The Rey Complex Figure (CF) is a popular test to assess visuospatial construction and visual memory, but its broader use in clinical research is limited by scoring complexity. To widen its application, we developed a new CF scoring system similar to the Benson Figure in which 10 primary CF elements are scored according to presence and location. A novel recognition task was also created for each of these 10 items consisting of a 4-choice recognition condition containing the primary rectangle and major interior lines with qualitative variations of target elements as distractors. The current investigation was designed to characterize the relationship between scoring methods and establish whether comparable results are obtained across both traditional and new CF scoring approaches.

Participants from the Emory Health Brain Study (EHBS) who had completed the Rey CF copy during their cognitive study visit were studied. All participants were self-identified as normal, and administered the CF according to our previously published procedure that included the Copy, Immediate Recall (∼ 30 seconds), and 30-minute Delayed Recall (Loring et al., 1990). Following delayed recall, CF recognition was assessed using the Meyers and Myers (1995) recognition followed by the newly developed forced choice recognition. The final sample included 155 participants ranging in age from 51.6 years to 80.0 years (M=64.9, SD=6.6). The average MoCA score was 26.8/30 (SD=6.6).

Mean performance levels across conditions and scoring approaches are included in the table. Correlations between Copy, Immediate Recall, Delayed Recall, and Recognition were calculated to evaluate the relationship between the traditional 18 item/36 point Osterrieth criteria and newly developed CF scoring criteria using both parametric and non-parametric approaches. Pearson correlations demonstrated high agreement between approaches when characterizing performance levels across all CF conditions (Copy r=.72, Immediate Recall r=.87, Delayed Recall r=.90, and Recognition r=.52). Similar correlations were present using non-parametric analyses (Copy ρ=.46, Immediate Recall ρ=.83, Delayed Recall ρ=.91, and Recognition ρ=.42). Table. Mean performance levels across conditions and scoring approaches

The high correlations, particularly for Immediate and Delayed Recall conditions, suggest that the modified simpler scoring system is comparable to the traditional approach, thereby suggesting potential equivalence between scoring methods. When comparing Rey’s original 47 point scoring approach to his 36 point scoring system, Osterrieth (1944) reported a correlation in fifty adults of ρ=.95 and a correlation in twenty 6-year-olds of ρ=.92. In this investigation, lower correlations were observed for copy and recognition conditions, in part representing smaller response distribution across participants. Although these preliminary results are encouraging, to implement the new EHBS scoring method in clinical evaluation, we are developing normative data in participants across the entire EHBS series, many of whom were not administered the new CF Recognition. We are also examining performances in patients undergoing DBS evaluation for Parkinson Disease to explore its clinical sensitivity. Simpler scoring will permit greater CF clinical and research application.

Construction of predictive algorithms of concussion symptom recovery at 4 and 12 weeks post-injury using an evidence-based assessment (EBA) model to guide clinical decision-making, extending the 2016 5P decision rule.

Children and adolescents, ages 8-18 (n=1,551; mean age=12.78; 62% male), followed over 12 weeks in the prospective multicenter cohort study (Predicting Persistent Post-Concussive Problems in Pediatrics, 5P; Zemek et al., 2016). The age-specific PostConcussion Symptom Inventory (PCSI) (8-12, 17 items; 1318 years, 20 items) was completed at six timepoints from the ED and at 1, 2, 4, 8, and 12-weeks post-injury. Logistic regression analysis was applied to the set of key variables including the PCSI Total Retrospective-Adjusted PostInjury Difference (RAPID) scores, patient demographics and pre-injury history, and injury characteristics to predict participant recovery status (Recovered, Not Recovered) at the 4- and 12-week endpoints. The resulting recovery-predictive equations identified the significant sets of variables with symptom scores at four successive post-injury timepoints (ED, 1, 2, 4 weeks). Logistic Regression Threshold values were established at the 90th CI against which individual patient data was applied to determine recovery status. Participants with sub-threshold sums were deemed recovered at the target endpoint (4- or 12-weeks post-injury).

A total of 19 predictive equations were generated for the two age groups across the recovery timeline. Four sets of equations were developed to predict symptom recovery status at 4-weeks post-injury for the two age groups (8-12 AUC=0.679-0.884; 13-18 AUC=0.752-0.909). Prediction of symptom recovery status at 12-weeks post-injury yielded six equations for the 8-12 age group (AUC=0.723-0.825), and five equations for the 13-18 age group (AUC=0.724-0.887). Total PCSI RAPID score was identified as a significant variable in each of these 19 equations. Participant sex was identified as significant in 18 of the 19 constructed equations. Other variables that were identified as significant at varying timepoints included age, pre-injury history of learning disability and migraines, and an early post-injury sign in the ED (answering questions more slowly than usual). Examples of the equations include: Week 1 predicting symptom recovery status at 4-weeks: 8-12 yr group-(Sex*.802)+(week 1 Total RAPID Score*.142)+(Age2* .053)+(-3.851) with AUC=0.808; 13-18 yr group-(Sex*.980)+(Week 1 Total RAPID Score*.071)+(-3.261) with AUC=0.861.

