Uncinate Fasciculus Fractional Anisotropy Research Articles

The mediating effect of the amygdala-frontal circuit on the association between depressive symptoms and cognitive function in Alzheimer’s disease

Depressive symptoms occur commonly in Alzheimer’s disease (AD). Although abnormalities in the amygdala-frontal circuit have been linked to emotional dysregulation and cognitive impairment, the neurological basis underlying these associations in AD patients with depressive symptoms (ADD) is unclear. We aimed to investigate the relationship between the amygdala-frontal circuit and depressive symptoms and cognitive function in ADD. We recruited 60 ADD, 60 AD patients without depressive symptoms (ADND), and 60 healthy controls (HC). Functional connectivity (FC) maps of the bilateral amygdala were compared. Fractional anisotropy (FA) of the amygdala-frontal circuit connected by the uncinate fasciculus (UF) was calculated using automated fiber quantification (AFQ). In addition, mediation analysis was performed to explore the effects of the amygdala-frontal circuit on the relationship between depressive symptoms and cognitive function. We found decreased bilateral amygdala FC with the inferior frontal gyrus (IFG) in the ADD group compared to the ADND and HC groups. Moreover, FA in the left frontal UF (nodes 64–97) was significantly lower in the ADD group than ADND group. Notably, amygdala-based FC with IFG and the left frontal UF FA mediated the relationship between depressive symptoms and cognitive function in ADD, with mediating effects ranging between 15 and 18%. Our study is the first to demonstrate the mediating effect of functional and microstructural abnormalities in the amygdala-frontal circuit in ADD. The findings suggest that the amygdala-frontal circuit may underlie emotional dysregulation in ADD, providing potential targets for treatment strategies.

Neighborhood disadvantage and parenting predict longitudinal clustering of uncinate fasciculus microstructural integrity and clinical symptomatology in adolescents

Parenting behaviors and neighborhood environment influence the development of adolescents’ brains and behaviors. Simultaneous trajectories of brain and behavior, however, are understudied, especially in these environmental contexts. In this four-wave study spanning 9–18 years of age (N=224 at baseline, N=138 at final assessment) we used longitudinal k-means clustering to identify clusters of participants with distinct trajectories of uncinate fasciculus (UF) fractional anisotropy (FA) and anxiety symptoms; we examined behavioral outcomes and identified environmental factors that predicted cluster membership. We identified three clusters of participants: 1) high UF FA and low symptoms (“low-risk”); 2) low UF FA and high symptoms (“high-risk”); and 3) low UF FA and low symptoms (“resilient”). Adolescents in disadvantaged neighborhoods were more likely to be in the resilient than high-risk cluster if they also experienced maternal warmth. Thus, neighborhood disadvantage may confer neural risk for psychopathology that can be buffered by maternal warmth, highlighting the importance of considering multiple environmental influences in understanding emotional and neural development in youth.

