Neurite density of the hippocampus is associated with trace eyeblink conditioning latency in 4- to 6-year-olds.

Limited options exist to evaluate the development of hippocampal function in young children. Research has established that trace eyeblink conditioning (EBC) relies on a functional hippocampus. Hence, we set out to investigate whether trace EBC is linked to hippocampal structure, potentially serving as a valuable indicator of hippocampal development. Our study explored potential associations between individual differences in hippocampal volume and neurite density with trace EBC performance in young children. We used onset latency of conditioned responses (CR) and percentage of conditioned responses (% CR) as measures of hippocampal-dependent associative learning. Using a sample of typically developing children aged 4 to 6 years (N = 30; 14 girls; M = 5.70 years), participants underwent T1- and diffusion-weighted MRI scans and completed a 15-min trace eyeblink conditioning task conducted outside the MRI. % CR and CR onset latency were calculated based on all trials involving tone-puff presentations and tone-alone trials. Findings revealed a connection between greater left hippocampal neurite density and delayed CR onset latency. Children with higher neurite density in the left hippocampus tended to blink closer to the onset of the unconditioned stimulus, indicating that structural variations in the hippocampus were associated with more precise timing of conditioned responses. No other relationships were observed between hippocampal volume, cerebellum volume or neurite density, hippocampal white matter connectivity and any EBC measures. Preliminary results suggest that trace EBC may serve as a straightforward yet innovative approach for studying hippocampal development in young children and populations with atypical development.

Direct and indirect effects of mother's spatial ability on child's spatial ability: What role does the home environment play?

Individual differences in spatial thinking are predictive of children's math and science achievement and later entry into Science, Technology, Engineering, and Mathematics (STEM) disciplines. Little is known about whether parent characteristics predict individual differences in children's spatial thinking. This study aims to understand whether, and to what extent, mother's intrinsic (i.e., mental rotation) and extrinsic (i.e., spatial scaling) spatial ability directly and indirectly, via the variation in home spatial environment, predicts children's intrinsic and extrinsic spatial ability. A total of 165 mothers and their 4-6-year-old children were recruited to participate in a remote video session with an experimenter. Mothers were administered a forced-choice Intrinsic Spatial Toy Preference Task gauging their preference for highly spatial versus less spatial toys and asked questions with the Home Intrinsic Spatial Environmental Questionnaire about the frequency with which they engage their child in spatial activities at home. Mothers completed a Mental Rotations Test and a Spatial Scaling Task adapted for adults. Children were administered the Picture Rotation Task, the Spatial Scaling Task, and the Peabody Picture Vocabulary Test. Structural equation modeling was used to examine direct and indirect, via home spatial environment and toy choices, influences of mother spatial ability on child spatial ability. Contrary to our predictions, we did not find direct, nor indirect, relations between mother and child spatial ability. These findings suggest that researchers should consider alternative conceptualizations of the early home spatial environment beyond the frequency of spatial play in the home. RESEARCH HIGHLIGHTS: The identification of factors that predict individual differences in children's spatial ability is important in order to maximize STEM learning outcomes. Data collection was conducted remotely rather than in traditional preschool or laboratory settings. Contrary to our pre-registered hypotheses, no significant relations between mother spatial ability, the early home spatial environment, and children's development of spatial skills were found. Future research should consider examining the amount of spatial language used in the home or the quality of parent-child interactions during spatial play as potential explanations for individual differences in children's spatial ability.

Family Well-Being During the COVID-19 Pandemic: The Risks of Financial Insecurity and Coping.

During the COVID-19 pandemic, families have experienced unprecedented financial and social disruptions. We studied the impact of preexisting psychosocial factors and pandemic-related financial and social disruptions in relation to family well-being among N = 4091 adolescents and parents during early summer 2020, participating in the Adolescent Brain Cognitive DevelopmentSM Study. Poorer family well-being was linked to prepandemic psychosocial and financial adversity and was associated with pandemic-related material hardship and social disruptions to routines. Parental alcohol use increased risk for worsening of family relationships, while a greater endorsement of coping strategies was mainly associated with overall better family well-being. Financial and mental health support may be critical for family well-being during and after a widespread crisis, such as the COVID-19 pandemic.