Clinicians’ management of the concussion recovery of children and adolescents can benefit from EBA guidance. The 5P dataset (Zemek et al., 2016) provides an important window into “typical” and “atypical” recovery trajectories, establishing an initial predictive decision rule for a 4-week recovery endpoint, at the ED timepoint only, reporting AUC=0.69. The current study extends the prediction modeling using successive post-injury timepoints reflecting a typical management timeline. Symptom reports from both 1- and 2-weeks post injury with patient demographics/ history predicted symptom recovery status at 4- and 12-weeks post-injury, significantly improve predictive accuracy over the ED timepoint alone. These predictive equations, when applied to the individual patient, can serve to assist the clinician’s understanding of the patients’ recovery trajectory, i.e., on track for a typical or atypical recovery, further informing the intervention strategy.

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease that results in progressive decline in motor function in all patients and cognitive impairment in a subset of patients. Evidence suggests that cognitive reserve (CR) may protect against cognitive and motor decline in ALS, but less is known about the impact of specific occupational skills and requirements on clinical outcomes in ALS. We expected that a history of working jobs with more complex cognitive demands would protect against cognitive decline, while jobs that require fine and complex motor skills would protect against motor dysfunction.

Participants were 150 ALS patients recruited from the University of Pennsylvania’s Comprehensive ALS Center. Participants underwent clinical and neuropsychological evaluations within 1 year of ALS diagnosis. Cognitive performance was measured using the Edinburgh Cognitive and Behavioral ALS Screen (ECAS), which includes ALS-Specific (e.g., verbal fluency, executive functions, language, social cognition) and NonSpecific (e.g., memory, visuospatial functions) composite scores. Motor functioning was measured using the Penn Upper Motor Neuron (UMN) scale and the ALS Functional Rating Scale (ALS-FRS). Occupational skills and requirements for each participant were assessed using data from the Occupational Information Network (O*NET) Database. O*NET data were assessed using principal components analysis, and 17 factor scores were derived representing distinct worker characteristics (n=5), occupational requirements (n=7), and worker requirements (n=5). These scores were entered as independent variables in multiple linear regression models using ECAS, UMN, and ALS-FRS scores as dependent variables covarying for education.

Preserved ECAS ALS-Specific performance was associated with jobs that involve greater reasoning abilities (ß=2.03, S.E.=0.79, p<.05), analytic skills (ß=3.08, S.E.=0.91, p<.001), and humanities knowledge (ß=1.20, S.E.=0.58, p<.05), as well as less exposure to environmental hazards (ß=-2.42, S.E.=0.76, p<.01) and fewer demands on visualperceptual (ß=-1.75, S.E.=0.73, p<.05) and technical skills (ß=-1.62, S.E.=0.63, p<.05). Preserved ECAS Non-Specific performance was associated with jobs that involve greater exposure to conflict (ß=0.82, S.E.=0.33, p<.05) and social abilities (ß=0.65, S.E.=0.29, p<.05). Jobs involving greater precision skills (ß=1.92, S.E.=0.79, p<.05) and reasoning ability (ß=2.10, S.E.=0.95, p<.05) were associated with greater disease severity on the UMN, while jobs involving more health services knowledge were associated with worse motor functioning on the ALS-FRS (ß=-1.30, S.E.=0.60, p<.05).

Specific occupational skills and requirements show protective effects on cognitive functioning in ALS, while others confer risk for cognitive and motor dysfunction. Preserved cognitive functioning was linked to a history of employment in jobs requiring strong reasoning abilities, social skills, and humanities knowledge, while poorer cognitive functioning was linked to jobs involving a high risk of exposure to environmental hazards and high visuo-perceptual and technical demands. In contrast, we did not find evidence of motor reserve, as no protective effects of occupational skills and requirements were found for motor symptoms, and jobs involving greater precision skills, reasoning abilities, and health services knowledge were linked to worse motor functioning. Our findings offer new insights into how occupational history may protect against cognitive impairment or confer elevated risk for cognitive and motor dysfunction in ALS.

Therapeutics targeting frontotemporal dementia (FTD) are entering clinical trials. There are challenges to conducting these studies, including the relative rarity of the disease. Remote assessment tools could increase access to clinical research and pave the way for decentralized clinical trials. We developed the ALLFTD Mobile App, a smartphone application that includes assessments of cognition, speech/language, and motor functioning. The objectives were to determine the feasibility and acceptability of collecting remote smartphone data in a multicenter FTD research study and evaluate the reliability and validity of the smartphone cognitive and motor measures.

