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Attention-deficit/hyperactivity disorder (ADHD) and persistent tic disorder (PTD) are two neurodevelopmental disorders that frequently co-occur. Contributions of each disorder to cognitive and behavioral deficits have been reported. In this paper, we tested 3 models of pathophysiology for the two disorders (additive, interactive, and phenotypic) using resting-state connectivity associated with each disorder separately and together.
Methods
Participants were 148 children (55 with ADHD only, 33 with ADHD and PTD, 27 with PTD only, and 33 healthy control subjects) at ages 8 to 12 years. Following diagnostic interviews and behavioral assessment, participants underwent a 128-channel electroencephalography recording. Resting-state, cortical source-level effective connectivity was analyzed across the 4 groups using a 2 × 2 factorial design with factors of ADHD (with/without) and PTD (with/without).
Results
ADHD diagnosis was the primary driver of cognitive and behavioral deficits, while deficits associated with PTD were primarily with thought problems and internalizing problems when compared with controls. Subadditive effects were observed in co-occurring ADHD+PTD for parent-rated behavioral problems and cognitive functions. Aberrant effective connectivity was primarily associated with ADHD, more specifically with lower posterior and occipital-frontal connectivity, while children with PTD exhibited greater left postcentral to precuneus connectivity. Weaker ADHD-related connectivity was associated with more severe behavioral problems, including internalizing behaviors, thought problems, and working memory deficits.
Conclusions
Similar to general behavioral deficits, aberrant resting-state neural connectivity in pediatric ADHD and PTD combines additively in co-occurring cases. The findings of this study support ADHD as a focus of treatment in comorbid cases, given the driving role of ADHD in both behavioral and neurophysiological deficits.
Attention-deficit/hyperactivity disorder (ADHD) and persistent tic disorder (PTD) are neurodevelopmental disorders that develop during childhood, with a prevalence in pediatric populations of approximately 6% for ADHD (
). Despite their differing symptomatology, the two disorders show particularly high rates of comorbidity with one another, with upward of 50% of children with PTD also meeting the criteria for an ADHD diagnosis (
Numerous transdiagnostic studies have been conducted comparing ADHD and PTD phenotypes to investigate the overlapping nature of the disorders and their unique influences on cognitive performance and behavioral functioning. Converging evidence from pediatric studies conducted to date suggests that ADHD is the primary driver of most neuropsychological deficits in comorbid cases (
Comparative study of the behavioral and neuropsychologic characteristics of tic disorder with or without attention-deficit hyperactivity disorder (ADHD).
). ADHD has also been strongly linked to both externalizing and internalizing problems, while PTD has primarily been related to internalizing behaviors (
), and some studies have indicated that ADHD with PTD is associated with more severe internalizing issues (anxiety, worsened social functioning, reduced quality of life) relative to ADHD alone (
). These behavioral findings support the idea of an additive model of pediatric ADHD and PTD pathophysiology, with ADHD and PTD being 2 separate diagnostic entities. This is in contrast to two other models that have been developed regarding combined ADHD and PTD diagnoses (
). One is an interactive model that suggests that comorbid cases are a unique diagnostic entity, evidence for which has been observed in young adults with comorbid ADHD and PTD (
). The other is a phenotypic model that considers comorbid cases to be a phenotypic subgroup with a pathological basis of either ADHD or PTD.
These hypothesized models have primarily been explored in behavioral studies. For example, evaluations of sleep alterations in ADHD and PTD found unique additive characteristics from each disorder in comorbid groups (
). Studies evaluating task-based performance deficits have reported conflicting findings regarding the combined impact of the two disorders on cognitive performance. Some cognitive control studies have noted performance deficits in both ADHD with PTD and ADHD without PTD (
Attentional performance in children and adolescents with tic disorder and co-occurring attention-deficit/hyperactivity disorder: New insights from a 2 × 2 factorial design study.