Structural and diffusion-weighted brain imaging predictors of attention-deficit/hyperactivity disorder and its symptomology in very young (4- to 7-year-old) children.

The current study aimed to identify the key neurobiology of attention-deficit/hyperactivity disorder (ADHD), as it relates to ADHD diagnostic category and symptoms of hyperactive/impulsive behaviour and inattention. To do so, we adapted a predictive modelling approach to identify the key structural and diffusion-weighted brain imaging measures and their relative standing with respect to teacher ratings of executive function (EF) (measured by the Metacognition Index of the Behavior Rating Inventory of Executive Function [BRIEF]) and negativity and emotion regulation (ER) (measured by the Emotion Regulation Checklist [ERC]), in a critical young age range (ages 4 to 7, mean age 5.52 years, 82.2% Hispanic/Latino), where initial contact with educators and clinicians typically take place. Teacher ratings of EF and ER were predictive of both ADHD diagnostic category and symptoms of hyperactive/impulsive behaviour and inattention. Among the neural measures evaluated, the current study identified the critical importance of the largely understudied diffusion-weighted imaging measures for the underlying neurobiology of ADHD and its associated symptomology. Specifically, our analyses implicated the inferior frontal gyrus as a critical predictor of ADHD diagnostic category and its associated symptomology, above and beyond teacher ratings of EF and ER. Collectively, the current set of findings have implications for theories of ADHD, the relative utility of neurobiological measures with respect to teacher ratings of EF and ER, and the developmental trajectory of its underlying neurobiology.

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

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.

Adverse childhood experiences predict neurite density differences in young children with and without attention deficit hyperactivity disorder.

Adverse childhood experiences (ACEs) put millions of children at risk for later health problems. As childhood represents a critical developmental period, it is important to understand how ACEs impact brain development in young children. In addition, children with attention-deficit/hyperactivity disorder (ADHD) are more likely than typically developing (TD) peers to experience ACEs. Therefore, the current study examined the impact of ACEs on early brain development, using a cumulative risk approach, in a large sample of children with and without ADHD. We examined 198 young children (Mage  = 5.45, 82.3% Hispanic/Latino; 52.5% ADHD) across measures of brain volume, cortical thickness, neurite density index (NDI), and orientation dispersion index (ODI). For the NDI measure, there was a significant interaction between group and cumulative risk (ß = .18, p = .048), such that for children with ADHD, but not TD children, greater cumulate risk was associated with increased NDI in corpus callosum. No other interactions were detected. Additionally, when examining across groups, greater cumulative risk was associated with reduced ODI and volume in the cerebellum, although these findings did not survive a correction for multiple comparisons. Our results highlight the role early cumulative ACEs play in brain development across TD and children with ADHD.

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

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.

Meaningful associations 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 children's 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.

Altered hippocampal microstructure and function in children who experienced Hurricane Irma.

Hurricane Irma was the most powerful Atlantic hurricane in recorded history, displacing 6 million and killing over 120 people in the state of Florida alone. Unpredictable disasters like Irma are associated with poor cognitive and health outcomes that can disproportionately impact children. This study examined the effects of Hurricane Irma on the hippocampus and memory processes previously related to unpredictable stress. We used an innovative application of an advanced diffusion-weighted imaging technique, restriction spectrum imaging (RSI), to characterize hippocampal microstructure (i.e., cell density) in 9- to 10-year-old children who were exposed to Hurricane Irma relative to a non-exposed control group (i.e., assessed the year before Hurricane Irma). We tested the hypotheses that the experience of Hurricane Irma would be associated with decreases in: (a) hippocampal cellularity (e.g., neurogenesis), based on known associations between unpredictable stress and hippocampal alterations; and (b) hippocampal-related memory function as indexed by delayed recall. We show an association between decreased hippocampal cellularity and delayed recall memory in children who experienced Hurricane Irma relative to those who did not. These findings suggest an important role of RSI for assessing subtle microstructural changes related to functionally significant changes in the developing brain in response to environmental events.

Measuring Cognitive Flexibility with the Flexible Item Selection Task: From fMRI Adaptation to Individual Connectome Mapping.

