Convergent neuroanatomical and behavioural evidence of an amygdala hypothesis of autism.

In this study we report a convergence of behavioural and neuroanatomical evidence in support of an amygdala hypothesis of autism. We find that people with high-functioning autism (HFA) show neuropsychological profiles characteristic of the effects of amygdala damage, in particular selective impairment in the recognition of facial expressions of fear, perception of eye-gaze direction, and recognition memory for faces. Using quantitative magnetic resonance (MR) image analysis techniques, we find that the same individuals also show abnormalities of medial temporal lobe (MTL) brain structure, notably bilaterally enlarged amygdala volumes. These results combine to suggest that developmental malformation of the amygdala may underlie the social-cognitive impairments characteristic of HFA. This malformation may reflect incomplete neuronal pruning in early development.

Face processing impairments after encephalitis: amygdala damage and recognition of fear.

Face processing and facial emotion recognition were investigated in five post-encephalitic people of average or above-average intelligence. Four of these people (JC, YW, RB and SE) had extensive damage in the region of the amygdala. A fifth post-encephalitic person with predominantly hippocampal damage and relative sparing of the amygdala (RS) participated, allowing us to contrast the effects of temporal lobe damage including and excluding the amygdala region. The findings showed impaired recognition of fear following bilateral temporal lobe damage when this included the amygdala. For JC, this was part of a constellation of deficits on face processing tasks, with impaired recognition of several emotions. SE, YW and RB, however, showed relatively circumscribed deficits. Although they all had some problems in recognizing or naming famous faces, and had poor memory for faces on the Warrington Recognition Memory Test, none showed a significant impairment on the Benton Test of Facial Recognition, indicating relatively good perception of the face's physical structure. In a test of recognition of basic emotions (happiness, surprise, fear, sadness, disgust and anger), SE, YW and RB achieved normal levels of performance in comparison to our control group for all emotions except fear. Their results contrast with those of RS, with relative sparing of the amygdala region and unimpaired recognition of emotion, pointing clearly toward the importance of the amygdala in the recognition of fear.

Hemispheric function in developmental language disorders and high-level autism.

Two groups of children with contrasting types of developmental language disorder (phonologic-syntactic and semantic-pragmatic) were compared with a group of children with high-level autism and with a control group of normal children on a broad battery of neuropsychological tests, known to be sensitive to left-right hemisphere damage. Significant differences found between the groups suggest contrasting forms of hemispheric dysfunction.

Social cognition in developmental language disorders and high-level autism.

Two groups of children with contrasting types of developmental language disorder (phonologic-syntactic and semantic-pragmatic) were compared with a group of children with high-level autism and with a control group of normal children on tests of social cognition (theory of mind; social comprehension; and detection of eye direction). The similarly poor performances of the semantic-pragmatic group and the autistic group suggest that semantic-pragmatic language disorder lies on the autistic spectrum.

Neuropsychological investigation of anterior and posterior cortical function in early-stage probable Alzheimer's disease.

In vivo neuroimaging studies have generally indicated a greater involvement of posterior cortical areas in early-stage dementia of the Alzheimer type (DAT) relative to frontal involvement. By contrast, some recent neuropsychological studies have shown that DAT patients perform poorly in frontal lobe tasks even in the early stages of the disease, although there is disagreement as to whether this necessarily implicates frontal pathology. The main aim of this study was to examine the hypothesis prompted by both neuroimaging studies and the traditional clinical conception of the disease, that, compared with the functioning of posterior association cortex, executive functions (thought to depend on frontal lobe integrity) are relatively spared in the early stages of DAT. A group of patients with a diagnosis of early-stage, probable DAT (n = 17) was compared with age- and IQ-matched controls (n = 17) across a range of neuropsychological tasks presumed to exercise frontal or temporoparietal functions. A profile of strengths and weaknesses was observed across 'anterior' and 'posterior' cognitive tests, including dissociations among some tests of temporoparietal function, in particular visual object perception (impaired) and spatial analysis skills (intact). Thus there was little support for the notion that the disease progresses cortically in a posterior-to-anterior direction. Possible reasons for the discrepancy between neurophysiological and neuropsychological observations are discussed, including the possibility that neuropsychological tests do not provide a valid indication of regional brain function when used in the context of DAT. Caution is urged in the clinical application of 'frontal lobe tests' for the differential diagnosis of DAT.

