Diagnostic Group Differences Research Articles

Deliberate synchronization of speech and gesture: effects of neurodiversity and development

Abstract The production of speech and gesture is exquisitely temporally coordinated. In autistic individuals, speech-gesture synchrony during spontaneous discourse is disrupted. To evaluate whether this asynchrony reflects motor coordination versus language production processes, the current study examined deliberately performed hand movements during speech in youth with autism spectrum disorder (ASD) compared to neurotypical youth. Neurotypical adult performance provided a mature baseline. Participants read aloud rhythmic nursery rhymes, while producing a beat-like hand movement. An automated pixel-change video measure identified kinematic peaks; using smoothed acoustic envelope analyses, we identified peaks in speech. Results indicated few diagnostic group differences in explicit speech-movement coordination, although adolescent performance differed from adults. Adults demonstrated higher tempo and greater rhythmicity in their coordination; this group difference suggests that the method is sufficiently subtle to reveal individual differences and that this form of complex coordination undergoes ongoing maturation beyond adolescence. The sample is small, and thus results are necessarily preliminary. In the context of prior speech-gesture coordination studies, these findings of intact synchrony are consistent with the hypothesis that it is the demands of discourse planning, rather than motor coordination, that have led to prior findings of asynchrony during spontaneous speech; this possibility awaits future research.

Location-based differences in cognition and functional capacity: Consistent levels of impairment in participants with schizophrenia compared to healthy controls

Cognitive performance manifests regional differences, correlated with education. There is less information available about regional differences in performance-based measures of functional capacity. In multi-national trials focused on cognitive enhancement, it may be impossible to validate every measure in all locations. It is unknown if regional differences in healthy controls’ (HC) performance affects relative levels of impairment in participants with schizophrenia (SCZ). A multi-site study comparing SCZ and HC administered the MATRICS Consensus Cognitive Battery (MCCB) and Virtual Reality Functional Capacity Assessment Tool (VRFCAT) to 164 HC participants and 164 with SCZ across three sites (Columbia, SC, Miami, and San Diego) and a representative sample of HC (n = 390) completed the VRFCAT in Durham, NC. Performance was compared between HC and SCZ participants at the validation sites. There were statistically significant cross-site differences in HC performance on both the MCCB and VRFCAT. Differences between HC and SCZ on MCCB and VRFCAT were substantial at all three sites, indicating that regional variations in HC performance did not induce reduced differences from SCZ participants. Regional differences were smaller than diagnostic group differences, suggesting that relative impairments of participants with SCZ is consistently preserved across performance differences in HC.

Categorizing and identifying preferred interests in autistic toddlers.

Preferred interests are characteristic of autism spectrum disorder and are reported by parents starting at an early age. However, limited research has explored the presentation of preferred interests in toddlerhood. Previous literature suggests that both the intensity and type of preferred interests held by autistic individuals differ from those held by peers with developmental delay and no diagnosis and that autistic interests are more unusual in nature. While preferred interests are seen in typical child development, previous research suggests that the presence of preferred interests in children with no diagnosis declines with age. Literature also indicates that the sex and cognitive ability of autistic children influences preferred interests. Identification of early preferred interests commonly held by autistic toddlers could serve as a useful clinical indicator of future diagnosis. This article explored whether diagnostic group, age, sex, and cognitive ability predict the likelihood that parents reported preferred interests in children aged 12-36 months with diagnoses of autism, developmental delay, and those with no diagnosis. Additionally, we explored potential diagnostic group differences in interest type. Results suggest that diagnostic group, but not age, sex, or cognitive ability, predicts the likelihood that parents report preferred interests. No differences in the type of interests among diagnostic groups were identified. These results support the use of preferred interests as an early sign of autism but suggest that interest type may not be a helpful clinical indicator of autism in toddlerhood.

Microstructural neural correlates of maximal grip strength in autistic children: the role of the cortico-cerebellar network and attention-deficit/hyperactivity disorder features.

