Gray Matter Volume In Prefrontal Cortex Research Articles

Racial Disparities in Adversity During Childhood and the False Appearance of Race-Related Differences in Brain Structure.

Black Americans in the United States are disproportionately exposed to childhood adversity compared with White Americans. Such disparities may contribute to race-related differences in brain structures involved in regulating the emotional response to stress, such as the amygdala, hippocampus, and prefrontal cortex (PFC). The authors investigated neuroanatomical consequences of racial disparities in adversity. The sample included 7,350 White American and 1,786 Black American children (ages 9-10) from the Adolescent Brain Cognitive Development Study (public data release 2.0). Structural MRI data, parent and child self-reports of adversity-related measures, and U.S. Census neighborhood data were used to investigate the relationship between racial disparities in adversity exposure and race-related differences in brain structure. Black children experienced more traumatic events, family conflict, and material hardship on average compared with White children, and their parents or caregivers had lower educational attainment, lower income, and more unemployment compared with those of White children. Black children showed lower amygdala, hippocampus, and PFC gray matter volumes compared with White children. The volumes of the PFC and amygdala, but not the hippocampus, also varied with metrics of childhood adversity, with income being the most common predictor of brain volume differences. Accounting for differences in childhood adversity attenuated the magnitude of some race-related differences in gray matter volume. The results suggest that disparities in childhood adversity contribute to race-related differences in gray matter volume in key brain regions associated with threat-related processes. Structural alterations of these regions are linked to cognitive-affective dysfunction observed in disorders such as posttraumatic stress disorder. More granular assessments of structural inequities across racial/ethnic identities are needed for a thorough understanding of their impact on the brain. Together, the present findings may provide insight into potential systemic contributors to disparate rates of psychiatric disease among Black and White individuals in the United States.

Common and distinct neural substrates of the compassionate and uncompassionate self-responding dimensions of self-compassion.

Self-compassion is beneficial for individuals' emotional health, but debates regarding its conceptualization are increasing. The present study aimed to explore the neural basis of self-compassion and its compassionate and uncompassionate dimensions and the indirect path from neural basis to emotional health. Structural MRI and Resting-state fMRI data were used to measure the gray matter volume (GMV) and the amplitude of low-frequency fluctuation (ALFF) in 88 healthy college students. We found that individuals with higher self-compassion had decreased GMV in the prefrontal cortex, cerebellum as well as lower ALFF in the occipital lobe. The compassionate and uncompassionate dimensions of self-compassion shared some similarities (e.g., common correlation with GMV in the medial prefrontal cortex, ALFF in the occipital lobe) but also had some differences (e.g., only uncompassionate dimensions correlated with GMV in the lateral prefrontal cortex, ALFF in medial temporal lobe/striatum). The indirect path analyses revealed that corresponding brain characteristics could have associations with emotional health through self-compassion, as well as its uncompassionate dimension, but not compassionate dimension. This exploratory whole-brain study showed some preliminary findings that compassionate and uncompassionate dimensions of self-compassion were related to distinct brain regions, which are both important to the current conceptualization of self-compassion and intervention study.

The relationship between glutamate, dopamine, and cortical gray matter: A simultaneous PET-MR study

Prefrontal cortex has been shown to regulate striatal dopaminergic function via glutamatergic mechanisms in preclinical studies. Concurrent disruption of these systems is also often seen in neuropsychiatric disease. The simultaneous measurement of striatal dopamine signaling, cortical gray matter, and glutamate levels is therefore of major interest, but has not been previously reported. In the current study, twenty-eight healthy subjects underwent 2 simultaneous [11C]-( + )-PHNO PET-MRI scans, once after placebo and once after amphetamine in a double-blind randomized cross-over design, to measure striatal dopamine release, striatal dopamine receptor (D2/3R) availability, anterior cingulate glutamate+glutamine (Glx) levels, and cortical gray matter volumes at the same time. Voxel-based morphometry was used to investigate associations between neurochemical measures and gray matter volumes. Whole striatum D2/3R availability was positively associated with prefrontal cortex gray matter volume (pFWE corrected = 0.048). This relationship was mainly driven by associative receptor availability (pFWE corrected = 0.023). In addition, an interaction effect was observed between sensorimotor striatum D2/3R availability and anterior cingulate Glx, such that in individuals with greater anterior cingulate Glx concentrations, D2/3R availability was negatively associated with right frontal cortex gray matter volumes, while a positive D2/3R-gray matter association was observed in individuals with lower anterior cingulate Glx levels (pFWE corrected = 0.047). These results are consistent with the hypothesis that the prefrontal cortex is involved in regulation of striatal dopamine function. Furthermore, the observed associations raise the possibility that this regulation may be modulated by anterior cingulate glutamate concentrations.

