bioRxiv Science⌕ Search

Biology subjects

Dick, A. S.

Publications and source records attributed to Dick, A. S..

16 recordsLinked to original sources

Brain Microstructure and Obesity Risk in Early Childhood: Insights from Restriction Spectrum Imaging

Pediatric obesity is a growing public health concern, yet little is known about the neurobiological underpinnings of obesity risk in early childhood. Using restriction spectrum imaging (RSI), we examined associations between adiposity and brain microstructure in a cross-sectional sample of 159 children aged 4-7 years, including 81 with ADHD and 78 typically developing (TD) peers. We focused on RSI-derived measures of restricted diffusion--specifically restricted normalized isotropic (RNI), directional (RND), and total (RNT) signals--as indicators of cellular density in subcortical and cortical regions implicated in reward and salience processing. Body mass index (BMI), percent body fat, waist circumference, and obesity status were assessed. Higher BMI, but not other adiposity measures, was significantly associated with increased RNI in the right insula, nucleus accumbens (NAcc), and putamen, as well as increased RNT in the right insula and pallidum. These findings suggest early microstructural alterations in reward-related circuits, consistent with theories of diet-related neuroinflammation. Contrary to hypotheses, ADHD diagnosis did not moderate the associations, and anthropometric profiles were similar between groups. This suggests a shared neural pathway linking early adiposity and brain structure, independent of diagnostic status. Our findings replicate and extend prior work in older children, highlighting BMI as the most sensitive marker of obesity-related brain differences in early childhood. These results underscore the potential of RSI as a tool for identifying early neural risk markers of obesity and inform future efforts to design preventive interventions during critical developmental windows.

neuroscience↗

Structural Development of Speech Networks in Young Children at Risk for Speech Disorder

Characterizing the structural development of the neural speech network in early childhood is important to understand speech acquisition. To investigate speech in the developing brain, 94 children aged 4-7-years-old were scanned using diffusion weighted imaging (DWI) magnetic resonance imaging (MRI). In order to increase sample size and performance variability, we included children who were diagnosed with attention-deficit hyperactivity disorder (ADHD) from a larger ongoing study. Additionally, each child completed the Syllable Repetition Task (SRT), a validated measure of phoneme articulation. The DWI data were modeled using restriction spectrum imaging (RSI) to measure restricted and hindered diffusion properties in both grey and white matter. Consequently, we analyzed the diffusion data using both whole brain analysis, and automated fiber quantification (AFQ) analysis to establish tract profiles for each of six fiber pathways thought to be important for supporting speech development. In the whole brain analysis, we found that SRT performance was associated with restricted diffusion in bilateral inferior frontal gyrus, pars opercularis, right pre-supplementary and supplementary motor area, and bilateral cerebellar grey matter (p < .005). Age moderated these associations in left pars opercularis and frontal aslant tract (FAT). However, in both cases only the cerebellar findings survived a cluster correction. We also found associations between SRT performance and restricted diffusion in cortical association fiber pathways, especially left FAT, and in the cerebellar peduncles. Analyses using automated fiber quantification (AFQ) highlighted differences in high and low performing children along specific tract profiles, most notably in left but not right FAT, in bilateral SLFIII, and in the cerebellar peduncles. These findings suggest that individual differences in speech performance are reflected in structural grey and white matter differences as measured by restricted and hindered diffusion metrics, and offer important insights into developing brain networks supporting speech in very young children.

neuroscience↗

Missing data approaches for longitudinal neuroimaging research: Examples from the Adolescent Brain and Cognitive Development (ABCD) Study

This paper addresses the challenges of managing missing values within expansive longitudinal neu-roimaging datasets, using the specific example of data derived from the Adolescent Brain and Cog-nitive Development (ABCD(R)) study. The conventional listwise deletion method, while widely used, is not recommended due to the risk that substantial bias can potentially be introduced with this method. Unfortunately, recommended alternative practices can be challenging to implement with large data sets. In this paper, we advocate for the adoption of more sophisticated statistical method-ologies, including multiple imputation, propensity score weighting, and full information maximum likelihood (FIML). Through practical examples and code using (ABCD(R)) data, we illustrate some of the benefits and challenges of these methods, with a review of how these advanced methodolo-gies bolster the robustness of analyses and contribute to the integrity of research findings in the field of developmental cognitive neuroscience.

neuroscience↗

Reduced recruitment of inhibitory control regions in very young children with ADHD during a modified Kiddie Continuous Performance Task: a fMRI study.