Maximal grip strength, a measure of how much force a person's hand can generate when squeezing an object, may be an effective method for understanding potential neurobiological differences during motor tasks. Grip strength in autistic individuals may be of particular interest due to its unique developmental trajectory. While autism-specific differences in grip-brain relationships have been found in adult populations, it is possible that such differences in grip-brain relationships may be present at earlier ages when grip strength is behaviorally similar in autistic and non-autistic groups. Further, such neural differences may lead to the later emergence of diagnostic-group grip differences in adolescence. The present study sought to examine this possibility, while also examining if grip strength could elucidate the neuro-motor sources of phenotypic heterogeneity commonly observed within autism. Using high resolution, multi-shell diffusion, and quantitative R1 relaxometry imaging, this study examined how variations in key sensorimotor-related white matter pathways of the proprioception input, lateral grasping, cortico-cerebellar, and corticospinal networks were associated with individual variations in grip strength in 68 autistic children and 70 non-autistic (neurotypical) children (6-11 years-old). In both groups, results indicated that stronger grip strength was associated with higher proprioceptive input, lateral grasping, and corticospinal (but not cortico-cerebellar modification) fractional anisotropy and R1, indirect measures concordant with stronger microstructural coherence and increased myelination. Diagnostic group differences in these grip-brain relationships were not observed, but the autistic group exhibited more variability particularly in the cortico-cerebellar modification indices. An examination into the variability within the autistic group revealed that attention-deficit/hyperactivity disorder (ADHD) features moderated the relationships between grip strength and both fractional anisotropy and R1 relaxometry in the premotor-primary motor tract of the lateral grasping network and the cortico-cerebellar network tracts. Specifically, in autistic children with elevated ADHD features (60% of the autistic group) stronger grip strength was related to higher fractional anisotropy and R1 of the cerebellar modification network (stronger microstructural coherence and more myelin), whereas the opposite relationship was observed in autistic children with reduced ADHD features. Together, this work suggests that while the foundational elements of grip strength are similar across school-aged autistic and non-autistic children, neural mechanisms of grip strength within autistic children may additionally depend on the presence of ADHD features. Specifically, stronger, more coherent connections of the cerebellar modification network, which is thought to play a role in refining and optimizing motor commands, may lead to stronger grip in children with more ADHD features, weaker grip in children with fewer ADHD features, and no difference in grip in non-autistic children. While future research is needed to understand if these findings extend to other motor tasks beyond grip strength, these results have implications for understanding the biological basis of neuromotor control in autistic children and emphasize the importance of assessing co-occurring conditions when evaluating brain-behavior relationships in autism.

Hypothalamic Subunit Volumes in Schizophrenia and Bipolar Spectrum Disorders.

The hypothalamus is central to many hormonal and autonomous nervous system pathways. Emerging evidence indicates that these pathways may be disrupted in schizophrenia and bipolar disorder. Yet, few studies have examined the volumes of hypothalamic subunits in these patient groups. We compared hypothalamic subunit volumes in individuals with psychotic disorders to healthy controls. We included 344 patients with schizophrenia spectrum disorders (SCZ), 340 patients with bipolar disorders (BPD), and 684 age- and-sex-matched healthy controls (CTR). Total hypothalamus and five hypothalamic subunit volumes were extracted from T1-weighted magnetic resonance imaging (MRI) using an automated Bayesian segmentation method. Regression models, corrected for age, age2, sex, and segmentation-based intracranial volume (sbTIV), were used to examine diagnostic group differences, interactions with sex, and associations with clinical symptoms, antipsychotic medication, antidepressants and mood stabilizers. SCZ had larger volumes in the left inferior tubular subunit and smaller right anterior-inferior, right anterior-superior, and right posterior hypothalamic subunits compared to CTR. BPD did not differ significantly from CTR for any hypothalamic subunit volume, however, there was a significant sex-by-diagnosis interaction. Analyses stratified by sex showed smaller right hypothalamus and right posterior subunit volumes in male patients, but not female patients, relative to same-sex controls. There was a significant association between BPD currently taking antipsychotic medication and the left inferior tubular subunits volumes. Our results show regional-specific alterations in hypothalamus subunit volumes in individuals with SCZ, with relevance to HPA-axis dysregulation, circadian rhythm disruption, and cognition impairment.

Social motivation by self- and caregiver-report: Reporter concordance and social correlates among autistic and neurotypical youth.

