Cortical Gyrification Morphology in Adult Males with Mild Traumatic Brain Injury.

Cortical gyrification, as a specific measure derived from magnetic resonance imaging, remains understudied in mild traumatic brain injury (mTBI). Local gyrification index (lGI) and mean curvature are related measures indexing the patterned folding of the cortex,ml which reflect distinct properties of cortical morphology and geometry. Using both metrics, we examined cortical gyrification morphology in 59 adult males with mTBI (n = 29) versus those without (n = 30) mTBI in the subacute phase of injury (between 2 weeks and 3 months). The effect of IQ on lGI and brain-symptom relations were also examined. General linear models revealed greater lGI in mTBI versus controls in the frontal lobes bilaterally, but reduced lGI in mTBI of the left temporal lobe. An age-related decrease in lGI was found in numerous areas, with no significant group-by-age interaction effects observed. Including other factors (i.e., mTBI severity, symptoms, and IQ) in the lGI model yielded similar results with few exceptions. Mean curvature analyses depicted a significant group-by-age interaction with the absence of significant main effects of group or age. Our results suggest that cortical gyrification morphology is adversely affected by mTBI in both frontal and temporal lobes, which are thought of as highly susceptible regions to mTBI. These findings contribute to understanding the effects of mTBI on neuromorphological properties, such as alterations in cortical gyrification, which reflect underlying microstructural changes (i.e., apoptosis, neuronal number, or white matter alterations). Future studies are needed to infer causal relationships between micro- and macrostructural changes after an mTBI and investigate potential sex differences.

In vivo imaging translocator protein (TSPO) in autism spectrum disorder.

Converging evidence points to the significant involvement of the immune system in autism spectrum disorders (ASD). Positron emission tomography (PET) can quantify translocator protein 18 kDa (TSPO), a marker with increased expression mainly in microglia and, to some extent astroglia during neuropsychiatric diseases with inflammation. This preliminary analysis explored, for the first time, whether TSPO binding was altered in male and female participants with ASD in vivo using full kinetic quantification. Thirteen individuals with ASD (IQ > 70 [n = 12], IQ = 62 [n = 1]), 5 F, 25 ± 5 years) were scanned with [18F]FEPPA PET. Data from 13 typically developing control participants with matching age and TSPO rs6971 polymorphism (9 F, age 24 ± 5 years) were chosen from previous studies for comparison. The two tissue compartment model (2TCM) was used to determine the total volume of distribution ([18F]FEPPA VT) in four previously identified regions of interest (ROI): prefrontal, temporal, cerebellar, and anterior cingulate cortices. We observe no significant difference in [18F]FEPPA VT relative to controls (F(1,26)= 1.74, p = 0.20). However, 2 ASD participants with higher VT had concurrent major depressive episodes (MDE), which has been consistently reported during MDE. After excluding those 2 ASD participants, in a post-hoc analysis, our results show lower [18F]FEPPA VT in ASD participants compared to controls (F(1,24)= 6.62, p = 0.02). This preliminary analysis provides evidence suggesting an atypical neuroimmune state in ASD.

Cortical Gyrification Morphology in ASD and ADHD: Implication for Further Similarities or Disorder-Specific Features?

Shared etiological pathways are suggested in ASD and ADHD given high rates of comorbidity, phenotypic overlap and shared genetic susceptibility. Given the peak of cortical gyrification expansion and emergence of ASD and ADHD symptomology in early development, we investigated gyrification morphology in 539 children and adolescents (6-17 years of age) with ASD (n=197) and ADHD (n=96) compared to typically developing controls (n=246) using the local Gyrification Index (lGI) to provide insight into contributing etiopathological factors in these two disorders. We also examined IQ effects and functional implications of gyrification by exploring the relation between lGI and ASD and ADHD symptomatology beyond diagnosis. General Linear Models yielded no group differences in lGI, and across groups, we identified an age-related decrease of lGI and greater lGI in females compared to males. No diagnosis-by-age interactions were found. Accounting for IQ variability in the model (n=484) yielded similar results. No significant associations were found between lGI and social communication deficits, repetitive and restricted behaviours, inattention or adaptive functioning. By examining both disorders and controls using shared methodology, we found no evidence of atypicality in gyrification as measured by the lGI in these conditions.

Mild traumatic brain injury is associated with dysregulated neural network functioning in children and adolescents.

Mild traumatic brain injury is highly prevalent in paediatric populations, and can result in chronic physical, cognitive and emotional impairment, known as persistent post-concussive symptoms. Magnetoencephalography has been used to investigate neurophysiological dysregulation in mild traumatic brain injury in adults; however, whether neural dysrhythmia persists in chronic mild traumatic brain injury in children and adolescents is largely unknown. We predicted that children and adolescents would show similar dysfunction as adults, including pathological slow-wave oscillations and maladaptive, frequency-specific, alterations to neural connectivity. Using magnetoencephalography, we investigated regional oscillatory power and distributed brain-wide networks in a cross-sectional sample of children and adolescents in the chronic stages of mild traumatic brain injury. Additionally, we used a machine learning pipeline to identify the most relevant magnetoencephalography features for classifying mild traumatic brain injury and to test the relative classification performance of regional power versus functional coupling. Results revealed that the majority of participants with chronic mild traumatic brain injury reported persistent post-concussive symptoms. For neurophysiological imaging, we found increased regional power in the delta band in chronic mild traumatic brain injury, predominantly in bilateral occipital cortices and in the right inferior temporal gyrus. Those with chronic mild traumatic brain injury also showed dysregulated neuronal coupling, including decreased connectivity in the delta range, as well as hyper-connectivity in the theta, low gamma and high gamma bands, primarily involving frontal, temporal and occipital brain areas. Furthermore, our multivariate classification approach combined with functional connectivity data outperformed regional power in terms of between-group classification accuracy. For the first time, we establish that local and large-scale neural activity are altered in youth in the chronic phase of mild traumatic brain injury, with the majority presenting persistent post-concussive symptoms, and that dysregulated interregional neural communication is a reliable marker of lingering paediatric 'mild' traumatic brain injury.

