ORCID Profile
0000-0001-9519-209X
Current Organisations
Centre for Addiction and Mental Health
,
University of Toronto
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Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.PNPBP.2017.11.008
Abstract: Although recent studies revealed impaired self-regulation (dysregulation) in autism spectrum disorder (ASD), neural correlates of dysregulation and its impacts on autistic neuroanatomy remain unclear. Voxel-based morphometry was applied on structural MRI images in 81 ASD and 61 typically developing (TD) boys aged 7-17years. Dysregulation was defined by the sum of T-scores of Attention, Aggression, and Anxiety/Depression subscales in the Child Behavior Checklist>180. There were 53 and 28 boys in the ASD+Dysregulation and ASD-Dysregulation groups, respectively. First, we compared regional gray matter (GM) volume for ASD and TD. Second, we investigated regional GM volumetric differences among the ASD+Dysregulation, ASD-Dysregulation and TD groups. Lastly, shared and distinct neurostructural correlates of dysregulation were investigated in the ASD and TD groups. The ASD-TD difference on neuroanatomy no longer existed after controlling the dysregulation severity. ASD+Dysregulation had larger regional GM volumes in the right fusiform gyrus, and smaller GM volumes in the anterior prefrontal cortex than ASD-Dysregulation and TD, respectively. ASD+Dysregulation had smaller GM volumes in the left lateral occipital/superior parietal cortex than TD boys. No GM difference was identified between ASD-Dysregulation and TD. ASD and TD had a shared association between GM volumes in the orbitofrontal cortex and dysregulation levels. Our findings suggest that atypical neuroanatomy associated with ASD might partially reflect a disproportionate level of impaired self-regulation. Categorical and dimensional considerations of dysregulation should be implemented in future ASD studies.
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.PNPBP.2018.11.008
Abstract: Altered inter-regional structural connectivity related to higher cognitive functions has been commonly reported in in iduals with autism spectrum disorder (ASD). However, whether these alterations similarly involve cortico-cerebellar motor circuitries remains largely elusive. Using a cross-modality approach accounting for in-scanner motion levels, we investigated white matter (WM) properties in motor circuits of 55 boys with ASD (aged 8-18 years) and 68 age-matched typically developing boys. Regional WM volumes in the primary motor, supplementary motor, somatosensory, and cerebellar areas were investigated using voxel-based morphometry. Diffusion spectrum imaging tractography was used to estimate WM integrity of the corticospinal, cortico-ponto-cerebellar (including fronto-ponto-cerebellar and parieto-ponto-cerebellar), and dentato-rubro-thalamo-cortical tracts. The reaction time test in the Cambridge Neuropsychological Test Automated Battery was used to assess motor performances. Boys with ASD had shorter movement time, increased WM volumes in the left somatosensory area, but decreased generalized fractional anisotropy value in the left parieto-ponto-cerebellar tract, compared to controls. A positive correlation between movement time and microstructural properties of the left parieto-ponto-cerebellar tract was found in boys with ASD. As the first study to demonstrate altered WM properties in the left somatosensory area, and its descending pathway connecting to the cerebellum in ASD, current results may highlight a potential new target of interventions for motor performance in ASD.
Publisher: Springer Science and Business Media LLC
Date: 31-10-2019
DOI: 10.1038/S41380-019-0554-6
Abstract: Adults with childhood-onset attention-deficit hyperactivity disorder (ADHD) show altered whole-brain connectivity. However, the relationship between structural and functional brain abnormalities, the implications for the development of life-long debilitating symptoms, and the underlying mechanisms remain uncharted. We recruited a unique s le of 80 medication-naive adults with a clinical diagnosis of childhood-onset ADHD without psychiatric comorbidities, and 123 age-, sex-, and intelligence-matched healthy controls. Structural and functional connectivity matrices were derived from diffusion spectrum imaging and multi-echo resting-state functional MRI data. Hub, feeder, and local connections were defined using diffusion data. In idual-level measures of structural connectivity and structure-function coupling were used to contrast groups and link behavior to brain abnormalities. Computational modeling was used to test possible neural mechanisms underpinning observed group differences in the structure-function coupling. Structural connectivity did not significantly differ between groups but, relative to controls, ADHD showed a reduction in structure-function coupling in feeder connections linking hubs with peripheral regions. This abnormality involved connections linking fronto-parietal control systems with sensory networks. Crucially, lower structure-function coupling was associated with higher ADHD symptoms. Results from our computational model further suggest that the observed structure-function decoupling in ADHD is driven by heterogeneity in neural noise variability across brain regions. By highlighting a neural cause of a clinically meaningful breakdown in the structure-function relationship, our work provides novel information on the nature of chronic ADHD. The current results encourage future work assessing the genetic and neurobiological underpinnings of neural noise in ADHD, particularly in brain regions encompassed by fronto-parietal systems.
Publisher: Cambridge University Press (CUP)
Date: 09-08-2013
DOI: 10.1017/S0033291713001955
Abstract: Increased intra-in idual variability (IIV) in reaction time (RT) across various tasks is one ubiquitous neuropsychological finding in attention deficit hyperactivity disorder (ADHD). However, neurobiological underpinnings of IIV in in iduals with ADHD have not yet been fully delineated. The ex-Gaussian distribution has been proved to capture IIV in RT. The authors explored the three parameters [ μ (mu), σ (sigma), τ (tau)] of an ex-Gaussian RT distribution derived from the Conners' continuous performance test (CCPT) and their correlations with the microstructural integrity of the frontostriatal–caudate tracts and the cingulum bundles. We assessed 28 youths with ADHD (8–17 years 25 males) and 28 age-, sex-, IQ- and handedness-matched typically developing (TD) youths using the CCPT, Wechsler Intelligence Scale for Children, 3rd edition and magnetic resonance imaging (MRI). Microstructural integrity, indexed by generalized fractional anisotropy (GFA), was measured by diffusion spectrum imaging tractrography on a 3-T MRI system. Youths with ADHD had larger σ ( s.d. of Gaussian distribution) and τ (mean of exponential distribution) and reduced GFA in four bilateral frontostriatal tracts. With increased inter-stimulus intervals of CCPT, the magnitude of greater τ in ADHD than TD increased. In ADHD youths, the cingulum bundles and frontostriatal integrity were associated with three ex-Gaussian parameters and with μ (mean of Gaussian distribution) and τ , respectively while only frontostriatal GFA was associated with μ and τ in TD youths. Our findings suggest the crucial role of the integrity of the cingulum bundles in accounting for IIV in ADHD. Involvement of different brain systems in mediating IIV may relate to a distinctive pathophysiological processing and/or adaptive compensatory mechanism.
Publisher: SAGE Publications
Date: 13-07-2020
Abstract: Objective: This study examined preschoolers with teacher-reported or parent-reported situational hyperactivity, and whether they differed in terms of behavioral problems, attentional problems, and parenting perceptions. Method: We used the Conners’ Kiddie Continuous Performance Test and the Color Flanker Task to assess 99 preschoolers with pervasive high-ADHD-symptoms (42), school-situational high-ADHD-symptoms (30), or home-situational high-ADHD-symptoms (27), plus 111 preschoolers with pervasive low-ADHD-symptoms. Parents and teachers reported externalizing/internalizing behavioral problems. Parenting perceptions were measured with the Parenting Stress Index-Short Form and a parenting perceptions scale. Results: Preschoolers with school-situational high-ADHD-symptoms had deficits in attentional control. Parents of preschoolers with home-situational high-ADHD-symptoms had higher levels of parental stress and perceived their parenting to be harsher. Preschoolers with pervasive high-ADHD-symptoms had deficits in attentional control, increased parental stress, and parents with harsher parenting perceptions. Conclusion: Preschoolers with situational high-ADHD-symptoms may have different contextual risk factors related to ADHD symptoms reported by parents versus teachers.