Faulty Executive Attention and Memory Interactions in Schizophrenia: Prefrontal Gray Matter Volume and Neuropsychological Impairment.

We hypothesized that neuropsychological disturbance in schizophrenia (SZ) may reflect faulty interactions of executive attention and episodic memory, emanating, in part, from reduced prefrontal cortex (PFC) gray matter volume. Participants with SZ (n = 84) and age-matched (n = 77) controls completed both the Wisconsin Card Sorting Test (WCST) and the Wechsler Memory Scale-Third Edition (WMS-III), used, respectively, as measures of executive attention and episodic memory. A subset of SZ (n = 27) and control (n = 17) groups also had available 3-T magnetic resonance imaging (MRI) studies of the PFC. For SZ, but not control groups, neuropsychological results indicated that executive attention interacted significantly with episodic memory, with failures of executive attention, as reflected by increased WCST perseverative errors, directly linked to poor performance on the WMS-III measure of delayed visual recall of action scenes. MRI results indicated reduced left PFC gray matter volume for SZ group, which in turn correlated significantly with their deficits in visual memory but not in executive attention. Results showed that 61% of the variance in neuropsychological performance in the SZ group was attributed to gray matter volume of left inferior prefrontal gyrus gray matter volume. PFC-mediated failure of executive attention-episodic memory interactions may represent an important mechanism in neuropsychological disturbance in SZ.

The human prefrontal cortex is special

Neuroscience The size and surface area of the cerebral cortex varies dramatically across mammals. It is well known that the human cortex is by far the largest among primates. However, there is no agreement about whether the human prefrontal cortex is larger, in relative terms, than those of other primates. Donahue et al. compared structural brain scan datasets from humans, chimpanzees, and macaques. They found a greater proportion of prefrontal cortex gray matter volume in humans than in the two nonhuman primate species, and they observed an even greater difference between species for white matter volume in the prefrontal cortex. This part of the association cortex, which is implicated in higher cognition and affect, is thus disproportionately large in humans relative to other primates. Proc. Natl. Acad. Sci. U.S.A. 115 , E5183 (2018).

Goal-Directed Correlates and Neurobiological Underpinnings of Adolescent Identity: A Multimethod Multisample Longitudinal Approach.

This multimethod multisample longitudinal study examined how neurological substrates associated with goal directedness and information seeking are related to adolescents' identity. Self-reported data on goal-directedness were collected across three biannual waves in Study 1. Identity was measured one wave later. Study 1 design and measurements were repeated in Study 2 and extended with structural brain data (nucleus accumbens [NAcc] and prefrontal cortex gray matter volume [PFC]), collected across three biannual waves. Study 1 included 497 adolescents (Mage T1 =13.03years) and Study 2 included 131 adolescents (Mage T1 =14.69years). Using latent growth curve models, goal directedness, NAcc, and PFC volume predicted a stronger identity one wave later. These findings provide crucial new insights in the underlying neurobiological architecture of identity.

The Reduction of Ventrolateral Prefrontal Cortex Gray Matter Volume Correlates with Loss of Economic Rationality in Aging