34 Severity of Traumatic Brain Injury Predicts Neurobehavioral Outcomes and White Matter Microstructure

Objective:Pediatric traumatic brain injury (TBI) is the leading cause of disability in children under the age of 15, often resulting in executive function deficits and poor behavioral outcomes. Damage to white matter tracts may be a driving force behind these difficulties. We examined if whether 1) greater TBI severity was associated with worse neurobehavioral outcome, 2) greater TBI severity was associated with tract-based white matter microstructure, and 3) worse neurobehavioral outcome was associated with white matter microstructure.Participants and Methods:Twelve children with complicated-mild TBI (cmTBI; Mage=12.59, nmale=9), 17 with moderate-to-severe TBI (msTBI; Mage =11.50, nmale=11), and 21 with orthopedic injury (OI; Mage =11.60, nmale=16), 3.94 years post injury on average, were recruited from a large midwestern children’s hospital with a Level 1 Trauma Center. Parents completed the Behavior Rating Inventory of Executive Function (BRIEF) and Child Behavior Checklist (CBCL) while children completed 64-direction diffusion tensor imaging in a Siemens 3T scanner. White matter microstructure was quantified with FMRIB’s Diffusion Toolbox (FSLv6.0.4). Tract-Based Spatial Statistics computed fractional anisotropy (FA) and mean diffusivity (MD) for the cingulum bundle (CB), inferior fronto-occipital fasciculus (IFOF), superior longitudinal fasciculus (SLF), and uncinate fasciculus (UF), bilaterally.Results:Group differences were assessed using one-way ANOVA. Children with msTBI were rated as having worse Sluggish Cognitive Tempo on the CBCL than children with cmTBI and OI (p=.02, eta2=.143); no other parent-rated differences reached significance. Group differences were found in left SLF FA (p=.031; msTBI<cmTBI=OI) and approached significance in left UF FA (p=.062, eta2=.114; msTBI<OI). Group differences were also found in right IFOF MD (p=.048; msTBI>OI) and left SLF MD (p=.013; msTBI>cmTBI=OI). Bivariate correlations assessed cross-domain associations. Higher left IFOF FA was associated with better BRIEF Metacognitive Skills (r=-.301, p=.030) and CBCL School Competence (r=.280; p=.049). Higher left SLF FA was associated with better BRIEF Behavioral Regulation and Metacognitive Skills (r=-.331, p=.017 and r=-.291, p=.036, respectively), and CBCL School Competence and Attention Problems (r=.398, p=.004 and r=-.435, p=.001, respectively). Similarly, higher right UF FA was broadly associated with better neurobehavioral outcomes, including Behavioral Regulation and Metacognitive Skills (r=-.324, p=.019 and r=-.359, p=.009, respectively), and School Competence, Attention Problems, and Sluggish Cognitive Tempo (r=.328, p=.020, r=-.398, p=.003, and r=-.356, p=.010, respectively). Higher right CB MD was associated with worse Behavioral Regulation (r=.327, p=.018) and more Attention Problems (r=.278, p=.046); higher left and right SLF MD was associated with Sluggish Cognitive Tempo (r=.363, p=.008, r=.408, p=.003, respectively).Conclusions:Children with TBI, particularly msTBI, were rated as having cognitive slowing; while other anticipated group differences in neurobehavioral outcomes were not found, this appears driven by milder difficulties in cmTBI and OI groups. In fact, across CBCL and BRIEF subscales, children with msTBI were rated as approaching or exceeding a full standard deviation deficit based on normative data. TBI severity was also associated with white matter microstructure and cross-domain associations linked microstructure with observable neurobehavioral morbidities, suggesting a possible mechanism post-injury. Future longitudinal studies would be useful to examine the temporal evolution of deficits.

Early life stress, sleep disturbances, and depressive symptoms during adolescence: The role of the cingulum bundle

Adolescence is often characterized by sleep disturbances that can affect the development of white matter tracts implicated in affective and cognitive regulation, including the cingulate portion of the cingulum bundle (CGC) and the uncinate fasciculus (UF). These effects may be exacerbated in adolescents exposed to early life adversity (ELA). We examined the longitudinal relations between sleep problems and CGC and UF microstructure during adolescence and their relation to depressive symptoms as a function of exposure to ELA. We assessed self-reported sleep disturbances and depressive symptoms and acquired diffusion-weighted MRI scans twice: in early adolescence (9–13 years) and four years later (13–17 years) (N = 72 complete cases). Independent of ELA, higher initial levels and increases in sleep problems were related to increases in depressive symptoms. Further, increases in right CGC fractional anisotropy (FA) mediated the association between sleep problems and depressive symptoms for youth who experienced lower, but not higher, levels of ELA. In youth with higher ELA, higher initial levels of and steeper decreases in sleep problems were associated with greater decreases in right UF FA, but were unrelated to depressive symptoms. Our findings highlight the importance of sleep quality in shaping fronto-cingulate-limbic tract development and depressive symptoms during adolescence.

Frontoamygdala hyperconnectivity predicts affective dysregulation in adolescent moderate-severe TBI.

