The cerebellum and dyslexia: perpetrator or innocent bystander?
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Biomedical subjects
Publications and source records attributed to T Zeffiro.
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The laryngeal pathophysiology underlying the speech disorder in idiopathic Parkinson disease (IPD) was addressed in this electromyographic study of laryngeal muscle activity. This muscle activity was examined during voice onset and offset gestures in 6 persons in the early stages of IPD who were not receiving medication. The purpose was to determine (a) if impaired voice onset and offset control for speech and vocal fold bowing were related to abnormalities in laryngeal muscle activity in the nonmedicated state and (b) if these attributes change with levodopa. Blinded listeners rated the IPD participants' voice onset and offset control before and after levodopa was administered. In the nonmedicated state, the IPD participants' vocal fold bowing was examined on nasoendoscopy, and laryngeal muscle activity levels were compared with normal research volunteers. The IPD participants were then administered a therapeutic dose of levodopa, and changes in laryngeal muscle activity for voice onset and offset gestures were measured during the same session. Significant differences were found between IPD participants in the nonmedicated state: those with higher levels of muscle activation had vocal fold bowing and greater impairment in voice onset and offset control for speech. Similarly, following levodopa administration, those with thyroarytenoid muscle activity reductions had greater improvements in voice onset and offset control for speech. In this study, voice onset and offset control difficulties and vocal fold bowing were associated with increased levels of laryngeal muscle activity in the absence of medication.
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Effects of spatially directed auditory attention on human brain activity, as indicated by changes in regional cerebral blood flow (rCBF), were measured with positron emission tomography (PET). Subjects attended to left-ear tones, right-ear tones, or foveal visual stimuli presented at rapid rates in three concurrent stimulus sequences. It was found that attending selectively to the right-ear input activated the auditory cortex predominantly in the left hemisphere and vice versa. This selective tuning of the left and right auditory cortices according to the direction of attention was presumably controlled by executive attention mechanisms of the frontal cortex, where enhanced activation during auditory attention was also observed.
To evaluate the hypothesis that self-paced movements are mediated primarily by the supplementary motor area, whereas externally triggered movements are mainly affected by the lateral premotor cortex, different movements in 6 healthy volunteers were studied while changes in regional cerebral blood flow (rCBF) were measured using positron emission tomography (PET) and 15O-labeled water. Subjects made a series of finger opposition movements initiated in a self-paced manner every 4 to 6 seconds, and separately, made continuous finger opposition movements at a frequency of 2 Hz paced by a metronome. The primary motor cortex, lateral area 6, cerebellum on both sides, and caudal cingulate motor area, and the putamen and thalamus on the contralateral side were more active during the metronome-paced movements. The increases in rCBF in these areas are likely the result of the larger number of movements per minute made with the externally triggered task. The anterior supplementary motor area and rostral cingulate motor area in the midline, prefrontal cortices bilaterally, and lobus parietalis inferior on the ipsilateral side were more active during the self-paced movements. Increases in rCBF in those areas, which include medial premotor structures, may be related to the increased time devoted to planning the movement in this condition.
Rapid improvements in functional magnetic resonance neuroimaging technology have resulted in impressive advances in our understanding of structure/function relationships in the human brain. The application of this new technology to the understanding of human brain disease is currently limited by difficulties in extracting task-related signal change from signal intensity time series that have been contaminated by artifacts arising from various intrinsic and extrinsic sources. Effects induced by interscan head motion are a major source of these artifacts. The correction of these artifacts by registration of pairs of reconstructed images has been a focus of research for the past few years and there are now a number of effective means to compensate for this source of noise. This paper discusses issues concerning the prevention and correction of interscan head motion as well as other sources of error variation in fMRI time series.
