The cumulative incidence of and risk factors for morphometric severe vertebral fractures in Japanese men and women: the ROAD study third and fourth surveys.

This population-based cohort study with a 3-year follow-up revealed that the annual incidence rates of vertebral fracture (VF) and severe VF (sVF) were 5.9%/year and 1.7%/year, respectively. The presence of mild VF at the baseline was a significant risk factor for incident sVF in participants without prevalent sVF. INTRODUCTION: This study aimed to estimate the incidence of morphometric vertebral fracture (VF) and severe VF (sVF) in men and women and clarify whether the presence of a mild VF (mVF) increases the risk of incident sVF. METHODS: Data from the population-based cohort study, entitled the Research on Osteoarthritis/Osteoporosis Against Disability (ROAD) study, were analyzed. In total, 1190 participants aged ≥ 40 years (mean age, 65.0 ± 11.2) years completed whole-spine lateral radiography both at the third (2012-2013, baseline) and fourth surveys performed 3 years later (2015-2016, follow-up). VF was defined using Genant's semi-quantitative (SQ) method: VF as SQ ≥ 1, mVF as SQ = 1, and sVF as SQ ≥ 2. Cumulative incidence of VF and sVF was estimated. Multivariate logistic regression analyses were performed to evaluate risk factors for incident sVF. RESULTS: The baseline prevalence of mVF and sVF were 16.8% and 6.0%, respectively. The annual incidence rates of VF and sVF were 5.9%/year and 1.7%/year, respectively. The annual incidence rates of sVF in participants without prevalent VF, with prevalent mVF, and with prevalent sVF were 0.6%/year, 3.8%/year, and 11.7%/year (p < 0.001), respectively. Multivariate logistic regression analyses in participants without prevalent sVF showed that the adjusted odds ratios for incident sVF were 4.12 [95% confident interval 1.85-9.16] and 4.53 [1.49-13.77] if the number of prevalent mVF at the baseline was 1 and ≥ 2, respectively. CONCLUSIONS: The annual incidence rates of VF and sVF were 5.9%/year and 1.7%/year, respectively. The presence of prevalent mVF was an independent risk factor for incident sVF.

Incidence rate and risk factors for radiographic hip osteoarthritis in Japanese men and women: a 10-year follow-up of the ROAD study.

OBJECTIVE: To investigate the incidence and progression rate of radiographic hip osteoarthritis (OA) and its risk factors in Japanese men and women using a large-scale population of a nationwide cohort study, Research on Osteoarthritis/osteoporosis Against Disability (ROAD). METHODS: From the baseline survey of the ROAD study, 2,975 participants (1,043 men and 1,932 women) aged 23-94 years (mean, 70.2 years) living in urban, mountainous, and coastal communities were followed up with hip radiography at 3, 7, and 10 years (mean follow-up, 7.1 years). Radiographs were scored using the Kellgren/Lawrence (K/L) grading system, and radiographic hip OA was defined as K/L ≥ 2. The incidence and progression rate of hip OA were examined. Acetabular dysplasia was defined as a central-edge angle <20°. Cox's proportional hazard model was used to assess risk factors for incident and progressive radiographic hip OA. RESULTS: The incidence rate of radiographic hip OA was 5.6/1,000 person-years and 8.4/1,000 person-years in men and women, respectively. The progression rate of hip OA was 2.2/1,000 person-years and 6.0/1,000 person-years in men and women, respectively. The significant risk factors for incident hip OA were age, obesity, and acetabular dysplasia at baseline (hazard risk [HR] 1.05, 95% confidence interval [CI] 1.03-1.08; 1.78, 1.10-2.75; 2.06, 1.30-3.17, respectively). The significant risk factors for progressive hip OA were baseline hip pain and acetabular dysplasia (HR 5.68, 95%CI 1.07-22.61; 14.78, 3.66-56.06, respectively). CONCLUSION: Continued longitudinal surveys of the ROAD study will contribute to knowledge about and potential prevention of incident and progressive hip OA.

Do sarcopenia and/or osteoporosis increase the risk of frailty? A 4-year observation of the second and third ROAD study surveys.

