White matter microstructure of children with sensory over-responsivity is associated with affective behavior.

BACKGROUND: Sensory processing dysfunction (SPD) is linked to altered white matter (WM) microstructure in school-age children. Sensory over-responsivity (SOR), a form of SPD, affects at least 2.5% of all children and has substantial deleterious impact on learning and mental health. However, SOR has not been well studied using microstructural imaging such as diffusion MRI (dMRI). Since SOR involves hypersensitivity to external stimuli, we test the hypothesis that children with SOR require compensatory neuroplasticity in the form of superior WM microstructural integrity to protect against internalizing behavior, leaving those with impaired WM microstructure vulnerable to somatization and depression. METHODS: Children ages 8-12 years old with neurodevelopmental concerns were assessed for SOR using a comprehensive structured clinical evaluation, the Sensory Processing 3 Dimensions Assessment, and underwent 3 Tesla MRI with multishell multiband dMRI. Tract-based spatial statistics was used to measure diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) metrics from global WM and nineteen selected WM tracts. Correlations of DTI and NODDI measures with measures of somatization and emotional disturbance from the Behavioral Assessment System for Children, 3rd edition (BASC-3), were computed in the SOR group and in matched children with neurodevelopmental concerns but not SOR. RESULTS: Global WM fractional anisotropy (FA) is negatively correlated with somatization and with emotional disturbance in the SOR group but not the non-SOR group. Also observed in children with SOR are positive correlations of radial diffusivity (RD) and free water fraction (FISO) with somatization and, in most cases, emotional disturbance. These effects are significant in boys with SOR, whereas the study is underpowered for girls. The most affected white matter are medial lemniscus and internal capsule sensory tracts, although effects of SOR are observed in many cerebral, cerebellar, and brainstem tracts. CONCLUSION: White matter microstructure is related to affective behavior in children with SOR.

An Open-Label Study of Cranial Electrotherapy Stimulation on Behavioral Regulation in a Mixed Neurodevelopmental Clinical Cohort.

OBJECTIVE: Individuals with neurodevelopmental disorders often report disturbances in the autonomic nervous system (ANS)-related behavioral regulation, such as sensory sensitivity, anxiety, and emotion dysregulation. Cranial electrotherapy stimulation (CES) is a method of non-invasive neuromodulation presumed to modify behavioral regulation abilities via ANS modulation. Here we examined the feasibility and preliminary effects of a 4-week CES intervention on behavioral regulation in a mixed neurodevelopmental cohort of children, adolescents, and young adults. METHODS: In this single-arm open-label study, 263 individuals aged 4-24 who were receiving clinical care were recruited. Participants received at-home CES treatment using an Alpha-Stim® AID CES device for 20 minutes per day, 5-7 days per week, for four weeks. Before and after the intervention, a parent-report assessment of sensory sensitivities, emotion dysregulation, and anxiety was administered. Adherence, side effects, and tolerance of the CES device were also evaluated at follow-up. RESULTS: Results showed a 75% completion rate, an average tolerance score of 68.2 (out of 100), and an average perceived satisfaction score of 58.8 (out of 100). Additionally, a comparison between pre- and post-CES treatment effects showed a significant reduction in sensory sensitivity, anxiety, and emotion dysregulation in participants following CES treatment. CONCLUSIONS: Results provide justification for future randomized control trials using CES in children and adolescents with behavioral dysregulation. SIGNIFICANCE: CES may be a useful therapeutic tool for alleviating behavioral dysregulation symptoms in children and adolescents with neurodevelopmental differences.

Maternal hair cortisol predicts periodic and aperiodic infant frontal EEG activity longitudinally across infancy.

Maternal stress is known to be an important factor in shaping child development, yet the complex pattern of associations between stress and infant brain development remains understudied. To better understand the nuanced relations between maternal stress and infant neurodevelopment, research investigating longitudinal relations between maternal chronic physiological stress and infant brain function is warranted. In this study, we leveraged longitudinal data to disentangle between- from within-person associations of maternal hair cortisol and frontal electroencephalography (EEG) power at three time points across infancy at 3, 9, and 15 months. We analyzed both aperiodic power spectral density (PSD) slope and traditional periodic frequency band activity. On the within-person level, maternal hair cortisol was associated with a flattening of frontal PSD slope and an increase in relative frontal beta. However, on the between-person level, higher maternal hair cortisol was associated with steeper frontal PSD slope, increased relative frontal theta, and decreased relative frontal beta. The within-person findings may reflect an adaptive neural response to relative shifts in maternal stress levels, while the between-person results demonstrate the potentially detrimental effects of chronically elevated maternal stress. This analysis offers a novel, quantitative insight into the relations between maternal physiological stress and infant cortical function.

