Visual-statistical interpretation of (18)F-FDG-PET images for characteristic Alzheimer patterns in a multicenter study: inter-rater concordance and relationship to automated quantitative evaluation.

BACKGROUND AND PURPOSE: The role of (18)F-FDG-PET in the diagnosis of Alzheimer disease is increasing and should be validated. The aim of this study was to assess the inter-rater variability in the interpretation of (18)F-FDG-PET images obtained in the Japanese Alzheimer's Disease Neuroimaging Initiative, a multicenter clinical research project. MATERIALS AND METHODS: This study analyzed 274 (18)F-FDG-PET scans (67 mild Alzheimer disease, 100 mild cognitive impairment, and 107 normal cognitive) as baseline scans for the Japanese Alzheimer's Disease Neuroimaging Initiative, which were acquired with various types of PET or PET/CT scanners in 23 facilities. Three independent raters interpreted all PET images by using a combined visual-statistical method. The images were classified into 7 (FDG-7) patterns by the criteria of Silverman et al and further into 2 (FDG-2) patterns. RESULTS: Agreement among the 7 visual-statistical categories by at least 2 of the 3 readers occurred in >94% of cases for all groups: Alzheimer disease, mild cognitive impairment, and normal cognitive. Perfect matches by all 3 raters were observed for 62% of the cases by FDG-7 and 76 by FDG-2. Inter-rater concordance was moderate by FDG-7 (κ = 0.57) and substantial in FDG-2 (κ = 0.67) on average. The FDG-PET score, an automated quantitative index developed by Herholz et al, increased as the number of raters who voted for the AD pattern increased (ρ = 0.59, P < .0001), and the FDG-PET score decreased as those for normal pattern increased (ρ = -0.64, P < .0001). CONCLUSIONS: Inter-rater agreement was moderate to substantial for the combined visual-statistical interpretation of (18)F-FDG-PET and was also significantly associated with automated quantitative assessment.

Brain activation during ideomotor praxis: imitation and movements executed by verbal command.

BACKGROUND: Ideomotor apraxia is a disorder of both imitation movements and movements executed by verbal command. Lesion studies have identified the left parietal lobe as the neural correlate for ideomotor praxis (IP), although there are opposing views. OBJECTIVES: To localise the neural substrates for IP using functional magnetic resonance imaging. Brain regions activated by both imitation and verbal command movements were tested against a simple self paced movement. METHODS: Twenty two young, right handed, healthy subjects were examined. Functional and anatomical data were acquired. The experiment comprised three motor conditions (imitation, movements executed by verbal command, and finger bending/unbending) and a rest condition. All motor tasks were performed using the left hand. Eighteen drawings of left hand postures were presented for the imitation condition. Identical postures were instructed verbally for the verbal command condition. The finger bending/unbending movement was self paced. Blood oxygenation level dependent (BOLD) signal increases were compared during two kinds of IP (imitation and verbal command movements) and during finger bending/unbending movements. RESULTS: The depth of the posterior part of the left intraparietal sulcus and bilateral precunei were activated during both imitation and verbal command movements. The difference in BOLD signal between imitation and verbal command movements was localised in the dorsal and ventral occipital areas. BOLD signal differences for movements executed by verbal command against imitation were observed in the superior temporal areas. CONCLUSIONS: The depth of the posterior part of the left intraparietal sulcus and bilateral precunei are the neural substrates for IP.

A functional MRI study on the neural substrates for writing.

Functional neuroanatomy of writing is relatively unknown compared to that of other linguistic processes. This study aimed at identifying brain regions crucial to the process of writing. Using functional magnetic resonance imaging (fMRI), brain hemodynamic activity was examined during three conditions that differentially engaged visual, linguistic, and/or motor functions: (1) writing names of pictures with the right index finger, (2) naming pictures silently, and (3) visually cued finger tapping. A writing minus naming comparison and a writing minus tapping comparison were performed, and brain regions commonly activated in these two contrasts were detected. Our main finding was that such common activation was observed in the anterior part of the left superior parietal lobule, the posterior part of the middle and superior frontal gyri, and the right cerebellum. The parietal and frontal regions were considered to subserve the process of writing as separated from that of naming and finger movements, which is consistent with the classical notion mainly proposed by studies of selective writing deficits called pure agraphia. The right cerebellar activation, on the other hand, was interpreted as the reflection of the execution of complex finger movements required for writing.