A diagnostically mixed sample of 207 participants with FTD or from familial FTD kindreds (CDR®+NACC-FTLD=0 [n=91]; CDR®+NACC-FTLD=0.5 [n=39]; CDR®+NACC-FTLD>1 [n=39]; unknown [n=38]) were asked to remotely complete a battery of tests on their smartphones three times over two weeks. Measures included five executive functioning (EF) tests, an adaptive memory test, and participant experience surveys. A subset completed smartphone tests of balance at home (n=31) and a finger tapping test (FTT) in the clinic (n=11). We analyzed adherence (percentage of available measures that were completed) and user experience. We evaluated Spearman-Brown split-half reliability (100 iterations) using the first available assessment for each participant. We assessed test-retest reliability across all available assessments by estimating intraclass correlation coefficients (ICC). To investigate construct validity, we fit regression models testing the association of the smartphone measures with gold-standard neuropsychological outcomes (UDS3-EF composite [Staffaroni et al., 2021], CVLT3-Brief Form [CVLT3-BF] Immediate Recall, mechanical FTT), measures of disease severity (CDR®+NACC-FTLD Box Score & Progressive Supranuclear Palsy Rating Scale [PSPRS]), and regional gray matter volumes (cognitive tests only).

Participants completed 70% of tasks. Most reported that the instructions were understandable (93%), considered the time commitment acceptable (97%), and were willing to complete additional assessments (98%). Split-half reliability was excellent for the executive functioning (r’s=0.93-0.99) and good for the memory test (r=0.78). Test-retest reliabilities ranged from acceptable to excellent for cognitive tasks (ICC: 0.70-0.96) and were excellent for the balance (ICC=0.97) and good for FTT (ICC=0.89). Smartphone EF measures were strongly associated with the UDS3-EF composite (ß's=0.6-0.8, all p<.001), and the memory test was strongly correlated with total immediate recall on the CVLT3-BF (ß=0.7, p<.001). Smartphone FTT was associated with mechanical FTT (ß=0.9, p=.02), and greater acceleration on the balance test was associated with more motor features (ß=0.6, p=0.02). Worse performance on all cognitive tests was associated with greater disease severity (ß's=0.5-0.7, all p<.001). Poorer performance on the smartphone EF tasks was associated with smaller frontoparietal/subcortical volume (ß's=0.4-0.6, all p<.015) and worse memory scores with smaller hippocampal volume (ß=0.5, p<.001).

These results suggest remote digital data collection of cognitive and motor functioning in FTD research is feasible and acceptable. These findings also support the reliability and validity of unsupervised ALLFTD Mobile App cognitive tests and provide preliminary support for the motor measures, although further study in larger samples is required.

Interventions using a cognitive training paradigm called the Useful Field of View (UFOV) task have shown to be efficacious in slowing cognitive decline. However, no studies have looked at the engagement of functional networks during UFOV task completion. The current study aimed to (a) assess if regions activated during the UFOV fMRI task were functionally connected and related to task performance (henceforth called the UFOV network), (b) compare connectivity of the UFOV network to 7 resting-state functional connectivity networks in predicting proximal (UFOV) and near-transfer (Double Decision) performance, and (c) explore the impact of network segregation between higher-order networks and UFOV performance.

336 healthy older adults (mean age=71.6) completed the UFOV fMRI task in a Siemens 3T scanner. UFOV fMRI accuracy was calculated as the number of correct responses divided by 56 total trials. Double Decision performance was calculated as the average presentation time of correct responses in log ms, with lower scores equating to better processing speed. Structural and functional MRI images were processed using the default pre-processing pipeline within the CONN toolbox. The Artifact Rejection Toolbox was set at a motion threshold of 0.9mm and participants were excluded if more than 50% of volumes were flagged as outliers. To assess connectivity of regions associated with the UFOV task, we created 10 spherical regions of interest (ROIs) a priori using the WFU PickAtlas in SPM12. These include the bilateral pars triangularis, supplementary motor area, and inferior temporal gyri, as well as the left pars opercularis, left middle occipital gyrus, right precentral gyrus and right superior parietal lobule. We used a weighted ROI-to-ROI connectivity analysis to model task-based within-network functional connectivity of the UFOV network, and its relationship to UFOV accuracy. We then used weighted ROI-to-ROI connectivity analysis to compare the efficacy of the UFOV network versus 7 resting-state networks in predicting UFOV fMRI task performance and Double Decision performance. Finally, we calculated network segregation among higher order resting state networks to assess its relationship with UFOV accuracy. All functional connectivity analyses were corrected at a false discovery threshold (FDR) at p<0.05.

ROI-to-ROI analysis showed significant within-network functional connectivity among the 10 a priori ROIs (UFOV network) during task completion (all pFDR<.05). After controlling for covariates, greater within-network connectivity of the UFOV network associated with better UFOV fMRI performance (pFDR=.008). Regarding the 7 resting-state networks, greater within-network connectivity of the CON (pFDR<.001) and FPCN (pFDR=. 014) were associated with higher accuracy on the UFOV fMRI task. Furthermore, greater within-network connectivity of only the UFOV network associated with performance on the Double Decision task (pFDR=.034). Finally, we assessed the relationship between higher-order network segregation and UFOV accuracy. After controlling for covariates, no significant relationships between network segregation and UFOV performance remained (all p-uncorrected>0.05).