In survivors of moderate to severe traumatic brain injury (msTBI), affective disruptions often remain underdetected and undertreated, in part due to poor understanding of the underlying neural mechanisms. We hypothesized that limbic circuits are integral to affective dysregulation in msTBI. To test this, we studied 19 adolescents with msTBI 17 months post-injury (TBI: M age 15.6, 5 females) as well as 44 matched healthy controls (HC: M age 16.4, 21 females). We leveraged two previously identified, large-scale resting-state (rsfMRI) networks of the amygdala to determine whether connectivity strength correlated with affective problems in the adolescents with msTBI. We found that distinct amygdala networks differentially predicted externalizing and internalizing behavioral problems in patients with msTBI. Specifically, patients with the highest medial amygdala connectivity were rated by parents as having greater externalizing behavioral problems measured on the BRIEF and CBCL, but not cognitive problems. The most correlated voxels in that network localize to the rostral anterior cingulate (rACC) and posterior cingulate (PCC) cortices, predicting 48% of the variance in externalizing problems. Alternatively, patients with the highest ventrolateral amygdala connectivity were rated by parents as having greater internalizing behavioral problems measured on the CBCL, but not cognitive problems. The most correlated voxels in that network localize to the ventromedial prefrontal cortex (vmPFC), predicting 57% of the variance in internalizing problems. Both findings were independent of potential confounds including ratings of TBI severity, time since injury, lesion burden based on acute imaging, demographic variables, and other non-amygdalar rsfMRI metrics (e.g., rACC to PCC connectivity), as well as macro- and microstructural measures of limbic circuitry (e.g., amygdala volume and uncinate fasciculus fractional anisotropy). Supporting the clinical significance of these findings, patients with msTBI had significantly greater externalizing problem ratings than healthy control participants and all the brain-behavior findings were specific to the msTBI group in that no similar correlations were found in the healthy control participants. Taken together, frontoamygdala pathways may underlie chronic dysregulation of behavior and mood in patients with msTBI. Future work will focus on neuromodulation techniques to directly affect frontoamygdala pathways with the aim to mitigate such dysregulation problems.

Electroconvulsive therapy induces remodeling of hippocampal co-activation with the default mode network in patients with depression

Introduction:Electroconvulsive therapy (ECT) is a highly efficient treatment for depression. Previous studies repeatedly reported an ECT-induced volume increase in the hippocampi. We assume that this also affects extended hippocampal networks. This study aims to investigate the structural and functional interplay between hippocampi, hippocampal pathways and core regions of the default mode network (DMN). Twenty patients with a current depressive episode receiving ECT-treatment and twenty age and sex matched healthy controls (HC) were included in the study. ECT-patients underwent multimodal magnetic resonance imaging (MRI)-scans (diffusion weighted imaging, resting state functional MRI) before and after an ECT-index series. HC were also scanned twice in a similar between-scan time-interval. Parahippocampal cingulum (PHC) and uncinate fasciculus (UF) were reconstructed for each participant using manual tractography. Fractional anisotropy (FA) was averaged across tracts. Furthermore, we investigated seed-based functional connectivity (FC) from bilateral hippocampi and from the PCC, a core region of the DMN. At baseline, FA in PHC and UF did not differ between groups. There was no baseline group difference of hippocampal-FC. PCC-FC was decreased in ECT-patients. ECT induced a decrease in FA in the left PHC in the ECT group. No longitudinal changes of FA were found in the UF. Furthermore, there was a decrease in hippocampal-PCC-FC, an increase in hippocampal-supplementary motor area-FC, and an increase in PCC-FC in the ECT-group, reversing group differences at baseline. Our findings suggest that ECT induces structural and functional remodeling of a hippocampal-DMN. Those changes may contribute to ECT-induced clinical response in patients with depression.

Longitudinal associations of absolute versus relative moderate-to-vigorous physical activity with brain microstructural decline in aging

Higher moderate-to-vigorous intensity (MVPA) may preserve brain structural integrity, but evidence is mostly cross-sectional and relies on absolute PA measures. We examined longitudinal associations of absolute MVPA using population-level activity count thresholds and relative MVPA using individual heart rate reserve (HRR) via Actiheart with subsequent changes in brain diffusion tensor imaging (DTI) over average of 3.8 years in 248 initially cognitively normal individuals (56−91 years). DTI markers included areas important for memory (temporal areas), executive (prefrontal cortex, superior longitudinal fasciculus), and motor function (precentral gyrus, putamen, caudate, body of corpus callosum). Associations of MVPA with changes in DTI markers were examined using linear mixed-effects models, adjusted for demographics and apolipoprotein e4 carrier status. Each additional 22 min of relative MVPA per day was significantly associated with less decline in fractional anisotropy of uncinate fasciculus and cingulum-hippocampal part and with less increase in mean diffusivity of entorhinal cortex and parahippocampal gyrus. Absolute MVPA was not associated with DTI changes. More time spent in relative MVPA by HRR may prevent brain microstructural decline in selected temporal areas.

