb. Materials and methods tsDCS (2xa0mA, 20xa0min) was delivered in 12 healthy volunteers (aged 22–50xa0yrs, 4 males) through a pair of surface electrodes placed over the spinous processes of T10-12 and above the right shoulder. The H reflex was elicited stimulating the median nerve at the elbow and recording the response with surface electrodes placed over the flexor carpi radialis muscle. Each subject underwent anodal and cathodal tsDCS in random order. H reflex was recorded (i) before tsDCS (T0); (ii) 5 (T1), 10 (T2), 15 (T3) minutes after tsDCS onset; (iii) immediately after tsDCS offset (T4). The H reflex size is expressed as percentage of baseline amplitude (=100%). Values are meanxa0±xa0SE. Results The two way ANOVA disclosed a significant “time”xa0×xa0“stimulation” interaction on the percentage change of H reflex amplitude. Post-hoc analysis revealed that anodal tsDCS significantly reduced the H reflex amplitude at T3 (78.3xa0±xa08.2%; pxa0=xa00,040) and at T4 (76.3 xa0±xa07.6%; pxa0=xa00.028), whereas cathodal tsDCS significantly increased the H reflex amplitude only at T1 (125.5xa0±xa011.0%; pxa0=xa00.018). Conclusion Dorsal tsDCS influences human cervical mono/oligosynaptic Ia-motoneuronal reflex in a polarity specific manner. Because the temporal dynamic of tsDCS-elicited H reflex changes differed between the two polarities, anodal and cathodal tsDCS might have different –not simply specular– mechanisms of action.

P183 Transcranial direct current stimulation improves sleep quality

Introduction Sleep disturbance has been recognized as a common and significant complication linked to decreased quality of life in patients with neuropsychiatric disease. Currently, pharmacological therapy is the most common treatment for sleep disturbance, although benefits tend to be limited. Objective We assessed whether transcranial direct current stimulation (tDCS) improves sleep quality in patients with neurological and psychiatric diseases. Materials & methods 26 neuropsychiatric patients (age 19–86, n xa0=xa02 stroke, n xa0=xa04 dysphagia, n xa0=xa03 pain, n xa0=xa08 hereditary spastic paraparesis, n xa0=xa04 Parkinson’s disease, n xa0=xa02 aphasia, n xa0=xa03 depression) underwent tDCS treatment. tDCS montage was different for each pathology. The intensity of stimulation was set at 2xa0mA and delivered for 20xa0min for 5 consecutive days. The Pittsburgh Sleep Quality Index (PSQI) ( Buysse, 1989 ) was used to assess sleep quality at baseline (T0) and after the tDCS treatment (T1). Results One way ANOVA analysis showed that anodal tDCS improved PSQI total score by 13% [(meanxa0±xa0SD) T0: 6.3xa0±xa04 vs T1: 5xa0±xa03.6; p xa0=xa00.004] and PSQI sub-item scores subjective quality of sleep by 22% (T0: 1.1xa0±xa00.7 vs T1: 0.92xa0±xa00.68; p xa0=xa0 0.016) and habitual sleep efficiency by 17% (T0: 0.31xa0±xa00.67 vs T1: 0.04xa0±xa00.19 p xa0=xa00.031). No differences were found between pathology. Conclusion Despite the small sample size and different tDCS montages, data from our observational study showed that anodal tDCS for five days improved sleep quality and efficiency. tDCS could be a non-invasive and valuable new tool for managing sleep disorders.

42. Functional Tremor: When neurophysiology makes the difference

Functional tremor (FT) still remains a challenge for clinicians; here, we propose a simple and fast test battery for an early diagnosis of FT. We enrolled ten patients with probable FT and compared them with patients with essential tremor (ET) or tremor-dominant Parkinson’s Disease (PD). Surface polymyography was bilaterally performed with arms relaxed, with arms outstretched at shoulder level without or with a 500-g mass attached to the wrist (“mass loading”), during voluntary contralateral motor activation and while performing ballistic movements. We also asked to the patient to use the index finger of the left hand to tap in time with a metronome at rates of 1, 3 and 5xa0Hz. At the end of the test, we recorded Blink Reflex Habituation. Polymyography revealed (a) a paradoxical increase of tremor amplitude with mass loading, (b) jerks’ synchronization between antagonistic muscles performing voluntary contralateral motor activation and (c) tremor inhibition during a ballistic movement. Co-activation sign was present. Finally, all the patients showed a Blink-Reflex habituation preserved. Our results prompt further studies to integrate clinical and electrodiagnostic criteria in the whole field of hyperkinetic movement disorders, exploring the floating border between organic and functional disease.

114. An unexpected target of Spinal Direct Current Stimulation: Interhemispheric connectivity in humans

Transcutaneous spinal Direct Current Stimulation (tsDCS) is a noninvasive technique based on the application of weak currents over spinal cord. We studied the effects of tsDCS on interhemispheric connectivity and visual processing by evaluating changes in ipsilateral Silent Period (iSP), Transcallosal Conduction Time (TCT) and hemifield Visual Evoked Potentials (hVEPs), before and at different intervals following sham, anodal and cathodal tsDCS (T10–T12 level, 2.0xa0mA, 20 ′ ). Motor Evoked Potentials (MEPs) were recorded from abductor pollicis brevis (APB), abductor hallucis (AH) and deltoid muscles. hVEPs were recorded bilaterally by reversal of a horizontal square wave grating. Anodal tsDCS increased TCT ( p p xa0=xa00.0003; P1: p p p xa0=xa00.0005; deltoid: p p