Neurophysiology of sustained attention in early infancy: Investigating longitudinal relations with recognition memory outcomes.

The ability to sustain attention is a critical cognitive domain that emerges in infancy and is predictive of a multitude of cognitive processes. Here, we used a heart rate (HR) defined measure of sustained attention to assess corresponding changes in frontal electroencephalography (EEG) power at 3 months of age. Second, we examined how the neural underpinnings of HR-defined sustained attention were associated with sustained attention engagement. Third, we evaluated if neural or behavioral sustained attention measures at 3-months predicted subsequent recognition memory scores at 9 months of age. Seventy-five infants were included at 3 months of age and provided usable attention and EEG data and 25 infants returned to the lab at 9 months and provided usable recognition memory data. The current study focuses on oscillatory power in the theta (4-6 Hz) frequency band during phases of HR-defined sustained attention and inattention phases. Results revealed that theta power was significantly higher during phases of sustained attention. Second, higher theta power during sustained attention was positively associated with proportion of time in sustained attention. Third, longitudinal analyses indicated a significant positive association between theta power during sustained attention on 9-month visual paired comparison scores such that higher theta power predicted higher visual paired comparison scores at 9-months. These results highlight the interrelation of the attention and arousal systems which have longitudinal implications for subsequent recognition memory processes.

Signal in the noise: Dimensions of predictability in the home auditory environment are associated with neurobehavioral measures of early infant sustained attention.

The home auditory environment influences the development of early language abilities, and excessive noise exposure is increasingly linked with deficits in language and reading scores in children. However, fewer studies have considered the role of noise exposure in shaping the development of attentional processing in early infancy, a foundational neurocognitive skill relevant for learning. Here, we used passive at-home auditory recording to investigate how multiple dimensions of infants' home auditory environments, including both the quantity and the predictability of auditory input, impacts neural and behavioral measures of sustained attention in a sociodemographically diverse sample of 3-month-old infants (N = 98 infants, 62 males; age M = 3.48 months, SD = 0.39; 52% Hispanic/Latino). Results indicated that infants who were exposed to more predictable patterns of auditory input in the home demonstrated longer overall time in sustained attention during laboratory assessments. In addition, infants' who experienced more predictable auditory input also demonstrated greater relative increases in electroencephalography frontal theta power during periods of sustained attention, a neural marker relevant to information processing and attentional control. These findings provide novel evidence into the importance of the predictability of early environmental inputs in shaping developing cortical circuitry and attentional systems from the first months of postnatal life.

Paid maternal leave is associated with infant brain function at 3 months of age.

The first months of life are critical for establishing neural connections relevant for social and cognitive development. Yet, the United States lacks a national policy of paid family leave during this important period of brain development. This study examined associations between paid leave and infant electroencephalography (EEG) at 3 months in a sociodemographically diverse sample of families from New York City (N = 80; 53 males; 48% Latine; data collection occurred 05/2018-12/2019). Variable-centered regression results indicate that paid leave status was related to differences in EEG power (ps < .02, R2 s > .12). Convergent results from person-centered latent profile analyses demonstrate that mothers with paid leave were 7.39 times as likely to have infants with EEG profiles characterized by increased higher-Hz power (95% CI, 1.9-36.9), potentially reflecting more mature patterns of brain activity.

Within-person changes in basal cortisol and caregiving modulate executive attention across infancy.

