Meta-analysis of regional brain volumes in schizophrenia

OBJECTIVE: The authors' goal was to determine whether patients with schizophrenia differ from comparison subjects in regional brain volumes and whether these differences are similar in male and female subjects. METHOD: They conducted a systematic search for structural magnetic resonance imaging (MRI) studies of patients with schizophrenia that reported volume measurements of selected cortical, subcortical, and ventricular regions in relation to comparison groups. They carried out a meta-analysis of the volumes of these regions in the patients with schizophrenia and the comparison subjects using a random effects model; they also used random effects regression analysis to examine the influence of gender on effect sizes. RESULTS: Fifty-eight studies were identified as suitable for analysis; these studies included 1,588 independent patients with schizophrenia. Assuming a volume of 100% in the comparison group, they found that the mean cerebral volume of the subjects with schizophrenia was smaller (98%), but the mean total ventricular volume of the subjects with schizophrenia was greater (126%). Relative to the cerebral volume differences, the regional volumes of the subjects with schizophrenia were 94% in the left and right amygdala, 94% in the left and 95% in the right hippocampus/amygdala, and 93% in the left and 95% in the right parahippocampus. Relative to the global ventricular system differences, the largest differences in ventricular subdivisions were in the right and left body of the lateral ventricle, where the volumes of schizophrenic subjects were 116% and 116%, respectively. For most regions, effect size was not significantly related to gender. CONCLUSIONS: Regional structural differences in patients with schizophrenia include bilaterally reduced volume of medial temporal lobe structures. There is a need for greater integration of results from structural MRI studies to avoid redundant research activity.     

Insight and regional brain volumes in schizophrenia

We have investigated the relationship between insight impairment and regional brain volumes (gray and white matter) in schizophrenia using voxel-based morphometry (VBM). Fifty patients with schizophrenia were evaluated using the Scale for Unawareness of Mental Disorders. Magnetic resonance images were acquired, segmented and spatially normalized using optimized VBM routines. No significant inverse correlations were detected between insight impairment and gray or white matter volumes in the prefrontal region (where significant findings had been predicted a priori), or in any other brain areas. Our results do not support previous hypotheses suggesting a relationship between frontal lobe atrophy and impaired insight in patients with schizophrenia.     

MEG based brain laterality: Sex differences in normal adults

Magnetoencephalographic (MEG) auditory evoked fields produced by short tone pips were recorded from 34 normal adults (17 males, 17 females) and the 100 msec latency component (M100) localized in left and right hemispheres. Absolute M100 location in the antero-posterior dimension was calculated for each subject. M100 sources were significantly further anterior in the right hemisphere of males. Magnetic resonance (MR) based anatomy of the superior temporal gyri (STG) in a subset of 17 subjects showed that in the left STG of both males and females M100 sources were located approximately midway on the STG. In the right hemisphere of males, however, M100 sources were significantly further anterior on the STG than was the case for females. The findings are compatible with a sex based difference in right STG functional anatomy, with evidence of greater hemispheric lateralization in males compared to females based upon a predominantly right hemisphere contribution.     

Cross-cultural differences in laterality

Twenty Hebrew speaking subjects identified sets of six digits paired with environmental sounds. Comparison of their performance with those of Japanese- and English-speakers (Hatta & Dimond, 1981) showed that while there were no group differences in overall level of performance, right ear superiority effects were larger for the English- than for the Hebrew- and Japanese-speakers. The data can be interpreted as reflecting the effects of either the linguistic properties of the native language, or of the sequence of language acquisition.     

Correlations between regional brain volumes and memory performance in anoxia

This study was aimed at investigating the quantitative relationship between regional brain volumes (hippocampus, amygdala, as well as cerebrum, frontal lobe, parietal lobe, temporal lobe) and performance on anterograde and retrograde memory tests in anoxic patients. We used high-resolution MRI to measure brain volumes in 13 anoxic patients. Neuropsychological testing was conducted contemporaneously with MRI. To control for age and sex, neuroanatomical volume residuals were calculated using regression equations derived from a group of 87 healthy comparison participants. We found that anoxic patients with severe amnesia had hippocampal volumes that were 36% smaller than normal, whereas patients with mild or no amnesia had normal hippocampal volumes. Regional gray matter volumes in severe amnesic anoxics were substantially smaller than expected. Performances on anterograde memory tests were significantly correlated with hippocampal and regional gray matter volume residuals. There was a significant correlation between white matter volume (but not hippocampal volume) and performance on the Visual Retention Test, a multi-dimensional test of cognitive function. There were no significant correlations between neuroanatomical measures and performance on a retrograde memory test. Our results indicate a strong quantitative relationship between performance on anterograde memory tests and hippocampal and regional gray matter volume residuals. Correlations between white matter volume residuals and performance on the VRT were found to be independent of hippocampal volume. Given the strong correlation between hippocampal volume and total gray matter volume residuals, a quantitative, normalized measure of total gray matter volume may provide a good indication of clinical outcome in anoxia.     