Attention-Deficit/Hyperactivity Disorder (ADHD) symptom profiles are known to undergo changes throughout development, rendering the neurobiological assessment of ADHD challenging across different developmental stages. Particularly in young children (ages 4 to 7 years), measuring inhibitory control network activity in the brain has been a formidable task due to the lack of child-friendly functional Magnetic Resonance Imaging (fMRI) paradigms. This study aims to address these difficulties by focusing on measuring inhibitory control in very young children within the MRI environment. A total of 56 children diagnosed with ADHD and 78 typically developing (TD) 4-7-year-old children were examined using a modified version of the Kiddie-Continuous Performance Test (K-CPT) during BOLD fMRI to assess inhibitory control. We concurrently evaluated their performance on the established and standardized K-CPT outside the MRI scanner. Our findings suggest that the modified K-CPT effectively elicited robust and expected brain activity related to inhibitory control in both groups. Comparisons between the two groups revealed subtle differences in brain activity, primarily observed in regions associated with inhibitory control, such as the inferior frontal gyrus, anterior insula, dorsal striatum, medial pre-supplementary motor area (pre-SMA), and cingulate cortex. Notably, increased activity in the right anterior insula was associated with improved response time (RT) and reduced RT variability on the K-CPT administered outside the MRI environment, although this did not survive statistical correction for multiple comparisons. In conclusion, our study successfully overcame the challenges of measuring inhibitory control in very young children within the MRI environment by utilizing a modified K-CPT during BOLD fMRI. These findings shed light on the neurobiological correlates of inhibitory control in ADHD and TD children, provide valuable insights for understanding ADHD across development, and potentially inform ADHD diagnosis and intervention strategies. The research also highlights remaining challenges with task fMRI in very young clinical samples.

neuroscience↗

Acculturative orientations among Hispanic/Latinx caregivers in the ABCD Study: Associations with caregiver and youth mental health and youth brain function

BackgroundPopulation-based neuroscience offers opportunities to examine important but understudied sociocultural factors, such as acculturation. Acculturation refers to the extent to which an individual retains their cultural heritage and / or adopts the receiving societys culture and is particularly salient among Hispanic/Latinx immigrants. Specific acculturative orientations have been linked to vulnerability to substance use, depression, and suicide and are known to influence family dynamics between caregivers and their children. MethodsWe investigated first- and second-generation Hispanic/Latinx caregivers in the ABCD Study and examined how caregivers acculturative orientation impacts their mental health, as well as the mental health of their children. In addition, we evaluated how caregiver orientation is associated with adolescent socio-affiliative neural function in the ventromedial prefrontal cortex, insula, and temporoparietal junction. ResultsWe identified two caregiver acculturation profiles: bicultural (retains heritage culture while adopting US culture) and detached (discards heritage culture and rejects US culture). Bicultural caregivers exhibited fewer symptoms of depression, avoidant behaviors, and inattention compared to detached caregivers; further, youth exhibited similar internalizing effects across caregiver profiles. Moreover, youth with bicultural caregivers displayed increased resting-state brain activity in the left insula; however, differences in long-range functional connectivity were not significant. ConclusionsCaregiver acculturation is an important familial-environmental factor in Hispanic/Latinx families linked to significant differences in caregiver and youth mental health and youth insula activity. Future work should examine sociocultural and neurodevelopmental changes across adolescence to assess health outcomes and determine whether localized, corticolimbic brain effects are ultimately translated into long-range connectivity differences.

neuroscience↗

Language and the cerebellum: structural connectivity to the eloquent brain

Neurobiological models of receptive language have focused on the left-hemisphere perisylvian cortex with the assumption that the cerebellum supports peri-linguistic cognitive processes such as verbal working memory. The goal of this study was to identify language-sensitive regions of the cerebellum then map the structural connectivity profile of these regions. Functional imaging data and diffusion-weighted imaging data from the Human Connectome Project (HCP) were analyzed. We found that (a) working memory, motor activity, and language comprehension activated partially overlapping but mostly unique subregions of the cerebellum; (b) the linguistic portion of the cerebello-thalamo-cortical circuit was more extensive than the linguistic portion of the cortico-ponto-cerebellar tract; (c) there was a frontal-lobe bias in the connectivity from the cerebellum to the cerebrum; (d) there was some degree of specificity; and (e) for some cerebellar tracts, individual differences in picture identification ability covaried with fractional anisotropy metrics. These findings yield insights into the structural connectivity of the cerebellum as relates to the uniquely human process of language comprehension.

neuroscience↗

Volumetric development of hippocampal subfields and hippocampal white matter connectivity: Relationship with episodic memory