White matter predictors of worsening of subthreshold hypomania severity in non-bipolar young adults parallel abnormalities in individuals with bipolar disorder

BackgroundIdentifying neural predictors of worsening subthreshold hypomania severity can help identify risk of progression to BD. While diffusion Magnetic Resonance Imaging (dMRI) studies reported white matter microstructural abnormalities in tracts supporting emotional regulation in individuals with BD, it remains unknown whether similar patterns of white matter microstructure predict worsening of subthreshold hypomania severity in non-BD individuals. MethodsdMRI data were collected in: 81 non-BD individuals recruited across a range of subthreshold depression and hypomania, and followed for six months; and independent samples of 75 BD and 58 healthy individuals. All individuals were assessed using standardized diagnostic assessments, mood and anxiety symptom rating scales. Global probabilistic tractography and a tract-profile approach examined fractional anisotropy (FA), a measure of fiber collinearity, in tracts supporting emotional regulation shown to have abnormalities in BD: forceps minor (FMIN), anterior thalamic radiation (ATR), cingulum bundle (CB), and uncinate fasciculus (UF). ResultsLower FA in left CB (middle, β = −0.22, P = 0.022; posterior, β = −0.32, P < 0.001), right CB (anterior, β = −0.30, P = 0.003; posterior, β = −0.27, P = 0.005), and right UF (frontal, β = −0.29, P = 0.002; temporal, β = −0.40, P < 0.001) predicted worsening of subthreshold hypomania severity in non-BD individuals. BD versus healthy individuals showed lower FA in several of these segments: middle left CB (F = 8.7, P = 0.004), anterior right CB (F = 9.8, P = 0.002), and frontal right UF (F = 7.0, P = 0.009). Non-BD individuals with worsening 6-month hypomania had lower FA in these three segments versus HC and non-BD individuals without worsening hypomania, but similar FA to BD individuals. LimitationsRelatively short follow-up. ConclusionsWhite matter predictors of worsening subthreshold hypomania in non-BD individuals parallel abnormalities in BD individuals, and can guide early risk identification and interventions.

Unilaterally disrupted structural and functional connectivity of the fronto-limbic system in idiopathic hypogonadotropic hypogonadism.

Idiopathic hypogonadotropic hypogonadism (IHH) is rare and can either be associated with normal or defective olfactory sensation, classified as normosmic IHH (nIHH) or Kallmann syndrome (KS). We do not yet understand the central processing pathways in the olfactory system. We aimed to compare the resting-state structural and functional connectivity (FC) of olfactory neural pathways in patients with IHH. We hypotheses that alterations of structuralconnectivity and FC may exist in the olfactory cortex pathways in IHH patients. STRUCTURAL AND FUNCTIONAL CONNECTIVITY DATA RESULTS BETWEEN TWO GROUPS WERE ANALYZED: Patients: Twenty-five IHH patients (13 nIHH patients and 12 KS patients) were recruited from the Department of Endocrinology and were assessed. A total of 25 age-matched healthy male controls were recruited from the community. All subjects underwent diffusion tensor imaging and functional magnetic resonance imaging (fMRI) scans. Structural and functional connectivity data analyses were then performed. Pearson's correlation analyses were performed to investigate the correlations between the fractional anisotropy (FA) value and FC strength, showing significant differences among the three groups separately. Compared with the HC group, FA value in the right uncinate fasciculus (UF) decreased significantly in the IHH group. The olfactory cortex FC values of the right gyrus rectus, orbitofrontal cortex (OFC) and right middle temporal gyrus in the IHH group were decreased compared with those in the HC group. Moreover, there were significant negative correlations between right UF FA and olfactory cortex-FC to both the gyrus rectus and OFC within the HC group (p &lt; .05). Our findings suggest that alterations of structural and FC support the presence of neurobiological disruptions in IHH patients, particularly a specific structural-functional asymmetry disruption may exist in the olfactory cortex pathways in IHH patients.

Individual variation in white matter microstructure is related to better recovery from negative stimuli.

