Conners Continuous Performance Research Articles

Validation of a Brief Cognitive Assessment for Concussion Delivered on a Mobile Device

AbstractPrevious research found the Conners Continuous Performance Test (3rd ed; CCPT3) to predict concussion outcomes, but delivery was on a desktop device which can undermine broad use. We examine whether a shortened, mobile CCPT3 predicts concussion symptom endorsement and severity, and evaluate whether the predictive validity changes after controlling for ADHD. From July 2021 to January 2022, 143 participants aged 11 to 23 (approximately 30% female), including 63 consecutively assessed individuals suspected of having a concussion, and 80 randomly selected healthy controls, completed the mobile CCPT3 and the 31-item CDC concussion symptom checklist with severity ratings. Regression analyses indicate the mobile CCPT3 accounts for 19% variance (p < 0.01, d = 0.97) in symptom severity and 17.2% variance (p < 0.01, d = 0.91) in symptom endorsement. Findings persist after controlling for the experience of ADHD. Moreover, CCPT3 scores can differentiate among those suspected of having a concussion, predicting 27.6% variance in total symptom severity (p = 0.02, d = 1.24). Thus, a brief, objective mobile cognitive assessment yields large effect sizes when predicting concussion symptoms, and findings are comparable to previous research. Because the mobile assessment can be administered almost immediately post-injury and in between clinical visits, it can further inform post-injury medical care, rehabilitation, and return-to-play decisions.

Diagnostic Utility of Conners Continuous Performance Test-3 for Attention Deficit/Hyperactivity Disorder: A Systematic Review

Objective: To review the literature on the utility of the Conners CPT-3 in persons with ADHD. Methods: A systematic review was conducted. Six databases were searched using inclusion criteria: research studies, year 2000+, English, and ages 8+. Two raters independently screened 1,480 title/abstracts and subsequently reviewed 399 full texts. Data extraction and critical appraisal were conducted. Reflective thematic analysis through inductive coding identified qualitative themes. Results: Thirteen studies met inclusion criteria with five themes identified. Five studies found CPT-3 was a weak or poor predictor of ADHD diagnosis while two found it was an adequate predictor. Two studies found CPT-3 could differentiate clients with comorbid ADHD/anxiety from ADHD or ADHD from obsessive-compulsive disorder. One found CPT-3 could not differentiate ADHD from ASD or comorbid ADHD/ASD. Conclusions: Results revealed CPT-3 as a standalone measure is a weak or poor predictor of ADHD. Multiple measures for evaluating persons with ADHD are recommended.

Theta/beta ratio in EEG correlated with attentional capacity assessed by Conners Continuous Performance Test in children with ADHD.

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder affecting children worldwide; however, diagnosing ADHD remains a complex task. Theta/beta ratio (TBR) derived from electroencephalography (EEG) recordings has been proposed as a potential biomarker for ADHD, but its effectiveness in children with ADHD remains controversial. Behavioral assessments, such as the Conners Continuous Performance Test-3rd edition (CPT-3), have been utilized to assess attentional capacity in individuals with ADHD. This study aims to investigate the correlation between TBR and CPT-3 scores in children and adolescents with ADHD. In a retrospective analysis, we examined patients regularly monitored for ADHD at Taipei Tzu Chi Hospital, who underwent both EEG and CPT-3 assessments. Severity of ADHD was evaluated using parent- and teacher-completed Swanson, Nolan, and Pelham (SNAP)-IV rating scales. The study encompassed 55 ADHD patients (41 with abnormal CPT-3 scores, 14 with normal CPT-3 scores) and 45 control subjects. TBR demonstrated elevation in ADHD patients with abnormal CPT-3 scores, indicating its potential to represent attentional capacity akin to behavioral assessments like CPT-3. However, significant correlations between TBR values and CPT-3 variables or SNAP-IV rating scales were not observed. Moreover, TBR values exhibited considerable overlap across the groups, leading to diminished sensitivity and negative predictive value as a potential neurophysiological ADHD biomarker. While our study underscores the utility of both TBR and CPT-3 in assessing attentional capacity, their sensitivity in diagnosing ADHD is limited. A comprehensive evaluation, integrating clinical expertise, parental input, and detailed neuropsychometric tests, remains pivotal for a thorough and precise diagnosis of ADHD.

Limited usefulness of neurocognitive functioning indices as predictive markers for treatment response to methylphenidate or neurofeedback@home in children and adolescents with ADHD.

