Abnormal vestibular responses to vertical head motion in cerebellar ataxia

Falls pose an important problem to neurologists caring for patients with cerebellar disorders. Normal human gait is characterized by prominent up-and-down linear head movements (vertical translations). Thus, we asked whether patients with cerebellar gait ataxia showed abnormal responses of otolithic vestibuloocular reflexes to this motion. Compared with healthy subjects, all cerebellar patients showed impaired otolith-ocular responses. Neurologists often test the rotational vestibuloocular reflexes in cerebellar patients, but our results indicate that vestibular responses to vertical linear motion are severely affected. Impairment of the corresponding otolith-spinal reflexes may contribute substantially to falls.     

Reduced cerebellar hemisphere size and its relationship to vermal hypoplasia in autism

Cerebellar hemisphere size was calculated in 10 autistic and 8 normal control subjects by summing the cross-sectional areas of cerebellar hemisphere tissue measured on paramidline sagittal magnetic resonance images. The areas of two cerebellar vermal regions (lobules I through V and lobules VI through VII) were also measured using the midsagittal image. Our cumulative slice area measure of cerebellar hemisphere size was significantly smaller in the autistic subjects than in the control group. The cumulative slice area correlated positively with the area of vermal lobules VI through VII only in the autistic subjects. Our results indicated that the decreased size of the cerebellar hemispheres and vermal lobules VI through VII was associated with autism.     

MRI analysis of cerebellar vermal abnormalities in bipolar disorder

OBJECTIVE: The authors sought to expand previous findings of vermal abnormalities in bipolar disorder patients. METHOD: Magnetic resonance imaging (MRI) morphometry was used to quantify vermal subregion volumes in 18 subjects with first-episode bipolar disorder, 21 subjects with multiple-episode bipolar disorder, and 32 healthy subjects. RESULTS: Vermal subregion V2 volume was significantly smaller in multiple-episode bipolar disorder subjects than in first-episode patients and healthy subjects. Vermal subregion V3 was significantly smaller in multiple-episode bipolar disorder subjects than in healthy subjects. CONCLUSIONS: These results suggest that posterior-inferior cerebellar vermal abnormalities are present in patients with multiple-episode bipolar disorder.     

Contribution of somatosensory cortex to evoked cerebellar blood flow responses

Projections from the trigeminocerebellar pathway and the somatosensory cortex coincide spatially in the granule cell layer of Crus I/II of the cerebellar hemisphere. A biphasic field potential was seen: one peak at 10 ms (trigeminal input) and another at 20 ms (somatosensory input). Linear correlation analysis revealed only a weak coupling between somatosensory input and cerebellar blood flow responses to infraorbital nerve stimulation. In separate experiments, cortical spreading depression attenuated the field potential peak at 20 ms while blood flow responses remained unaltered. Thus, trigeminocerebellar activity explained the evoked blood flow responses. Our data provide further evidence that activity-dependent blood flow responses are context-sensitive and that interaction between excitatory neuronal circuits targeting the same cells may occlude vascular responses.     

The primary vestibular projection to the cerebellar cortex in the pigeon (Columba livia)

The cerebellar cortex of the pigeon receiving direct vestibular afferents was delineated by anterograde transport of [3H]-amino acids injected into the vestibular nerve. Labelled mossy fiber rosettes in the granular layer were concentrated in lobule X (nodulus) and to a lesser extent, in the ventral portion of lobule IXd (uvula and paraflocculus). A few solitary labelled rosettes were also found in more dorsal portions of lobule IX, as well as in the anterior lobe between lobule II and IV. The lingula remained unlabelled. Discrete injections of [3H]-leucine into the cristae of each of the three semicircular canals or the utricular macula yielded a similar distribution of fewer labelled rosettes. A few primary mossy fiber terminals labelled after cochlear injections are attributed to afferents from the lagenar macula. Since effective diffusion of label from the injection site was excluded by controls, it is concluded that projection of individual canal and macula nerves to the vestibulocerebellar cortex is not topographically separated. It is proposed that this extensive convergence of various afferents is required by the cerebellum to compute precise and directionally specific control signals during head rotation in all conceivable planes.     