In this 4-year follow-up study including 1083 subjects (≥ 60 years), the prevalence of frailty was estimated to be 5.6%; osteoporosis was found to be significantly associated with frailty. Moreover, the presence of both osteoporosis and sarcopenia increased the risk of frailty compared to the presence of osteoporosis or sarcopenia alone. INTRODUCTION: This study aims to examine the contribution of sarcopenia and osteoporosis to the occurrence of frailty using 4-year follow-up information of a population-based cohort study. METHODS: The second survey of the Research on Osteoarthritis/Osteoporosis Against Disability (ROAD) study was conducted between 2008 and 2010; 1083 subjects (aged ≥ 60 years, 372 men, 711 women) completed all examinations on frailty, sarcopenia, and osteoporosis, which were defined using Fried's definition, Asian Working Group for Sarcopenia criteria, and WHO criteria, respectively. The third survey was conducted between 2012 and 2013; 749 of 1083 individuals enrolled from the second survey (69.2%, 248 men, 501 women) completed assessments identical to those in the second survey. RESULTS: The prevalence of frailty in the second survey was 5.6% (men, 3.8%; women, 6.6%). The cumulative incidence of frailty was 1.2%/year (men, 0.8%/year; women, 1.3%/year). After adjustment for confounding factors, logistic regression analysis indicated that osteoporosis was significantly associated with the occurrence of frailty (odds ratio, 3.07; 95% confidence interval, 1.26-7.36; p = 0.012). Moreover, the occurrence of frailty significantly increased according to the presence of osteoporosis and sarcopenia (odds ratio vs. neither osteoporosis nor sarcopenia: osteoporosis alone, 2.50; osteoporosis and sarcopenia, 5.80). CONCLUSIONS: Preventing osteoporosis and coexistence of osteoporosis and sarcopenia may help reduce the risk of frailty.

Radiographic measurements of the hip joint and their associations with hip pain in Japanese men and women: the Research on Osteoarthritis/osteoporosis Against Disability (ROAD) study.

OBJECTIVE: To investigate radiographic measurements of the hip joint and their associations with hip pain, and the prevalence of acetabular dysplasia defined by radiographic measurements of the hip joint in Japanese men and women using the large-scale population-based cohort of the Research on Osteoarthritis/osteoporosis Against Disability (ROAD) study. METHODS: From the baseline survey of the ROAD study (cross-sectional study), 2963 participants (1040 men, 1923 women; mean age, 70.2 years) were analyzed. All participants underwent radiographic examinations of both hips using an anteroposterior view under weight-bearing. Minimum joint space width (mJSW), central-edge (CE) angle, acetabular depth-to-width ratio (ADR), and acetabular head index (AHI) were measured. Associations between these radiographic measurements and hip pain were assessed by calculating odds ratios (ORs) using multivariable logistic-regression analysis. Acetabular dysplasia was defined as a CE angle <20°. RESULTS: Mean radiographic measurements of the hip joint for men were: mJSW, 3.8 mm; CE angle, 30.6°; ADR, 262.1 per 1000; and AHI, 81.4%. For women, these values were: mJSW, 3.4 mm; CE angle, 29.9°; ADR, 262.7 per 1000; and AHI, 81.2%. Associations were seen between hip pain and each of mJSW, CE angle, ADR, and AHI (OR 4.52, 95% confidence interval 3.45-5.97; 1.14, 1.11-1.18; 1.31, 1.24-1.40; and 1.15, 1.12-1.18, respectively). Acetabular dysplasia showed an overall prevalence of 13.9%, and was significantly more prevalent in women than in men (P = 0.012). CONCLUSION: The present study of radiographic measurements of the hip joint showed that mJSW, CE angle, ADR, and AHI were associated with hip pain.

Is osteoporosis a predictor for future sarcopenia or vice versa? Four-year observations between the second and third ROAD study surveys.