Differences in social motivation underlie the core social-communication features of autism according to several theoretical models, with decreased social motivation among autistic youth relative to neurotypical peers. However, research on social motivation often relies on caregiver reports and rarely includes firsthand perspectives of children and adolescents with autism. Furthermore, social motivation is typically assumed to be constant across social settings when it may actually vary by social context. Among a sample of 58 verbally fluent youth (8-13 years old; 22 with autism, 36 neurotypical), we examined correspondence between youth and caregiver reports of social motivation with peers and with adults, as well as diagnostic group differences and associations with social outcomes. Results suggest youth and caregivers provide overlapping but distinct information. Autistic youth had lower levels of social motivation relative to neurotypical youth, and reported relatively consistent motivation toward peers and adults. Youth self- and caregiver-report were correlated for motivation toward adults, but not toward peers. Despite low correspondence between self- and caregiver-reported motivation toward peers, autistic youths' self-report corresponded to caregiver-reported social skills and difficulties whereas caregiver-report of peer motivation did not. For neurotypical youth, self- and caregiver-reported motivation toward adults was correlated, but motivation by both reporters was largely independent of broader social outcomes. Findings highlight the unique value of self-report among autistic children and adolescents, and warrant additional work exploring the development, structure, and correlates of social motivation among autistic and neurotypical youth.

Amyloid PET across the cognitive spectrum in former professional and college American football players: findings from the DIAGNOSE CTE Research Project

BackgroundExposure to repetitive head impacts (RHI) in American football players can lead to cognitive impairment and dementia due to neurodegenerative disease, particularly chronic traumatic encephalopathy (CTE). The pathognomonic lesion of CTE consists of perivascular aggregates of hyper-phosphorylated tau in neurons at the depths of cortical sulci. However, it is unclear whether exposure to RHI accelerates amyloid-β (Aβ) plaque formation and increases the risk for Alzheimer’s disease (AD). Although the Aβ neuritic plaques characteristic of AD are observed in a minority of later-stage CTE cases, diffuse plaques are more common. This study examined whether former professional and college American football players, including those with cognitive impairment and dementia, have elevated neuritic Aβ plaque density, as measured by florbetapir PET. Regardless of cognitive and functional status, elevated levels of florbetapir uptake were not expected.MethodsWe examined 237 men ages 45–74, including 119 former professional (PRO) and 60 former college (COL) football players, with and without cognitive impairment and dementia, and 58 same-age men without a history of contact sports or TBI (unexposed; UE) and who denied cognitive or behavioral symptoms at telephone screening. Former players were categorized into four diagnostic groups: normal cognition, subjective memory impairment, mild cognitive impairment, and dementia. Positive florbetapir PET was defined by cortical-cerebellar average SUVR of ≥ 1.10. Multivariable linear regression and analysis of covariance (ANCOVA) compared florbetapir average SUVR across diagnostic and exposure groups. Multivariable logistic regression compared florbetapir positivity. Race, education, age, and APOE4 were covariates.ResultsThere were no diagnostic group differences either in florbetapir average SUVR or the proportion of elevated florbetapir uptake. Average SUVR means also did not differ between exposure groups: PRO-COL (p = 0.94, 95% C.I. = [− 0.033, 0.025]), PRO-UE (p = 0.40, 95% C.I. = [− 0.010, 0.029]), COL-UE (p = 0.36, 95% CI = [0.0004, 0.039]). Florbetapir was not significantly associated with years of football exposure, cognition, or daily functioning.ConclusionsCognitive impairment in former American football players is not associated with PET imaging of neuritic Aβ plaque deposition. These findings are inconsistent with a neuropathological diagnosis of AD in individuals with substantial RHI exposure and have both clinical and medico-legal implications.Trial registrationNCT02798185.

Diagnostic group differences and exploratory sex differences in intrinsic connectivity during fMRI Stroop in individuals with and without cocaine use disorder

