Modulation of corticospinal activity by strong emotions evoked by pictures and classical music: a transcranial magnetic stimulation study.

Using transcranial magnetic stimulation and skin conductance responses, we sought to clarify if, and to what extent, emotional experiences of different valences and intensity activate the hand-motor system and the associated corticospinal tract. For that purpose, we applied a newly developed method to evoke strong emotional experiences by the simultaneous presentation of musical and pictorial stimuli of congruent emotional valence. We uncovered enhanced motor-evoked potentials, irrespective of valence, during the simultaneous presentation of emotional music and picture stimuli (Combined conditions) compared with the single presentation of the two modalities (Picture/Music conditions). In contrast, vegetative arousal was enhanced during both the Combined and Music conditions, compared with the Picture conditions, again irrespective of emotional valence. These findings strongly indicate that arousal is a necessary, but not sufficient, prerequisite for triggering the motor system of the brain. We offer a potential explanation for this discrepant, but intriguing, finding in the paper.

APPLICATION OF THE BRAINSTEM EVOKED RESPONSE (BER) TO NEUROTOXICITY EVALUATION OF THE AUDITORY SYSTEM: ASSESSMENT OF INORGANIC LEAD-INDUCED OTOTOXICITY

An experimental procedure was developed using the Brainstem Evoked Response (BER) electrophysiological technique to assess the effect of neurotoxic substances on the auditory system. The procedure utilizes Sprague-Dawley albino rats who have had dural electrodes implanted in their skulls, allowing neuroelectric evoked potentials to be recorded from their brainstems. Latency and amplitude parameters derived from the evoked potentials help assess the neuroanatomical integrity of the auditory pathway in the brainstem. Moreover, since frequency-specific auditory stimuli are used to evoke the neural responses, additional audiometric information is obtainable. An investigation on non-exposed control animals shows the BER threshold curve obtained by tests at various frequencies very closely approximates that obtained by behavioral audibility tests. Thus, the BER appears to be a valid measure of both functional and neuroanatomical integrity of the afferent auditory neural pathway.^ To determine the usefulness of the BER technique in neurobehavioral toxicology research, a known neurotoxic agent, Pb, was studied. Female Sprague-Dawley rats were dosed for 45 days with low levels of Pb acetate in their drinking water, after which BER recordings were obtained. The Pb dosages were determined from the findings of an earlier pilot study. One group of 6 rats received normal tap water, one group of 7 rats received a solution of 0.1% Pb, and another group of 7 rats received a solution of 0.2% Pb. After 45 days, the three groups exhibited blood Pb levels of 4.5 (+OR-) 0.43 (mu)g/100 ml, 37.8 (+OR-) 4.8 (mu)g/100 ml and 47.3 (+OR-) 2.7 (mu)g/100 ml, respectively.^ The results of the BER recording indicated evoked response waveform latency abnormalities in both the Pb-treated groups when midrange frequency (8 kHz to 32 kHz) stimuli were used. For the most part, waveform amplitudes did not vary significantly from control values. BER recordings obtained after a 30-day recovery period indicated the effects seen in the 0.1% Pb group had disappeared. However, those anomalies exhibited by the 0.2% Pb group either remained or increased in number. This outcome indicates a longer lasting or possibly irreversible effect on the auditory system from the higher dose of Pb. The auditory pathway effect appears to be in the periphery, at the level of the cochlea or the auditory (VIII) nerve. The results of this research indicate the BER technique is a valuable and sensitive indicator of low-level toxic effects on the auditory system.^

Neural fate of seen and unseen faces in visuospatial neglect: A combined event-related functional MRI and event-related potential study