). Another study involving reinforcement learning demonstrated that in children with PTD, the presence of ADHD did not impact acquisitional learning but did impact the ability to modify learned behaviors (
). An impaired ability to modify learned behaviors may have a particularly negative impact on response to behavioral and pharmacotherapy treatment regimens for PTD (
Electroencephalography (EEG) and neuroimaging approaches provide methods to characterize and assess the neural mechanisms underlying ADHD and PTD. However, to date there have been relatively few transdiagnostic studies comparing atypical neurophysiological attributes of the two disorders using these approaches. Investigations into reward processing have indicated a relationship between ADHD severity and nucleus accumbens activation, irrespective of PTD presence (
). Decreased midline theta power has been noted during a NoGo task in pediatric ADHD without PTD but not in comorbid cases, suggesting subadditive effects of the two disorders (
). Another pediatric study observed an association between greater spontaneous frontal theta activity during selective attention and the presence of ADHD, but stronger early event-related theta activity in co-occurring ADHD+PTD (
Increased event-related theta activity as a psychophysiological marker of comorbidity in children with tics and attention-deficit/hyperactivity disorders.
). This could suggest that simple or resting-state tasks may involve additive effects, while complex cognitive tasks may result in interactions between disorders. Functional connectivity studies have suggested atypical network interactions between the default mode network (DMN) and frontoparietal network within each disorder individually (
Combining disrupted and discriminative topological properties of functional connectivity networks as neuroimaging biomarkers for accurate diagnosis of early Tourette syndrome children.
). Graph theory analyses have indicated diagnostic group differences in local efficiency and clustering coefficients, with lower connectivity among frontoparietal network nodes in PTD relative to ADHD and lower connectivity among DMN nodes in PTD relative to controls (
). Frontoparietal network connectivity in the comorbid ADHD+PTD group was also observed to be more similar to the PTD group than to the ADHD group, suggesting that tics may have a stronger influence on this network.
Further exploration of these disorders, particularly from a whole-brain network approach, could help provide important insight into the unique region-to-region communication patterns associated with each disorder. While functional connectivity measures reflect correlations between brain regions, they do not reveal the underlying directionality of influences (
). To date, these directional neural dynamics have remained unexplored in the context of co-occurring ADHD and PTD. Further parsing of the neural mechanisms of each disorder may be beneficial in understanding behavioral, cognitive, and treatment response in these disorders. This study aimed to fill this gap by examining EEG-based cortical source-level, resting-state effective connectivity in a sample of 8- to 12-year-old children. A 2 × 2 factorial design was utilized with factors of ADHD (present/not present) and PTD (present/not present), providing the following 4 groups for the analysis: ADHD without PTD (ADHD), PTD without ADHD (PTD), co-occurring ADHD and PTD (ADHD+PTD), and healthy control subjects (HCs). We expected to replicate results of prior studies suggesting that ADHD is the primary driver of behavioral and cognitive deficits and hypothesized that atypical neural communication would also be principally driven by ADHD, with deficits primarily in DMN nodes due to the resting-state paradigm. We also hypothesized that these deficits would follow the additive ADHD/PTD model that has been supported by results of prior clinical pediatric studies, with the two disorders making unique contributions to atypical regional communication.
Methods and Materials
Participants
The sample consisted of 148 children ages 8 to 12 years; 55 with ADHD (without PTD); 33 with comorbid ADHD+PTD; 27 with PTD (without ADHD); and 33 typically developing HCs. The participants with ADHD were recruited and assessed during the baseline visit of a clinical trial before any treatment was administered. The PTD, comorbid ADHD+PTD, and HC groups were assessed as part of an EEG study on PTD. Both the studies ran concurrently, and study participants were assessed using the same diagnostic protocols and EEG equipment. Participants were recruited through community advertisements and Internet postings and from an academic medical center anxiety and tic disorder clinic. Participants and their parents received verbal and written explanations of study criteria and provided informed consent/assent prior to screening and any study procedures. All study procedures were approved by the local institutional review board.