Earlier studies exploring the value of executive functioning (EF) indices for assessing treatment effectiveness and predicting treatment response in attention-deficit/hyperactivity disorder (ADHD) mainly focused on pharmacological treatment options and revealed rather heterogeneous results. Envisioning the long-term goal of personalized treatment selection and intervention planning, this study comparing methylphenidate treatment (MPH) and a home-based neurofeedback intervention (NF@Home) aimed to expand previous findings by assessing objective as well as subjectively reported EF indices and by analyzing their value as treatment and predictive markers. Children and adolescents (n = 146 in the per protocol sample) aged 7-13 years with a formal diagnosis of an inattentive or combined presentation of ADHD were examined. We explored the EF performance profile using the Conners Continuous Performance Task (CPT) and the BRIEF self-report questionnaire within our prospective, multicenter, randomized, reference drug-controlled NEWROFEED study with sites in five European countries (France, Spain, Switzerland, Germany, and Belgium). As primary outcome for treatment response, the clinician-rated ADHD Rating Scale-IV was used. Patients participating in this non-inferiority trial were randomized to either NF@home (34-40 sessions of TBR or SMR NF depending on the pre-assessed individual alpha peak frequency) or MPH treatment (ratio: 3:2). Within a mixed-effects model framework, analyses of change were calculated to explore the predictive value of neurocognitive indices for ADHD symptom-related treatment response. For a variety of neurocognitive indices, we found a significant pre-post change during treatment, mainly in the MPH group. However, the results of the current study reveal a rather limited prognostic value of neurocognitive indices for treatment response to either NF@Home or MPH treatment. Some significant effects emerged for parent-ratings only. Current findings indicate a potential value of self-report (BRIEF global score) and some objectively measured neurocognitive indices (CPT commission errors and hit reaction time variability) as treatment markers (of change) for MPH. However, we found a rather limited prognostic value with regard to predicting treatment response not (yet) allowing recommendation for clinical use. Baseline symptom severity was revealed as the most relevant predictor, replicating robust findings from previous studies.

Abnormal wiring of the structural connectome in adults with ADHD.

Current knowledge of white matter changes in large-scale brain networks in adult attention-deficit/hyperactivity disorder (ADHD) is scarce. We collected diffusion-weighted magnetic resonance imaging data in 40 adults with ADHD and 36 neurotypical controls and used constrained spherical deconvolution-based tractography to reconstruct whole-brain structural connectivity networks. We used network-based statistic (NBS) and graph theoretical analysis to investigate differences in these networks between the ADHD and control groups, as well as associations between structural connectivity and ADHD symptoms assessed with the Adult ADHD Self-Report Scale or performance in the Conners Continuous Performance Test 2 (CPT-2). NBS revealed decreased connectivity in the ADHD group compared to the neurotypical controls in widespread unilateral networks, which included subcortical and corticocortical structures and encompassed dorsal and ventral attention networks and visual and somatomotor systems. Furthermore, hypoconnectivity in a predominantly left-frontal network was associated with higher amount of commission errors in CPT-2. Graph theoretical analysis did not reveal topological differences between the groups or associations between topological properties and ADHD symptoms or task performance. Our results suggest that abnormal structural wiring of the brain in adult ADHD is manifested as widespread intrahemispheric hypoconnectivity in networks previously associated with ADHD in functional neuroimaging studies.

Birth-Related Risk Factors Impact Cognitive and Academic Outcomes in Children with Sickle Cell Disease

Pre- and peri-natal-related risk factors are associated with slowed neurocognitive development and increased risk of learning difficulties in the general population. A recent study reported expressive language deficits were associated with preterm birth in young children with sickle cell disease (SCD) (Bills et al., 2021); however, no studies to date have examined the long-term impact of low birth weight in children and adolescents with SCD. In this cohort study, we examined associations between low birth weight (<2500g) and cognitive and academic outcomes, including formal school support services (i.e., 504 Plan or Individual Education Program), in children with SCD. Gestational age and neonatal intensive care unit (NICU) admission were investigated as covariates. Participants were children ages 8-18 years old with SCD enrolled in the Sickle Cell Clinical Research and Intervention Program (SCCRIP), an observational cohort study of clinical outcomes in SCD. Participants received targeted neurocognitive evaluations as standard of care every 3-4 years. Performance-based neurocognitive measures were used to assess cognitive and academic abilities, including the Wechsler Abbreviated Scale of Intelligence, Second Edition; Wechsler Intelligence Scale for Children, Fourth and Fifth Editions; Wechsler Adult Intelligence Scale, Fourth Edition; Delis Kaplan Executive Function System; Conners Continuous Performance Test, Second and Third Editions; and Woodcock-Johnson Tests of Achievement, Third and Fourth Editions. Multivariable generalized linear regression examined associations between birth-related risk factors (i.e., birth weight, gestational age, and NICU admission) and cognitive outcomes, academic achievement, and need for school support services after adjusting for age, sex, hydroxyurea treatment, sickle genotype, and socioeconomic status. P-values <0.05 were considered significant. False discovery rate-adjusted p-values or q-values were calculated across the outcomes and all birth-related risk factors to correct for multiple corrections. Of the 326 participants in SCCRIP who completed neurocognitive evaluations, 282 children had normal birth weight (HbSS/HbSβ 0thalassemia=56%) and 44 children were born with low birth weight (HbSS/HbSβ 0=45%). Birth weight groups (<2500g and >2500g) were matched for demographic and disease characteristics (Table 1). The mean age at time of cognitive evaluation was 11.16 (SD= 3.27) years and half of participants were male (51%). Low birth weight was associated with worse word reading (p=0.011; Table 2). Across all participants, admission in the NICU was associated with lower verbal reasoning (p=0.022), processing speed (p=0.017), working memory (p=0.044), word reading (p=0.021), and math fluency (p=0.05). Similarly, across all participants, earlier gestational age was associated with lower verbal fluency (p=0.011). Low birth weight and gestational age predicted need for school support services (p=0.003 and p=0.007, respectively). History of birth-related risk factors should be considered a comorbidity for neurodevelopmental differences in SCD. Specifically, children with SCD who are born with low birth weight or admitted to the NICU are at increased risk for difficulties with processing speed, working memory, language, and academics. The need for formal school support services in SCD is associated with gestational age and birth weight.