To compare neural activity produced by visual events that escape or reach conscious awareness, we used event-related MRI and evoked potentials in a patient who had neglect and extinction after focal right parietal damage, but intact visual fields. This neurological disorder entails a loss of awareness for stimuli in the field contralateral to a brain lesion when stimuli are simultaneously presented on the ipsilateral side, even though early visual areas may be intact, and single contralateral stimuli may still be perceived. Functional MRI and event-related potential study were performed during a task where faces or shapes appeared in the right, left, or both fields. Unilateral stimuli produced normal responses in V1 and extrastriate areas. In bilateral events, left faces that were not perceived still activated right V1 and inferior temporal cortex and evoked nonsignificantly reduced N1 potentials, with preserved face-specific negative potentials at 170 ms. When left faces were perceived, the same stimuli produced greater activity in a distributed network of areas including right V1 and cuneus, bilateral fusiform gyri, and left parietal cortex. Also, effective connectivity between visual, parietal, and frontal areas increased during perception of faces. These results suggest that activity can occur in V1 and ventral temporal cortex without awareness, whereas coupling with dorsal parietal and frontal areas may be critical for such activity to afford conscious perception.

Prenatal monocular enucleation induces a selective loss of low-spatial-frequency cortical responses to the remaining eye.

During early development, interactions between the two eyes are critical in the formation of eye-specific domains within the lateral geniculate nucleus and the visual cortex. When monocular enucleation is done early in prenatal life, it induces remarkable anatomical and functional reorganizations of the visual pathways. Behavioral data have shown a loss in sensitivity to low-spatial-frequency gratings in cats. To correlate the behavioral observations with a possible change in the analysis of contrast at the level of primary visual areas we recorded visual evoked potentials at the 17/18 border in two cats enucleated prenatally (gestational age at enucleation, 39-42 days), three neonatal, two control animals, and one animal with a surgical removal of Y-ganglion fibers. Our results show a strong attenuation in the amplitude of response at all contrast values for gratings of low spatial frequency in prenatally enucleated cats, whereas neonatally enucleated and control animals present responses of comparable amplitude. We conclude that the behavioral results reflect the reduced sensitivity for low frequencies of visual cortical neurons. In addition, we define a critical period for the development of the contrast-sensitivity function that seems to be limited to the prenatal gestation period. We suggest that the prenatal interruption of binocular interactions leads to a functional elimination of the Y-ganglion system.

Visual function studies during exposure to a mixture of diabasic esters (DBE) in Long-Evans rats : cooperative research and development agreement with E.I. Du Pont de Nemours & Company.

Mode of access: Internet.

The topographic distribution of the magnetic P100M to full- and half-field stimulation

Visual evoked magnetic responses were recorded to full-field and left and right half-field stimulation with three check sizes (70′, 34′ and 22′) in five normal subjects. Recordings were made sequentially on a 20-position grid (4 × 5) based on the inion, by means of a single-channel direct current-Superconducting Quantum Interference Device second-order gradiometer. The topographic maps were consistent on the same subjects recorded 2 months apart. The half-field responses produced the strongest signals in the contralateral hemisphere and were consistent with the cruciform model of the calcarine fissure. Right half fields produced upper-left-quadrant outgoing fields and lower-left-quadrant ingoing fields, while the left half field produced the opposite response. The topographic maps also varied with check size, with the larger checks producing positive or negative maximum position more anteriorly than small checks. In addition, with large checks the full-field responses could be explained as the summation of the two half fields, whereas full-field responses to smaller checks were more unpredictable and may be due to sources located at the occipital pole or lateral surface. In addition, dipole sources were located as appropriate with the use of inverse problem solutions. Topographic data will be vital to the clinical use of the visual evoked field but, in addition, provides complementary information to visual evoked potentials, allowing detailed studies of the visual cortex. © 1992 Kluwer Academic Publishers.