All children completed semistructured diagnostic interviews, cognitive testing, and an EEG recording during a single experimental session. Children in all groups were male or female ages 8 to 12 years with an estimated Full Scale IQ ≥ 85 based on the Wechsler Abbreviated Scale of Intelligence (
Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (K-SADS-PL): Initial reliability and validity data.
J Am Acad Child Adolesc Psychiatry.1997; 36: 980-988
) was administered to assess for DSM-5 diagnoses of ADHD, PTD, and all potential comorbid disorders. Additional inclusion criteria for children in the ADHD groups were an ADHD-IV Rating Scale score ≥ 24 (
). Exclusion criteria for all diagnostic groups included a history of major depression, autism spectrum disorder, bipolar disorder, psychosis, mania, seizure disorder, panic disorder, head injury resulting in concussion, or suicidality. Children in the patient groups (ADHD, PTD, ADHD+PTD) were required to discontinue stimulant medications for 24 hours prior to participation. HCs were excluded if they had any major Axis 1 diagnosis or were on a psychoactive medication.
EEG Recording
Participants performed a 5-minute, eyes-open resting-state condition while EEG was recorded using a 128-channel Electrical Geodesics (EGI) GES300 system. Data were referenced to Cz and sampled at 1000 Hz with an electrode impedance threshold of 50 kΩ (per manufacturer standard). Electrode coordinates were obtained using a digitizer software (Polhemus Inc.), using the nasion and preauricular notches as anatomical reference locations.
Continuous EEG data was processed and cleaned using EEGLAB software (
). Data were downsampled to 250 Hz and filtered using a 0.5 to 55 Hz bandpass filter. Artifact Subspace Reconstruction (https://github.com/sccn/clean_rawdata) (
) was performed via the EEGLAB plugin clean_rawdata() to remove channel artifacts and interpolate nonstationary high amplitude bursts, as well as remove channels with more than 5 seconds of flat signal and those that were poorly correlated (r < 0.85) with adjacent channels. Data were then further downsampled to 100 Hz, and adaptive mixture independent component analysis (
) was utilized to decompose scalp-level data into independent source-level components (ICs). Locations of source dipoles were then estimated using FieldTrip (
) when they displayed over 15% residual variance or the brain was not the highest probability source. To facilitate proper fitting of the multivariate autoregressive model for connectivity, participants were limited to their top 15 ranked ICs.
Connectivity Analysis
Effective connectivity aims to estimate the direction and magnitude of information flow (which is used interchangeably with connectivity) between brain regions, whereby past values from Region A provide supplemental predictive information about the future activity of a separate Region B (
). Through the use of a multivariate autoregressive model, effective connectivity estimates can be extended beyond a single pair of regions by modeling past activity from several regions to estimate causal relationships between each pair. Here, we have utilized a multivariate autoregressive model fitted from the Vieira-Morf algorithm. For each participant, information flow between cortical sources (ICs) was estimated in the form of renormalized partial directed coherence (
). The renormalized version of partial directed coherence was selected because it allows for comparisons between different magnitudes of partial directed coherence values. Additionally, cortical source connectivity, rather than channel-level, was utilized to localize underlying neural mechanisms (rather than scalp mechanisms) as well as to avoid volume conduction issues inherent to measures of channel-level connectivity (
To facilitate comparisons of connectivity across participants, we then estimated whole-brain activity from the cortical source ICs. Using the approach of Loo et al. (
), a 3D Gaussian kernel (full width at half maximum of 20 mm, truncated at 3σ) spatially smoothed dipoles from point sources into probabilistic densities. The head model was then segmented into 76 regions of interest based on the automated anatomical labeling atlas (
). Within each participant, activity at each region of interest was estimated based on the weighted-average contribution of Gaussian-smoothed dipoles. Connections that maintained 80% of unique participants were included in the analysis.
