Frontal Lobe Gray Matter Volumes Research Articles

Parenting Influences on Frontal Lobe Gray Matter and Preterm Toddlers' Problem-Solving Skills.

Children born preterm often face challenges with self-regulation during toddlerhood. This study examined the relationship between prematurity, supportive parent behaviors, frontal lobe gray matter volume (GMV), and emotion regulation (ER) among toddlers during a parent-assisted, increasingly complex problem-solving task, validated for this age range. Data were collected from preterm toddlers (n = 57) ages 15-30 months corrected for prematurity and their primary caregivers. MRI data were collected during toddlers' natural sleep. The sample contained three gestational groups: 22-27 weeks (extremely preterm; EPT), 28-33 weeks (very preterm; VPT), and 34-36 weeks (late preterm; LPT). Older toddlers became more compliant as the Tool Task increased in difficulty, but this pattern varied by gestational group. Engagement was highest for LPT toddlers, for older toddlers, and for the easiest task condition. Parents did not differentiate their support depending on task difficulty or their child's age or gestational group. Older children had greater frontal lobe GMV, and for EPT toddlers only, more parent support was related to larger right frontal lobe GMV. We found that parent support had the greatest impact on high birth risk (≤27 gestational weeks) toddler brain development, thus early parent interventions may normalize preterm child neurodevelopment and have lasting impacts.

Brain insulin signaling and neurodegeneration: IRS‐1 isolated from neuronal enriched extracellular vesicles associates with frontal lobe gray matter volume in cognitively unimpaired adults

AbstractBackgroundBrain insulin signaling, as measured by insulin signaling proteins in neuronal enriched extracellular vesicles (nEVs), has previously been associated with gray matter (GM) volume in the temporal lobe of nondemented older adults and in multiple brain regions in those with Alzheimer’s clinical syndrome (Walker et al, 2021; Mullins et al, 2017). We sought to extend these findings by performing a voxel‐wise analysis to test the relationship between whole‐brain GM volume and nEV tyrosine phosphorylated IRS‐1 (pY‐IRS‐1) in a cognitively unimpaired sample enriched for AD risk.MethodCognitively‐unimpaired adults (n=47) from the Wisconsin Registry for Alzheimer’s Prevention underwent MRI and blood collection (Table 1). nEVs were isolated from plasma samples by immunoprecipitation targeting neuronal marker L1CAM. pY‐IRS‐1 was measured in nEVs using an electrochemiluminescence assay (Meso Scale Discovery, Rockville, Maryland) (Mustapic et al, 2017). T1‐weighted images were analyzed using the FMRIB Software Library (FSL), where images were first normalized to MNI space and segmented into WM, GM, and CSF using FSL’s FLIRT, FNIRT, and FAST tools and resulting GM maps were smoothed with a Gaussian kernel (sigma = 3.5mm). General linear models and non‐parametric testing (FSL randomise) were used to assess voxelwise associations between nEV pY‐IRS‐1 concentration and GM volume, while controlling for sex and age effects. Significant associations between GM volume and nEV pY‐IRS‐1 were defined as p < 0.01, uncorrected.ResultWe observed lateralized positive associations between nEV pY‐IRS‐1 and GM volume in the right frontal lobe (Figures 1 and 2). After correcting for multiple comparisons, we observed no significant relationships between nEV pY‐IRS‐1 concentration and GM volume.ConclusionPrevious studies indicate that lower nEV pY‐IRS‐1 is associated with lower GM volume in regions such as the temporal and parietal lobes. Here, we determined that lower nEV pIRS‐1 concentrations were associated with lower GM volume laterally in the right frontal lobe of healthy middle‐aged and older adults. Future studies are needed to determine the mechanism by which disrupted insulin signaling in the brain may cause GM loss in these regions.

Beery VMI and Brain Volumetric Relations in Autism Spectrum Disorder.