In a 4-year follow-up study that enrolled 1099 subjects aged ≥60 years, sarcopenia prevalence was estimated at 8.2%. Moreover, the presence of osteoporosis was significantly associated with short-term sarcopenia occurrence, but the reciprocal relationship was not observed, suggesting that osteoporosis would increase the risk of osteoporotic fracture and sarcopenia occurrence. INTRODUCTION: The present 4-year follow-up study was performed to clarify the prevalence, incidence, and relationships between sarcopenia (SP) and osteoporosis (OP) in older Japanese men and women. METHODS: We enrolled 1099 participants (aged, ≥60 years; 377 men) from the second survey of the Research on Osteoarthritis/Osteoporosis against Disability (ROAD) study (2008-2010) and followed them up for 4 years. Handgrip strength, gait speed, skeletal muscle mass, and bone mineral density were assessed. SP was defined according to the Asian Working Group for Sarcopenia. OP was defined based on the World Health Organization criteria. RESULTS: SP prevalence was 8.2% (men, 8.5%; women, 8.0%) in the second survey. In those with SP, 57.8% (21.9%; 77.6%) had OP at the lumbar spine L2-4 and/or femoral neck. SP cumulative incidence was 2.0%/year (2.2%/year; 1.9%/year). Multivariate regression analysis revealed that OP was significantly associated with SP occurrence within 4 years (odds ratio, 2.99; 95% confidence interval, 1.46-6.12; p < 0.01), but the reciprocal relationship was not significantly observed (2.11; 0.59-7.59; p = 0.25). CONCLUSIONS: OP might raise the short-term risk of SP incidence. Therefore, OP would not only increase the risk for osteoporotic fracture but may also increase the risk for SP occurrence.

High-resolution copy number variation analysis of schizophrenia in Japan.

Recent schizophrenia (SCZ) studies have reported an increased burden of de novo copy number variants (CNVs) and identified specific high-risk CNVs, although with variable phenotype expressivity. However, the pathogenesis of SCZ has not been fully elucidated. Using array comparative genomic hybridization, we performed a high-resolution genome-wide CNV analysis on a mainly (92%) Japanese population (1699 SCZ cases and 824 controls) and identified 7066 rare CNVs, 70.0% of which were small (<100 kb). Clinically significant CNVs were significantly more frequent in cases than in controls (odds ratio=3.04, P=9.3 × 10-9, 9.0% of cases). We confirmed a significant association of X-chromosome aneuploidies with SCZ and identified 11 de novo CNVs (e.g., MBD5 deletion) in cases. In patients with clinically significant CNVs, 41.7% had a history of congenital/developmental phenotypes, and the rate of treatment resistance was significantly higher (odds ratio=2.79, P=0.0036). We found more severe clinical manifestations in patients with two clinically significant CNVs. Gene set analysis replicated previous findings (e.g., synapse, calcium signaling) and identified novel biological pathways including oxidative stress response, genomic integrity, kinase and small GTPase signaling. Furthermore, involvement of multiple SCZ candidate genes and biological pathways in the pathogenesis of SCZ was suggested in established SCZ-associated CNV loci. Our study shows the high genetic heterogeneity of SCZ and its clinical features and raises the possibility that genomic instability is involved in its pathogenesis, which may be related to the increased burden of de novo CNVs and variable expressivity of CNVs.

Abnormal asymmetries in subcortical brain volume in schizophrenia.

Subcortical structures, which include the basal ganglia and parts of the limbic system, have key roles in learning, motor control and emotion, but also contribute to higher-order executive functions. Prior studies have reported volumetric alterations in subcortical regions in schizophrenia. Reported results have sometimes been heterogeneous, and few large-scale investigations have been conducted. Moreover, few large-scale studies have assessed asymmetries of subcortical volumes in schizophrenia. Here, as a work completely independent of a study performed by the ENIGMA consortium, we conducted a large-scale multisite study of subcortical volumetric differences between patients with schizophrenia and controls. We also explored the laterality of subcortical regions to identify characteristic similarities and differences between them. T1-weighted images from 1680 healthy individuals and 884 patients with schizophrenia, obtained with 15 imaging protocols at 11 sites, were processed with FreeSurfer. Group differences were calculated for each protocol and meta-analyzed. Compared with controls, patients with schizophrenia demonstrated smaller bilateral hippocampus, amygdala, thalamus and accumbens volumes as well as intracranial volume, but larger bilateral caudate, putamen, pallidum and lateral ventricle volumes. We replicated the rank order of effect sizes for subcortical volumetric changes in schizophrenia reported by the ENIGMA consortium. Further, we revealed leftward asymmetry for thalamus, lateral ventricle, caudate and putamen volumes, and rightward asymmetry for amygdala and hippocampal volumes in both controls and patients with schizophrenia. Also, we demonstrated a schizophrenia-specific leftward asymmetry for pallidum volume. These findings suggest the possibility of aberrant laterality in neural pathways and connectivity patterns related to the pallidum in schizophrenia.

Prevalence of radiographic hip osteoarthritis and its association with hip pain in Japanese men and women: the ROAD study.

