Activation of the human posterior parietal and temporoparietal cortices during audiotactile interaction.

We recorded cortical-evoked responses with a whole-scalp neuromagnetometer to study human brain dynamics associated with audiotactile interaction. The subjects received unilateral auditory (A) or tactile (T) stimuli, or both stimuli simultaneously (AT), alternating to the left and right side. Responses to AT stimuli differed significantly from the algebraic sum of responses to A and T stimuli (A + T) at 75-85 and 105-130 ms and indicated suppressive audiotactile interaction. Source modeling revealed that the earlier interaction occurred in the contralateral posterior parietal cortex and the later interaction in the contralateral parietal opercula between the SII cortex and the auditory cortex. The interaction was significantly stronger in the left than the right hemisphere. In most subjects, AT responses were far more similar to T than to A responses, suggesting suppression of auditory processing during the spatially and temporally concordant audiotactile stimuli in which the tactile component was subjectively more salient.

Comparative MR analysis of the entorhinal cortex and hippocampus in diagnosing Alzheimer disease.

BACKGROUND AND PURPOSE: Our purpose was to use volumetric MR imaging to compare the extent of atrophy and discriminative ability of the volumes of two temporal lobe structures, the entorhinal cortex and the hippocampus, between patients with Alzheimer disease and control subjects. METHODS: The study group consisted of 30 patients with probable Alzheimer disease diagnosed according to the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria and 32 healthy control subjects. The MR volumes of the entorhinal cortex and the hippocampus were used for the discriminant function and receiver operator characteristic analysis as well as multivariate analysis of variance for repeated measures to compare their discriminative power. RESULTS: Compared with control subjects, patients with Alzheimer disease had significantly smaller volumes of the entorhinal cortex and the hippocampus on both sides. Both the receiver operator characteristic and the discriminant function analyses using both volumes classified control subjects and Alzheimer patients with a high degree of accuracy (approximately 90%). Significant group x region interaction favoring hippocampal volumetry was determined by multivariate analysis of variance. CONCLUSION: The volumetric measurements of both the entorhinal cortex and hippocampus have comparably high discriminative power in diagnosing Alzheimer disease. In clinical practice, hippocampal volumetry may be more feasible, because the method is easier to use and has less variability.

Semantic processing of spoken words in Alzheimer's disease: an electrophysiological study.

Patients suffering from Alzheimer's disease (AD) have severe difficulties in tasks requiring the use of semantic knowledge. The semantic deficits associated with AD have been extensively studied by using behavioral methods. Many of these studies indicate that AD patients have a general deficit in voluntary access to semantic representations but that the structure of the representations themselves might be preserved. However, several studies also provide evidence that to some extent semantic representations in AD may in fact be degraded. Recently, a few studies have utilized event-related brain potentials (ERPs) that are sensitive to semantic factors in order to investigate the electrophysiological correlates of the semantic impairment in AD. Interest has focused on the N400 component, which is known to reflect the on-line semantic processing of linguistic and pictorial stimuli. The results from studies of N400 changes in AD remain somewhat controversial: Some studies report normal or enlarged N400 components in AD, whereas others report diminished ones. One issue not reported in previous studies is whether word-elicited ERPs other than N400 remain normal in AD. In the present study our aim was to find out whether the ERP waveforms N1, P2, N400, and Late Positive Component (LPC) to semantically congruous and incongruous spoken words are abnormal in AD and whether such abnormalities specifically reflect deficiencies in semantic activation in AD. Auditory ERPs from 20 scalp sites to semantically congruous and incongruous final words in spoken sentences were recorded from 17 healthy elderly adults and 9 AD patients. The early ERP waveforms N1 and P2 were relatively normal for the AD patients, but the N400 and LPC effects (amplitude difference between congruous and incongruous conditions) were significantly reduced. We interpret the present results as showing that semantic-conceptual activation and other high-level integration processes are defective in AD. However, a word congruity effect earlier than N400 (phonological mismatch negativity), reflecting lexical selection processes, is at least to some extent preserved in AD.

Major decrease in the volume of the entorhinal cortex in patients with Alzheimer's disease carrying the apolipoprotein E epsilon4 allele.

