Biomedical subjects
E Courchesne
Publications and source records attributed to E Courchesne.
Contribution of the cerebellum to neuropsychological functioning: evidence from a case of cerebellar degenerative disorder.
A detailed neuropsychological evaluation was performed on a patient with an idiopathic cerebellar degenerative disorder. Significant deficits were found in verbal and nonverbal intelligence, verbal associative learning, and visuospatial skills. These deficits were not readily explained by motor control difficulties. In contrast to the patient's moderately impaired language abilities, he was severely impaired on a test of verbal fluency and demonstrated mild naming deficits. Severe cerebellar parenchymal volume loss was demonstrated by magnetic resonance examination. Supratentorial structures showed only minimal posterior parietal and occipital sulcal prominence. On neurological examination, this patient had signs of severe involvement of the cerebellar systems and mild-to-moderate dysfunction of the corticospinal tract. As is characteristic of patients with cerebellar degeneration, there was neurophysiological evidence of subclinical involvement of auditory and somatosensory pathways at the level of the brain stem. Since relatively little cerebral cortical atrophy was noted in this patient, these findings suggest that an intact cerebellum is important for normal cognitive functions.
Auditory processing abilities in non-retarded adolescents and young adults with developmental receptive language disorder and autism.
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A new role for the cerebellum in cognitive operations.
Over the last 2 centuries, the predominant view of the cerebellum has been that it is part of a motor control system. Evidence is now presented that the neocerebellum, the evolutionarily newest region of the cerebellum, may also be involved in a key mental operation: the voluntary shift of selective attention between sensory modalities. It is theorized that this newly recognized function may operate via previously described sensory modulation properties of the cerebellum and its many connections with areas known to be important for selective attention, such as the pulvinar, the superior colliculus, and the parietal and frontal cortices.
Cerebellar and cerebral abnormalities in Rett syndrome: a quantitative MR analysis.
Rett syndrome is a neurodegenerative disease of young girls that begins in early childhood with autismlike behavior and loss of language skills, and progresses with marked deterioration of the motor system in the second decade of life. The purpose of this study was to determine if neuroanatomic changes detected with MR imaging could help to explain the clinical presentation and progression of signs and symptoms in these patients. Accordingly, computer-assisted planimetry was used to measure various dimensions of cerebral, cerebellar, and brainstem structures on sagittal and transverse MR images of 13 patients with Rett syndrome and 10 healthy volunteers. Dimensions of the cerebrum, basal ganglia, cerebellum, and brainstem were measured on transverse images. Areas of cerebellar vermian lobules, the fourth ventricle, the pituitary gland, and the corpus callosum were measured on sagittal images. Fourteen dimensions and areas were measured in each patient and each control subject; according to two-tailed Student's t tests, all but two values were significantly smaller in the patients with Rett syndrome than in control subjects. Graphing the measurements against age by using simple linear regression revealed progressive cerebellar atrophy without evidence of atrophy of the brainstem or cerebrum. Our results indicate that patients with Rett syndrome have global hypoplasia of the brain and progressive cerebellar atrophy increasing with age. Cerebellar atrophy with age may contribute to the deterioration of the motor system seen in older patients with Rett syndrome.
Absence of magnetic resonance imaging evidence of pontine abnormality in infantile autism.
In vivo studies involving magnetic resonance imaging and studies of neuropathologic specimens have shown that autism is most consistently associated with developmental hypoplasia of the neocerebellum. We investigated whether the cerebellar hypoplasia was accompanied by gross structural abnormalities in the major input (cerebrocerebellar) and output (cerebrorubral) pathways to the cerebellum by measuring the area of the ventral pons (including the pontine nuclei and the transverse fibers) and the midbrain on midsagittal magnetic resonance images in 34 autistic and 44 subjects. The area of the entire pons and several regions of interest within the midbrain (including the superior and inferior colliculi) were also determined with midsagittal magnetic resonance images. We found no significant difference between measurements of the pons and midbrain in autistic and control subjects. Our data show no evidence of gross anatomic abnormalities in the input and output pathways to the cerebellum in autism, a finding that is consistent with previous studies of neuropathologic specimens; rather, the reduced size of the neocerebellum in autism appears to be the result of maldevelopment within the cerebellum itself.
