Aurelio Piazza

Contralateral neglect induced by right posterior parietal rTMS in healthy subjects.

&NA; We applied repetitive transcranial magnetic stimulation (rTMS) in order to induce interference on visuo‐spatial perception in 11 healthy subjects. Subjects performed a visuo‐spatial task requiring judgements about the symmetry of prebisected lines. Visual stimuli consisted of symmetrically or asymmetrically transected lines, tachystoscopically presented for 50 ms on a computer‐monitor. Performance was examined in basal condition and during rTMS trains of 10 stimuli at 25 Hz, delivered through a focal coil over right or left posterior parietal cortex (P5 and P6 sites) and triggered synchronously with visual stimulus. Randomly intermixed sham rTMS trains were employed to control for non‐specific effects. Right parietal rTMS induced a significant rightward bias in symmetry judgements as compared with basal and sham rTMS conditions. No differences emerged between other conditions.

1 Hz repetitive transcranial magnetic stimulation of the unaffected hemisphere ameliorates contralesional visuospatial neglect in humans

The aim of the study was to investigate whether low-frequency repetitive transcranial magnetic stimulation (rTMS) over the unaffected hemisphere can ameliorate visuospatial neglect. We treated three right brain damaged patients with left neglect. 900 pulses (1 Hz frequency) were given over left posterior parietal cortex every other day for 2 weeks. Patients performed a computerized task requiring length judgement of prebisected lines, tachistoscopically presented for 150 ms. With respect to rTMS the task was given 15 days before, at the beginning, at the end and 15 days after. At these times patients performed also line bisection and clock drawing tasks. rTMS induced a significant improvement of visuo-spatial performance that remained quite unchanged 15 days after. Patients performance at Time 3 and 4 improved also as concerns line bisection and clock drawing tasks.

rTMS of the unaffected hemisphere transiently reduces contralesional visuospatial hemineglect

To verify the role of interhemispheric influences on manifestations of neglect, the authors investigated the effects of a transient repetitive transcranial magnetic stimulation (rTMS)-induced disruption of the unaffected hemisphere on contralesional visuospatial neglect in two left- and five right-brain-damaged patients. Parietal rTMS of the unaffected hemisphere during the execution of a computerized task of bisected line’s length judgment transiently decreased the magnitude of neglect as expressed in the number of errors.

rTMS of the prefrontal cortex in the treatment of chronic migraine: a pilot study.

A recent fMRI study showed that dorsolateral prefrontal cortex (DLPFC) exerts an inhibitory control on pain pathways in humans. We investigated whether high-frequency rTMS over left DLPFC could ameliorate chronic migraine. Treatment consisted of 12 rTMS sessions, delivered in alternate days over left DLPFC. Sham rTMS was used as placebo. Eleven patients were randomly assigned to the rTMS (n=6) or to the placebo (n=5) treatment. Measures of attack frequency, headache index, number of abortive medications (outcome measures) were recorded in the month before, during and in the month after treatment. Subjects treated by rTMS showed a significant reduction of the outcome measures during and in the month after the treatment as compared to the month before treatment. No significant differences in the outcome measures were observed in the placebo group. High-frequency rTMS over left DLPFC was able to ameliorate chronic migraine. This is in agreement with the suggested role of DLPFC in pain control.

Modulatory effects of low‐ and high‐frequency repetitive transcranial magnetic stimulation on visual cortex of healthy subjects undergoing light deprivation

The aim of the present study was to explore further the effects of light deprivation (LD) on visual cortex excitability. Healthy subjects reporting reliable induction of phosphenes by occipital transcranial magnetic stimulation (TMS) underwent 60 min of complete LD. Phosphene threshold (PT) was measured before (T0), after 45 min (T1) and 60 min (T2) of LD, and then every 10 min after light re‐exposure until recovery to T0 values. Repetitive TMS (rTMS) (at 1 or 10 Hz) was applied in separate sessions during the last 15 min of LD. PTs significantly decreased after 45 min of LD. rTMS differentially modified the effects of 60 min LD on PTs depending on stimulation frequency. One hertz rTMS did not change the decreasing of PT values as observed in baseline condition, but significantly prolonged the time to recover T0 PT values after light re‐exposure. By contrast, 10 Hz rTMS significantly increased PT and the time to recover T0 PT values after light re‐exposure was shortened. The results of this study show that the modulatory effects of different rTMS frequencies on visual cortex critically depend on the pre‐existing excitability state of inhibitory and facilitatory circuits, and provide novel insights into the neurophysiological changes that take place in the visual cortex following functional visual deafferentation.