Association of structural polymorphisms in the human period3 gene with delayed sleep phase syndrome.

Recent progress in biological clock research has facilitated genetic analysis of circadian rhythm sleep disorders, such as delayed sleep phase syndrome (DSPS) and non-24-h sleep-wake syndrome (N-24). We analyzed the human period3 (hPer3) gene, one of the human homologs of the Drosophila clock-gene period (Per), as a possible candidate for rhythm disorder susceptibility. All of the coding exons in the hPer3 gene were screened for polymorphisms by a PCR-based strategy using genomic DNA samples from sleep disorder patients and control subjects. We identified six sequence variations with amino acid changes, of which five were common and predicted four haplotypes of the hPer3 gene. One of the haplotypes was significantly associated with DSPS (Bonferroni's corrected P = 0.037; odds ratio = 7.79; 95% CI 1.59-38.3) in our study population. Our results suggest that structural polymorphisms in the hPer3 gene may be implicated in the pathogenesis of DSPS.

Learning Chinese characters may improve visual recall.

From elementary through high school, Japanese children are required to memorize a large number of distinct visual forms, i.e., roughly 2,000 Chinese characters, and tremendous effort is expended in learning to read and write them. We hypothesized that early training in memorizing Chinese characters and the use of these characters in daily life shapes brain development and facilitates recall of visual forms in general, including geometrical figures in visual recall tests. To demonstrate whether the learning of Chinese character is correlated with specific aspects of memory, we administered the Wechsler Memory Scale-Revised (WMS-R) to a representative sample of the normal Japanese population (316 persons, 100% Japanese) and compared their scores with data previously obtained from a representative sample of the normal U.S. population (316 persons, 82.5% Caucasian). The WMS-R has 12 memory subtests, each measuring a different aspect of memory and includes two visual recall subtests (Visual Reproduction I and II). Compared to the Americans, the Japanese group obtained significantly higher scores on these two visual recall subtests in each of the six age groups tested (16 to 74 years old). Further, the scores of Japanese on the two visual recall subtests did not decline across age groups as much as scores for the U.S. group. Japanese also scored significantly higher on the Visual Memory Span subtest in three age groups.

[The right hemisphere language].

A large number of observations since the mid-nineteenth century have shown that damage to the left but not the right hemisphere destroys language function. These observations lead to the formation of the "classic" view that the left hemisphere has language function but not the right hemisphere. It thus came as a considerable surprise in the early 1960's when tests on commissurotomy or split-brain patients suggested the presence of a considerable capacity for reading comprehension in the right hemisphere. It has been suggested that the spared regions in the left hemisphere normally act to prevent the expression of latent language functions within the undamaged right hemisphere. Thus, only after the intact right hemisphere has been released from the disruptive and suppressive influences of the damaged left hemisphere by section of the corpus callosum, can its own residual function become effective. Some investigators have argued, however, that the split-brain evidence is misleading because the language of the split-brain patients is presented in both hemispheres even pre-operatively. Our investigation with functional MRI is in progress to decide which hypothesis is appropriate. In addition to the functional MRI study of split-brain patient, the functional MRI study of aphasia recovery will also provide opportunities to clarify the right hemisphere language function since the right hemisphere is generally intact in the right-handed aphasic.

Neural substrates for the recognition of newly learned faces: a functional MRI study.