Although diminished proficiency on tasks that require visual-motor integration (VMI) has been reported in individuals with autism spectrum disorder (ASD), very few studies have examined the association between VMI performance and neuroanatomical regions of interest (ROI) involved in motor and perceptual functioning. To address these issues, the current study included an all-male sample of 41 ASD (ages 3-23 years) and 27 typically developing (TD) participants (ages 5-26 years) who completed the Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery VMI) as part of a comprehensive neuropsychological battery. All participants underwent 3.0 T magnetic resonance imaging (MRI) with image quantification (FreeSurfer software v5.3). The groups were statistically matched on age, handedness, and intracranial volume (ICV). ASD participants performed significantly lower on VMI and IQ measures compared with the TD group. VMI performance was significantly correlated with FSIQ and PIQ in the TD group only. No pre-defined neuroanatomical ROIs were significantly different between groups. Significant correlations were observed in the TD group between VMI and total precentral gyrus gray matter volume (r = .51, p = .006) and total frontal lobe gray matter volume (r = .46, p = .017). There were no significant ROI correlations with Beery VMI performance in ASD participants. At the group level, despite ASD participants exhibiting reduced visuomotor abilities, no systematic relation with motor or sensory-perceptual ROIs was observed. In the TD group, results were consistent with the putative role of the precentral gyrus in motor control along with frontal involvement in planning, organization, and execution monitoring, all essential for VMI performance. Given that similar associations between VMI and ROIs were not observed in those with ASD, neurodevelopment in ASD group participants may not follow homogenous patterns making correlations in these brain regions unlikely to be observed.

Gray Matter Alterations in Post-Traumatic Stress Disorder, Obsessive-Compulsive Disorder, and Social Anxiety Disorder.

Post-traumatic stress disorder (PTSD), obsessive–compulsive disorder (OCD), and social anxiety disorder (SAD) all bear the core symptom of anxiety and are separately classified in the new DSM-5 system. The aim of the present study is to obtain evidence for neuroanatomical difference for these disorders. We applied voxel-based morphometry (VBM) with Diffeomorphic Anatomical Registration Through Exponentiated Lie to compare gray matter volume (GMV) in magnetic resonance images obtained for 30 patients with PTSD, 29 patients with OCD, 20 patients with SAD, and 30 healthy controls. GMV across all four groups differed in left hypothalamus and left inferior parietal lobule and post hoc analyses revealed that this difference is primarily due to reduced GMV in the PTSD group relative to the other groups. Further analysis revealed that the PTSD group also showed reduced GMV in frontal lobe, temporal lobe, and cerebellum compared to the OCD group, and reduced GMV in frontal lobes bilaterally compared to SAD group. A significant negative correlation with anxiety symptoms is observed for GMV in left hypothalamus in three disorder groups. We have thus found evidence for brain structure differences that in future could provide biomarkers to potentially support classification of these disorders using MRI.

Salient measures of inhibition and switching are associated with frontal lobe gray matter volume in healthy middle-aged and older adults.

To investigate brain-behavior relationships between morphometric brain measures and salient executive function (EF) measures of inhibition and switching. One hundred participants (49-80 years) performed the Color Word Interference Test from the Delis-Kaplan Executive Function System (D-KEFS). Salient measures of EF components of inhibition and switching, of which the effect of more fundamental skills were regressed out, were analyzed using linear models and a conditional inference trees analysis taking intercorrelations between predictor variables (brain volumes, age, gender, and education) into account. The conditional inference trees analysis demonstrated a primary role of the middle frontal gyrus (MFG) in explaining variations in the salient EF measure of switching and combined inhibition/switching. Age predicted measures of inhibition. The study highlights the importance of considering fundamental cognitive skills and the use of a statistical method taking possible complex relationships between predictor variables into account when interpreting standard EF test results. Further studies should include MRI measures representing neural networks that may relate to CWIT performance, and longitudinal studies are required to investigate any causal relationships.