To date, this is the first study to assess task-based functional connectivity during completion of the UFOV task. We observed that coherence within 10 a priori ROIs significantly predicted UFOV performance. Additionally, enhanced within-network connectivity of the UFOV network predicted better performance on the Double Decision task, while conventional resting-state networks did not. These findings provide potential targets to optimize efficacy of UFOV interventions.

General cognitive ability (g) is central to our understanding of human cognition, as it accounts for nearly half of individual differences in performances on diverse cognitive tests. There is growing interest in the brain networks necessary for g because such knowledge could elucidate neural mechanisms of g. Prior work highlighted the association between g and frontoparietal functional networks. However, the specificity of this relationship has been questioned. Moreover, no studies have compared the relative importance of structural and functional networks for g, and most studies have relied on data from neurologically healthy individuals, which limits causal brain-behavior inference. Lesion network mapping (LNM) can overcome such limitations. LNM integrates lesion location and structural and functional brain network data, and allows for inference upon networks necessary for cognitive functions. Here, we used data from three cohorts of patients with focal brain lesions to perform a large-scale LNM study of g. We also compared the relative value of lesion-behavior mapping, and structural and functional LNM, for predicting g across cohorts.

Using data from 402 individuals with chronic, focal brain lesions from the Iowa Neurological Patient Registry, we created a bifactor model to estimate g from the shared variance across neuropsychological tests. To create “cognitive comparisons,” we also estimated the unique aspects of domain-specific abilities (visuospatial processing, memory, and processing speed) by removing domain-general variance from each. Next, we used multivariate lesion-behavior mapping to create statistically weighted maps linking deficits in g and domain-specific abilities to regions of focal brain damage. To perform LNM, the local maxima of the lesion-behavior maps were used as seeds for structural and functional connectivity analyses based on normative diffusion-weighted imaging and resting-state functional connectivity data, respectively. The resulting maps were collapsed using principal components analysis (PCA). We quantified the overlap between each map and the lesion volumes of patients from two validation cohorts (n = 101, n = 100). We used these scores to predict observed g in the validation cohorts while controlling for lesion volume. We also compared the relative predictive value of the lesion-behavior maps, and the structural and functional LNMs.

Lesion-behavior mapping indicated that lesions of left frontal white matter, bilateral frontal operculum/insula, and a region of white matter in the posterior left hemisphere were associated with impairments in g. Across all lesion-behavior mapping and LNM results, only two of the structural LNM maps linked to g were statistically significantly predictive of g in both validation cohorts: a map corresponding to the anterior thalamic radiation, and another corresponding to left frontal pyramidal projections. Both added value beyond lesion-behavior mapping and functional LNM.

The results are notable in several respects: they highlight the importance of structural networks for g, de-emphasize the relevance of functional networks for g, and suggest novel brain circuitry involved in g. Our findings are consistent with animal studies implicating anterior thalamic nuclei in working memory, a cognitive function central to g. Clinically, our study highlights the importance of considering domain-general deficits and the effects of focal lesions on distributed cognitive networks.

Set-shifting/switching tasks, among other measures of executive functioning, are typically thought to represent frontal lobe functioning. However, the neuroanatomical correlates of these tests are not fully established. The aim of this study was to examine associations between individual measures of set-shifting/switching and cortical thickness. We hypothesized that performance on each switching measure would strongly correlate with aggregated cortical thickness within the frontal lobe.

Measures of interest included set-shifting subtests of the Delis-Kaplan Executive Function System (DKEFS): Color-Word Inhibition Switching, Category Switching, and Trail Making Test Number-Letter Switching. Archival data from an outpatient memory disorders clinic were reviewed to identify individuals whose neuropsychological evaluations included the measures of interest and had quality-assessed, volumetric MRI data available (n=243; 53.1% male, 81.9% Caucasian, Mage=72.4, SDage=6.7). Cortical thickness values were generated by FreeSurfer and averages were calculated for both frontal and temporal lobes, separately. Using partial correlations, controlling for age, we explored associations between each switching trial separately with right and left, frontal and temporal cortical thickness. The strength of associations within each lobe were then compared using Fisher's r-to-z transformations.

Category Switching was significantly correlated with left and right hemisphere temporal thickness (r=0.38 and 0.31, respectively), but was not significantly correlated with left or right frontal lobe cortical thickness (r=.12 and .07, respectively). Fisher's r-to-z transformations revealed significantly stronger relationships between Category Switching and temporal thickness, rather than frontal thicknesses. Trails Switching was also significantly correlated with left and right temporal cortical thickness (r=-0.28, and =-0.23, respectively) and bore weaker associations with frontal cortical thickness (r=-.13 and r = -.14 for left and right hemispheres, respectively). In contrast, Color-Word Inhibition-Switching did not show a significant relationship with frontal or temporal cortical thickness.

