Mirror writing and cortical hypometabolism in Parkinson's disease.

Mirror writing (MW) is the production of individual letters, words, or word strings in the reverse direction. Parkinson's disease (PD) is a progressive neurodegenerative disorder, and high MW rates have been reported in patients with PD. Thus, the present study sought to identify the factors that cause MW in patients with PD. We examined the frequency of MW in patients with PD and investigated the area of the brain where such frequency inversely correlates with reduced regional cerebral metabolic rates of glucose (rCMRglc). We also examined whether this area satisfied the motor and visual monitoring hypotheses of MW that have been presented in previous studies. Thirty-six subjects with idiopathic PD and 23 healthy controls were included in the study. We asked the participants to write down words, numerals, and sentences from left to right using their dominant and non-dominant hands. Patients with PD underwent an 18F-fluorodeoxyglucose positron emission tomography scan to measure the rCMRglc. Neither the patients with PD nor the healthy subjects exhibited MW in the use of the right hand. In the use of the left hand, MW occurred in 15 of the 36 patients with PD, but in none of the healthy controls. The right intraparietal sulcus was identified as the area where rCMRglc was inversely correlated with the number of left-right reversed characters. Previous functional imaging studies have suggested that the right superior parietal cortex and intraparietal sulcus play an important role in recognizing left-right reversed letters. Therefore, dysfunction in the intraparietal sulcus may hinder the recognition of left-right reversed characters, resulting in MW. Consequently, our findings in patients with PD are consistent with the visual-monitoring hypothesis of MW.

Neural substrates underlying progressive micrographia in Parkinson's disease.

INTRODUCTION: The neural substrates associated with the development of micrographia remain unknown. We aimed to elucidate the neural substrates underlying micrographia in Parkinson's disease (PD) patients. METHODS: Forty PD patients and 20 healthy controls underwent handwriting tests that involved free writing and copying. We measured the size of each letter and the resting cerebral glucose metabolic rate of the PD patients and another group of age- and sex-matched 14 healthy controls (HCs), who had not participated in the writing tests, using resting-state 18F-fluorodeoxyglucose positron emission tomography. RESULTS: In the PD patients, the prevalence of consistent micrographia (CM) associated with free writing was 2.5% for both tasks. Alternatively, the prevalence of progressive micrographia (PM) was 15% for free writing and 17.5% for copying. In the PD patients, there was no significant difference in the letter sizes between these tasks, whereas the variability of the letter sizes for copying was significantly different from that for free writing. The means and decrements in letter sizes in either task were not significantly correlated with the severity of brady/hypokinesia in the PD patients. For free writing, the PD patients with PM showed glucose hypometabolism in the anterior part of the right middle cingulate cortex, including the rostral cingulate motor area, compared with those without PM. For copying, the PD patients with PM showed glucose hypometabolism in the right superior occipital gyrus, including V3A, compared with those without PM. CONCLUSIONS: These findings suggest that PM in free writing in PD patients is caused by the difficulty of monitoring whether the actual handwriting movements are desirable for maintaining letter size during self-paced handwriting. By contrast, PM in copying in PD patients is evoked by a lack of visual information about the personal handwriting and hand motions that are used as cues for maintaining letter sizes.

Regional cerebral blood flow and abnormal eating behavior in Prader-Willi syndrome.

BACKGROUND: Prader-Willi syndrome (PWS) is a genetically determined neurodevelopmental disorder and is generally regarded as a genetic model of obesity. Individuals with PWS exhibit behavioral symptoms including temper tantrums, rigid thinking, and compulsive behavior. The most striking feature of PWS is abnormal eating behavior, including hyperphagia, intense preoccupation with food, and incessant food seeking. To explore brain regions associated with the behavioral symptoms of PWS, we investigated differences in resting-state regional cerebral blood flow (rCBF) between individuals with PWS and healthy controls. Correlation analyses were also performed to examine the relationship between rCBF and altered eating behavior in PWS individuals. METHODS: Twelve adults with PWS and 13 age- and gender-matched controls underwent resting-state single photon emission computerized tomography (SPECT) with N-isopropyl-p-[(123)I] iodoamphetamine (IMP). The rCBF data were analyzed on a voxel-by-voxel basis using SPM5 software. RESULTS: The results demonstrated that compared with controls, individuals with PWS had significantly lower rCBF in the right thalamus, left insular cortex, bilateral lingual gyrus, and bilateral cerebellum. They had significantly higher rCBF in the right inferior frontal gyrus, left middle/inferior frontal gyrus (anterior and posterior clusters), and bilateral angular gyrus. Additionally, rCBF in the left insula, which was significantly lower in PWS individuals, was negatively correlated with the eating behavior severity score. CONCLUSIONS: These results suggest that specific brain regions, particularly the left insula, may be partly responsible for the behavioral symptoms in PWS.

The effects of aging and Alzheimer's disease on associative recognition memory.