The population of people above 65 years old continues to grow, and there is mounting evidence that as humans age they are more likely to make errors. However, the specific effect of neuroanatomical aging on the efficiency of economic decision-making is poorly understood. We used whole-brain voxel-based morphometry analysis to determine where reduction of gray matter volume in healthy female and male adults over the age of 65 years correlates with a classic measure of economic irrationality: violations of the Generalized Axiom of Revealed Preference. All participants were functionally normal with Mini-Mental State Examination scores ranging between 26 and 30. While our elders showed the previously reported decline in rationality compared with younger subjects, chronological age per se did not correlate with rationality measures within our population of elders. Instead, reduction of gray matter density in ventrolateral prefrontal cortex correlates tightly with irrational behavior. Interestingly, using a large fMRI sample and meta-analytic tool with Neurosynth, we found that this brain area shows strong coactivation patterns with nearly all of the value-associated regions identified in previous studies. These findings point toward a neuroanatomic locus for economic rationality in the aging brain and highlight the importance of understanding both anatomy and function in the study of aging, cognition, and decision-making.SIGNIFICANCE STATEMENT Age is a crucial factor in decision-making, with older individuals making more errors in choices. Using whole-brain voxel-based morphometry analysis, we found that reduction of gray matter density in ventrolateral prefrontal cortex correlates with economic irrationality: reduced gray matter volume in this area correlates with the frequency and severity of violations of the Generalized Axiom of Revealed Preference. Furthermore, this brain area strongly coactivates with other reward-associated regions identified with Neurosynth. These findings point toward a role for neuroscientific discoveries in shaping long-standing economic views of decision-making.

Prefrontal Lobe Gray Matter, Cognitive Control and Episodic Memory in Healthy Cognition

Objective: We combined neuropsychological and structural magnetic resonance imaging (MRI) measures to examine the neural and informational processes underlying episodic memory in healthy participants. Method: The Doors-and-People Test (DPT) provided a detailed assessment of episodic memory, including recall and recognition tasks of matched difficulty for social (e.g., people) and non-social (e.g., shape) content. The Wisconsin Card Sorting (WCS) test provided a measure of category learning that relies heavily on executive control and inhibition. A subset of participants also had available high-resolution, 3-T MRI gray matter volume studies of prefrontal cortex (PFC) parcellated into four regions: 1) frontal pole; 2) superior frontal gyrus; 3) middle frontal gyrus; and 4) inferior frontal gyrus. Results: Bivariate neuropsychological correlations revealed a highly statistically significant relationship of reduced WCS perseverative errors and stronger recall for people but not for shapes. By contrast, WCS perseveration did not correlate with any recognition measures. Hierarchical regression revealed that perseverative errors and people recall test scores combined to account for approximately 29.98% to 57.78% of the variance in left PFC gray matter volume. Conclusions: These results may point to an important role of the PFC in mnemonic process of retrieval inhibition in episodic memory for recall of social content in healthy participants.

Emotion recognition and theory of mind are related to gray matter volume of the prefrontal cortex in schizophrenia

Investigations of social cognition in schizophrenia have demonstrated consistent impairments compared to healthy controls. Functional imaging studies in schizophrenia patients and healthy controls have revealed that social cognitive processing depends critically on the amygdala and the prefrontal cortex (PFC). However, the relationship between social cognition and structural brain abnormalities in these regions in schizophrenia patients is less well understood. Measures of facial emotion recognition and theory of mind (ToM), two key social cognitive abilities, as well as face perception and IQ, were assessed in 166 patients with schizophrenia and 134 healthy controls. MRI brain scans were acquired. Automated parcellation of the brain to determine gray matter volume of the amygdala and the superior, middle, inferior and orbital PFC was performed. Between-group analyses showed poorer recognition of angry faces and ToM performance, and decreased amygdala and PFC gray matter volumes in schizophrenia patients as compared to healthy controls. Moreover, in schizophrenia patients, recognition of angry faces was associated with inferior PFC gray matter volume, particularly the pars triangularis (p=0.006), with poor performance being related to reduced pars triangularis gray matter volume. In addition, ToM ability was related to PFC gray matter volume, particularly middle PFC (p=0.001), in that poor ToM skills in schizophrenia patients were associated with reduced middle PFC gray matter volume. In conclusion, reduced PFC, but not amygdala, gray matter volume is associated with social cognitive deficits in schizophrenia.

Physical activity, fitness, glucose homeostasis, and brain morphology in twins.