Is the Conners’ continuous performance test helpful for assessing attention deficit hyperactivity disorder in a clinical setting?

Background Despite lacking validation for Norwegian populations, the Conners Continuous Performance Test II (CCPT-II) is applied to almost one-third of children receiving an ADHD diagnosis. However, evidence of the CCPT-II’s ability to differentiate between children with and without ADHD is contradictory. Thus, this study examines how CCPT-II results correlate with ADHD symptoms reported by mothers and teachers in a sample representing ordinary child and adolescent mental health services and explores the extent to which the CCPT-II influences the diagnostic result. Methods Correlations between CCPT-II results and ADHD Rating Scale scores and a clinical diagnosis of ADHD were analysed in children aged 6–15 years (N = 69) referred to a child and adolescent psychiatric outpatient clinic. Results Total ADHD symptom scores rated by mothers correlated with hit reaction time (HRT) block change (.260), HRT inter-stimulus interval (ISI) change (.264) and CCPT-II overall index (.263), while hyperactivity subscale scores correlated with omissions (.285), HRT (.414) and variability (.400). In teachers’ ratings, total ADHD and both subscale scores correlated with commissions (.280–.382), while hyperactivity scores correlated with variability (.265). A higher number of commissions was the only significant difference in CCPT-II performance between children diagnosed with and children without ADHD. Conclusions Correlations between CCPT-II results and ADHD symptoms were all small to moderate. As such, CCPT-II results should be interpreted with caution, because they correspond to a limited degree with other sources of information.

27 Differentiating Attention-deficit/Hyperactivity Disorder (ADHD) Subtype Using Continuous Performance Tests Among Children with Comorbid ADHD and Anxiety

Objective:Continuous performance tests (CPT) are often considered the gold standard for the diagnosis attention-deficit/hyperactivity disorder (ADHD), particularly when parent and teacher rating scales are inconclusive. Prior work has indicated that CPT can also help differentiate between ADHD subtypes. However, the ability of CPT to differentiate ADHD subtype has not been examined among youth with comorbid ADHD and anxiety (ADHD+A). This is particularly concerning as the extant literature suggests that anxiety symptoms may exacerbate deficits associated with ADHD (e.g.. , working memory, attention) and attenuate others (e.g., inhibition); thus, anxiety may influence expected patterns on the CPT. This study therefore seeks to examine the role of ADHD subtype on the relationship between ADHD+A and performance on a CPT among youth with ADHD+A.Participants and Methods:Participants included 54 children ranging from 6 to 20 years old (Mage=11.83, 54% female) who were diagnosed with ADHD+A via neuropsychological evaluation. In terms of ADHD subtype, 51.9% (n=28) were diagnosed with ADHD combined or ADHD primarily hyperactive and 48.1% (n=26) were diagnosed with ADHD primarily inattentive. Approximately 46.30% (N=25) of participants were medication naive. Analyses were conducted using data from the Conners Kiddie Continuous Performance Test -Second Edition (KCPT-2), Conners Continuous Performance - Second Edition (CPT-2) and the Conners Continuous Performance - Third Edition (CPT-3), which are part of the same family of performance-based attention measures. Independent samples t-tests were conducted to examine performance differences in aspects of attention (e.g., inattentiveness, sustained attention) and hyperactivity (e.g., impulsivity, inhibition).Results:ADHD subtype was not significantly related to measures of inattentiveness. This includes the number of targets missed (omissions; (t(39)=-.532, p=.59)) and variability in response time (variability; (t(39)=-0.30, p=.77)). In terms of sustained attention, ADHD subtype was not related to variability in response speed across blocks (Hit SEBC/HRT Block Change; (t(39)=-0.26, p=.79)). Importantly, these results were consistent regardless of ADHD medication status. ADHD subtype was also not significantly related to impulsivity. This includes responses to nontargets (commissions; (t(39)=-1.05, p=.30)), random or anticipatory responding (perseverations; (t(39)=-0.19, p=.85)), and mean response speed of correct responses (HR; (t(39)=-0.72, p=.48)).Conclusions:The extant literature suggests that CPT can help clinicians differentiate between ADHD subtypes. However, the results of this study indicate that there are no performance differences on the CPT among youth with comorbid ADHD and anxiety. There are several limitations to consider. First, this study had a relatively small sample size, which also limited the ability to examine ADHD primarily hyperactive/impulsive as a distinct subtype. Additionally, this study did not examine the effect of individual anxiety disorders (i.e., generalized anxiety disorder, specific phobias). Finally, these findings may not generalize to other standardized measures of attention or more ecologically valid measures. Despite these limitations, this study is an important step in understanding the relationship between ADHD+A and performance on attention measures. Clinicians should be cautious in using results from CPT to distinguish between ADHD subtype among children with comorbid anxiety.