Perinatal brain injury and cerebellar vermal lobules I-X in schizophrenia

Several studies, including our own, have reported atrophy of the cerebellar vermis in some schizophrenic patients. A recent report by Courchesne et al (1988) of hypoplasia of a developmentally specific region of the cerebellar vermis in autism prompted us to hypothesize that the cerebellar "atrophy" in some schizophrenic patients may also have developmental origins. We measured the area of the vermal lobules in 30 male schizophrenics. Contrary to expectation, the patients as a group had consistently larger cerebellar structures than the controls. Patients with perinatal injury had smaller structures than the nonperinatally injured group, but these measures were still larger than in the control subjects. Patients without perinatal injury differed from controls, having larger lobules VI-VII (p less than 0.03). These preliminary findings tentatively suggest a role for developmental factors for cerebellar structures in schizophrenia. Further research is needed to clarify the cerebellar vermal changes observed in some schizophrenic patients.     

Mapping cerebellar vermal morphology and cognitive correlates in prenatal alcohol exposure

Prenatal exposure to alcohol can result in neuroanatomical and neurocognitive deficits. High-resolution magnetic resonance imaging, surface-based image analytic methods, and neuropsychological measures were used to characterize the cerebellar vermis and to evaluate potential cognitive correlates of vermal morphology in 21 children and adolescents with prenatal alcohol exposure and 21 normally developing individuals. Alcohol-exposed individuals showed statistically significant reductions in the midline sagittal areas of the anterior vermis and posterior-inferior vermis, and significant displacement of the anterior and posterior-inferior vermal regions. Anterior vermal dysmorphology was negatively correlated with verbal learning and memory performance within the alcohol-exposed group. These observations expand on previous reports of cerebellar abnormalities in prenatal alcohol exposure, in that they localize the specific pattern of cerebellar vermal dysmorphology.     

Integrative versus delay line characteristics of cerebellar cortex.

In order to determine which of two general models ("tapped delay line" or "integrator") provides a more accurate desciption of mammalian Purkinje cell (P-cell) activation by natural stimulation, the spatial and temporal characteristics of a population of neurons in cerebellar cortex responsive to small controlled stretches of forelimb muscles were examined in awake, locally anesthetized cats. Stretch of a single wrist muscle excited P-cells over a distance of about 1 mm in the long axis of a folium, a span which is at most half the length of parallel fibers. Both granule cells and molecular layer interneurons were excited over a wider zone than P-cells. Furthermore, P-cells across a response zone all fired on the average at the same time, as determined by computing peristimulus cross-interval histograms from pairs of simultaneously recorded neurons. Consistent delays could only be demonstrated in the minimal response latencies as measured from peristimulus time histograms. These delays, however, were longer than could be ascribed to parallel fiber conduction velocity. No evidence, therefore, was found in cat cerebellum to support the "tapped delay line" model, which postulates the successive activation of P-cells as an excitatory volley travels along a parallel fiber beam. Instead, an integrative mode of operation seems to predominate: a relatively wide substratum of activated granule cells simultaneously activates a narrower focus of P-cells centrally situated with respect to the granule cell population. The role of inhibitory interneurons in promoting the "integrator" model is discussed.     