Real-time imaging of human cortical activity evoked by painful esophageal stimulation

Background & Aims: Current models of visceral pain processing derived from metabolic brain imaging techniques fail to differentiate between exogenous (stimulus-dependent) and endogenous (non-stimulus-specific) neural activity. The aim of this study was to determine the spatiotemporal correlates of exogenous neural activity evoked by painful esophageal stimulation. Methods: In 16 healthy subjects (8 men; mean age, 30.2 ± 2.2 years), we recorded magnetoencephalographic responses to 2 runs of 50 painful esophageal electrical stimuli originating from 8 brain subregions. Subsequently, 11 subjects (6 men; mean age, 31.2 ± 1.8 years) had esophageal cortical evoked potentials recorded on a separate occasion by using similar experimental parameters. Results: Earliest cortical activity (P1) was recorded in parallel in the primary/secondary somatosensory cortex and posterior insula (∼85 ms). Significantly later activity was seen in the anterior insula (∼103 ms) and cingulate cortex (∼106 ms; P = .0001). There was no difference between the P1 latency for magnetoencephalography and cortical evoked potential (P = .16); however, neural activity recorded with cortical evoked potential was longer than with magnetoencephalography (P = .001). No sex differences were seen for psychophysical or neurophysiological measures. Conclusions: This study shows that exogenous cortical neural activity evoked by experimental esophageal pain is processed simultaneously in somatosensory and posterior insula regions. Activity in the anterior insula and cingulate - brain regions that process the affective aspects of esophageal pain - occurs significantly later than in the somatosensory regions, and no sex differences were observed with this experimental paradigm. Cortical evoked potential reflects the summation of cortical activity from these brain regions and has sufficient temporal resolution to separate exogenous and endogenous neural activity. © 2005 by the American Gastroenterological Association.

Cortical processing of human gut sensation: an evoked potential study

The rectum has a unique physiological role as a sensory organ and differs in its afferent innervation from other gut organs that do not normally mediate conscious sensation. We compared the central processing of human esophageal, duodenal, and rectal sensation using cortical evoked potentials (CEP) in 10 healthy volunteers (age range 21-34 yr). Esophageal and duodenal CEP had similar morphology in all subjects, whereas rectal CEP had two different but reproducible morphologies. The rectal CEP latency to the first component P1 (69 ms) was shorter than both duodenal (123 ms; P = 0.008) and esophageal CEP latencies (106 ms; P = 0.004). The duodenal CEP amplitude of the P1-N1 component (5.0 µV) was smaller than that of the corresponding esophageal component (5.7 µV; P = 0.04) but similar to that of the corresponding rectal component (6.5 µV; P = 0.25). This suggests that rectal sensation is either mediated by faster-conducting afferent pathways or that there is a difference in the orientation or volume of cortical neurons representing the different gut organs. In conclusion, the physiological and anatomic differences between gut organs are reflected in differences in the characteristics of their afferent pathways and cortical processing.

Large diameter optic nerve axon fibres in Alzheimer's disease

A variety of visual symptoms have been associated with Alzheimer's disease (AD). These include delays in flash visual evoked potentials which indicate a disruption of the integrity of the visual pathway. Examination of the visual cortex has revealed the presence of both senile plaques and neurofibrillary tangles. The purpose of this study was to determine whether there were differences in the number and/or size of optic nerve axons between AD patients and non-demented age-matched controls. Five optic nerves from AD patients and five from age-matched controls were embedded in epon resin and 1 micron sections prepared on a Reichert ultramicrotome. The sections were then stained in toluidine blue and examined at x400 magnification. The numbers of axons were counted in photographs of three fields taken at random from each section. To evaluate the axon diameters, 70 axons were chosen at random from each patient and measured using a calibrated eyepiece graticule. The total axon counts revealed no significant differences between the AD optic nerves and the age-matched controls. However, the frequency distribution of axon diameters was significantly different in the two groups. In particular, there were fewer larger diameter axons in patients with AD as previously reported. Degeneration of the large diameter axons suggests involvement of the magnocellular as opposed to the parvocellular pathways. Hence, there could be differences in visual performance of AD patients compared with normals which could be important in clinical diagnosis.