The hippocampus is a complex structure composed of several distinct subfields and has been at the center of scientific study examining the neural foundations of episodic memory. To date, there is little consensus regarding the structural development of the hippocampus and its subfields assessed both volumetrically and through anatomical connectivity, nor how the development of the related substructures influences episodic memory. In the current cross-sectional study, using a large sample of 830, 3- to 21-year-olds from a unique and publicly available dataset we examined the following questions: 1) Is there elevated grey matter volume of the hippocampus and its respective 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 the connectivity of the hippocampus with cortex as measured by diffusion-weighted imaging, with episodic memory performance? We found hippocampal subfield volumes exhibited a non-linear relation with age. Specifically, hippocampal subfield volumes 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 grey matter volume, several distinct subfields are 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.

neuroscience↗

Hippocampal Volume, Neurite Density and Trace Eye-Blink Conditioning in Young Children

The current study examined the relations between hippocampal structure (e.g., volume and neurite density) and performance on a trace eye blink conditioning (EBC) task in young children. Our first aim assessed whether individual differences in hippocampal volume were associated with trace EBC performance, using both percent Conditioned Responses (% CR) and CR onset latency or the average latency (ms) at which the child started their blink, as measures of hippocampal-dependent associative learning. Our second aim evaluated whether individual differences in hippocampal neurite density were associated with EBC performance using the same outcome measures. Typically developing 4- to 6-year-olds (N = 31; 14 girls; Mage = 5.67; SDage = 0.89) completed T1 and diffusion-weighted MRI scans and a 15-minute trace eyeblink conditioning task outside of the scanner. % CR and CR onset latency were computed across all tone-puff and tone-alone trials. While hippocampal volume was not associated with any of our EBC measures, greater hippocampal neurite density bilaterally, was associated with later CR onset. In other words, children with greater left and right hippocampal neurite density blinked closer to the US (i.e., air puff) than children with less hippocampal neurite density, indicating that structural changes in the hippocampus assisted in the accurate timing of conditioned responses.

neuroscience↗

Meaningful Effects in the Adolescent Brain Cognitive Development Study

The Adolescent Brain Cognitive Development (ABCD) Study is the largest single-cohort prospective longitudinal study of neurodevelopment and childrens health in the United States. A cohort of n= 11,880 children aged 9-10 years (and their parents/guardians) were recruited across 22 sites and are being followed with in-person visits on an annual basis for at least 10 years. The study approximates the US population on several key sociodemographic variables, including sex, race, ethnicity, household income, and parental education. Data collected include assessments of health, mental health, substance use, culture and environment and neurocognition, as well as geocoded exposures, structural and functional magnetic resonance imaging (MRI), and whole-genome genotyping. Here, we describe the ABCD Study aims and design, as well as issues surrounding estimation of meaningful associations using its data, including population inferences, hypothesis testing, power and precision, control of covariates, interpretation of associations, and recommended best practices for reproducible research, analytical procedures and reporting of results.

neuroscience↗

Neural vulnerability and hurricane-related media predict posttraumatic stress in youth

As natural disasters increase in frequency and severity1, 2, mounting evidence reveals that their human toll extends beyond death, injury, and loss. Posttraumatic stress (PTS) can be common among directly exposed individuals, and children are particularly vulnerable3, 4. Curiously, PTS can even be found among youth far removed from harms way, and media-based exposure may partially account for this phenomenon5-8. Unfortunately, susceptibility to media effects has been difficult to characterize because most research is initiated post-event, precluding examination of pre-disaster factors. In this study, we mitigate this issue with data from nearly 400 9-to 11-year-old children collected prior to and after Hurricane Irma. We evaluate whether preexisting neural patterns moderate associations between hurricane experiences and later Irma-related PTS. We show that "dose" of both objective exposure and Irma-related media exposure predicted Irma-related PTS, the latter even among children dwelling thousands of kilometers away from the hurricane. Furthermore, we show, using pre-hurricane functional magnetic resonance imaging data, that neural responses in brain regions associated with anxiety and stress confer particular vulnerability to the psychological effects of hurricane exposure among certain children. Surprisingly, this was even the case for media exposure- we found that that right amygdala reactivity to fearful stimuli moderated the association between Irma-related media exposure and PTS symptoms, with the media-PTS association strongest for children showing pre-hurricane heightened amygdala reactivity to Fear vs Neutral Faces. In contrast, in bilateral orbitofrontal cortex and left parahippocampal gyrus, children showing a weak response to the Fear condition relative to the Neutral condition were especially susceptible to PTS as a result of Irma-related media exposure. Collectively, these findings run counter to outdated "bullseye" models of disaster exposure that assume negative effects are narrowly circumscribed around a disasters geographic epicenter9. In contrast, for some youth with measurable preexisting vulnerability, consumption of extensive disaster-related media appears to offer an alternative pathway to disaster exposure that transcends geography and objective risk. This preventable exposure should be considered in disaster-related mental health efforts.

neuroscience↗

Is there any incremental benefit to conducting neuroimaging and neurocognitive assessments in the diagnosis of ADHD in young children? A machine learning investigation.