Protocols to establish genotype-phenotype correlations in Down syndrome.
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Neuroanatomic imaging in autism.
Based on neuroimaging and autopsy research, in autism no common site or type of abnormality appears in the cerebral hemispheres, thalamus, lenticular nuclei, and caudate nucleus. Nonetheless, further imaging and autopsy studies on this issue can be anticipated. Limbic system abnormalities have been reported at autopsy by one laboratory but not another, and no abnormality was found by the one quantitative MR study to measure a limbic structure. More autopsy and imaging research on the limbic system is needed. The cerebellum is the only anatomical structure for which there is both imaging and autopsy evidence of abnormality based on data gathered by many laboratories. Also, the only autopsy study to conduct statistical analyses of cerebellar cell loss found statistically significant Purkinje cell loss in both the vermis and hemispheres. Despite this, normal findings on routine radiologic examination are not of diagnostic significance at this time. On the one hand, the autopsy data show that most, if not all, autistic individuals have cerebellar cell loss, but on the other, research shows that MR images of the cerebellum in a substantial proportion of autistic individuals (perhaps 20% to 50%) will be indistinguishable from normal. Thus, it is likely that MR technology is not yet sufficiently sensitive to detect cerebellar abnormalities in all autistic persons who have them. Finally, the cerebellum seems an unlikely site of damage for a developmental disorder of higher cognition such as autism. However, new neurophysiologic and neuropsychologic studies of children with hemicerebellar resections and children with hemicerebellar resections and children with autism present an entirely new picture of the role of the cerebellum in normal human cognition in general and in the development of the social and communication deficits in autism in particular. These studies show that autistic subjects and patients with acquired cerebellar damage are unable to rapidly shift their mental focus of attention.
Increased distractibility in schizophrenic patients. Electrophysiologic and behavioral evidence.
The inability of schizophrenics to filter irrelevant information has often been implicated in the psychopathology of schizophrenia. Despite numerous attempts at characterizing the behavior of schizophrenics in the presence of distractors, evidence of increased distractibility has been equivocal due to the difficulty of assessing simultaneously the behavioral and neurophysiological effects of distracting stimuli. We report the results of an experiment in which event-related potential and performance measures were used to assess distractibility during reaction time tasks under different distracting conditions. The results supported the view of an increased distractibility in schizophrenic patients. Event-related potential data suggested that in schizophrenic patients, a reduced amount of processing resources is allocated to process external stimuli and attention is abnormally apportioned to task-irrelevant vs task-relevant stimuli.
Effects of focused selective attention tasks on event-related potentials in autistic and normal individuals.
Event-related potentials (ERPs) and behavioral responses were recorded from autistic and normal subjects under two focused selective attention conditions. In each condition, subjects were presented with an identical stimulus paradigm--a random sequence of 50 msec sounds and flashes occurring at interstimulus intervals ranging between 0.5 and 1.5 sec. The sequence consisted of rare auditory (12.5%), rare visual (12.5%), standard auditory (37.5%) and standard visual (37.5%) stimuli. In the focal auditory condition, subjects pressed a button to the rare auditory target, and in a focal visual condition, they pressed a button to the rare visual stimuli. When normal subjects detected target stimuli in a given attended modality, all stimuli in the attended modality produced enhanced negative ERP responses at frontal electrode sites (i.e., auditory Nde, Ndl, and Nc; visual N270 and Nc) and enhanced positive ERP responses at posterior electrode sites (i.e., P3b and visual P400). In the autistic subjects, in contrast, all auditory and visual attention-related negativities recorded in the auditory and visual focused attention tasks were not in evidence. P3b was significantly diminished in size. The results suggest that abnormalities in the neurophysiological mechanisms of selective attention may underlie the cognitive deficits in autism. The present report and its companion papers are the first reports of the neurophysiological correlates of selective attention in autism.
Effects of rare non-target stimuli on brain electrophysiological activity and performance.
