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OBJECTIVE: Cognitive loss in older adults is a growing issue in our society, and there is a need to develop inexpensive, simple, effective in-home treatments. This study was conducted to explore the use of olfactory enrichment at night to improve cognitive ability in healthy older adults. METHODS: Male and female older adults (N = 43), age 60-85, were enrolled in the study and randomly assigned to an Olfactory Enriched or Control group. Individuals in the enriched group were exposed to 7 different odorants a week, one per night, for 2 h, using an odorant diffuser. Individuals in the control group had the same experience with de minimis amounts of odorant. Neuropsychological assessments and fMRI scans were administered at the beginning of the study and after 6 months. RESULTS: A statistically significant 226% improvement was observed in the enriched group compared to the control group on the Rey Auditory Verbal Learning Test and improved functioning was observed in the left uncinate fasciculus, as assessed by mean diffusivity. CONCLUSION: Minimal olfactory enrichment administered at night produces improvements in both cognitive and neural functioning. Thus, olfactory enrichment may provide an effective and low-effort pathway to improved brain health.

Introduction: Schizophrenia (SCZ) is a complex neurodevelopmental disorder characterised by functional and structural brain dysconnectivity and disturbances in perception, cognition, emotion, and social functioning. In the present study, we investigated whether the microstructural organisation of the uncinate fasciculus (UF) was associated with emotion recognition (ER) performance. Additionally, we investigated the usefulness of an unbiased hit rate (UHR) score to control for response biases (i.e., participant guessing) during an emotion recognition task (ERT). Methods: Fifty-eight individuals diagnosed with SCZ were included. The CANTAB ERT was used to measure social cognition. Specific ROI manual tract segmentation was completed using ExploreDTI and followed the protocol previously outlined by Coad et al. (2020). Results: We found that the microstructural organisation of the UF was significantly correlated with physical neglect and ER outcomes. Furthermore, we found that the UHR score was more sensitive to ERT subscale emotion items than the standard HR score. Finally, given the association between childhood trauma (in particular childhood neglect) and social cognition in SCZ, a mediation analysis found evidence that microstructural alterations of the UF mediated an association between childhood trauma and social cognitive performance. Discussion: The mediating role of microstructural alterations in the UF on the association between childhood trauma and social cognitive performance suggests that early life adversity impacts both brain development and social cognitive outcomes for people with SCZ. Limitations of the present study include the restricted ability of the tensor model to correctly assess multi-directionality at regions where fibre populations intersect. [ABSTRACT FROM AUTHOR]

Background: Neighborhood- or area-level socioeconomic disadvantage is associated with neural alterations across the life span. However, few studies have examined the effects of neighborhood disadvantage on white matter microstructure during adolescence, an important period of development that coincides with increased risk for psychopathology. Methods: In 200 adolescents (ages 13–20 years; 54.5% female, 4% nonbinary) recruited from 2 studies enriched for early adversity and depression, we examined whether neighborhood socioeconomic disadvantage derived from census tract data was related to white matter microstructure in several major white matter tracts. We also examined whether depressive symptoms and sex moderated these associations. Results: Greater neighborhood socioeconomic disadvantage was associated with lower fractional anisotropy (FA) in the left arcuate fasciculus (β = −0.24, false discovery rate [FDR]–corrected p = .035) and right uncinate fasciculus (β = −0.32, FDR-corrected p = .002) above and beyond the effects of family-level socioeconomic status. Depressive symptoms significantly moderated the association between left arcuate fasciculus FA and both neighborhood (β = 0.17, FDR-corrected p = .026) and unemployment (β = 0.22, FDR-corrected p = .004) disadvantage such that these associations were only significant in adolescents who reported less severe depression. Sex did not moderate the association between socioeconomic disadvantage and FA in these tracts. Conclusions: Greater neighborhood socioeconomic disadvantage, particularly poverty and educational attainment levels, was associated with lower FA in the arcuate fasciculus and uncinate fasciculus above and beyond the effects of family-level measures of socioeconomic status. These patterns were only observed in adolescents with low levels of depression, suggesting that we must be cautious about generalizing these findings to youths who struggle with mental health difficulties.

The model of the four streams of the prefrontal cortex proposes 4 streams of information: motor through Brodmann area (BA) 8, emotion through BA 9, memory through BA 10, and emotional-related sensory through BA 11. Although there is a surge of functional data supporting these 4 streams within the PFC, the structural connectivity underlying these neural networks has not been fully clarified. Here we perform population-based high-definition tractography using an averaged template generated from data of 1,065 human healthy subjects acquired from the Human Connectome Project to further elucidate the structural organization of these regions. We report the structural connectivity of BA 8 with BA 6, BA 9 with the insula, BA 10 with the hippocampus, BA 11 with the temporal pole, and BA 11 with the amygdala. The 4 streams of the prefrontal cortex are subserved by a structural neural network encompassing fibers of the anterior part of the superior longitudinal fasciculus-I and II, corona radiata, cingulum, frontal aslant tract, and uncinate fasciculus. The identified neural network of the four streams of the PFC will allow the comprehensive analysis of these networks in normal and pathological brain function. [ABSTRACT FROM AUTHOR]

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.

IntroductionSchizophrenia (SCZ) is a complex neurodevelopmental disorder characterised by functional and structural brain dysconnectivity and disturbances in perception, cognition, emotion, and social functioning. In the present study, we investigated whether the microstructural organisation of the uncinate fasciculus (UF) was associated with emotion recognition (ER) performance. Additionally, we investigated the usefulness of an unbiased hit rate (UHR) score to control for response biases (i.e., participant guessing) during an emotion recognition task (ERT).MethodsFifty-eight individuals diagnosed with SCZ were included. The CANTAB ERT was used to measure social cognition. Specific ROI manual tract segmentation was completed using ExploreDTI and followed the protocol previously outlined by Coad et al. (2020).ResultsWe found that the microstructural organisation of the UF was significantly correlated with physical neglect and ER outcomes. Furthermore, we found that the UHR score was more sensitive to ERT subscale emotion items than the standard HR score. Finally, given the association between childhood trauma (in particular childhood neglect) and social cognition in SCZ, a mediation analysis found evidence that microstructural alterations of the UF mediated an association between childhood trauma and social cognitive performance.DiscussionThe mediating role of microstructural alterations in the UF on the association between childhood trauma and social cognitive performance suggests that early life adversity impacts both brain development and social cognitive outcomes for people with SCZ. Limitations of the present study include the restricted ability of the tensor model to correctly assess multi-directionality at regions where fibre populations intersect.