21 Toxic Wounds are Associated with Cognitive Decrements in Women Veterans of the 1991 Gulf War

Objective:Gulf War Illness (GWI) is a debilitating multi-symptom condition that affects nearly a third of 1990-91 Gulf War (GW) veterans. Symptoms include chronic pain, debilitating fatigue, gastrointestinal issues, and cognitive decrements. Prior studies have documented reduced cognitive functioning in this affected population, particularly in the areas of memory, attention and response inhibition. To date, research has focused on cognitive functioning in male and female veterans together. Very limited research has reported on GW women's cognitive functioning separately mostly due to scarcity of data on women veterans. In this study, we had the unique opportunity to utilize a newly combined neuropsychological test dataset from women GW veterans in the Boston, Biorepository and Integrative Network (BBRAIN) for GWI. The aim was to compare neuropsychological outcomes with toxicant exposures in women veterans with and without GWI.Participants and Methods:Cognitive data from the BBRAIN biorepository was used for this study. The sample consisted of 62 women veterans who were deployed to the Persian Gulf War from 1990-91. Neuropsychological test scores included the Conners Continuous Performance Test Third Edition (CPT3), Delis-Kaplan Executive Function System (D-KEFS) Color-Word Interference, and the California Verbal Learning Test Second Edition (CVLT-II). War-related exposure to chemical weapons, anti-nerve gas pills and pesticides were measured by a self-reported survey. For analysis, war-related exposure was classified into three groups: controls with 0-6 days of exposure; cases with 0-6 days of exposure and cases with 7 or more days of exposure. Multiple linear regression modeling was used to measure differences in neuropsychological scores across the three groups by each war-related exposure.Results:After adjusting for age, education and other exposures, an increase in duration of exposure to pesticides was significantly associated with worse CPT3 commission errors, fewer words correct in the CVLT-II trials 1-5, and an increase in self-corrected errors on DKEFS Color-Word Interference Test Trials 1, 2 and 4 (p<0.05). More days reported hearing chemical alarms and seeing smoke from oil well fires was significantly associated with fewer words correct on all CVLT-II trials, and more self-corrected errors on Color-Word Interference Trials 2 and 4 (p<0.05). An increase in exposure duration to pyridostigmine bromide anti-nerve gas pills was associated with fewer words correct on the CVLT-II learning Trials 1-5 and short delay recall and an increase in self-corrected errors on Color-Word Interference Trials 2, 3, and 4 (p<0.05). When associations were adjusted for PTSD, all significant associations stayed constant (p<0.05).Conclusions:In this study, women veterans with GWI who had higher levels of exposure to pesticides, oil well fires and who took more antinerve gas pills during the war are showing increased learning difficulties and more deficits in attention and response inhibition. Future research should examine if similar patterns of neuropsychological symptoms are also present in male GW veterans with higher war-time related toxicant exposures.

43 Chronic Neurobehavioral and Cognitive Symptoms in Combat Deployed Military Service Personnel With and Without History of Blast-Related Mild Traumatic Brain Injury

Objective:Investigate the relationship of chronic neurobehavioral and cognitive symptoms in military personnel with history of blast-related mild TBI and compare to a well-matched group of combat-deployed controls.Participants and Methods:274 participants (mean age=34 years; mean education=14.75 years; 91.2% male) enrolled in the EVOLVE longitudinal study of combat-deployed military personnel were subdivided into those with history of blast TBI (n=165) and controls without history of blast exposure and TBI (n=109). As part of a larger study, we conducted a sub-analysis of 5-year follow up data. We focused on group differences (Mann-Whitney U) and correlational relationships between self-report neurobehavioral symptoms via the Frontal Systems Behavior Scale (FrSBE) and cognitive performances on measures of attention, working memory, processing speed, and executive functioning including D-KEFS Color Word Interference (CWI), Trailmaking A and B, and the Conners Continuous Performance Test (CPT).Results:The Blast TBI group reported higher levels of neurobehavioral symptoms on the FrSBE (p<.001), including domains of apathy (p<.001), disinhibition (p<.001), and executive dysfunction (p<.001), compared to Controls. On cognitive measures, group differences were observed on CWI Inhibition/Switching (p=.008), Trails B time (p=.010), and CPT commission errors (p=.014), such that the Blast TBI group performed worse than Controls. No significant group differences were observed for CPT omission errors or CPT hit rate (p’s>.05). After adjustment for multiple comparisons, greater FrSBE apathy correlated with slower performance on Trails A for Blast TBI (r=0.22, p=.014) but not Controls. Apathy endorsement was not significantly related to CPT omission errors for either group (p’s>.05). Higher endorsement of disinhibition symptoms was associated with worse performance on CWI Inhibition (Blast TBI: r=-0.19, p=.036; Controls: r=-0.28, p=.012) and Inhibition/Switching (Blast TBI: r=-0.23, p=.010; Controls: r=-0.29, p=.010) conditions for both groups, whereas only the Blast TBI group showed significant relationships between disinhibition symptoms and Trails B-A time (r=0.20, p=.025) and CPT commission errors (r=.18, p=.038). Higher endorsement of executive dysfunction correlated with poorer performance for Trails B-A for both groups (Blast TBI: r=.24, p=.009; Controls: r=.24, p=.030).Conclusions:Our findings reveal that at 5-year follow up, military personnel with history of blast-related mild TBI reported significantly greater neurobehavioral symptoms and performed lower on standardized measures of executive functioning, relative to combat-deployed controls without TBI or blast exposure. Significant relationships between neurobehavioral symptoms and cognitive performance were present in both groups. However, these relationships were more pronounced in the Blast TBI group, including greater apathy associated with slower visual tracking as well as greater endorsement of disinhibition associated with set-switching. Objective measures of response inhibition were related to disinhibition endorsement for both groups, though impulsive errors were more pronounced for the Blast TBI group. Our results suggest chronic cognitive and neurobehavioral symptoms are present in military personnel with history of blast TBI exposure, and also discrepant from a well-matched control group of combat deployed military personnel. Future studies of this population should explore models to predict cognitive performance from neurobehavioral symptoms in military personnel, as this could inform treatment approaches for those at greatest risk of cognitive change.