Face recognition is critical to the appreciation of our social and physical relations. Functional magnetic resonance imaging (fMRI) was used to identify brain regions involved in the recognition of newly learned faces. Two experiments were conducted. Experiment 1 contrasted a fixation control task with a face recognition task in which subjects were exposed solely to previously viewed faces (all-target). Experiment 2 compared a fixation control with another face recognition task in which subjects were presented with both novel and viewed faces (half-target). Compared to the fixation control, the all-target face recognition was associated with activation in the bilateral occipital and occipitotemporal regions, whereas the half-target face recognition produced activation in the right parietal and prefrontal regions, in addition to the occipital and occipitotemporal. The all-target minus half-target comparison revealed significant activation in the bilateral fusiform gyrus, suggesting stronger fusiform activity during the all-target than the half-target face recognition. The half-target minus all-target comparison showed significant activation in the superior and inferior parietal lobules and several regions in the right frontal lobe. These findings demonstrated that the bilateral fusiform gyrus is involved, not only in face perception, but in a certain aspect of face recognition memory and that this aspect is related to the actual recognition of previously viewed faces rather than the processing of novel ones, which results are consistent with previous lesion work. The right parietal and frontal regions, in contrast, are differentially more associated with the processes related to the detection of novel faces or retrieval effort.

Diffusion-weighted imaging demonstrates transient cytotoxic edema involving the corpus callosum in a patient with diffuse brain injury.

Reversible T2 hyperintense signal abnormality in the corpus callosum, although frequently seen after diffuse brain injury, has not been well clarified. With some accumulated evidence, we report a case of diffuse brain injury in a 24-year-old man. Magnetic resonance imaging (MRI) demonstrated T2 hyperintense signals in the trunk and the splenium of the corpus callosum 12 days postinjury. Echo-planar diffusion-weighted imaging was also performed on the same day, which revealed decreased diffusion (hyperintense signals) in the same site and almost the same size as T2 hyperintense signals. T1-weighted images were normal. Neuropsychological examination of the patient did not show callosal syndrome, namely hemialexia, unilateral agraphia and unilateral apraxia. Repeat MRI on day 20 demonstrated a signal decrease of both T2-weighted images and diffusion-weighted images (DWI) in the lesion. Follow-up MRI at 6 months showed complete resolution of the T2 signal abnormalities and of the corresponding decreased diffusion. Considering that diffusion-weighted imaging showed transient decreased diffusion, the lesion in the corpus callosum indicated the existence of cytotoxic edema. Also, transient DWI hyperintensity, namely cytotoxic edema, in the trunk and the splenium of the corpus callosum does not necessarily reveal callosal deficits.

The precuneus in motor imagery: a magnetoencephalographic study.

Magnetoencephalography was applied to subjects who imagined themselves hurdling in self-centered space. In three of six subjects all 300 trials in the motor imagery condition revealed the precuneus dipole. When we divided the 300 trials into four overlapping blocks (one block = 150 trials), all six subjects showed precuneus activity. The latency of the precuneus dipole was about 220 ms. We suggest that the precuneus activity during motor imagery involves retrieval of spatial information and/or setting up spatial attributes. Only in one subject but twice, the current dipole located in the supplementary motor area was observed 60 ms after activation of the precuneus, which suggests that the signal from the precuneus for motor imagery is transferred to the supplementary motor area.

Genetic polymorphisms of human melatonin 1b receptor gene in circadian rhythm sleep disorders and controls.

Recent studies suggest that melatonin 1b (Mel1b) receptor, as well as melatonin 1a (Mel1a) receptor, is involved in the modulation of circadian rhythms in mammals. Mutational analysis was performed in the entire coding region of the human Mel1b receptor gene using genomic DNA from sleep disorder subjects. We have identified two missense mutations, G24E and L66F. However, neither is likely to be associated with sleep disorders in our study population. One of the subjects with non-24-h sleep-wake syndrome carries missense mutations in both the Mel1a and Mel1b receptor genes.

Alleic variants of human melatonin 1a receptor: function and prevalence in subjects with circadian rhythm sleep disorders.

