P. Schlindwein

Cortical representation of saccular vestibular stimulation: VEMPs in fMRI

Short tone bursts trigger a vestibular evoked myogenic potential (VEMP), an inhibitory potential which reflects a component of the vestibulocollic reflex (VCR). These potentials arise as a result of activation of the sacculus and are expressed through the vestibulo-collic reflex (VCR). Up to now, the ascending projections of the sacculus are unknown in humans, only the representation of the semicircular canals or the entire vestibular nerve has been demonstrated. The aim of this study was to determine whether a sacculus stimulus that evoked VEMPs could activate vestibular cortical areas in fMRI. To determine this, we studied the differential effects of unilateral VEMP stimulation in 21 healthy right-handers in a clinical 1.5 T scanner while wearing piezo electric headphones. A unilateral VEMP stimulus and two auditory control stimuli were given in randomized order over the stimulated ear. A random effects statistical analysis was done with SPM2 (p<0.05, corrected). After exclusion of the auditory effects, the major findings were as follows: (i) significant activations were located in the multisensory cortical vestibular network within both hemispheres, including the posterior insular cortex, the middle and superior temporal gyri, and the inferior parietal cortex. (ii) The activation pattern was elicited bilaterally with a predominance of the right hemisphere in right-handers. (iii) Saccular vestibular projection was predominantly ipsilateral, whereas (iv) pure acoustic stimuli were processed with a predominance of the respective contralateral and mainly in the left hemisphere. This is the first demonstration by means of fMRI of the cortical representation of the saccular input at cortical level. The activation pattern is similar to that known from the stimulation of the entire vestibular nerve or the horizontal semicircular canal. Our data give evidence of a task-dependent separation of the processing within the vestibular otolith and the auditory systems in the two hemispheres.

Metabolic changes in vestibular and visual cortices in acute vestibular neuritis

Five right‐handed patients with a right‐sided vestibular neuritis were examined twice with fluorodeoxyglucose positron emission tomography while lying supine with eyes closed: once during the acute stage (mean, 6.6 days) and then 3 months later when central vestibular compensation had occurred. Regional cerebral glucose metabolism (rCGM) was significantly increased (p < 0.001 uncorrected) during the acute stage in multisensory vestibular cortical and subcortical areas (parietoinsular vestibular cortex in the posterior insula, posterolateral thalamus, anterior cingulate gyrus [Brodmann area 32/24], pontomesencephalic brainstem, hippocampus). Simultaneously, there was a significant rCGM decrease in the visual (Brodmann area 17 to 19) and somatosensory cortex areas in the postcentral gyrus as well as in parts of the auditory cortex (transverse temporal gyrus). Fluorodeoxyglucose positron emission tomography thus allows imaging of the cortical activation pattern that is induced by unilateral peripheral vestibular loss. It was possible to demonstrate that the central vestibular system including the vestibular cortex exhibits a visual‐vestibular activation–deactivation pattern during the acute stage of vestibular neuritis similar to that in healthy volunteers during unilateral labyrinthine stimulation. Contrary to experimental vestibular stimulation, the activation of the vestibular cortex was not bilateral but was unilateral and contralateral to the right‐sided labyrinthine failure. Ann Neurol 2004

Neural correlates of hemispheric dominance and ipsilaterality within the vestibularsystem

Earlier functional imaging studies on the processing of vestibular information mainly focused on cortical activations due to stimulation of the horizontal semicircular canals in right-handers. Two factors were found to determine its processing in the temporo-parietal cortex: a dominance of the non-dominant hemisphere and an ipsilaterality of the neural pathways. In an investigation of the role of these factors in the vestibular otoliths, we used vestibular evoked myogenic potentials (VEMPs) in a fMRI study of monaural saccular-otolith stimulation. Our aim was to (1) analyze the hemispheric dominance for saccular-otolith information in healthy left-handers, (2) determine if there is a predominance of the ipsilateral saccular-otolith projection, and (3) evaluate the impact of both factors on the temporo-parieto-insular activation pattern. A block design with three stimulation and rest conditions was applied: (1) 102 dB-VEMP stimulation; (2) 65 dB-control-acoustic stimulation, (3) 102 dB-white-noise-control stimulation. After subtraction of acoustic side effects, bilateral activations were found in the posterior insula, the superior/middle/transverse temporal gyri, and the inferior parietal lobule. The distribution of the saccular-otolith activations was influenced by the two factors but with topographic disparity: whereas the inferior parts of the temporo-parietal cortex were mainly influenced by the ipsilaterality of the pathways, the upper parts reflected the dominance of the non-dominant hemisphere. This is in contrast to the processing of acoustic stimulation, which showed a predominance of the contralateral pathways. Our study proves the importance of the hemispheric preponderance also in left-handers, which is of relevance in the superior parts of the insula gyrus V, the inferior parietal lobule, and the superior temporal gyri.