A mass-univariate analysis was implemented wherein for each frequency bin of each connection, a 2 × 2 factorial analysis of variance was performed on the 4 groups, with factors of ADHD (with vs. without ADHD) and PTD (with vs. without PTD). Statistics (F values) for main effects of ADHD and PTD as well as interaction effects were obtained. Because connectivity values among neighboring frequency bins are not fully independent, a cluster-based approach was used, which aimed to find frequency ranges (e.g., groups of adjacent frequency bins) where significant connectivity effects were present. To facilitate this, connectivity values in each array were first masked at a p < .05 level of significance, and groups of neighboring frequency bins with surviving F statistics were then summed together to form F-statistic-weighted mass of clusters representing frequency ranges of significant effects.
Cluster-level correction was implemented for control of generalized familywise error rate using permutation tests (i.e., to determine which connectivity effects survived statistical correction) (
). To build surrogate statistics representing the null hypothesis (i.e, no group effect), group labels of renormalized partial directed coherence arrays were iteratively shuffled (N = 1000), and statistical comparisons were repeated for each iteration for each graph edge. Observing across all edges, the second maximum F-statistic-weighted mass of clusters was extracted from each iteration to form a unique null distribution for each effect, resulting in 3 null distributions (the main effect of ADHD, the main effect of PTD, and the interaction between ADHD and PTD). For each effect, true F-statistic-weighted mass of clusters were compared with their respective null distribution using a p < .05 significance threshold, and surviving results were analyzed.
Statistical Analysis
All statistics were performed in the R programing environment. Factorial analyses of variance (with factors of ADHD and PTD) were first conducted on CBCL, BRIEF, and attentional performance [measured using congruent and incongruent trials from a modified Erikson arrow-flanker task (
)] scores to examine behavioral deficits associated with each disorder. Pairwise group differences in behavioral measures, as well as connectivity measures, were observed using Tukey’s honestly significant difference post hoc tests.
To aid functional interpretations and assess relationships between neural connectivity and severity of behavioral deficits, Pearson correlations were calculated between significant connectivity measures and CBCL/BRIEF scores. False discovery rate correction was implemented at a p = .05 level of significance to control the type 1 error rate.
Results
As shown in Table 1, demographics across the 4 groups of participants were well matched in terms of age and gender. Estimated intelligence (IQ) was significantly different across the groups, with lower IQ, albeit still within the average range, in the ADHD group relative to controls. A total of 10 participants in the comorbid group and 2 participants in the PTD group were on nonstimulant psychotropic medication. Four participants in the comorbid group were taking a prescribed stimulant, which was discontinued 24 hours prior to their visit. No participants in the ADHD group were taking any prescribed psychotropic or stimulant medications.
Table 1Sample Demographics and Behavioral Scores
Measure
Groups
Diagnostic Effect (F Value Unless Otherwise Indicated)
Factorial analysis of variance analyses on clinical scores revealed a significant main effect of ADHD for higher problem scores on all subscales of the CBCL and BRIEF measures and a significant main effect of PTD for greater thought problems and internalizing problems. Interaction effects between the two disorders were observed for the attention problems and total problems subscales from the CBCL, as well as for the BRIEF scales of inhibition, initiation, planning/organization, task monitoring, and working memory. Post hoc comparisons indicated that the ADHD and comorbid groups were more clinically impaired than the PTD and HC groups on most measures. However, for several measures (attention problems, inhibition, planning/organization, task monitoring, and working memory), the comorbid group showed less clinical impairment compared with the ADHD group (although comorbid group participants still had significantly higher scores than the PTD and HC groups), suggesting an apparent subadditive combination of the two disorders on parent-rated cognitive functioning.