Publisher: Springer Science and Business Media LLC
Date: 12-02-2019
DOI: 10.1038/S41398-019-0418-5
Abstract: Structural neuroimaging studies suggest altered brain maturation in autism spectrum disorder (ASD) compared with typically developing controls (TDC). However, the prognostic value of whole-brain structural connectivity analysis in ASD has not been established. Diffusion magnetic imaging data were acquired in 27 high-functioning young ASD participants (2 females) and 29 age-matched TDC (12 females age 8–18 years) at baseline and again following 3–7 years. Whole-brain structural connectomes were reconstructed from these data and analyzed using a longitudinal statistical model. We identified distinct patterns of widespread brain connections that exhibited either significant increases or decreases in connectivity over time ( p 0.001). There was a significant interaction between diagnosis and time in brain development ( p 0.001). This was expressed by a decrease in structural connectivity within the frontoparietal network—and its broader connectivity—in ASD during adolescence and early adulthood. Conversely, these connections increased with time in TDC. Crucially, stronger baseline connectivity in this subnetwork predicted a lower symptom load at follow-up ( p = 0.048), independent of the expression of symptoms at baseline. Our findings suggest a clinically meaningful relationship between the atypical development of frontoparietal structural connections and the dynamics of the autism phenotype through early adulthood. These results highlight a potential marker of future outcome.
Publisher: Elsevier BV
Date: 08-2021
DOI: 10.1016/J.PNPBP.2021.110325
Abstract: Emotion dysregulation (ED) is prevalent in youths with attention-deficit hyperactivity disorder (ADHD) and causes more social impairment and poor adaptive function. Alterations in the integrity of white matter (WM) tracts might have important implications for affective processing related to ED. However, little is known about the WM correlates underpinning ED in ADHD. Using diffusion spectrum image tractography, we obtained generalized fractional anisotropy (GFA) values of 76 WM tracts in 77 children with ADHD and 105 typically developing controls (TDC). ED severity was defined by the dysregulation profile from the child behavior checklist. Canonical correlation analysis (CCA) was performed to identify modes that relate WM microstructural property to ED severity and cognitive measures. The application of CCA identified one significant mode (r = 0.638, FWE-corrected p = 0.046) of interdependencies between WM property patterns and diagnosis, ADHD total symptom levels, dysregulation by diagnosis interaction, and full-scale intellectual quotient (FIQ). GFA values of 19 WM tracts that were linked to affective-processing, sensory-processing and integration, and cognitive control circuitry were positively correlated with ED severity in TDC but negatively correlated with ED severity in ADHD. ADHD symptom severity and diagnosis were negatively associated with the GFA patterns of this set of tract bundles. In contrast, FIQ was positively correlated with this set of tract bundles. This study used the CCA to show that children with ADHD and TDC had distinct multivariate associations between ED severity (diagnosis by ED interaction) and microstructural property in a set of WM tracts. These tracts interconnect the cortical regions that are principally involved in emotion processing, integration, and cognitive control in multiple brain systems. The WM microstructure integrity impairment might be an essential correlate of emotion dysregulation in ADHD.
Publisher: Wiley
Date: 15-09-2016
DOI: 10.1002/HBM.23367
Publisher: Cold Spring Harbor Laboratory
Date: 19-09-2017
DOI: 10.1101/190660
Abstract: Childhood-onset attention-deficit hyperactivity disorder (ADHD) in adults is clinically heterogeneous and commonly presents with different patterns of cognitive deficits. It is unclear if this clinical heterogeneity expresses a dimensional or categorical difference in ADHD. We first studied differences in functional connectivity in multi-echo resting-state functional magnetic resonance imaging (rs-fMRI) acquired from 80 medication-naïve adults with ADHD and 123 matched healthy controls. We then used canonical correlation analysis (CCA) to identify latent relationships between symptoms and patterns of altered functional connectivity (dimensional biotype) in patients. Clustering methods were implemented to test if the in idual associations between resting-state brain connectivity and symptoms reflected a non-overlapping categorical biotype. Adults with ADHD showed stronger functional connectivity compared to healthy controls, predominantly between the default-mode, cingulo-opercular and subcortical networks. CCA identified a single mode of brain-symptom co-variation, corresponding to an ADHD dimensional biotype. This dimensional biotype is characterized by a unique combination of altered connectivity correlating with symptoms of hyperactivity-impulsivity, inattention, and intelligence. Clustering analyses did not support the existence of distinct categorical biotypes of adult ADHD. Overall, our data advance a novel finding that the reduced functional segregation between default-mode and cognitive control networks supports a clinically important dimensional biotype of childhood-onset adult ADHD. Despite the heterogeneity of its presentation, our work suggests that childhood-onset adult ADHD is a single disorder characterized by dimensional brain-symptom mediators.
Publisher: Wiley
Date: 23-05-2023
DOI: 10.1002/AUR.2954
Abstract: Although previous open‐label trials suggest the therapeutic potential of inhibitory repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) in autism spectrum disorder (ASD), methodological caveats exist. We conducted an 8‐week randomized, double‐blind sham‐controlled trial to investigate the efficacy of inhibitory continuous theta burst stimulation (cTBS, a variant of rTMS) over the left DLPFC in in iduals with ASD. Sixty children, adolescents and young adults (aged 8–30 years) with ASD without co‐occurring intellectual disabilities were randomized to a 16‐session 8‐week cTBS versus sham stimulation course, with a follow‐up 4 weeks after the trial. The Active group was not superior to the Sham group in any clinical or neuropsychological metrics at Week 8 or Week 12. Time effects of 8‐week cTBS on symptoms and executive function were remarkable in both Active and Sham groups, with comparable response rates and effect sizes of changes in symptoms/cognition between groups. Our results from a sufficiently powered s le do not endorse the superior efficacy of cTBS over the left DLPFC to the shamed stimulation for children, adolescents and adults with ASD. These findings suggest that earlier positive open‐label trial findings may be generalized by generalized lacebo effects. This highlights the urgent need for more rTMS/TBS studies with rigorous trial designs in ASD.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2012
Publisher: Cambridge University Press (CUP)
Date: 04-2015
DOI: 10.1017/S135561771500020X
Abstract: The frontoparietal control network, anatomically and functionally interposed between the dorsal attention network and default mode network, underpins executive control functions. In iduals with attention-deficit/hyperactivity disorder (ADHD) commonly exhibit deficits in executive functions, which are mainly mediated by the frontoparietal control network. Involvement of the frontoparietal control network based on the anterior prefrontal cortex in neurobiological mechanisms of ADHD has yet to be tested. We used resting-state functional MRI and seed-based correlation analyses to investigate functional connectivity of the frontoparietal control network in a s le of 25 children with ADHD (7–14 years mean 9.94±1.77 years 20 males), and 25 age-, sex-, and performance IQ-matched typically developing (TD) children. All participants had limited in-scanner head motion. Spearman’s rank correlations were used to test the associations between altered patterns of functional connectivity with clinical symptoms and executive functions, measured by the Conners’ Continuous Performance Test and Spatial Span in the Cambridge Neuropsychological Test Automated Battery. Compared with TD children, children with ADHD demonstrated weaker connectivity between the right anterior prefrontal cortex (PFC) and the right ventrolateral PFC, and between the left anterior PFC and the right inferior parietal lobule. Furthermore, this aberrant connectivity of the frontoparietal control network in ADHD was associated with symptoms of impulsivity and opposition-defiance, as well as impaired response inhibition and attentional control. The findings support potential integration of the disconnection model and the executive dysfunction model for ADHD. Atypical frontoparietal control network may play a pivotal role in the pathophysiology of ADHD. ( JINS , 2015, 21 , 271–284)
Publisher: American Psychiatric Association Publishing
Date: 08-2021
Publisher: Springer Science and Business Media LLC
Date: 06-2017
Publisher: Springer Science and Business Media LLC
Date: 08-10-2019
DOI: 10.1038/S41380-019-0545-7
Abstract: The norepinephrine transporter gene (SLC6A2) and deficits in visual memory and attention were associated with attention-deficit/hyperactivity disorder (ADHD). The present study aimed to examine whether the SLC6A2 rs36011 (T)/rs1566652 (G) haplotype affected the intrinsic brain activity in children with ADHD and whether these gene-brain modulations were associated with visual memory and attention in this population. A total of 96 drug-naive children with ADHD and 114 typically developing children (TDC) were recruited. We analyzed intrinsic brain activity with regional homogeneity (ReHo) and degree centrality (DC). Visual memory and visual attention were assessed by the delayed matching to s le (DMS) and rapid visual information processing (RVIP) tasks, respectively. The SNP genotyping of rs36011 and rs1566652 was performed. Children with ADHD showed lower ReHo and DC in the cuneus and lingual gyri than TDC. The TG haplotype was associated with significantly increased DC in the right precentral and postcentral gyri. Significant interactions of ADHD status and the TG haplotype were found in the right postcentral gyrus and superior parietal lobule for ReHo. For the ADHD-TG group, we found significant correlations of performance on the DMS and RVIP tasks with ReHo in bilateral precentral-postcentral gyri and the right postcentral gyrus-superior parietal lobule and DC in bilateral precentral-postcentral gyri. A novel gene-brain-behavior association was identified in which the intrinsic brain activity of the sensorimotor and dorsal attention networks was related to visual memory and visual attention in ADHD children with the SLC6A2 rs36011 (T)/rs1566652 (G) haplotype.