One pathway by which environments of socioeconomic risk are thought to affect cognitive development is through stress physiology. The biological systems underpinning stress and attention undergo a sensitive period of development during infancy. Psychobiological theory emphasizes a dynamic pattern of context-dependent development, however, research has yet to examine how basal cortisol and attention dynamically covary across infancy in ecologically valid contexts. Thus, to address these gaps, we leveraged longitudinal, multilevel analytic methods to disentangle between- from within-person associations of hypothalamic-pituitary-adrenal (HPA) axis activity and executive attention behaviors across infancy. We use data from a large longitudinal sample (N = 1,292) of infants in predominantly low-income, nonurban communities at 7-, 15-, and 24-months of age. Using multilevel models, we investigated longitudinal associations of infant attention and basal cortisol levels and examined caregiving behaviors as moderators of this relationship. Results indicated a negative between- and within-person association between attention and cortisol across infancy and a within-person moderation by caregiver responsiveness. In other words, on the within-person level, higher levels of cortisol were concomitantly associated with lower infant attention across the first 2 years of life. However, variation in the caregiver's level of responsiveness either buffered or sensitized the executive attention system to the negative effects of physiological stress.

Prenatal mother-father cortisol linkage predicts infant executive functions at 24 months.

The present study investigated associations between prenatal mother-father cortisol linkage and infant executive functions. Data come from an international sample (N = 358) of predominantly white and middle- to upper-class first-time parents. During late pregnancy, parents collected diurnal salivary cortisol samples and reported on levels of psychological stress. At 24 months, children completed a battery of executive function tasks. Parent cortisol linkage was operationalized as the time-dependent, within-dyad association between maternal and paternal diurnal cortisol. Results indicated that prenatal linkage was positively related to infant executive functions, suggesting that stronger mother-father cortisol linkage was associated with higher executive function scores. Additionally, this relation was moderated by paternal average cortisol levels such that executive function scores were lower when fathers had higher average cortisol levels and linkage was weak. This association suggests that elevated paternal cortisol amplifies the negative relation between lower cortisol linkage and lower infant executive function scores. Importantly, these findings were observed while controlling for observational measures of caregiving and self-report measures of psychosocial functioning and infant social-emotional behavior. These results suggest that prenatal linkage of mother's and father's stress physiology plays a potentially important part in programming and regulating infant neurocognitive development.

Deprivation and threat as developmental mediators in the relation between early life socioeconomic status and executive functioning outcomes in early childhood.

There has been a shift in the study of childhood adversity towards a focus on dimensions of adversity as opposed to a focus on cumulative risk or specific adversities. The Dimensional Model of Adversity and Psychopathology (DMAP) proposes deprivation and threat as core dimensions of childhood adversity. Previous work using DMAP has found links between deprivation and cognitive development and threat and emotional development in adolescence, but few studies have applied this framework to a poverty context, in which children are at heightened risk for adversity experiences, and none have examined outcomes in early childhood. We use data from the Family Life Project (n = 1292) to examine deprivation and threat at child age 24 months as developmental mediators in the association between socioeconomic status (SES) measured at 15 months and executive functions (EF) measured at 48 months. In a multiple mediation model, lower SES was related to higher deprivation and threat. Deprivation was negatively associated with EF, and threat was not associated with EF. Deprivation fully mediated association between SES and EF. These results expand previous work using the DMAP and point to new directions in understanding children's cognitive adaptations to adversity.

Joint attention partially mediates the longitudinal relation between attuned caregiving and executive functions for low-income children.

Using data from a large longitudinal sample (N = 1,292) of children and their caregivers in predominantly low-income, nonurban communities, we investigated longitudinal relations between attuned caregiving in infancy, joint attention in toddlerhood, and executive functions in early childhood. The results from path analysis demonstrated that attuned caregiving during infancy predicted more joint attention in toddlerhood, which was in turn associated with better executive function performance in early childhood. Joint attention was a stronger predictor of executive functions for lower-income families. Moreover, joint attention mediated the relation between attuned caregiving and executive functions, and this mediation was amplified for lower-income families. These results highlight joint attention as a key mechanism through which attuned caregiving supports the development of executive functions, particularly for low-income families. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Altered Cerebellar White Matter in Sensory Processing Dysfunction Is Associated With Impaired Multisensory Integration and Attention.

