We used functional magnetic resonance imaging (FMRI) to study possible cerebral activation patterns associated with unilateral postural tremor in 12 patients with essential tremor (ET), with mimicked postural tremor in 15 control subjects, and with passive wrist oscillation in both groups. During essential tremor, patients showed mainly contralateral activation of the primary motor and primary sensory areas, the globus pallidus, and the thalamus, but bilateral activation of the nucleus dentatus, the cerebellar hemispheres, and the red nucleus. Only 2 patients presented with activity in the medulla close to the olivary nucleus. Unilateral passive wrist oscillation of ET patients resulted in only unilateral activation of the cerebellum, nuclei dentati, and red nuclei. In contrast to the involuntary tremor condition of ET patients, the mimicked tremor condition of the control subjects was not associated with bilateral activity in the cerebellum, nuclei dentati, or red nuclei. Involuntary tremor of ET patients was associated with a significantly larger extent of activation in the cerebellar hemispheres and the red nucleus (p < 0.003) compared with mimicked tremor in the control group. Our FMRI study indicates that ET is mainly associated with an additional contralateral cerebellar pathway activation and overactivity in the cerebellum, red nucleus, and globus pallidus without significant intrinsic olivary activation.

The differential effects of optokinetic stimulation with and without fixation suppression were analysed in an fMRI study in 10 right-handed healthy subjects. Horizontal and vertical small-field optokinetic stimulation activated the same multiple visual, ocular motor and vestibular cortical and subcortical areas in both hemispheres. The extent of activation in each hemisphere was independent of the stimulus direction. All activated areas representing cortical (occipitotemporal cortex, posterior parietal cortex, precentral and posterior median frontal gyrus, prefrontal cortex, medial part of the superior frontal gyrus) and subcortical (caudate nucleus, putamen, globus pallidus and paramedian thalamus) ocular motor structures were activated during optokinetic stimulation as well as during fixation suppression of optokinetic nystagmus. However, the activation was significantly stronger with optokinetc nystagmus compared with fixation suppression. The only relatively increased activity during fixation suppression was seen in the medial part of the superior frontal gyrus (supplementary eye field) and the anterior cingulate gyrus. The anterior insula and the posterior insula (human homologue of the parieto-insular vestibular cortex) were activated during optokinetic nystagmus but not during fixation suppression. A significant right hemispheric predominance (regardless of stimulus direction) was found under both conditions in the visual motion-sensitive and ocular motor areas of the cortex, except the supplementary eye field and anterior cingulate gyrus. This was most prominent in the occipitotemporal cortex, but did not occur in the primary visual cortex and in subcortical ocular motor structures (putamen, globus pallidus and caudate nucleus). Thus, cortical and subcortical activation patterns did not differ for horizontal and vertical optokinetic stimulation, and there was distinct right-hemisphere dominance for visual motion-sensitive and cortical ocular motor areas and the thalamus. Fixation suppression of optokinetic nystagmus yielded four different results: (i) increased activation in the supplementary eye field and anterior cingulate gyrus; (ii) unchanged activation in the visual cortex; (iii) decreased activation in most of the ocular motor areas; and (iv) suppressed activation in the anterior and posterior insula and the thalamus. Activation of the parieto-insular vestibular cortex may be related to ocular motor function rather than self-motion perception.

The pathophysiology of periodic limb movements and sensory leg discomfort in the restless legs syndrome is unknown. With high-resolution functional magnetic resonance imaging, we localized for the first time cerebral generators associated with sensory leg discomfort and periodic limb movements in 19 patients with restless legs syndrome. During sensory leg discomfort there was mainly bilateral activation of the cerebellum and contralateral activation of the thalamus. During the combined periodic limb movement and sensory leg discomfort conditions, patients also showed activity in the cerebellum and thalamus. In contrast to the sensory leg discomfort condition alone, the combined condition was associated with additional activation in the red nuclei and brainstem close to the reticular formation. Voluntary imitation of periodic limb movements by patients and control subjects was not associated with brainstem activity, but with additional activation in the globus pallidus and motor cortex. These findings indicate that cerebellar and thalamic activation may occur because of sensory leg discomfort and that the red nucleus and brainstem are involved in the generation of periodic limb movements in patients with restless legs syndrome.

Cerebral activation was investigated with functional magnetic resonance imaging (fMRI) during galvanic stimulation of the mastoid in 6 normal volunteers. Cutaneous stimulation at the neck C4-5 level served as a control. During mastoid stimulation, bilateral vestibular activation occurred in the posterior insula (parietoinsular vestibular cortex, PIVC), the transverse temporal (Heschl's) gyrus, and thalamic pulvinar. The cutaneous pain elicited by galvanic stimulation caused bilateral activity of the medial part of the insula and the anterior median thalamus. Thus, galvanic stimulation at the mastoid level activates cortical areas of three different sensory systems in the insulathalamic region, the vestibular, the auditory, and the nociceptive systems.

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The differential effects of fixation suppression on this complex pattern of cerebellar activation in part allow us to separate visual and attentional from ocular motor processing. Our data agree with behavioral and physiologic animal data about ocular motor processes and motor learning in the vestibulospinal and optokinetic reflex. This suggests that hemispheric cerebellar activity may be mainly associated with changes in attention, whereas vermal activity seems to be associated with ocular motor control, and activity of the dentate nuclei and the cerebellar peduncles seems to be associated with both.

Self-motion or object motion can elicit optokinetic nystagmus (OKN), which is an integral part of dynamic spatial orientation. We used functional MR imaging during horizontal OKN to study cerebral activation patterns in sensory and ocular motor areas in 10 subjects. We found activation bilaterally in the primary visual cortex, the motion-sensitive areas in the occipitotemporal cortex (the middle temporal and medial superior temporal areas), and in areas known to control several types of saccades such as the precentral and posterior median frontal gyrus, the posterior parietal cortex, and the medial part of the superior frontal gyrus (frontal, parietal, and supplementary eye fields). Additionally, we observed cortical activation in the anterior and posterior parts of the insula and in the prefrontal cortex. Bilateral activation of subcortical structures such as the putamen, globus pallidus, caudate nucleus, and the thalamus traced the efferent pathways of OKN down to the brainstem. Functional MRI during OKN revealed a complex cerebral network of sensorimotor cortical and subcortical activation.

Voluntary blinks and saccades are associated with similar loci of activation patterns; however, the quantitative distribution of activation suggests that the middle part of the frontal gyrus and posterior parietal cortex are of special significance for voluntary blinks. The results argue for the importance of considering quantitative distributional properties of parallel cortical activities associated with saccades and blinks.