Publisher: Springer Science and Business Media LLC
Date: 18-05-2022
DOI: 10.1186/S13229-022-00499-1
Abstract: Neuroimage literature of autism spectrum disorder (ASD) has a moderate-to-high risk of bias, partially because those combined with intellectual impairment (II) and/or minimally verbal (MV) status are generally ignored. We aimed to provide more comprehensive insights into white matter alterations of ASD, inclusive of in iduals with II (ASD-II-Only) or MV expression (ASD-MV). Sixty-five participants with ASD (ASD-Whole 16.6 ± 5.9 years comprising 34 intellectually able youth, ASD-IA, and 31 intellectually impaired youth, ASD-II, including 24 ASD-II-Only plus 7 ASD-MV) and 38 demographic-matched typically developing controls (TDC 17.3 ± 5.6 years) were scanned in accelerated diffusion-weighted MRI. Fixel-based analysis was undertaken to investigate the categorical differences in fiber density (FD), fiber cross section (FC), and a combined index (FDC), and brain symptom/cognition associations. ASD-Whole had reduced FD in the anterior and posterior corpus callosum and left cerebellum Crus I, and smaller FDC in right cerebellum Crus II, compared to TDC. ASD-IA, relative to TDC, had no significant discrepancies, while ASD-II showed almost identical alterations to those from ASD-Whole vs. TDC. ASD-II-Only had greater FD/FDC in the isthmus splenium of callosum than ASD-MV. Autistic severity negatively correlated with FC in right Crus I. Nonverbal full-scale IQ positively correlated with FC/FDC in cerebellum VI. FD/FDC of the right dorsolateral prefrontal cortex showed a diagnosis-by-executive function interaction. We could not preclude the potential effects of age and sex from the ASD cohort, although statistical tests suggested that these factors were not influential. Our results could be confounded by variable psychiatric comorbidities and psychotropic medication uses in our ASD participants recruited from outpatient clinics, which is nevertheless closer to a real-world presentation of ASD. The outcomes related to ASD-MV were considered preliminaries due to the small s le size within this subgroup. Finally, our study design did not include intellectual impairment-only participants without ASD to disentangle the mixture of autistic and intellectual symptoms. ASD-associated white matter alterations appear driven by in iduals with II and potentially further by MV. Results suggest that changes in the corpus callosum and cerebellum are key for psychopathology and cognition associated with ASD. Our work highlights an essential to include understudied subpopulations on the spectrum in research.
Publisher: Oxford University Press (OUP)
Date: 16-09-2015
DOI: 10.1093/IJNP/PYV094
Publisher: Mary Ann Liebert Inc
Date: 04-2020
Publisher: Springer Science and Business Media LLC
Date: 21-05-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 22-12-2021
Publisher: Elsevier BV
Date: 08-2022
Publisher: Mary Ann Liebert Inc
Date: 09-2015
Abstract: The efficacy of both methylphenidate and atomoxetine has been established in placebo-controlled trials. The present study aimed to directly compare the efficacy of methylphenidate and atomoxetine in improving symptoms among children with attention-deficit/hyperactivity disorder (ADHD). The study s le included 160 drug-naïve children and adolescents 7-16 years of age, with DSM-IV-defined ADHD, randomly assigned to osmotic-release oral system methylphenidate (OROS-methylphenidate) (n=80) and atomoxetine (n=80) in a 24 week, open-label, head-to-head clinical trial. The primary efficacy measure was the score of the ADHD Rating Scale-IV Parents Version: Investigator Administered and Scored (ADHD-RS-IV). The secondary efficacy measures included the Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) and Chinese Swanson, Nolan, and Pelham IV scale (SNAP-IV), based on the ratings of investigators, parents, teachers, and subjects. At week 24, mean changes in ADHD-RS-IV Inattention scores were 13.58 points (Cohen's d, -3.08) for OROS-methylphenidate and 12.65 points (Cohen's d, -3.05) for atomoxetine and mean changes in ADHD-RS-IV Hyperactivity-Impulsivity scores were 10.16 points (Cohen's d, -1.75) for OROS-methylphenidate and 10.68 points (Cohen's d, -1.87) for atomoxetine. In terms of parent-, teacher-, and self-ratings on behavioral symptoms, both of the two treatment groups significantly decreased on the SNAP-IV scores at the end-point, with effect sizes ranging from 0.9 to 0.96 on the Inattention subscale and from 0.61 to 0.8 on the Hyperactivity/Impulsivity subscale for OROS-methylphenidate and from 0.51 to 0.88 on the Inattention subscale and from 0.29 to 0.57 on the Hyperactivity/Impulsivity subscale for atomoxetine. No statistically significant differences between treatment groups were observed on the outcome measures. Vomiting, somnolence, and dizziness were reported more often for atomoxetine than for OROS-methylphenidate, whereas insomnia was reported more often for OROS-methylphenidate than for atomoxetine. After 24 weeks of treatment, OROS-methylphenidate and atomoxetine had comparable efficacy in reducing core ADHD symptoms in drug-naïve children and adolescents with ADHD.
Publisher: Springer Science and Business Media LLC
Date: 11-01-2021
DOI: 10.1186/S12888-021-03040-5
Abstract: Despite the effectiveness of methylphenidate for treating ADHD, up to 30% of in iduals with ADHD show poor responses to methylphenidate. Neuroimaging biomarkers to predict medication responses remain elusive. This study characterized neuroanatomical features that differentiated between clinically good and poor methylphenidate responders with ADHD. Using a naturalistic observation design selected from a larger cohort, we included 79 drug-naive in iduals (aged 6–42 years) with ADHD without major psychiatric comorbidity, who had acceptable baseline structural MRI data quality. Based on a retrospective chart review, we defined responders by in iduals’ responses to at least one-month treatment with methylphenidate. A nonparametric mass-univariate voxel-based morphometric analysis was used to compare regional gray matter volume differences between good and poor responders. A multivariate pattern recognition based on the support vector machine was further implemented to identify neuroanatomical indicators to predict an in idual’s response. 63 and 16 in iduals were classified in the good and poor responder group, respectively. Using the small-volume correction procedure based on the hypothesis-driven striatal and default-mode network masks, poor responders had smaller regional volumes of the left putamen as well as larger precuneus volumes compared to good responders at baseline. The machine learning approach identified that volumetric information among these two regions alongside the left frontoparietal regions, occipital lobes, and posterior/inferior cerebellum could predict clinical responses to methylphenidate in in iduals with ADHD. Our results suggest regional striatal and precuneus gray matter volumes play a critical role in mediating treatment responses in in iduals with ADHD.