BackgroundSex-/gender-related differences in cognitive control and how they relate to addictions may inform novel treatment options. Cognitive control, including Stroop performance, has been linked to addictions and treatment outcomes. The extent to which women and men with cocaine use disorder (CUD) show brain and behavioral differences relating to Stroop performance has not been previously studied. We examined sex-related differences in Stroop-related brain connectivity in female and male CUD and healthy-comparison (HC) subjects. Methods40 individuals with CUD (20 female) and 40 HC (20 female) subjects matched on age, race, and ethnicity completed an fMRI Stroop task. Intrinsic connectivity distribution (ICD) and mean-adjusted ICD analyses were conducted to identify differences related to sex and diagnostic group. Stroop task performance was also considered. ResultsBehavioral results confirmed a Stroop effect. A main effect of diagnostic group indicated that the CUD versus HC group showed lower connectivity in the prefrontal cortex, frontal gyrus, cingulate gyrus, precuneus, cerebellum, and somatosensory, visual, and auditory areas. An exploratory main effect of sex suggested that males may show relatively lower connectivity than females in the cerebellum and brainstem, although connectivity was largely similar across sexes. ConclusionsIntrinsic connectivity during cognitive control varied by diagnostic group and possibly by sex. The findings suggest that interventions targeting cognitive control in CUD should consider sex.

Altered Sex Differences in Hippocampal Subfield Volumes in Schizophrenia.

The hippocampus is a heterogenous brain structure that differs between the sexes and has been implicated in the pathophysiology of psychiatric illnesses. Here, we explored sex and diagnostic group differences in hippocampal subfield volumes, in individuals with schizophrenia spectrum disorder (SZ), bipolar disorders (BD), and healthy controls (CTL). One thousand and five hundred and twenty-one participants underwent T1-weighted magnetic resonance imaging (SZ, n = 452, mean age 30.7 ± 9.2 [SD] years, males 59.1%; BD, n = 316, 33.7 ± 11.4, 41.5%; CTL, n = 753, 34.1 ± 9.1, 55.6%). Total hippocampal, subfield, and intracranial volumes were estimated with Freesurfer (v6.0.0). Analysis of covariance and multiple regression models were fitted to examine sex-by-diagnostic (sub)group interactions in volume. In SZ and BD, separately, associations between volumes and clinical as well as cognitive measures were examined between the sexes using regression models. Significant sex-by-group interactions were found for the total hippocampus, dentate gyrus, molecular layer, presubiculum, fimbria, hippocampal-amygdaloid transition area, and CA4, indicating a larger volumetric deficit in male patients relative to female patients when compared with same-sex CTL. Subgroup analyses revealed that this interaction was driven by males with schizophrenia. Effect sizes were overall small (partial η < 0.02). We found no significant sex differences in the associations between hippocampal volumes and clinical or cognitive measures in SZ and BD. Using a well-powered sample, our findings indicate that the pattern of morphological sex differences in hippocampal subfields is altered in individuals with schizophrenia relative to CTL, due to higher volumetric deficits in males.

Sex differences in atypical fronto-subcortical structural connectivity among children with attention-deficit/hyperactivity disorder: Associations with delay discounting

PurposeAtypical fronto-subcortical neural circuitry has been implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD), including connections between prefrontal cortical regions involved in top-down cognitive control and subcortical limbic structures (striatum and amygdala) involved in bottom-up reward and emotional processing. The integrity of fronto-subcortical connections may also relate to interindividual variability in delay discounting, or a preference for smaller, immediate over larger, delayed rewards, which is associated with ADHD, with recent evidence of ADHD-related sex differences. MethodsWe applied diffusion tensor imaging to compare the integrity of the white matter connections within fronto-subcortical tracts among 187 8–12 year-old children either with ADHD ((n = 106; 29 girls) or typically developing (TD) controls ((n = 81; 28 girls). Analyses focused on diagnostic group differences in fractional anisotropy (FA) within fronto-subcortical circuitry implicated in delay discounting, connecting subregions of the striatum (dorsal executive and ventral limbic areas) and amygdala with prefrontal regions of interest (dorsolateral [dlPFC], orbitofrontal [OFC] and anterior cingulate cortex [ACC]), and associations with two behavioral assessments of delay discounting. ResultsChildren with ADHD showed reduced FA in tracts connecting OFC with ventral striatum, regardless of sex, whereas reduced FA in the OFC-amygdala and ventral ACC-amygdala tracts were specific to boys with ADHD. Across diagnostic groups and sex, reduced FA in the dorsal ACC-executive striatum tract correlated with greater game time delay discounting. ConclusionsThese results suggest a potential neurobiological substrate of heightened delay discounting in children with ADHD and support the need for additional studies including larger sample sizes of girls with ADHD to further elucidate ADHD-related sex differences in these relationships.