Given the negative trajectories of early behavior problems associated with Attention-Deficit/Hyperactivity Disorder (ADHD), early diagnosis of ADHD is considered critical to enable early intervention and treatment. To this end, the current investigation employed machine learning to evaluate the relative predictive value of parent/teacher ratings, as well as behavioral and neural measures of executive function in predicting ADHD diagnostic category in a sample consisting of 162 young children (53.7% ADHD, ages 4 to 7, mean age 5.55, 67.9% male, 82.6% Hispanic/Latino). Among all the target measures assessed in the study, teacher ratings of executive function were identified as by far the most important measure in predicting ADHD diagnostic category. While a more extensive evaluation of neural measures, such as diffusion-weighted imaging, may provide more information as they relate to the underlying cognitive deficits associated with ADHD, the current study indicates that commonly used structural imaging measures of cortical thickness, as well as widely used cognitive measures of executive function, have little incremental value in differentiating typically developing children from those diagnosed with ADHD. Future research evaluating the importance of such measures in predicting childrens functional impairment in academic and social areas would provide additional insight into their contributing role in ADHD.

neuroscience↗

White matter connectivity of uncinate fasciculus and inferior fronto-occipital fasciculus: A possible early biomarker for callous-unemotional behaviors in young children with ADHD

BackgroundCallous-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 1) explore differences in the white matter microstructure in the UF and other major fiber tracks (inferior longitudinal fasciculus [ILF], inferior fronto-occipital fasciculus [IFOF], cingulum, and corticospinal tract [CST]) between young typically developing (TD) children and those with Attention-Deficit/Hyperactivity Disorder (ADHD), and 2) explore, within the ADHD group, whether individual differences in these white matter microstructures relate to co-occurring CP and CU behaviors, respectively. MethodsParticipants included 198 young children (78% boys, Mage = 4.95 years; 80% Latinx; 49% 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. ResultsRelative to TD children, children with ADHD had reduced FA on four out of the five fiber tracks we examined (except for cingulum). Within the ADHD 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 and a host of covariates including whole brain FA, CU behaviors were independently related to reduced FA in bilateral UF and left IFOF. ConclusionsThe bilateral UF and IFOF may be a biomarker of CU behaviors, even in very young children.

neuroscience↗

In vivo Restricted-Diffusion Imaging (RDI) is sensitive to differences in axonal density in typical children and adults

BackgroundThe ability to dissociate axonal density in vivo from other microstructural properties of white matter is important for the diagnosis and treatment of neurologic disease, and new methods to do so are being developed. We investigated one such method-restricted diffusion imaging (RDI)-to see whether it can more accurately replicate histological axonal density patterns in the corpus callosum (CC) of adults and children compared to diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging (NODDI), and generalized q-sampling imaging (GQI) methods. To do so, we compared known axonal density patterns defined by histology to to diffusion-weighted imaging (DWI) scans of 840 healthy 20- to 40-year-old adults, and, in a replication and extension, to DWI scans of 129 typically developing 7-month-old to 18-year-old children and adolescents. Contrast analyses were used to to compare pattern similarities between the in-vivo metric and previously-published histological density models. We found that RDI was effective at mapping axonal density of small (Cohens d= 2.60) and large fiber sizes (Cohens d= 2.84) in adults. The same pattern was observed in the developing sample (Cohens d= 3.09 and 3.78, respectively). Other metrics, notably NODDIs intracellular volume fraction (ICVF), were also sensitive to differences in axonal density across the longitudinal axis of the CC. In conclusion, the study showed that RDI is effective at measuring axonal density of small and large axons in adults and children, with both single- and multi-shell acquisition DWI data. Its effectiveness and availability to be used on standard as well as advanced DWI acquisitions makes it a promising method in clinical settings.

neuroscience↗

Image processing and analysis methods for the Adolescent Brain Cognitive Development Study