Publisher: Springer Science and Business Media LLC
Date: 22-07-2020
DOI: 10.1007/S11682-020-00338-Y
Abstract: Attention-deficit hyperactivity disorder (ADHD) has a high prevalence of co-occurring with emotion dysregulation (ED). Youths with ADHD and ED are more likely to have increased functional impairment. There is accumulating research on defining the features, behavioral, and physiological manifestations of ED, but there are currently few studies elucidating neuroanatomical correlations of ED in ADHD. Structural magnetic resonance imaging data from 118 children (aged 7-18 years) with ADHD (50 ADHD+high ED, 68 ADHD+low ED), and 104 typically developing controls (TDC) were processed using voxel-based morphometry. We used both dichotomous and continuous indices of ED to examine the possible correspondence between ED and ADHD. Relative to ADHD+high ED, ADHD+low ED had greater gray matter (GM) volumes over the left anterior prefrontal cortex (PFC). ADHD+low ED and ADHD+high ED shared a negative association of ED levels with the left middle temporal pole GM volume. TDC and ADHD+low ED also shared negative relationships of ED levels with the right temporal volume, and positive relationships with the left dorsolateral PFC volume. Besides, ED-by-group interactions were also noted. Specifically, medial PFC GM volumes increased and decreased with ED severity in ADHD+low ED and ADHD+high ED, respectively and left cerebellum Crus GM volumes decreased and increased with ED severity in ADHD+low ED and ADHD+high ED, respectively. Our findings add to the evidence that some specific neural correlates are underpinning ED across ADHD and TDC. These findings suggest the importance of incorporating ED problems when considering heterogeneity in studies of ADHD.
Publisher: Cambridge University Press (CUP)
Date: 13-02-2018
DOI: 10.1017/S0033291718000144
Abstract: The dopamine transporter gene ( DAT1 ) and visual memory deficits have been consistently reported to be associated with attention-deficit/hyperactivity disorder (ADHD). This study aimed to examine whether a DAT1 haplotype affected functional and structural brain alterations in children with ADHD and whether those alterations were associated with visual memory. We recruited a total of 37 drug-naïve children with ADHD (17 with the DAT1 rs27048 (C)/rs429699 (T) haplotype and 20 without the CT haplotype) and 37 typically developing children (17 with the CT haplotype and 20 without the CT haplotype). Visual memory was assessed by the pattern recognition memory (PRM) and spatial recognition memory (SRM) tasks. We analyzed functional and structural brain architecture with regional homogeneity (ReHo) and gray matter volume (GMV). The CT haplotype was associated with decreased ReHo in the left superior occipital gyrus, cuneus, and precuneus and decreased GMV in the left superior occipital gyrus, cuneus, and precuneus, and in the right angular gyrus. Significant interactions of ADHD and the CT haplotype were found in the right postcentral gyrus for ReHo and in the right supplementary motor area for GMV. For the ADHD-CT group, we found negative correlations of total correct responses in PRM and SRM and positive correlations of mean latency of correct responses in PRM with the GMV in the left superior occipital gyrus, cuneus, and precuneus. Our findings suggest that the DAT1 -related GMV alterations in the posterior cortical regions may contribute to visual memory performance in children with ADHD.
Publisher: Springer Science and Business Media LLC
Date: 06-07-2022
DOI: 10.1038/S41380-022-01636-1
Abstract: The neurodevelopmental model of schizophrenia is supported by multi-level impairments shared among schizophrenia and neurodevelopmental disorders. Despite schizophrenia and typical neurodevelopmental disorders, i.e., autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), as disorders of brain dysconnectivity, no study has ever elucidated whether whole-brain white matter (WM) tracts integrity alterations overlap or erge between these three disorders. Moreover, whether the linked dimensions of cognition and brain metrics per the Research Domain Criteria framework cut across diagnostic boundaries remains unknown. We aimed to map deviations from normative ranges of whole-brain major WM tracts for in idual patients to investigate the similarity and differences among schizophrenia (281 patients subgrouped into the first-episode, subchronic and chronic phases), ASD (175 patients), and ADHD (279 patients). Sex-specific WM tract normative development was modeled from diffusion spectrum imaging of 626 typically developing controls (5-40 years). There were three significant findings. First, the patterns of deviation and idiosyncrasy of WM tracts were similar between schizophrenia and ADHD alongside ASD, particularly at the earlier stages of schizophrenia relative to chronic stages. Second, using the WM deviation patterns as features, schizophrenia cannot be separated from neurodevelopmental disorders in the unsupervised machine learning algorithm. Lastly, the canonical correlation analysis showed schizophrenia, ADHD, and ASD shared linked cognitive dimensions driven by WM deviations. Together, our results provide new insights into the neurodevelopmental facet of schizophrenia and its brain basis. In idual's WM deviations may contribute to erse arrays of cognitive function along a continuum with phenotypic expressions from typical neurodevelopmental disorders to schizophrenia.
Publisher: Cold Spring Harbor Laboratory
Date: 11-04-2019
DOI: 10.1101/606228
Abstract: Adults with childhood-onset attention-deficit hyperactivity disorder (ADHD) show altered whole-brain connectivity. However, the relationship between structural and functional brain abnormalities, the implications for the development of life-long debilitating symptoms, and the underlying mechanisms remain uncharted. We recruited a unique s le of 80 medication-naive adults with a clinical diagnosis of childhood-onset ADHD without psychiatric comorbidities, and 123 age-, sex-, and intelligence-matched healthy controls. Structural and functional connectivity matrices were derived from diffusion spectrum imaging and multi-echo resting-state functional MRI data. Hub, feeder, and local connections were defined using diffusion data. In idual-level measures of structural connectivity and structure-function coupling were used to contrast groups and link behavior to brain abnormalities. Computational modeling was used to test possible neural mechanisms underpinning observed group differences in the structure-function coupling. Structural connectivity did not significantly differ between groups but, relative to controls, ADHD showed a reduction in structure-function coupling in feeder connections linking hubs with peripheral regions. This abnormality involved connections linking fronto-parietal control systems with sensory networks. Crucially, lower structure-function coupling was associated with higher ADHD symptoms. Results from our computational model further suggest that the observed structure-function decoupling in ADHD is driven by heterogeneity in neural noise variability across brain regions. By highlighting a neural cause of a clinically meaningful breakdown in the structure-function relationship, our work provides novel information on the nature of chronic ADHD. The current results encourage future work assessing the genetic and neurobiological underpinnings of neural noise in ADHD, particularly in brain regions encompassed by fronto-parietal systems.
Publisher: Elsevier BV
Date: 2021
DOI: 10.1016/J.JAAC.2019.11.012
Abstract: Although there are frequent reports of shared neurofunctional and neurostructural alterations among probands with attention-deficit/hyperactivity disorder (ADHD) and their unaffected siblings, there is little knowledge regarding whether abnormalities in the resting-state functional connectivity of ADHD probands is also expressed in unaffected siblings, or whether this unaffected (but at-risk) cohort manifests distinct patterns. We used a multivariate connectome-wide association study examining intrinsic functional connectivity with resting-state functional magnetic resonance imaging (MRI) in a s le (aged 8-17 years) of medication-naive ADHD probands (n = 56), their unaffected siblings (n = 55), and typically developing (TD) youths (n = 106). ADHD probands showed, relative to TD youths, increased connectivity between the default-mode network (DMN) and task-positive networks. Relative to ADHD and TD groups, respectively, unaffected siblings showed increased connectivity within the salience network and reduced connectivity between the DMN and salience network. No shared alterations in functional connectivity among ADHD probands and their unaffected siblings were identified. These findings were largely confirmed by complementary pairwise connectomic comparisons. However, the main connectivity differences between ADHD and unaffected siblings were not replicated in a tightly age- and sex-matched subs le (20 proband-sibling pairs and 60 TD youths). Our findings suggest that increased functional segregation related to the attention networks, especially the salience (ventral attention) system, may be a potential feature of at-risk siblings who remain unaffected by ADHD expression. Further replications are needed in other larger and sex-matched s les. Structural and Functional Connectivity of Frontostriatal and Frontoparietal Networks as Endophenotypes of ADHD clinicaltrials.gov/ NCT01682915.