OBJECTIVE: Although hip osteoarthritis (OA) is a major cause of hip pain and disability in elderly people, few epidemiologic studies have been performed. We investigated the prevalence of radiographic hip OA and its association with hip pain in Japanese men and women using a large-scale population of a nationwide cohort study, Research on Osteoarthritis/osteoporosis Against Disability (ROAD). METHODS: From the baseline survey of the ROAD study, 2975 participants (1043 men and 1932 women), aged 23-94 years (mean 70.2 years), living in urban, mountainous, and coastal communities were analyzed. The radiographic severity at both hips was determined by the Kellgren/Lawrence (K/L) grading system. Radiographic hip OA was defined as K/L ≥ 2, and severe radiographic hip OA as K/L ≥ 3. RESULTS: The crude prevalence of radiographic hip OA was 18.2% and 14.3% in men and women, respectively, that of severe radiographic hip OA was 1.34% and 2.54%, and that of symptomatic K/L ≥ 2 OA was 0.29% and 0.99%, respectively. The crude prevalence of hip OA, including severe OA, was not age-dependent in men or women. Male sex was a risk factor for radiographic hip OA, whereas female sex was a risk factor for severe radiographic hip OA and hip pain. Compared with K/L = 0/1, hip pain was significantly associated with K/L ≥ 3, but not with K/L = 2. CONCLUSION: The present cross-sectional study revealed the prevalence of radiographic hip OA and severe hip OA in Japanese men and women. Hip pain was strongly associated with K/L ≥ 3.

Common variants at 1p36 are associated with superior frontal gyrus volume.

The superior frontal gyrus (SFG), an area of the brain frequently found to have reduced gray matter in patients with schizophrenia, is involved in self-awareness and emotion, which are impaired in schizophrenia. However, no genome-wide association studies of SFG volume have investigated in patients with schizophrenia. To identify single-nucleotide polymorphisms (SNPs) associated with SFG volumes, we demonstrated a genome-wide association study (GWAS) of gray matter volumes in the right or left SFG of 158 patients with schizophrenia and 378 healthy subjects. We attempted to bioinformatically ascertain the potential effects of the top hit polymorphism on the expression levels of genes at the genome-wide region. We found associations between five variants on 1p36.12 and the right SFG volume at a widely used benchmark for genome-wide significance (P<5.0 × 10(-8)). The strongest association was observed at rs4654899, an intronic SNP in the eukaryotic translation initiation factor 4 gamma, 3 (EIF4G3) gene on 1p36.12 (P=7.5 × 10(-9)). No SNP with genome-wide significance was found in the volume of the left SFG (P>5.0 × 10(-8)); however, the rs4654899 polymorphism was identified as the locus with the second strongest association with the volume of the left SFG (P=1.5 × 10(-6)). In silico analyses revealed a proxy SNP of rs4654899 had effect on gene expression of two genes, HP1BP3 lying 3' to EIF4G3 (P=7.8 × 10(-6)) and CAPN14 at 2p (P=6.3 × 10(-6)), which are expressed in moderate-to-high levels throughout the adult human SFG. These results contribute to understand genetic architecture of a brain structure possibly linked to the pathophysiology of schizophrenia.

Neural substrates participating in acquisition of facial familiarity: an fMRI study.

The amygdala is related to recognition of faces and emotions, and functional magnetic resonance imaging (fMRI) studies have reported that the amygdala is habituated over time with repetition of facial stimuli. When subjects are presented repeatedly with unfamiliar faces, they come to gradually recognize the unfamiliar faces as familiar. To investigate the brain areas participating in the acquisition of familiarity to repeatedly presented unfamiliar faces, we conducted an fMRI study in 16 healthy subjects. During the task periods, the subjects were instructed to see presented unfamiliar faces repeatedly and to judge whether the face was male or female or whether the face had emotional valences. The experiment consisted of nine sessions. To clarify the brain areas that showed increasing or decreasing activation as the experimental session proceeded, we analyzed the fMRI data using specified linear covariates in the face recognition task from the first session to the ninth session. Imaging data were investigated on a voxel-by-voxel basis for single-group analysis according to the random effect model using Statistical Parametric Mapping. The bilateral posterior cingulate cortices showed significant increases in activity as the experimental sessions proceeded, while the activation in the right amygdala and the left medial fusiform gyrus decreased. Thus, the posterior cingulate cortex may play an important role in the acquisition of facial familiarity.

