White matter loss in healthy ageing: a postmortem analysis.

Age-related brain changes are widely documented. Because of differences in measurement methods and case selection, the reported effects of age on regional grey and white matter brain volumes, however, are much more pronounced and widespread in neuroimaging than in postmortem studies. Consequently, the magnitude of the effect that is specific to chronological age remains unresolved. We present postmortem volume measurements for 26 cortical, subcortical and white matter regions, in 24 human brains aged 46-92 years, free of neuropathological abnormalities. Significant age-related loss was observed in anterior and posterior white matter but not in total grey matter volumes. Further analyses on five cortical subregions previously reported to exhibit large age-related loss on MRI yielded negative results. These analyses demonstrate smaller changes with age than those reported in imaging studies. Although this discrepancy between postmortem and imaging studies may partly be explained by the increase in noise of the neuroimaging data with age, our results suggest that healthy brain ageing is a process affecting predominantly white matter not grey matter.

Volumetric analysis of a specific language region - the planum temporale.

Planum temporale volumes were determined for 42 control children (ages 4.2-15.7 years) using magnetic resonance imaging. The mean left planum temporale volume was 2729 mm3 (SD = 567) and the mean right planum temporale volume was 2758 mm3 (SD = 546). No significant hemispheric asymmetry was demonstrated. Analysis of co-variance (ANCOVA) showed that the absolute and proportional planum temporale volumes were not significantly associated with age or gender. We also demonstrated a reproducible method for planum temporale volume measurement by acquiring images in the coronal plane and then visualising the sagittal plane to improve accuracy for the posterior border.

The left human speech-processing cortex is thinner but longer than the right.

We present histological data from 21 post-mortem, adult human cases that indicate the neocortex on the left planum temporale (secondary auditory cortex) is thinner but longer than that on the right side. The volumes of the left and right regions are approximately equal. Thus, the left planum temporale cortex is long and thin and the right short and thick. The present data fit excellently with previous studies of the volume, surface area, cytoarchitectonics, and neuronal structures of these areas. From these studies we suggest that the hemispheric differences arise from a so-called "balloon model" of cortical development. In this the cortex is extended and stretched by white matter growth. The stretching is greater on the left side, leaving greater distances between neuronal columns and more tangentially (to the pial surface) oriented dendrites on that side. This difference in fine structure can result in more independent activity of individual columns on the left, and could be an anatomical factor in the usual dominance of the left hemisphere for speech perception (Seldon, 1982, 1985).

Cortical degeneration associated with phonologic and semantic language impairments in AD.

OBJECTIVE: To compare the pattern of cortical degeneration associated with different language deficits in cases of AD. METHODS: Cases for detailed neuropathologic analysis (Patients 1 and 2) were selected because of their detailed clinical and neuropsychological assessments of language dysfunction in AD. Patient 1 had severe phonologic impairment with relatively preserved semantic aspects of language. Patient 2 had severe semantic language impairment with relatively preserved phonologic skills. The tissue volume of cortical regions associated with speech and language function was measured using standardized three-dimensional techniques. Neuronal areal fraction was also measured from histologic tissue samples. The degree of volume atrophy and neuronal loss was calculated in comparison to control measures (n = 10 men and 11 women). Measurements more than 2 SD from controls were considered abnormal. RESULTS: Both AD cases had significant degeneration of the superior temporal gyrus and area 37. Cortical language regions affected only in Patient 1 included the anterior and posterior insula and part of Broca's area. In contrast, Patient 2 had a greater degree of degeneration in the temporal gyri and their white matter connections with the hippocampal/entorhinal complex. CONCLUSIONS: Variable patterns of neurodegeneration underlie the clinical differences observed in patients with AD. Disconnection within the temporal lobe appears associated with semantic language difficulties, whereas disconnection of the anterior and posterior language areas appears associated with phonologic and grammatical impairment.

The functional neuroanatomy of simple calculation and number repetition: A parametric PET activation study.

