Behavioral alterations in rats prenatally exposed to valproic acid: Animal model of autism

• We analyze the behavioral and motor disturbances in childhood autism. On the basis of analogy to signs and conditions seen in adult neurology, we propose that the syndrome results from dysfunction in a system of bilateral neural structures that includes the ring of mesolimbic cortex located in the mesial frontal and temporal lobes, the neostriatum, and the anterior and medial nuclear groups of the thalamus. The mesolimbic cortex is cytoarchitectonically, angioarchitectonically, and neurochemically distinct and, along with the striatum, forms the entire target area of dopaminergic mesencephalic neurons. This raises the possibility that autism is related to neuromediator imbalance in those structures. Such dysfunction might be the result of macroscopic or microscopic changes in the target area or in structures functionally influencing them, consequent to a variety of causes such as perinatal viral infection, insult to the periventricular watershed area, or genetically determined neurochemical abnormalities.

A Neurological Model for Childhood Autism

As part of an autopsy research project, the brains of four autistic subjects were examined and compared with those of three comparison subjects without CNS pathology and one with phenytoin toxicity. The cerebellum was selected for initial investigation because pathognomonic symptoms and neurophysiological measures suggest that pathology may exist in the cerebellar-vestibular axis in certain patients. Total Purkinje cell counts were significantly lower in the cerebellar hemisphere and vermis of each autistic subject than in the comparison subjects.

Lower Purkinje cell counts in the cerebella of four autistic subjects: initial findings of the UCLA-NSAC Autopsy Research Report.

Rhythmical stereotypies in normal human infants

This article considers the evidence for an imitative deficit in autism and for the possible role of deficiencies in the representation of actions. An argument is developed for the claim that the imitation problem is diagnostic of a basic information-processing rather than a social dysfunction. Reviews are offered of the empirical literature on gestural imitation in autism (and other developmental disorders) and the more anecdotal evidence for problems in the domain of action development in autism. An account that may help to integrate these areas is suggested, as are directions for future research.

Imitation and action in autism: A critical review.

The EEG and rapid eye movements during REM sleep in normal and autistic children.

EXTENSIVE clinical observations of children usually diagnosed as autistic, schizophrenic, symbiotic-psychotic, and with "atypical ego development" indicate that they manifest similar features and can be best understood as suffering from variants of a single disease 1 . Their symptoms can be grouped into five subclusters which make their similarities clear: (1) disturbances of perception, (2) disturbances of motor behaviors, (3) disturbances in the ability to relate to others, (4) absent or pathologic language development, and (5) disturbances of developmental rate. The disturbances of perception appear to be fundamental to the other aspects of the disease. The total symptom complex suggests that there is an underlying neuropathology 2 which leads to periodic overloading and underloading of the central nervous system. These alternating states of excessive facilitation and inhibition vary the child's awareness and response to the same stimuli and causes what we have termed perceptual inconstancy.

Steven La Franchi

Papers

The EEG and rapid eye movements during REM sleep in normal and autistic children.

Frequency of Repetitive Behaviors in Early Infantile Autism and Its Variants

The effect of sleep onset on the auditory averaged evoked response.

Effects of imipramine on the sleep-dream cycle: An EEG study in boys