Interhemispheric differences in regional density of the normal brain

In a study of regional variations in cerebral X-ray attenuation as measured by computed tomography, a relationship between bone-related beam hardening and lateralized hemispheric density differences was sought. The CT scans of 22 normal right-handed individuals were evaluated by calculating regional mean attenuation values and regional left-right differences in attenuation, comparing these to regional measurements of skull thickness. A statistically insignificant number of significant correlations was found. This is interpreted to mean that observed left-right hemispheric density differences are not due to beam-hardening through bone. It was also found that left-right differences in density persisted over the entirety of the evaluated slices, suggesting that this finding is due to inherent hemispheric structural differences.     

Ferritin levels and their association with regional brain volumes in Tourette's syndrome

OBJECTIVE: A previous small study showed lower serum ferritin levels in subjects with Tourette's syndrome than in healthy subjects. The authors measured peripheral iron indices in a large group of Tourette's syndrome and comparison subjects and explored associations of ferritin levels with regional brain volumes. METHOD: Ferritin was measured in 107 children and adults (63 Tourette's syndrome, 44 comparison); serum iron was measured in 73 (41 Tourette's syndrome, 32 comparison). Magnetic resonance imaging scans were used to measure volumes of the basal ganglia and cortical gray matter. RESULTS: Ferritin and serum iron were significantly lower in the Tourette's syndrome subjects, although still within the normal range. No association was found between tic severity and either iron index. In the Tourette's syndrome subjects, ferritin did not correlate significantly with caudate volume but did correlate positively with putamen volume. In the comparison subjects, ferritin correlated inversely with caudate volume but did not correlate significantly with putamen volume. Irrespective of diagnosis, ferritin correlated positively with volumes of the sensorimotor, midtemporal, and subgenual cortices. CONCLUSIONS: The lower peripheral ferritin and iron levels in persons with Tourette's syndrome are consistent with findings in other movement disorders and suggest that lower iron availability may have a causal role in the pathophysiology of tic disorders. Lower iron stores may contribute to hypoplasia of the caudate and putamen, increasing vulnerability to developing tics or to having more severe tics. Lower iron stores may also contribute to smaller cortical volumes and consequently to reduced inhibitory control of tics.     

Age, sex and regional brain volumes predict perceptual-motor skill acquisition

Neural mechanisms of skill acquisition across the lifespan are largely unknown. Neuroimaging in younger adults and research on neurodegenerative disorders suggests that perceptual-motor learning relies on the striatum, cerebellum, and prefrontal cortex. Our objective in this study was to explore whether individual differences in regional brain volumes modify the effects of age and sex on the acquisition of a perceptual-motor skill in healthy adults. The participants (N = 85, age 22-80) performed five 5-trial blocks of a mirror-drawing task on three separate days (for a total of 25 trials). Index of performance was time to completion and number of errors committed. All participants improved with practice, but younger adults performed better than their older counterparts, and women performed better than men. Four brain regions--lateral prefrontal cortex (LPFC), hippocampus (HC), cerebellar hemispheres (Cb) and the caudate nucleus (Cd)--were selected on the basis of the relevant literature and measured on MRI scans. All regional volumes were negatively associated with age, although the magnitude of association differed from LPFC (the strongest) to Cd (the weakest). Larger lateral PFC was associated with better performance on the mirror drawing task, and this link was stronger in the older participants and was strengthened at the later stages of learning. Larger caudate was related to better performance, especially at later learning, among men, but among women the link was evident only during early learning. Thus, mirror-drawing represents a task that, despite its visual-spatial nature, favors women, and may exhibit sexually dimorphic brain substrates.     

Response format,magnitude of laterality effects,and sex differences in laterality

The present study examined the evidence for the claim that response format might affect the magnitude of laterality effects by means of a meta-analysis. The analysis included the 396 effect sizes drawn from 266 studies retrieved by Voyer (1996) and relevant to the main effect of laterality and sex differences in laterality for verbal and non-verbal tasks in the auditory, tactile, and visual sensory modality. The response format used in specific studies was the only moderator variable of interest in the present analysis, resulting in four broad response categories (oral, written, computer, and pointing). A meta-analysis analogue to ANOVA showed no significant influence of response format on either the main effect of laterality or sex differences in laterality when all sensory modalities were combined. However, when modalities were considered separately, response format affected the main effect of laterality in the visual modality, with a clear advantage for written responses. Further pointed analyses revealed some specific differences among response formats. Results are discussed in terms of their implications for the measurement of laterality.     