The uncinate fasciculus is a white matter tract that may facilitate emotion regulation by carrying connections from the prefrontal cortex to regions of the temporal lobe, including the amygdala. Depression and anxiety are associated with reduced uncinate fasciculus fractional anisotropy (FA)-a diffusion tensor imaging measure related to white matter integrity. In the current study, we tested whether FA in the uncinate fasciculus is associated with individual differences in emotional recovery measured with corrugator supercilii electromyography in response to negative, neutral, and positive images in 108 participants from the Midlife in the US (MIDUS; http://midus.wisc.edu) Refresher study. Corrugator activity is linearly associated with changes in affect, and differentiated negative, neutral, and positive emotional responses. Higher uncinate fasciculus FA was associated with lower corrugator activity 4-8 seconds after negative image offset, indicative of better recovery from negative provocation. In an exploratory analysis, we found a similar association for the inferior fronto-occipital, inferior longitudinal and superior longitudinal fasciculi. These results suggest that the microstructural features of the uncinate fasciculus, and these other association white matter fibers, may support emotion regulatory processes with greater white matter integrity facilitating healthier affective functioning. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Heritability of abnormalities in limbic networks of autism spectrum disorder children: Evidence from an autism spectrum disorder twin study.

Although the limbic system is closely related to emotion and social behaviors, little is known about the integrity of limbic pathways and how genetics influence the anatomical abnormalities of limbic networks in children with autism spectrum disorder (ASD). Therefore, we used an ASD twin study design to evaluate the microstructural integrity and autism-related differences in limbic pathways of young children with ASD and to estimate the heritability of limbic tracts microstructure variance. We obtained diffusion tensor imaging scans from 33 pairs of twins with ASD aged 2-9 years and 20 age-matched typically developing children. The ACE model was used to estimate the relative effects of additive genetic factors (A), shared environmental factors (C) and specific environmental factors (E) on the variability of diffusivity measurements. We found a significant decrease in fractional anisotropy (FA) in the bilateral fornix and uncinate fasciculus (UF), as well as increased mean diffusivity (MD) and radial diffusivity (RD) in the bilateral fornix and right UF of ASD children. Correlation analysis showed that FA, MD, and lateralization indices of UF were correlated with autism diagnostic observation schedule scores. The ACE model revealed that genetic effects may drive some of the variability of microstructure in the bilateral fornix, cingulum, and left UF. In conclusion, in children with ASD, there are abnormalities in the white matter microstructure of the limbic system, which is related to the core symptoms; these abnormalities may be related to the relative contribution of genetic and environmental effects on specific tracts. LAY SUMMARY: Autism spectrum disorder (ASD) children have abnormal white matter structure in limbic system related to ASD symptoms, and genetic factors play an important role in the development of limbic tracts.

Adverse Childhood Experience Is Associated With Disrupted White Matter Integrity in Autism Spectrum Disorder: A Diffusion Tensor Imaging Study.

Individuals with autism spectrum disorder (ASD) have an increased risk of adverse childhood experiences (ACEs) than typically developed (TD) children. Since multiple lines of studies have suggested that ACEs are related to myelination in the frontal lobe, an exposure to ACEs can be associated with white matter microstructural disruption in the frontal lobe, which may be implicated in subsequential psychological deficits after the adulthood. In this study, we investigated the relationship between ACEs and microstructural integrity on frontal lobe-related white matter tracts using diffusion tensor imaging in 63 individuals with ASD and 38 TD participants. Using a tractography-based analysis, we delineated the uncinate fasciculus (UF), dorsal cingulum (Ci), and anterior thalamic radiation (ATR), which are involved in the neural pathology of ASD, and estimated each diffusion parameter. Compared to the TD participants, individuals with ASD displayed significantly lower fractional anisotropy (FA) and higher radial diffusivity (RD) in the left ATR. Then, ASD individuals exposed to severe ACEs displayed higher RD than those exposed to mild ACEs and TD participants in the left ATR. Moreover, the severity of ACEs, particularly neglect, correlated with lower FA and higher RD in the left UF and ATR in individuals with ASD, which was not observed in TD participants. These results suggest that an exposure to ACEs is associated with abnormality in the frontal lobe-related white matter in ASD.