Contrary to our hypothesis, stronger associations were observed with temporal lobe cortical thickness for Category Switching. Category Switching involves a language production component which could explain the strong association with temporal cortical thickness compared to frontal cortical thickness. Additionally, the pattern of associations between Trails Switching and frontal and temporal thickness was non-specific. Perhaps most striking is the lack of association between each switching measure and frontal cortical thickness, which was unexpected, given that these measures are used to assess executive functioning, broadly localized to the frontal lobe. Future directions involve examining the associations of these measure with subcortical structures and replicating these findings in larger datasets.

White matter hyperintensity (WMH) burden is greater, has a frontal-temporal distribution, and is associated with proxies of exposure to repetitive head impacts (RHI) in former American football players. These findings suggest that in the context of RHI, WMH might have unique etiologies that extend beyond those of vascular risk factors and normal aging processes. The objective of this study was to evaluate the correlates of WMH in former elite American football players. We examined markers of amyloid, tau, neurodegeneration, inflammation, axonal injury, and vascular health and their relationships to WMH. A group of age-matched asymptomatic men without a history of RHI was included to determine the specificity of the relationships observed in the former football players.

240 male participants aged 45-74 (60 unexposed asymptomatic men, 60 male former college football players, 120 male former professional football players) underwent semi-structured clinical interviews, magnetic resonance imaging (structural T1, T2 FLAIR, and diffusion tensor imaging), and lumbar puncture to collect cerebrospinal fluid (CSF) biomarkers as part of the DIAGNOSE CTE Research Project. Total WMH lesion volumes (TLV) were estimated using the Lesion Prediction Algorithm from the Lesion Segmentation Toolbox. Structural equation modeling, using Full-Information Maximum Likelihood (FIML) to account for missing values, examined the associations between log-TLV and the following variables: total cortical thickness, whole-brain average fractional anisotropy (FA), CSF amyloid ß42, CSF p-tau181, CSF sTREM2 (a marker of microglial activation), CSF neurofilament light (NfL), and the modified Framingham stroke risk profile (rFSRP). Covariates included age, race, education, APOE z4 carrier status, and evaluation site. Bootstrapped 95% confidence intervals assessed statistical significance. Models were performed separately for football players (college and professional players pooled; n=180) and the unexposed men (n=60). Due to differences in sample size, estimates were compared and were considered different if the percent change in the estimates exceeded 10%.

In the former football players (mean age=57.2, 34% Black, 29% APOE e4 carrier), reduced cortical thickness (B=-0.25, 95% CI [0.45, -0.08]), lower average FA (B=-0.27, 95% CI [-0.41, -.12]), higher p-tau181 (B=0.17, 95% CI [0.02, 0.43]), and higher rFSRP score (B=0.27, 95% CI [0.08, 0.42]) were associated with greater log-TLV. Compared to the unexposed men, substantial differences in estimates were observed for rFSRP (Bcontrol=0.02, Bfootball=0.27, 994% difference), average FA (Bcontrol=-0.03, Bfootball=-0.27, 802% difference), and p-tau181 (Bcontrol=-0.31, Bfootball=0.17, -155% difference). In the former football players, rFSRP showed a stronger positive association and average FA showed a stronger negative association with WMH compared to unexposed men. The effect of WMH on cortical thickness was similar between the two groups (Bcontrol=-0.27, Bfootball=-0.25, 7% difference).

These results suggest that the risk factor and biological correlates of WMH differ between former American football players and asymptomatic individuals unexposed to RHI. In addition to vascular risk factors, white matter integrity on DTI showed a stronger relationship with WMH burden in the former football players. FLAIR WMH serves as a promising measure to further investigate the late multifactorial pathologies of RHI.

The locus coeruleus (LC) innervates the cerebrovasculature and plays a crucial role in optimal regulation of cerebral blood flow. However, no human studies to date have examined links between these systems with widely available neuroimaging methods. We quantified associations between LC structural integrity and regional cortical perfusion and probed whether varying levels of plasma Alzheimer’s disease (AD) biomarkers (Aß42/40 ratio and ptau181) moderated these relationships.

64 dementia-free community-dwelling older adults (ages 55-87) recruited across two studies underwent structural and functional neuroimaging on the same MRI scanner. 3D-pCASL MRI measured regional cerebral blood flow in limbic and frontal cortical regions, while T1-FSE MRI quantified rostral LC-MRI contrast, a well-established proxy measure of LC structural integrity. A subset of participants underwent fasting blood draw to measure plasma AD biomarker concentrations (Aß42/40 ratio and ptau181). Multiple linear regression models examined associations between perfusion and LC integrity, with rostral LC-MRI contrast as predictor, regional CBF as outcome, and age and study as covariates. Moderation analyses included additional terms for plasma AD biomarker concentration and plasma x LC interaction.