Supplemental Material for Salient Measures of Inhibition and Switching Are Associated With Frontal Lobe Gray Matter Volume in Healthy Middle-Aged and Older Adults

Supplemental Material for Salient Measures of Inhibition and Switching Are Associated With Frontal Lobe Gray Matter Volume in Healthy Middle-Aged and Older Adults

Thalamofrontal neurodevelopment in new-onset pediatric idiopathic generalized epilepsy

Quantitative MRI techniques have demonstrated thalamocortical abnormalities in idiopathic generalized epilepsy (IGE). However, there are few studies examining IGE early in its course and the neurodevelopmental course of this region is not adequately defined. We examined the 2-year developmental course of the thalamus and frontal lobes in pediatric new-onset IGE (i.e., within 12 months of diagnosis). We performed whole-brain MRI in 22 patients with new-onset IGE and 36 age-matched healthy controls. MRI was repeated 24 months after baseline MRI. Quantitative volumetrics were used to examine thalamic and frontal lobe volumes. The IGE group showed significant differences in thalamic volume within 1 year of seizure onset (baseline) and went on to show thalamic volume loss at a significantly faster rate than healthy control children over the 2-year interval. The control group also showed a significantly greater increase in frontal white matter expansion than the IGE group. In contrast, frontal lobe gray matter volume differences were moderate at baseline and persisted over time, indicating similar developmental trajectories with differences early in the disease process that are maintained. Brain tissue abnormalities in thalamic and frontal regions can be identified very early in the course of IGE and an abnormal trajectory of growth continues over a 2-year interval.

Neuroimaging correlates of parent ratings of working memory in typically developing children.

The purpose of the present study was to investigate construct validity of parent ratings of working memory in children, using a multi-trait/multi-method design including neuroimaging, rating scales, and performance-based measures. Thirty-five typically developing children completed performance-based tests of working memory and nonexecutive function (EF) skills, received volumetric MRI, and were rated by parents on both EF-specific and broad behavior rating scales. After controlling for total cerebral volume and age, parent ratings of working memory were significantly correlated with frontal gray, but not temporal, parietal, or occipital gray, or any lobar white matter volumes. Performance-based measures of working memory were also moderately correlated with frontal lobe gray matter volume; however, non-EF parent ratings and non-EF performance-based measures were not correlated with frontal lobe volumes. Results provide preliminary support for the convergent and discriminant validity of parent ratings of working memory, and emphasize their utility in exploring brain-behavior relationships in children. Rating scales that directly examine EF skills may potentially have ecological validity, not only for "everyday" function, but also as correlates of brain volume. (JINS, 2009, 15, 31-41.).

Cortical development in brown capuchin monkeys: A structural MRI study

Relative to other primates, Cebus monkeys display unusually fast postnatal brain growth and motor skill development. The neonatal capuchin brain, at approximately 29–34 g, is a smaller proportion of the adult brain weight ( c. 50%) than is the brain of other primates except humans and great apes. Here we describe, from a cross-sectional sample, brain development in 29 brown capuchin monkeys ( Cebus apella) using high-resolution structural magnetic resonance images, focusing on growth patterns in total brain volume, cortical gray and white matter volume, frontal lobe gray and white matter volume, and corpus callosum area. Non-linear age-related changes in total brain volume, cortical white matter volume and frontal white matter volume were detected from birth – 5 years. Sex differences in corpus callosum:brain ratio were also found, with males having a 10% smaller corpus callosum:brain ratio than females regardless of age. Female corpus callosum:brain ratio showed significant age-related related changes, whereas males did not display any significant changes across age. Sex differences were also found in cortical gray and frontal lobe gray matter volumes, with males having larger volumes than females. These findings support the conclusion that capuchins undergo rapid neurological change during the first few years of life.

Preliminary Evidence for Sensitive Periods in the Effect of Childhood Sexual Abuse on Regional Brain Development

Preliminary Evidence for Sensitive Periods in the Effect of Childhood Sexual Abuse on Regional Brain Development

Cerebral Cortical Gray Matter Overgrowth and Functional Variation of the Serotonin Transporter Gene in Autism