White matter microstructure associated with anhedonia among individuals with bipolar disorders and high-risk for bipolar disorders

BackgroundAnhedonia - a key symptom of depression - is highly associated with poorer outcomes and suicidal behavior. Alterations in the circuitry of reward-related brain regions have been robustly associated with anhedonia in unipolar depression, but not bipolar disorder (BD). We investigated white matter microstructures associated with anhedonia in participants with BD types I and II and first-degree relatives of patients with BD (BD-siblings). MethodsEighty participants (BD types I and II: 56 [70%], and BD-siblings: 24 [30%]) underwent diffusion tensor imaging (DTI); Fractional anisotropy (FA) of different tracts were computed. Anhedonia was assessed using item 8, (“inability to feel'') of the MADRS scale. General linear models were used to compare the FA of different tracts in participants with and without anhedonia controlling for several clinical and demographic variables. ResultsThe mean age of the sample was 37 (± 11) years old, and 68.8% were female. Participants with anhedonia (32.5%) presented lower mean FA in the left uncinate fasciculus (UF) (p = 0.005), right temporal endings of the superior longitudinal fasciculus (SLFT) (p = 0.04), and in the left and right parietal endings of the superior longitudinal fasciculus (SLFP) (p = 0.003, and p = 0.04, respectively). Similar comparisons between participants with or without current depressive episodes and between participants with or without inner tension according to the MADRS did not show significant differences, specificity of the findings for anhedonia. ConclusionsLower FA in the left UF and SLF are potential neuroimaging markers of anhedonia in individuals with BD and high-risk for BD.

Relative Vigorous-Intensity Physical Activity Predicts Brain Microstructural Changes in Older Adults

Physical activity especially at moderate-to-vigorous intensity may preserve brain structure in old age. However, current findings are cross-sectional and rely on absolute intensity. This study aimed to examine whether relative or absolute vigorous-intensity physical activity (VPA) predicts brain microstructural changes. We analyzed 260 initially cognitively normal and well-functioning participants(age=70.5yrs) who had VPA data via ActiHeart and longitudinal brain microstructure by DTI(follow-up=3.7yrs). Associations of VPA with microstructural changes were examined using linear mixed-effects models, adjusted for demographics. Each SD higher relative VPA defined by heart rate reserve (i.e. 21 min/day) was significantly associated with less decline in memory-related microstructural integrity, including mean diffusivity of entorhinal cortex and parahippocampal gyrus and fractional anisotropy of uncinate fasciculus and cingulum-hippocampal part, and not executive/motor-related microstructure. Absolute VPA was not associated with microstructural markers. Among well-functioning older adults, participating in VPA defined by heart rate reserve may predict less brain microstructural decline in memory-related areas.

Baseline associations of cardiometabolic risk factors, executive function, and white matter microstructure in the DIRECT‐PLUS trial

AbstractBackgroundCardiometabolic risk factors including mid‐life obesity, diabetes and hypertension are associated with accelerated cognitive decline, e.g. in executive function, and brain aging, e.g. alterations in white matter (WM) microstructure [1].Method290 participants (34 females, mean age= 49 y (30 – 79 y) of the DIRECT‐PLUS trial (clinicaltrials.gov ID: NCT03020186, [2]) participated in diffusion‐weighted imaging on a 3T Philips. Tract‐based spatial statistics provided hemisphere‐averaged fractional anisotropy (FA) of 9 fiber tracts (genu/body of corpus callosum, body and crus of fornix, (hippocampal) cingulum, inferior/superior longitudinal fasciculus (i/sLF) and uncinate fasciculus. We tested the association of age, sex, five risk factors (body mass index (BMI), systolic blood pressure (SBP), glycated hemoglobin, high and low‐density lipoprotein), four measures of executive function from the brief executive function battery and average FA of these WM tracts with correlations and linear regression models, adjusting for age and sex, in R version 3.6.1, corrected for multiple testing using false discovery rate (FDR).ResultAge was associated with lower FA in the cingulum (r=‐0.56, p&lt;0.001), uncinate fasciculus (r=‐0.51, p&lt;0.001), hippocampus cingulum (r=‐0.39, p&lt;0.001), iLF (‐0.19, p=0.001) and sLF (r=‐0.18, p=0.001). FA in the fornix, hippocampus cingulum and iLF were higher in men as compared to women (p&lt;0.05 for all). Among cardiometabolic risk factors, higher BMI was associated with significantly lower FA in iILF (β = ‐0.002, p=0.0009, padj=0.035), and higher SBP was associated with lower FA in uncinate fasciculus (β= ‐0.0006, p=0.0012, padj=0.035)None of the executive function measures was significantly related to FA of WM tracts after adjusting for age and sex and controlling for FDR.ConclusionOur findings corroborate previous findings of the adverse impacts of cardiometabolic risk on WM microstructure. Upcoming longitudinal investigations in this dataset will show whether improved cardiometabolic function, induced by a dietary intervention, will modify the trajectories of WM microstructure and cognitive performance. Figure 1: Higher BMI and higher SBP were significantly associated with lower FA in two major WM tracts (blue: ILF, green: uncinate fasciculus)[1] Wassenaar, TM., et al. NBA (2019) [2] Tsaban, G, et al. Heart (2020).