Publisher: Elsevier BV
Date: 02-2022
DOI: 10.1016/J.JFMA.2021.06.003
Abstract: Increased intra-in idual variability (IIV) in reaction time (RT) is a key feature of attention-deficit/hyperactivity disorder (ADHD). However, little is known about neurobiology underpinnings of IIV in ADHD. We assessed 55 youths with ADHD, and 55 in idually-matched typically developing control (TDC) with the MRI and Conners' Continuous Performance Test. The ex-Gaussian distribution of RT was estimated to capture IIV with the parameters σ (sigma) and τ (tau). The regional brain volumes, analyzed by voxel-based morphometry, were correlated with IIV parameters. We found both distinct and shared correlations among ADHD and TDC. For grey matter, there were significant σ-by-group interactions in the cingulate cortex and thalamus and also a τ-by-group interaction in the right inferior frontal gyrus. There was also shared negative associations between σ and regional volumes of the right posterior cerebellum and a positive association between τ and the right anterior insula. For white matter, there was a significant σ-by-group interaction in the genu of the corpus callosum and significant τ-by-group interactions in the right anterior corona radiata, the left splenium of the corpus callosum, and bilateral posterior cerebellum. There were also shared patterns that increased τ was associated with increased regional volumes of the right anterior corona radiata and decreased regional volumes of the right posterior limb of the internal capsule. This study highlights that brain regions responsible for the motor, salience processing and multimodal information integration are associated with increased IIV in youths with ADHD.
Publisher: Informa UK Limited
Date: 30-05-2018
DOI: 10.1080/15374416.2018.1452151
Abstract: Increased intrasubject variability in reaction times (RT-ISV) is frequently found in in iduals with autism spectrum disorder (ASD). However, how dimensional attention deficit/hyperactivity disorder (ADHD) symptoms impact RT-ISV in in iduals with ASD remains elusive. We assessed 97 high-functioning youths with co-occurring ASD and ADHD (ASD+ADHD), 124 high-functioning youths with ASD only, 98 youths with ADHD only, and 249 typically developing youths, 8-18 years of age, using the Conners Continuous Performance Test (CCPT). We compared the conventional CCPT parameters (omission errors, commission errors, mean RT and RT standard error (RTSE) as well as the ex-Gaussian parameters of RT (mu, sigma, and tau) across the four groups. We also conducted regression analyses to assess the relationships between RT indices and symptoms of ADHD and ASD in the ASD group (i.e., the ASD+ADHD and ASD-only groups). The ASD+ADHD and ADHD-only groups had higher RT-ISV than the other two groups. RT-ISV, specifically RTSE and tau, was significantly associated with ADHD symptoms rather than autistic traits in the ASD group. Regression models also revealed that sex partly accounted for RT-ISV variance in the ASD group. A post hoc analysis showed girls with ASD had higher tau and RTSE values than their male counterparts. Our results suggest that RT-ISV is primarily associated with co-occurring ADHD symptoms/diagnosis in children and adolescents with ASD. These results do not support the hypothesis of response variability as a transdiagnostic phenotype for ASD and ADHD and warrant further validation at a neural level.
Publisher: Elsevier BV
Date: 08-2022
Publisher: Springer Science and Business Media LLC
Date: 02-2019
DOI: 10.1007/S10802-018-00508-Z
Abstract: Reaction times (RTs) are typically slower and more variable in in iduals with attention-deficit/hyperactivity disorder (ADHD). Analysis of the ex-Gaussian RT distribution, which is described by mu, sigma (mean and standard deviation, respectively, of the normal distribution) and tau (that of exponential distribution), reveals that in iduals with ADHD do not display overall slower RTs but have a high proportion of extremely slow RTs, represented by a high tau value. Although this is a vital component for describing ADHD-related RT variability in school-aged children, adolescents, and adults, it has not been thoroughly studied at the preschool age. We assessed 65 preschoolers at risk of ADHD and 98 typically developing preschoolers with the Conners' Kiddie Continuous Performance Test (K-CPT) and parental and teacher reports of ADHD symptoms. We found that preschoolers at risk of ADHD had greater values for RT standard deviation, sigma, and tau than typically developing preschoolers at long inter-stimulus intervals (ISIs) (3 s), but not at short ISIs (1.5 s). This suggests that attention problems in preschool children may only be apparent in the tasks with a relatively slow event rate. Our study demonstrates that the ex-Gaussian tau value is essential for describing the inattentive component of task performance in preschoolers with heightened ADHD symptoms. Furthermore, the fact that the tau effect was modulated by ISI suggests that the longer duration (3 s vs. 1.5 s) is a non-optimal energetic state in preschoolers at risk of ADHD, and that this might account for the subtle attentional flaw in task performance.
Publisher: Public Library of Science (PLoS)
Date: 12-04-2023
DOI: 10.1371/JOURNAL.PONE.0282114
Abstract: Severe behavioral problems (SBPs) are common contributors to morbidity and reduced quality of life for adults with intellectual and developmental disabilities (IDD) and their families. Current medications for SBPs show equivocal effectiveness and are associated with a high risk of side effects. New and safe treatments are urgently needed. While preliminary studies suggest that medical cannabinoids, particularly the synthetic cannabinoid nabilone, are plausible treatment options for SBPs in adults with IDD, data on the tolerability, safety and efficacy of nabilone in this population has never been investigated. Thus, we propose this first-ever Phase I pre-pilot open-label clinical trial to obtain preliminary data on the adherence, tolerability and safety profiles of nabilone in adults with IDD, and explore changes in SBPs pre- to post-treatment. We hypothesize that nabilone has favorable tolerability and safety profile for adults with IDD. The preliminary results will inform the next-stage pilot randomized controlled trials, followed by fully powered clinical trials eventually. This research helps fill the evidence gap in the use of cannabinoids in in iduals with IDD to meet the needs of patients, families, and service providers.
Publisher: Springer Science and Business Media LLC
Date: 23-03-2011
Publisher: Cambridge University Press (CUP)
Date: 30-08-2016
DOI: 10.1017/S0033291716001938
Abstract: Methylphenidate and atomoxetine are commonly prescribed for treating attention deficit hyperactivity disorder (ADHD). However, their therapeutic neural mechanisms remain unclear. After baseline evaluation including cognitive testing of the Cambridge Neuropsychological Test Automated Battery (CANTAB), drug-naive children with ADHD ( n = 46), aged 7–17 years, were randomly assigned to a 12-week treatment with methylphenidate ( n = 22) or atomoxetine ( n = 24). Intrinsic brain activity, including the fractional litude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo), was quantified via resting-state functional magnetic resonance imaging at baseline and week 12. Reductions in inattentive symptoms were related to increased fALFF in the left superior temporal gyrus and left inferior parietal lobule for ADHD children treated with methylphenidate, and in the left lingual gyrus and left inferior occipital gyrus for ADHD children treated with atomoxetine. Hyperactivity/impulsivity symptom reductions were differentially related to increased fALFF in the methylphenidate group and to decreased fALFF in the atomoxetine group in bilateral precentral and postcentral gyri. Prediction analyses in the atomoxetine group revealed negative correlations between pre-treatment CANTAB simple reaction time and fALFF change in the left lingual gyrus and left inferior occipital gyrus, and positive correlations between pre-treatment CANTAB simple movement time and fALFF change in bilateral precentral and postcentral gyri and left precuneus, with a negative correlation between movement time and the fALFF change in the left lingual gyrus and the inferior occipital gyrus. Our findings suggest differential neurophysiological mechanisms for the treatment effects of methylphenidate and atomoxetine in children with ADHD.