Sensory processing dysfunction (SPD) is characterized by a behaviorally observed difference in the response to sensory information from the environment. While the cerebellum is involved in normal sensory processing, it has not yet been examined in SPD. Diffusion tensor imaging scans of children with SPD (n = 42) and typically developing controls (TDC; n = 39) were compared for fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) across the following cerebellar tracts: the middle cerebellar peduncles (MCP), superior cerebellar peduncles (SCP), and cerebral peduncles (CP). Compared to TDC, children with SPD show reduced microstructural integrity of the SCP and MCP, characterized by reduced FA and increased MD and RD, which correlates with abnormal auditory behavior, multisensory integration, and attention, but not tactile behavior or direct measures of auditory discrimination. In contradistinction, decreased CP microstructural integrity in SPD correlates with abnormal tactile and auditory behavior and direct measures of auditory discrimination, but not multisensory integration or attention. Hence, altered cerebellar white matter organization is associated with complex sensory behavior and attention in SPD, which prompts further consideration of diagnostic measures and treatments to better serve affected individuals.

Elevated infant cortisol is necessary but not sufficient for transmission of environmental risk to infant social development: Cross-species evidence of mother-infant physiological social transmission.

Environmental adversity increases child susceptibility to disrupted developmental outcomes, but the mechanisms by which adversity can shape development remain unclear. A translational cross-species approach was used to examine stress-mediated pathways by which poverty-related adversity can influence infant social development. Findings from a longitudinal sample of low-income mother-infant dyads indicated that infant cortisol (CORT) on its own did not mediate relations between early-life scarcity-adversity exposure and later infant behavior in a mother-child interaction task. However, maternal CORT through infant CORT served as a mediating pathway, even when controlling for parenting behavior. Findings using a rodent "scarcity-adversity" model indicated that pharmacologically blocking pup corticosterone (CORT, rodent equivalent to cortisol) in the presence of a stressed mother causally prevented social transmission of scarcity-adversity effects on pup social behavior. Furthermore, pharmacologically increasing pup CORT without the mother present was not sufficient to disrupt pup social behavior. Integration of our cross-species results suggests that elevated infant CORT may be necessary, but without elevated caregiver CORT, may not be sufficient in mediating the effects of environmental adversity on development. These findings underscore the importance of considering infant stress physiology in relation to the broader social context, including caregiver stress physiology, in research and interventional efforts.

Maternal psychological stress moderates diurnal cortisol linkage in expectant fathers and mothers during late pregnancy.

Using data from a large international sample (N = 385) of first-time expectant parents, the current analysis investigated whether parents demonstrated diurnal cortisol linkage in late pregnancy and whether self-reported psychological stress moderated this linkage. At approximately 36 weeks gestation, mothers and fathers collected saliva samples in their home at three times on two consecutive days and reported on their psychological stress. Results from multilevel models indicated that there was significant positive within-couple diurnal cortisol linkage on average for the whole sample. However, this linkage was moderated by maternal self-reported psychological stress. Specifically, for couples with higher maternal psychological stress, cortisol linkage was strong. Conversely, for couples with lower maternal psychological stress, maternal and paternal cortisol were unrelated. These findings suggest that among higher-maternal-stress couples, lower paternal cortisol may buffer maternal cortisol, whereas higher paternal cortisol may amplify maternal cortisol. Our results support the idea that interpersonal psychological and physiological stress in close relationships is interdependent and mutually influenced. Further, our findings contribute to the field's understanding of interpersonal processes during pregnancy, which may have health-related implications in the prenatal and postnatal periods for both parents and the developing child.

Enhancing Executive Functions Through Social Interactions: Causal Evidence Using a Cross-Species Model.

It has long been theorized that humans develop higher mental functions, such as executive functions (EFs), within the context of interpersonal interactions and social relationships. Various components of social interactions, such as interpersonal communication, perspective taking, and conforming/adhering to social rules, may create important (and perhaps even necessary) opportunities for the acquisition and continued practice of EF skills. Furthermore, positive and stable relationships facilitate the development and maintenance of EFs across the lifespan. However, experimental studies investigating the extent to which social experiences contribute causally to the development of EFs are lacking. Here, we present experimental evidence that social experiences and the acquisition of social skills influence the development of EFs. Specifically, using a rat model, we demonstrate that following exposure to early-life adversity, a socialization intervention causally improves working memory in peri-adolescence. Our findings combined with the broader literature promote the importance of cultivating social skills in support of EF development and maintenance across the lifespan. Additionally, cross-species research will provide insight into causal mechanisms by which social experiences influence cognitive development and contribute to the development of biologically sensitive interventions.