Timing of right parietal and frontal cortex activity in visuo-spatial perception: a TMS study in normal individuals

In a recent study we showed that repetitive transcranial magnetic stimulation (rTMS) with train duration of 400 ms over right frontal and right posterior parietal cortices gives rise to transitory contralateral visuo-spatial neglect in normal subjects. In the present experiment we investigated whether using single-pulse TMS it is possible to obtain information about the timing of cortical activity related to spatial cognition. Nine healthy subjects performed in baseline condition and during TMS a tachistoscopic task, requiring a forced-choice estimation of the length of the two segments of prebisected horizontal lines. Single-pulse TMS was triggered at various time intervals (150 ms, 225 ms, 300 ms) after visual stimulus onset with a focal coil over P6 and F4 (according to 10/20 EEG system). Relative transitory rightward bias was observed only when parietal TMS was delivered 150 ms after visual stimulus presentation. Frontal stimulation induced no effect on visuo-spatial perception with the time intervals explored.

1 Hz rTMS enhances extrastriate cortex activity in migraine Evidence of a reduced inhibition

We recently reported a paradoxical facilitatory effect of 1 Hz repetitive TMS (rTMS) on the primary visual cortex in migraine possibly due to the failure of inhibitory circuits, unable to be upregulated by low frequency rTMS. To investigate if inhibitory circuit dysfunction extends beyond striate cortex in migraine with aura, we studied the effects of 1 Hz rTMS over the right extrastriate cortex on perception of illusory contours in these patients. Low-frequency rTMS enhanced activity of extrastriate cortex in migraineurs, speeding up reaction times on illusory contour perception. This finding supports the view of a failure of inhibitory circuits also involving the extrastriate cortex in migraine with aura.

Low-frequency transcranial magnetic stimulation in patients with cortical dysplasia - a preliminary study.