Brainstem and cerebellar fMRI-activation during horizontal and vertical optokinetic stimulation.

Animal studies have shown that not only cortical, but also brainstem and cerebellar areas are involved in the initiation and generation of optokinetic nystagmus (OKN), e.g., cortico-(pretecto)pontine-olivo-cerebellar pathways. The aim of this fMRI study was to identify and differentiate brainstem and cerebellar areas involved in horizontal and vertical OKN (h/vOKN) in humans. In a group of nine healthy volunteers, hOKN and vOKN were statistically compared with a stationary control condition. There were common activated regions for hOKN and vOKN directions located in the transition zone between the posterior thalamus and the mesencephalon bilaterally covering the pretectal nucleus complex, which is known to be a major structure within the afferent branch of the optokinetic system. Furthermore, during hOKN, activation occurred bilaterally in the mediodorsal and dorsolateral ponto-medullary brainstem, which could be best attributed to the reticular formation, especially the paramedian pontine reticular formation (PPRF). For vOKN, additional activated areas in the dorsal mesencephalic brainstem could be best localized to the ocular motor nuclei and the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF). For both OKN directions, the cerebellar activation was localized in the oculomotor vermis (declive VI, folium and tuber VIIA/B, in part pyramis VIIIA), and the flocculus bilaterally as well as widespread in the cerebellar hemispheres. In conclusion, fMRI allowed first attributions of neuronal substrates in the cerebellum and brainstem to hOKN and vOKN in humans. Consistent with the animal data, the dorsal ponto-medullary routes were involved bilaterally for hOKN, whereas the rostral mesencephalic routes were involved for vOKN.

Direction-dependent visual cortex activation during horizontal optokinetic stimulation (fMRI study).

Looking at a moving pattern induces optokinetic nystagmus (OKN) and activates an assembly of cortical areas in the visual cortex, including lateral occipitotemporal (motion‐sensitive area MT/V5) and adjacent occipitoparietal areas as well as ocular motor areas such as the prefrontal cortex, frontal, supplementary, and parietal eye fields. The aim of this functional MRI (fMRI) study was to investigate (1) whether stimulus direction‐dependent effects can be found, especially in the cortical eye fields, and (2) whether there is a hemispheric dominance of ocular motor areas. In a group of 15 healthy subjects, OKN in rightward and leftward directions was visually elicited and statistically compared with the control condition (stationary target) and with each other. Direction‐dependent differences were not found in the cortical eye fields, but an asymmetry of activation occurred in paramedian visual cortex areas, and there were stronger activations in the hemisphere contralateral to the slow OKN phase (pursuit). This can be explained by a shift of the mean eye position of gaze (beating field) in the direction of the fast nystagmus phases of approximately 2.6 degrees, causing asymmetrical visual cortex stimulation. The absence of a significant difference in the activation pattern of the cortical eye fields supports the view that the processing of eye movements in both horizontal directions is mediated in the same cortical ocular motor areas. Furthermore, no hemispheric dominance for OKN processing was found in right‐handed volunteers. Hum Brain Mapp, 2005.

