E. Tolu

Effects of volitional contraction on intracortical inhibition and facilitation in the human motor cortex

Short‐interval intracortical inhibition (SICI), intracortical facilitation (ICF) and short‐interval intracortical facilitation (SICF) were assessed in the cortical motor area of the first dorsal interosseous muscle (FDI) of 16 healthy subjects. Paired‐pulse TMS was delivered to the left hemisphere at the following interstimulus intervals (ISIs): 2 and 3 ms for SICI, 10 and 15 ms for ICF and 1–5 ms for SICF. Motor‐evoked potentials were recorded from the resting and active right FDI. The effects exerted on SICI and ICF by four intensities (60–90% of active motor threshold, AMT) of the conditioning stimulus (S1) and by three levels of muscle contraction (10%, 25%, 50% of maximal voluntary contraction, MVC) were evaluated. The effects exerted on SICF were evaluated with two intensities (90% and 70% of AMT) of the test stimulus (S2) and with the same levels of muscle contraction. Results showed that: (i) during 10% MVC, maximum SICI was observed with S1 = 70% AMT; (ii) the amount of SICI obtained with S1 = 70% AMT was the same at rest as during 10% MVC, but decreased at higher contraction levels; (iii) ICF was observed only at rest with S1 = 90% AMT; (iv) SICF was facilitated at 10% and 25% MVC, but not at 50% MVC. We conclude that during muscle activation, intracortical excitability reflects a balance between activation of SICI and SICF systems. Part of the reduction in SICI during contraction is due to superimposed recruitment of SICF. Low intensity (70% AMT) conditioning stimuli can test SICI independently of effects on SICF at low contraction levels.

Neurogenic myocardial arrhythmias in experimental focal epilepsy

Summary: The potential for cardiac arrhythmia was studied in an experimental focal epilepsy induced in hemispherectomized rats by topical application of buffered penicillin G onto the thalamus. The epileptic burst triggered cardiac and hemodynamic responses, as simultaneously monitored by arterial pressure, and hypothalamic and heart activity. During interictal epileptic activity, the single burst triggered a short‐latency cardiac arrhythmia, characterized by sinus bradyarrhythmia and junctional rhythm, and lengthening of intervals between sphygmic waves with significant reduction of diastolic pressure. When the epileptic burst stopped, the cardiac activity resumed normal rhythm, and diastolic pressure returned to basal value. During ictal epileptic activity, the sinus and junctional bradyarrhythmic episodes lasted longer, and supraventricular extrasystoles, sinus arrest, and bigeminal ventricular extrasystoles were observed. Both systolic and diastolic pressures decreased from 120/85 to 100/65 mm Hg. The end of the ictal episode always marked resumption of normal cardiac rhythm and systemic pressure. Considering the absence of metabolic complications (blood‐gas analytic parameters and acid‐base balance being controlled) and the short latency of the cardiac and hemodynamic responses, it is suggested that during paroxysmal hypothalamic activity the observed cardiac arrhythmias and the hemodynamic modifications were neurogenic in origin. A role for cardiovascular alterations in sudden unexplained epileptic death is postulated.

A short latency vestibulomasseteric reflex evoked by electrical stimulation over the mastoid in healthy humans

We describe EMG responses recorded in active masseter muscles following unilateral and bilateral electrical vestibular stimulation (EVS, current pulses of 5 mA intensity, 2 ms duration, 3 Hz frequency). Averaged responses in unrectified masseter EMG induced by unilateral EVS were examined in 16 healthy subjects; effects induced by bilateral (transmastoid) stimulation were studied in 10 subjects. Results showed that unilateral as well as bilateral EVS induces bilaterally a clear biphasic response (onset latency ranging from 7.2 to 8.8 ms), that is of equal amplitude and latency contra‐ and ipsilateral to the stimulation site. In all subjects, unilateral cathodal stimulation induced a positive—negative response termed p11/n15 according to its mean peak latency; the anodal stimulation induced a response of opposite polarity (n11/p15) in 11/16 subjects. Cathodal responses were significantly larger than anodal responses. Bilateral stimulation induced a p11/n15 response significantly larger than that induced by the unilateral cathodal stimulation. Recordings from single motor units showed that responses to cathodal stimulation corresponded to a brief (2–4 ms) silent period in motor unit discharge rate. The magnitude of EVS‐induced masseter response was linearly related to current intensity and scaled with the mean level of EMG activity. The size of the p11/n15 response was asymmetrically modulated when subjects were tilted on both sides; in contrast head rotation did not exert any influence. Control experiments excluded a possible role of cutaneous receptors in generating the masseter response. We conclude that transmastoid electrical stimulation evokes vestibulomasseteric reflexes in healthy humans at latencies consistent with a di‐trisynaptic pathway.

