Gionata Strigaro

Cerebellar modulation of human associative plasticity.

Key point  •  Increases in the strength of synaptic connections in the motor cortex (long term potentiation) can be induced in humans by repetitively pairing peripheral nerve stimuli and motor cortex transcranial magnetic stimuli given 21–25 ms apart – paired associative stimulation (PAS). •  This ‘associative plasticity’ effect has been assumed to relate to synchronicity between sensory input and motor output, with a similar mechanism proposed to underlie effects at all interstimulus intervals. •  Here we show that modulation of cerebellar activity using transcranial direct current stimulation can abolish associative plasticity in the motor cortex, but only for sensory/motor stimuli paired at 25 ms, not at 21.5 ms. •  The results indicate that human associative plasticity can be affected by cerebellar activity and that at least two different mechanisms are involved in the effects previously reported in studies using PAS at different inter‐stimulus intervals.

Measuring the level and content of consciousness during epileptic seizures: The Ictal Consciousness Inventory

Ictal alterations of the level of general awareness and subjective content of consciousness play a pivotal role in the clinical phenomenology of epilepsy, and reflect the pathological involvement of different neurobiological substrates. However, no self-reported measures have been proposed for patients experiencing altered conscious states during seizures. This study describes the development and validation of a new scale for the quantitative assessment of the level and content of ictal consciousness, the Ictal Consciousness Inventory (ICI). The ICI is a 20-item questionnaire generated on the basis of interviews with patients, literature review, and consultation with experts. It was tested on a sample of 110 patients attending three different epilepsy clinics in Northern Italy, who also completed standardized clinical scales. Standard psychometric methods were used to demonstrate that this scale satisfies criteria for acceptability, reliability, and validity. The ICI is proposed as a user-friendly and clinically sound instrument for the measurement of ictal alterations of consciousness in patients with epilepsy.

TMS, cortical excitability and epilepsy: The clinical impact

Paired-pulse transcranial magnetic stimulation (ppTMS) is a well-established method for non-invasive measurement of cortical excitability, alterations of which are the core background of epilepsy. For the past 20 years this technique has been extensively used to assess patients with epilepsy. We present here a critical overview of these studies, with emphasis on their translation to the clinical practice.

Defective visual inhibition in photosensitive idiopathic generalized epilepsy

Purpose:  To assess the visual system excitability of photosensitive patients with idiopathic generalized epilepsy (IGE) with the paired‐pulse flash‐evoked potential (paired F‐VEP) technique.

Intermittent photic stimulation affects motor cortex excitability in photosensitive idiopathic generalized epilepsy

PURPOSE To assess the effect of intermittent photic stimulation (IPS) at a common activating frequency, i.e. 20Hz, on motor cortex excitability by means of transcranial magnetic stimulation (TMS) in photosensitive patients with idiopathic generalized epilepsy (IGE). METHODS We studied 15 photosensitive IGE patients showing a photoparoxysmal response (PPR) to IPS at 20Hz. Nineteen normal subjects of similar age and sex acted as controls. After the resting motor threshold (rMT) was measured, we studied the corticomotor excitability in two conditions randomly delivered, during IPS (5s) at 20Hz and without IPS. Motor evoked potentials (MEPs) were recorded from the right first dorsal interosseous muscle (FDI). We determined the cortical silent period (cSP), the short-latency intracortical inhibition (SICI) at the interstimulus interval (ISI) of 3 and 4ms and the intracortical facilitation (ICF) at ISIs of 12 and 14ms. Data were analyzed by means of rmANOVAs. RESULTS IPS at 20Hz is significantly shortening the cSP in normal subjects, while no significant changes were detected in patients. The rMT was significantly higher in patients than controls, as expected by the concurrent antiepileptic treatment. Other corticomotor excitability measures were unaffected. CONCLUSIONS We confirm that IPS has a weak influence on the motor cortical output in patients with IGE and PPR. The loss of the normal shortening of the cSP, otherwise present in healthy subjects in response to IPS, may have a possible protective nature.