Functional imaging of sympathetic activation during mental stress

Activation of the sympathetic nervous system (SNS) is essential in adapting to environmental stressors and in maintaining homeostasis. This reaction can also turn into maladaptation, associated with a wide spectrum of stress-related diseases. Up to now, the cortical mechanisms of sympathetic activation in acute mental stress have not been sufficiently characterized. We therefore investigated cerebral activation applying functional magnetic resonance imaging (fMRI) during performance of a mental stress task with graded levels of difficulty, i.e. four versions of a Stroop task (Colour Word Interference Test, CWT) in healthy subjects. To analyze stress-associated sympathetic activation, skin conductance and heart rate were continuously recorded. The results show that sympathetic activation through mental stress is associated with distinct cerebral regions being immediately involved in task performance (visual, motor, and premotor areas). Other activated regions (right insula, dorsolateral superior frontal gyrus, cerebellar regions) are unrelated to task performance. These latter regions have previously been considered to be involved in mediating different stress responses. The results might furthermore serve as a basis for future investigations of the connection between these cortical regions in the generation of stress-related diseases.

Sympathetic activity at rest and motor brain areas: FDG-PET study

Although recent studies identified brain areas which are involved in short term activation of the sympathetic nervous system, little is known about brain mechanisms which generate the individual variability of basal autonomic activity. In this fluorodeoxyglucose positron emission tomography study (FDG-PET), we aimed to identify brain regions, which covary with function parameters of the autonomic nervous system at rest. Therefore, FDG-PET (Siemens, Germany) was performed twice in 14 healthy resting subjects (7 m, 7 f; mean age 29.5 years) while different parameters of autonomic function were assessed simultaneously: Blood pressure, heart rate, power spectra of heart rate variability (HF/LF ratio) and plasma catecholamines. In order to control for attention, subjects had to focus visual affective neutral presentations during the experiment. Correlation analysis was performed as a region of interest analysis using SPM2 software (p<0.001 uncorrected). Sympathetic activity at rest varied substantially between subjects. There were significant positive correlations between increase of regional cerebral glucose metabolism (rCGM) of the heads of caudate nuclei on both sides and the HF/LF ratio of heart rate variability. Furthermore, significant negative correlations between both heart rate and plasma catecholamines and rCGM decreases of caudate nuclei heads were found. In addition, there was a positive correlation between plasma catecholamines and primary motor cortex activation. Autonomic nervous system at rest seems to be partially interlocked with activity of motor brain regions - the caudate nuclei and the motor cortex. This might have clinical implications for the understanding of stress-related disorders, which are frequently accompanied by increased sympathetic activity as well as muscle tone.

P13. Compensation processes for central vestibular dysfunction in patients with acute medullary infarctions (FDG-PET study)

VAS). Strong TPS lead to clear changes in the autonomic reflexes (vasoconstriction, increase in blood pressure). In the first experiment the contralateral S1 cortex was activated during FS, whereas TPS lead to bilateral activation of S1. The S2 and insular region were bilaterally activated by both stimuli. In S2 the center of gravity of the activation during FS was more medial/posterior compared to TPS. The anterior and medial parts of the insular cortex were activated stronger by TPS. In the anterior cingulate gyrus, FS induced a stronger activation of the posterior part. Differential activations were also found in motor and frontal areas. The second experiment indicated that activation induced by strong TPS is in most cases identical with the areas activated by TPS in the first experiment. Only in the medial frontal and right superior frontal gyri an inverse relationship between pain intensity and BOLD contrast was found. It is concluded that the cortical network activated by TPS is in some respects different from that of FS – in the somatotopically organized regions as well as in the medial pain projection system.

3.5. Saccular activations in the brainstem and the cerebellum (fMRI)

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Eye movements induced by short tone burst stimulation: A video-oculography study

Fig. 1A corresponds to the right central spikes (n = 609), and the one on Fig. 1B correlates with the right temporal spike localization (n = 74), in a patient with right-sited polymicrogyria in the area of the Sylvian fissure. Negative BOLD responses may differentiate pediatric from adult epilepsy patients Kobayashi et al., 2005,. Developmental aspects as well as influence of vigilance on the BOLD signal may explain a specific hemodynamic response in young subjects. Difficulties applying EEG-fMRI technique in children will be discussed and methodological suggestions will be provided. Conclusion: Simultaneous EEG-fMRI recordings in a 3-T scanner may be successfully used to localize the irritative zones in children suffering from focal epilepsies, and revealed negative BOLD responses in this area. Nature and origin of the negative BOLD in many young subjects will be investigated in future studies.