We examined cerebral activation patterns with positron emission tomography (PET) in 12 right-handed normal volunteers while they were completing simple calculation tasks or merely repeating numbers. Using a parametric experimental design, during calculation we found activation in the medial frontal/cingulate gyri, left dorsolateral prefrontal cortex, left anterior insular cortex and right anterior insular cortex/putamen, left lateral parietal cortex, and the medial thalamus. Number repetition engaged bilateral inferior sensorimotor cortex, bilateral temporal areas, and left inferior frontal cortex. These results suggest a functional anatomical network for simple calculation, which includes aspects of attention, auditory, and motor processing and the phonological store and articulatory loop components of working memory; they add some support for a special role of the parietal cortex in calculation tasks.

Specific temporoparietal gyral atrophy reflects the pattern of language dissolution in Alzheimer's disease.

The aim of this study was to determine the topography and degree of atrophy in speech and language-associated cortical gyri in Alzheimer's disease. The post-mortem brains of 10 patients with pathologically confirmed Alzheimer's disease and 21 neurological and neuropathological controls were sectioned in serial 3 mm coronal slices and grey and white matter volumes were determined for specific cortical gyri. All Alzheimer's disease patients had prospectively documented impairments in verbal and semantic memory with concomitant global decline. The cortical regions of interest included the planum temporale, Heschl's gyri, the anterior superior temporal gyri, the middle and inferior temporal gyri, area 37 at the inferior temporoparietal junction, areas 40 and 39 (supramarginal and angular gyri) and Broca's frontal regions. Although most patients had end-stage disease, the language-associated cortical regions were affected to different degrees, with some regions free of atrophy. These included Broca's regions in the frontal lobe and Heschl's gyri on the superior surface of the temporal lobe. In contrast, the inferior temporal and temporoparietal gyri (area 37) were severely reduced in volume. The phonological processing regions in the superior temporal gyri (the planum temporale) were also atrophic in all Alzheimer's disease patients while the anterior superior temporal gyri were only atrophic in female patients. Such atrophy may underlie the more severe language impairments previously described in females with Alzheimer's disease. The present study is the first to analyse the volumes of language-associated gyri in post-mortem patients with confirmed Alzheimer's disease. The results show that atrophy is not global but site-specific. Atrophied gyri appear to reflect a specific network of language and semantic memory dissolution seen in the clinical features of patients with Alzheimer's disease. Females showed greater atrophy than males in the anterior superior temporal gyri.

Language-associated cortical regions are proportionally larger in the female brain.

BACKGROUND: Many studies have demonstrated significant sexual dimorphism in verbal ability. However, few studies have examined anatomical differences between the sexes that may underlie such dimorphism. OBJECTIVE: To examine sex differences in the absolute and proportional volumes of the main language-associated regions of the cerebral cortex. DESIGN AND MAIN OUTCOME MEASURES: Control neuropathological case series of consecutive autopsies from a teaching hospital. No significant age-related volume changes were identified in the sample. Two language-associated cortical regions, the superior temporal gyrus (part of the Wernicke area) and its subdivisions (planum temporale, Heschl gyrus, and anterior superior temporal gyrus) and the inferior frontal gyrus (Broca area in the dominant hemisphere), and a non-language-associated region, the frontal pole, were measured using stereological techniques in brains fixed with formaldehyde solution serially sectioned at 3-mm intervals. Volume comparisons between the sexes and between brain hemispheres were performed using 2-way analysis of variance. SETTING: Studies were conducted at the University of Sydney and the Prince of Wales Medical Research Institute, Sydney, Australia. PATIENTS: Ten males and 11 females free from neurologic or neuropathological abnormalities. RESULTS: The volume of the superior temporal cortex, expressed as a proportion of total cerebral volume, was significantly larger in females compared with males (17.8% increase; P = .04). This was accounted for by 1 section of the superior temporal cortex, the planum temporale, which was 29.8% larger in females (P = .04). In addition, the cortical volume fraction of the Broca area in females was 20.4% larger than in males (P = .05). In contrast, no significant differences were found in the proportional volume of the frontal pole or in regional volumes between the left and right hemispheres in either sex group. CONCLUSIONS: Our results suggest that females have proportionally larger Wernicke and Broca language-associated regions compared with males. These anatomical differences may correlate with superior language skills previously demonstrated in females.

Topography of brain atrophy during normal aging and Alzheimer's disease.