Taste laterality in the split brain

Two patients with corpus callosum resection, one complete and the other sparing the genu and the rostrum, were tested for discrimination of three basic taste stimuli (sour, bitter, salty) applied to the right or left sides of the tongue. Responses were made by pointing with either hand to written words or images of visual objects corresponding to the stimuli, a language-based discrimination. In both patients, response accuracy was significantly above chance for both hemitongues but there was a significant advantage for the left side. Reaction time was shorter for left stimuli than for right stimuli but the difference was not significant. Eight normal controls matched for age with the patients performed equally well with right and left hemitongue stimuli and so did a third callosotomy patient with sparing of the posterior callosum, including the splenium. Tactile and visual tests showed that the left hemisphere was responsible for language-based responses in the first two patients. The results confirm and extend previous findings in another callosotomy patient, indicating that: (i) taste information from either side of the tongue can reach the left hemisphere in the absence of the corpus callosum; (ii) the ipsilateral input from the tongue to the left hemisphere is more potent functionally than the contralateral input and (iii) in the normal brain, the corpus callosum, specifically its posterior part including the splenium, appears to equalize the effects of the ipsilateral and contralateral gustatory inputs on the left hemisphere. Taken together with evidence about lateralized taste deficits following unilateral cortical lesions, the results also suggest that the gustatory pathways from tongue to cortex are bilaterally-distributed with an ipsilateral predominance that may be subject to individual variations.     

Response format, magnitude of laterality effects, and sex differences in laterality

The present study examined the evidence for the claim that response format might affect the magnitude of laterality effects by means of a meta-analysis. The analysis included the 396 effect sizes drawn from 266 studies retrieved by Voyer (1996) and relevant to the main effect of laterality and sex differences in laterality for verbal and non-verbal tasks in the auditory, tactile, and visual sensory modality. The response format used in specific studies was the only moderator variable of interest in the present analysis, resulting in four broad response categories (oral, written, computer, and pointing). A meta-analysis analogue to ANOVA showed no significant influence of response format on either the main effect of laterality or sex differences in laterality when all sensory modalities were combined. However, when modalities were considered separately, response format affected the main effect of laterality in the visual modality, with a clear advantage for written responses. Further pointed analyses revealed some specific differences among response formats. Results are discussed in terms of their implications for the measurement of laterality.     

Differences in visual attention and task interference between males and females reflect differences in brain laterality

Two cognitive tasks (a letter memory task and a spatial memory task) designed to selectively activate the left or right hemisphere were combined with attentional probe tasks to measure how hemispheric activation affects attention to left and right hemifields. The probe task in Experiment 1 required the identification of digits in the left and right hemifield. During the letter task, male subjects identified more probes from the left hemifield than from the right. Their accuracy varied little across the two hemifields during the dots task.Experiment 2 tested whether this pattern is due to either spatial attention or interference in character processing. Instead of identifying digits, the probe task required subjects to respond to a black square that appeared in the periphery of the screen. For male subjects, the pattern was opposite of that from Experiment 1. During the letter task they responded faster to the probe in the right hemifield than in the left. Their response times were equivalent across the two hemifields during the dots task.These results indicate two separate effects of laterality in male subjects. The activation of one hemisphere produced more attention to the contralateral hemifield in Experiment 2, and the letter memory task interfered with the processing of other characters in the right visual field more than those in the left visual field in Experiment 1. Neither of these effects appeared in female subjects, corroborating earlier claims that female brains are less lateralized than male brains.     

Memory performance and normalized regional brain volumes in patients with pediatric-onset multiple sclerosis

Studies in adults with multiple sclerosis (MS) have associated regional brain abnormalities with memory impairment. While memory problems in children with MS are often reported, little is known about the neural correlates that may contribute to these difficulties. We measured verbal and nonverbal memory using the Test of Memory and Learning (TOMAL-2) in 32 children and adolescents with MS and 26 age- and sex-matched healthy controls. Memory performance was correlated with volumetric measures of the whole brain, hippocampus, amygdala, and thalamus. Brain volumes were normalized for age and sex using magnetic resonance imaging (MRI) data from the National Institutes of Health MRI Study of Normal Brain development. With the exception of story recall, performance on memory tests was similar to that of the control group. Relative to controls, patient with MS showed reduced volume in the whole brain (p < .001), amygdala (p < .005), and thalamus (p < .001), but not the hippocampus. In the patient group, word-list learning correlated with whole brain volume (r = .53) and hippocampal volume (r = .43), whereas visual recognition memory correlated with thalamic volume (r = .48). Findings are consistent with the well-established role of the hippocampus in learning and consolidation and also highlight the importance of diffuse brain pathology on memory function.     