The uncinate fasciculus (UF) connects fronto-insular and temporal gray matter regions involved in visceral emotional reactivity and semantic appraisal, but the precise role of this tract in socioemotional functioning is not well-understood. Using the Revised-Self Monitoring (RSMS) informant questionnaire, we examined whether fractional anisotropy (FA) in the right UF corresponded to socioemotional sensitivity during face-to-face interactions in 145 individuals (40 healthy older adults [NC], and 105 patients with frontotemporal lobar degeneration [FTLD] syndromes in whom this tract is selectively vulnerable, including 31 behavioral variant frontotemporal dementia [bvFTD], 39 semantic variant primary progressive aphasia [svPPA], and 35 nonfluent variant primary progressive aphasia [nfvPPA]). Voxelwise and region-of-interest-based DWI analyses revealed that FA in the right but not left UF significantly predicted RSMS score in the full sample, and in NC and svPPA subgroups alone. Right UF integrity did not predict RSMS score in the bvFTD group, but gray matter volume in the right orbitofrontal cortex adjacent to the UF was a significant predictor. Our results suggest that better socioemotional sensitivity is specifically supported by right UF white matter, highlighting a key neuro-affective relationship found in both healthy aging and neurologically affected individuals. The finding that poorer socioemotional sensitivity corresponded to right UF damage in svPPA but was more robustly influenced by gray matter atrophy adjacent to the UF in bvFTD may have important implications for endpoint selection in clinical trial design for patients with FTLD.

(1) Background: To investigate the correlation between the integrity of the left dual-stream frontotemporal network mediated by the arcuate fasciculus (AF) and uncinate fasciculus (UF), and acute/subacute post-stroke aphasia (PSA). (2) Methods: Thirty-six patients were recruited and received both a language assessment and a diffusion tensor imaging (DTI) scan. Correlations between diffusion indices in the bilateral LSAF/UF and language performance assessment were analyzed with correlation analyses. Multiple linear regression analysis was also implemented to investigate the effects of the integrity of the left LSAF/UF on language performance. (3) Results: Correlation analyses showed that the diffusion indices, including mean fractional anisotropy (FA) values and the fiber number of the left LSAF rather than the left UF was significantly positively associated with language domain scores (p < 0.05). Multiple linear regression analysis revealed an independent and positive association between the mean FA value of the left LSAF and the percentage score of language subsets. In addition, no interaction effect of the integrity of the left LSAF and UF on language performance was found (p > 0.05). (4) Conclusions: The integrity of the left LSAF, but not the UF, might play important roles in supporting residual language ability in individuals with acute/subacute PSA; simultaneous disruption of the dual-stream frontotemporal network mediated by the left LSAF and UF would not result in more severe aphasia than damage to either pathway alone. [ABSTRACT FROM AUTHOR]

Objective: Cognitive loss in older adults is a growing issue in our society, and there is a need to develop inexpensive, simple, effective in-home treatments. This study was conducted to explore the use of olfactory enrichment at night to improve cognitive ability in healthy older adults. Methods: Male and female older adults (N  =  43), age 60–85, were enrolled in the study and randomly assigned to an Olfactory Enriched or Control group. Individuals in the enriched group were exposed to 7 different odorants a week, one per night, for 2  h, using an odorant diffuser. Individuals in the control group had the same experience with de minimis amounts of odorant. Neuropsychological assessments and fMRI scans were administered at the beginning of the study and after 6  months. Results: A statistically significant 226% improvement was observed in the enriched group compared to the control group on the Rey Auditory Verbal Learning Test and improved functioning was observed in the left uncinate fasciculus, as assessed by mean diffusivity. Conclusion: Minimal olfactory enrichment administered at night produces improvements in both cognitive and neural functioning. Thus, olfactory enrichment may provide an effective and low-effort pathway to improved brain health. [ABSTRACT FROM AUTHOR]

Across species, unpredictable patterns of maternal behavior are emerging as novel predictors of aberrant cognitive and emotional outcomes later in life. In animal models, exposure to unpredictable patterns of maternal behavior alters brain circuit maturation and cognitive and emotional outcomes. However, whether exposure to such signals in humans alters the development of brain pathways is unknown. In mother-child dyads, we tested the hypothesis that exposure to more unpredictable maternal signals in infancy is associated with aberrant maturation of corticolimbic pathways. We focused on the uncinate fasciculus, the primary fiber bundle connecting the amygdala to the orbitofrontal cortex and a key component of the medial temporal lobe-prefrontal cortex circuit. Infant exposure to unpredictable maternal sensory signals was assessed at 6 and 12 months. Using high angular resolution diffusion imaging, we quantified the integrity of the uncinate fasciculus using generalized fractional anisotropy (GFA). Higher maternal unpredictability during infancy presaged greater uncinate fasciculus GFA in children 9-11 years of age (n = 69, 29 female). In contrast to the uncinate, GFA of a second corticolimbic projection, the hippocampal cingulum, was not associated with maternal unpredictability. Addressing the overall functional significance of the uncinate and cingulum relationships, we found that the resulting imbalance of medial temporal lobe-prefrontal cortex connectivity partially mediated the association between unpredictable maternal sensory signals and impaired episodic memory function. These results suggest that unbalanced maturation of corticolimbic circuits is a mechanism by which early unpredictable sensory signals may impact cognition later in life.SIGNIFICANCE STATEMENT Our prior work across species demonstrated that unpredictable patterns of maternal care are associated with compromised memory function. However, the neurobiological mechanisms by which this occurs in humans remain unknown. Here, we identify an association of exposure to unpredictable patterns of maternal sensory signals with the integrity of corticolimbic circuits involved in emotion and cognition using state-of-the-art diffusion imaging techniques and analyses. We find that exposure to early unpredictability is associated with higher integrity of the uncinate fasciculus with no effect on a second corticolimbic pathway, the cingulum. The resulting imbalance of corticolimbic circuit development is a novel mediator of the association between unpredictable patterns of maternal care and poorer episodic memory.

Alterations in white matter integrity have been demonstrated in a number of psychiatric disorders involving emotional disruptions. One such pathway - the uncinate fasciculus - connects the orbitofrontal cortex (OFC) to the medial temporal lobes (MTL) and has been associated with early life adversity, maltreatment, anxiety, and depression. While it is purported to play a role in episodic memory and discrimination, its exact function remains poorly understood. We have previously described the role of the amygdala and dentate (DG)/CA3 fields of the hippocampus in the mnemonic discrimination of emotional experiences (i.e. emotional pattern separation). However, how this computation may be modulated by connectivity with the orbitofrontal cortex remains unknown. Here we asked if the uncinate fasciculus plays a role in influencing MTL subregional activity during emotional pattern separation. By combining diffusion imaging with high-resolution fMRI, we found that reduced integrity of the UF is related to elevated BOLD fMRI activation of the DG/CA3 subregions of the hippocampus during emotional lure discrimination. We additionally report that higher levels of DG/CA3 activity are associated with poorer memory performance, suggesting that greater activation in this network (possibly driven by CA3 recurrent collaterals) is associated with memory errors. Based on this work we suggest that the UF is one pathway that may allow the OFC to exert control on this network and improve discrimination of emotional experiences, although further work is necessary to fully evaluate this possibility. This work provides novel insight into the role of prefrontal interactions with the MTL, particularly in the context of emotional memory.