Publisher: Springer International Publishing
Date: 2023
Publisher: Mary Ann Liebert Inc
Date: 04-2021
Publisher: SAGE Publications
Date: 21-01-2020
Abstract: While a considerable number of youth with autism spectrum disorder exhibit impaired self-regulation (dysregulation), little is known about the neural correlates of dysregulation in autism spectrum disorder. In a s le of intellectually able boys with autism spectrum disorder (further categorized as those with and without dysregulation) and typically developing boys (aged 7–17 years), we conducted a multivariate connectome-wide association study to examine the intrinsic functional connectivity with resting-state functional magnetic resonance imaging. Dysregulation was defined by the sum of Attention, Aggression, and Anxiety/Depression subscales on the Child Behavior Checklist. We identified that both categorical and dimensional neural correlates of dysregulation in youth with autism spectrum disorder involved atypical connectivity among the components of multiple brain networks, especially between those subserving sensorimotor processing and salience encoding, beyond higher-level cognitive control circuitries. Interaction within the attention network might serve as autism spectrum disorder–specific neural correlates underpinning dysregulation. Our results highlight that the inter-in idual variability in dysregulation might contribute to the inconsistency in the neuroimaging literature of autism spectrum disorder. Collectively, the present findings provide evidence to suggest that dysregulation might be considered as both categorical and dimensional moderators to parse heterogeneity of autism spectrum disorder. Impaired self-regulation (i.e., dysregulation in affective, behavioral, and cognitive control), is commonly present in young people with autism spectrum disorder (ASD). However, little is known about what is happening in people’s brains when self-regulation is impaired in young people with ASD. We used a technique called functional MRI (which measures brain activity by detecting changes associated with blood flow) at a resting state (when participants are not asked to do anything) to research this in intellectually able young people with ASD. We found that brains with more connections, especially between regions involved in sensorimotor processing and regions involved in the processes that enable peoples to focus their attention on the most pertinent features from the sensory environment (salience processing), were related to more impaired self-regulation in young people with and without ASD. We also found that impaired self-regulation was related to increased communication within the brain system involved in voluntary orienting attention to a sensory cue (the dorsal attention network) in young people with ASD. These results highlight how different people have different degrees of dysregulation, which has been largely overlooked in the earlier brain imaging reports on ASD. This might contribute to understanding some of the inconsistencies in the existing published literature on this topic.
Publisher: Cambridge University Press (CUP)
Date: 07-02-2018
DOI: 10.1017/S0033291718000028
Abstract: Childhood-onset attention-deficit hyperactivity disorder (ADHD) in adults is clinically heterogeneous and commonly presents with different patterns of cognitive deficits. It is unclear if this clinical heterogeneity expresses a dimensional or categorical difference in ADHD. We first studied differences in functional connectivity in multi-echo resting-state functional magnetic resonance imaging (rs-fMRI) acquired from 80 medication-naïve adults with ADHD and 123 matched healthy controls. We then used canonical correlation analysis (CCA) to identify latent relationships between symptoms and patterns of altered functional connectivity (dimensional biotype) in patients. Clustering methods were implemented to test if the in idual associations between resting-state brain connectivity and symptoms reflected a non-overlapping categorical biotype. Adults with ADHD showed stronger functional connectivity compared to healthy controls, predominantly between the default-mode, cingulo-opercular and subcortical networks. CCA identified a single mode of brain–symptom co-variation, corresponding to an ADHD dimensional biotype. This dimensional biotype is characterized by a unique combination of altered connectivity correlating with symptoms of hyperactivity-impulsivity, inattention, and intelligence. Clustering analyses did not support the existence of distinct categorical biotypes of adult ADHD. Overall, our data advance a novel finding that the reduced functional segregation between default-mode and cognitive control networks supports a clinically important dimensional biotype of childhood-onset adult ADHD. Despite the heterogeneity of its presentation, our work suggests that childhood-onset adult ADHD is a single disorder characterized by dimensional brain–symptom mediators.
Publisher: Springer Science and Business Media LLC
Date: 16-02-2021
DOI: 10.1186/S12888-021-03096-3
Abstract: An amendment to this paper has been published and can be accessed via the original article.
Publisher: Elsevier BV
Date: 2023
Publisher: Springer Science and Business Media LLC
Date: 14-08-2020
DOI: 10.1038/S41598-020-70836-Y
Abstract: Previous studies demonstrated distinct neural correlates underpinning impaired self-regulation (dysregulation) between in iduals with autism spectrum disorder (ASD) and typically developing controls (TDC). However, the impacts of dysregulation on white matter (WM) microstructural property in ASD and TDC remain unclear. Diffusion spectrum imaging was acquired in 59 ASD and 62 TDC boys. We investigated the relationship between participants’ dysregulation levels and microstructural property of 76 WM tracts in a multivariate analysis (canonical correlation analysis), across diagnostic groups. A single mode of brain-behavior co-variation was identified: participants were spread along a single axis linking diagnosis, dysregulation, diagnosis-by-dysregulation interaction, and intelligence to a specific WM property pattern. This mode corresponds to diagnosis-distinct correlates underpinning dysregulation, which showed higher generalized fractional anisotropy (GFA) associated with less dysregulation in ASD but greater dysregulation in TDC, in the tracts connecting limbic and emotion regulation systems. Moreover, higher GFA of the tracts implicated in memory, attention, sensorimotor processing, and perception associated with less dysregulation in TDC but worse dysregulation in ASD. No shared WM correlates of dysregulation between ASD and TDC were identified. Corresponding to previous studies, we demonstrated that ASD and TDC have broad distinct white matter microstructural property underpinning self-regulation.
Publisher: SAGE Publications
Date: 23-02-2016
Abstract: Intra-in idual variability in reaction time (IIV-RT) is common in in iduals with attention-deficit/hyperactivity disorder (ADHD). It can be improved by stimulants. However, the effects of atomoxetine on IIV-RT are inconclusive. We aimed to investigate the effects of atomoxetine on IIV-RT, and directly compared its efficacy with methylphenidate in adults with ADHD. An 8–10 week, open-label, head-to-head, randomized clinical trial was conducted in 52 drug-naïve adults with ADHD, who were randomly assigned to two treatment groups: immediate-release methylphenidate ( n=26) thrice daily (10–20 mg per dose) and atomoxetine once daily ( n=26) (0.5–1.2 mg/kg/day). IIV-RT, derived from the Conners’ continuous performance test (CCPT), was represented by the Gaussian (reaction time standard error, RTSE) and ex-Gaussian models (sigma and tau). Other neuropsychological functions, including response errors and mean of reaction time, were also measured. Participants received CCPT assessments at baseline and week 8-10 (60.4±6.3 days). We found comparable improvements in performances of CCPT between the immediate-release methylphenidate- and atomoxetine-treated groups. Both medications significantly improved IIV-RT in terms of reducing tau values with comparable efficacy. In addition, both medications significantly improved inhibitory control by reducing commission errors. Our results provide evidence to support that atomoxetine could improve IIV-RT and inhibitory control, of comparable efficacy with immediate-release methylphenidate, in drug-naïve adults with ADHD. Shared and unique mechanisms underpinning these medication effects on IIV-RT awaits further investigation.
Publisher: Public Library of Science (PLoS)
Date: 10-10-2017
Publisher: Cambridge University Press (CUP)
Date: 09-11-2016
DOI: 10.1017/S0033291716002695
Abstract: Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder, yet the search for definite genetic etiologies remains elusive. Delineating ASD endophenotypes can boost the statistical power to identify the genetic etiologies and pathophysiology of ASD. We aimed to test for endophenotypes of neuroanatomy and associated intrinsic functional connectivity (iFC) via contrasting male youth with ASD, their unaffected brothers and typically developing (TD) males. The 94 participants (aged 9–19 years) – 20 male youth with ASD, 20 unaffected brothers and 54 TD males – received clinical assessments, and undertook structural and resting-state functional magnetic resonance imaging scans. Voxel-based morphometry was performed to obtain regional gray and white matter volumes. A seed-based approach, with seeds defined by the regions demonstrating atypical neuroanatomy shared by youth with ASD and unaffected brothers, was implemented to derive iFC. General linear models were used to compare brain structures and iFC among the three groups. Assessment of familiality was investigated by permutation tests for variance of the within-family pair difference. We found that atypical gray matter volume in the mid-cingulate cortex was shared between male youth with ASD and their unaffected brothers as compared with TD males. Moreover, reduced iFC between the mid-cingulate cortex and the right inferior frontal gyrus, and increased iFC between the mid-cingulate cortex and bilateral middle occipital gyrus were the shared features of male ASD youth and unaffected brothers. Atypical neuroanatomy and iFC surrounding the mid-cingulate cortex may be a potential endophenotypic marker for ASD in males.