Cortical gyrification morphology in PTSD: A neurobiological risk factor for severity?

Post-traumatic stress disorder (PTSD) is a prevalent psychiatric disorder, particularly among military personnel and veterans. Cortical gyrification, as a specific metric derived from structural MRI, is an index of the convoluted folding and patterning of the gyri and sulci, and is thought to facilitate the efficiency of local neuronal wiring. It has the potential to act as a neurobiological risk factor for emergent psychiatric disorders - to date, it has been understudied in PTSD. Here, using a local measure of the degree of gyrification (local Gyrification Index, lGI) we investigate cortical gyrification morphology in 48 adult male soldiers with (n = 23) and without (n = 25) a PTSD diagnosis. We also examine the relation between lGI and PTSD severity within the PTSD group. General linear models yielded significant between-group differences with greater lGI found in PTSD in a cluster located in the medial occipito-parietal lobe on the left hemisphere and reduced lGI in a cluster located on the lateral surface of the parietal lobe on the right hemisphere. Brain-behaviour analyses within the PTSD group yielded significant positive associations between lGI and PTSD severity in a cluster located in the frontal cortex of the left hemisphere and scattered clusters located within all lobes of the right hemisphere. After accounting for the effects of comorbid psychiatric symptoms common in PTSD, the associations in the right hemisphere reduced to clusters only located in the frontal lobe, while the cluster in the left hemisphere remained significant. Our results suggest that atypical cortical gyrification in parietal and occipital regions may be implicated in the psychopathology of PTSD diagnosis, and properties of prefrontal gyrification associated with the emergent severity of PTSD after trauma. The importance of these regions in PTSD may be attributed to a pre-existing neurobiological risk factor, or neuromorphological changes after trauma precipitating emergent psychiatric illness. Our brain-behaviour relations provide support for the existing literature by highlighting the importance of the frontal lobe in the pathogenesis of PTSD. Future large-scale longitudinal studies including female participants may infer causal implications of atypical gyrification in PTSD and shed light on the potential effect of sex on this brain metric.

Cortical Gyrification Morphology in Individuals with ASD and ADHD across the Lifespan: A Systematic Review and Meta-Analysis.

Autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) are common neurodevelopmental disorders (NDDs) that may impact brain maturation. A number of studies have examined cortical gyrification morphology in both NDDs. Here we review and when possible pool their results to better understand the shared and potentially disorder-specific gyrification features. We searched MEDLINE, PsycINFO, and EMBASE databases, and 24 and 10 studies met the criteria to be included in the systematic review and meta-analysis portions, respectively. Meta-analysis of local Gyrification Index (lGI) findings across ASD studies was conducted with SDM software adapted for surface-based morphometry studies. Meta-regressions were used to explore effects of age, sex, and sample size on gyrification differences. There were no significant differences in gyrification across groups. Qualitative synthesis of remaining ASD studies highlighted heterogeneity in findings. Large-scale ADHD studies reported no differences in gyrification between cases and controls suggesting that, similar to ASD, there is currently no evidence of differences in gyrification morphology compared with controls. Larger, longitudinal studies are needed to further clarify the effects of age, sex, and IQ on cortical gyrification in these NDDs.

Feasibility study of TSPO quantification with [18F]FEPPA using population-based input function.

PURPOSE: The input function (IF) is a core element in the quantification of Translocator protein 18 kDa with positron emission tomography (PET), as no suitable reference region with negligible binding has been identified. Arterial blood sampling is indeed needed to create the IF (ASIF). In the present manuscript we study individualization of a population based input function (PBIF) with a single arterial manual sample to estimate total distribution volume (VT) for [18F]FEPPA and to replicate previously published clinical studies in which the ASIF was used. METHODS: The data of 3 previous [18F]FEPPA studies (39 of healthy controls (HC), 16 patients with Parkinson's disease (PD) and 18 with Alzheimer's disease (AD)) was reanalyzed with the new approach. PBIF was used with the Logan graphical analysis (GA) neglecting the vascular contribution to estimate VT. Time of linearization of the GA was determined with the maximum error criteria. The optimal calibration of the PBIF was determined based on the area under the curve (AUC) of the IF and the agreement range of VT between methods. The shape of the IF between groups was studied while taking into account genotyping of the polymorphism (rs6971). RESULTS: PBIF scaled with a single value of activity due to unmetabolized radioligand in arterial plasma, calculated as the average of a sample taken at 60 min and a sample taken at 90 min post-injection, yielded a good interval of agreement between methods and optimized the area under the curve of IF. In HC, gray matter VTs estimated by PBIF highly correlated with those using the standard method (r2 = 0.82, p = 0.0001). Bland-Altman plots revealed PBIF slightly underestimates (~1 mL/cm3) VT calculated by ASIF (including a vascular contribution). It was verified that the AUC of the ASIF were independent of genotype and disease (HC, PD, and AD). Previous clinical results were replicated using PBIF but with lower statistical power. CONCLUSION: A single arterial blood sample taken 75 minute post-injection contains enough information to individualize the IF in the groups of subjects studied; however, the higher variability produced requires an increase in sample size to reach the same effect size.