Both left and right posterior parietal activations contribute to compensatory processes in normal aging

Older adults often exhibit greater brain activation in prefrontal cortex compared to younger adults, and there is some evidence that this increased activation compensates for age-related neural degradation that would otherwise adversely affect cognitive performance. Less is known about aging and compensatory recruitment in the parietal cortex. In this event-related functional magnetic resonance imaging study, we presented healthy young and old participants with two Stroop-like tasks (number magnitude and physical size). In young, the number magnitude task activated right parietal cortex and the physical size task activated left parietal cortex. In older adults, we observed contralateral parietal recruitment that depended on the task: in the number magnitude task older participants recruited left posterior parietal cortex (in addition to the right parietal activity observed in young) while in the physical size task they recruited right (in addition to left) posterior parietal cortex. In both cases, the additional parietal activity was associated with better performance suggesting that it played a compensatory role. Older adults also recruited left prefrontal cortex during both tasks and this common activation was also associated with better performance. The results provide evidence for task-specific compensatory recruitment in parietal cortex as well as task-independent compensatory recruitment in prefrontal cortex in normal aging.     

Subgenual prefrontal cortex of child and adolescent bipolar patients: a morphometric magnetic resonance imaging study

The subgenual prefrontal cortex (SGPFC) plays an important role in emotional processing. We carried out a magnetic resonance imaging (MRI) study comparing the volume of the SGPFC in child and adolescent bipolar patients and healthy controls. The sample consisted of 15 children and adolescents who met DSM-IV criteria for bipolar disorder (mean age +/- S.D.=15.5 +/- 3.5 years) and 21 healthy adolescents (mean age +/- S.D.=16.9 +/- 3.8 years). MR images were obtained with a 1.5 T GE Signa Imaging System with Signa 5.4.3 software. SGPFC volumes were measured with the semi-automated software MedX (Sensor Systems, Sterling, VA, USA). ANCOVA was performed to compare SGPFC volumes between groups, using age, gender and intra-cranial volume (ICV) as covariates. The volumes (mean +/- S.D.) of the right and left SGPFC for bipolar patients were 291.27 +/- 88.70 mm(3) and 284.86 +/- 83.98 mm(3), respectively. For healthy controls, the right and left SGPFC volumes were 284.95 +/- 73.33 mm(3) and 307.55 +/- 73.67 mm(3), respectively. There were no statistically significant differences between groups regarding right or left SGPFC volumes. We found no evidence of volumetric abnormalities in the SGPFC of bipolar children and adolescents.     

Neural activation patterns of successful episodic encoding: Reorganization during childhood,maintenance in old age

The two-component framework of episodic memory (EM) development posits that the contributions of medial temporal lobe (MTL) and prefrontal cortex (PFC) to successful encoding differ across the lifespan. To test the framework’s hypotheses, we compared subsequent memory effects (SME) of 10–12 year-old children, younger adults, and older adults using functional magnetic resonance imaging (fMRI). Memory was probed by cued recall, and SME were defined as regional activation differences during encoding between subsequently correctly recalled versus omitted items. In MTL areas, children’s SME did not differ in magnitude from those of younger and older adults. In contrast, children’s SME in PFC were weaker than the corresponding SME in younger and older adults, in line with the hypothesis that PFC contributes less to successful encoding in childhood. Differences in SME between younger and older adults were negligible. The present results suggest that, among individuals with high memory functioning, the neural circuitry contributing to successful episodic encoding is reorganized from middle childhood to adulthood. Successful episodic encoding in later adulthood, however, is characterized by the ability to maintain the activation patterns that emerged in young adulthood.     

Gray matter volume decreases in elderly patients with schizophrenia: a voxel-based morphometry study

Background: Aged patients (>50 years old) with residual schizophrenic symptoms differ from young patients. They represent a subpopulation with a more unfavorable Kraepelinian course and have an increased risk (up to 30%) for dementia of unknown origin. However, our current understanding of age-related brain changes in schizophrenia is derived from studies that included less than 17% of patients who were older than 50 years of age. This study investigated the anatomical distribution of gray matter (GM) brain deficits in aged patients with ongoing schizophrenia. Methods: Voxel-based morphometry was applied to 3D-T1 magnetic resonance images obtained from 27 aged patients with schizophrenia (mean age of 60 years) and 40 age-matched normal controls. Results: Older patients with schizophrenia showed a bilateral reduction of GM volume in the thalamus, the prefrontal cortex, and in a large posterior region centered on the occipito-temporo-parietal junction. Only the latter region showed accelerated GM volume loss with increasing age. None of these results could be accounted for by institutionalization, antipsychotic medication, or cognitive scores. Conclusions: This study replicated most common findings in patients with schizophrenia with regard to thalamic and frontal GM deficits. However, it uncovered an unexpected large region of GM atrophy in the posterior tertiary cortices. The latter observation may be specific to this aged and chronically symptomatic subpopulation, as atrophy in this region is rarely reported in younger patients and is accelerated with age.     

