Trigeminal nerve stimulation modulates brainstem more than cortical excitability in healthy humans.

Multiple sites in the central nervous system (CNS) have been hypothesized to explain the beneficial effects of transcutaneous trigeminal nerve stimulation (TNS) on several disorders. This work investigated the acute effects of TNS on the excitability of brainstem and intracortical circuits, as well as on sensorimotor integration processes at cortical level in physiological conditions. Brainstem excitability was evaluated in seventeen healthy subjects measuring the R1 and R2 areas of the blink reflex (BR) and its recovery cycle, with cortical excitability and sensorimotor integration assessed by probing short-interval (SICI) and long-interval (LICI) intracortical inhibition, with short-interval (SICF), intracortical facilitation (ICF), short-latency (SAI) and long-latency (LAI) inhibition measuring motor potentials evoked in the first dorsal interosseous muscle by TMS of the contralateral motor cortex. Neurophysiological parameters were assessed, in seventeen healthy subjects, before and after cyclic 20-min TNS delivered bilaterally to the infraorbital nerve. After TNS, the area of the R2 was significantly reduced (p = 0.018). By contrast, R1 area and R2 recovery cycle were unaffected. Similarly, SICI, ICF, LICI, SICF, SAI and LAI appeared unaltered after TNS. These data suggest that, in normal subjects, TNS mainly acts on brainstem polysynaptic circuits mediating the R2 component of the BR and plays a minor role in modifying the activity of higher-level structures involved in the R2 recovery cycle and in modulation of cortical excitability. A further investigation of a chronic TNS-induced effect may disclose a higher potential for TNS in producing measurable after effects on its CNS targets.

Current Knowledge on the Preparation and Benefits of Cruciferous Vegetables as Relates to In Vitro, In Vivo, and Clinical Models of Inflammatory Bowel Disease.

Inflammatory bowel disease is a chronic condition with a significant economic and social burden. The disease is complex and challenging to treat because it involves several pathologies, such as inflammation, oxidative stress, dysbiosis, and intestinal damage. The search for an effective treatment has identified cruciferous vegetables and their phytochemicals as potential management options for inflammatory bowel disease because they contain prebiotics, probiotics, and anti-inflammatory and antioxidant metabolites essential for a healthy gut. This critical narrative style review provides a robust insight into the pharmacological effects and benefits of crucifers and their documented bioactive compounds in in vitro and in vivo models, as well as clinical inflammatory bowel disease. The review highlights the significant impact of crucifer preparation and the presence of glucosinolates, isothiocyanates, flavonoids, and polyphenolic compounds, which are essential for the anti-inflammatory and antioxidative benefits of cruciferous vegetables, as well as their ability to promote the healthy microbial community and maintain the intestinal barrier. This review may serve as a viable nutritional guide for future research on methods and features essential to developing experiments, preventions, and treatments for inflammatory bowel disease. There is limited clinical information and future research may utilize current innovative tools, such as metabolomics, for adequate knowledge and effective translation into clinical therapy.

Intracortical circuits, sensorimotor integration and plasticity in human motor cortical projections to muscles of the lower face.

Previous studies of the cortical control of human facial muscles documented the distribution of corticobulbar projections and the presence of intracortical inhibitory and facilitatory mechanisms. Yet surprisingly, given the importance and precision in control of facial expression, there have been no studies of the afferent modulation of corticobulbar excitability or of the plasticity of synaptic connections in the facial primary motor cortex (face M1). In 25 healthy volunteers, we used standard single- and paired-pulse transcranial magnetic stimulation (TMS) methods to probe motor-evoked potentials (MEPs), short-intracortical inhibition, intracortical facilitation, short-afferent and long-afferent inhibition and paired associative stimulation in relaxed and active depressor anguli oris muscles. Single-pulse TMS evoked bilateral MEPs at rest and during activity that were larger in contralateral muscles, confirming that corticobulbar projection to lower facial muscles is bilateral and asymmetric, with contralateral predominance. Both short-intracortical inhibition and intracortical facilitation were present bilaterally in resting and active conditions. Electrical stimulation of the facial nerve paired with a TMS pulse 5-200 ms later showed no short-afferent inhibition, but long-afferent inhibition was present. Paired associative stimulation tested with an electrical stimulation-TMS interval of 20 ms significantly facilitated MEPs for up to 30 min. The long-term potentiation, evoked for the first time in face M1, demonstrates that excitability of the facial motor cortex is prone to plastic changes after paired associative stimulation. Evaluation of intracortical circuits in both relaxed and active lower facial muscles as well as of plasticity in the facial motor cortex may provide further physiological insight into pathologies affecting the facial motor system.