The model of the four streams of the prefrontal cortex proposes 4 streams of information: motor through Brodmann area (BA) 8, emotion through BA 9, memory through BA 10, and emotional-related sensory through BA 11. Although there is a surge of functional data supporting these 4 streams within the PFC, the structural connectivity underlying these neural networks has not been fully clarified. Here we perform population-based high-definition tractography using an averaged template generated from data of 1,065 human healthy subjects acquired from the Human Connectome Project to further elucidate the structural organization of these regions. We report the structural connectivity of BA 8 with BA 6, BA 9 with the insula, BA 10 with the hippocampus, BA 11 with the temporal pole, and BA 11 with the amygdala. The 4 streams of the prefrontal cortex are subserved by a structural neural network encompassing fibers of the anterior part of the superior longitudinal fasciculus-I and II, corona radiata, cingulum, frontal aslant tract, and uncinate fasciculus. The identified neural network of the four streams of the PFC will allow the comprehensive analysis of these networks in normal and pathological brain function.

Aberrant microstructure of the uncinate fasciculus (UNC), a white matter (WM) tract implicated in emotion regulation, has been hypothesized as a neurobiological mechanism of depression. However, studies testing this hypothesis have yielded inconsistent results. The present meta-analysis consolidates evidence from 44 studies comparing fractional anisotropy (FA) and radial diffusivity (RD), two metrics characterizing WM microstructure, of the UNC in individuals with depression (n = 5016) to healthy individuals (n = 18 425). We conduct meta-regressions to identify demographic and clinical characteristics that contribute to cross-study heterogeneity in UNC findings. UNC FA was reduced in individuals with depression compared to healthy individuals. UNC RD was comparable between individuals with depression and healthy individuals. Comorbid anxiety explained inter-study heterogeneity in UNC findings. Depression is associated with perturbations in UNC microstructure, specifically with respect to UNC FA and not UNC RD. The association between depression and UNC microstructure appears to be moderated by anxiety. Future work should unravel the cellular mechanisms contributing to aberrant UNC microstructure in depression; clarify the relationship between UNC microstructure, depression, and anxiety; and link UNC microstructure to psychological processes, such as emotion regulation. [ABSTRACT FROM AUTHOR]

Verbal short-term memory (STM) deficits are associated with language processing impairments in people with aphasia. Importantly, the integrity of STM can predict word learning ability and anomia therapy gains in aphasia. While the recruitment of perilesional and contralesional homologous brain regions has been proposed as a possible mechanism for aphasia recovery, little is known about the white-matter pathways that support verbal STM in post-stroke aphasia. Here, we investigated the relationships between the language-related white matter tracts and verbal STM ability in aphasia. Nineteen participants with post-stroke chronic aphasia completed a subset of verbal STM subtests of the TALSA battery including nonword repetition (phonological STM), pointing span (lexical-semantic STM without language output) and repetition span tasks (lexical-semantic STM with language output). Using a manual deterministic tractography approach, we investigated the micro- and macrostructural properties of the structural language network. Next, we assessed the relationships between individually extracted tract values and verbal STM scores. We found significant correlations between volume measures of the right Uncinate Fasciculus and all three verbal STM scores, with the association between the right UF volume and nonword repetition being the strongest one. These findings suggest that the integrity of the right UF is associated with phonological and lexical-semantic verbal STM ability in aphasia and highlight the potential compensatory role of right-sided ventral white matter language tracts in supporting verbal STM after aphasia-inducing left hemisphere insult. [ABSTRACT FROM AUTHOR]

Background: Although the specific role of the uncinate fasciculus (UF) in emotional processing in patients with obsessive-compulsive disorder (OCD) has been investigated, the exact focal abnormalities in the UF have not been identified. The aim of the current study was to identify focal abnormalities in the white matter (WM) microstructure of the UF and to determine the associations between clinical features and structural neural substrates. Methods: In total, 71 drug-naïve patients with OCD and 81 age- and sexmatched healthy controls (HCs) were included. Automated fiber quantification (AFQ), a tract-based quantitative approach, was adopted to measure alterations in diffusion parameters, including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD), along the trajectory of the UF. Additionally, we utilized partial correlation analyses to explore the relationship between the altered diffusion parameters and clinical characteristics. Results: OCD patients showed significantly higher FA and lower RD at the level of the temporal and insular portions in the left UF than HCs. In the insular segments of the left UF, increased FA was positively correlated with the Hamilton Anxiety Scale (HAMA) score, while decreased RD was negatively correlated with the duration of illness. Conclusion: We observed specific focal abnormalities in the left UF in adult patients with OCD. Correlations with measures of anxiety and duration of illness underscore the functional importance of the insular portion of left UF disturbance in OCD patients. [ABSTRACT FROM AUTHOR]

Much is known about the role of cortical areas in language processing. The shift towards network approaches in recent years has highlighted the importance of uncovering the role of white matter in connecting these areas. However, despite a large body of research, many of these tracts’ functions are not well-understood. We present a comprehensive review of the empirical evidence on the role of eight major tracts that are hypothesized to be involved in language processing (inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, uncinate fasciculus, extreme capsule, middle longitudinal fasciculus, superior longitudinal fasciculus, arcuate fasciculus, and frontal aslant tract). For each tract, we hypothesize its role based on the function of the cortical regions it connects. We then evaluate these hypotheses with data from three sources: studies in neurotypical individuals, neuropsychological data, and intraoperative stimulation studies. Finally, we summarize the conclusions supported by the data and highlight the areas needing further investigation. [ABSTRACT FROM AUTHOR]