The Adolescent Brain Cognitive Development (ABCD) Study is an ongoing, nationwide study of the effects of environmental influences on behavioral and brain development in adolescents. The ABCD Study is a collaborative effort, including a Coordinating Center, 21 data acquisition sites across the United States, and a Data Analysis and Informatics Center (DAIC). The main objective of the study is to recruit and assess over eleven thousand 9-10-year-olds and follow them over the course of 10 years to characterize normative brain and cognitive development, the many factors that influence brain development, and the effects of those factors on mental health and other outcomes. The study employs state-of-the-art multimodal brain imaging, cognitive and clinical assessments, bioassays, and careful assessment of substance use, environment, psychopathological symptoms, and social functioning. The data will provide a resource of unprecedented scale and depth for studying typical and atypical development. Here, we describe the baseline neuroimaging processing and subject-level analysis methods used by the ABCD DAIC in the centralized processing and extraction of neuroanatomical and functional imaging phenotypes. Neuroimaging processing and analyses include modality-specific corrections for distortions and motion, brain segmentation and cortical surface reconstruction derived from structural magnetic resonance imaging (sMRI), analysis of brain microstructure using diffusion MRI (dMRI), task-related analysis of functional MRI (fMRI), and functional connectivity analysis of resting-state fMRI.\n\nHighlightsO_LIAn overview of the MRI processing pipeline for the ABCD Study\nC_LIO_LIA discussion on the challenges of large, multisite population studies\nC_LIO_LIA methodological reference for users of publicly shared data from the ABCD Study\nC_LI

neuroscience↗

The frontal aslant tract (FAT) and its role in speech, language and executive function

In this review, we examine the structural connectivity of a recently-identified fiber pathway, the frontal aslant tract (FAT), and explore its function. We first review structural connectivity studies using tract-tracing methods in non-human primates, and diffusion-weighted imaging and electrostimulation in humans. These studies suggest a monosynaptic connection exists between the lateral inferior frontal gyrus and the pre-supplementary and supplementary motor areas of the medial superior frontal gyrus. This connection is termed the FAT. We then review research on the left FATs putative role in supporting speech and language function, with particular focus on speech initiation, stuttering and verbal fluency. Next, we review research on the right FATs putative role supporting executive function, namely inhibitory control and conflict monitoring for action. We summarize the extant body of empirical work by suggesting that the FAT plays a domain general role in the planning, timing, and coordination of sequential motor movements through the resolution of competition among potential motor plans. However, we also propose some domain specialization across the hemispheres. On the left hemisphere, the circuit is proposed to be specialized for speech actions. On the right hemisphere, the circuit is proposed to be specialized for general action control of the organism, especially in the visuo-spatial domain. We close the review with a discussion of the clinical significance of the FAT, and suggestions for further research on the pathway.\n\nHighlightsO_LIThe frontal aslant tract (FAT) is a recently identified fiber pathway\nC_LIO_LIIt connects inferior frontal gyrus with medial frontal motor areas\nC_LIO_LIThe left FAT has been associated with speech and language function\nC_LIO_LIThe right FAT has been associated with inhibitory control\nC_LIO_LIBoth FAT pathways may function in sequential motor planning\nC_LI

neuroscience↗

Laterality of the frontal aslant tract (FAT) explains externalizing behaviors through its association with executive function.

We investigated the development of a recently-identified white matter pathway, the frontal aslant tract (FAT) and its association to executive function and externalizing behaviors in a sample of 129 neurotypical children ranging in age from 7 months to 19-years. We found that the FAT could be tracked in 92% of those children, and that the pathway showed age-related differences into adulthood. The change in white matter microstructure was very rapid until about 6-years, and then plateaued, only to show age-related increases again after the age of 11-years. In a subset of those children (5-18-years; n = 70), left laterality of the microstructural properties of the FAT was associated with greater attention problems as measured by the Child Behavior Checklist (CBCL). However, this relationship was fully mediated by higher executive dysfunction as measured by the Behavior Rating Inventory of Executive Function (BRIEF). This relationship was specific to the FAT--we found no relationship between laterality of the white matter of the brain in general and attention problems, or executive function. These findings suggest that the degree to which the developing brain favors a right lateralized structural dominance of the FAT is directly associated with executive function and attention. This novel finding provides a new potential structural biomarker to assess attention deficit hyperactivity disorder (ADHD) and associated executive dysfunction during development.\n\nSignificance StatementTo investigate the function of a recently-identified white matter fiber pathway, the frontal aslant tract (FAT), we tracked the pathway in 129 typically developing children using diffusion-weighted magnetic resonance imaging (DW-MRI). We then examined whether laterality of the tract is associated with attention problems and executive function. We found that reduced right laterality of the tract was associated with greater executive dysfunction, which predicted increased reports of attention problems. The findings suggest that the degree to which the developing brain favors a right lateralized structural dominance of the FAT is directly associated with executive function and attention. This novel finding provides a new potential structural biomarker to assess attention deficit hyperactivity disorder (ADHD) and associated executive dysfunction during development.

neuroscience↗