The main aim of the present study (FITFATTWIN) was to investigate how physical activity level is associated with body composition, glucose homeostasis, and brain morphology in young adult male monozygotic twin pairs discordant for physical activity. From a population-based twin cohort, we systematically selected 10 young adult male monozygotic twin pairs (age range, 32-36 yr) discordant for leisure time physical activity during the past 3 yr. On the basis of interviews, we calculated a mean sum index for leisure time and commuting activity during the past 3 yr (3-yr LTMET index expressed as MET-hours per day). We conducted extensive measurements on body composition (including fat percentage measured by dual-energy x-ray absorptiometry), glucose homeostasis including homeostatic model assessment index and insulin sensitivity index (Matsuda index, calculated from glucose and insulin values from an oral glucose tolerance test), and whole brain magnetic resonance imaging for regional volumetric analyses. According to pairwise analysis, the active twins had lower body fat percentage (P = 0.029) and homeostatic model assessment index (P = 0.031) and higher Matsuda index (P = 0.021) compared with their inactive co-twins. Striatal and prefrontal cortex (subgyral and inferior frontal gyrus) brain gray matter volumes were larger in the nondominant hemisphere in active twins compared with those in inactive co-twins, with a statistical threshold of P < 0.001. Among healthy adult male twins in their mid-30s, a greater level of physical activity is associated with improved glucose homeostasis and modulation of striatum and prefrontal cortex gray matter volume, independent of genetic background. The findings may contribute to later reduced risk of type 2 diabetes and mobility limitations.

Lower subcortical gray matter volume in both younger smokers and established smokers relative to non-smokers.

Although established adult smokers with long histories of nicotine dependence have lower neural tissue volume than non-smokers, it is not clear if lower regional brain volume is also observed in younger, less established smokers. The primary goal of this study was to investigate neural tissue volume in a large group of smokers and non-smokers, with a secondary goal of measuring the impact of age on these effects. We used voxel-based morphometry to compare regional gray matter volume in 118 individuals (59 smokers, 59 age- and gender-matched non-smokers). Younger smokers had significantly lower gray matter volume in the left thalamus and the left amygdala than their non-smoking peers (family-wise error-corrected clusters, P < 0.05). There was no correlation between smoking use variables and tissue volume among younger smokers. Established smokers had significantly lower gray matter volume than age-matched non-smokers in the insula, parahippocampal gyrus and pallidum. Medial prefrontal cortex gray matter volume was negatively correlated with pack-years of smoking among the established smokers, but not the younger smokers. These data reveal that regional tissue volume differences are not limited exclusively to established smokers. Deficits in young adults indicate that cigarette smoking may either be deleterious to the thalamus and amygdala at an earlier age than previously reported, or that pre-existing differences in these areas may predispose individuals to the development of nicotine dependence.

Illness-course modulates suicidality-related prefrontal gray matter reduction in women with bipolar disorder.

Explore interrelationships between suicide attempt history (Objective 1) or suicide attempt severity (Objective 2) with prefrontal cortex gray matter (PFCGM ) volume and illness-course in patients with bipolar disorder (BD). Ninety-three women with BD-I or -II diagnosis (51 with and 42 without suicide attempt history) underwent structural MRI and filled out questionnaires. Measured were GM volumes of 11 PFC regions, BD illness-course, and attempt history and severity. Effects were examined with repeated measures GLM or logit analyses. Objective 1: Attempt history was associated with increased trait impulsivity and aggression, and higher prevalence of BD-I, past drug use disorder, and past psychiatric hospitalization. PFCGM volume was lower in patients with than without attempt history in those with past psychiatric hospitalization. PFCGM volume was higher in patients with than without attempt history in those without hospitalization. Higher trait aggression predicted attempt history. Objective 2: Increased frontal pole volume and younger age at first hospitalization predicted many suicide attempts. Attempt history in patients with BD related to PFCGM volume reduction or increase. Volume modulation by psychiatric hospitalization could reflect effects of illness-course or care. Attempt severity was not related to volume reduction. Research on suicidality-brain relationships should include illness-course and attempt severity measures.

A neurogenetics approach to defining differential susceptibility to institutional care

An individual’s neurodevelopmental and cognitive sequelae to negative early experiences may, in part, be explained by genetic susceptibility. We examined whether extreme differences in the early caregiving environment, defined as exposure to severe psychosocial deprivation associated with institutional care compared to normative rearing, interacted with a biologically informed genoset comprising BDNF (rs6265), COMT (rs4680), and SIRT1 (rs3758391) to predict distinct outcomes of neurodevelopment at age 8 (N = 193, 97 males and 96 females). Ethnicity was categorized as Romanian (71%), Roma (21%), unknown (7%), or other (1%). We identified a significant interaction between early caregiving environment (i.e., institutionalized versus never institutionalized children) and the a priori defined genoset for full-scale IQ, two spatial working memory tasks, and prefrontal cortex gray matter volume. Model validation was performed using a bootstrap resampling procedure. Although we hypothesized that the effect of this genoset would operate in a manner consistent with differential susceptibility, our results demonstrate a complex interaction where vantage susceptibility, diathesis stress, and differential susceptibility are implicated.