A mechanism for type III vestibular responses of frog cerebellar purkinje cells

Type III Purkinje cells (P-cells), which are excited with both directions of horizontal rotation, are found in high numbers in the frog auricular lobe and adjacent cerebellar areas. To examine the mechanisms underlying these responses, recordings were made from P-cells in curarized animals during rotational stimulation of the horizontal canals. The horizontal canal input to these cells was then modified unilaterally by VIIth nerve section, intraperilymphatic injection of local anesthetic, or by caloric stimulation. Control recordings were also obtained from peripheral canal neurons. Type III responses were abolished by unilateral lesions or reversible blockage of the VIIIth nerve with local anesthetic. The remaining responses were attributable only to the unaffected horizontal canal, ie. only type II or type I responses were observed upon interruption of the ipsi-or contralateral nerve, respectively. The level of spontaneous activity of cerebellar input fibers was low and during rotation produced 'cell silencing' response waveform asymmetries (facilitation greater than disfacilitation). When the level of peripheral resting activity was increased (warm water irrigation), thereby increasing horizontal canal response symmetry, type III responses were reduced in magnitude or abolished. Conversely, cold water irrigation, which decreases the resting rate and response symmetry of input fibers, enhanced type III response magnitudes. On the basis of these results, it is suggested that type III responses result from the fact that single P-cells receive a facilitatory input from both horizontal canals. Since these inputs are 180 degrees phase-reversed and their response waveforms asymmetrical, their resulting postsynaptic effect is a net excitation during both portions of the stimulus cycle.     

Ocular torsion responses to electrical vestibular stimulation in vestibular schwannoma

Objectives

We determined if eye movements evoked by Electrical Vestibular Stimulation (EVS) can be used to detect vestibular dysfunction in patients with unilateral vestibular schwannoma (VS).

Isolated vestibular syndromes due to brainstem and cerebellar lesions

Dizziness/vertigo is the most common symptoms of posterior circulation strokes. Isolated vestibular symptoms and signs without other neurologic deficits have been found in infarctions involving the brainstem and cerebellum. In the brainstem, infarctions responsible for isolated vestibular syndrome are usually restricted to the dorsal portion that contains the vestibular nucleus and the nucleus prepositus hypoglossi. Cerebellar lesions confined to the flocculus, tonsil, and nodulus also produce isolated vertigo and imbalance. The cerebellar peduncle, as a conduit between the brainstem and cerebellum, can also produce isolated vestibular syndrome when damaged. Recognition of these isolated central vestibular syndromes aids in defining the function of each structure and in localizing the involved neural structures based upon the vestibular and ocular motor findings.     

Anterior cerebellar vermal stimulation: Effect on behavior and basal forebrain neurochemistry in rat

Stimulation of the anterior cerebellar vermis (ACV) has been shown to be of therapeutic value in several patients with chronic intractable psychiatric disorders, although the mechanism of action of ACV stimulation remains obscure. The present study sought to clarify how cerebellar stimulation might function by investigating the behavioral and biochemical effects of ACV stimulation in rats. Stimulation was found to increase the amplitude of the acoustic startle response and to produce a borderline enhancement of the potentiated startle effect, results that were interpreted as evidence that ACV stimulation enhances responsiveness to significant environmental cues. A concurrent increase in dopamine turnover and a decrease in serotonin release in the nucleus accumbens suggest possible mechanisms of action of the stimulation. It is proposed that cerebellar stimulation may exert a positive therapeutic effect only in Type II schizophrenia (negative symptomatology), a category of cases possibly associated with an underactive mesolimbic dopamine pathway and, hence, not responsive to neuroleptic treatment.     

Reduced cerebellar left hemisphere and vermal volume in adults with PTSD from a community sample

Background

Traumatic events exposure is a necessary condition for developing posttraumatic stress disorder (PTSD), but not all individuals exposed to the same trauma will develop PTSD. Human studies have suggested that the cerebellum is involved in human fear perception, anticipation, and recollection. In this context, the current study evaluated whether cerebellar volume is associated with PTSD.

Methods

Eighty-four victims of violence, 42 who fulfilled the DSM-IV-TR criteria for PTSD and 42 resilient controls, were identified through an epidemiologic survey conducted in the city of São Paulo. Subjects were evaluated using the Clinician-Administered PTSD Scale (CAPS), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), and Early Trauma Inventory (ETI). All subjects underwent a magnetic resonance imaging (MRI) scan to evaluate their cerebellar hemispheres and vermis.