Cognitive flexibility, the ability to appropriately adjust behavior in a changing environment, has been challenging to operationalize and validate in cognitive neuroscience studies. Here, we investigate neural activation and directed functional connectivity underlying cognitive flexibility using an fMRI-adapted version of the Flexible Item Selection Task (FIST) in adults (n = 32, ages 19-46 years). The fMRI-adapted FIST was reliable, showed comparable performance to the computer-based version of the task, and produced robust activation in frontoparietal, anterior cingulate, insular, and subcortical regions. During flexibility trials, participants directly engaged the left inferior frontal junction, which influenced activity in other cortical and subcortical regions. The strength of intrinsic functional connectivity between select brain regions was related to individual differences in performance on the FIST, but there was also significant individual variability in functional network topography supporting cognitive flexibility. Taken together, these results suggest that the FIST is a valid measure of cognitive flexibility, which relies on computations within a broad corticosubcortical network driven by inferior frontal junction engagement.

The phonological loop: is speech special?

It has been proposed that the maintenance of phonological information in verbal working memory (vWM) is carried by a domain-specific short-term storage center-the phonological loop-which is composed of a phonological store and an articulatory rehearsal system. Several brain regions including the left posterior inferior frontal gyrus (pIFG) and anterior supramarginal gyri (aSMG) are thought to support these processes. However, recent behavioral evidence suggests that verbal and non-verbal auditory information may be processed as part of a unique domain general short-term storage center instead of through specialized subsystems such as the phonological loop. In the current study, we used a single-pulse transcranial magnetic stimulation (TMS)-delayed priming paradigm with speech (syllables) and acoustically complex non-speech sounds (bird songs) to examine whether the pIFG and aSMG are involved in the processing of verbal information or, alternatively, in the processing of any complex auditory information. Our results demonstrate that TMS delivered to both regions had an effect on performance for speech and non-speech stimuli, but the nature of the effect was different. That is, priming was reduced for the speech sounds because TMS facilitated the detection of different but not identical stimuli, and accuracy was decreased for non-speech sounds. Since TMS interfered with both speech and non-speech sounds, these findings support the existence of an auditory short-term storage center located within the dorsal auditory stream.

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 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 is a resource of unprecedented scale and depth for studying typical and atypical development. The aim of this manuscript is to describe the baseline neuroimaging processing and subject-level analysis methods used by ABCD. 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. This manuscript serves as a methodological reference for users of publicly shared neuroimaging data from the ABCD Study.

The role of the arcuate and middle longitudinal fasciculi in speech perception in noise in adulthood.

In this article, we used High Angular Resolution Diffusion Imaging (HARDI) with advanced anatomically constrained particle filtering tractography to investigate the role of the arcuate fasciculus (AF) and the middle longitudinal fasciculus (MdLF) in speech perception in noise in younger and older adults. Fourteen young and 15 elderly adults completed a syllable discrimination task in the presence of broadband masking noise. Mediation analyses revealed few effects of age on white matter (WM) in these fascicles but broad effects of WM on speech perception, independently of age, especially in terms of sensitivity and criterion (response bias), after controlling for individual differences in hearing sensitivity and head size. Indirect (mediated) effects of age on speech perception through WM microstructure were also found, after controlling for individual differences in hearing sensitivity and head size, with AF microstructure related to sensitivity, response bias and phonological priming, and MdLF microstructure more strongly related to response bias. These findings suggest that pathways of the perisylvian region contribute to speech processing abilities, with relatively distinct contributions for the AF (sensitivity) and MdLF (response bias), indicative of a complex contribution of both phonological and cognitive processes to age-related speech perception decline. These results provide new and important insights into the roles of these pathways as well as the factors that may contribute to elderly speech perception deficits. They also highlight the need for a greater focus to be placed on studying the role of WM microstructure to understand cognitive aging.

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 with executive function and externalizing behaviors in a sample of 129 neurotypical male and female human 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 a control pathway, or of the white matter of the brain in general, and attention and 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.

Fiber pathways supporting early literacy development in 5-8-year-old children.