We compared the effect of valproate (VPA) on cerebral metabolic rate for glucose (CMRGlc) and cerebral blood flow (CBF), measured with 18F-2-deoxyglucose (18FDG) and 15O water positron emission tomography (PET), in 10 normal volunteers. Mean VPA dose was 17.7 mg/kg, and mean VPA level was 82.1 mg/L (+/-16.5) for 4 weeks. VPA reduced global CMRGlc by 9.4% (9.60 +/- 0.76 vs. 8.59 +/- 1.02 mg Glc/min/100 g, p < 0.05) and regionally in all anatomic areas (p < 0.05 for 11 of 26 areas). VPA diminished global CBF by 14.9% (56.55 +/- 6.70 vs. 47.48 +/- 4.42 ml/min/100 g, p < 0.002) and regionally in all anatomic areas (p < 0.05 for 12 of 26 areas). No significant correlation was noted between VPA level and either global CMRGlc or CBF. The effect of VPA on global CMRGlc is similar to that of carbamazepine (CBZ) and phenytoin but less than that of phenobarbital, valium, or combination therapy with VPA and CBZ. VPA reduced regional CBF (rCBF) but not CMRGlc in the thalamus, an effect that may be associated with VPA's mechanism of action against generalized seizures.
OBJECTIVE: To design a test of motor learning using arm movements in normal subjects and patients with cerebellar disease. METHODS: Elbow angle was continuously displayed as a cursor (a dot) on a computer screen, and subjects made ballistic elbow flexion and extension movements to try to move the cursor between two targets on the screen. The relation between the arm movement and its visual feedback was changed, and the subjects reacted by adapting the amplitude of their movements in subsequent trials. RESULTS: The consecutive errors showed exponential learning curves during adaptation, which were quantified by their steepness. Ten patients with isolated cerebellar or olivopontocerebellar degeneration had less steep learning curves than normal subjects, indicating a failure of adaptation motor learning in cerebellar disease. The results show that this test may be useful for the analysis of motor learning.
The brain regions controlling self-paced sequential finger movements in patients with cerebellar degeneration were studied by measuring changes in regional cerebral blood flow (rCBF) in eight patients using bolus injections of H2(15)O and PET. The results were compared with those obtained in eight normal age-matched control subjects. Patients and control subjects performed a self-paced sequential finger opposition task with the right hand, completing a sequence of movements every 4-6 s. Both groups had strong increases in the adjusted rCBF contralaterally in the primary motor cortex (M1) and ventral premotor area (PMv), in the caudal supplementary motor area (SMA) and cingulate motor area (CMA), and bilaterally in the prefrontal cortex (PFC), the lobus parietalis inferior (LPI), putamen and cerebellum. The cerebellum, PMv, rostral CMA, PFC and LPI were more active in the control subjects than in the patients, and the M1, SMA, caudal CMA and putamen were more active in the patients than in the control subjects. The reduced activity of the cerebellar neurons in the patients produced a complex pattern of rCBF increases and decreases in other brain regions. Our results suggest that for the preparation and execution of sequential finger movements, patients with cerebellar degeneration use a medial premotor system, including the SMA and caudal CMA, as well as the M1 and putamen, rather than the PMv, PFC, LPI and rostral CMA.
OBJECTIVE: To study explicit and implicit memory processes in patients with Parkinson's disease. DESIGN: Case-control design. All subjects were given a neuropsychological test battery, and the test scores were compared among the groups. SETTING: Government-funded research facility. All subjects were examined as outpatients. PATIENTS: We tested nondemented (n = 13) and demented (n = 5) patients with Parkinson's disease and normal controls (n = 12) matched for age, gender, and educational level. MAIN OUTCOME MEASURES: Memory for verbal and pictorial stimuli under both explicit and implicit retrieval conditions. RESULTS: Both nondemented and demented patients with Parkinson's disease exhibited impairment on tests of explicit memory. Their impairment could be graded based on the level of effort required by the task: impaired free recall in nondemented patients and impaired free recall, cued recall, and recognition in demented patients. By contrast, neither group showed evidence of impairment on automatic (modality monitoring and word frequency estimation) or implicit (word and picture fragment identification) memory tasks. Correlation analyses did not support any association between the effortful memory deficits and neurologic variables, mood, or performance on executive function tests. CONCLUSIONS: Memory deficits in patients with Parkinson's disease primarily involve the conscious, effortful strategic aspects of searching long-term memory.