No significant effects of diagnosis were observed on task performance for flanker task accuracy; however, main effects of ADHD and PTD were noted for congruent and incongruent trial reaction time (RT) and RT variability. Notably, these effects were in opposite directions, with a PTD diagnosis being associated with faster RT and lower RT variability and an ADHD diagnosis being associated with slower RT and higher RT variability. Post hoc Tukey’s honestly significant difference tests on performance measures indicated pairwise group differences between the ADHD and PTD groups (ADHD > PTD) in congruent trial RT as well as RT variability for both trial types. These directional effects also resulted in a significant difference in RT variability between the ADHD and comorbid groups, aligning with the prior observed subadditivity of behavioral measures of attention and inhibition.
Effective Connectivity Findings
Utilizing 80% participant inclusion criteria for connections, 254 connections were included in the analysis. Of these, several aberrant neural connections with significant main effects of ADHD and PTD were detected, along with one atypical connection common to both disorders (Figure 1). Frequency ranges of these connectivity effects are shown in Table 2. Connections with a main effect of ADHD exhibited lower information flow among occipital-frontal (right calcarine to right superior frontal cortex [F1,122 = 10.2, p = .002]) and several right to left intraoccipital connections: right cuneus to left cuneus (F1,124 = 7.0, p = .009), right cuneus to left superior occipital (F1,123 = 8.2, p = .005), and right cuneus to left midoccipital cortex (F1,122 = 10.5, p = .002). Children with ADHD also displayed lower information flow from the precuneus to the left midtemporal cortex (F1,119 = 8.1, p = .005). Pairwise group comparisons (Tukey’s honestly significant difference) indicated that the ADHD group had significantly lower connectivity than the non-ADHD groups (Table 2).
Figure 1Resting-state connectivity by diagnosis. Attention-deficit/hyperactivity disorder (ADHD) diagnosis was associated with lower resting-state information flow among posterior and occipital-frontal connections, while persistent tic disorder (PTD) diagnosis was related to higher left postcentral to precuneus connectivity. Lower connectivity in ADHD and PTD groups from the left occipital cortex to the right precuneus compared with healthy control subjects (HCs) was common in both disorders. Visualization was created using BrainNet Viewer (
A main effect of PTD was higher information flow from the left postcentral cortex to the right precuneus (F1,127 = 6.0, p = .02). PTD was also associated with lower connectivity from the left cuneus to the right precuneus (F1,133 = 4.57, p = .03), with ADHD showing trend-level (F1,133 = 3.21, p = .07) differences in that direction. Pairwise post hoc comparisons indicated that the HC group had significantly higher connectivity relative to the 3 affected groups, suggesting that lower connectivity between the left cuneus and right precuneus might be a deficit that is shared by the two disorders. No significant diagnostic interaction effects of connectivity were observed.
Correlations Between Connectivity and Behavior
Correlation analyses revealed significant relationships between connections, with a main effect of ADHD and several CBCL/BRIEF measures after false discovery rate correction (Table 3). These included broadband CBCL measures of internalizing problems (anxiety/depression, thought problems) and total problems as well as more cognition-based BRIEF measures of initiation, organization, and working memory. All of the observed correlations were negative in direction, indicating that greater clinical and cognitive deficits were associated with lower information flow among posterior and occipital-frontal connections. The connection with a main effect of PTD (i.e., right precuneus to left postcentral cortex) did not show any significant relationship with behavioral deficits .
Table 3Pearson Correlations Between Network Connections and Behavioral Measures
Pearson correlations are false discovery rate corrected. Behavioral scores are from the Child Behavior Checklist unless noted as being from the Behavioral Inventory of Executive Function.
L, left; R, right; Sup, superior.
a p < .05.
b Behavioral score from the Behavioral Inventory of Executive Function.