Greater rostral LC-MRI contrast was linked to lower regional perfusion in limbic regions, such as the amygdala (ß = -0.25, p = 0.049) and entorhinal cortex (ß = -0.20, p = 0.042), but was linked to higher regional perfusion in frontal cortical regions, such as the lateral (ß = 0.28, p = 0.003) and medial (ß = 0.24, p = 0.05) orbitofrontal (OFC) cortices. Plasma amyloid levels moderated the relationship between rostral LC and amygdala CBF (Aß42/40 ratio x rostral LC interaction term ß = -0.31, p = 0.021), such that as plasma Aß42/40 ratio decreased (i.e., greater pathology), the strength of the negative relationship between rostral LC integrity and amygdala perfusion decreased. Plasma ptau181levels moderated the relationship between rostral LC and entorhinal CBF (ptau181 x rostral LC interaction term ß = 0.64, p = 0.001), such that as ptau181 increased (i.e., greater pathology), the strength of the negative relationship between rostral LC integrity and entorhinal perfusion decreased. For frontal cortical regions, ptau181 levels moderated the relationship between rostral LC and lateral OFC perfusion (ptau181 x rostral LC interaction term ß = -0.54, p = .004), as well as between rostral LC and medial OFC perfusion (ptau181 x rostral LC interaction term ß = -0.53, p = .005), such that as ptau181 increased (i.e., greater pathology), the strength of the positive relationship between rostral LC integrity and frontal perfusion decreased.

LC integrity is linked to regional cortical perfusion in non-demented older adults, and these relationships are moderated by plasma AD biomarker concentrations. Variable directionality of the associations between the LC and frontal versus limbic perfusion, as well as the differential moderating effects of plasma AD biomarkers, may signify a compensatory mechanism and a shifting pattern of hyperemia in the presence of aggregating AD pathology. Linking LC integrity and cerebrovascular regulation may represent an important understudied pathway of dementia risk and may help to bridge competing theories of dementia progression in preclinical AD studies.

White matter hyperintensities (WMH) are a radiological marker of small vessel cerebrovascular disease that are related to cognition and memory decline in aging and Alzheimer’s disease (AD). However, the mechanisms that link WMH to memory impairment and whether they interact with or act independently of AD pathophysiology are unclear. The transentorhinal cortex (BA35) is among the earliest anatomical regions to show tau deposition and subsequent atrophy, and baseline posterior WMH is related to longitudinal cortical thinning of the entorhinal cortex. However, it is unclear whether regional WMH are related to BA35 volume specifically, and whether this relationship is influenced by amyloid-β (Aβ) burden. We hypothesized that WMH in the vascular territory of the posterior cerebral artery (PCA), which perfuses both posterior and medial temporal lobe regions, would be associated with reduced BA35 volume and with lower memory in older adults independently of Aβ.

114 older adults without dementia, aged 60 to 98 years (mean (SD) = 78.31 (11.02), 71 (62.8%) women), were included. Regional WMH volumes were derived from T2-FLAIR images using ANTs, a vascular territory atlas and manual editing. Global Aβ was assessed with 18F-florbetapir PET, using SUVR of a cortical composite region (FBP mean SUVR) with a cerebellar reference region. Total transentorhinal (BA35) volume was derived using T1 and T2-weighted images using ASHS. To assess hippocampal pattern separation ability, an index of episodic memory, participants completed both object (MDT-O) and spatial (MDT-S) versions of a mnemonic discrimination task, with the lure discrimination index as the outcome. Using linear regressions, we first tested for associations among PCA-defined WMH, Aβ, BA35 volume, and MDT-S and MDT-O scores. We then tested whether the relationship between PCA-defined WMH and MDT-O performance was mediated by BA35 volume and whether this mediation was moderated by Aβ. All models adjusted for age, sex, and education.

PCA-defined WMH were related to higher FBP mean SUVR (b=0.287, p=0.042) and lower BA35 volume (b=-0.222, p=0.038). PCA-defined WMH were also negatively related to MDT-O performance (b=-0.229, p=0.044), but not to MDT-S (b=-0.171, p=0.118). FBP mean SUVR was not related to BA35 volume (b=-0.131, p=0.344) or MDT performance (MDT-S: b=-0.138, p=0.348; MDT-O: b=0.059, p=0.690). Furthermore, FBP mean SUVR did not interact with PCA-defined WMH to predict memory performance (interaction b=-0.039, p=0.973), nor BA35 volume (interaction b=-0.140, p=0.894). The association of PCA-defined WMH to MDT-O was fully mediated by BA35 volume (indirect effect b=-0.0005, 95% CI (-0.0014, -0.0003)). This mediation was not moderated by FBP mean SUVR (indirect effect b=-0.00001, 95% CI (-0.001, 0.001)).