OBJECTIVE: Recent evidence indicates that the apolipoprotein E (ApoE) epsilon4 allele is a risk factor for developing Alzheimer's disease. It has also been proposed that it is associated with increased counts of amyloid plaques and neurofibrillary tangles that in turn are neuropathological hallmarks initially appearing in the medial temporal lobe structures in Alzheimer's disease. In this study, the effect of the ApoE epsilon4 allele on the volume of the entorhinal cortex was evaluated in vivo. METHODS: The volume of the entorhinal cortex was measured on MR images using a recently designed histology based protocol in 16 patients with Alzheimer's disease with ApoE epsilon4 (mean age 70.4 (SD 9.9)), 11 patients with Alzheimer's disease without ApoE epsilon4 (mean age 69.1 (SD7.1)), and in 31 healthy age and sex matched normal controls (72.2 (SD 3.9)). The patients met the NINCDS-ADRDA criteria for probable Alzheimer's disease and were in mild to moderate stages of the disease. MRI was performed with a 1.5 Tesla Magnetom and a 3D technique permitting the reconstruction of 2.0 mm thick contiguous slices perpendicular to the axis of the anterior-posterior commissure. RESULTS: The patients with Alzheimer's disease without the ApoE epsilon4 allele had atrophy in the entorhinal cortex, the volume was reduced by 27% compared with control subjects. However, the most prominent shrinkage (45%) in the entorhinal cortex was seen in patients with Alzheimer's disease with the ApoE epsilon4 allele (p=0.0001). The effect of epsilon4 on the entorhinal cortex volume was especially prominent in female patients with Alzheimer's disease compared to male patients with Alzheimer's disease (p=0.014). Additionally, patients with the ApoE epsilon4 allele had inferior performance in verbal and visual memory functions than those without the allele CONCLUSIONS: Volumetric MRI measurements disclose that ApoE epsilon4 is associated with the degree of atrophy in the entorhinal cortex in early Alzheimer's disease, this effect being especially prominent in female patients with Alzheimer's disease.

MR volumetric analysis of the human entorhinal, perirhinal, and temporopolar cortices.

PURPOSE: Our purpose was to investigate the normal volumes of the human entorhinal, perirhinal, and temporopolar cortices on MR imaging studies using a customized program. METHODS: We designed a protocol in which the volumes of the entorhinal, perirhinal, and temporopolar cortices were determined from coronal MR images using anatomic landmarks defined on the basis of cytoarchitectonic analyses of 49 autopsy cases. MR volumetry of these cortical areas was performed in 52 healthy volunteers. RESULTS: The overall mean volumes were 1768 +/- 328 mm3/1558 +/- 341 mm3 (right/left) for the entorhinal cortex, 2512 +/- 672 mm3/2572 +/- 666 mm3 for the perirhinal cortex, and 2960 +/- 623 mm3/3091 +/- 636 mm3 for the temporopolar cortex. The right entorhinal cortex was 12% larger than the left. The volume of the temporopolar cortex was reduced bilaterally by 13% in the older age group compared with younger subjects, while the volumes of the entorhinal and perirhinal cortices were unaffected by age. There were no differences between men and women in the volumes of any of the three cortices. CONCLUSION: Our method provides a tool by which to measure volumes of the entorhinal, perirhinal, and temporopolar cortices on coronal MR images.

Abnormal frequency mismatch negativity in mentally retarded children and in children with developmental dysphasia.

The auditory event-related potential waveform termed "mismatch negativity" was examined in 12 mentally retarded children with delayed development of speech and language (aged 5-8 years) and in 13 children with developmental dysphasia (aged 5-9 years). The mismatch negativity waves were elicited with pure sine-wave tone stimuli using the oddball paradigm. We measured the peak latency and peak amplitude of mismatch negativity responses to frequency (500/553 Hz) difference. The mismatch negativity patterns were compared with those of 10 children with normal development of linguistic skills (aged 5-9 years). In both the mentally retarded and dysphasic groups, the peak amplitude of the frequency mismatch negativity was significantly attenuated when compared with the control group, but no significant difference was observed between the mentally retarded and dysphasic groups. Attenuated frequency mismatch negativity was related to impairment of linguistic skills irrespective of the child's cognitive skills. Because the mismatch negativity response reflects central auditory processing and is modal specific for auditory stimuli, this change-specific response can serve as an objective tool to elucidate central auditory deficits in children.