Medial prefrontal cortex gray matter volume is associated with lifetime substance use severity in abstinent addiction treatment patients

Medial prefrontal cortex gray matter volume is associated with lifetime substance use severity in abstinent addiction treatment patients

Brain structural basis of cognitive reappraisal and expressive suppression

Cognitive reappraisal and expressive suppression, two major emotion regulation strategies, are differentially related to emotional well-being. The aim of this study was to test the association of individual differences in these two emotion regulation strategies with gray matter volume of brain regions that have been shown to be involved in the regulation of emotions. Based on high-resolution magnetic resonance images of 96 young adults voxel-based morphometry was used to analyze the gray matter volumes of the a priori regions of interest, including amygdala, insula, dorsal anterior cingulate and paracingulate cortex, medial and lateral prefrontal cortex (PFC) and their association with cognitive reappraisal and expressive suppression usage as well as neuroticism. A positive association of cognitive reappraisal with right and tendentially left amygdala volume and of neuroticism with left amygdala volume (marginally significant) was found. Expressive suppression was related to dorsal anterior cingulate/paracingulate cortex and medial PFC gray matter volume. The results of this study emphasize the important role of the amygdala in individual differences in cognitive reappraisal usage as well as neuroticism. Additionally, the association of expressive suppression usage with larger volumes of the medial PFC and dorsal anterior/paracingulate cortex underpins the role of these regions in regulating emotion-expressive behavior.

The impulsivity behavior is correlated with prefrontal cortex gray matter volume reduction in heroin-dependent individuals

PurposeChronic exposure to heroin induced cerebral structural abnormalities may underlie heroin-related behaviors. The aim of this study was to: (1) identify cerebral structural abnormalities in heroin-dependent individuals (HDIs) by an automated and unbiased morphometric technique. (2) Define the correlation between these cerebral structural abnormalities and the impulsivity characteristic in HDIs. Methods24 HDIs and 24 control subjects were completed with (1) high resolution structural magnetic resonance imaging scanning and analysis of gray matter volume using voxel-based morphometry implemented in Statistical Parametric Mapping and (2) a Chinese translation Barratt Impulsiveness Scale-11 questionnaire survey. Differences in regional gray matter volume were tested using an analysis of covariance model, co-varying for global gray matter and age. Statistical maps were set at p<0.05, corrected for multiple comparisons. The abnormal brain regions were correlated with the duration of heroin use and impulsivity scores. ResultsAfter adjusting for effects of age and total gray matter volume, cortical gray matter volume in the bilateral medial prefrontal cortex, bilateral dorsal lateral prefrontal cortex, and right fusiform cortex were significantly reduced in HDIs. Moreover, the gray matter volume in prefrontal cortex that showed group differences was negatively correlated with the duration of heroin use and negatively correlated with the impulsivity characteristic in HDIs. ConclusionThese findings reveal the prefrontal cortex was impaired in HDIs, meanwhile, indicate the changes in gray matter volume are relating to the duration of heroin use and the impulsivity characteristic of the HDIs.

Corticostriatal-Limbic Gray Matter Morphology in Adolescents With Self-reported Exposure to Childhood Maltreatment

To study the relationship between self-reported exposure to childhood maltreatment (CM) and cerebral gray matter (GM) morphology in adolescents without psychiatric diagnoses. Associations were examined between regional GM morphology and exposure to CM (measured using a childhood trauma self-report questionnaire for physical, emotional, and sexual abuse and for physical and emotional neglect). University hospital. Forty-two adolescents without psychiatric diagnoses. Correlations between childhood trauma self-report questionnaire scores and regional GM volume were assessed in voxel-based analyses of structural magnetic resonance images. Relationships among GM volume, subtypes of exposure to CM, and sex were explored. Childhood trauma self-report questionnaire total scores correlated negatively (P<.005) with GM volume in prefrontal cortex, striatum, amygdala, sensory association cortices, and cerebellum. Physical abuse, physical neglect, and emotional neglect were associated with rostral prefrontal reductions. Decreases in dorsolateral and orbitofrontal cortices, insula, and ventral striatum were associated with physical abuse. Decreases in cerebellum were associated with physical neglect. Decreases in dorsolateral, orbitofrontal, and subgenual prefrontal cortices, striatum, amygdala, hippocampus, and cerebellum were associated with emotional neglect. Decreases in the latter emotion regulation regions were also associated with childhood trauma self-report questionnaire scores in girls, while caudate reductions (which may relate to impulse dyscontrol) were seen in boys. Exposure to CM was associated with corticostriatal-limbic GM reductions in adolescents. Even if adolescents reporting exposure to CM do not present with symptoms that meet full criteria for psychiatric disorders, they may have corticostriatal-limbic GM morphologic alterations that place them at risk for behavioral difficulties. Vulnerabilities may be moderated by sex and by subtypes of exposure to CM.