Interaction between visual and motor cortex: a transcranial magnetic stimulation study

The major link between the visual and motor systems is via the dorsal stream pathways from visual to parietal and frontal areas of cortex. Although the pathway appears indirect, there is evidence that visual input can reach the motor cortex at relatively short latency. To shed some light on its neural bases, we studied the visuo-motor interaction using paired transcranial magnetic stimulation (paired-TMS). Motor evoked potentials (MEPs) were recorded from the right FDI in sixteen healthy volunteers. A conditioning stimulus (CS) was applied over the phosphene hotspot of visual cortex, followed by a test stimulus (TS) over left M1 at random interstimulus intervals (ISIs, 12-40 ms). The effects of paired stimulation were re-tested during visual and auditory reaction-time tasks (RT). Finally, we measured the effects of a CS on short-interval intracortical inhibition (SICI). At rest, a CS over the occiput significantly (p Language: enWe studied the interaction between the primary visual cortex and the primary motor cortex using paired transcranial magnetic stimulation (TMS) with an interstimulus interval (ISI) in the range 12–40 ms. The connection is inhibitory at rest and possibly mediated by inhibitory interneurones in the motor cortex. The effect with an ISI of 40 ms reverses into facilitation during a visuomotor (but not audiomotor) reaction task. By contrast, there is no change in inhibition with an ISI of 18 ms, suggesting that separate pathways can be probed at different ISIs. We conclude that a physiologically relevant occipito‐motor connection can be activated by means of TMS. It may contribute to visuomotor integration, as well as being involved in certain types of visual epilepsy.

Overactive visuomotor connections underlie the photoparoxysmal response. A TMS study.

The photoparoxysmal response (PPR) involves rapid spread of epileptic activity from visual to parietal and frontal areas. We used a transcranial magnetic stimulation (TMS) technique to assess the physiologic connections between primary visual (V1) and motor (M1) areas in patients with idiopathic generalized epilepsy (IGE). We hypothesized that in PPR‐positive patients, M1 would respond excessively to inputs from V1.

Health-related quality of life measures and psychiatric comorbidity in patients with migraine

Background and purpose:  The identification of factors associated to health‐related quality of life (HRQoL) measures in patients with migraine has major implications in terms of prognosis and treatment. This study aimed at investigating associations between HRQoL and comorbid mood and anxiety disorders.

Transcranial Direct Current Stimulation Effects on Single and Paired Flash Visual Evoked Potentials

Transcranial direct current stimulation (tDCS) applied over the occipital cortex has a controversial effect on the visual cortex excitability. Paired flash visual evoked potentials (paired F-VEPs) offer a unique method to express neural inhibition within the visual system. However, no studies have explored the effects of tDCS on F-VEPs in humans. The aim of this study was to evaluate the changes of single- and paired-F-VEPs during and after tDCS in healthy humans. Twenty-six healthy volunteers participated. F-VEPs were recorded from occipital electrodes with closed eyes. Stimuli were single flashes, intermingled to flash pairs at the interstimulus interval of 125, 62.5, 50, 33.3, 16.6, and 11.1 ms (internal frequency of 8, 16, 20, 30, 60, and 90 Hz). The single F-VEP was split into a “main complex” and a “late response.” As to paired stimuli, the “test” F-VEP emerged from electronic subtraction of the single-F-VEP to the paired-F-VEP. In experiment 1, the return electrode was located on the scalp and we studied changes in F-VEPs after anodal, cathodal (1 mA, 15 min) and sham stimulation. A second experiment was performed in which F-VEPs were recorded before, during and after tDCS stimulation (anodal and cathodal) with the return electrode on the neck. F-VEPs recorded in experiment 1 did not detect any significant change after tDCS. In experiment 2 anodal polarization significantly increased the P2 latency (P = .031) and reduced the amplitude of the “late response” of the single F-VEP (P = .008). As for the paired F-VEPs, no significant changes were detected. In conclusion, low-intensity anodal tDCS has weak inhibitory aftereffects on the single F-VEP and no effects on the paired F-VEPs. Further methodological studies are needed to improve polarization efficacy.

Cortical excitability changes associated with fixation-off sensitivity: a case report.

“Fixation‐off sensitivity” (FOS) is an ideal human model for studying the features of epileptic discharges. Physiologically, FOS is expected to correspond to enhanced excitability of widespread cortical structures. To test this hypothesis, we measured by transcranial magnetic stimulation (TMS), the excitability level of the primary motor area in a 22‐year‐old woman with eyelid myoclonias and absences, who presented with generalized FOS. We also explored her visual system by pattern‐reversal and flash‐visual evoked potentials (VEPs). Both outside and within FOS, the cortical silent period was dramatically short, indicating defective γ‐aminobutyric acid (GABA)B inhibition as a persistent background factor. The same was true for the short‐interval intracortical inhibition, a TMS marker of cortical GABAA inhibition. The FOS state corresponded then to a pathologic enhancement of intracortical facilitation, a TMS marker of Glu/Asp transmission. During FOS, the flash VEP exhibited a hugely enhanced afterdischarge, expressing a pathologic overactivity of secondary visual areas. Within the limits of a single‐case study, we thus provide electrophysiologic evidence supporting a grossly imbalanced cortical excitability, in both the frontal and posterior areas, as an important correlate of the present FOS subtype.