Volumes of the entorhinal and perirhinal cortices in Alzheimer's disease.

We measured the volumes of the entorhinal, perirhinal, and temporopolar cortices on magnetic resonance images by using a recently designed histology-based protocol in 30 patients with early Alzheimer's disease (AD) and 32 healthy control subjects. Compared to the controls, all of these cortical regions were significantly atrophied in AD patients (p < 0.0001). However, the entorhinal cortex was the most severely involved brain region studied, with 40% volume loss, and this region provided the highest discriminative accuracy (92%) in separating patients with AD from healthy control subjects. Importantly, the entorhinal volume loss was evident already in mild AD. In addition, the volume of the entorhinal cortex was not dependent on age, but it did correlate significantly with the severity of the disease. Because it assesses the major site of initial neuropathological changes in AD, magnetic resonance imaging volumetric measurement of the entorhinal cortex can offer a tool for distinguishing AD patients even in the very early stages of the disease from healthy aged subjects.

Attenuated auditory event-related potential (mismatch negativity) in children with developmental dysphasia.

An attention-independent negative wave-form termed 'mismatch negativity' (MMN) of the auditory event-related potentials (ERPs) was studied in ten children (3-6 years) with developmental dysphasia and in fourteen control children (3-7 years) with normal speech and language development. The MMNs were elicited with pure sine tone stimuli using the oddball paradigm. The peak latency and peak amplitude of MMN response to frequency (500/553 H2) difference was measured. The grand average amplitude of frequency MMN was significantly attenuated in dysphasic children as compared to controls, but no significant difference was observed in the latency of peak frequency MMN. The results indicate that dysphasic children have a defect in automatic auditory processing of frequency differences. Because the MMN response reflects central auditory processing and is modal specific for auditory stimuli we argue that the MMN method can serve as an objective tool to assess central auditory deficits in children.

MRI volumetry of the hippocampus: the effect of slice thickness on volume formation.

The hippocampus is a mesial temporal lobe structure of complex shape and the main locus of temporal lobe epilepsy and also affected early in Alzheimer's disease. Magnetic resonance imaging of the hippocampus has been found to be a helpful diagnostic tool for these conditions. Measurement of hippocampal volumes has been found to be not only the most accurate approach to evaluation of the hippocampal pathology, but the most demanding and time consuming as well. One of the factors contributing to this is the slice thickness-the thinner the slice, the more time is required. On the other hand, it has been hypothesized, that the use of thick slice would result in volume aberrations due to, for example, the volume averaging effect. We therefore measured the volumes of the hippocampus on coronal slices in 10 healthy, young control subjects using slice thicknesses of 1, 3 and 5 mm, and evaluated the effect of the slice thickness on the volume formation. No significant difference between the volumes of the hippocampus using different thicknesses was found. Therefore, it appears that use of the thick slices would not necessarily introduce systematic bias to the volumetric measurement. Yet, we do not feel compelled to advise the use of "thick" slices either, since the use of "thin" slices seems the most authoritative and less vulnerable to being affected by a single false estimate.

Dissimilar age influences on two ERP waveforms (LPC and N400) reflecting semantic context effect.

Age-related changes in semantic context effects were examined using late event-related brain potentials (ERPs). Auditory ERPs to semantically congruous and incongruous final words in spoken sentences were recorded in 16 children (aged 5-11 years) and 16 adults. Previous findings concerning age-related effects on N400 were replicated: the N400 effect was significantly larger in children than in adults. The main new finding was that a late positive component (LPC) following N400 and modulated by semantic context in adults was not found in children. Thus, the common generalization that semantic context effects decline with age holds only for ERP components occurring in the N400 time window or earlier. The cognitive function reflected by the semantic LPC we observed is not clear, but it seems to have a role different from that of the N400, although in adults the components often co-exist as an N400-LPC complex.