Simple Summary: This article reviews the use of diffusion tensor imaging (DTI) to evaluate changes in white matter microstructure within two specific fiber tracts in Parkinson's disease patients. It also examines how these structural changes may be related to cognitive impairments seen in advanced PD patients and provides insight into developing more targeted treatments for different types of Parkinson's disease. Diffusion tensor imaging (DTI) is gaining traction in neuroscience research as a tool for evaluating neural fibers. The technique can be used to assess white matter (WM) microstructure in neurodegenerative disorders, including Parkinson disease (PD). There is evidence that the uncinate fasciculus and the cingulum bundle are involved in the pathogenesis of PD. These fasciculus and bundle alterations correlate with the symptoms and stages of PD. PRISMA 2022 was used to search PubMed and Scopus for relevant articles. Our search revealed 759 articles. Following screening of titles and abstracts, a full-text review, and implementing the inclusion criteria, 62 papers were selected for synthesis. According to the review of selected studies, WM integrity in the uncinate fasciculus and cingulum bundles can vary according to symptoms and stages of Parkinson disease. This article provides structural insight into the heterogeneous PD subtypes according to their cingulate bundle and uncinate fasciculus changes. It also examines if there is any correlation between these brain structures' structural changes with cognitive impairment or depression scales like Geriatric Depression Scale-Short (GDS). The results showed significantly lower fractional anisotropy values in the cingulum bundle compared to healthy controls as well as significant correlations between FA and GDS scores for both left and right uncinate fasciculus regions suggesting that structural damage from disease progression may be linked to cognitive impairments seen in advanced PD patients. This review help in developing more targeted treatments for different types of Parkinson's disease, as well as providing a better understanding of how cognitive impairments may be related to these structural changes. Additionally, using DTI scans can provide clinicians with valuable information about white matter tracts which is useful for diagnosing and monitoring disease progression over time. [ABSTRACT FROM AUTHOR]

Probiotics are suggested to improve depressive symptoms via the microbiota-gut-brain axis. We have recently shown a beneficial clinical effect of probiotic supplementation in patients with depression. Their underlying neural mechanisms remain unknown. A multimodal neuroimaging approach including diffusion tensor imaging, resting-state functional MRI, and arterial spin labeling was used to investigate the effects of a four-weeks probiotic supplementation on fronto-limbic brain structure, function, and perfusion and whether these effects were related to symptom changes. Thirty-two patients completed both imaging assessments (18 placebo and 14 probiotics group). Probiotics maintained mean diffusivity in the left uncinate fasciculus, stabilized it in the right uncinate fasciculus, and altered resting-state functional connectivity (rsFC) between limbic structures and the temporal pole to a cluster in the precuneus. Moreover, a cluster in the left superior parietal lobule showed altered rsFC to the subcallosal cortex, the left orbitofrontal cortex, and limbic structures after probiotics. In the probiotics group, structural and functional changes were partly related to decreases in depressive symptoms. This study has a rather small sample size. An additional follow-up MRI session would be interesting for seeing clearer changes in the relevant brain regions as clinical effects were strongest in the follow-up. Probiotic supplementation is suggested to prevent neuronal degeneration along the uncinate fasciculus and alter fronto-limbic rsFC, effects that are partly related to the improvement of depressive symptoms. Elucidating the neural mechanisms underlying probiotics' clinical effects on depression provide potential targets for the development of more precise probiotic treatments. • Probiotic add-on intervention improved depressive symptoms in patients. • However, underlying neural mechanisms still remain unknown. • Probiotics impact fronto-limbic structure and function. • These brain changes are partly associated with clinical improvements. [ABSTRACT FROM AUTHOR]

ObjectiveCognitive loss in older adults is a growing issue in our society, and there is a need to develop inexpensive, simple, effective in-home treatments. This study was conducted to explore the use of olfactory enrichment at night to improve cognitive ability in healthy older adults.MethodsMale and female older adults (N = 43), age 60–85, were enrolled in the study and randomly assigned to an Olfactory Enriched or Control group. Individuals in the enriched group were exposed to 7 different odorants a week, one per night, for 2 h, using an odorant diffuser. Individuals in the control group had the same experience with de minimis amounts of odorant. Neuropsychological assessments and fMRI scans were administered at the beginning of the study and after 6 months.ResultsA statistically significant 226% improvement was observed in the enriched group compared to the control group on the Rey Auditory Verbal Learning Test and improved functioning was observed in the left uncinate fasciculus, as assessed by mean diffusivity.ConclusionMinimal olfactory enrichment administered at night produces improvements in both cognitive and neural functioning. Thus, olfactory enrichment may provide an effective and low-effort pathway to improved brain health.

Maternal inflammation during pregnancy can alter the trajectory of fetal brain development and increase risk for offspring psychiatric disorders. However, the majority of relevant research to date has been conducted in animal models. Here, in humans, we focus on the structural connectivity of frontolimbic circuitry as it is both critical for socioemotional and cognitive development, and commonly altered in a range of psychiatric disorders associated with intrauterine inflammation. Specifically, we test the hypothesis that elevated maternal concentration of the proinflammatory cytokine interleukin-6 (IL-6) during pregnancy will be associated with variation in microstructural properties of this circuitry in the neonatal period and across the first year of life. Pregnant mothers were recruited in early pregnancy and maternal blood samples were obtained for assessment of maternal IL-6 concentrations in early (12.6 ± 2.8 weeks [S.D.]), mid (20.4 ± 1.5 weeks [S.D.]) and late (30.3 ± 1.3 weeks [S.D.]) gestation. Offspring brain MRI scans were acquired shortly after birth (N = 86, scan age = 3.7 ± 1.7 weeks [S.D.]) and again at 12-mo age (N = 32, scan age = 54.0 ± 3.1 weeks [S.D.]). Diffusion Tensor Imaging (DTI) was used to characterize fractional anisotropy (FA) along the left and right uncinate fasciculus (UF), representing the main frontolimbic fiber tract. In N = 30 of the infants with serial MRI data at birth and 12-mo age, cognitive and socioemotional developmental status was characterized using the Bayley Scales of Infant Development. All analyses tested for potentially confounding influences of household income, prepregnancy Body-Mass-Index, obstetric risk, smoking during pregnancy, and infant sex, and outcomes at 12-mo age were additionally adjusted for the quality of the postnatal caregiving environment. Maternal IL-6 concentration (averaged across pregnancy) was prospectively and inversely associated with FA (suggestive of reduced integrity under high inflammatory conditions) in the newborn offspring (bi-lateral, p

Much is known about the role of cortical areas in language processing. The shift towards network approaches in recent years has highlighted the importance of uncovering the role of white matter in connecting these areas. However, despite a large body of research, many of these tracts’ functions are not well-understood. We present a comprehensive review of the empirical evidence on the role of eight major tracts that are hypothesized to be involved in language processing (inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, uncinate fasciculus, extreme capsule, middle longitudinal fasciculus, superior longitudinal fasciculus, arcuate fasciculus, and frontal aslant tract). For each tract, we hypothesize its role based on the function of the cortical regions it connects. We then evaluate these hypotheses with data from three sources: studies in neurotypical individuals, neuropsychological data, and intraoperative stimulation studies. Finally, we summarize the conclusions supported by the data and highlight the areas needing further investigation.

