Andrew R. Mayes

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.

Voxel-Based Morphometry Reveals Increased Gray Matter Density in Broca's Area in Male Symphony Orchestra Musicians

Brocas area is a major neuroanatomical substrate for spoken language and various musically relevant abilities, including visuospatial and audiospatial localization. Sight reading is a musician-specific visuospatial analysis task, and spatial ability is known to be amenable to training effects. Musicians have been reported to perform significantly better than nonmusicians on spatial ability tests, which is supported by our findings with the Benton judgement of line orientation (JOL) test (P < 0.001). We hypothesised that use-dependent adaptation would lead to increased gray matter density in Brocas area in musicians. Voxel-based morphometry (VBM) and stereological analyses were applied to high-resolution 3D MR images in male orchestral musicians (n = 26) and sex, handedness, and IQ-matched nonmusicians (n = 26). The wide age range (26 to 66 years) of volunteers permitted a secondary analysis of age-related effects. VBM with small volume correction (SVC) revealed a significant (P = 0.002) region of increased gray matter in Brocas area in the left inferior frontal gyrus in musicians. We observed significant age-related volume reductions in cerebral hemispheres, dorsolateral prefrontal cortex subfields bilaterally and gray matter density in the left inferior frontal gyrus in controls but not musicians; a positive correlation between JOL test score and age in musicians but not controls; a positive correlation between years of playing and the volume of gray matter in a significant region identified by VBM in under-50-year-old musicians. We suggest that orchestral musical performance promotes use-dependent retention, and possibly expansion, of gray matter involving Brocas area and that this provides further support for shared neural substrates underpinning expressive output in music and language.

Does Context Discriminate Recollection from Familiarity in Recognition Memory

Five experiments were conducted to examine subjects’ ability to make contextual judgements about recognized items for which they report recollective experience or only familiarity within the context of the experiment. In the first four experiments, subjects were able to make judgements of the spatiotemporal context of items that were accompanied by recollective experience significantly better than for items they merely found familiar. In only one of the four studies did subjects display above-chance performance on spatiotemporal judgements for merely familiar items. A fifth experiment examined the frequency with which subjects report the presence of different kinds of contextual knowledge during a standard recognition experiment. All aspects of contextual knowledge were reported with higher frequencies for recollected items than for items only found familiar, although no single contextual feature was strongly associated with recollective experience. Thus, the five studies together provide converging evidence for the validity of the “recollect-know” distinction in recognition memory and supplement studies that have already demonstrated that the two kinds of response are dissociable. The implications of these data for group comparisons of memory-impaired patients, and the role of context in recognition memory are discussed.

Dissociation Between Recall and Recognition Memory Performance in an Amnesic Patient with Hippocampal Damage Following Carbon Monoxide Poisoning

Abstract Some patients with relatively selective hippocampal damage have shown proportionate recall and recognition deficits. Moreover, familiarity as well as recollection have been found to be impaired in some of these patients. In contrast, other patients with apparently similar damage presented with relatively preserved recognition despite having severely impaired recall, and some of these patients have been shown to have preserved familiarity. We report here the case of an amnesic patient who suffered bilateral hippocampal damage and temporoparietal atrophy after carbon monoxide poisoning. On tests matched for difficulty, his recall performance was more severely impaired than his recognition memory, for verbal as well as for visual materials. Moreover, he performed within the range of healthy matched subjects on nine recognition tests out of ten. In a task using the process dissociation procedure, the patients familiarity was preserved although his recollection was impaired. These findings indicate that recall and recognition memory can be dissociated in amnesic patients with hippocampal lesions even when temporoparietal cortical atrophy is also present.

Differential involvement of the hippocampus and temporal lobe cortices in rapid and slow learning of new semantic information.

The present study examined the rapid and slow acquisition of new semantic information by two patients with differing brain pathology. A partial double dissociation was found between the patterns of new learning shown by these two patients. Rapid acquisition was impaired in a patient (YR) who had relatively selective hippocampal damage, but it was unimpaired in another patient (JL) who, according to structural MRI, had an intact hippocampus but damage to anterolateral temporal cortex accompanied by epileptic seizures. Slow acquisition was impaired in both patients, but was impaired to a much greater extent in JL. The dissociation suggests that the mechanisms underlying rapid and slow acquisition of new semantic information are at least partially separable. The findings indicate that rapid acquisition of semantic, as well as episodic information, is critically dependent on the hippocampus. However, they suggest that hippocampal processing is less important for the gradual acquisition of semantic information through repeated exposure, although it is probably necessary for normal levels of such learning to be achieved.

Long-term amnesia: a review and detailed illustrative case study.