In order to assess the effects of non-target stimuli on task performance and electrophysiological activity, 16 subjects performed reaction time (RT) experiments under 3 conditions. In all conditions, subjects had to press a button upon detection of rare (15%) target stimuli (1600 Hz) presented among frequent (85%) non-target stimuli. The 3 conditions differed based on their non-target stimuli. In one condition, the non-targets consisted of 'standard' stimuli (900 Hz). In the two other conditions, rare and deviant non-target stimuli were randomly added to the standard stimuli. These deviant non-target stimuli consisted of either constant (700-Hz tones) or novel (buzzes, filtered noises and other unusual sounds) stimuli. Both the rare target and non-target stimuli elicited P300, responses. Behavioral (RT) and electrophysiological (event-related potential) data showed that stimuli that followed standard stimuli were processed differently compared to stimuli that followed deviant non-target stimuli. In the conditions containing deviant non-target stimuli, the P3b to the target stimuli was smaller and later, and the mean RT longer than in the condition with no deviant stimuli. These behavioral and electrophysiological changes induced by the deviant non-target stimuli were discussed with reference to two factors, distraction and increased level of task difficulty. It was suggested that each of these factors were differentially sensitive to the novelty of the rare deviant stimuli.
The cerebellum: 3. Anatomic-MR correlation in the coronal plane.
Thin (5-mm) coronal high-field (1.5-T) MR images of four human brain specimens and 14 normal volunteers were correlated with myelin-stained microtomic sections of the specimen cerebella. The primary white-matter tracts innervating several hemispheric (posterior quadrangular, superior, and inferior semilunar, gracile, biventer, tonsil) and vermian (declive, folium, tuber) lobules are oriented perpendicularly to the coronal plane of section and are shown well on proton-density-weighted (long TR/short TE) and T2-weighted (long TR/long TE) spin-echo images, which provide excellent contrast between gray and white matter. Several of the surface sulci and fissures of the cerebellar hemispheres (including the superior posterior, horizontal, secondary, and posterolateral fissures) also course perpendicular to the coronal plane and are depicted well on T1-weighted (short TR/short TE) and T2-weighted images, which maximize contrast between CSF and parenchyma. The opportunity for side-to-side comparison of the hemispheres is a distinct advantage of the coronal view. Nevertheless, more obliquely oriented surfaces (preculminate, primary, inferior posterior, inferior anterior, and intrabiventral fissures) and deep hemispheric structures (primary white-matter tracts to central, anterior quadrangular, and floccular lobules) may be obscured by volume-averaging in the coronal plane; moreover, much of the finer anatomy of the vermis is depicted poorly. The constant surface and deep anatomy of the cerebellum revealed on coronal images in normal volunteers encourages detailed mapping. MR imaging in the coronal plane should be especially useful in identifying, localizing, and quantifying normal and abnormal morphologic differences between the cerebellar hemispheres.
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.
Brainstem and middle latency auditory evoked potentials in autism and developmental language disorder.
Brainstem auditory evoked potentials (BAEP) and middle latency responses (MLR) were studied in 8 nonretarded subjects with infantile autism (mean age = 23.3, SD = 2.8), 8 subjects with receptive developmental language disorder (mean age = 16.3, SD = 1.4), and normal control subjects matched to each group for age, gender, and Performance IQ. Click stimuli were delivered monaurally to the left and the right ear and binaurally for both the BAEPs (70-dB HL, 7/sec) and the MLRs (60-dB HL, 13/sec). Amplitudes and latencies (Waves I to VI), interwave latencies (III-V, I-V, and I-III), and Wave I/V amplitude ratio of the BAEPs were determined for each group. For the MLR study, Wave Na, Pa, and Nb latencies, and Wave Na-Pa and Pa-Nb amplitudes were calculated. There were no consistent differences in the BAEP and MLR characteristics of the control and the experimental groups. These results suggest that the abnormal cognitive processes indexed by the cognitive and attention-related event-related potential components in infantile autism and receptive developmental language disorder are not due to abnormal sensory processing in the brainstem and in areas central to the brainstem whose activity generates the BAEPs and MLRs.
Pathophysiologic findings in nonretarded autism and receptive developmental language disorder.