The hippocampus is a complex structure composed of distinct subfields. It has been central to understanding neural foundations of episodic memory. In the current cross‐sectional study, using a large sample of 830, 3‐ to 21‐year‐olds from a unique, publicly available dataset we examined the following questions: (1) Is there elevated grey matter volume of the hippocampus and subfields in late compared to early development? (2) How does hippocampal volume compare with the rest of the cerebral cortex at different developmental stages? and (3) What is the relation between hippocampal volume and connectivity with episodic memory performance? We found hippocampal subfield volumes exhibited a nonlinear relation with age and showed a lag in volumetric change with age when compared to adjacent cortical regions (e.g., entorhinal cortex). We also observed a significant reduction in cortical volume across older cohorts, while hippocampal volume showed the opposite pattern. In addition to age‐related differences in gray matter volume, dentate gyrus/cornu ammonis 3 volume was significantly related to episodic memory. We did not, however, find any associations with episodic memory performance and connectivity through the uncinate fasciculus, fornix, or cingulum. The results are discussed in the context of current research and theories of hippocampal development and its relation to episodic memory. [ABSTRACT FROM AUTHOR]

(1) Background: To investigate the correlation between the integrity of the left dual-stream frontotemporal network mediated by the arcuate fasciculus (AF) and uncinate fasciculus (UF), and acute/subacute post-stroke aphasia (PSA). (2) Methods: Thirty-six patients were recruited and received both a language assessment and a diffusion tensor imaging (DTI) scan. Correlations between diffusion indices in the bilateral LSAF/UF and language performance assessment were analyzed with correlation analyses. Multiple linear regression analysis was also implemented to investigate the effects of the integrity of the left LSAF/UF on language performance. (3) Results: Correlation analyses showed that the diffusion indices, including mean fractional anisotropy (FA) values and the fiber number of the left LSAF rather than the left UF was significantly positively associated with language domain scores (p < 0.05). Multiple linear regression analysis revealed an independent and positive association between the mean FA value of the left LSAF and the percentage score of language subsets. In addition, no interaction effect of the integrity of the left LSAF and UF on language performance was found (p > 0.05). (4) Conclusions: The integrity of the left LSAF, but not the UF, might play important roles in supporting residual language ability in individuals with acute/subacute PSA; simultaneous disruption of the dual-stream frontotemporal network mediated by the left LSAF and UF would not result in more severe aphasia than damage to either pathway alone.

When given a long list of items to remember, people typically prioritize the memorization of the most valuable items. Prior neuroimaging studies have found that cues denoting the presence of high value items can lead to increased activation of the mesolimbic dopaminergic reward circuit, including the nucleus accumbens (NAcc) and ventral tegmental area (VTA), which in turn results in up-regulation of medial temporal lobe encoding processes and better memory for the high value items. Value cues may also trigger the use of elaborative semantic encoding strategies which depend on interactions between frontal and temporal lobe structures. We used diffusion tensor imaging (DTI) to examine whether individual differences in anatomical connectivity within these circuits are associated with value-induced modulation of memory. DTI data were collected from 19 adults who also participated in an functional magnetic resonanceimaging (fMRI) study involving a value-directed memory task. In this task, subjects encoded words with arbitrarily assigned point values and completed free recall tests after each list, showing improved recall performance for high value items. Motivated by our prior fMRI finding of increased recruitment of left-lateralized semantic network regions during the encoding of high value words (Cohen et al., 2014), we predicted that the robustness of the white matter pathways connecting the ventrolateral prefrontal cortex (VLPFC) with the temporal lobe might be a determinant of recall performance for high value items. We found that the mean fractional anisotropy (FA) of each subject's left uncinate fasciculus (UF), a fronto-temporal fiber bundle thought to play a critical role in semantic processing, correlated with the mean number of high value, but not low value, words that subjects recalled. Given prior findings on reward-induced modulation of memory, we also used probabilistic tractography to examine the white matter pathway that links the NAcc to the VTA. We found that the number of fibers projecting from left NAcc to VTA was reliably correlated with subjects' selectivity index, a behavioral measure reflecting the degree to which recall performance was impacted by item value. Together, these findings help to elucidate the neuroanatomical pathways that support verbal memory encoding and its modulation by value.

White matter (WM) degeneration is suggested to predict the early signs of Alzheimer's disease (AD). The exact structural regions of brain circuitry involved are not known. This study aims to examine the associations between WM tract integrity, represented by the diffusion tensor imaging (DTI) measures, and AD diagnosis and to denote the key substrates in predicting AD. It included DTI measures of mean diffusivity (MD), fractional anisotropy, radial diffusivity and axial diffusivity of 18 main WM tracts in 84 non‐Hispanic white participants from the Alzheimer's Disease Neuroimaging Initiative dataset. The multivariable general linear model was used to examine the association of AD diagnosis with each DTI measure adjusting for age, gender and education. The corpus callosum, fornix, cingulum hippocampus, uncinate fasciculus, sagittal striatum, left posterior thalamic radiation and fornix‐stria terminalis showed significant increases in MD, radial and axial diffusivity, whereas the splenium of corpus callosum and the fornix showed significant decreases in fractional anisotropy among AD patients. Variable cluster analysis identified that hippocampus volume, mini‐mental state examination (MMSE), cingulate gyrus/hippocampus, inferior fronto‐occipital fasciculus and uncinate fasciculus are highly correlated in one cluster with MD measures. In conclusion, there were significant differences in DTI measures between the brain WM of AD patients and controls. Age is the risk factor associated with AD, not gender or education. Right cingulum gyrus and right uncinate fasciculus are particularly affected, correlating well with a cognitive test MMSE and MD measures for dementia in AD patients and could be a region of focus for AD staging. [ABSTRACT FROM AUTHOR]

While there is strong evidence from lesion and functional imaging studies implicating the left anterior temporal pole (LTP) in naming unique entities, less is known about white matter tracts in category-specific naming. We present evidence that implicates the uncinate fasciculus (UF) in proper noun naming. First, we describe two patients with left LTP gliomas who developed category specific worsening in proper noun naming in real time during awake surgery when the UF was surgically involved. We then describe a third case involving targeted electrical stimulation of the UF using stereo-electroencephalography (sEEG) that resulted in category specific naming disturbance for proper nouns.. [ABSTRACT FROM AUTHOR]