Corticosterone administration targeting a hypo-reactive HPA axis rescues a socially-avoidant phenotype in scarcity-adversity reared rats.

It is well-established that children from low-income, under-resourced families are at increased risk of altered social development. However, the biological mechanisms by which poverty-related adversities can "get under the skin" to influence social behavior are poorly understood and cannot be easily ascertained using human research alone. This study utilized a rodent model of "scarcity-adversity," which encompasses material resource deprivation (scarcity) and reduced caregiving quality (adversity), to explore how early-life scarcity-adversity causally influences social behavior via disruption of developing stress physiology. Results showed that early-life scarcity-adversity exposure increased social avoidance when offspring were tested in a social approach test in peri-adolescence. Furthermore, early-life scarcity-adversity led to blunted hypothalamic-pituitary-adrenal (HPA) axis activity as measured via adrenocorticotropic hormone (ACTH) and corticosterone (CORT) reactivity following the social approach test. Western blot analysis of brain tissue revealed that glucocorticoid receptor levels in the dorsal (but not ventral) hippocampus and medial prefrontal cortex were significantly elevated in scarcity-adversity reared rats following the social approach test. Finally, pharmacological repletion of CORT in scarcity-adversity reared peri-adolescents rescued social behavior. Our findings provide causal support that early-life scarcity-adversity exposure negatively impacts social development via a hypocorticosteronism-dependent mechanism, which can be targeted via CORT administration to rescue social behavior.

Sustained attention in infancy: A foundation for the development of multiple aspects of self-regulation for children in poverty.

There are many avenues by which early life poverty relates to the development of school readiness. Few studies, however, have examined the extent to which sustained attention, a central component of self-regulation in infancy, mediates relations between poverty-related risk and cognitive and emotional self-regulation at school entry. To investigate longitudinal relations among poverty-related risk, sustained attention in infancy, and self-regulation prior to school entry, we analyzed data from the Family Life Project, a large prospective longitudinal sample (N = 1292) of children and their primary caregivers in predominantly low-income and nonurban communities. We used structural equation modeling to assess the extent to which a latent variable of infant sustained attention, measured in a naturalistic setting, mediated the associations between cumulative poverty-related risk and three domains of self-regulation. We constructed a latent variable of infant sustained attention composed of a measure of global sustained attention and a task-based sustained attention measure at 7 and 15 months of age. Results indicated that infant sustained attention was negatively associated with poverty-related risk and positively associated with a direct assessment of executive function abilities and teacher-reported effortful control and emotion regulation in pre-kindergarten. Mediation analysis indicated that the association between poverty-related risk and each self-regulation outcome was partially mediated by infant attention. These results provide support for a developmental model of self-regulation whereby attentional abilities in infancy act as a mechanism linking the effects of early-life socioeconomic adversity with multiple aspects of self-regulation in early childhood.

White Matter Connectome Correlates of Auditory Over-Responsivity: Edge Density Imaging and Machine-Learning Classifiers.