We found that PCA-defined WMH were related to memory performance in older adults, and this association is fully mediated by transentorhinal volume. While PCA-defined WMH are related to higher global Aβ burden, there is no interaction between PCA-defined WMH and Aβ on BA35 volume. These findings point to an amyloid-independent vascular pathway towards memory decline in aging and AD. Future work should examine whether the pathway linking PCA-defined WMH to transentorhinal cortex atrophy and subsequent memory decline is mediated by regional tau pathology.

Fetal alcohol spectrum disorder (FASD) is a common neurodevelopmental condition associated with deficits in cognitive functioning (executive functioning [EF], attention, working memory, etc.), behavioral impairments, and abnormalities in brain structure including cortical and subcortical volumes. Rates of comorbid attention-deficit/hyperactivity disorder (ADHD) are high in children with FASD and contribute to significant functional impairments. Sluggish cognitive tempo (SCT) includes a cluster of symptoms (e.g. underactive/slow-moving, confusion, fogginess, daydreaming) found to be related to but distinct from ADHD, and previous research suggests that it may be common in FASD. We explored SCT by examining the relationship between SCT and both brain volumes (corpus callosum, caudate, and hippocampus) and objective EF measures in children with FASD vs. typically developing controls.

This is a secondary analysis of a larger longitudinal CIFASD study that consisted of 35 children with prenatal alcohol exposure (PAE) and 30 controls between the ages of 9 to 18 at follow-up. Children completed a set of cognitive assessments (WISC-IV, DKEFS, & NIH Toolbox) and an MRI scan, while parents completed the Child Behavior Checklist (CBCL), which includes a SCT scale. We examined group differences between PAE and controls in relation to SCT symptoms, EF scores, and subcortical volumes. Then, we performed within-and between-group comparisons with and without controlling for total intracranial volume, age, attention problems, and ADHD problems between SCT and subcortical brain volumes. Finally, we performed correlations between SCT and EF measures for both groups.

Compared to controls, participants with PAE showed significantly more SCT symptoms on the CBCL (t [57] = 3.66, p = 0.0006), more parent-rated attention problems and ADHD symptoms, lower scores across several EF measures (DKEFS Trail-Making and Verbal Fluency; WISC-IV Digit Span, Symbol Search, and Coding; effect sizes ranging from 0.44 to 1.16), and smaller regional volumes in the caudate, hippocampus, and posterior areas of the corpus callosum. In the PAE group, a smaller hippocampus was associated with more SCT symptoms (controlling for parent-rated attention problems and ADHD problems, age, and intracranial volume). However, in the control group, a larger mid posterior and posterior corpus callosum were significantly associated with more SCT symptoms (controlling for parent-rated attention problems, intracranial volume, and age; r [24] = 0.499, p = 0.009; r [24] = 0.517, p = 0.007). In terms of executive functioning, children in the PAE group with more SCT symptoms performed worse on letter sequencing of the Trail-Making subtest (controlling attention problems & ADHD symptoms). In comparison, those in the control group with more SCT symptoms performed better on letter sequencing and combined number letter sequencing of the Trail-Making subtest (controlling attention problems).

Findings suggest that children with FASD experience elevated SCT symptoms compared to typically developing controls, which may be associated with worse performance on EF tasks and smaller subcortical volumes (hippocampus) when taking attention difficulties and ADHD symptoms into account. Additional research into the underlying causes and correlates of SCT in FASD could result in improved tailoring of interventions for this population.

Fetal alcohol spectrum disorder (FASD) is a life-long condition, and few interventions have been developed to improve the neurodevelopmental course in this population. Early interventions targeting core neurocognitive deficits have the potential to confer long-term neurodevelopmental benefits. Time-targeted choline supplementation is one such intervention that has been shown to provide neurodevelopmental benefits that emerge with age during childhood. We present a long-term follow-up study evaluating the neurodevelopmental effects of early choline supplementation in children with FASD approximately 7 years on average after an initial efficacy trial. In this study, we examine treatment group differences in executive function (EF) outcomes and diffusion MRI of the corpus callosum using the Neurite Orientation Dispersion and Density Index (NODDI) biophysical model.

The initial study was a randomized, double-blind, placebo-controlled trial of choline vs. placebo in 2.5- to 5-year-olds with FASD. Participants in this long-term follow-up study included 18 children (9 placebo; 9 choline) seen 7 years on average following initial trial completion. The mean age at follow-up was 11 years old. Diagnoses were 28% fetal alcohol syndrome (FAS), 28% partial FAS, and 44% alcohol-related neurodevelopmental disorder. The follow-up evaluation included measures of executive functioning (WISC-V Picture Span and Digit Span; DKEFS subtests) and diffusion MRI (NODDI).