Both men and women scoring high on psychopathy exhibit similar structural and functional neural abnormalities, including reduced volume of the orbitofrontal cortex (OFC) and reduced hemodynamic activity in the amygdala during affective processing experimental paradigms. The uncinate fasciculus (UF) is a white matter (WM) tract that connects the amygdala to the OFC. Reduced structural integrity of the UF, measured via fractional anisotropy (FA), is commonly associated with men scoring high on psychopathy. However, only one study to date has investigated the relationship between psychopathic traits and UF structural integrity in women, recruiting participants from a community sample. Here, we investigated whether Hare Psychopathy Checklist-Revised (PCL-R) facet scores (measuring interpersonal, affective, lifestyle/behavioral, and antisocial psychopathic traits, respectively) were associated with reduced FA in the left and right UF in a sample of 254 incarcerated women characterized by a wide range of psychopathy scores. We observed that PCL-R Facet 3 scores, assessing lifestyle/behavioral psychopathic traits, were associated with reduced FA in the left and right UF, even when controlling for participant's age and history of previous substance use. The results obtained in the current study help improve our understanding of structural abnormalities associated with women scoring high on psychopathy. Specifically, reduced UF structural integrity may contribute to some of the deficits commonly associated with women scoring high on psychopathy, including emotion dysregulation. [ABSTRACT FROM AUTHOR]

Diffusion tensor imaging (DTI) is gaining traction in neuroscience research as a tool for evaluating neural fibers. The technique can be used to assess white matter (WM) microstructure in neurodegenerative disorders, including Parkinson disease (PD). There is evidence that the uncinate fasciculus and the cingulum bundle are involved in the pathogenesis of PD. These fasciculus and bundle alterations correlate with the symptoms and stages of PD. PRISMA 2022 was used to search PubMed and Scopus for relevant articles. Our search revealed 759 articles. Following screening of titles and abstracts, a full-text review, and implementing the inclusion criteria, 62 papers were selected for synthesis. According to the review of selected studies, WM integrity in the uncinate fasciculus and cingulum bundles can vary according to symptoms and stages of Parkinson disease. This article provides structural insight into the heterogeneous PD subtypes according to their cingulate bundle and uncinate fasciculus changes. It also examines if there is any correlation between these brain structures’ structural changes with cognitive impairment or depression scales like Geriatric Depression Scale-Short (GDS). The results showed significantly lower fractional anisotropy values in the cingulum bundle compared to healthy controls as well as significant correlations between FA and GDS scores for both left and right uncinate fasciculus regions suggesting that structural damage from disease progression may be linked to cognitive impairments seen in advanced PD patients. This review help in developing more targeted treatments for different types of Parkinson’s disease, as well as providing a better understanding of how cognitive impairments may be related to these structural changes. Additionally, using DTI scans can provide clinicians with valuable information about white matter tracts which is useful for diagnosing and monitoring disease progression over time.

Objectives: To detect the whole-brain reduced myelin density in unmedicated patients with major depressive disorder (MDD) using the inhomogeneous magnetization transfer (ihMT) imaging technology. Compared to other technologies, the ihMT provides high specificity and sensitivity to detect myelin.Method: In this prospective study, fifty unmedicated patients (mean age 25.36 years, 40% men) with MDD and 57 age- and sex-matched healthy controls (HCs) (mean age 25.02 years, 53% men) were recruited between January 2019 and December 2019. All participants underwent ihMT imaging, and pseudo-quantitative ihMT (qihMT) and ihMT ratio (ihMTR) were obtained. The mean values of qihMT and ihMTR extracted from the 50 WM masks (extracted from the International Consortium for Brain Mapping, ICBM-152) in each participant were compared between participants in the MDD and HCs groups. The symptoms of patients were evaluated using the 24-item Hamilton Depression Rating scale (HDRS).Results: Compared with the HC group, the MDD group showed significantly decreased qihMT and ihMTR values in the left inferior fronto-occipital fasciculus (IFOF) (t = -4.057, p < 0.001; t = -3.662, p < 0.001) and the left uncinate fasciculus (UF) (t = -4.776, p < 0.001; t = -3.800, p < 0.001) after Bonferroni correction. The correlation analysis displayed a significant negative correlation between qihMT values of the left IFOF and HDRS total scores in patients with MDD (r = -0.390, p = 0.012).Limitations: This was a cross-sectional study with a relative small sample.Conclusions: These findings suggest the reduced myelin density in the IFOF and UF in patients with MDD, which might be associated with the pathophysiology of MDD. [ABSTRACT FROM AUTHOR]

Chronic pain is often present at more than one anatomical location, leading to chronic overlapping pain conditions. Whether chronic overlapping pain conditions represent a distinct pathophysiology from the occurrence of pain at only one site is unknown. Using genome-wide approaches, we compared genetic determinants of chronic single-site versus multisite pain in the UK Biobank. We found that different genetic signals underlie chronic single-site and multisite pain with much stronger genetic contributions for the latter. Among 23 loci associated with multisite pain, nine loci replicated in the HUNT cohort, with the DCC netrin 1 receptor (DCC) as the top gene. Functional genomics identified axonogenesis in brain tissues as the major contributing pathway to chronic multisite pain. Finally, multimodal structural brain imaging analysis showed that DCC is most strongly expressed in subcortical limbic regions and is associated with alterations in the uncinate fasciculus microstructure, suggesting that DCC-dependent axonogenesis may contribute to chronic overlapping pain conditions via corticolimbic circuits. [ABSTRACT FROM AUTHOR]

• This study is the first to relate peripheral inflammation with FA in human adolescents. • Higher peripheral levels of cytokines are associated with lower FA in the corpus callosum genu. • Lower FA in the corpus callosum genu has previously been found to be a neurophenotype of depression. • Peripheral inflammation may contribute to neurophenotypes of depression. Adolescent depression is characterized by heightened inflammation and altered connectivity of fronto-cingulate-limbic tracts, including the genu of the corpus callosum (CCG) and the uncinate fasciculus (UF). No studies, however, have yet examined the association between inflammation, measured by peripheral levels of cytokines, and white matter connectivity of fronto-cingulate-limbic tracts in adolescents. Here, 56 depressed adolescents (32 females, 3 non-binary; 16.23 ± 1.28 years) and 19 controls (10 females; 15.72 ± 1.17 years) completed a diffusion-weighted MRI scan at 3 Tesla. We conducted deterministic tractography to segment bilateral corpus callosum (genu and splenium) and UF and computed mean fractional anisotropy (FA) in each tract. A subset of participants (43 depressed and 17 healthy controls) also provided dried blood spot samples from which we assayed interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-ɑ) using a Luminex multiplex array. Depressed participants did not differ from controls in FA of the corpus callosum or UF (all FDR-corrected p s > 0.056) but exhibited higher levels of inflammation than did controls (IL-6: β = 0.91, FDR-corrected p = 0.006; TNF-α: β = 0.76, FDR-corrected p = 0.006). Although diagnostic group did not moderate the associations between inflammatory cytokines and FA in the CCG and UF, across both groups, greater peripheral inflammation was associated with lower FA in the CCG (IL-6: β = −0.38; FDR-corrected p = 0.044; TNF-ɑ: β = −0.41, FDR-corrected p = 0.044). This study is the first to examine associations between peripheral inflammation and white matter microstructure of fronto-cingulate-limbic tracts in depressed and nondepressed adolescents. Future mechanistic studies are needed to confirm our findings; nevertheless, our results suggest that heightened inflammation is an important component of neurophenotypes that are relevant to adolescent depression. [ABSTRACT FROM AUTHOR]