Nutrient Intake in Children 4-13 Years Old in Ibadan, Nigeria.

The paucity of adequate data on dietary and nutrient intakes of school-age children is a barrier to addressing malnutrition and associated risks in Nigeria. This study included 955 children aged 4-13 years from Ibadan, Nigeria, using a stratified random sampling design. Information on family socio-demographic characteristics was reported, and child anthropometrics were measured. Dietary intake data were collected using a multi-pass 24 h dietary recall method; 20% of subjects completed a second 24 h recall to estimate usual nutrient intakes. Means and distributions of usual intakes of energy and nutrients as well as prevalence of inadequacy were estimated. Usual energy intake (kcal/day) was 1345 and 1590 for younger (4-8 years) and older (9-13 years) age groups, respectively. The macronutrient intakes of most children did not conform to Adequate Macronutrient Distribution Ranges (AMDRs), which were characterized by a higher proportion of energy from carbohydrates and lower proportion from total fats. Protein intake was largely within the AMDR. Compared to recommendations, over 60% of 4-8-year-old children had inadequate intakes of calcium, copper, iron, folate, and vitamins A, D, and E. There were more micronutrient inadequacies in the older children. This study identifies nutrition gaps and suggests future research and education to improve child nutrition in Nigeria.

Paired neurophysiological and clinical study of the brainstem at different stages of Parkinson's Disease.

OBJECTIVE: To study brainstem function in Parkinson's Disease (PD) at different stages, through a battery of vestibular-evoked myogenic potentials (VEMPs) and compare the results with scores on clinical scales assessing the presence of symptoms linked to brainstem involvement. METHODS: Cervical, masseter and ocular VEMPs were recorded in patients with early PD (n=14, disease duration 1.42±0.7years), advanced PD (n=19, disease duration 7.26±2.9years) and in 27 age-matched controls. In PD, the following clinical scales were administered: Mini-BESTest, REM sleep Behavior Disorder Screening Questionnaire (RBD-SQ), PD Sleep Scale, Epworth Sleepiness Scale and Geriatric Depression Scale. RESULTS: Rate of VEMPs alterations was higher (p<0.001) in PD than controls, but similar within PD groups. However, early and advanced PD showed a different pattern of abnormalities (p=0.02), being latency delay prevalent in the former and absence in the latter. VEMP impairment correlated directly with RBD-SQ scores in both PD cohorts and inversely with Mini-BESTest scores in advanced PD. CONCLUSIONS: VEMPs displayed progressive severity of alterations at different stages of PD, with remarkable correlations with presence of postural instability and RBD. SIGNIFICANCE: The combined use of VEMPs may provide interesting insights into the pathophysiological mechanisms of PD at the earliest and prodromal stage of the disease.

Modulation of rat medial vestibular nucleus neurone activity by vasopressin and noradrenaline in vitro.

In the present study, we examined the effects of bath application of vasopressin and noradrenaline on the spontaneous tonic discharge of medial vestibular nucleus (MVN) neurones and investigated if there is an interaction between the two drugs in an in vitro slice preparation of the rat brainstem containing the MVN. The results showed that vasopressin did not affect the spontaneous discharge rate of MVN neurones when applied either as a 60 s pulse or when the drug continuously perfused the slice for a period of 10 min. In contrast, noradrenaline affected the spontaneous discharge rate of the majority of cells tested (53/60, 88%). Noradrenaline excited the majority (46/53, 87%) of MVN neurones through both alpha1 and beta noradrenergic receptor-linked mechanisms. The remaining cells (7/53, 13%) were inhibited by noradrenaline through an alpha2 noradrenergic receptor-linked mechanism. Neither the excitatory nor inhibitory effects of noradrenaline were modified by vasopressin when the two drugs were applied together.