Face processing impairments after amygdalotomy.

We report an investigation of face processing impairments in D.R., a 51-year-old woman with a partial bilateral amygdalotomy. D.R. was able to recognize pre-operatively familiar faces, but she showed generalized problems of name retrieval and a more circumscribed deficit affecting the recognition of faces learnt post-operatively. In contrast to her poor memory for new faces, D.R.'s ability to match simultaneously presented photographs of unfamiliar faces was unimpaired. However, D.R. also experienced deficits in expression processing which compromised the recognition of emotion from people's faces: she was poor both at matching and at identifying photographs of emotional facial expressions. In addition, her interpretation of eye gaze direction was defective, showing a more general problem in reading social signals from the face. The presence of impairments affecting the learning of new faces and the comprehension of gaze direction and facial expressions of emotion is consistent with the hypothesis of a role for the amygdala in learning and social behaviour.

The effects of scopolamine on retrieval from semantic memory.

The effects of two doses of scopolamine (0.6 and 1.2 mg p.o.) on retrieval from semantic memory in normal young volunteers were examined using tests of verbal fluency and categorization latency. A visual contrast sensitivity test, which has previously shown a scopolamine-induced impairment at these doses (Broks et al., 1988), was also administered. In agreement with the work of Dunne (1990) and others, no evidence for a scopolamine deficit in semantic retrieval was found; in fact scopolamine improved letter fluency. However, scopolamine did produce the expected decrease in visual contrast sensitivity. The doses of scopolamine used here have also been shown to impair learning and attention (Broks et al., 1988). It is possible that earlier studies which found a scopolamine deficit on semantic retrieval, did so because they used elderly subjects and/or large drug doses.

Effects of lorazepam on memory, attention and sedation in man: antagonism by Ro 15-1788.

In this study we examined the effects of lorazepam (2.0 mg PO) plus either placebo or one of three doses of the benzodiazepine antagonist Ro 15-1788 (0.3 mg, 1.0 mg or 3.0 mg IV) on measures of memory, attention and sedation. We found that lorazepam impaired verbal secondary memory performance, but also produced subjective and objective sedation; it increased reaction time, reduced critical flicker fusion thresholds and caused subjects to make more errors on a sustained attention task and rate themselves as drowsy. Ro 15-1788 dose dependently blocked the deficit in secondary memory produced by lorazepam, but also showed monotonic dose-related antagonism of its effects on indices of sedation (with the exception of the critical flicker fusion deficit, which was unaffected). These results demonstrate that lorazepam-induced cognitive deficits can be blocked by a benzodiazepine receptor antagonist. They also suggest that the memory deficits produced in this pharmacological model of organic amnesia are not readily dissociated from deficits in attention.

Effects of lorazepam on memory, attention and sedation in man.

The effects of three doses of lorazepam (0.5, 1.0 and 2.0 mg PO) on various aspects of memory, attention and sedation are described. Lorazepam produced dose-related deficits in verbal secondary memory, choice reaction time and a novel vigilance task. It also produced a dose-dependent increase in subjective sedation, and an enhancement of visual contrast sensitivity. These results are compared with those reported earlier using the muscarinic antagonist scopolamine, and discussed in relation to models of Alzheimer's disease.

Modelling dementia: effects of scopolamine on memory and attention.