Among youths with conduct disorder, those with callous-unemotional traits are at increased risk for persistent antisocial behaviour. Although callous-unemotional traits have been found to be associated with white-matter brain abnormalities, previous diffusion imaging studies were conducted in small samples, preventing examination of potential sex by callous-unemotional traits interaction effects on white matter. Here, we used tract-based spatial statistics at a whole-brain level and within regions of interest to compare the white matter correlates of callous-unemotional traits in female vs. male youths with conduct disorder, in a sample (n = 124) recruited through a multi-site protocol. A sex-specific association between callous-unemotional traits and white matter was found in the left uncinate fasciculus, where callous-unemotional traits were positively associated with axial diffusivity in males, while an opposite pattern was found in females. These findings are in line with previous studies suggesting that the uncinate fasciculus is a key tract implicated in the development of psychopathy, but also add to recent evidence showing that sexual dimorphism needs to be taken into account when examining the structural correlates of mental disorders in general, and callous-unemotional traits in conduct disorder in particular. [ABSTRACT FROM AUTHOR]

Williams syndrome (WS) is a genetic condition characterized by a hypersocial personality and desire to form close relationships, juxtaposed with significant anxieties of nonsocial events. The neural underpinnings of anxiety in individuals with WS are currently unknown. Aberrations in the anatomical and microstructural integrity of the uncinate fasciculus (UF) have been recently implicated in social and generalized anxiety disorders. Based on these findings, we tested the hypothesis that the reported anxieties in individuals with WS share similar neuropathological correlates. Toward this end, diffusion tensor imaging (DTI) methods were employed to examine the microstructural integrity (fractional anisotropy, mean diffusivity, longitudinal diffusivity) of the UF in 18 WS and 15 typically developing adults (TD). Anxiety and sociability questionnaires were administered to determine associations with DTI indices of UF across groups. Results revealed comparable white matter integrity of the UF across groups, yet elevated subjective experience of anxiety in those with WS. Additionally, sociability and UF microstructural properties were dissociated across both groups. Whereas no relationships were found between DTI indices and anxiety in TD participants, strong negative associations were observed between these constructs in individuals with WS. Findings indicated that increased anxiety manifested by individuals with WS was associated with DTI measures of the UF and may signal structural or possibly physiological aberration involving this tract within the prefrontal-temporal network.

Background: Bipolar disorder (BD) is a severe mental disorder, characterized by prominent mood swings and emotion regulation (ER) deficits. The uncinate fasciculus (UF), a white matter tract connecting the amygdala and the ventral prefrontal cortex, has been implicated in ER. Aberrancies in UF microstructure may be an endophenotype associated with increased risk for BD. However, studies in individuals with BD and their first-degree relatives (REL) have yielded inconsistent findings. This meta-analysis takes a region-of-interest approach to consolidate the available evidence and elucidate the role of the UF in the risk-architecture of BD.Methods: Using web-based search engines, we identified diffusion tensor imaging (DTI) studies focusing on the left and right UF and conducted meta-analyses comparing fractional anisotropy (FA) and radial diffusivity (RD) between BD or REL and healthy control participants (HC).Results: We included 32 studies (nBD=1186, nREL=289, nHC=2315). Compared to HC, individuals with BD showed lower FA in the right (WMD=-0.31, p<0.0001) and left UF (WMD=-0.21, p = 0.010), and higher RD in the right UF (WMD=0.32, p = 0.009). We found no significant differences between REL and HC. In the right but not left UF, REL showed higher FA than BD (p = 0.043).Conclusion: Our findings support aberrant UF microstructure, potentially related to alterations in myelination, as a mechanism, but not as an endophenotype of BD. However, given the limited power in the REL subsample, the latter finding must be considered preliminary. Studies examining the role of the UF in individuals at familial risk for BD are warranted. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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. Conclusions: Alterations in the white matter microstructure within bilateral UF and left IFOF may be biomarkers of CU behaviors, even in very young children. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Social anxiety disorder (SAD) is one of the most common mental health disorders in youth, defined by a persistent and intense fear of negative evaluation by others. Recent research has examined its neurological underpinnings, including structural connectivity changes in the brain. This has been examined through measurement of the white matter (WM) structure of fibre pathways. Previous studies have shown inconsistent results. This study attempts to resolve these inconsistencies by utilising a recently proposed, advanced method for diffusion MRI analysis, known as fixel based analysis (FBA). This technique enables examination of WM macro- and micro-structure with measures of fibre density (FD), fibre bundle cross-section (FC) and fibre density-cross-section (FDC). This study evidenced increased FDC in a region of the right superior longitudinal fasciculus (SLF) from a whole brain FBA, along with increased FC and FDC from an analysis restricted to a-priori tracts of interest, in regions of the right inferior longitudinal fasciculus (R-ILF). The average FDC of the left uncinate fasciculus (L-UF) was also increased. To examine the relationship between WM structure and severity of symptoms, these FBA metrics were correlated with Leibowitz Social Anxiety Scale (LSAS) scores. From the tract-restricted analysis an inverse correlation between FC and LSAS scores was found in the R-ILF. The average FC of the R-ILF was also inversely correlated with symptom severity. By utilising a more sensitive and fibre-specific method of analysis than previous studies, these findings highlight innovative outcomes relating to white matter in numerous fibre tracts. [ABSTRACT FROM AUTHOR]

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.