Neonatal White Matter Microstructure and Emotional Development during the Preschool Years in Children Who Were Born Very Preterm.

Children born very preterm (<33 weeks of gestation) are at a higher risk of developing socio-emotional difficulties compared with those born at term. In this longitudinal study, we tested the hypothesis that diffusion characteristics of white matter (WM) tracts implicated in socio-emotional processing assessed in the neonatal period are associated with socio-emotional development in 151 very preterm children previously enrolled into the Evaluation of Preterm Imaging study (EudraCT 2009-011602-42). All children underwent diffusion tensor imaging at term-equivalent age and fractional anisotropy (FA) was quantified in the uncinate fasciculus (UF), inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), and superior longitudinal fasciculus (SLF). Children’s socio-emotional development was evaluated at preschool age (median = 4.63 years). Exploratory factor analysis conducted on the outcome variables revealed a three-factor structure, with latent constructs summarized as: “emotion moderation,” “social function,” and “empathy.” Results of linear regression analyses, adjusting for full-scale IQ and clinical and socio-demographic variables, showed an association between lower FA in the right UF and higher “emotion moderation” scores (β = −0.280; p < 0.001), which was mainly driven by negative affectivity scores (β = −0.281; p = 0.001). Results further showed an association between higher full-scale IQ and better social functioning (β = −0.334, p < 0.001). Girls had higher empathy scores than boys (β = −0.341, p = 0.006). These findings suggest that early alterations of diffusion characteristics of the UF could represent a biological substrate underlying the link between very preterm birth and emotional dysregulation in childhood and beyond.

Individual differences in white matter of the uncinate fasciculus and inferior fronto-occipital fasciculus: possible early biomarkers for callous-unemotional behaviors in young children with disruptive behavior problems.

Callous-unemotional (CU) behaviors are important for identifying severe patterns of conduct problems (CP). One major fiber tract implicated in the development of CP is the uncinate fasciculus (UF), which connects amygdala and orbitofrontal cortex (OFC). The goals of the current study were to (a) explore differences in the white matter microstructure in the UF and other major fiber tracks between young typically developing (TD) children and those with a disruptive behavior disorder (DBD) and (b) explore, within the DBD group, whether individual differences in these white matter tracts relate to co-occurring CP and CU behaviors. Participants included 198 young children (69% boys, Mage = 5.66 years; 80% Latinx; 48.5% TD). CU behaviors and CP were measured via a combination of teacher/parent ratings. Non-invasive diffusion-weighted imaging (DWI) was used to measure fractional anisotropy (FA), an indirect indicator of white matter properties. Relative to TD children, children in the DBD group had reduced FA on four out of the five fiber tracks we examined (except for cingulum and right ILF), even after accounting for whole brain FA, sex, movement, parental income, and IQ. Within the DBD group, no associations were found between CP and reduced white matter integrity across any of the fiber tracks examined. However, we found that even after accounting for CP, ADHD symptomology, and a host of covariates (whole brain FA, sex, movement, parental income, and IQ), CU behaviors were independently related to reduced FA in bilateral UF and left inferior fronto-occipital fasciculus (IFOF) in the DBD group, but this was not the case for TD children. Alterations in the white matter microstructure within bilateral UF and left IFOF may be biomarkers of CU behaviors, even in very young children.

Glucocorticoid treatment for non-cerebral diseases in children and adolescents is associated with differences in uncinate fasciculus microstructure.