Involvement of the inferior olivary neurons in vestibular compensation.

Vestibular decompensation induced by spinal cord transection in left labyrinthectomized guinea pigs provoked asymmetrical excitability of the inferior olivary nuclei. In the right nucleus, spinal deafferentation induced a significantly increased response to electrical stimulation of the contralateral radial nerve and decreased response to ipsilateral radial nerve stimulation. In the left nucleus, opposite results were obtained. Increased responses were recorded in the I.O. neurons during electrical stimulation of the radial nerve ipsilateral to a previous hemilabyrinthectomy, and reduced responses during the electrical stimulation of the radial nerve of the opposite side. Since the inferior olive impinges on the vestibular nuclei both directly and indirectly through the cerebellar loop, it is possible that the inferior olive is involved in the spinal compensation of the vestibular deficits resulting from the hemilabyrinthectomy.

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.

Analysis of central cardioarrhythmogenic triggers in experimental epilepsy.

The cardioarrhythmogenic potential of epileptic foci induced at mesencephalic and rhombencephalic levels was analyzed in hemispherectomized rats. Topical application of penicillin-G onto the mesencephalic quadrigeminal lamina or onto the fourth ventricle induced paroxysmal activity at the mesencephalic or bulbar neurone level. At the mesencephalic levels, the paroxysmal activity was characterized by a significant increase in the spontaneous frequency of the neurones, with the appearance of multiunit activity and rhythmical outbursts. The simultaneous recording of myocardial electrical activity and blood pressure showed that the paroxysmal activity triggered short-latency sinus bradyarrhythmias with wandering of the sinus pacemaker, the appearance of biphasic or negative P waves, some premature ventricular contractions and non-significant reduction of systolic and diastolic pressures. When the paroxysmal activity stopped, the cardiac rhythm and blood pressure returned to basal values. At the bulbar level, the paroxysmal activity appeared with longer latency and usually the rhythmical outbursts were not observed. Following bulbar paroxysmal activity only short-lasting episodes of sinus bradyarrhythmias appeared. Midcollicular transection eliminated paroxysmal activity at the bulbar level, and blood pressure and cardiac rhythm resumed basal values. After transection, an additional application of convulsant drug (penicillin-G or pentylenetetrazole) onto the fourth ventricle did not induce the reappearance of paroxysmal activity and the consequent cardiovascular alterations. The results showed the existence of a cardioarrhythmogenic trigger localized at the mesencephalic level which spreads paroxysmal activity upwards. A hypothesis to explain the appearance of fetal haemodynamic modifications and life-threatening arrhythmias has been proposed.

Hypoglossal responses to macular stimulation in the rabbit.

This paper describes preliminary work on the role of the vestibular system in the hypoglossal neurons modulation. Natural stimulation of the otolith organ showed that hypoglossal motoneurons are responsive to gravity stimulation. The spontaneous firing rate of single cells, antidromically identified, was significantly modified during ipsi- or contralateral static tilting of the whole animal. Several response patterns were observed. These results infer that vestibular macular receptors may modulate hypoglossal nucleus activity in response to static head displacement.

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.

Relationship between cerebral nystagmogenic area and spinal cord.