22 Neuropsychological Outcomes Vary by Sex in Neurotoxicant Exposed Veterans with Gulf War Illness

Objective:More than 30 years after the 199091 Gulf War (GW), approximately 200,000 veterans are still suffering from Gulf War Illness (GWI). Veterans who have this multi-symptom disorder experience impaired cognition, chronic pain, sustained fatigue, and gastrointestinal issues. GWI is believed to be associated with neurotoxicant exposures during the war. Prior research has shown cognitive deficits in combined samples of male and female GW veterans with GWI. These studies have shown that veterans with GWI have cognitive decrements in memory, learning and sustained attention. Studies have yet to compare neuropsychological outcomes by sex. This is mainly due to the lack of collected data on women GW veterans in the past. This study aims to analyze neuropsychological differences in males compared with female veterans with GWI and in those with neurotoxicant exposures from the Boston, Biorepository and Integrative Network (BBRAIN) for GWI repository dataset.Participants and Methods:The total sample included 297 veterans with GWI (women n=50, men n=247) who were deployed to the 1990-91 Gulf War with an average age of 52 years. GWI case status was defined by the Kansas GWI criteria. Neuropsychological data including the Conners Continuous Performance Test Third Edition (CPT3), Delis-Kaplan Executive Function System (D-KEFS) Color-Word Interference Test, and the California Verbal Learning Test (CVLT-II) were combined from the BBRAIN repository datasets. War-related exposures, including chemical weapons, anti-nerve gas pills and pesticides were measured by a self-reported survey. Multiple linear regression was used to analyze the association between sex, war-related exposures, and neuropsychological test score outcomes.Results:After adjusting for age, education level and PTSD, men had a significantly lower number of words correct in the CVLT-II learning Trials 1-5, short delay recall and long delay recall compared with women veterans (p<0.05). The two groups also differed significantly in CPT3 commission scores, and total time on the D-KEFs Color-Word Inference total times in Trials 1 and 2 with men performing worse (p<0.05). Reported exposure to chemical weapons, pesticides, pyridostigmine bromide (PB) anti-nerve gas pills or smoke from oil well fires were all significantly associated with fewer words correctly recalled on all learning trials of the CVLT-II, long delay, and short delay to a greater degree in men as compared to women (p<0.05). Reported exposure to chemical weapons or smoke from oil well fires were significantly associated with more commission errors on CPT3 in men with GWI (p<0.05). Chemical alarms, smoke from oil well fires and PB were associated with slower response time on the Color-Word Interference test Trial 1 in men compared with women veterans.Conclusions:In this study, men with GWI demonstrated significantly poorer performance in verbal memory, learning, response speed and attention. Male veterans reporting neurotoxicant exposures during the war also showed worse learning and verbal memory, impulsivity and response speed decrements compared to exposed women veterans. Future research should consider men and women separately when examining outcomes from war-related exposures.

B - 46 Diagnostic Utility of Conners CPT-3 for ADHD: a Systematic Review.

There is ongoing debate about the diagnostic utility of Conners Continuous Performance Test 3 (CPT-3) for attention deficit/hyperactivity disorder (ADHD). Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA, 2020) reporting standards, a systematic review was conducted. Six bibliographic databases including MEDLINE, PsycINFO, and PsycARTICLES were searched using terms related to continuous performance tests and ADHD in January 2022 and again in October 2022. Inclusion criteria included research studies published since 2000, English language, and ages 8+. Screening was conducted independently by two reviewers, with 1480 title/abstracts reviewed followed by 399 full text articles. Any discrepancies were resolved by a third reviewer. A data extraction template was developed and piloted and critical appraisal of included studies was conducted using the Quality Assessment Tool for Quantitative Studies. Study results were analyzed using reflective thematic analysis through inductive coding (Braun & Clarke, 2006, 2019). Thirteen studies met the criteria and five qualitative themes were identified. Five studies found CPT-3 was a weak or poor predictor of the diagnosis of ADHD while two found it as an adequate predictor. Two studies found the CPT-3 could differentiate clients with comorbid ADHD/anxiety from ADHD or ADHD from obsessive-compulsive disorder. One study, however, found that CPT-3 could not differentiate ADHD from autism spectrum disorder (ASD) or comorbid ADHD/ASD. This systematic review revealed that CPT-3 as a standalone measure is a weak or poor predictor of ADHD and clinicians are recommended to use multiple measures for evaluating persons with ADHD.