Alzheimer’s disease and the eye

Dementia, including Alzheimer’s disease (AD), is a major disorder causing visual problems in the elderly population. The pathology of AD includes the deposition in the brain of abnormal aggregates of ß-amyloid (Aß) in the form of senile plaques (SP) and abnormally phosphorylated tau in the form of neurofibrillary tangles (NFT). A variety of visual problems have been reported in patients with AD including loss of visual acuity (VA), colour vision and visual fields; changes in pupillary response to mydriatics, defects in fixation and in smooth and saccadic eye movements; changes in contrast sensitivity and in visual evoked potentials (VEP); and disturbances of complex visual functions such as reading, visuospatial function, and in the naming and identification of objects. Many of these changes are controversial with conflicting data in the literature and no ocular or visual feature can be regarded as particularly diagnostic of AD. In addition, some pathological changes have been observed to affect the eye, visual pathway, and visual cortex in AD. The optometrist has a role in helping a patient with AD, if it is believed that signs and symptoms of the disease are present, so as to optimize visual function and improve the quality of life. (J Optom 2009;2:103-111 ©2009 Spanish Council of Optometry)

Migraine, A study of environmental and intrapersonal factors

A study was carried out of 45 migrainous patients with visually induced migraine (VIM), and 25 migrainous students, each having an age and sex matched control. The study utilised questionnaires, interviews, electroencephalography (EEG) and visual evoked potentials (VEP). The experimental work and analysis was carried out in the Neuropsychology Unit in collaboration with the Birmingham Migraine Clinic, over a period of five years. The study suggests: 1. The literature on a possible relationship between migraine and epilepsy hitherto published is unreliable (supporting evidence is given). 2. That a much greater precision is needed in defining migraine for research purposes. 3. A revised methodology for the selection of controls is needed and this is proposed. 4. That despite what are now seen to be superficial similarities, there are clear distinctions of a fundamental nature between photo-sensitive epilepsy (PSE) and VIM. 5. Caution be used when taking headache as a symptom, since many of the precipitants of migrainous headache can also precipitate non-migrainous headache (NMH). 6. The list of visual precipitants of migraine is expanded (particularly flicker and pattern). 7. That colour (principally red) is a previously unreported precipitant of migraine. 8. The extended range of responses to flicker (the 'H' response) has no significant difference in its frequency of occurrence in patients and normal controls, which contradicts previous literature. 9. The mechanisms thought to underlie migraine serve to explain previously unexplained EEG findings. 10. Further research is needed and proposed.

Marqueurs électrophysiologiques des dysfonctions attentionnelles et de leur récupération suite à un traumatisme craniocérébral léger

L’objectif principal de cette thèse était d’obtenir, via l’électrophysiologie cognitive, des indices de fonctionnement post-traumatisme craniocérébral léger (TCCL) pour différents niveaux de traitement de l’information, soit l’attention sélective, les processus décisionnels visuoattentionnels et les processus associés à l’exécution d’une réponse volontaire. L’hypothèse centrale était que les mécanismes de production des lésions de même que la pathophysiologie caractérisant le TCCL engendrent des dysfonctions visuoattentionnelles, du moins pendant la période aiguë suivant le TCCL (i.e. entre 1 et 3 mois post-accident), telles que mesurées à l’aide d’un nouveau paradigme électrophysiologique conçu à cet effet. Cette thèse présente deux articles qui décrivent le travail effectué afin de rencontrer ces objectifs et ainsi vérifier les hypothèses émises. Le premier article présente la démarche réalisée afin de créer une nouvelle tâche d’attention visuospatiale permettant d’obtenir les indices électrophysiologiques (amplitude, latence) et comportementaux (temps de réaction) liés aux processus de traitement visuel et attentionnel précoce (P1, N1, N2-nogo, P2, Ptc) à l’attention visuelle sélective (N2pc, SPCN) et aux processus décisionnels (P3b, P3a) chez un groupe de participants sains (i.e. sans atteinte neurologique). Le deuxième article présente l’étude des effets persistants d’un TCCL sur les fonctions visuoattentionelles via l’obtention des indices électrophysiologiques ciblés (amplitude, latence) et de données comportementales (temps de réaction à la tâche et résultats aux tests neuropsychologiques) chez deux cohortes d’individus TCCL symptomatiques, l’une en phase subaigüe (3 premiers mois post-accident), l’autre en phase chronique (6 mois à 1 an post-accident), en comparaison à un groupe de participants témoins sains. Les résultats des articles présentés dans cette thèse montrent qu’il a été possible de créer une tâche simple qui permet d’étudier de façon rapide et peu coûteuse les différents niveaux de traitement de l’information impliqués dans le déploiement de l’attention visuospatiale. Par la suite, l’utilisation de cette tâche auprès d’individus atteints d’un TCCL testés en phase sub-aiguë ou en phase chronique a permis d’objectiver des profils d’atteintes et de récupération différentiels pour chacune des composantes étudiées. En effet, alors que les composantes associées au traitement précoce de l’information visuelle (P1, N1, N2) étaient intactes, certaines composantes attentionnelles (P2) et cognitivo-attentionnelles (P3a, P3b) étaient altérées, suggérant une dysfonction au niveau des dynamiques spatio-temporelles de l’attention, de l’orientation de l’attention et de la mémoire de travail, à court et/ou à long terme après le TCCL, ceci en présence de déficits neuropsychologiques en phase subaiguë surtout et d’une symptomatologie post-TCCL persistante. Cette thèse souligne l’importance de développer des outils diagnostics sensibles et exhaustifs permettant d’objectiver les divers processus et sous-processus cognitifs susceptible d’être atteints après un TCCL.