Long-term amnesia is a slowly developing form of anterograde amnesia accompanied by retrograde amnesia of variable severity (Kapur, 1996; 1997) often associated with damage to the anterior temporal neocortex and epileptic seizures. The precise neural and functional deficits that underlie this condition are unknown. A patient, JL, who has this condition following a closed-head injury, is described in detail. Her injury caused bilateral anterior temporal neocortex damage that was more extensive on the left and right-sided damage to the perirhinal and orbitofrontal cortices. The hippocampus appeared to be intact bilaterally. Epilepsy developed within two years of JLs injury. Apart from her memory impairments, JLs cognitive functions, including high-level visual perception, attention, semantic memory and executive functions were well preserved. Her memory also seemed well preserved for at least 30 minutes following encoding. The one exception was the patients relatively greater impairment at difficult visual recognition tests for which verbalization may not have been an effective strategy. This problem may have been caused by JLs right-sided perirhinal and orbitofrontal cortex damage. Her recall and recognition was clearly impaired after a three-week delay. She also showed a retrograde amnesia, which appeared to be milder than her remote post-morbid memory deficit. JLs remote memory was preserved for information first encountered in either the pre- or post-morbid period provided the information had received sufficient rehearsal over long periods of time. Her long-term amnesia may have been caused by anterior temporal neocortex damage, possibly in association with her epileptic seizures. Whether the condition is heterogeneous, involves a deficit in slow consolidation, disruption of unconsolidated memories, or blockage of maintenance or disruption of insufficiently rehearsed memories whether or not these have been slowly consolidated is discussed.

A combined clinical, neuropsychological, and neuroanatomical study of adults with high functioning autism

Introduction. Three hypotheses concerning associations between neuroanatomical abnormalities, neuropsychological impairments, and the behavioural manifestations of autism were investigated. The primary hypothesis was that the social interaction impairments diagnostic of autism are associated with deficits of socioemotional perception and abnormalities of the amygdala. One subsidiary hypothesis was that the learning and language impairments that occur in less able individuals with autism are associated with impaired memory, and with abnormalities of hippocampal regions. A second subsidiary hypothesis was that the repetitive behaviour diagnostic of autism is associated with executive deficits and with abnormalities of the prefrontal cortex. Associations between the neuroanatomical regions investigated were also examined.Methods. Ten adult males with high functioning autism (HFA) were compared with 10 healthy controls matched for age, sex, verbal and nonverbal ability. Hypothesis-driven structural MRI and neuropsychological tests were used to collect neuroanatomical and neuropsychological data on all subjects. A version of the Wing Autism Diagnostic Interview Checklist was used to collect clinical data on the HFA subjects.Results. Strong convergent evidence in support of the amygdala hypothesis was obtained, and preliminary support for the hippocampal/parahippocampal hypothesis. No clear evidence was obtained in support of the prefrontal hypothesis. Patterns of associations amongst volume measures within and between medial temporal and prefrontal regions suggest stronger within-region and weaker between-region associations in the HFA group compared with controls.Conclusions. These findings are discussed in terms of a model of autism in which selective abnormalities of the amygdala and hippocampus (in all cases) and of the parahippocampal gyrus (in lower functioning cases) are implicated, and in which a disruption of coordinated limbic and prefrontal activity may be critical.

Visual paired comparison performance is impaired in a patient with selective hippocampal lesions and relatively intact item recognition

In this study, we have examined visual recognition memory in a patient, YR, with discrete hippocampal damage who has shown normal or nearly normal item recognition over a large number of tests. We directly compared her performance as measured using a visual paired comparison task (VPC) with her performance on delayed matching to sample (DMS) tasks. We also investigated the effect of retention interval between familiarisation and test. YR shows good visual recognition with the DMS task up to 10 s after the familiarisation period, but only shows recognition with the VPC task for the shortest retention interval (0 s). Our results are consistent with the view that hippocampal damage disrupts recollection and recall, but not item familiarity memory.

The Hippocampus and Delayed Recall: Bigger is not Necessarily Better?

Healthy young female participants were tested on a measure of delayed verbal recall and then received volumetric Magnetic Resonance Imaging (MRI) scans. The analysis of the MRI scans focused on the volume of the hippocampus. Left hippocampal volume was negatively associated with the level of delayed verbal recall performance. This relationship was confirmed in further testing. This finding is consistent with a previous report of a similar relationship in healthy elderly individuals, but not in patients with Alzheimers disease, in whom the opposite relationship was observed. An explanation of these findings in terms of impaired neural pruning of the hippocampus is advanced, whereby insufficient pruning of the hippocampus during childhood and adolescence (following adequate growth) may lead to reduced mnemonic efficiency.

An exploratory study of the relationship between face recognition memory and the volume of medial temporal lobe structures in healthy young males.

A rigorous new methodology was applied to the study of structure function relationships in the living human brain. Face recognition memory (FRM) and other cognitive measures were made in 29 healthy young male subjects (mean age = 21.7 years) and related to volumetric measurements of their cerebral hemispheres and of structures in their medial temporal lobes, obtained using the Cavalieri method in combination with high resolution Magnetic Resonance Imaging (MRI. Greatest proportional variability in volumes was found for the lateral ventricles (57%) for the cerebral hemispheres (8%) in the mean volumes of the hippocampus, parahippocampal gyrus, amygdala, caudate nucleus, temporal pole and temporal lobe on the right and left sides of the brain. The volumes of the right and left parahippocampal gyrus, temporal pole, temporal lobe, and left hippocampus were, prior to application of the Bonferroni correction to take account of 12 multiple comparisons, significantly correlated with the volume of the corresponding hemisphere(p < 0.05). The volumes of all structures were highly correlated (p < 0.0002 for all comparisons) between the two cerebral hemispheres. There were no positive relationships between structure volumes and FRM score. However, the volume of the right amygdala was, prior to application of the Bonferroni correction to take account of 38~multiple comparisons, found to be significantly smaller in the five most consistent high scorers compared to the five most consistent low scorers (t = 2.77,p = 0.025). The implications for possible relationships between healthy medial temporal lobe structures and memory are discussed.