Claudin-5, occludin, zonulin and tricellulin levels of children with attention-deficit/hyperactivity disorder

Background and objectivesAccumulating studies have pointed out that gut-blood and blood-brain barrier dysfunctions due to the alterations in permeability may play a role in the pathophysiology of neurodevelopmental disorders. Tight junctions are crucial components of these barriers and some peptides including claudin-5, occludin, zonulin and tricellulin are important components of these structures. This study aimed to investigate the relationship between these molecules and attention deficit hyperactivity disorder (ADHD) in children and adolescents. MethodsA total of 57 children with ADHD and 60 controls aged between 6 and 12 years were included in the study. The severity of ADHD symptoms was assessed through a parent-rated questionnaire, and Conner's Continuous Performance Test was administered to the study group. Serum levels of biochemical variables were measured using enzyme-linked immunosorbent assay kits. Biochemical parameter levels and scale scores were compared using Mann-Whitney U or Student's t tests. In addition, a multivariate analysis of covariance (MANCOVA) and a one-way analysis of covariance (ANCOVA) was performed on the outcome variables. Finally, a hierarchical regression model was conducted on the study group. ResultsSerum claudin-5 and tricellulin levels were significantly lower in the ADHD group compared to the control group. The difference between the groups in terms of serum claudin-5 and tricellulin levels remained significant after controlling for confounding factors such as age, gender and autistic characteristics. There was no significant difference between the groups in terms of serum zonulin and occludin levels. ConclusionThese results reveal that claudin-5 and tricellulin levels vary in patients with ADHD. Alterations in these peptides may affect the brain by leading to a dysregulation in intestinal or blood-brain barrier permeability. The causal relationship between these peptides and ADHD requires further investigation.

Inflamed but not impulsive: Acute inflammatory cytokine response does not impact prepotent response inhibition

BackgroundPrior evidence has linked inflammation with impulsivity, but most of this evidence is cross-sectional. In this study, we provoked an acute inflammatory cytokine response to see whether it lowered prepotent response inhibition on three cognitive tasks. MethodThis study features secondary analyses from a randomized crossover trial in which 171 postmenopausal breast cancer survivors (Stage I-IIIA) each received a typhoid capsular polysaccharide vaccination and a saline placebo injection in a random sequence at two separate visits at least one month apart. Participants completed the Stroop Color-Discrepant Task, the 2-back, and the Conners Continuous Performance Test (CPT) on the computer between 5 and 7 h after the injections. They had their blood drawn once before and repeatedly after the injection to measure interleukin-1 receptor antagonist and interleukin-6 responses. ResultsWomen committed marginally fewer errors on the Stroop color-discrepant trials after the typhoid vaccine (M = 0.36, SE = 0.08), compared to placebo (M = 0.54, SE = 0.09, p = .076). Injection type did not predict 2-back accuracy (p = .80) or CPT commission errors (p = .47). Inflammatory cytokine responses were also unrelated to the outcomes of interest (ps>.16). ConclusionWe found no evidence that an acute inflammatory cytokine response provokes response disinhibition – an important facet of impulsivity. In fact, our only marginally non-significant result suggested that women were better able to inhibit their prepotent responses on the Stroop after receiving the typhoid vaccine, compared to placebo. Further experimental tests of the acute inflammatory cytokine response's effect on other aspects of impulsivity are warranted. LimitationsThe sample was female, primarily White, highly educated cancer survivors, and recruitment was not premised on impulsive traits or diagnosis with an impulsive-related disorder. Also, there are many facets of impulsivity, and this study only measured response inhibition.

Depression, Inflammation, and Intestinal Permeability: Associations with Subjective and Objective Cognitive Functioning throughout Breast Cancer Survivorship.

About one-in-three breast cancer survivors have lingering cognitive complaints and objective cognitive impairment. Chronic inflammation and intestinal permeability (i.e., leaky gut), two risk factors for cognitive decline, can also fuel depression-another vulnerability for cognitive decline. The current study tested whether depression accompanied by high levels of inflammation or intestinal permeability predicted lower subjective and objective cognitive function in breast cancer survivors. We combined data from four breast cancer survivor studies (n = 613); some had repeated measurements for a total of 1015 study visits. All participants had a blood draw to obtain baseline measures of lipopolysaccharide binding protein-a measure of intestinal permeability, as well as three inflammatory markers that were incorporated into an inflammatory index: C-reactive protein, interleukin-6, and tumor necrosis factor-α. They reported depressive symptoms on the Center for Epidemiological Studies depression scale (CES-D), and a binary variable indicated clinically significant depressive symptoms (CES-D ≥ 16). The Kohli (749 observations) and the Breast Cancer Prevention Trial (591 observations) scales assessed subjective cognitive function. Objective cognitive function tests included the trail-making test, Hopkins verbal learning test, Conners continuous performance test, n-back test, FAS test, and animal-naming test (239-246 observations). Adjusting for education, age, BMI, cancer treatment type, time since treatment, study visit, and fatigue, women who had clinically elevated depressive symptoms accompanied by heightened inflammation or intestinal permeability reported poorer focus and marginally poorer memory. However, poorer performance across objective cognitive measures was not specific to inflammation-associated depression. Rather, there was some evidence of lower verbal fluency; poorer attention, verbal learning and memory, and working memory; and difficulties with visuospatial search among depressed survivors, regardless of inflammation. By themselves, inflammation and intestinal permeability less consistently predicted subjective or objective cognitive function. Breast cancer survivors with clinically significant depressive symptoms accompanied by either elevated inflammation or intestinal permeability may perceive greater cognitive difficulty, even though depression-related objective cognitive deficits may not be specific to inflammation- or leaky-gut-associated depression.