The development of fluent reading is an extended process that requires the recruitment of a comprehensive system of perisylvian brain regions connected by an extensive network of fiber pathways. In the present cross-sectional study, we focused on fiber pathways-the arcuate fasciculus (AF), inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF), and vertical occipital fasciculus (VOF)-proposed to support early literacy in typical 5-8-year-old children. We related quantitative metrics of fiber pathway microstructure in these pathways to early literacy measures of phonological awareness and decoding. We found that diffusion properties of the AF, ILF, and VOF not only show age-related differences, but also are predictive of early literacy skills after controlling for the effects of age, general white matter development, sex, IQ, and phonological skill. Perhaps most novel, we provide evidence supporting the involvement of the recently re-identified VOF in early literacy, and further, we provide evidence that a bilateral network of fiber pathways supports early literacy development.

Interhemispheric functional connectivity following prenatal or perinatal brain injury predicts receptive language outcome.

Early brain injury alters both structural and functional connectivity between the cerebral hemispheres. Despite increasing knowledge on the individual hemispheric contributions to recovery from such injury, we know very little about how their interactions affect this process. In the present study, we related interhemispheric structural and functional connectivity to receptive language outcome following early left hemisphere stroke. We used functional magnetic resonance imaging to study 14 people with neonatal brain injury, and 25 age-matched controls during passive story comprehension. With respect to structural connectivity, we found that increased volume of the corpus callosum predicted good receptive language outcome, but that this is not specific to people with injury. In contrast, we found that increased posterior superior temporal gyrus interhemispheric functional connectivity during story comprehension predicted better receptive language performance in people with early brain injury, but worse performance in typical controls. This suggests that interhemispheric functional connectivity is one potential compensatory mechanism following early injury. Further, this pattern of results suggests refinement of the prevailing notion that better language outcome following early left hemisphere injury relies on the contribution of the contralesional hemisphere (i.e., the "right-hemisphere-take-over" theory). This pattern of results was also regionally specific; connectivity of the angular gyrus predicted poorer performance in both groups, independent of brain injury. These results present a complex picture of recovery, and in some cases, such recovery relies on increased cooperation between the injured hemisphere and homologous regions in the contralesional hemisphere, but in other cases, the opposite appears to hold.

Frontal and temporal contributions to understanding the iconic co-speech gestures that accompany speech.

In everyday conversation, listeners often rely on a speaker's gestures to clarify any ambiguities in the verbal message. Using fMRI during naturalistic story comprehension, we examined which brain regions in the listener are sensitive to speakers' iconic gestures. We focused on iconic gestures that contribute information not found in the speaker's talk, compared with those that convey information redundant with the speaker's talk. We found that three regions-left inferior frontal gyrus triangular (IFGTr) and opercular (IFGOp) portions, and left posterior middle temporal gyrus (MTGp)--responded more strongly when gestures added information to nonspecific language, compared with when they conveyed the same information in more specific language; in other words, when gesture disambiguated speech as opposed to reinforced it. An increased BOLD response was not found in these regions when the nonspecific language was produced without gesture, suggesting that IFGTr, IFGOp, and MTGp are involved in integrating semantic information across gesture and speech. In addition, we found that activity in the posterior superior temporal sulcus (STSp), previously thought to be involved in gesture-speech integration, was not sensitive to the gesture-speech relation. Together, these findings clarify the neurobiology of gesture-speech integration and contribute to an emerging picture of how listeners glean meaning from gestures that accompany speech.

The development of cognitive flexibility beyond the preschool period: an investigation using a modified Flexible Item Selection Task.

We explored the development of cognitive flexibility in typically developing 6-, 8-, and 10-year-olds and adults by modifying a common cognitive flexibility task, the Flexible Item Selection Task (FIST). Although performance on the standard FIST reached ceiling by 8 years, FIST performance on other variations continued to improve until 10 years of age. Within a detailed task analysis, we also explored working memory storage and processing components of executive function and how these contribute to the development of cognitive flexibility. The findings reinforce the notion that cognitive flexibility is a multifaceted construct but that the development of working memory contributes in part to age-related change in this ability.

Does it talk the talk? On the role of basal ganglia in emotive speech processing.

Ackermann et al.'s phylogenetic account of speech argues that the basal ganglia imbue speech with emotive content. However, a body of work on auditory/emotive processing is inconsistent with attributing this function exclusively to these structures. The account further overlooks the possibility that the emotion-integration function may be at least in part mediated by the cortico-ponto-cerebellar system.

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.