In nonretarded autistic, receptive developmental language disordered, and normal subject groups, we recorded in auditory and visual target detection tasks two neurophysiological components of the event-related brain potential, Nc and P3b. Existent research shows that, in normals, Nc and P3b appear early in development, are associated with attention and memory processes, and are endogenous which means that they are triggered by internal, consciously initiated attentional and cognitive mechanisms and that they can be triggered even by the omission of sensory stimulation so long as it has meaning or importance for the subject. In this report, Nc and P3b were recorded in response to auditory and visual stimulation and to the omission of auditory and visual stimulation. Consistent with the hypothesis that non-retarded autism involves abnormal attentional and cognitive responses to important information, P3b was found to be smaller than normal and Nc was small and often absent in the nonretarded autistic group even under the condition when no auditory language or sensory processing was required. Receptive developmental language disorder has been linked with difficulties in processing sequences of auditory stimuli, and in this study P3b was found to be somewhat enlarged in this group even under the conditions when P3b was elicited by stimuli separated by 1 sec and also when P3b was elicited by the omission of stimulation.
Brainstem auditory evoked potentials in receptive developmental language disorder.
It has been hypothesized that receptive developmental language disorder (RDLD) may be explained by an auditory processing deficit. The neuroanatomical locus of this deficit is unknown. Brainstem auditory evoked potentials (BAEPs) reflect the functioning of the auditory nerve and auditory brainstem pathways to high-frequency acoustical stimulation in humans and reflect the first stages of auditory processing. These were studied in 12 subjects with RDLD (four females and eight males, ages 12 to 19) and twelve control subjects (three females and nine males, ages 14 to 24). Click intensity and rate of stimulation were varied. The BAEPs for the RDLD group were comparable to the control group as well as to hospital norms across intensity levels and stimulation rates. The evidence obtained suggests that a disorder in the neurophysiological systems underlying the BAEPs and reflecting initial stages of auditory processing is not essential for RDLD.
The cerebellum in sagittal plane--anatomic-MR correlation: 1. The vermis.
Correlation of thin (5-mm) sagittal high-field (1.5-T) MR images of three brain specimens and 11 normal volunteers with microtome sections of the human cerebellar vermis and hemispheres demonstrates that proton-density-weighted (long TR/short TE) and T2-weighted (long TR/long TE) spin-echo pulse sequences provide the greatest contrast between gray and white matter. These images also can display (1) the corpus medullare and primary white-matter branches to the vermian lobules, including the lingula, centralis, culmen, declive, folium, tuber, pyramis, uvula, and nodulus; and (2) several finer secondary branches to individual folia within the lobules. Surface features of the vermis including the deeper fissures (e.g., preculminate, primary, horizontal, and prepyramidal) and shallower sulci are best delineated by T1-weighted (short TR/short TE) and T2-weighted images, which provide greatest contrast between CSF and parenchyma. Given that the width of the normal vermis varied from 6 to 12 mm in our volunteers, the acquisition of thin slices (less than or equal to 5 mm) was required to minimize volume averaging of the cerebellar hemispheres with the vermis on a midline sagittal MR section. Knowledge of the detailed normal anatomy of the cerebellar vermis on sagittal MR images can assist in the identification of various pathologic alterations.
The cerebellum in sagittal plane--anatomic-MR correlation: 2. The cerebellar hemispheres.
Thin (5-mm) sagittal high-field (1.5-T) MR images of the cerebellar hemispheres display (1) the superior, middle, and inferior cerebellar peduncles; (2) the primary white-matter branches to the hemispheric lobules including the central, anterior, and posterior quadrangular, superior and inferior semilunar, gracile, biventer, tonsil, and flocculus; and (3) several finer secondary white-matter branches to individual folia within the lobules. Surface features of the hemispheres including the deeper fissures (e.g., horizontal, posterolateral, inferior posterior, and inferior anterior) and shallower sulci are best delineated on T1-weighted (short TR/short TE) and T2-weighted (long TR/long TE) sequences, which provide greatest contrast between CSF and parenchyma. Correlations of MR studies of three brain specimens and 11 normal volunteers with microtone sections of the anatomic specimens provides criteria for identifying confidently these structures on routine clinical MR. MR should be useful in identifying, localizing, and quantifying cerebellar disease in patients with clinical deficits.