Marqueurs électrophysiologiques des dysfonctions attentionnelles et de leur récupération suite à un traumatisme craniocérébral léger

L’objectif principal de cette thèse était d’obtenir, via l’électrophysiologie cognitive, des indices de fonctionnement post-traumatisme craniocérébral léger (TCCL) pour différents niveaux de traitement de l’information, soit l’attention sélective, les processus décisionnels visuoattentionnels et les processus associés à l’exécution d’une réponse volontaire. L’hypothèse centrale était que les mécanismes de production des lésions de même que la pathophysiologie caractérisant le TCCL engendrent des dysfonctions visuoattentionnelles, du moins pendant la période aiguë suivant le TCCL (i.e. entre 1 et 3 mois post-accident), telles que mesurées à l’aide d’un nouveau paradigme électrophysiologique conçu à cet effet. Cette thèse présente deux articles qui décrivent le travail effectué afin de rencontrer ces objectifs et ainsi vérifier les hypothèses émises. Le premier article présente la démarche réalisée afin de créer une nouvelle tâche d’attention visuospatiale permettant d’obtenir les indices électrophysiologiques (amplitude, latence) et comportementaux (temps de réaction) liés aux processus de traitement visuel et attentionnel précoce (P1, N1, N2-nogo, P2, Ptc) à l’attention visuelle sélective (N2pc, SPCN) et aux processus décisionnels (P3b, P3a) chez un groupe de participants sains (i.e. sans atteinte neurologique). Le deuxième article présente l’étude des effets persistants d’un TCCL sur les fonctions visuoattentionelles via l’obtention des indices électrophysiologiques ciblés (amplitude, latence) et de données comportementales (temps de réaction à la tâche et résultats aux tests neuropsychologiques) chez deux cohortes d’individus TCCL symptomatiques, l’une en phase subaigüe (3 premiers mois post-accident), l’autre en phase chronique (6 mois à 1 an post-accident), en comparaison à un groupe de participants témoins sains. Les résultats des articles présentés dans cette thèse montrent qu’il a été possible de créer une tâche simple qui permet d’étudier de façon rapide et peu coûteuse les différents niveaux de traitement de l’information impliqués dans le déploiement de l’attention visuospatiale. Par la suite, l’utilisation de cette tâche auprès d’individus atteints d’un TCCL testés en phase sub-aiguë ou en phase chronique a permis d’objectiver des profils d’atteintes et de récupération différentiels pour chacune des composantes étudiées. En effet, alors que les composantes associées au traitement précoce de l’information visuelle (P1, N1, N2) étaient intactes, certaines composantes attentionnelles (P2) et cognitivo-attentionnelles (P3a, P3b) étaient altérées, suggérant une dysfonction au niveau des dynamiques spatio-temporelles de l’attention, de l’orientation de l’attention et de la mémoire de travail, à court et/ou à long terme après le TCCL, ceci en présence de déficits neuropsychologiques en phase subaiguë surtout et d’une symptomatologie post-TCCL persistante. Cette thèse souligne l’importance de développer des outils diagnostics sensibles et exhaustifs permettant d’objectiver les divers processus et sous-processus cognitifs susceptible d’être atteints après un TCCL.

