Cerebellar activation during optokinetic stimulation and saccades.

OBJECTIVE: To investigate the activation pattern of cerebellar structures during small-field optokinetic stimulation (OKN) by functional MRI (fMRI) and compare it with that obtained during voluntary saccades and fixation suppression of OKN. METHODS: Functional images were acquired from oblique transverse slices of eight healthy, right-handed volunteers using a radio frequency-spoiled, single-slice, fast low-angle shot (FLASH) pulse sequence with high-spatial resolution. RESULTS: Horizontal OKN and saccades were associated with bilateral activity in the cerebellar hemispheres (superior semilunar lobule, simple lobule, quadrangular lobule, inferior semilunar lobule), the middle cerebellar peduncle, the dentate nucleus, and medially in the culmen and uvula of cerebellar nuclei. The pattern and extent of activation were independent of the stimulus direction for OKN and saccades. During fixation suppression, the extent of activation was significantly diminished (hemispheres) or even absent (uvula, culmen). CONCLUSION: 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.

Cortical activation patterns during voluntary blinks and voluntary saccades.

OBJECTIVE: To investigate the activation of frontal, parietal, and occipital areas in normal volunteers during voluntary blinks and during voluntary saccades using functional MRI (fMRI). BACKGROUND: A previous fMRI study revealed the activation of the precentral and posterior middle frontal gyrus ("frontal eye field" [FEF]), the medial part of the superior frontal gyrus ("supplementary eye field" [SEF]), and the visual cortex. The parietal cortex was not included in this study. Frontal and occipital cortical areas involved in voluntary blinking have not been shown previously using fMRI. METHODS: A 1.5-T standard clinical scanner was used for both anatomic and functional studies in 12 observers. To conduct data analyses the authors used voxel-by-voxel cross-correlation. RESULTS: Voluntary blinks led to the activation (p < 0.05) of the FEF, the SEF, the posterior parietal cortex ("parietal eye field" [PEF]), and the visual cortex. Voluntary blinking produced activity in the same cerebral structures as voluntary saccades. However, the number of activated voxels was smaller during voluntary blinking than during voluntary saccades in the visual cortex and in the FEF (p < 0.01). In contrast, the extent of activation was significantly higher (p < 0.003) in the SEF and in the PEF during voluntary blinking. CONCLUSIONS: 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.

Effects of galvanic vestibular stimulation on otolithic and semicircular canal eye movements and perceived vertical.

OBJECTIVE: The aim of this study was to determine the otolithic and semicircular canal effects of galvanic vestibular stimulation with increasing current strengths on eye movements and the perception of verticality. METHODS: We measured (1) 3-dimensional eye movements, (2) subjective tilt of the peripheral visual field, and (3) subjective tilt of a central vertical line in 12 healthy subjects during galvanic vestibular stimulation. A rectangular, unipolar binaural electric current was applied to each subject's mastoid. RESULTS: Anodal stimulation of the right mastoid led to an ipsiversive tonic ocular torsion of up to 5.4 degrees, to a contralateral tilt of both the peripheral visual field (1-9 degrees), and a central vertical line (0.5-6.2 degrees) increasing in amplitude with increasing current strengths applied. This reflects otolith stimulation. In most subjects, current strengths of 3 mA or more elicited a slight (horizontal-) torsional nystagmus (amplitude 1-2 degrees) that was superimposed on static torsion. This reflects horizontal and vertical semicircular canal stimulation. A correlation was found in the amount of the 3 measured parameters and the strength of the applied current. CONCLUSIONS: Thus, galvanic vestibular stimulation at low current intensities (1-3 mA) preferably excites otolith responses, which increase with increasing current intensity. With higher current intensity above 3 mA, additional semicircular canal responses are elicited in the form of horizontal-rotatory nystagmus superimposed on static torsional deviations. The lack of a vertical deviation and nystagmus can be explained by the counterdirected vertical components of the anterior and posterior semicircular canal.

Bilateral functional MRI activation of the basal ganglia and middle temporal/medial superior temporal motion-sensitive areas: optokinetic stimulation in homonymous hemianopia.

OBJECTIVE: To determine to what extent sensorimotor control is achieved for each hemisphere separately or interactively during small-field optokinetic stimulation in patients with complete homonymous hemianopia. DESIGN: Functional and structural neuroimaging using high-resolution magnetic resonance imaging. SETTING: University medical center research facility. PATIENTS: Three patients with complete homonymous hemianopia after acute infarction of the right posterior cerebral artery. MAIN OUTCOME MEASURES: Anatomical location of activated structures during horizontal optokinetic stimulation and T2-weighted anatomical magnetic resonance imaging. RESULTS: Occipitotemporal cortical areas (Brodmann areas 39 and 40) were the only activated cortical structures that showed statistically significant (P<.01) activation on the affected hemisphere. Of the subcortical areas, activation of thalamic nuclei appeared to be missing on the affected side, whereas the basal ganglia (putamen, globus pallidus, and caudate nucleus) were bilaterally activated. CONCLUSIONS: Bilateral activation of the basal ganglia confirms the concept of the basal ganglia-thalamocortical motor loop and of the efference copy of oculomotor pathways from each hemisphere. Our findings suggest 2 possible explanations for the activation of occipitotemporal areas (the human homolog of middle temporal/medial superior temporal areas) on the infarcted hemisphere: involvement of direct extrastriatal visual pathways or interhemispheric callosal connections between right and left middle temporal/medial superior temporal areas.