Results

PTSD subjects had relative smaller left hemisphere (p = 0.04) and vermis (p < 0.01) volumes persisted after controlling for gender, age, and brain volume. In PTSD group, left cerebellar hemisphere volume correlated negatively with PTSD (p = 0.01) and depressive symptoms (p = 0.04). Vermal volume correlated negatively with PTSD symptoms (p < 0.01), early traumatic life events (p < 0.01), depressive symptoms (p = 0.04) and anxiety (p = 0.01).

Conclusion

The cerebellum is involved in emotion modulation, and our results suggest that cerebellar volumetric reduction is associated with mood, anxiety and PTSD symptoms. Early traumatic life experiences are related to vermal volume reduction and may be a risk factor for future PTSD development.     

Auditory responses in the posterior vermis of the cat: the buried cerebellar cortex

Although an auditory area has been found over the exposed area of lobules VI-VIII in the posterior cerebellar vermis of the cat, there has been little information on its buried portion. This point should be of some concern, since very little of the brain tissue in lobules VI-VIII of the cerebellar cortex is exposed. We have systematically explored the posterior vermis with long electrode tracks and compared auditory responses recorded from neurons within the granule cell layer in the folial crown with those in the buried cortex. There was a similarity between neural activities recorded from the exposed surface area and those from the buried portion both in the temporal discharge pattern of neurons to sound and in the spatial distribution pattern of auditory responses.     

A tryptophan-deficient corn-based diet induces plastic responses in cerebellar cortex cells of rat offspring

Sprague-Dawley male rats, fed with a tryptophan-deficient and 8% protein corn-based diet were compared with a group of animals fed with 8% protein alone, and with a group fed with Chow Purina containing 23% protein. Retardation of Bergmann glial cell maturation and a concomitant retardation in granule cell migration were observed in the corn-fed group at 21 days. At 30 days of age, the dendrites of granule cells of both hypoproteic and corn-fed groups were larger than those of the Chow-fed animals. At 60 days of age, dendritic arborization of Purkinje cells was more profuse in both the hypoproteic and corn-fed rats compared with the Chow-fed group. This retardation in granule cell migration could be partially due to Bergmann glial cell immaturity. Consequently, several plastic and maybe compensatory events in both granule and Purkinje cells could have occurred, due to tryptophan deficiency resulting from the corn-based diet.     

Asymmetry of balance responses to monaural galvanic vestibular stimulation in subjects with vestibular schwannoma

ObjectiveWe investigated the potential of galvanic vestibular stimulation (GVS) to quantify lateralised asymmetry of the vestibulospinal pathways by measuring balance responses to monaural GVS in 10 subjects with vestibular schwannoma and 22 healthy control subjects.MethodsSubjects standing without vision were stimulated with 3 s, 1 mA direct current stimuli delivered monaurally. The mean magnitude and direction of the evoked balance responses in the horizontal plane were measured from ground-reaction forces and from displacement and velocity of the trunk. Vestibular-evoked myogenic potentials (VEMPs) to 500 Hz air and bone-conducted tones were also recorded.ResultsIn healthy subjects, the magnitudes of the force, velocity and displacement responses were not significantly different for left compared to right ear stimulation. Their individual asymmetry ratios were always <30%. Subjects with vestibular schwannoma had significantly smaller force, velocity and displacement responses to stimulation of the affected compared with non-affected ear. Their mean asymmetry ratios were significantly elevated for all three measures (41.2 ± 10.3%, 40.3 ± 15.1% and 21.9 ± 14.6%).ConclusionsAsymmetry ratios of balance responses to monaural GVS provide a quantitative and clinically applicable lateralising test of the vestibulospinal pathways.SignificanceThis method offers a more clinically relevant measure of standing balance than existing vestibular function tests which assess only vestibuloocular and vestibulocollic pathways.