Sirs: Because of the increasing attention to the potential therapeutic role of repetitive transcranial magnetic stimulation (rTMS) in intractable epilepsy [2, 4], the aim of this study was to find out whether patients with medically refractory epilepsy due to cortical dysplasia could benefit from low-frequency rTMS. 1 Hz rTMS have been able to decrease motor cortex excitability [1]. Lower stimulation frequencies (0,33 and 0.5 Hz) have been successfully employed in the treatment of seizures in humans and experimental animals [2–4]. In this open pilot study we investigated the effect of 0.5 Hz rTMS in four patients (1 M, 3 F mean age 29.5 ± 2.6, range 27–33 years) with very frequent partial and secondary generalized seizures due to a single frontal focus (2 patients: 1a, 2a) or to multiple foci (2 patients: 1b, 2b) of cortical dysplasia evidenced by ictal video-EEG monitoring and MRI. Patients gave their informed consent to participate in the study, which was approved by the local ethics committee. rTMS was performed biweekly for four consecutive weeks by means of a Cadwell high frequency magnetic stimulator with monophasic stimulus configuration (pulse width 200 μs). Each session consisted of 100 pulses at 0.5 Hz frequency delivered at 90 % of motor threshold through a water-cooled eightshaped coil positioned tangential to the scalp with the handle pointing backwards parallel to the midline. Locations for TM stimulation were determined according to 10–20 EEG coordinate system: over the EEG site of focal epileptic activity in patients with single focus and at Cz point (vertex) in patients with multifocal epilepsy. The average stimulus intensity (expressed as % of maximum stimulator output) was 65 ± 3.7 %. Patients tolerated rTMS treatment well and no adverse events were observed. They recorded every definite seizure or any seizure-like event from one month before to one month after the treatment. Patients were on antiepileptic polytherapy with each drug in its therapeutic range (the most effective combination of lamotrigine and sodium valproate in patients with single epileptic focus, and of phenobarbital, carbamazepine and clobazam in patients with multifocal epilepsy). During the study period medication was kept constant. The number of seizures during the month before stimulation (time I) was compared with that of the month during stimulation (time II) and after stimulation (time III). rTMS markedly reduced number and severity of seizures in patients with a single dysplasic focus. The improvement was predominantly in the disappearance of secondary generalization and was still persistent one month after the end of the treatment. The overall number of seizures at times I, II and III was respectively 19,13, and 12 for patient 1a and 19, 11 and 13 for patient 2a (see Fig. 1 A). By contrast, no changes in seizure frequency and severity were observed in patients with multiple foci (the overall number of seizures at times I, II and III was 33, 43, and 27 respectively for patient 1b and 39, 33 and 47 for patient 2b). Our results suggest that a longlasting depression of a cortical dysplasic area may improve intractable epilepsy. Focal phenomena of synaptic plasticity induced by lowfrequency rTMS at the site of stimulation might reduce hyperactivity of the affected hemisphere that would be part of the underlying physiology of the seizure. On such a basis the distance of epileptic foci from the site of stimulation (at the vertex) could explain the inefficacy of the treatment in patients with multifocal epilepsy. In this case it would have been more reasonable to use a non-focal round coil at the vertex to cause a widespread cortical stimulation, but the overheating with the long rTMS trains employed limited its use. On the other hand the effect observed in patients with single focus suggests the opportunity of serial administration of rTMS over each of the dysplasic foci in multifocal epilepsy. These data are preliminary and need to be confirmed by controlled studies with longer follow-up, in larger series of patients.

Magnetic stimulation study during observation of motor tasks

The aim of the study was to assess if the observation of single or more complex muscle movements activates the premotor cortex in man. We stimulated by transcranial magnetic stimulation the right and left motor cortex recording from the abductor pollicis brevis of eight normal subjects, during observation of different movements performed by the examiner: (1) single movements: thumb abduction, arm elevation; (2) motor sequences: finger opposing movements performed in an ordinate sequence: 1-2, 1-3, 1-4, 1-5, 1-2ellipsis, and in a non-consecutive non-repetitive order: 1-3, 1-5, 1-4, 1-2, 1-5, 1-2ellipsis We found an increased excitability of the right cortex during observation of isolated muscle movement regardless of which muscle is moved. At the stimulation of the left cortex, MEPs were significantly increased during observation of complex muscular synergies.

Hemispheric cerebellar rTMS to treat drug-resistant epilepsy: case reports.

Electrical stimulation of the cerebellar cortex by implanted electrodes has been shown to ameliorate refractory epilepsy. We investigated the potential therapeutic role of high-frequency cerebellar rTMS in patients affected by refractory epilepsy due to single or multiple foci. Six patients, three with single and three with multiple epileptic foci, underwent 20 rTMS sessions. Each session was given daily, excluding weekends, and consisted of two trains of 50 stimuli (5 Hz frequency and 90% motor threshold intensity), separated by 50s interval. rTMS was delivered through a focal coil (2 cm below and lateral to the inion) bilaterally in patients with multiple foci (two trains for hemisphere: 100 stimuli each side) and contralaterally to the epileptic focus in the others. Seizure frequency was monitored four weeks before stimulation (pre-rTMS), during the four-week treatment (rTMS) and four weeks after the treatment (post-rTMS). The rTMS over the cerebellar cortex was associated with a significant decrease of rTMS versus pre-rTMS seizure frequency both in patients with single and multiple epileptic foci. However, during the post-rTMS period seizure frequency was back to the pre-rTMS frequency. Although the results are still preliminary, they encourage further studies on larger series of patients. In particular, this rTMS approach, as compared with others, might be more useful in patients with multiple epileptic foci.