Horizontal or vertical optokinetic stimulation activates visual motion-sensitive, ocular motor and vestibular cortex areas with right hemispheric dominance. An fMRI study.

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.

Cerebral functional magnetic resonance imaging of vestibular, auditory, and nociceptive areas during galvanic stimulation.

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.

Sensorimotor cerebral activation during optokinetic nystagmus. A functional MRI study.

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.

Functional MRI mapping of occipital and frontal cortical activity during voluntary and imagined saccades.

We investigated the activation of frontal and occipital cortical areas in 14 normal volunteers during voluntary saccades in light or dark and during imagined saccades using functional magnetic resonance imaging (FMRI) with electro-oculogram monitoring. Voluntary saccades in light or dark and imagined saccades led to a significant activation (p < 0.005) of the precentral and posterior medial frontal gyrus (frontal eye field). The medial part of the superior frontal gyrus (supplementary eye field) also showed significant activity during voluntary saccades in all subjects, but only in four subjects during imagined saccades. In addition to frontal activity we found an activated primary visual cortex during voluntary saccades, both in light and in dark. In contrast to executed saccades, imagined eye movements revealed to occipital response under either condition. Our FMRI study supports the concept of frontal eye fields during voluntary saccades and demonstrates that occipital areas are associated with the generation of voluntary eye movements. However, the primary visual cortex is not active when eye movement is only imagined.

Cerebral generators involved in the pathogenesis of the restless legs syndrome.

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.

Activation mapping in essential tremor with functional magnetic resonance imaging.

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.

Reflex studies and MRI in the restless legs syndrome.

Brainstem and spinal pathways of untreated patients with idiopathic restless legs syndrome (RLS) were examined using magnetic resonance imaging (MRI), blink reflex, first and second exteroceptive suppression (ES1, ES2) of temporalis muscle, and H reflex. MRI of 25 patients elicited no structural lesions beyond age-related atrophy or white matter lesions on proton density- and T2-weighted coronal and axial images. All patients showed a normal latency of the soleus H reflex (mean +/- SD latency = 31.22 +/- 2.81 ms) and the H/M ratio was 48 +/- 17%. The duration and onset latency of the direct and indirect blink reflex responses were normal in all patients compared with those of controls (p > 0.5). There was no significant difference in ES1 and ES2 latencies or duration between patients and controls (p > 0.5). These results suggest that the etiology of RLS symptoms does not involve structural lesions.

Pallidal lesions. Structural and functional magnetic resonance imaging.

OBJECTIVE: To study noninvasively the functional anatomy and pathophysiologic characteristics of the globus pallidus external (GPe) and internal (GPi) divisions. DESIGN: Structural and functional neuroimaging using high-resolution magnetic resonance imaging. SETTING: University medical center research facility. SUBJECTS. Seven patients with pallidal lesions, 4 with an akinetic-rigid syndrome and 3 with a dystonic syndrome, and 15 age-matched volunteers. MAIN OUTCOME MEASURES: T2-weighted anatomical magnetic resonance imaging and number of activated voxels in the GP during rapid supination and pronation of the hand. RESULTS: T2-weighted images showed hyperintense bilateral lesions in the GP of all patients. Patients with dystonic syndromes had isolated lesions in the GPi. Patients with signs of akinetic-rigid syndromes showed abnormalities in the GPe or in central portions of the GP (GPc). Patients with lesions in both parts of the GP had akinetic-rigid or dystonic syndromes. All patients showed activation in the areas of the lesions. The number of activated voxels in the GP was significantly smaller (P < .005, Wilcoxon signed rank test) in patients than in control subjects. Activation of the GP was predominantly contralateral to the moving hand. CONCLUSIONS: Lesions in the GPi result in a loss of inhibitory pallidal projections to the thalamus, which may explain the hyperkinetic signs. Lesions in the GPe lead to an increased inhibition of the thalamus, which may explain the hypokinetic signs. Neuronal activation in lesion sites suggests the presence of remaining functionally vital tissue.

Electrophysiological pattern of involuntary limb movements in the restless legs syndrome.

Patients with restless legs syndrome (RLS) suffer from involuntary limb movements during the day. We studied these leg movements in 18 idiopathic (n = 8) and uremic (n = 10) patients at rest. Electromyographically measured muscle contractions were preceded by sensory discomfort in all patients. The mean duration of the contractions ranged between 0.67 and 5.71 s with a mean frequency of 244 epochs of muscle activity per hour. Seven of 18 patients showed a constant order of recruitment with propagation of muscle activity up or down spinal segments (L3 to S1 and vice versa). No difference in electrophysiologically recorded patterns was observed between patients with idiopathic and uremic RLS. We suggest a brainstem disinhibition phenomenon as the pathological mechanism that activates a spinal generator. The spinal origin of the involuntary limb movements in patients with RLS is confirmed by the long duration of jerks, the recruitment characteristics, and the periodicity of the jerks. No jerk could be elicited by sensory reflexes.