Sensory over-responsivity (SOR) commonly involves auditory and/or tactile domains, and can affect children with or without additional neurodevelopmental challenges. In this study, we examined white matter microstructural and connectome correlates of auditory over-responsivity (AOR), analyzing prospectively collected data from 39 boys, aged 8-12 years. In addition to conventional diffusion tensor imaging (DTI) maps - including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD); we used DTI and high-resolution T1 scans to develop connectome Edge Density (ED) maps. The tract-based spatial statistics was used for voxel-wise comparison of diffusion and ED maps. Then, stepwise penalized logistic regression was applied to identify independent variable (s) predicting AOR, as potential imaging biomarker (s) for AOR. Finally, we compared different combinations of machine learning algorithms (i.e., naïve Bayes, random forest, and support vector machine (SVM) and tract-based DTI/connectome metrics for classification of children with AOR. In direct sensory phenotype assessment, 15 (out of 39) boys exhibited AOR (with or without neurodevelopmental concerns). Voxel-wise analysis demonstrates extensive impairment of white matter microstructural integrity in children with AOR on DTI maps - evidenced by lower FA and higher MD and RD; moreover, there was lower connectome ED in anterior-superior corona radiata, genu and body of corpus callosum. In stepwise logistic regression, the average FA of left superior longitudinal fasciculus (SLF) was the single independent variable distinguishing children with AOR (p = 0.007). Subsequently, the left SLF average FA yielded an area under the curve of 0.756 in receiver operating characteristic analysis for prediction of AOR (p = 0.008) as a region-of-interest (ROI)-based imaging biomarker. In comparative study of different combinations of machine-learning models and DTI/ED metrics, random forest algorithms using ED had higher accuracy for AOR classification. Our results demonstrate extensive white matter microstructural impairment in children with AOR, with specifically lower connectomic ED in anterior-superior tracts and associated commissural pathways. Also, average FA of left SLF can be applied as ROI-based imaging biomarker for prediction of SOR. Finally, machine-learning models can provide accurate and objective image-based classifiers for identification of children with AOR based on white matter tracts connectome ED.

White Matter Microstructure Associations of Cognitive and Visuomotor Control in Children: A Sensory Processing Perspective.

Objective: Recent evidence suggests that co-occurring deficits in cognitive control and visuomotor control are common to many neurodevelopmental disorders. Specifically, children with sensory processing dysfunction (SPD), a condition characterized by sensory hyper/hypo-sensitivity, show varying degrees of overlapping attention and visuomotor challenges. In this study, we assess associations between cognitive and visuomotor control abilities among children with and without SPD. In this same context, we also examined the common and unique diffusion tensor imaging (DTI) tracts that may support the overlap of cognitive control and visuomotor control. Method: We collected cognitive control and visuomotor control behavioral measures as well as DTI data in 37 children with SPD and 25 typically developing controls (TDCs). We constructed regressions to assess for associations between behavioral performance and mean fractional anisotropy (FA) in selected regions of interest (ROIs). Results: We observed an association between behavioral performance on cognitive control and visuomotor control. Further, our findings indicated that FA in the anterior limb of the internal capsule (ALIC), the anterior thalamic radiation (ATR), and the superior longitudinal fasciculus (SLF) are associated with both cognitive control and visuomotor control, while FA in the superior corona radiata (SCR) uniquely correlate with cognitive control performance and FA in the posterior limb of the internal capsule (PLIC) and the cerebral peduncle (CP) tract uniquely correlate with visuomotor control performance. Conclusions: These findings suggest that children who demonstrate lower cognitive control are also more likely to demonstrate lower visuomotor control, and vice-versa, regardless of clinical cohort assignment. The overlapping neural tracts, which correlate with both cognitive and visuomotor control suggest a possible common neural mechanism supporting both control-based processes.

Shared and Divergent Auditory and Tactile Processing in Children with Autism and Children with Sensory Processing Dysfunction Relative to Typically Developing Peers.

The aim of this study was to compare sensory processing in typically developing children (TDC), children with Autism Spectrum Disorder (ASD), and those with sensory processing dysfunction (SPD) in the absence of an ASD. Performance-based measures of auditory and tactile processing were compared between male children ages 8-12 years assigned to an ASD (N=20), SPD (N=15), or TDC group (N=19). Both the SPD and ASD groups were impaired relative to the TDC group on a performance-based measure of tactile processing (right-handed graphesthesia). In contrast, only the ASD group showed significant impairment on an auditory processing index assessing dichotic listening, temporal patterning, and auditory discrimination. Furthermore, this impaired auditory processing was associated with parent-rated communication skills for both the ASD group and the combined study sample. No significant group differences were detected on measures of left-handed graphesthesia, tactile sensitivity, or form discrimination; however, more participants in the SPD group demonstrated a higher tactile detection threshold (60%) compared to the TDC (26.7%) and ASD groups (35%). This study provides support for use of performance-based measures in the assessment of children with ASD and SPD and highlights the need to better understand how sensory processing affects the higher order cognitive abilities associated with ASD, such as verbal and non-verbal communication, regardless of diagnostic classification.