The present study investigated the effect of age on total and regional brain volumes and compared age-associated changes in 20 healthy controls with those observed in 12 patients with Alzheimer's disease (AD). Weights and volumes of the whole brain and cerebrum, as well as the fractional volumes of the frontal, temporal, and parieto-occipital cortices, medial temporal structures, deep brain structures, and white matter were measured. Males had larger and heavier brains than females of comparable age. A small decline in brain volume with age was found (approximately 2 ml per year), but only within the white matter. In comparison, no further loss of white matter occurred in AD; however, the cerebral cortex was significantly reduced in volume, with the greatest loss from the medial temporal structures. This loss was related to disease progression; greater proportional loss was associated with more rapid decline in older patients. This study suggests that significant brain atrophy is not a consequence of advancing age. In addition, it suggests a regional specificity of damage in AD.

Reproducible sampling regimen for specific cortical regions: application to speech-associated areas.

The variability in the external gyri pattern of human brains has made the identification of specific cortical areas difficult. Studies correlating cortical structure and function have not consistently controlled for this variability. The aim of the present study was to develop a reliable and reproducible regimen for sampling five speech-associated and one non-speech associated cortical region in the human brain. The gyri of interest were labelled using non-aqueous dye prior to coronal slicing of brains at 3 mm intervals. Using the labelled gyri, a set of internal brain landmarks was established to aid in sampling one block of each cortical region of interest. The position of each internal landmark was determined as a percentage of the total brain length and breadth. The variability in the position of each internal landmark was investigated using analysis of variance and found to be consistent in three dimensions in all cases. The correlation of the sampled cortical region to the internal landmark was consistent in different cases with point to point agreement of 100%. This contrasts with the variability between cases in external gyri features. The sampled region was tested to determine cytoarchitectural variability by measuring the depth of each cortical layer. This technique found that the same cytoarchitectural regions were sampled in each case. As expected, these regions were distinguishable by the significant difference in the depth of different cortical layers. Accurate identification of both the external gyri and internal landmarks occurred with interrater point to point agreement of 90-100%.

Glial fibrillary acidic protein (GFAP) immunohistochemistry in human cortex: a quantitative study using different antisera.

Glial fibrillary acidic protein (GFAP) is the principal marker for brain astrocytes. The present study aims to examine the variability in GFAP immunohistochemistry in formalin-fixed human brain. Four commercially-available antisera were tested using standardised protocols in the cerebral cortex of three cases with prominent glial reactions and one control. GFAP immunoreactivity was largely confined to the pial surface and white matter in control cortex, with the number of astrocytic cell bodies and processes as well as intensity of staining markedly increased in damaged cortices. A dramatic difference in the pattern of GFAP staining using different antisera was observed and may account for discrepancies between past studies. This variance has important practical implications for the interpretation of results using GFAP immunohistochemistry in human tissue.

Quantification of cortical atrophy in a case of progressive fluent aphasia.

A patient with a rapidly developing fluent progressive aphasia was tested prospectively up to the time of death and examined neuropathologically. Severe impairment in accessing semantic skills with substantially intact phonological, syntactic and discourse skills was found. Some social behavioural difficulties were also noted. This case presented a unique opportunity to relate this significant language impairment to the pattern of neurodegeneration, a difficult task in most neuropathological studies of severe end-stage dementia. A detailed neuropathological examination revealed focal atrophy with neuronal loss without neuronal inclusions (Pick bodies, Lewy bodies, neurofibrillary tangles or senile plaques) or neuronal changes (shrinkage or swelling). In addition, spongiform degeneration (confined to layer two of the cortex) and gliosis were detected at atrophic sites. To establish the amount of tissue loss and pathology associated with the focal language deficit, volume analyses were performed and compared with two age- and sex-matched, neurologically normal controls. Both the left and right angular gyri and Brodmann's area 37 showed marked volume reduction compared with controls. The predominant language impairment seen in this case is likely to reflect these marked changes in the posterior parieto-temporal areas. The milder unilateral atrophy was concentrated in the right temporal lobe as well as the right hemisphere homologue of Broca's area. Recent work suggests a relationship between such unilateral changes and the social behavioural difficulties which were noted in this case. The hippocampus and other gyri such as the supramarginal gyrus showed no volume loss compared with controls correlating with the relative preservation of other language skills.