Oscillatory mechanisms of conscious perception and attention

Although the prominent role of neural oscillations in perception and cognition has been continuously investigated, some critical questions remain unanswered. My PhD thesis was aimed at addressing some of them. First, can we dissociate oscillatory underpinnings of perceptual accuracy and subjective awareness? Current work would strongly suggest that this dissociation can be drawn. While the fluctuations in alpha-amplitude decide perceptual bias and metacognitive abilities, the speed of alpha activity (i.e., alpha-frequency) dictates sensory sampling, shaping perceptual accuracy. Second, how are these oscillatory mechanisms integrated during attention? The obtained results indicate that a top-down visuospatial mechanism modulates neural assemblies in visual areas via oscillatory re-alignment and coherence in the alpha/beta range within the fronto-parietal brain network. These perceptual predictions are reflected in the retinotopically distributed posterior alpha-amplitude, while perceptual accuracy is explained by the higher alpha-frequency at the to-be-attended location. Finally, sensory input, elaborated via fast gamma oscillations, is linked to specific phases of this slower activity via oscillatory nesting, enabling integration of the feedback-modulated oscillatory activity with sensory information. Third, how can we relate this oscillatory activity to other neural markers of behaviour (i.e., event-related potentials)? The obtained results favour the oscillatory model of ERP genesis, where alpha-frequency shapes the latency of early evoked-potentials, namely P1, with both neural indices being related to perceptual accuracy. On the other hand, alpha-amplitude dictates the amplitude of later P3 evoked-response, whereas both indices shape subjective awareness. Crucially, by combining different methodological approaches, including neurostimulation (TMS) and neuroimaging (EEG), current work identified these oscillatory-behavior links as causal and not just as co-occurring events. Current work aimed at ameliorating the use of the TMS-EEG approach by explaining inter-individual differences in the stimulation outcomes, which could be proven crucial in the way we design entrainment experiments and interpret the results in both research and clinical settings.

Central and peripheral mediation of human force sensation following eccentric or concentric contractions

Fatigue was induced in the triceps brachii of the experimental arm by a regimen of either eccentric or concentric muscle actions. Estimates of force were assessed using a contralateral limb-matching procedure, in which target force levels (25 %, 50 % or 75 % of maximum) were defined by the unfatigued control arm. Maximum isometric force-generating capacity was reduced by 31 % immediately following eccentric contractions, and remained depressed at 24 (25 %) and 48 h (13 %) post-exercise. A less marked reduction (8.3 %) was observed immediately following concentric contractions. Those participants who performed prior eccentric contractions, consistently (at all force levels), and persistently (throughout the recovery period), overestimated the level of force applied by the experimental arm. In other words, they believed that they were generating more force than they actually achieved. When the forces applied by the experimental and the control arm, were each expressed as a proportion of the maximum force that could be attained at that time, the estimates matched extremely closely. This outcome is that which would be expected if the estimates of force were based on a sense of effort. Following eccentric exercise, the amplitude of the EMG activity recorded from the experimental arm was substantially greater than that recorded from the control arm. Cortically evoked potentials recorded from the triceps brachii (and extensor carpi radialis) of the experimental arm were also substantially larger than those elicited prior to exercise. The sense of effort was evidently not based upon a corollary of the central motor command. Rather, the relationship between the sense of effort and the motor command appears to have been altered as a result of the fatiguing eccentric contractions. It is proposed that the sense of effort is associated with activity in neural centres upstream of the motor cortex.