Measurement of brain regional alpha-[11C]methyl-L-tryptophan trapping as a measure of serotonin synthesis in medication-free patients with major depression

CONTEXT: The serotonin hypothesis of depression invokes a relative or absolute deficit of serotonin neurotransmission. Reduced synthesis of serotonin in the brain pathways mediating the expression of mood (ie, the limbic cortex) is a plausible candidate mechanism. OBJECTIVES: To measure and compare, using the alpha-[(11)C]methyl-l-tryptophan/positron emission tomography method, the brain trapping constant of alpha-[(11)C]methyl-l-tryptophan (K*, milliliters per gram per minute), an index of serotonin synthesis, in brain areas involved in the regulation of mood in patients with major depression (MD) and age- and sex-matched controls. DESIGN: Between-group comparison. SETTING: Department of Psychiatry and Montreal Neurological Institute, McGill University. PARTICIPANTS: Seventeen medication-free outpatients with a current episode of MD (9 women: mean +/- SD age, 41 +/- 11 years; 8 men: mean +/- SD age, 41 +/- 11 years) and 17 controls (9 women: mean +/- SD age, 37 +/- 15 years; 8 men: mean +/- SD age, 32.5 +/- 9.9 years).Main Outcome Measure Normalized K*, normalized to the global mean, was measured in the dorsolateral prefrontal, anterior cingulate, and mesial temporal cortices; the thalamus; and the caudate nucleus. RESULTS: Compared with age- and sex-matched controls, normalized K* was significantly decreased bilaterally in female patients with MD in the anterior cingulate cortex, in the left anterior cingulate cortex in male patients with MD, and in the left mesial temporal cortex in male and female patients with MD (P<.001 for all). Exploratory analyses identified additional patient-control differences for normalized K* (eg, inferior frontal gyrus and superior parietal lobule), most of which, once corrected for 38 multiple comparisons, lost their significance. Morphometric measurements of the cingulate cortex divisions confirmed that the reduction of normalized K* in depressed patients was not attributable to a reduction in gray matter volume. Normalized K* in the anterior cingulate cortex did not correlate with ratings of depression severity collected at the time of scan. CONCLUSIONS: Reduction of normalized K*, an index of serotonin synthesis, in parts of the limbic and paralimbic cortices may contribute to the biochemical alterations associated with MD.     

Reduced dorsal and orbital prefrontal gray matter volumes in schizophrenia

BACKGROUND: Converging neuroanatomic, neurophysiological, and neurobehavioral evidence implicate prefrontal subregions in schizophrenia. Neuroanatomic studies with magnetic resonance (MR) imaging enable regional volume parcellation. Inconsistent reports may relate to variable methods and small samples. We attempted to resolve volume differences within sectors of the prefrontal lobe in a large sample, relating volumes to clinical and neurocognitive features. METHODS: Magnetic resonance imaging was performed in 70 patients with schizophrenia (40 men and 30 women; 29 neuroleptic naive and 41 previously treated) and 81 healthy controls (34 men and 47 women). Gray and white matter volumes of the dorsolateral, dorsomedial, orbitolateral, and orbitomedial prefrontal cortex were quantified. Symptoms, functioning, and neurocognition were assessed concurrently. RESULTS: Reduced prefrontal gray matter volume was observed in patients. The reduction was evident for the dorsolateral area in men (9%) and women (11%), for the dorsomedial area only in men (9%), and for orbital regions only in women (23% and 10% for lateral and medial, respectively). The reduction of orbital volume in women was associated with poorer premorbid functioning, more severe negative symptoms, and depression. Volume of dorsal cortex was positively associated with better performance on abstraction and attention tasks across all groups. CONCLUSIONS: Schizophrenia is associated with reduced gray matter volume in prefrontal cortex, which affects men and women in the dorsolateral sector. The effects are moderated by sex for dorsomedial and orbital regions and are related to symptom severity and cognitive function. This is not a by-product of treatment, since the differences are evident in neuroleptic-naive patients.     

Reduced number of mediodorsal and anterior thalamic neurons in schizophrenia.