This is the first EEG study to utilize a resting-state effective connectivity approach to examine shared and distinct neural features of ADHD and PTD. The findings indicate that ADHD is the primary driver of behavioral, cognitive, and neural connectivity deficits in these 2 frequently co-occurring disorders. In the connectivity analyses, all but one of the group differences were related to ADHD, particularly lower information flow among posterior and occipital-frontal connections. Both behavioral deficits and aberrant resting-state neural connectivity in pediatric ADHD and PTD combine additively in co-occurring cases. Negative correlations between information flow and behavioral scores (CBCL/BRIEF scores) suggest that lower connectivity is associated with a higher level of clinical impairment.
Consistent with findings from this study, prior clinical reports that have examined co-occurring ADHD and PTD have implicated ADHD as the primary contributor to behavioral and cognitive performance deficits among comorbid pediatric populations (
Comparative study of the behavioral and neuropsychologic characteristics of tic disorder with or without attention-deficit hyperactivity disorder (ADHD).
), significantly increased impairment was not observed in comorbid children. However, total Yale Global Tic Severity Scale scores were significantly higher in the comorbid group than in the PTD group, suggesting more severe tics among those with comorbid ADHD and PTD. In contrast, several behavioral measures showed significantly reduced clinical severity in comorbid children (relative to children with ADHD but without PTD), including measures of attention, inhibition, planning/organization, task monitoring, and working memory. Additionally, while flanker task RT variability was significantly higher in ADHD and in agreement with past studies (
), it was also significantly lower in comorbid children relative to children with ADHD alone. Similar subadditive effects have been reported during a Go/NoGo paradigm, with reduced inhibitory control performance and atypical EEG activity in children with ADHD alone but not in children with ADHD with comorbid tics (
). It is possible that these subadditive effects are related to compensatory or adaptive changes in neural organization that are thought to occur in children with PTD (
), which may assist with certain cognitive functions in children with comorbid ADHD and PTD. Alternatively, this may be explained by some comorbid ADHD symptoms being driven by PTD-related issues (e.g., internal tic distraction) (
), thus affecting cognitive functioning differently than ADHD-driven issues.
Aberrant connectivity followed a trend similar to the behavioral deficits that were observed, with the majority of atypical connections being associated with the presence of ADHD. Nodes of these connections comprise several frequently implicated networks in ADHD including the DMN (precuneus, midtemporal gyrus), cognitive control (right superior frontal gyrus), and visual networks (bilateral occipital cortex) [for meta-analysis, see Sutcubasi et al. (
). Significant negative correlations between the present connections and behavioral deficits provide support for a neurophysiological basis of behavioral deficits. In PTD, greater resting-state information flow from the left postcentral cortex to the right precuneus has been reported by prior studies noting increased sensorimotor network connectivity (
). This connection was not significantly correlated with any clinical behaviors, suggesting that greater information flow may instead represent overactive sensorimotor communication related to tic generation and execution. Lastly, lower connectivity from the left cuneus to right precuneus was observed in the 3 diagnostic groups relative to HCs. Atypical communication between these regions may be a common deficit in ADHD and PTD and could be a contributing factor in their comorbid diagnoses. It should be noted that while studies have indicated that frontal regions are a common area of deficits in both the disorders (
), only 1 atypical connection was noted here (right calcarine to right superior frontal) for ADHD-related deficits. This may be due to the analysis utilizing a factorial approach rather than a 4-group approach, as well as the frequency and nature of the underlying frontal causal activations.
No interactions between diagnoses were observed for connectivity measures, suggesting an additive model for the unique regional communication impairments present in each disorder. Similar additive effects of functional connectivity have been observed in the frontoparietal network and DMN in comorbid groups (
). It is possible that the additive/interactive nature of behavioral deficits may vary as a function of cognitive demand. For example, a prior selective attention study reported that additive effects were seen primarily in spontaneous theta activity whereas interactive effects were seen primarily during event-related (poststimulus) theta activity (
Increased event-related theta activity as a psychophysiological marker of comorbidity in children with tics and attention-deficit/hyperactivity disorders.