Experiences of and recommendations on clinical trial design in Alzheimer’s disease from the participant’s point of view: a mixed-methods study in two clinical trial centers in the Netherlands

IntroductionIn the context of the development of pharmaceutical interventions, expectations and experiences of participants are essential. Their insights may be particularly helpful to address the challenges of recruiting and retaining participants for Alzheimer’s disease (AD) clinical trials. We examined clinical trial participants’ experiences to optimize trial design in Alzheimer’s disease (AD).MethodIn this mixed-methods study, we included adults who participated in sponsor-initiated AD trials at Brain Research Center, a clinical trial organization in the Netherlands. Participants (N = 71, age 69 ± 6.5, 54%F, 19 cognitively normal (CN), 19 mild cognitive impairment (MCI), and 33 AD dementia) first completed an online survey. Diagnostic group differences were investigated using chi-square tests or one-way ANOVAs. Next, a subsample (N = 12; 8 = CN, 4 = MCI) participated in focus groups to gain in-depth insight into their opinions on optimizing trial design from a participants’ point of view. Audio recordings from focus group interviews were transcribed verbatim and analyzed by thematic content analysis by two independent researchers.ResultsMost reported motives for enrolment included “to benefit future generations” (89%), followed by “for science” (66%) and “better monitoring” (42%). Frequent suggestions for increasing willingness to participate included a smaller chance to receive placebo (n = 38, 54%), shorter travel times (n = 27, 38%), and sharing individual results of different assessments (n = 57, 80%), as well as receiving trial results (n = 52, 73). Highest visual analogue burden scores (0–100) were found for the lumbar puncture (M = 47.2, SD = 38.2) and cognitive assessments (M = 27.2, SD = 25.7). Results did not differ between diagnostic groups, nor between patient and caregiver participants (all p-values>.05). Two additional themes emerged from the focus groups: “trial design,” such as follow-up visit(s) after participating, and “trial center,” including the relevance of a professional and empathic staff.ConclusionRelevant factors include expectation management and careful planning of high-burden assessments, provision of individual feedback, and prioritizing professionalism and empathy throughout conduct of the trial. Our findings provide insight into participants’ priorities to increase willingness to participate and can be used to optimize trial success.

Topics and timing of sexuality and relationship education for autistic and non-autistic adults in the United States

IntroductionSexuality and relationship education is a learning area that historically has been overlooked, especially for autistic individuals. To inform future programming, we are in need of evidence-based reasoning to guide program design, such as what to cover and when. In particular, the social aspects of sexuality and relationship education, which are less commonly addressed, need further scrutiny. ObjectiveTo identify sexuality and relationship education priorities and timelines based on feedback from autistic and non-autistic adults. MethodsAn online anonymous survey of adults in the United States posed questions about sexuality and relationship education, sexual and relationship experiences, and autistic traits. ResultsComparisons by diagnostic group (autistic and non-autistic) revealed no significant differences in the timing of sexual experiences. Autistic individuals were significantly more likely to indicate that they wanted to learn more about gender identity, sexual orientation, consent, and assertiveness than non-autistic peers. However, the majority of all participants across diagnostic groups wanted more information across all surveyed topics. ConclusionsLack of differences in timing of sexuality-related experiences highlights the importance of beginning sexuality and relationship education early for all learners. Important diagnostic group differences highlight critical areas of development for sexuality and relationship education programming. The importance of incorporating needs of autistic learners into program design is highlighted for future work. Overall findings support the idea that more sexuality and relationship education across the lifespan would best meet the learning needs of all people.

Central Posterior Envelopes for Bayesian Functional Principal Component Analysis.