Proliferative activity of canine mast cell tumours evaluated by bromodeoxyuridine incorporation and Ki-67 expression.

The proliferative activity of 91 canine mast cell tumours was assessed on the basis of the Ki-67 positive index (Ki-67 PI) and mitotic index (MI) and, in 15 cases, also by the labelling index of bromodeoxyuridine (BrdU; an analogue of tritiated thymidine) incorporated in vivo into S-phase cells. BrdU and Ki-67 were detected immunohistochemically. The tumours were graded histologically (I, II or III). The BrdU labelling index (BrdU LI) tended to increase as the grade became higher. In terms of the mean values of Ki-67 PI, significant differences were found between histological tumour grades I and II (P < 0.01) and between grades II and III (P < 0.01). In terms of mean MI, grades I and II were found to differ significantly (P < 0.05). With Spearman rank correlation coefficient and linear regression analysis, the BrdU LI and Ki-67 PI showed a highly significant correlation. This strong correlation indicated that Ki-67 was, like BrdU, a useful marker for proliferative potential in canine mast cell tumours; moreover, its use did not require the prior administration of any reagent to the live animal.

Differential amygdala response during facial recognition in patients with schizophrenia: an fMRI study.

Human lesion or neuroimaging studies suggest that amygdala is involved in facial emotion recognition. Although impairments in recognition of facial and/or emotional expression have been reported in schizophrenia, there are few neuroimaging studies that have examined differential brain activation during facial recognition between patients with schizophrenia and normal controls. To investigate amygdala responses during facial recognition in schizophrenia, we conducted a functional magnetic resonance imaging (fMRI) study with 12 right-handed medicated patients with schizophrenia and 12 age- and sex-matched healthy controls. The experiment task was a type of emotional intensity judgment task. During the task period, subjects were asked to view happy (or angry/disgusting/sad) and neutral faces simultaneously presented every 3 s and to judge which face was more emotional (positive or negative face discrimination). Imaging data were investigated in voxel-by-voxel basis for single-group analysis and for between-group analysis according to the random effect model using Statistical Parametric Mapping (SPM). No significant difference in task accuracy was found between the schizophrenic and control groups. Positive face discrimination activated the bilateral amygdalae of both controls and schizophrenics, with more prominent activation of the right amygdala shown in the schizophrenic group. Negative face discrimination activated the bilateral amygdalae in the schizophrenic group whereas the right amygdala alone in the control group, although no significant group difference was found. Exaggerated amygdala activation during emotional intensity judgment found in the schizophrenic patients may reflect impaired gating of sensory input containing emotion.

MRI white matter hyperintensities, (1)H-MR spectroscopy and cognitive function in geriatric depression: a comparison of early- and late-onset cases.

UNLABELLED: BACKGROUND AND OBJECTIVES Geriatric depression is often thought to differ from that at other times of adulthood. Recently, several studies have shown that the incidence of white matter hyperintense lesions identified by brain MRI is higher in patients with geriatric depression than in healthy elderly subjects, but a consensus has not yet been reached on the relationship between the severity of white matter lesions and either cognitive impairment or depressive symptoms. METHOD: Forty-seven patients aged 50 to 75 years with major depression were divided into two groups based on age at onset of depression: early-onset (< 50 years) group (20 patients; mean age, 62.7 +/- 6.7) and late-onset (> or =50 years) group (27 patients; mean age, 65.6 +/- 5.4). The severity of hyperintense white matter lesions on MRI was classified by region, then a proton magnetic resonance spectroscopy ((1)H-MRS) focusing on the white matter of the frontal lobes, multidimensional neuropsychological tests and evaluation of depressive symptoms were conducted. RESULTS: The severity of the deep white matter lesions, the deterioration of cognitive function related to subcortical/frontal brain system and clinician-rated depressive symptoms were all more pronounced in the late-onset group compared with those in the early-onset group. It was further observed that the more severe the deep white matter lesions, the lower the levels of N-acetylaspartate/creatine. With the age of onset as the covariate, the patients with moderate deep white matter lesions had more pronounced cognitive impairment and clinician-rated depressive symptoms than those with none and/or mild lesions. CONCLUSION: These results suggest that subcortical/frontal type cognitive impairment and the persistence of depressive symptoms in geriatric depression is related to moderate deep white matter lesions more often complicated in the late-onset group. The (1)H-MRS findings were suggested to be a useful indicator of neuronal/axonal loss in the white matter of the frontal lobes which precedes cognitive impairment.