We investigated the effects of aging and Alzheimer's disease (AD) on item and associative recognition memory. Three groups of participants (younger adults, elderly adults, and AD patients) studied photographs of common objects that were located on either the left or the right side of a black computer screen inside either a red or a blue square. In a subsequent old/new recognition memory test, the participants were presented with four kinds of stimuli: "intact" stimuli, which were presented as they were during the study phase; "location-altered" stimuli, which were presented in a different location; "color-altered" stimuli, which were presented with a different surrounding color; and "new" stimuli, which consisted of photographs that had not been presented during the study phase. Compared with younger adults, the older adults showed equivalent performance in simple item recognition but worse performance in discriminating location-altered and color-altered stimuli. Compared with older adults, the AD patients showed equivalent performance in discriminating color-altered stimuli but worse performance in simple item recognition and the discrimination of location-altered stimuli. We speculate that distinct structural and functional changes in specific brain regions that are caused by aging and AD are responsible for the different patterns of memory impairment.

False item recognition in patients with Alzheimer's disease.

Recent evidence suggests that patients with Alzheimer's disease (AD), as compared with normal individuals, exhibit increased false recognition by stimulus repetition in the Deese-Roediger-McDermott (DRM) task or associative recognition memory tasks, probably due to impaired recollection-based monitoring. However, because of possible alternative explanations for the findings of these previous studies, the evidence for impaired recollection-based monitoring in AD patients remains inconclusive. In this study, we employed stimulus repetition in old/new recognition judgments of single-item picture memory without a factor of association between the stimuli and examined whether AD patients showed increased false item recognition as compared with healthy controls. AD patients and healthy controls studied single-item pictures presented either once or three times. They were later asked to make an old/new recognition judgment in response to (a) Same pictures, pictures identical to those seen at encoding, (b) Similar lures, novel pictures similar to but not identical to those seen at encoding, and (c) Dissimilar lures, novel pictures not similar to those seen at encoding. For Same pictures, repeated presentation of stimuli increased the proportion of "old" responses in both groups. For Similar lures, repeated presentation of stimuli increased the rate of "old" responses in AD patients but not in control subjects. The results of the present study clearly demonstrated elevated false recognition by stimulus repetition in single-item recognition in AD patients. The present findings strongly support the view that AD patients are impaired in their ability to use item-specific recollection in order to avoid false recognition.

Small gray matter volume in orbitofrontal cortex in Prader-Willi syndrome: a voxel-based MRI study.

Prader-Willi syndrome (PWS) is a genetically determined neurodevelopmental disorder presenting with behavioral symptoms including hyperphagia, disinhibition, and compulsive behavior. The behavioral problems in individuals with PWS are strikingly similar to those in patients with frontal pathologies, particularly those affecting the orbitofrontal cortex (OFC). However, neuroanatomical abnormalities in the frontal lobe have not been established in PWS. The aim of this study was to look, using volumetric analysis, for morphological changes in the frontal lobe, especially the OFC, of the brains of individuals with PWS. Twelve adults with PWS and 13 age- and gender-matched control subjects participated in structural magnetic resonance imaging (MRI) scans. The whole-brain images were segmented and normalized to a standard stereotactic space. Regional gray matter volumes were compared between the PWS group and the control group using voxel-based morphometry. The PWS subjects showed small gray-matter volume in several regions, including the OFC, caudate nucleus, inferior temporal gyrus, precentral gyrus, supplementary motor area, postcentral gyrus, and cerebellum. The small gray-matter volume in the OFC remained significant in a separate analysis that included total gray matter volume as a covariate. These preliminary findings suggest that the neurobehavioral symptoms in individuals with PWS are related to structural brain abnormalities in these areas.

Frontal behavioral syndromes in Prader-Willi syndrome.

BACKGROUND: Prader-Willi syndrome (PWS) is a genetically determined neurodevelopmental disorder presenting with behavioral problems including hyperphagia, emotional aberration, and compulsion-like behaviors. This combination of behavioral problems is likely to be caused by damage to the orbitofrontal cortices and anterior temporal lobes or to circuits involving them. OBJECTIVES: To investigate the prevalence of eating and non-eating behavioral disturbances in PWS by using assessment tools developed originally for patients with frontotemporal dementia and with frontal lobe injury. METHOD: The questionnaire consisted of 35 questions related to three categories of behavior: eating behaviors (including four domains: appetite, food preference, eating habits, and other oral behaviors), stereotypy (including four domains: roaming, speaking, movements, and daily rhythm), and collecting behaviors. It was administered in Japan to the parents of 250 individuals aged 1-42 years with a clinical diagnosis of PWS. RESULTS: The prevalence rates of symptoms in all categories were high. Each domain involved in eating behaviors was significantly correlated with stereotypy and collecting behaviors. The prevalence rates and severity scores of some eating and non-eating behaviors were higher in the older groups. CONCLUSION: Abnormal eating behaviors, stereotyped behaviors, and collecting behaviors were common in the PWS subjects. There was also a potential link between abnormal eating and non-eating behaviors related to frontal behavioral syndromes. It is likely that these behavioral abnormalities reflect dysfunction of the orbitofrontal cortices and anterior temporal lobes.