Bayesian methods provide direct inference in functional data analysis applications without reliance on bootstrap techniques. A major tool in functional data applications is the functional principal component analysis which decomposes the data around a common mean function and identifies leading directions of variation. Bayesian functional principal components analysis (BFPCA) provides uncertainty quantification on the estimated functional model components via the posterior samples obtained. We propose central posterior envelopes (CPEs) for BFPCA based on functional depth as a descriptive visualization tool to summarize variation in the posterior samples of the estimated functional model components, contributing to uncertainty quantification in BFPCA. The proposed BFPCA relies on a latent factor model and targets model parameters within a mixed effects modeling framework using modified multiplicative gamma process shrinkage priors on the variance components. Functional depth provides a center-outward order to a sample of functions. We utilize modified band depth and modified volume depth for ordering of a sample of functions and surfaces, respectively, to derive at CPEs of the mean and eigenfunctions within the BFPCA framework. The proposed CPEs are showcased in extensive simulations. Finally, the proposed CPEs are applied to the analysis of a sample of power spectral densities (PSD) from resting state electroencephalography (EEG) where they lead to novel insights on diagnostic group differences among children diagnosed with autism spectrum disorder and their typically developing peers across age.

Diagnostic group differences in return to work and subsequent detachment from employment following cardiovascular disease: a nationwide cohort study.

Return to work and employment maintenance following cardiovascular disease (CVD) are important rehabilitation goals for people of working age. To identify people in particular need of vocational rehabilitation, we examined differences in return to work and subsequent detachment from employment among people with atrial fibrillation (AF), heart failure (HF), heart valve disease, and ischaemic heart disease. We conducted a nationwide cohort study and included all individuals of working age (35-65 years) who were employed when diagnosed with incident CVD in 2018. We estimated sex- and age-standardized probabilities of remaining employed at 3, 6, and 12 months after diagnosis, and of detachment from employment within 6 months after having returned to work. Of 46 912 individuals diagnosed in 2018, 8187 were of working age and employed at diagnosis. The mean age was 54.7 years (SD = 6.7), and 74.0% were men. Within 1 year, 89.8% had returned to work, but within the subsequent 6 months, 23.5% of these experienced detachment from employment. At 3, 6, and 12 months after diagnosis the highest standardized probability of being employed was found among people with AF, whereas the lowest probability was found among people with HF {78.9% [95% confidence interval (CI): 77.3-80.4] vs. 62.2% [95% CI: 59.0-65.4] at 12 months}. Similarly, the highest probability of detachment was found for people with HF [30.3% (95% CI: 26.9-33.7)]. People with HF present the highest probability of not returning to work. There is a need for developing and documenting effects of vocational rehabilitation strategies within comprehensive cardiac rehabilitation programmes.

Individual Differences in Multisensory Attention Skills in Children with Autism Spectrum Disorder Predict Language and Symptom Severity: Evidence from the Multisensory Attention Assessment Protocol (MAAP).

Children with autism spectrum disorders (ASD) show atypical attention, particularly for social events. The new Multisensory Attention Assessment Protocol (MAAP) assesses fine-grained individual differences in attention disengagement, maintenance, and audiovisual matching for social and nonsocial events. We investigated the role of competing stimulation on attention, and relations with language and symptomatology in children with ASD and typical controls. Findings revealed: (1) the MAAP differentiated children with ASD from controls, (2) greater attention to social events predicted better language for both groups and lower symptom severity in children with ASD, (3) different pathways from attention to language were evident in children with ASD versus controls. The MAAP provides an ideal attention assessment for revealing diagnostic group differences and relations with outcomes.

An unsupervised machine learning approach using passive movement data to understand depression and schizophrenia

IntroductionSchizophrenia and Major Depressive Disorder (MDD) are highly burdensome mental disorders, with significant cost to both individuals and society. Despite these disorders representing distinct clinical categories, they are each heterogenous in their symptom profiles, with considerable transdiagnostic features. Although movement and sleep abnormalities exist in both disorders, little is known of the precise nature of these changes longitudinally. Passively-collected longitudinal data from wearable sensors is well suited to characterize naturalistic features which may cross traditional diagnostic categories (e.g., highlighting behavioral markers not captured by self-report information). MethodsThe present analyses utilized raw minute-level actigraphy data from three diagnostic groups: individuals with schizophrenia (N = 23), individuals with depression (N = 22), and controls (N = 32), respectively, to interrogate naturalistic behavioral differences between groups. Subjects' week-long actigraphy data was processed without diagnostic labels via unsupervised machine learning clustering methods, in order to investigate the natural bounds of psychopathology. Further, actigraphic data was analyzed across time to determine timepoints influential in model outcomes. ResultsWe find distinct actigraphic phenotypes, which differ between diagnostic groups, suggesting that unsupervised clustering of naturalistic data aligns with existing diagnostic constructs. Further, we found statistically significant inter-group differences, with depressed persons showing the highest behavioral variability. LimitationsHowever, diagnostic group differences only consider biobehavioral trends captured by raw actigraphy information. ConclusionsPassively-collected movement information combined with unsupervised deep learning algorithms shows promise in identifying naturalistic phenotypes in individuals with mental health disorders, specifically in discriminating between MDD and schizophrenia.