Executive and motor function in children with autism spectrum disorder.

The purpose of this study was to investigate the relationship between executive function, mainly attention and impulse control, and motor function impairment in children with ASD. Fifteen children with ASD (ages 8-14years) were examined on their executive function using the Conners continuous performance test-3 and motor function using the movement assessment battery for children-2 (MABC-2). It was found that children with ASD were delayed on executive and motor function. This means that those effects were also observed in male children with Autism Spectrum Disorder (ASD) who had similar characteristics as the participants in the study. This study may have practical implications in the relationship between executive function and motor performance in children with ASD and for clinicians and educators working with children with ASD. Furthermore, the findings suggest that variability in reaction time may be a useful predictor of motor skill performance in children with ASD and may reflect underlying difficulties in executive function and future research is suggested.

Association of markers of inflammation on attention and neurobehavioral outcomes in survivors of childhood acute lymphoblastic leukemia.

Survivors of childhood acute lymphoblastic leukemia (ALL) are at-risk of developing cognitive impairment and neurobehavioral symptoms. Inflammation induced by a compromised health status during cancer survivorship is proposed as a pathophysiological mechanism underlying cognitive impairment in cancer survivors. To evaluate the associations of biomarkers of inflammation with attention and neurobehavioral outcomes in survivors of childhood ALL, and to identify clinical factors associated with biomarkers of inflammation in this cohort. We recruited patients who were diagnosed with ALL at ≤ 18 years old and were currently ≥5 years post-cancer diagnosis. The study outcomes were attention (Conners Continuous Performance Test) and self-reported behavioral symptoms (Adult Self-Report [ASR] checklist). Using a commercial screening kit, survivors' plasma (5ml) was assayed for 17 cytokines/chemokine cell-signaling molecules that are associated with neurodegenerative diseases. The final panel of the targeted markers included interleukin (IL)-8, IL-13, interferon-gamma (IFN-γ), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1β, and tumor necrosis factor-α. Biomarker levels were rank-ordered into tertiles based on the sample distribution. Multivariable general linear modeling was used to test for associations between biomarkers and study outcomes in the overall cohort and stratified by gender. This study included 102 survivors (55.9% males, mean[SD] age 26.2[5.9] years; 19.3[7.1] years post-diagnosis). Survivors within top tertiles of IFN-γ (Estimate =6.74, SE=2.26; P=0.0037) and IL-13 (Estimate =5.10, SE=2.27; P=0.027) demonstrated more inattentiveness. Adjusting for age, gender and treatment, more self-reported thought (Estimate=3.53, SE=1.78; P=0.050) and internalizing problems (Estimate =6.52, SE=2.91; P=0.027) correlated with higher IL-8. Higher levels of IL-13 (RR = 4.58, 95% CI: 1.01-11.10) and TNF-α (RR = 1.44, 95% CI: 1.03-4.07) were observed in survivors had developed chronic health conditions (n=26, 25.5%). The stratified analysis showed that association of IFN-γ with attention was stronger in male survivors than in female survivors. Inflammation due to cancer-related late effects may potentially be mechanistic mediators of neurobehavioral problems in pediatric ALL survivors. Markers of inflammation can potentially be applied to assess or monitor the effectiveness of interventions, particularly behavioral interventions, in improving cognitive outcomes in survivors. Future work includes understanding the underlying gender-specific pathophysiology behind functional outcomes in the population.

Self-reported sleep difficulties and association with cognitive function in pediatric cancer survivors.

10065 Background: Preventing and ameliorating cognitive impairment following treatment for pediatric cancer remains a persistent challenge, with recent literature examining lifestyle factors as possible targets for intervention. An association between sleep and cognitive impairment has been identified in adult cancer patients and survivors, yet information is limited for pediatrics. Thus, the primary goal of our retrospective study was to explore self-reported sleep difficulties in pediatric patients and survivors with mixed cancers. A secondary aim was to explore the impact sleep problems on specific cognitive functions. Methods: Children and adolescents who completed neuropsychological assessments at two large pediatric cancer centers (N = 298) were identified via medical record review. In addition to demographic data, clinically collected cognitive tests included Wechsler Working Memory (WMI), Processing Speed (PSI), and General Ability (GAI) indices. Objective attention measures included Conners Continuous Performance Test (versions II and 3) Omissions (O), Commissions (C), and Reaction Time (RT). Sleep Disturbance (SD) and Sleep-Related Impairment (SRI) were captured using pediatric self-report PROMIS scales. PROMIS cut points were used to categorize sleep issues within the study population and PROMIS scores were compared to reference population means. Multiple linear regression was used to identify relationships between cognitive domains and sleep factors. Common cancer-related clinical and demographic characteristics were controlled as covariates. Results: 21.5% of patients reported severe SD, while 12.8%, 15.9% and 49.7% reported moderate, mild, and within normal limits (WNL) SD, respectively. For SRI, 13.3% reported severe SRI, while 20.0%, 15.9% and 50.8% reported moderate, mild and WNL SRI, respectively. Mean SD and SRI were higher than in the reference populations (p = 0.000 for both measures). Pearson correlation results suggested a moderate relationship between SD and SRI (r = 0.489, p = 0.000). After controlling for covariates, multiple linear regressions indicated significant relationships between SD and GAI (p = 0.006), SD and O (p = 0.018), and SRI and WM (p = 0.006). Conclusions: Results suggested that ~50% of our pediatric cancer patients and survivors reported SD and SRI. SD was correlated with SRI in our sample, and regression analysis indicates a significant relationship between sleep problems and O, WM, and GAI in our sample. Findings from this retrospective study suggest a relationship between sleep problems and cognitive performance in pediatric cancer survivors. As a potentially modifiable factor to improve cognitive function in pediatric cancer survivors, sleep difficulties warrant more research to potentially guide interventions to better manage and improve cognitive function in this population.