BACKGROUND: The thalamus is a brain region of interest in the study of schizophrenia because it provides critical input to brain regions such as the prefrontal, cingulate, and temporal cortices, where abnormalities have been repeatedly observed in patients with schizophrenia. Postmortem anatomic studies have rarely investigated the thalamus in this population. METHODS: Postmortem tissue was obtained from the left hemisphere of eight male schizophrenic patients and eight male age-matched control subjects. The optical dissector stereologic procedure was used to count neurons in the mediodorsal (MD) and anteroventral/anteromedial (AV/AM) nuclei of the thalamus. RESULTS: The number of neurons and volume of the MD were significantly reduced by 35% and 24%, respectively. The MD cell number reduction was a consistent finding; every control subject had more and every schizophrenic subject had fewer than 3.5 million neurons. Neuron number was also significantly reduced (16%) in the AV/AM nuclei. CONCLUSIONS: The present data indicate that schizophrenia is associated with robust reductions in nerve cell numbers in nuclei that communicate with the prefrontal cortex and limbic system. These thalamic anatomic deficits may be responsible, in part, for previous reports of such prefrontal cortical abnormalities as reduced synaptic density, reduced volume, and metabolic hypofunction.     

年轻人与老年人简单乘法运算之功能磁共振成像研究

目的应用fMRI技术探讨中国青年和老年人群在简单运算任务下脑激活模式及其与行为学之间的关系。方法分别对青年组(19例)和老年组(20例)健康志愿者进行对照任务和简单运算任务下的fMRI检查。结果两组受试者受教育程度(P=0.125)、智力水平(P=0.921),以及完成对照任务(P=0.142)和简单乘法运算任务(P=0.880)之正确率差异无统计学意义,但老年组受试者完成对照任务(P=0.000)和简单乘法运算任务(P=0.005)反应时间明显延长。青年组受试者在任务刺激下可激活右侧缘上回并向顶内沟和颞中上回后部延伸,中央前回和运动前区、前额叶,左侧缘上回并向颞上回后部和角回延伸,顶内沟区域、颞中下回,内侧后扣带回、楔前叶、辅助运动区、海马沟、海马旁回及前额叶内侧;老年组受试者则分别激活右侧缘上回和顶下区域并向颞中上回后部延伸,中央前回和运动前区、前额叶,左侧缘上回和角回并向顶下延伸,中央前回和运动前区、岛叶及前额叶,内侧后扣带回和中央旁小叶、前扣带回及前额叶内侧;两组受试者共激活脑区包括顶下区域、楔前叶、中央前后回和额顶叶网络,以及颞叶、海马旁回、钩回、屏状核和后扣带回等皮质下结构。结论数学事实提取相关网络的主要成分受年龄影响较小,老年人群的任务激活脑区主要向任务相关顶区集中。     

Age-related changes in right middle frontal gyrus volume correlate with altered episodic retrieval activity

Age-related deficits in episodic retrieval have been associated with volume reductions in the middle frontal gyrus (MFG). However, it remains unclear how this age-related reduction in MFG volume correlates with neural activity during retrieval. To address this, we conducted in vivo volumetry of the frontal cortex in young and older human adults and found more volume loss on the right than on the left MFG with age. We then examined how left and right MFG volume correlated with fMRI activity during successful retrieval of item, spatial context, and temporal context information in both age groups. In young adults, larger right MFG volume was positively correlated with greater activity in a commonly found episodic retrieval network that included bilateral dorsolateral prefrontal cortex (DLPFC) and bilateral inferior parietal cortex. Within this network, left DLPFC and right inferior parietal cortex activity predicted memory performance. In older adults, a positive structure-function association in DLPFC for either left or right MFG/DLPFC was not observed. Instead, right MFG volume was negatively correlated with activity in several regions in older adults, including the parahippocampal cortex (PHC) and anterior cingulate. Less activity in the PHC region predicted better item memory, and less activity in the anterior cingulate predicted better spatial context accuracy in older adults. We conclude that age-related change in the structure-function association in MFG/DLPFC impacts retrieval activity and performance, and those older adults with larger right MFG volume attempt to compensate for this change by modifying activity in other brain regions to help retrieval performance.     

The effect of perspective and content on brain activation during mentalizing in young females

In the present functional magnetic resonance imaging (fMRI) study, we investigated the role of different brain regions in separate aspects of mentalizing. Young females aged 18-19 years were asked to imagine a social situation and answer a question. Perspective, self and other, as well as content, emotion, and behavior, were varied. Activation was observed in the left precuneus, left temporoparietal junction, left medial prefrontal cortex and left middle temporal gyrus. Left precuneus and left temporoparietal junction were recruited more when taking the perspective of other than when taking the perspective of self. Medial prefrontal areas might be more involved during mentalizing about emotion versus baseline than about behavior versus baseline.