The human melatonin 1a (hMella) receptor gene was screened for mutations using genomic DNA samples from patients with circadian rhythm sleep disorders and control subjects by single strand conformational polymorphism analysis (SSCP). We found seven mutations, two of which predict amino acid changes R54W and A157V, respectively. The prevalence of the R54W variant and that of the A157V variant were several times more common in non-24-h sleep-wake syndrome subjects than among control subjects, although the incidence was not significant in our study group. When expressed in COS-7 cells, the R54W mutant receptor exhibited significantly reduced B(max) and slightly enhanced affinity (reduced K(d)) compared to the wild type receptor, while the A157V variant receptor showed similar binding characteristics to the wild type. The identification of variants in the hMella receptor will provide a useful tool for analyzing genetic predisposition toward various diseases related to melatonin function and to clarify the physiological role of melatonin receptors in humans.

Dichotic listening in patients with situs inversus: brain asymmetry and situs asymmetry.

In order to investigate the relation between situs asymmetry and functional asymmetry of the human brain, a consonant-vowel syllable dichotic listening test known as the Standard Dichotic Listening Test (SDLT) was administered to nine subjects with situs inversus (SI) that ranged in age from 6 to 46 years old (mean of 21.8 years old, S.D. = 15.6); the four males and five females all exhibited strong right-handedness. The SDLT was also used to study twenty four age-matched normal subjects that were from 6 to 48 years old (mean 21.7 years old, S.D. = 15.3); the twelve males and twelve females were all strongly right-handed and served as a control group. Eight out of the nine subjects (88.9%) with SI more often reproduced the sounds from the right ear than sounds from the left ear; this is called right ear advantage (REA). The ratio of REA in the control group was almost the same, i.e., nineteen out of the twenty-four subjects (79.1%) showed REA. Results of the present study suggest that the left-right reversal in situs inversus does not involve functional asymmetry of the brain. As such, the system that produces functional asymmetry in the human brain must independently recognize laterality from situs asymmetry.

Partial seizure with aphasic speech arrest caused by watching a popular animated TV program.

On the evening of December 16, 1997, about 700 children across Japan were hospitalized because of convulsive seizures or vomiting experienced while watching a popular animated TV program that included blue and red stimuli that alternated at 12 flashes per second. In one case, an 11-year-old girl developed a hallucination in the right visual field and a subsequent cramp on the right side of her face, with aphasic speech arrest. She had no history of seizures. Her electroencephalogram (EEG) showed normal background activity and no epileptiform discharges. Intermittent photic stimulation provoked a photoparoxysmal response. Her main clinical manifestation was a TV-induced left occipital lobe seizure spreading toward the left inferior frontal lobe. This suggested a functional link from the occipital lobe to the frontal operculum.

Reversible memory disturbance and intelligence impairment induced by long-term anticholinergic therapy.

It is controversial whether long-term anticholinergic therapy (AC-T) can cause short-term memory disturbance, long-term memory disturbance or intelligence impairment. Ninety patients with Parkinson's disease were examined prospectively to clarify the existence of memory and intelligence impairment induced by long-term AC-T. Neuropsychological tests detected eight patients with at least one of four types of deficits; intelligence impairment in four patients, verbal delayed recall impairment in eight, verbal short-term memory disturbance in five, and verbal long-term memory disturbance in six. Two types of verbal memory disturbance (short-term one and long-term one) appeared with double dissociation, suggesting that there may be an independence between the two types of verbal memory system. Older patients were more prone to suffer from these reversible deficits. Moreover, all of the patients who resumed AC-T, showed recurrence of the deficits acutely. These observations should indicate the tight relation between long-term AC-T and neuropsychological deficits.

Cognitive deficits of mild dementia: A comparison between dementia of the Alzheimer's type and vascular dementia.

This study was designed to examine the profiles of cognitive deficits in 11 mildly demented patients with dementia of Alzheimer's type (DAT), five with vascular dementia with multiple subcortical lacunar infarcts (VDS), and seven with vascular dementia with extensive white matter lesions (VDW) in comparison with 23 aged individuals without dementia. Memory, attention, abstract thinking, and visuospatial function were assessed using the Japanese translation of the Wechsler Memory Scale-Revised (WMS-R) and the Japanese version of the Wechsler Adult Intelligence Scale-Revised (WAIS-R). Compared with normal aged individuals, three dementia groups were significantly impaired in the memory and abstract thinking. However, the performances on several tests on attention (i.e. Mental Control and Visual Memory Span Backward from WMS-R) and visuospatial function (i.e. Object Assembly from WAIS-R) differed significantly between the DAT and VDS groups, with VDS being the worst in terms of performance than was DAT. This study suggests that, in the mildly demented stage, the patients with DAT have few problems in the attention and visuospatial function, but those with VDS have impairments in these cognitive abilities.