Scopolamine, a muscarinic cholinergic antagonist, is capable of inducing transient memory impairment in normal subjects. Against the background of the cholinergic hypothesis of Alzheimer's disease (AD) the present study was designed to investigate the effects of low oral doses of scopolamine on a range of cognitive functions known or hypothesized to be affected in AD. Twenty healthy volunteers (18-48 yr) performed a battery of automated cognitive tasks under each of five treatments: oral scopolamine 0.3 mg, 0.6 mg, 1.2 mg; oral methylscopolamine 0.6 mg; placebo. Alongside analogous tests of verbal and non-verbal memory, the battery enabled assessments of a range of attentional functions: alerting, sustained attention, selective attention, and covert orientation. A profile of effects was observed within and beyond the realm of memory. While some functions were unaffected by the drug (e.g. alerting) and others were impaired at the highest dose (e.g. verbal learning) still others were affected in a linear dose-dependent manner (sustained attention; visual contrast sensitivity). These observations are discussed in the context of the "scopolamine model" of AD.

The scopolamine model of dementia: determination of central cholinomimetic effects of physostigmine on cognition and biochemical markers in man.

Administration of the muscarinic antagonist scopolamine has been proposed as a pharmacological model for Alzheimer's disease. We have attempted to characterize the cognitive deficits produced by the administration of scopolamine (0.2 and 0.4 mg intra muscularly) to normal volunteers. We have also demonstrated reversal of these deficits by the cholinesterase inhibitor physostigmine (1.2 mg intramuscularly). Physostigmine also elevated subjects' plasma ACTH levels, a marker of central cholinergic activity. In the cognitive study, we found that scopolamine impaired subjects' performance on verbal learning, spatial learning and choice reaction time. These changes were associated with subjective sedation as measured by analogue rating scales. Physostigmine attenuated the impairment in verbal learning and reduced subjective sedation. In the biochemical study we examined the effects of the same drug regimes on plasma ACTH levels. Physostigmine administered with a peripherally active cholinergic antagonist (glycopyrrolate 0.2 mg intramuscularly) produced a rise in ACTH level which reached a peak 30 min after drug administration. Such a rise was not apparent when the physostigmine was coadministered with scopolamine. These results suggest that cognitive and neuroendocrine indices of central cholinergic activity such as these may be useful in determining the effectiveness of potential new therapeutic agents for Alzheimer's disease.

Ear by visual-field interaction on a cross-modal syllable-matching task.

Twenty-eight subjects (15 male, 13 female) performed a visual/auditory cross-modal matching task involving same/different judgements of CVC nonsense syllables. In the visual modality stimuli were presented either unilaterally or at the midline, and in the auditory modality, binaurally or monaurally--giving nine combinations of simultaneous input. Predictions for RT under each condition were derived by aggregating the assumed effects of single modality lateralized presentation on the basis of a simplistic anatomical model. An unpredicted ear X visual-field interaction emerged which, it is speculated, may in part reflect the operation of transcallosal inhibitory effects. Cross-modal matching is proposed as a paradigm for future investigations of interhemispheric integration.

Effect of o-(beta-hydroxyethyl)-rutoside in lymphangiography.

In 30 patients who underwent lymphography of the retroperitoneal lymph nodes, the lymph vessels of one leg were pretreated with 5 ml of 10% o(beta-hydroxyethyl)-rutoside (HR) prior to administration of Lipiodol Ultrafluid. There were no untoward clinical effects associated with the pretreatment. Legs pretreated with HR showed significantly fewer extravasations of contrast material than those untreated. HR appears to reduce the permeability of the lymph vessels, thus preventing or diminishing the occurrence of extravasations.

Pulmonary lesions caused by blunt chest injury.

This discussion of pulmonary lesions caused by blunt chest injury points out the importance of chest X-rays, particularly in the case of costal fractures, contusion of the lungs, and respiratory distress syndrome.

Radiological features of pulmonary venous hypertension in pulmonary emphysema.

In pulmonary emphysema, the normal features of pulmonary venous hypertension are often disturbed due to destruction of pulmonary tissue. The abnormal features are described.