Differential effects of partial hepatectomy and carbon tetrachloride administration on induction of liver cell foci in a model for detection of initiation activity.

Differential effects of partial hepatectomy (PH) and carbon tetrachloride (CCl(4)) administration on induction of glutathione S-transferase placental form (GST-P)-positive foci were investigated in a model for detection of initiation activity. Firstly, we surveyed cell proliferation kinetics and fluctuation in cytochrome P450 (CYP) mRNA levels by means of relative-quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and CYP 2E1 apoprotein amount by immunoblotting (experiment I) after PH or CCl(4) administration. Next, to assess the interrelationships among cell proliferation, fluctuation of CYPs after PH or CCl(4) administration and induction of liver cell foci, the non-hepatocarcinogen, 1,2-dimethylhydrazine (DMH) was administered to 7-week-old male F344 rats and initiated populations were selected using the resistant hepatocyte model (experiment II). In experiment I, the values of all CYP isozyme mRNAs after PH or CCl(4) administration were drastically decreased at the 12-h time point. From 72 h, mRNAs for all CYP isozymes began increasing, with complete recovery after 7 days. The CYP 2E1 apoprotein content in the PH group fluctuated weakly, whereas in the CCl(4) group it had decreased rapidly after 12 h and was still low at the 48 h point. In experiment II, induction of GST-P-positive foci was related to cell kinetics in the PH group, with about a 6-h time lag between time for carcinogen administration giving greatest induction of GST-P-positive foci and peaks in bromodeoxyuridine (BrdU) labeling, presumably due to the necessity for bioactivation of DMH. With CCl(4) administration, induction of foci appeared dependent on the recovery of CYP 2E1. In conclusion, PH was able to induce cell proliferation with maintenance of CYP 2E1, therefore being advantageous for induction of liver cell foci in models to detect initiation activity.

An fMRI study of the functional neuroanatomy of picture encoding in younger and older adults.

Age-related changes in the neural mechanisms of picture encoding were investigated using functional magnetic resonance imaging (fMRI). Seven younger and seven older adults were studied while they were encoding pairs of concrete-related, concrete-unrelated, and abstract pictures. Functional (T2*-weighted) and anatomical (T1-weighted) images of the brain were obtained using a 1.5 T MRI scanner. The results in the younger adults showed that the left dorsal prefrontal cortex (PFC) was activated during associative learning of the concrete-unrelated or abstract pictures. The results also suggest that both ventral and dorsal visual pathways are involved in the encoding of abstract pictures, and that the right superior parietal lobule likely mediates spatial information of the abstract pictures. The older adults showed significant activation in the left dorsal PFC under concrete-unrelated and abstract conditions. However, the older adults failed to activate either the left ventral and right dorsal PFC under the concrete-unrelated condition, or the parietal areas under abstract condition. A direct comparison between the two age groups demonstrates that the older adults had a reduced activation in the bilateral parieto-temporo-occipital areas under abstract condition, and in the right temporo-occipital area extending to the fusiform gyrus under the concrete-unrelated condition. Finally, age difference was found in correlation between memory performance and amplitude of signal change in the parahippocampal gyrus and fusiform gyrus under the concrete-unrelated and abstract conditions. These changes in neural response likely underlie the age-related memory decline in relation to pictorial information.

Neural interaction of the amygdala with the prefrontal and temporal cortices in the processing of facial expressions as revealed by fMRI.

Some involvement of the human amygdala in the processing of facial expressions has been investigated in neuroimaging studies, although the neural mechanisms underlying motivated or emotional behavior in response to facial stimuli are not yet fully understood. We investigated, using functional magnetic resonance imaging (fMRI) and healthy volunteers, how the amygdala interacts with other cortical regions while subjects are judging the sex of faces with negative, positive, or neutral emotion. The data were analyzed by a subtractive method, then, to clarify possible interaction among regions within the brain, several kinds of analysis (i.e., a correlation analysis, a psychophysiological interaction analysis and a structural equation modeling) were performed. Overall, significant activation was observed in the bilateral fusiform gyrus, medial temporal lobe, prefrontal cortex, and the right parietal lobe during the task. The results of subtraction between the conditions showed that the left amygdala, right orbitofrontal cortex, and temporal cortices were predominantly involved in the processing of the negative expressions. The right angular gyrus was involved in the processing of the positive expressions when the negative condition was subtracted from the positive condition. The correlation analysis showed that activity in the left amygdala positively correlated with activity in the left prefrontal cortex under the negative minus neutral subtraction condition. The psychophysiological interaction revealed that the neural responses in the left amygdala and the right prefrontal cortex underwent the condition-specific changes between the negative and positive face conditions. The right amygdaloid activity also had an interactive effect with activity in the right hippocampus and middle temporal gyrus. These results may suggest that the left and right amygdalae play a differential role in effective processing of facial expressions in collaboration with other cortical or subcortical regions, with the left being related with the bilateral prefrontal cortex, and the right with the right temporal lobe.