[Possibilities of technical and methodological optimization of functional magnetic resonance tomography]. / Möglichkeiten der technischen und methodischen Optimierung der funktionellen Magnetresonanztomographie.

The techniques of in vivo functional magnetic resonance imaging (fMRI) have been established over the past few years. Signal changes resulting from small differences in the magnetic resonance signal caused by variations in the oxygenation state of the venous vasculature are used to map neuronal activity of the brain. While many of the advantages for using MRI for functional neuroimaging are quite obvious (high spatial and temporal resolution, direct anatomic correlation, noninvasiveness), the underlying mechanisms and problems are not fully known. This article focuses on selected topics of fMRI techniques and their problems, such as field strength B0, different types of sequences and their parameters, 2D and 3D data acquisition, different statistical methods and motion artifacts. The authors favor the use of a 1.5 T clinical scanner with EPI capabilities, 2D FLASH sequences with a TR < 60 ms, TE = 30-40 ms, alpha < 20 degrees for high resolution and sensitivity, fMRI and multislice EPI for high temporal and overview and fMRI as well as cross-correlation for post-processing.

[Functional magnetic resonance tomography of the basal ganglia. Use of FLASH sequences for mapping activity with BOLD contrast ane high resolution]. / Funktionelle Magnetresonanztomographie der Basalganglien. Einsatz von FLASH-Sequenzen zum Aktivitätsmapping mit BOLD-Kontrast und Hochauflösung.

The activation pattern of putamen, internal and external division of globus pallidus was investigated during rapid pronation and supination of the right and left hand in 12 normal volunteers using a FLASH sequence with high resolution for functional magnetic resonance imaging (fMRI) at 1.5 T. The chosen paradigm for motor function led to a signal increase within the basal ganglia between 3 and 23%, depending on the structure and individual subject. In all cases significant activation could be found contralateral to the moving hand. In six cases activation was also found on the ipsilateral side. The activated areas within putamen, internal and external division of globus pallidus were less than 5 mm2. These first results indicate that fMRI studies of basal ganglia are feasible and might be suitable for analyzing basal ganglia disorders.

High-resolution activation mapping of basal ganglia with functional magnetic resonance imaging.

We investigated the activation of the putamen and the external and internal division of the globus pallidus in 12 normal volunteers during rapid supination and pronation of their right or left hand, using functional MRI (fMRI). We observed an increase in signal intensity varying from 3.1 +/- 1.2% to 23.4 +/- 2.3% during activation. Activated areas were predominantly contralateral to the moving hand and smaller than 5 mm2. These findings indicate that fMRI allows study of the normal function of basal ganglia and may be of value in the investigation of basal ganglia disorders.

Epidemiological, genetic, pharmacological, kinesiological, nuclear medical (IBZM-SPECT), standard and functional MRI studies on Parkinson's disease and related disorders and economic evaluation of Parkinson's disease therapy--clinical projects in the BMFT-research program Munich: "Parkinson's disease and other basal ganglia disorders".

The results of selected clinical research projects related to epidemiological, genetic, pharmacological, kinesiological, and neuroimaging aspects (SPECT, PET, MRI, functional MRI) of basal ganglia disorders such as Parkinson's disease, Progressive Supranuclear Palsy, Multiple System Atrophy and Wilson's disease are summarized. A retrospective pharmacoeconomic analysis of Parkinson's disease is presented. These studies are part of a nationwide research program of the German ministry of research and technology (BMFT) entitled "Parkinson's disease and other basal ganglia disorders" and were carried out at the Department of Neurology, LMU München.

Bereitschaftspotential in idiopathic and symptomatic restless legs syndrome.

Patients with idiopathic and symptomatic restless legs syndrome (RLS) suffer from "dyskinesia while awake" or "daytime myoclonus" when at rest preceded by sensory symptoms. In order to characterise the RLS either as reflex movement or as voluntary movement we measured movement-related cortical potentials in 5 idiopathic and 8 uraemic RLS patients. Movements from both legs were polygraphically recorded concomitantly with cortical activity 2000 msec before to 500 msec after onset of EMG activity. These data were compared with a voluntary simulation of each patient's movement pattern and with 5 age-matched controls performing dorsiflexion of the right, left and both feet. Cortical activity preceding daytime myoclonus was absent in RLS patients whereas self-initiated leg movements in patients elicited onset times (1180-1380 msec) and amplitudes of Bereitschaftspotential (readiness potential) not significantly different from readiness potentials in control subjects (P > 0.05). Lack of movement-related potentials in myoclonus and/or dyskinesias during daytime in RLS patients is compatible with an involuntary mechanism of induction and points towards a subcortical or spinal origin of RLS.