Evidence suggests that fronto-limbic brain regions and connecting white matter fibre tracts in the left hemisphere are more sensitive to glucocorticoids than in the right hemisphere. It is unknown whether treatment with glucocorticoids in childhood is associated with microstructural differences of the uncinate fasciculus and cingulum bundle, which connect fronto-limbic brain regions. Here, we tested the hypothesis that prior glucocorticoid treatment would be associated with differences in fractional anisotropy (FA) of the left relative to right uncinate fasciculus and cingulum bundle. We performed diffusion-weighted imaging in 28 children and adolescents aged 7-16 years previously treated with glucocorticoids for nephrotic syndrome or rheumatic disease and 28 healthy controls. Patients displayed significantly different asymmetry in the microstructure of uncinate fasciculus with higher left but similar right uncinate fasciculus FA and axial diffusivity compared to controls. No apparent differences were observed for the cingulum. Notably, higher cumulative glucocorticoid doses were significantly associated with higher uncinate fasciculus FA and axial diffusivity bilaterally. Our findings indicate that previous glucocorticoid treatment for non-cerebral diseases in children and adolescents is associated with long-term changes in the microstructure of the uncinate fasciculi, and that higher cumulative glucocorticoid doses have a proportional impact on the microstructure. It is unknown if treatment with glucocorticoids in childhood have long-term effects on fronto-limbic white matter microstructure. The study examined if children and adolescents previously treated with glucocorticoids for nephrotic syndrome or rheumatic disorder differed in fronto-limbic white matter microstructure compared to healthy controls. The nephrotic and rheumatic patients had higher left but similar right uncinate fasciculus FA and axial diffusivity. Higher bilateral uncinate fasciculus FA and axial diffusivity was associated with higher cumulative glucocorticoid doses. We revealed new evidence suggesting that previous glucocorticoid treatment for non-cerebral diseases in children and adolescents is associated with long-term changes in uncinate fasciculi microstructure.

Neurocognitive Outcomes and Their Diffusion Tensor Imaging Correlates in Children With Mild Traumatic Brain Injury.

This study aimed to assess the neurocognitive outcomes and their diffusion tensor imaging correlates in children (aged 6-16 years) with mild traumatic brain injury. This prospective analysis included 74 children with mild traumatic brain injury (52 boys; mean age: 9.5 [±2.7] years). Wechsler Intelligence Scale for Children-Indian adaptation (WISC-IV), Child Behavior Checklist, and Children's Sleep Habits Questionnaire were administered for 57 cases (at 3 months postinjury) and 51 controls of similar age. The findings of diffusion tensor imaging (done within 7 days of injury) were correlated with various WISC-IV indices. The presenting features at the time of injury were loss of consciousness (53%), confusion or disorientation (47%), and post-traumatic amnesia (10%). Other features in the acute phase included drowsiness (86%), headache (78%), balance problems (62%), nausea (47%), fatigue (45%), vomiting (35%), nasal or ear bleed (12%), sensitivity to sound and light (12%), etc. At 3 months postinjury, the children with mild traumatic brain injury performed poorly in terms of Intelligence Quotient, perceptual reasoning index, and processing speed index as compared to controls. Based on the Child Behavior Checklist, 17% of children with mild traumatic brain injury had internalizing behavioral problems in comparison with 4% of controls. Prevalence of poor sleepers in the mild traumatic brain injury cohort and controls was 12.3% and 2% respectively. Headache, reduced attention span, and fatigue were common postconcussion symptoms. There was a positive correlation between right uncinate fasciculus fractional anisotropy and verbal comprehension index (r = 0.32; P < .05).

Integrity of the uncinate fasciculus is associated with the onset of bipolar disorder: a 6-year followed-up study

Patients with Bipolar Disorder (BD) are associated with aberrant uncinate fasciculus (UF) that connects amygdala-ventral prefrontal cortex (vPFC) system, but the casual relationship is still uncertain. The research aimed to investigate the integrity of UF among offspring of patients with BD and investigate its potential causal association with subsequent declaration of BD. The fractional anisotropy (FA) and mean diffusivity (MD) of UF were compared in asymptomatic offspring (AO, n = 46) and symptomatic offspring (SO, n = 45) with a parent with BD, and age-matched healthy controls (HCs, n = 35). Logistic regressions were performed to assess the predictive effect of UF integrity on the onset of BD. The three groups did not differ at baseline in terms of FA and MD of the UF. Nine out of 45 SO developed BD over a follow-up period of 6 years, and the right UF FA predicted the onset of BD (p = 0.038, OR = 0.212, 95% CI = 0.049–0.917). The ROC curve revealed that the right UF FA predicted BD onset (area-under-curve = 0.859) with sensitivity of 88.9% and specificity of 77.3%. The complementary whole-brain tract-based spatial statistics (TBSS) showed that widespread increases of FA were found in the SO group compared with HCs, but were not associated with the onset of BD. Our data provide evidence supporting the causal relationship between the white matter structural integrity of the amygdala-vPFC system and the onset of BD in genetically at-risk offspring of BD patients.