Intracortical modulation of cortical-bulbar responses for the masseter muscle

Short interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were evaluated in the masseter muscles of 12 subjects and the cortical silent period (SP) in nine subjects. Motor evoked potentials (MEPs) were recorded from contralateral (cMM) and ipsilateral (iMM) masseters, activated at 10% of maximal voluntary contraction (MVC). Interstimulus intervals (ISIs) were 2 and 3 ms for SICI, 10 and 15 ms for ICF. TMS of the left masseteric cortex induced MEPs that were larger in the cMM than the iMM; stimulation of right masseteric cortex produced a similar asymmetry in response amplitude. SICI was only observed using a CS intensity of 70% AMT and was equal in both cMM and iMM. SICI was stronger at higher TS intensities, was abolished by muscle activation greater than 10% MVC, and was unaffected by coil orientation changes. Control experiments confirmed that SICI was not contaminated by any inhibitory peripheral reflexes. However, ICF could not be obtained because it was masked by bilateral reflex depression of masseter EMG caused by auditory input from the coil discharge. The SP was bilateral and symmetric; its duration ranged from 35 to 70 ms depending on TS intensity and coil orientation. We conclude that SICI is present in the cortical representation of masseter muscles. The similarity of SICI in cMM and iMM suggests either that a single pool of inhibitory interneurons controls ipsi‐ and contralateral corticotrigeminal projections or that inhibition is directed to bilaterally projecting corticotrigeminal fibres. Finally, the corticotrigeminal projection seems to be weakly influenced by inhibitory interneurons mediating the cortical SP.

Vestibular units during decompensation

Typical modifications of the unitary discharge of vestibular units have been recorded following the transection of the spinal cord of hemilabyrinthectomized and compensated guinea-pigs. These results support the concept that the spinal cord is essential in the compensation of the symptoms resulting from a lesion of one labyrinth.

Vestibular ampullar modulation of hypoglossal neurons

This paper describes preliminary observations on vestibular ampullar involvement in the control mechanism of the hypoglossal nucleus activity. Thermic stimulation of the labyrinth, performed by irrigating the external auditory meatus with cold water (20 degrees C), significantly modified the spontaneous electrical activity of hypoglossal neurons localized in the medio-caudal part of the nucleus. Tonic spontaneous discharge of the units following labyrinthine stimulation was modified into a phasic activity and bursts with multi-unit recruitment appeared. This modified activity was observed during 5-6 minutes after the onset of ear irrigation. Similar response patterns, but with shorter duration, were recorded following contralateral stimulation of the labyrinth. These results show that hypoglossal neurons are triggered by the vestibular system following dynamic conditions in response to every spatial head displacement.

Nitric oxide increases the spontaneous firing rate of rat medial vestibular nucleus neurons in vitro via a cyclic GMP‐mediated PKG‐independent mechanism