The effects of divided attention on encoding- and retrieval-related brain activity: A PET study of younger and older adults.

Divided attention (DA) disrupts episodic encoding, but has little effect on episodic retrieval. Furthermore, normal aging is associated with episodic memory impairments, and when young adults are made to encode information under DA conditions, their memory performance is reduced and resembles that of old adults working under full attention (FA) conditions. Together, these results suggest a common neurocognitive mechanism by which aging and DA during encoding disrupt memory performance. In the current study, we used PET to investigate younger and older adults' brain activity during encoding and retrieval under FA and DA conditions. In FA conditions, the old adults showed reduced activity in prefrontal regions that younger adults activated preferentially during encoding or retrieval, as well as increased activity in prefrontal regions young adults did not activate. These results indicate that prefrontal functional specificity of episodic memory is reduced by aging. During encoding, DA reduced memory performance, and reduced brain activity in left-prefrontal and medial-temporal lobe regions for both age groups, indicating that DA during encoding interferes with encoding processes that lead to better memory performance. During retrieval, memory performance and retrieval-related brain activity were relatively immune to DA for both age groups, suggesting that DA during retrieval does not interfere with the brain systems necessary for successful retrieval. Finally, left inferior prefrontal activity was reduced similarly by aging and by DA during encoding, suggesting that the behavioral correspondence between these effects is the result of a reduced ability to engage in elaborate encoding operations.

Brain regions involved in verbal or non-verbal aspects of facial emotion recognition.

To depict the neural substrates for facial emotion recognition and to determine whether their activation is confounded by a verbal factor, we studied eight normal volunteers with functional magnetic resonance imaging (fMRI). Verbal and non-verbal sample stimuli were used in a facial emotion matching task and a gender matching task (control condition). Compared with the gender tasks, the emotion tasks significantly activated the right ventral prefrontal cortex, the right lingual cortex, and the left lateral fusiform cortex, irrespective of sample stimuli. The visual association cortices showed a significant interaction between the task and the material presented, as the activation for verbal materials was higher than for non-verbal materials during the emotion matching tasks. By contrast, no significant interaction was found in the right ventral prefrontal cortex. These results suggest that the verbal factor has a different effect on the neural networks for facial emotion, processing.

The effect of divided attention on encoding and retrieval in episodic memory revealed by positron emission tomography.

The effects of divided attention (DA) on episodic memory encoding and retrieval were investigated in 12 normal young subjects by positron emission tomography (PET). Cerebral blood flow was measured while subjects were concurrently performing a memory task (encoding and retrieval of visually presented word pairs) and an auditory tone-discrimination task. The PET data were analyzed using multivariate Partial Least Squares (PLS), and the results revealed three sets of neural correlates related to specific task contrasts. Brain activity, relatively greater under conditions of full attention (FA) than DA, was identified in the occipital-temporal, medial, and ventral-frontal areas, whereas areas showing relatively more activity under DA than FA were found in the cerebellum, temporo-parietal, left anterior-cingulate gyrus, and bilateral dorsolateral-prefrontal areas. Regions more active during encoding than during retrieval were located in the hippocampus, temporal and the prefrontal cortex of the left hemisphere, and regions more active during retrieval than during encoding included areas in the medial and right-prefrontal cortex, basal ganglia, thalamus, and cuneus. DA at encoding was associated with specific decreases in rCBF in the left-prefrontal areas, whereas DA at retrieval was associated with decreased rCBF in a relatively small region in the right-prefrontal cortex. These different patterns of activity are related to the behavioral results, which showed a substantial decrease in memory performance when the DA task was performed at encoding, but no change in memory levels when the DA task was performed at retrieval.