Palatal tremor (brief, rhythmic involuntary movements of the soft palate) apparently comprises two different nosological entities: essential palatal tremor (EPT) and symptomatic palatal tremor (SPT). The site of the abnormality in EPT is unknown, whereas SPT is believed to arise from a lesion of the brainstem or cerebellum (within the Guillain-Mollaret triangle). The clinical and physiological properties of these conditions were studied in four patients with EPT and six patients with SPT. Patients with EPT had normal cerebellar function, but those with SPT had clinical signs of cerebellar dysfunction. The palatal movements were consistent with activation of the tensor veli palatini muscle in EPT and of the levator veli palatini muscle in SPT. During sleep, EPT stopped, whereas SPT continued with only slight variations in the tremor rate. The cycle of palatal tremor could not be reset by stimulation of trigeminal afferents in either EPT or SPT patients, and Valsalva's manoeuvre did not consistently affect the rhythm of the tremor in either group. The palatal tremor cycle exerted remote effects on the tonic electromyographic activity of the upper and lower extremities only in patients with SPT. These effects were present only on the side of the cerebellar signs (opposite the side with the enlarged inferior olive) in patients with a unilateral syndrome. Essential palatal tremor patients had only polysynaptic brainstem reflex abnormalities, whereas SPT patients had abnormalities of monosynaptic, oligosynaptic and polysynaptic brainstem reflexes. Magnetic resonance imaging showed no evidence of structural abnormalities in EPT patients, but SPT patients had a hyperdense signal of the ventral upper medulla (the region of the inferior olive) on T2-weighted images. These observations support the hypothesis that EPT and SPT are two different diseases. In SPT, cerebellar dysfunction ipsilateral to the palatal tremor may be due, in part, to abnormal function of the contralateral hypertrophic inferior olive. The proposed basis of SPT is a disturbance of electrotonic coupling between the cells of the inferior olive induced by a lesion of the dentato-olivary pathway. Similar mechanisms could be responsible for postural tremors in general. The pathophysiological basis of EPT remains unknown.
Regions of cerebral cortex activated in normal subjects making simple, repetitive, voluntary wrist movements were studied with positron emission tomography (PET). The regional cerebral metabolic rate of glucose utilization was studied with 2-[18F]fluoro-2-deoxy-D-glucose (FDG), and regional cerebral blood flow was studied with 15O-labeled water. No significant activation was found with the cerebral metabolic rate studies. Studies of regional cerebral blood flow showed significant activation of the contralateral sensorimotor cortex region of 42%, of the ipsilateral sensorimotor cortex region of 19%, and of the medial frontal cortex of 30% compared with the resting state. Increases in blood flow in the contralateral sensorimotor cortex and medial frontal cortex were visible on every activated scan. Measurement of regional cerebral blood flow seems to be more sensitive than regional cerebral metabolic rate of glucose utilization for studying cortical activation with voluntary movement.
The effects of photic stimulation on the visual cortex of human brain were studied by means of gradient-echo echo-planar imaging (EPI). Whole-body 4 and 1.5 T MRI systems, equipped with a small z axis head gradient coil, were used. Variations of image intensity of up to 28% at 4 T, and up to 7% at 1.5 T, were observed in primary visual cortex, corresponding to an increase of blood oxygenation in regions of increased neural activity. The larger effects at 4 T are due to the increased importance of the susceptibility difference between deoxygenated and oxygenated blood at high fields.
The physiology of rigidity in Parkinson's disease (PD) can be investigated by the study of reflexes. Cutaneous reflexes (CR) were measured in 10 patients with PD and in 10 age- and sex-matched normal volunteers. EMG activity was recorded from the first dorsal interosseous muscle with surface electrodes, rectified and averaged. The index finger was stimulated with an intensity four times the sensory threshold. The subjects abducted the index finger with 20% of maximal force. While the latencies of the different reflex components and the amplitudes of the excitatory peaks were not different in the two groups, the first inhibitory component was less pronounced in patients with PD as compared with normals. This effect is partially reversed with dopaminergic drug treatment. The results are compatible with the loss of an inhibitory spinal mechanism elicited by cutaneous afferents, and can be a partial explanation for increased tone in PD.
An alcoholic, hyponatremic woman developed central pontine myelinolysis (CPM) and improved from a decerebrate, comatose state to alertness and full ambulation. NMR, using inversion-recovery and spin-echo pulse sequences, was performed sequentially from 4 weeks to 8 months after onset of symptoms and revealed a well-defined lesion with prolonged relaxation times. The lesion was anatomically consistent with CPM and was initially also visualized by CT. NMR showed no definite temporal change in the qualitative appearance of the lesion until the 8-month scan; however, quantitatively, a reduction of relaxation times was noted with each serial study.
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