Preserved musical abilities following right temporal lobectomy.

It has been widely accepted that the right temporal lobe plays a major role in the processing of music. One of the main lines of evidence was derived from Milner's study, published in 1962, which reported that right temporal lobectomy led to a decline in patient scores on four of the six subtests (Tonal Memory, Timbre, Loudness, and Time subtests) of the Seashore Measures of Musical Talents. That finding had led some surgeons and patients to hesitate in choosing right temporal lobectomy as a treatment for intractable epilepsy. The authors examined performance on the Seashore Measures before and after operations in 20 patients with right temporal lobectomy and nine patients with left temporal lobectomy. No disturbances in the Seashore Measures were detected after temporal lobectomy on either side. The extent of these temporal lobectomies was smaller than that of the temporal lobectomies in Milner's study, as measured along the sylvian fissure (1.5-4 cm; mean 2.7 cm, standard deviation (SD) 0.92 cm) and the base of the temporal lobe (3.5-5.5 cm; mean 4.7 cm, SD 0.63 cm). These findings indicate that the region resected on right temporal lobectomy in the present study is not essential for basic musical processing.

Functional magnetic resonance imaging (fMRI) during mental writing with phonograms.

Functional magnetic resonance imaging (fMRI) at 1.5 T using a gradient echo echo-planar sequence was employed to identify brain regions activated during the performance of a mental writing task using phonograms. Four regions were activated in all six subjects; the region surrounding the left intraparietal sulcus, the region surrounding the middle part of the left precentral sulcus and the posterior part of the left superior frontal sulcus, the region surrounding the right intraparietal sulcus, and the region surrounding either or both of the left and right cingulate sulci. The left intraparietal region was usually the most extensively activated. The results suggest that these four regions particularly the left intraparietal region, are essential in writing with phonograms. Since the left hemisphere was more extensively activated than the right, fMRI during the mental writing task is a good candidate for determining non-invasively which hemisphere is dominant for language.

Modality specific naming and gesture disturbances: a case with optic aphasia, bilateral tactile aphasia, optic apraxia and tactile apraxia.

This study reports a patient who manifested optic aphasia, tactile aphasia, optic apraxia, and tactile apraxia following an operation for epidural left parietal haematoma. He could neither name nor pantomime the use of objects presented visually or tactually, but correctly performed semantic association tasks, thus demonstrating preserved recognition. He could name and pantomime the use of auditorily presented objects. Experimental results disproved that pantomime disorders were secondary to naming disorders, and suggested that modality specific aphasia and modality specific apraxia are independent clinical syndromes. CT scans showed injury to the posterior callosal radiations, the white matter of the angular gyrus, and the medial portion of the occipital lobe in the left hemisphere. We suggest that modality specific aphasia and modality specific apraxia can be explained by assuming a common semantic memory store.

Positron emission tomography of reversible intellectual impairment induced by long-term anticholinergic therapy.

Long-term oral anticholinergic (AC) therapy can occasionally produce intellectual impairment. We investigated a patient with Parkinson's disease accompanied by intellectual impairment induced by long-term AC therapy. The intellectual impairment of the patient disappeared after cessation of AC therapy. Positron emission tomography (PET), during and after long-term oral AC therapy, revealed that it causes bilateral diffuse decrease of glucose metabolism in the cortex, basal ganglia, thalamus, hippocampus and cerebellum. Cessation of the therapy resulted in diffuse increase of glucose metabolism in all of the above regions. Cranial CT and magnetic resonance imaging (MRI) showed no abnormalities. Our results suggest that long-term AC therapy causes reversible bilateral diffuse glucose hypometabolism.