Infants later diagnosed with autism have lower canonical babbling ratios in the first year of life

BackgroundCanonical babbling—producing syllables with a mature consonant, full vowel, and smooth transition—is an important developmental milestone that typically occurs in the first year of life. Some studies indicate delayed or reduced canonical babbling in infants at high familial likelihood for autism spectrum disorder (ASD) or who later receive an ASD diagnosis, but evidence is mixed. More refined characterization of babbling in the first year of life in infants with high likelihood for ASD is needed.MethodsVocalizations produced at 6 and 12 months by infants (n = 267) taking part in a longitudinal study were coded for canonical and non-canonical syllables. Infants were categorized as low familial likelihood (LL), high familial likelihood diagnosed with ASD at 24 months (HL-ASD) or not diagnosed (HL-Neg). Language delay was assessed based on 24-month expressive and receptive language scores. Canonical babble ratio (CBR) was calculated by dividing the number of canonical syllables by the number of total syllables. Generalized linear (mixed) models were used to assess the relationship between group membership and CBR, controlling for site, sex, and maternal education. Logistic regression was used to assess whether canonical babbling ratios at 6 and 12 months predict 24-month diagnostic outcome.ResultsNo diagnostic group differences in CBR were detected at 6 months, but HL-ASD infants produced significantly lower CBR than both the HL-Neg and LL groups at 12 months. HL-Neg infants with language delay also showed reduced CBR at 12 months. Neither 6- nor 12-month CBR was significant predictors of 24-month diagnostic outcome (ASD versus no ASD) in logistic regression.LimitationsSmall numbers of vocalizations produced by infants at 6 months may limit the reliability of CBR estimates. It is not known if results generalize to infants who are not at high familial likelihood, or infants from more diverse racial and socioeconomic backgrounds.ConclusionsLower canonical babbling ratios are apparent by the end of the first year of life in ASD regardless of later language delay, but are also observed for infants with later language delay without ASD. Canonical babbling may lack specificity as an early marker when used on its own.

Frontal corticostriatal functional connectivity reveals task positive and negative network dysregulation in relation to ADHD, sex, and inhibitory control

Frontal corticostriatal circuits (FCSC) are involved in self-regulation of cognition, emotion, and motor function. While these circuits are implicated in attention-deficit/hyperactivity disorder (ADHD), the literature establishing FCSC associations with ADHD is inconsistent. This may be due to study variability in considerations of how fMRI motion regression was handled between groups, or study specific differences in age, sex, or the striatal subregions under investigation. Given the importance of these domains in ADHD it is crucial to consider the complex interactions of age, sex, striatal subregions and FCSC in ADHD presentation and diagnosis. In this large-scale study of 362 8–12 year-old children with ADHD (n = 165) and typically developing (TD; n = 197) children, we investigate associations between FCSC with ADHD diagnosis and symptoms, sex, and go/no-go (GNG) task performance. Results include: (1) increased striatal connectivity with age across striatal subregions with most of the frontal cortex, (2) increased frontal-limbic striatum connectivity among boys with ADHD only, mostly in default mode network (DMN) regions not associated with age, and (3) increased frontal-motor striatum connectivity to regions of the DMN were associated with greater parent-rated inattention problems, particularly among the ADHD group. Although diagnostic group differences were no longer significant when strictly controlling for head motion, with motion possibly reflecting the phenotypic variance of ADHD itself, the spatial distribution of all symptom, age, sex, and other ADHD group effects were nearly identical to the initial results. These results demonstrate differential associations of FCSC between striatal subregions with the DMN and FPN in relation to age, ADHD, sex, and inhibitory control.