). As suggested by the authors, resting-state processes may tend toward additive models of disorder-independent deficits in regional activations and communication, while cognitive functions requiring greater resources may lead to more complex interactions among implicated networks. However, 2 studies utilizing cognitive control paradigms have reported additive effects on event-related potentials and event-related theta power when examining ADHD and PTD groups (
). This may suggest that additive or interactive effects may be additionally dependent on the unique cognitive demands required, along with how these specific cognitive functions may be altered in each disorder. Further studies simultaneously evaluating both resting-state and task-based connectivity may be beneficial for further understanding the full model of co-occurring ADHD and PTD and their unique interactions.
Strengths of this study include a large sample and well-matched age and gender distributions in each group. One potential limitation of this study is that tics were present among participants with PTD, which may have caused instances of unique cognitive activity and transient noise in the resting-state data. While noise was handled well using the data cleaning algorithms, event-related activity associated with tic expression may have contributed to the underlying resting-state connectivity measurements. A second limitation is that the statistical cluster-level correction that was implemented favors broadband spectral effects. It is possible that additional narrowband connectivity effects present among the diagnostic groups were not detected due to statistical methodology. Third, some participants in the comorbid and PTD groups were taking prescribed medications, while those in the ADHD only group were not. While rerunning the analyses with medication status as a covariate did not alter any findings, future studies may strive to limit variations in medication status between study populations more stringently. A final limitation is the nature of pediatric studies, where children are undergoing dynamic developmental and disorder-related brain changes and adaptations. This study, along with other pediatric studies, may not be fully comparable with adult populations in which disorder and developmental states are more stabilized. For example, some prior longitudinal reports examining co-occurring ADHD and PTD have indicated transitions away from an additive model as development progresses toward adulthood (
). Additional longitudinal neurophysiological studies spanning childhood to adulthood may be beneficial in understanding how developmental trajectories for ADHD, PTD, and comorbid ADHD+PTD change across development.
In conclusion, this study identified shared and unique patterns of atypical resting-state functional connectivity with respect to diagnoses of ADHD and PTD. The majority of atypical connections were associated with the presence of ADHD, in concurrence with frequently reported ADHD-driven behavioral deficits. Similar to general behavioral deficits, aberrant resting-state neural connectivity in pediatric ADHD and PTD combines additively in co-occurring cases. Significant associations between lower connectivity within DMN and cognitive control network nodes and ADHD-related behavior problems suggest that neural network activity affects clinical impairment. The one unique PTD connectivity feature may be linked to tic generation and expression. Given the heterogeneity and frequent comorbidity of the two disorders, transdiagnostic studies can provide insight into the degree to which the disorders, individually and in combination, may contribute to impaired behavioral, cognitive, and neurophysiological impairments and warrant attention for treatment.
Acknowledgments and Disclosures
This work was supported by funding provided by National Institutes of Neurological Disease and Stroke (Grant Nos. 80160 and 97484 [to SKL]) and National Institute of Mental Health (Grant No. R34 MH10182 [to SKL]).
The Swartz Center for Computational Neuroscience was founded in 2001 by a generous gift from founding donor Dr Jerome Swartz of The Swartz Foundation (Old Field, New York). We thank all the families that participated in this research.
The authors report no biomedical financial interests or potential conflicts of interest.
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Comparative study of the behavioral and neuropsychologic characteristics of tic disorder with or without attention-deficit hyperactivity disorder (ADHD).
Attentional performance in children and adolescents with tic disorder and co-occurring attention-deficit/hyperactivity disorder: New insights from a 2 × 2 factorial design study.
Increased event-related theta activity as a psychophysiological marker of comorbidity in children with tics and attention-deficit/hyperactivity disorders.
Combining disrupted and discriminative topological properties of functional connectivity networks as neuroimaging biomarkers for accurate diagnosis of early Tourette syndrome children.
Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (K-SADS-PL): Initial reliability and validity data.
J Am Acad Child Adolesc Psychiatry.1997; 36: 980-988
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