Publisher: SAGE Publications
Date: 25-02-2021
Abstract: The posterior superior temporal sulcus is a potential therapeutic target of brain stimulation for autism spectrum disorder. We conducted a 4-week randomized, single-blind parallel sham-controlled trial, followed by additional 4-week open-label intervention to evaluate the feasibility and efficacy regarding intermittent theta burst stimulation over the bilateral posterior superior temporal sulcus in autism spectrum disorder. In total, 78 intellectually able children and adolescents were randomized to the active ( n = 40) and sham groups ( n = 38). During the first 4 weeks, the active group received two-session/week intermittent theta burst stimulation, whereas the sham group received the same number of sham stimulation. After unblinding, both groups received eight-session real stimulation over the additional 4 weeks. In total, 91% participants completed the protocol with mild and transitory side-effects. There was no significant group-by-time interaction for active versus sham group on clinical symptoms and social cognitive performances in the first 4 weeks. The within-group analysis revealed 8 weeks (including a 4-week blind trial and a 4-week open-label intervention) of intermittent theta burst stimulation achieved greater efficacy than 4-week interventions. Participants with higher intelligence, better social cognitive performances, alongside less attention-deficit hyperactivity disorder severity at baseline, were more likely to be responders. Our study demonstrated the feasibility of long-term intermittent theta burst stimulation over the posterior superior temporal sulcus in children and adolescents with autism spectrum disorder. However, the findings from the first 4-week blind trial do not support the therapeutic efficacy of intermittent theta burst stimulation over the posterior superior temporal sulcus on the clinical symptoms and cognitive performance of social impairment, given the current stimulation protocol. The exploratory analyses suggest that the therapeutic efficacy might be moderated by several in idual characteristics and more intermittent theta burst stimulation sessions. Intermittent theta burst stimulation is a varied form of repetitive transcranial magnetic non-invasive brain stimulation technique used to treat several neurological and psychiatric disorders. Its feasibility and therapeutic effects on the bilateral posterior superior temporal sulcus in children with autism are unknown. We conducted a single-blind, sham-controlled parallel randomized clinical trial in a hitherto largest s le of intellectually able children with autism ( N = 78). Participants randomized to the active group received two-session/week intermittent theta burst stimulation for continuous 8 weeks. Those in the sham group received two-session/week sham stimulations in the first 4 weeks and then active intervention for the following 4 weeks after unblinding. First, we found that continuous 8-week intermittent theta burst stimulation on the bilateral posterior superior temporal sulcus in children with autism is safe and tolerable. Second, we found that 8-week intermittent theta burst stimulation produced greater therapeutic efficacy, although we did not find any significant effects of 4-week intermittent theta burst stimulation on core symptoms and social cognitive performances in autism. Further analysis revealed that participants with higher intelligence and better social cognitive performance, alongside less attention-deficit hyperactivity disorder severity at baseline, were more likely to be responders. This study identified that the factors contribute to responders and the results suggest that longer courses of non-invasive brain stimulation may be needed to produce therapeutic benefits in autism, with consideration of heterogeneous responses.
Publisher: Springer Science and Business Media LLC
Date: 08-08-2019
Publisher: Wiley
Date: 28-01-2015
DOI: 10.1002/AUR.1457
Abstract: The posterior right temporo-parietal junction (pRTPJ) is a key brain region representing other's mental status. Despite reports of atypical activation at pRTPJ during mentalizing in in iduals with autism spectrum disorder (ASD), the intrinsic functional connectivity (iFC) of the pRTPJ remains under-investigated. We examined whether boys with ASD show altered resting-state iFC of the pRTPJ, and whether atypical iFC of the pRTPJ is associated with social deficits in ASD in a s le of 40 boys with high-functioning ASD (aged 9-17 years, mean age, 12.38 ± 2.17 mean IQ, 105.60 ± 16.06) and 42 typically developing (TD) boys (aged 9-17 years, mean age, 11.64 ± 2.71 mean IQ, 111.29 ± 13.45). Both groups received resting-state fMRI assessment after imaging data quality control for in-scanner head motion and spatial coverage. Seed-based approach was used to investigate iFC of the pRTPJ. TD and ASD boys demonstrated a resting-state pRTPJ iFC pattern comparable to the known spatial involvement of the default-mode network. Boys with ASD showed pRTPJ hyperconnectivity relative to TD boys in the right ventral occipito-temporal cortex. This atypically increased iFC in the ASD group was positively correlated with social deficits assessed by the Chinese version of the Autism Diagnostic Interview-Revised and the Social Responsive Scale. Our findings provide empirical support for functional "dysconnectivity," that is, atypical functional integration among brain regions, as an integral component of the atypical neurobiology of ASD.
Publisher: Cold Spring Harbor Laboratory
Date: 13-10-2021
DOI: 10.1101/2021.10.11.464005
Abstract: Neuroimage literature of autism spectrum disorder (ASD) has a moderate-to-high risk of bias, partially because those combined with intellectual impairment (II) and/or minimally verbal (MV) status are generally ignored. We aimed to provide more comprehensive insights into white matter alterations of ASD, inclusive of in iduals with II (ASD-II-Only) or MV expression (ASD-MV). Sixty-five participants with ASD (ASD-Whole 16.6±5.9 years comprising 34 intellectually able youth, ASD-IA, and 31 intellectually impaired youth, ASD-II, including 24 ASD-II-Only plus 7 ASD-MV) and 38 demographic-matched typically developing controls (TDC 17.3±5.6 years) were scanned in accelerated diffusion-weighted MRI. Fixel-based analysis was undertaken to investigate the categorical differences in fiber density (FD), fiber cross-section (FC), and a combined index (FDC), and brain-symptom/cognition associations. ASD-Whole had reduced FD in the anterior and posterior corpus callosum and left cerebellum Crus I, and smaller FDC in right cerebellum Crus II, compared to TDC. ASD-II, relative to TDC, showed almost identical alterations to those from ASD-Whole vs. TDC. ASD-II-Only had greater FD/FDC in the isthmus-splenium of callosum than ASD-MV. Autistic severity negatively correlated with FC in right Crus I. Non-verbal full-scale IQ positively correlated with FC/FDC in cerebellum VI. FD/FDC of the right dorsolateral prefrontal cortex showed a diagnosis-by-executive function interaction. We could not preclude the potential effects of age and sex from the ASD cohort, although statistical tests suggested that these factors were not influential. Our results could be confounded by variable psychiatric comorbidities and psychotropic medication uses in our ASD participants recruited from outpatient clinics, which is nevertheless closer to a real-world presentation of ASD. The outcomes related to ASD-MV were considered preliminaries due to the small s le size within this subgroup. Finally, our study design did not include intellectual impairment-only participants without ASD to disentangle the mixture of autistic and intellectual symptoms. ASD-associated white matter alterations appear driven by in iduals with II and potentially further by MV. Results suggest that changes in the corpus callosum and cerebellum are key for psychopathology and cognition associated with ASD. Our work highlights an essential to include understudied sub-populations on the spectrum in research.
Publisher: Wiley
Date: 22-01-2015
DOI: 10.1111/ACPS.12393
Abstract: Intra-in idual variability in reaction time (IIV-RT), defined by standard deviation of RT (RTSD), is considered as an endophenotype for attention-deficit/hyperactivity disorder (ADHD). Ex-Gaussian distributions of RT, rather than RTSD, could better characterize moment-to-moment fluctuations in neuropsychological performance. However, data of response variability based on ex-Gaussian parameters as an endophenotypic candidate for ADHD are lacking. We assessed 411 adolescents with clinically diagnosed ADHD based on the DSM-IV-TR criteria as probands, 138 unaffected siblings, and 138 healthy controls. The output parameters, mu, sigma, and tau, of an ex-Gaussian RT distribution were derived from the Conners' continuous performance test. Multi-level models controlling for sex, age, comorbidity, and use of methylphenidate were applied. Compared with unaffected siblings and controls, ADHD probands had elevated sigma value, omissions, commissions, and mean RT. Unaffected siblings formed an intermediate group in-between probands and controls in terms of tau value and RTSD. There was no between-group difference in mu value. Conforming to a context-dependent nature, unaffected siblings still had an intermediate tau value in-between probands and controls across different interstimulus intervals. Our findings suggest IIV-RT represented by tau may be a potential endophenotype for inquiry into genetic underpinnings of ADHD in the context of heterogeneity.