The effect of section of the spinal cord upon the cerebral nystagmogenic area was investigated in rabbits. Cervical transection was found to result in an increase of excitability of such area, which is demonstrated by lowering of the threshold for cerebral eye nystagmus, whereas dorsal spinal transection does not affect the cerebral nystagmogenic area. Moreover, it was found that stimulation of the proximal stump of the spinal cord, at level of the dorsal quadrants, depresses the excitability of the cerebral nystagmogenic area, while ventral quadrants stimulation has a facilitating effect on the CNA. Modification of the excitability of the cerebral nystagmogenic area was also studied recording NPPs (Non-Primary Potentials) and unitary responses to photic stimulation prior to and after cervical transection as well as following dorsal and ventral quadrants stimulation. The Authors suggest that since the nystagmogenic area is located in the perivisual fields it receives visual and sensitive afferent impulses from the upper part of the body and it, in turn, projects onto the oculomotor nuclei, so that it could be considered as an integrator center for extrinsic musculature of the eye.

Penicillin-induced paroxysmal activity in brainstem neurons.

The spontaneous electrical activity of single mesencephalic and bulbar neurons was recorded in hemispherectomized rats, following topical application of the GABA-antagonist penicillin-G on the mesencephalon or on the rhombencephalon, to investigate whether these structures could develop a specific penicillin paroxysmal activity independently of the upper structures. Twenty minutes following penicillin-G, the mesencephalic neurons developed paroxysmal activity characterized by a significant increase in the spontaneous electrical activity, the appearance of multiunit activity and, frequently, phasic activity with rhythmical outbursts. The paroxysmal activity at bulbar level appeared later than that observed in the mesencephalon and was characterized by a significant increase of the spontaneous firing rate of the neurons, single short bursts and sometimes rhythmical outbursts. The bulbar outbursts always discharged at lower frequency than those at the mesencephalic level. Following a midcollicular transection the paroxysmal bulbar activity abruptly disappeared. This phenomenon might be explained by a loss of facilitation from superior structures on the bulbar neurons which in roditors show a poor GABA-receptor distribution. In other words, penicillin alone, due to the scarcity of GABA receptors, might not be sufficient to induce paroxysmal activity in bulbar neurons but the simultaneous presence of both the superior facilitation and the drug might enhance neuronal excitability to a critical level. However, the diffusion of the drug upwards to the mesencephalon, with consequent activation of a system allowing the downward propagation of paroxysmal activity, cannot be excluded. In conclusion, while the mesencephalic neurons demonstrate a proper ability to develop penicillin paroxysmal discharge, the bulbar neurons must be sustained by intact connections with upper structures to be able to do so.

Inner ear pressure changes modify ADH secretion in freely moving guinea pig.

The present study was designed to elucidate the relationship between endolymphatic pressure and plasma ADH levels in conscious guinea pigs. Plasma ADH (pADH) was measured in basal conditions and after having applied positive or negative pressure of 20 cmH2O to the inner ear. The experimental protocol was designed to avoid any interference on ADH release caused by anesthesia and surgical stress. There was no change in blood pressure, heart rate, plasma Na (pNa) and osmolality (pOsm) after inner ear pressure (IEP) modifications. However, pADH was inversely related with IEP: pADH averaged 31.4 +/- 7.0 pg/ml (mean +/- S.D.) in basal conditions, rising to 48.8 +/- 19.3 when IEP was lowered and falling to 16.6 +/- 10.3 when IEP was raised. These results confirm that structures in the inner ear help control of ADH release.

Convergence of central and peripheral signals on vestibular cells.

Nerve and cortical input convergence patterns, representing the fore- and hindlimb, were studied in single cells located in the lateral vestibular nucleus of the cat. Deitersian cells responded with excitation to cortical stimulation with a latency ranging from 4 to 14 msec, while responses ranged from 9 to 12 msec to radial nerve stimulation and from 14 to 18 msec to sciatic nerve stimulation. Lateral vestibular nuclear neurons responding to radial nerve stimulation also receive the main cortical input from the sensorimotor cortical area concerned with the forelimb. Neurons responding to sciatic nerve stimulation receive an equal cortical input from both fore- and hindlimb areas of the sensorimotor cortex. In a few cells different combinations of convergence of cortical and peripheral inputs were also observed.

The vestibular system modulates masseter muscle activity.