Cognitive performance in schizophrenia: relationship to regional brain volumes and psychiatric symptoms

In an all-male sample of schizophrenic patients stabilized by medication (n=62) and normal controls (n=27), we obtained neuropsychological test data and high-resolution whole brain magnetic resonance scans, as well as detailed psychiatric rating scales on a subset of the patients (n=47). Schizophrenic patients had significantly worse overall age-adjusted cognitive performance than normal controls (average z-score=-0.90, range=-0.60 to -1.81), which included relatively more severe deficits with different types of memory, psychomotor speed, verbal fluency and verbal abstraction. Schizophrenic patients also had significantly smaller bilateral volumes in gray but not white matter in the prefrontal region, superior temporal gyrus and whole temporal lobe, but no group differences were observed in the hippocampus and parahippocampus. Correlations between the brain regions and cognitive performance revealed different sets of significant relationships for the two groups, particularly in the prefrontal and hippocampal regions. In addition, inverse correlations were observed between certain cognitive abilities (psychomotor speed, cognitive flexibility and verbal fluency) and patients' psychiatric ratings, especially with measures of negative symptoms. The convergence of findings for schizophrenic patients regarding the prefrontal region, negative symptoms, psychomotor speed and cognitive flexibility suggests that schizophrenic negative symptoms may involve disruption of frontal-subcortical connections.     

Father-infant interactions and infant regional brain volumes: A cross-sectional MRI study

Fathers play a crucial role in their children’s socio-emotional and cognitive development. A plausible intermediate phenotype underlying this association is father’s impact on infant brain. However, research on the association between paternal caregiving and child brain biology is scarce, particularly during infancy. Thus, we used magnetic resonance imaging (MRI) to investigate the relationship between observed father–infant interactions, specifically paternal sensitivity, and regional brain volumes in a community sample of 3-to-6-month-old infants (N = 28). We controlled for maternal sensitivity and examined the moderating role of infant communication on this relationship. T2-weighted MR images were acquired from infants during natural sleep. Higher levels of paternal sensitivity were associated with smaller cerebellar volumes in infants with high communication levels. In contrast, paternal sensitivity was not associated with subcortical grey matter volumes in the whole sample, and this was similar in infants with both high and low communication levels. This preliminary study provides the first evidence for an association between father-child interactions and variation in infant brain anatomy.     

Moral values are associated with individual differences in regional brain volume

Moral sentiment has been hypothesized to reflect evolved adaptations to social living. If so, individual differences in moral values may relate to regional variation in brain structure. We tested this hypothesis in a sample of 70 young, healthy adults examining whether differences on two major dimensions of moral values were significantly associated with regional gray matter volume. The two clusters of moral values assessed were "individualizing" (values of harm/care and fairness) and "binding" (deference to authority, in-group loyalty, and purity/sanctity). Individualizing was positively associated with left dorsomedial pFC volume and negatively associated with bilateral precuneus volume. For binding, a significant positive association was found for bilateral subcallosal gyrus and a trend to significance for the left anterior insula volume. These findings demonstrate that variation in moral sentiment reflects individual differences in brain structure and suggest a biological basis for moral sentiment, distributed across multiple brain regions.     

Effects of reward sensitivity and regional brain volumes on substance use initiation in adolescence

This longitudinal study examines associations between baseline individual differences and developmental changes in reward [i.e. behavioral approach system (BAS)] sensitivity and relevant brain structures’ volumes to prospective substance use initiation during adolescence. A community sample of adolescents ages 15–18 with no prior substance use was assessed for substance use initiation (i.e. initiation of regular alcohol use and/or any use of other substances) during a 2-year follow-up period and for alcohol use frequency in the last year of the follow-up. Longitudinal ‘increases’ in BAS sensitivity were associated with substance use initiation and increased alcohol use frequency during the follow-up. Moreover, adolescents with smaller left nucleus accumbens at baseline were more likely to initiate substance use during the follow-up period. This study provides support for the link between developmental increases in reward sensitivity and substance use initiation in adolescence. The study also emphasizes the potential importance of individual differences in volumes of subcortical regions and their structural development for substance use initiation during adolescence.     

Remote memory for public figures in Alzheimer's disease: relationships to regional cortical and limbic brain volumes.

This study examined the relationships between regional cortical and hippocampal brain volumes and components of remote memory (recall, recognition, sequencing, and photo naming of presidential candidates) in 13 individuals with Alzheimer's disease (AD). Recognition and sequencing of remote memory for public figures were associated with regional cortical volumes. Specifically, lower recognition and sequencing scores were associated with smaller parietal-occipital cortical volumes; poorer sequencing was also associated with smaller prefrontal cortical volumes. By contrast, poorer anterograde but not remote memory scores were correlated with smaller hippocampal volumes. Within the constraints of the brain regions measured, these findings highlight the importance of the posterior cortical areas for selective remote memory processes and provide support for the dissociation between cortically mediated remote memory and hippocampally mediated anterograde memory.