Publisher: Cambridge University Press (CUP)
Date: 07-01-2020
DOI: 10.1017/S0033291719003830
Abstract: The dopamine transporter gene ( DAT1 ), striatal network dysfunction, and visual memory deficits have been consistently reported to be associated with attention-deficit/hyperactivity disorder (ADHD). This study aimed to examine the effects of the DAT1 rs27048 (C)/rs429699 (T) haplotype on striatal functional connectivity and visual memory performance in youths with ADHD. After excluding those who had excessive head motion, a total of 96 drug-naïve youths with ADHD and 114 typically developing (TD) youths were assessed with the resting-state functional magnetic resonance imaging and the delayed matching to s le (DMS) task for visual memory. We examined the effects of ADHD, DAT1 CT haplotype, and the ADHD × CT haplotype interaction on the functional connectivity of five striatal seeds. We also correlated visual memory performance with the functional connectivity of striatal subregions, which showed significant diagnosis × genotype interactions. Compared with TD youths, ADHD youths showed significant hypoconnectivity of the left dorsal caudate (DC) with bilateral sensorimotor clusters. Significant diagnosis × genotype interactions were found in the connectivity between the left DC and the right sensorimotor cluster, and between the right DC and the left dorsolateral prefrontal/bilateral anterior cingulate clusters. Furthermore, the connectivity of the left DC showing significant diagnosis × genotype interactions was associated with DMS performance in youths with ADHD who carried the DAT1 CT haplotype. A novel gene-brain-behavior association between the left DC functional connectivity and visual memory performance in ADHD youths with the DAT1 rs27048 (C)/rs429699 (T) haplotype suggests a differential effect of DAT1 genotype altering specific brain function causing neuropsychological dysfunction in ADHD.
Publisher: SAGE Publications
Date: 23-08-2023
DOI: 10.1177/13623613221117444
Abstract: The Early Start Denver Model is an evidence-based, comprehensive naturalistic developmental behavioral intervention for young and very young children with autism spectrum disorder. This interdisciplinary model is suitable for the Taiwanese public health system. In this study, we evaluated the effectiveness of an Early Start Denver Model program with adaptation, including a lower intensity, shorter duration, and delivery in general hospitals by multidisciplinary professionals. A quasi-experimental study with pre-, post-intervention, and 6-month follow-up was conducted. Forty-five young children with autism spectrum disorder, aged 2–4 years, were grouped into the Early Start Denver Model and control (the usual community treatment) groups. The Early Start Denver Model group received 6 months of one-on-one intervention for approximately 8–9 h per week. Compared with the control group, the Early Start Denver Model group showed greater improvements in overall development quotient and nonverbal development quotient from pre- to post-intervention, but these differences (a Group-by-Time interaction) did not sustain at the 6-month follow-up. Being mindful of some potential threats to internal validity associated with clinical trial designs and implementation, this study provides preliminary evidence to support the effectiveness of the Early Start Denver Model intervention in regional general hospital settings in the context of Han-Chinese-mainly culture. The Early Start Denver Model is an evidence-based early intervention program for young and very young children with autism. This interdisciplinary model is used by many types of professionals, such as psychologists, occupational therapists, speech pathologists, early child special educators, and paraprofessionals, as well as by parents. Most previous studies on the Early Start Denver Model were conducted in the West, and there are scarce studies on the topics of generalization in culture and countries outside the Western world. In this study, we evaluated the effect of the Early Start Denver Model with some adaptations, including a lower intensity, shorter duration, and delivery in regional general hospitals in Northern Taiwan. In total, 45 young children with autism, aged 2–4 years, were ided into the Early Start Denver Model and community-based control groups. The children in the Early Start Denver Model group received one-on-one intervention for approximately 8–9 h per week for 6 months. The results revealed that compared with the control group, the Early Start Denver Model group showed greater gains in overall development ability and nonverbal development ability from pre- to post-intervention. However, these differences did not sustain at the 6-month follow-up after the completion of the intervention. Being mindful of some caveats in trial designs, this study provides preliminary evidence to support the effectiveness of the Early Start Denver Model intervention in the regional general hospital settings in the context of Han-Chinese-mainly culture. Our findings can provide helpful information to stakeholders and policymakers of early intervention service systems for children with autism in Taiwan, as well as in Asian countries.
Publisher: Frontiers Media SA
Date: 31-08-2022
DOI: 10.3389/FPSYT.2022.904380
Abstract: The World Health Organization (WHO) developed the Caregiver Skills Training for Families of Children with Developmental Delays and Disabilities (CST) with support from Autism Speaks to address the resource gaps and worldwide needs for interventions for children with developmental disorders or delays, especially those with autism spectrum disorder (ASD), and their families. Evidence has indicated that parent-mediated interventions benefit both caregivers and children by strengthening caregivers' knowledge and confidence and children's social communication skills and behavioral regulation. The CST-Taiwan team began the prepilot field trial in 2017 and developed the project to serve families in various locations. This study (1) delineated the adaptations and promotion of CST-Taiwan (2) determined the program's effectiveness in the promotional stage, in terms of caregiver and child outcomes, and (3) examined the maintenance of its effects. The materials, delivery, and facilitator training procedure of the original CST were adapted to Taiwan. The quantitative data indicated that CST-Taiwan is a promising program, it positively affected caregiver knowledge and confidence and reduced the severity of the children's autistic symptoms. The 3-month follow-up results suggested that the effects persisted. Thus, CST-Taiwan, and its promotional strategies are feasible and effective.
Publisher: Springer Science and Business Media LLC
Date: 11-09-2019
DOI: 10.1007/S11682-019-00199-0
Abstract: Although impaired self-regulation (dysregulation) in autism spectrum disorder (ASD) garnered increasing awareness, the neural mechanism of dysregulation in ASD are far from conclusive. To complement our previous voxel-based morphometry findings, we estimated the cortical thickness, surface area, and local gyrification index based on the surface-based morphometry from structural MRI images in 85 ASD and 65 typically developing control (TDC) boys, aged 7-17 years. Levels of dysregulation were measured by the sum of T-scores of Attention, Aggression, and Anxiety/Depression subscales on the Child Behavior Checklist. We found both ASD and TDC shared similar relationships between dysregulation and cortical folding patterns in the left superior and inferior temporal gyri and the left premotor cortex. Significant diagnosis by dysregulation interactions in cortical folding patterns were identified over the right middle frontal and right lateral orbitofrontal regions. The statistical significance of greater local gyrification index in ASD than TDC in several brain regions disappeared when the level of dysregulation was considered. The findings of shared and distinct neural correlates underpinning dysregulation between ASD and TDC may facilitate the development of targeted interventions in the future. The present work also demonstrates that inter-subject variations in self-regulation may explain some extents of ASD-associated brain morphometric differences, likely suggesting that dysregulation is one of the yardsticks for dissecting the heterogeneity of ASD.
Publisher: Wiley
Date: 05-08-2022
DOI: 10.1111/ACPS.13484
Abstract: In iduals with intellectual and/or developmental disability (IDD) are often prescribed antipsychotics (APs). However, despite their known propensity to cause metabolic adverse effects, including weight gain, diabetes, and increased risk of cardiovascular events, there is currently a limited body of literature describing the metabolic consequences of AP use in this population. We searched MEDLINE, EMBASE, PsychINFO, CENTRAL, and CINAHL databases to identify all randomized trials that reported on the metabolic effects of APs in in iduals with IDD. Random effects meta‐analyses were used to examine weight gain as both a continuous and dichotomous outcome. Eighteen randomized trials met our inclusion criteria with a total of 1376 patients across a variety of IDDs. AP use was associated with significantly greater weight gain compared with placebo (Continuous: mean difference = 1.10 kg, [0.79, 1.40], p 0.00001, I 2 = 54% Dichotomous: odds ratio = 3.94, [2.15, 7.23], p 0.00001, I 2 = 0). Sub‐group analysis revealed no significant effect of AP type. Data regarding the effects of APs on other metabolic outcomes were limited. This review (PROSPERO # CRD42021255558) demonstrates that AP use is associated with significant weight gain among patients with IDD. Concerningly, most reported studies were in children and adolescents, which sets up an already vulnerable population for adverse medical sequalae at an early age. There was also a lack of long‐term studies in adults with IDD. Further studies are required to better understand how AP use affects metabolic parameters in this group of in iduals.
Location: Taiwan, Province of China
No related grants have been discovered for Hsiang-Yuan Lin.