Regional prefrontal cortex gray matter volumes in youth at familial risk for schizophrenia from the Harvard Adolescent High Risk Study

Background: Regional prefrontal cortex gray matter reductions have been identified in schizophrenia, likely reflecting a combination of genetic vulnerability and disease effects. Few morphometric studies to date have examined regional prefrontal abnormalities in non-psychotic biological relatives who have not passed through the age range of peak risk for onset of psychosis. We conducted a region-of-interest morphometric study of prefrontal subregions in adolescent and young adult relatives of schizophrenia patients. Methods: Twenty-seven familial high-risk (FHR) first-degree relatives of schizophrenia patients and forty-eight control subjects without a family history of psychosis (ages 13–28) underwent high-resolution magnetic resonance imaging at 1.5 Tesla. The prefrontal cortex was parcellated into polar, dorsolateral, ventrolateral, ventromedial and orbital subregions. The Chapman scales measured subpsychotic symptoms. General linear models examined associations of prefrontal subregion volumes with familial risk and subpsychotic symptoms. Results: FHR subjects had significantly reduced bilateral ventromedial prefrontal and frontal pole gray matter volumes compared with controls. Ventromedial volume was significantly negatively correlated with magical ideation and anhedonia scores in FHR subjects. Conclusions: Selective, regional prefrontal gray matter reductions may differentially mark genetic vulnerability and early symptom processes among non-psychotic young adults at familial risk for schizophrenia.

Development of the declarative memory system in the human brain

Brain regions that are involved in memory formation, particularly medial temporal lobe (MTL) structures and lateral prefrontal cortex (PFC), have been identified in adults, but not in children. We investigated the development of brain regions involved in memory formation in 49 children and adults (ages 8-24), who studied scenes during functional magnetic resonance imaging. Recognition memory for vividly recollected scenes improved with age. There was greater activation for subsequently remembered scenes than there was for forgotten scenes in MTL and PFC regions. These activations increased with age in specific PFC, but not in MTL, regions. PFC, but not MTL, activations correlated with developmental gains in memory for details of experiences. Voxel-based morphometry indicated that gray matter volume in PFC, but not in MTL, regions reduced with age. These results suggest that PFC regions that are important for the formation of detailed memories for experiences have a prolonged maturational trajectory.

Increased Prefrontal Gyrification in a Large High-Risk Cohort Characterizes Those Who Develop Schizophrenia and Reflects Abnormal Prefrontal Development

In our cohort considered at high risk (HR) of developing schizophrenia, we previously found a significant difference in extent of right prefrontal cortical folding between those who subsequently developed schizophrenia and a matched group who remained well. This study aimed to determine if this preexisting difference distinguished 17 individuals who developed schizophrenia from the 128 HR individuals in the cohort who remained well and to explore possible underlying differences in cortical composition. Prefrontal cortical folding was measured by an automated version of the Gyrification Index (A-GI), a ratio reflecting extent of folding. Multivariate logistic regression assessed the probability that prefrontal A-GI predicts diagnostic outcome and subsequently assessed the effect on A-GI of regional cerebrospinal fluid and gray and white matter. High-risk individuals who subsequently developed schizophrenia were distinguished from the remaining cohort by increased right prefrontal cortex (PFC) A-GI. Mean right PFC gray matter volume also differed between groups, but white matter volume did not. Correlations of age with gray and white matter further distinguished groups and a linear regression analysis showed a significant interaction between age and diagnosis on mean volume of right PFC white matter. Increased A-GI appears to indicate abnormal right prefrontal development in those who develop schizophrenia.