The effects of nitric oxide (NO) on the discharge rate of medial vestibular nucleus neurons (MVNn) were investigated in rat brainstem slices. The NO‐donor sodium nitroprusside (SNP, 200 µm) caused a marked enhancement (+36.7%) of MVNn spontaneous firing rate, which was prevented by the NO‐scavenger, carboxy‐PTIO (300 µm). The SNP effects were not modified (+37.4%) by synaptic uncoupling, suggesting that NO influences intrinsic membrane properties of MVNn rather than the synaptic input they receive. The excitatory action of SNP was virtually abolished by slice pretreatment with the soluble guanylyl cyclase inhibitor, ODQ (10 µm), and it was mimicked (+33.1%) by the cGMP analogue 8‐Br‐cGMP (400 µm). Protein kinase G (PKG) and cAMP/protein kinase A (PKA) were both excluded as downstream effectors of the NO/cGMP‐induced excitation. However, the cyclic nucleotide‐gated (CNG) channel blockers, l‐cis‐diltiazem (LCD, 100 µm) and Sp‐8‐Br‐PET‐cGMPS (100 µm), significantly reduced the firing rate increase produced by 8‐Br‐cGMP. Moreover, LCD alone decreased spontaneous MVNn firing (−19.7%), suggesting that putative CNG channels may contribute to the tonic control of resting MVNn discharge. 8‐Br‐cAMP (1 mm) also elicited excitatory effects in MVNn (+40.8%), which occluded those induced by 8‐Br‐cGMP, indicating that the two nucleotides share a common target. Finally, nested‐polymerase chain reaction assay revealed the expression of CNG channel α subunit transcript in MVNn. Our data provide the first demonstration that NO/cGMP signalling modulates MVNn spontaneous firing through a mechanism that is independent of PKG or PKA and probably involves activation of CNG channels.

Labyrinthine projection to the hypoglossal nucleus

Evoked potentials and responses of single hypoglossal neurons were recorded in response to electrical stimulation of the labyrinth. In addition, the spontaneous electrical activity of hypoglossal neurons was significantly modified in response to ipsi- and contralateral static tilt of the whole animal and thermic stimulation of the labyrinth. The experiment showed that the labyrinth modulates the electrical activity of hypoglossal neurons with phasic inputs in response to ampullar stimulation and with tonic inputs in response to macular stimulation. The vestibular phasic influence of hypoglossal neurons represents the most adequate functional pattern to obtain a quick, short lasting response of the tongue muscles instantly modifiable with every abrupt head displacement. On the contrary, the vestibular tonic influence of hypoglossal neurons represents the most adequate functional pattern to obtain not only adjustment but also maintenance of the muscular lingual response to static displacement of the head.

Improvement of Vestibular Plasticity in the Guinea Pig with a Calcium Entry Blocker

The influence of flunarizine on vestibular compensation was investigated in hemilabyrinthectomized guinea pigs. The results showed that the vestibular deficits from hemilabyrinthectomy disappeared more rapidly in the treated animals than in the controls. To elucidate the mechanism by which the drug could affect the compensatory process, further studies on the spontaneous and evoked activity of vestibular nuclei were performed in normal, labyrinthectomized and labyrinthectomized-cerebellectomized animals. These electrophysiological data implied that flunarizine improved the vestibular compensation by inhibiting the receptor and nuclear activities of the intact labyrinth. The drug excited the cerebellar cortex, which modulated the activity of the vestibular nuclei of both sides, restoring the balance disrupted by hemilabyrinthectomy.

Exploring brainstem function in multiple sclerosis by combining brainstem reflexes, evoked potentials, clinical and MRI investigations

OBJECTIVE To investigate vestibulo-masseteric (VMR), acoustic-masseteric (AMR), vestibulo-collic (VCR) and trigemino-collic (TCR) reflexes in patients with multiple sclerosis (MS); to relate abnormalities of brainstem reflexes (BSRs) to multimodal evoked potentials (EPs), clinical and Magnetic Resonance Imaging (MRI) findings. METHODS Click-evoked VMR, AMR and VCR were recorded from active masseter and sternocleidomastoid muscles, respectively; TCR was recorded from active sternocleidomastoid muscles, following electrical stimulation of the infraorbital nerve. EPs and MRI were performed with standard techniques. RESULTS Frequencies of abnormal BSRs were: VMR 62.1%, AMR 55.1%, VCR 25.9%, TCR 58.6%. Brainstem dysfunction was identified by these tests, combined into a four-reflex battery, in 86.9% of cases, by EPs in 82.7%, MRI in 71.7% and clinical examination in 37.7% of cases. The sensitivity of paired BSRs/EPs (93.3%) was significantly higher than combined MRI/clinical testing (70%) in patients with disease duration ⩽6.4years. BSR alterations significantly correlated with clinical, EP and MRI findings. CONCLUSIONS The four-BSR battery effectively increases the performance of standard EPs in early detection of brainstem impairment, otherwise undetected by clinical examination and neuroimaging. SIGNIFICANCE Multiple BSR assessment usefully supplements conventional testing and monitoring of brainstem function in MS, especially in newly diagnosed patients.