Autism is a heritable neurodevelopmental disorder characterized biologically by enlargement of the head and brain and abnormalities of serotonin neurotransmission. To evaluate whether 5-HTTLPR, a functional promoter polymorphism of the serotonin transporter gene SLC6A4, influences cerebral cortical structure volumes in young male children with autism. Association study of a genetic variant with quantitative traits. Autism research centers at the University of North Carolina (UNC), Chapel Hill, and the University of Washington (UW), Seattle. Forty-four male children, 2 to 4 years old, with autism participating in longitudinal brain magnetic resonance imaging studies. Cerebral cortical and cerebellar gray and white matter volumes. We found that 5-HTTLPR genotype influenced gray matter volumes of the cerebral cortex (F(2,23) = 7.29, P = .004) and of 3 lobe-based subregions in the UNC sample of 29 children (frontal lobe gray matter: F(2,23) = 6.36, P = .01). The 5-HTTLPR short allele appeared to be additively associated with increasing gray matter volumes, an observation affirmed by tests of linear genotype effects (cortical gray matter: F(1,24) = 14.11, P = .001; frontal lobe gray matter: F(1,24) = 13.20, P = .001). Genotype did not influence cerebellar volumes. Confirmation was pursued by means of the UW sample of 15 children. While effects were not significant in the UW sample alone, the patterns of adjusted means resembled those found in the UNC sample. Positive Cochran-Mantel-Haenszel test results supported the concordance of relationships across the 2 sites, and analyses of covariance of the combined sample that included a site covariate showed significant linear genotype effects on structure volumes (cortical gray matter: F(1,38) = 5.73, P = .02; frontal lobe gray matter: F(1,38) = 11.73, P = .002). Effect sizes of 5-HTTLPR genotype on total cortical and frontal lobe gray matter volumes were 10% and 16%, respectively. The SLC6A4 promoter polymorphism 5-HTTLPR influences cerebral cortical gray matter volumes in young male children with autism.

Abnormal CNV in chronic heavy drinkers.

We used the contingent negative variation (CNV), a slow negative shift in the human electroencephalogram, to investigate the effects of heavy chronic alcohol use on frontal lobe function. Event-related potentials (ERPs) were recorded from 30 heavy drinkers (HD) and 30 age-, sex-, and education-matched light or non-drinkers (LD), using a classical two-stimulus reaction time (RT) paradigm. Structural magnetic resonance images and neuropsychological tests were also administered. The amplitude of the late CNV was significantly reduced in HD relative to light drinkers. Moreover, diminished CNV amplitudes in HD appear to be closely related to the amount of recent alcohol consumption. There were no significant differences in neuropsychological measures of frontal lobe function and frontal lobe volume between light and HD. However, in HD, reduced late CNV amplitudes were associated with decreased frontal lobe gray matter volume and poor performance on the Trail Making Test B. In LD but not in HD, late CNV amplitude correlated positively with RT, suggesting that the late CNV reflects some aspect of motor and cognitive preparation. The inverse relationships between frontal lobe gray matter volume, performance on the Trail Making Test B, and late CNV amplitude in HD suggest that the ERP abnormalities observed in the current study may be indices of alcohol-related damage to the frontal lobe. The lack of a significant relationship between CNV amplitude and RT in HD suggests that chronic heavy alcohol use may disrupt response preparation.

The relationship between P300 amplitude and regional gray matter volumes depends upon the attentional system engaged

Event-related potentials (ERPs) and brain magnetic resonance images (MRIs) were acquired from 28 normal men, age 21–60 years. ERPs were recorded during 3 paradigms designed to elicit automatic or effortful attention, and a combination of both. MRI-derived measures of brain gray matter, white matter and cerebral spinal fluid (CSF) volumes were computed from frontal, parietal and temporal lobes. P300 amplitude correlated significantly with gray matter volumes but not with white matter or CSF volumes. Furthermore, the relationships between P300 amplitude and gray matter volumes reflected functional rather than direct topographical relationships: P300 recorded at Pz during automatically elicited attention correlated significantly with frontal but not parietal lobe gray matter volumes, P300 recorded during effortful attention correlated significantly with parietal but not frontal lobe gray matter volumes, and P300 recorded when both types of attention were invoked correlated significantly with both frontal and parietal gray matter volumes. Startle blinks, also elicited during automatic attention-engaging paradigms, were significantly correlated with frontal but not parietal lobe gray matter volumes. There was no evidence for a direct spatial relationship between P300 amplitude and the gray matter volumes underlying the recording electrode.