The uncinate fasciculus (UF) connects fronto-insular and temporal gray matter regions involved in visceral emotional reactivity and semantic appraisal, but the precise role of this tract in socioemotional functioning is not well-understood. Using the Revised-Self Monitoring (RSMS) informant questionnaire, we examined whether fractional anisotropy (FA) in the right UF corresponded to socioemotional sensitivity during face-to-face interactions in 145 individuals (40 healthy older adults [NC], and 105 patients with frontotemporal lobar degeneration [FTLD] syndromes in whom this tract is selectively vulnerable, including 31 behavioral variant frontotemporal dementia [bvFTD], 39 semantic variant primary progressive aphasia [svPPA], and 35 nonfluent variant primary progressive aphasia [nfvPPA]). Voxelwise and region-of-interest-based DWI analyses revealed that FA in the right but not left UF significantly predicted RSMS score in the full sample, and in NC and svPPA subgroups alone. Right UF integrity did not predict RSMS score in the bvFTD group, but gray matter volume in the right orbitofrontal cortex adjacent to the UF was a significant predictor. Our results suggest that better socioemotional sensitivity is specifically supported by right UF white matter, highlighting a key neuro-affective relationship found in both healthy aging and neurologically affected individuals. The finding that poorer socioemotional sensitivity corresponded to right UF damage in svPPA but was more robustly influenced by gray matter atrophy adjacent to the UF in bvFTD may have important implications for endpoint selection in clinical trial design for patients with FTLD.

Abstract Background Individuals with autism spectrum disorder (ASD) have social interaction deficits and difficulties in emotional regulation. The neural substrates for these socio-affective deficits are not yet clear, but one potential candidate is maldevelopment of the uncinate fasciculus (UF), a white matter tract thought to be involved in socio-affective processing. However, the developmental trajectory of the UF in young children with social interaction deficits has not been examined. The present study was designed to describe the developmental growth trajectory of the UF and the relationships between UF development and social deficits in ASD. Methods Eigenvalues of the UF were measured by diffusion tensor imaging (DTI)-based tractography in 37 children with ASD and 27 matched 2–3-year-old subjects with developmental delay (DD) at baseline (time 1) and at 2-year follow-up (time 2). Growth rates of the UF were compared between groups and associations with social deficit scores according to the Autism Diagnostic Interview-Revised (ADI-R) analyzed by Pearson’s correlations. Results At time 1, axial diffusivity (AD) of the left UF was significantly larger in the ASD group than the DD group. At time 2, left UF fractional anisotropy (FA) was significantly higher and radial diffusivity (RD) significantly lower in the ASD group than the DD group. The rate of UF growth during this 2-year interval was faster in children with ASD than DD. Significant negative correlations were found between the rise in ADI-R social deficit measures and both right UF RD and left UF mean diffusivity (MD). Conclusions Young children with ASD demonstrate UF overgrowth during the 2-year development period between 2 and 3 and 4–5 years of age, and this white matter abnormality is directly associated with the progression of social deficits. Trial registration World Health Organization class I registered international clinical trial platform, ChiCTR-ROC-17012877.

Recent studies advocate a connectivity pattern wider than previously believed of the uncinate fasciculus that extends to the ventrolateral and dorsolateral prefrontal cortices. These new percepts on the connectivity of the tract suggest a more expansive role for the uncinate fasciculus. Our aim was to shed light on this controversy through fiber dissections. Twenty normal adult human formalin-fixed cerebral hemispheres were used. Focused dissections on the insular, orbitofrontal, ventromedial, ventrolateral, and dorsolateral prefrontal areas were performed to record the topography of the frontal terminations of the uncinate fasciculus. Three discrete fiber layers were consistently disclosed: the first layer was recorded to terminate at the posterior orbital gyrus and pars orbitalis, the second layer at the posterior two thirds of the gyrus rectus, and the last layer at the posterior one third of the paraolfactory gyrus. The insular apex was documented as a crucial landmark regarding the topographic differentiation of the uncinate and occipitofrontal fasciculi (i.e., fibers that travel ventrally belong to the uncinate fasciculus whereas those traveling dorsally are occipitofrontal fibers). The frontal terminations of the uncinate fasciculus were consistently documented to project to the posterior orbitofrontal area. The area of the insular apex is introduced for the first time as a crucial surface landmark to effectively distinguish the stems of the uncinate and occipitofrontal fasciculi. This finding could refine the spatial resolution of awake subcortical mapping, especially for insular lesions, and improve the accuracy of in vivo diffusion tensor imaging protocols. [ABSTRACT FROM AUTHOR]

Beta-amyloid (Aβ) and tau proteins, the pathological hallmarks of Alzheimer’s disease (AD), are believed to spread through connected regions of the brain. Combining diffusion imaging and positron emission tomography, we investigated associations between white matter microstructure specifically in bundles connecting regions where Aβ or tau accumulates and pathology. We focused on free-water-corrected diffusion measures in the anterior cingulum, posterior cingulum, and uncinate fasciculus in cognitively normal older adults at risk of sporadic AD and presymptomatic mutation carriers of autosomal dominant AD. In Aβ-positive or tau-positive groups, lower tissue fractional anisotropy and higher mean diffusivity related to greater Aβ and tau burden in both cohorts. Associations were found in the posterior cingulum and uncinate fasciculus in preclinical sporadic AD, and in the anterior and posterior cingulum in presymptomatic mutation carriers. These results suggest that microstructural alterations accompany pathological accumulation as early as the preclinical stage of both sporadic and autosomal dominant AD.

Schizophrenia (SCZ) is associated with increased risk of violence compared to the general population. Neuroimaging research suggests SCZ to be a disorder of disrupted connectivity, with diffusion tensor imaging (DTI) indicating white matter (WM) abnormalities. It has been hypothesized that SCZ patients with a history of violence (SCZ-V) have brain abnormalities distinguishing them from SCZ patients with no history of violence (SCZ-NV). Yet, a thorough investigation of the neurobiological underpinnings of state and trait measures of violence and aggression in SCZ derived from DTI indices is lacking. Using tract-based spatial statistics, we compared DTI-derived microstructural indices: fractional anisotropy (FA), mean, axial (AD) and radial diffusivity across the brain; (1) between SCZ-V (history of murder, attempted murder, or severe assault towards other people, n = 24), SCZ-NV (n = 52) and healthy controls (HC, n = 94), and (2) associations with current aggression scores among both SCZ groups. Then, hypothesis-driven region of interest analyses of the uncinate fasciculus and clinical characteristics including medication use were performed. SCZ-V and SCZ-NV showed decreased FA and AD in widespread regions compared to HC. There were no significant differences on any DTI-based measures between SCZ-V and SCZ-NV, and no significant associations between state or trait measures of aggression and any of the DTI metrics in the ROI analyses. The DTI-derived WM differences between SCZ and HC are in line with previous findings, but the results do not support the hypothesis of specific brain WM microstructural correlates of violence or aggression in SCZ. [ABSTRACT FROM AUTHOR]