The Role of The Predominant Polarity on Neurocognitive and Social Cognitive Dysfunctions in Patients with Bipolar Disorder

IntroductionBipolar disorder (BD) is characterized by significant inter-individual variation in terms of course and outcome. The most important factors associated with the outcome are subsyndromal depression and cognitive disability. Predominant polarity (PP), which is a proposed course specifier for BD, can be associated with various clinical differences such as psychotic feature, suicidality, hospitalization, while it is thought to be associated with the severity of cognitive impairment.ObjectivesTo elucidate the role of the predominant polarity on cognitive dysfunction in patients with BD.MethodsPatients with BD in remission (n=84) and healthy control volunteers (HC, n=27) participated in the study. Patients were divided into 3 subgroups according to their PP characteristics: manic (MPP, n=31), depressive (DPP, n=25), and undetermined (UPP, n=28). Structured Clinical Interview for DSM-5 Disorders-Clinician Version (SCID-5/CV), WAIS-R-Vocabulary Subtest, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Young Mania Rating Scale, Rey’s Auditory Verbal Learning Test (RAVLT), Trail Making Test (TMT), Stroop Test (ST), WMS-R Visual Reproduction Subtest, Controlled Oral Word Association Test (COWAT), Auditory Consonant Trigrams Test (ACT), Reading the Mind in the Eyes Test (RMET), Hinting Test (HT), Wisconsin Card Sorting Test (WCST), and Conners Continuous Performance Test (CCPT) were administered. Scores that do not show normal distribution were transformed using the two-step normalization method. Principal component analysis (PCA) with direct oblimin rotation was applied as a dimension reduction technique to identify different neurocognitive domains. Single-factorial PCA was also applied to calculate global cognition scores.ResultsIn MPP group compared to HC, worse performance was observed in ACT (d=1.24), COWAT (d=1.16), RMET (d=1.03), HT (d=1.78), WCST correct answers (d=0.99), CCPT correct target section (d=0.99) and a prolongation in TMT-A (d=1.00). Compared to DPP, MPP had a weak performance in COWAT (d=0.89), RMET (d=0.86) and HT (d=1.00). MPP (d=1.18) and UPP (d=1.03) groups showed deterioration in processing speed compared to HC. MPP group showed impairment in working memory (d=1.17) and attention (d=0.70) compared to HC. In problem-solving and reasoning, deterioration was found in MPP compared to HC (d=1.16) and UPP (d=0.67), also in DPP compared to HC (d=0.74).ConclusionsThe MPP group yielded more severe cognitive impairment in verbal fluency and social cognition tests compared to DPP. Predominant polarity may also be related to cognitive impairment patterns seen in BD.Disclosure of InterestNone Declared

The Conners Continuous Performance Test CPT3™: Is it a reliable marker to predict neurocognitive dysfunction in Myalgic encephalomyelitis/chronic fatigue syndrome?

The main objective is to delimit the cognitive dysfunction associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in adult patients by applying the Continuous Performance Test (CPT3™). Additionally, provide empirical evidence on the usefulness of this computerized neuropsychological test to assess ME/CFS. The final sample (n = 225; 158 Patients/67 Healthy controls) were recruited in a Central Sensitization Syndromes (CSS) specialized unit in a tertiary hospital. All participants were administered this neuropsychological test. There were significant differences between ME/CFS and healthy controls in all the main measures of CPT3™. Mainly, patients had a worse indicator of inattentiveness, sustained attention, vigilance, impulsivity, slow reaction time, and more atypical T-scores, which is associated with a likelihood of having a disorder characterized by attention deficits, such as Attention Deficit Hyperactivity Disorder (ADHD). In addition, relevant correlations were obtained between the CPT3™ variables in the patient's group. The most discriminative indicators of ME/CFS patients were Variability and Hit Reaction Time, both measures of response speed. The CPT3™ is a helpful tool to discriminate neurocognitive impairments from attention and response speed in ME/CFS patients, and it could be used as a marker of ME/CFS severity for diagnosing or monitoring this disease.