Beier Sentence Completion Test Profiles of Adolescents and Emerging Adults With Internalizing and Externalizing Disorders

Background: Understanding adolescents' and emerging adults' psychiatric complaints and their relations with psychiatric disorders can be challenging. Beier Sentence Completion Test (BSCT), as a projective test, can be promising in this respect. However, relations between BSCT profiles and adolescent psychopathology are not well known. Aim: This study aimed to examine and compare BSCT profiles of adolescents and emerging adults with internalizing and externalizing disorders. As well as that, the relation of BSCT profiles with depression and anxiety scores was investigated. Objective: To achieve this aim, we retrospectively collected the hospital records of 300 adolescents and emerging adults (aged. 14-21) admitted to an Adolescent Psychiatry Outpatient Unit. Method: The psychiatric diagnosis of the patients was classified as Internalizing (n = 100) and Externalizing (n = 100) disorder groups; the control group (n = 100) consisted of adolescents and young adults without any psychiatric diagnosis. BSCT, the Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) were administered on the first admission to all cases before psychiatric evaluation and treatment. BSCT total subfactor (positive, negative, neutral, and non-response) statement scores were compared between groups, and their correlations with BDI and BAI were investigated. Besides, multivariate logistic regression analyses were conducted for estimating any diagnostic group differences, as well as bivariate logistic regression analyses for estimating BDI and BAI cutoff scores with models that included BSCT total subfactor statement scores. Results: It was revealed that lower positive and non-response statements were crucial for distinguishing externalizing and internalizing disorders and that positive and negative statements were correlated with depression and anxiety scores.In the multivariate regression model, these correlations were predictive only for the relationship between internalizing disorders group and low positive statement scores, not higher negative statement scores that can be associated with lack of positive emotional processing in this group. Also, nonresponse statement scores were found to be predictive for externalizing disorder groups. Similarly, BDI cut-off scores were predicted with low positive statement scores. Conclusion: BSCT profiles can be promising for understanding adolescents and emerging adults with internalizing and externalizing disorders. Lack of positive attributions to the self and other domains of life can be important for differentiating adolescent psychopathology.

Comparison of diffusion weighted, imaging‐derived, fractional anisotropy with a novel MRI contrast‐weighted ratio method for measuring myelin in older adults at risk for Alzheimer’s disease

AbstractBackgroundMRI measures sensitive to myelin integrity have been investigated as potential AD biomarkers. T1‐weighted/T2‐weighted ratio is a simple yet informative measure, but many cohorts have transitioned to only T1‐weighted and T2‐weighted Fluid Attenuated Inversion Recovery (FLAIR) acquisitions. We previously obtained similar results using FLAIR instead of T2 (T1w/T2FLAIRw). Our goal now is to compare T1w/T2FLAIRw to fractional anisotropy (FA) from diffusion weighted imaging (DWI).MethodPearson’s correlations of T1w/T2FLAIRw and FA values of hippocampal white matter (WM) integrity were calculated in two independent cohorts acquired on different scanners: Cohort 1 (21 CN; 7 SCD; 20 MCI; 4 AD) and Cohort 2 (40 CN; 43 SCD; 45 MCI; 20 AD). Image‐processing algorithms were designed in‐house, building on previous methods and implemented using SPM12 and FSL dtifit. Diagnostic group differences were assessed in both cohorts using one‐way ANOVA and independent sample T‐tests with Tukey correction.ResultCohort 1 demonstrated significant correlation of WM integrity values between methods in the left hippocampus (p=.002) and approached significance in the right (p = .074). Between‐group analyses showed significant differences in left hippocampal WM between cognitively unimpaired (CU [CN and SCD]) and cognitively impaired (CI [MCI and AD]) groups, with follow‐up tests showing differences between CN and AD patients in both methods. Right hippocampal T1w/T2FLAIRw ratio values showed significant differences between CU and CI, though no significant diagnostic group differences. Right hippocampal FA values were not significant.Cohort 2 demonstrated significant bilateral correlation between imaging methods (p &lt; .001), with bilateral significant differences between CU and CI groups in both methods. CN and MCI right hippocampal values were significantly different from each other in both methods. Box plots demonstrated clear similarities in patterns of diagnostic profile between methods.ConclusionA similar overall pattern was observed across the T1w/T2FLAIRw and DWI‐FA methods. This may reflect myelin disruption although further studies are needed to address source of signal differences on imaging. Differences in FA effect sizes for the hippocampus across samples and scanners merits further exploration.