The aim of this study was to investigate whether, and in what way, the vestibular input may influence the activity of the masseter muscles. The variations in the spontaneous electrical activity and the evoked responses in the masseter motor units to natural or electrical activation of the vestibular afferents were recorded in anesthetized guinea pigs. The effects of a unilateral lesion of the labyrinth on the firing rate of the masseter motor units were also studied. Results show that: 1) vestibular input elicited an excitatory tonic control on masseter muscle activity; 2) a faster labyrinthine control is driven to the contralateral than the homolateral masseter muscles; 3) vestibular macular input does exert an asymmetrical control on masseteric muscles of both sides, in relation to the head displacement in space. The latencies of responses recorded from the masseter motor units suggest that polysynaptic pathways are involved in connecting the vestibular system to the trigeminal complex. The possible anatomical substrates for this vestibulomasseteric reflex are discussed.

Vestibular and somatosensory afferents modulate masseter muscle activity.

The aim of the research was to investigate whether somatosensory impulses starting from the forelimbs could modulate masseter muscle activity in anesthetized guinea pigs. The effect of interactions between radial nerve and vestibular stimulations on the masseter motor unit responses was also studied. Results show that electrical stimulation of both radial nerves induces responses in the masseter motor units most frequently characterized by excitation at latency ranging from 14 to 29 ms. The radial nerve responses were strongly reduced by conditioning electrical stimulation of the vestibular ampullar receptors. Similarly, the vestibular responses were reduced by conditioning radial nerve stimulation. The natural activation of the vestibular macular receptors can either decrease or increase the masseter motor unit responses evoked by electrical stimulation of the radial nerve. These complex inhibitory-excitatory interactions between the two sensory inputs could control the masseter postural tone in relation to the head and limb positions in space.

Responses of hypoglossal motoneurons to mechanical stimulation of the teeth in rats.

Reflex discharges were evoked in the XIIth nerve single fibers and in the genioglossal muscle following mechanical stimulation of the homolateral incisor tooth in rats. The tooth mechanoreceptors affected the firing rate of 70% of the tested motoneurons mainly localized in the ventral region of the hypoglossal nucleus. Different types of response in relation to stimulus direction were recorded. Type A responded with excitation to labio-lingual and with inhibition to linguo-labial stimulus direction. Opposite effects were observed in type B motoneurons. However, these neurons did not respond to mechanical stimuli applied in medio-distal or disto-medial directions. Type C showed excitatory or inhibitory responses to mechanical stimulation in all directions. Type D only responded to one direction of stimulation. The stimulus was often able to excite motoneurons previously silent (type E). Some motoneurons showed complex responses to one stimulus direction. The results demonstrate that stimulation of the periodontal mechanoreceptors can evoke hypoglossal responses probably aimed at controlling tongue position in the mouth during mastication.

Vestibular nuclei of hemilabyrinthectomized guinea pigs during decompensation.

1. The effects of the post-brachial section of the spinal cord on the field potentials recorded from the vestibular nuclei during stimulation of the right vestibular receptors have been studied in left hemilabyrinthectomized and then compensated guinea pigs. 2. Facilitation of the field potentials in the right vestibular nuclear complex and inhibition in the left nuclei have been observed. 3. These results confirm that the spinal cord is involved in the compensation of the release syndrome brought about by the lesion of one labyrinth. 4. The possible mechanisms underlying such a compensation are discussed.

Distribution of visual input to the vestibular nuclei.

The electrical activity of individual vestibular nuclear neurons was recorded in anesthetized and paralyzed cats and their responses to photic stimulation of the retina were studied. The visual input produced various types of unit responses. The cells of the superior vestibular nucleus showed a predominant excitatory response, the neurons of the medial vestibular nucleus displayed different combinations of excitatory and inhibitory effects, while those of the descending vestibular nucleus responded with excitation followed by inhibition. Photic stimulation of the retina elicited responses of vestibular nuclei with different latencies. The superior and medial vestibular nuclei showed shorter latencies. It is concluded tht the visual input may reach the vestibular complex thus participating in the reflex control of the ocular motoneurons.