Children who received choline early in development outperformed those in the placebo group across a majority of EF tasks at long-term follow-up (effect sizes ranged from -0.09 to 1.27). Children in the choline group demonstrated significantly better performance on several tasks of lower-order executive function skills (i.e., DKEFS Color Naming [Cohen's d = 1.27], DKEFS Word Reading [Cohen's d = 1.13]) and showed potentially better white matter microstructure organization (as indicated by lower orientation dispersion; Cohen's d = -1.26) in the splenium of the corpus callosum compared to the placebo group. In addition, when collapsing across treatment groups, higher white matter microstructural organization was associated with better performance on several EF tasks (WISC-V Digit Span; DKEFS Number Sequencing and DKEFS Word Reading).

These findings highlight long-term benefits of choline as a neurodevelopmental intervention for FASD and suggest that changes in white matter organization may represent an important target of choline in this population. Unique to this study is the use of contemporary biophysical modeling of diffusion MRI data in youth with FASD. Findings suggest this neuroimaging approach may be particularly useful for identifying subtle white matter differences in FASD as well as neurobiological responses to early intervention associated with important cognitive functions.

Motor skills have been linked to executive functions (EFs) in typically developing school-, and preschool-age children. Yet fine motor skills have been more consistently correlated with EFs than gross motor skills, perhaps because they are more frequently investigated. Preterm born children are vulnerable to deficits in both gross and fine motor skills, even after exclusion of neurological cases. In addition to motor skills, EFs may also be compromised in preterm born preschoolers. Because premature birth increases the odds for atypical brain development, and since adverse effects on brain functioning tend to yield increased dispersion of performance scores, we wished to determine whether fine and gross motor skills are differentially linked to performance on tasks measuring EF skills in nonhandicapped preschoolers born preterm.

We studied 99 preterm (born < 34 weeks) singleton preschoolers (3-4 years of age; 50 females), all graduates of the Neonatal Intensive Care Unit at William Beaumont Hospital, Royal Oak, MI. Motor skills were assessed with the Peabody Developmental Motor Scales - (Second Edition) which provide Fine and Gross Motor Quotients (FMQ, and GMQ, respectively). Three core EFs were measured: working memory, motor inhibition, and verbal fluency. Working memory skills were assessed with two Clinical Evaluation of Language Fundamentals - Preschool -Second Edition subtests: Recalling Sentences (RS) and Concepts and Following Directions (CFD). Motor inhibition and verbal fluency were assessed with the NEPSY-II Statue and Word Generation (WG) subtests, respectively. Children with a history of moderate to severe intracranial pathology or cerebral palsy were excluded.

We conducted linear regression analyses using scaled scores from the Statue, WG, RS, and CFD subtests as the predicted variables. Predictors of interest were the FMQ and GMQ. We adjusted for sociodemographic factors (SES and sex) and perinatal risk (gestational age, sum of antenatal complications and birth weight SD). The GMQ was significantly associated with all four EF measures (Statue, t(84) = 4.13, p < .001; CFD, t(92) = 3.83, p < .001; WG, t(84) = 3.38, p = .001; RS, t(90) = 3.37, p = .001). The FMQ was significantly associated with three of four EF measures (Statue, t(84) = 3.41, p = .001; CFD, t(92) = 3.97, p < .001; WG, t(84) = 1.96, p = .054; RS, t(90) = 2.91, p = .005).

Both fine and gross motor skills were associated with EF in nonhandicapped preterm-born singletons. Lower motor functioning in either motor domain was linked to reduction in performance on diverse EF measures. It should be emphasized that motor performance contributed to explaining variance in EFs even after statistical adjustment for early medical risk. In addition to the obvious conclusion that motor skills may underpin EF skills, it is likely that early risk factors not captured by the medical risk variables used in our analyses were nonetheless tapped by variability in motor performance. As preschool EFs are essential for subsequent academic performance, the significance of age-appropriate motor development in the preschool age should not be underestimated in our at-risk population.

Children born preterm are at increased risk of deviation from the typical developmental trajectory. The probability of adverse developmental sequelae is increased in those with history of major perinatal complications. Retinopathy of prematurity (ROP) is a pathological disordered growth of retinal blood vessels occurring in very preterm neonates who require supplemental oxygen. ROP has been linked to intermittent hypoxemic events and blood gas derangements occurring in the Neonatal Intensive Care Unit (NICU), particularly in ventilated infants. Though presence and severity of ROP have been linked to neurodevelopmental impairment, little is known about the relationship between ROP severity and motor development in the preschool age. Because the same hypoxemic events and blood gas changes that lead to severe ROP may also lead to greater developmental deficits in motor control, we hypothesized that ROP severity will be inversely linked to the quality of motor functioning even in NICU graduates without neurological impairments.

We included 95 preterm (23.6 - 33.6 weeks gestation) preschoolers (49 females, 44 members of twin pairs or triplets). The participants' age ranged from 3.3 - 4.1 years (adjusted for prematurity). ROP screening was conducted during NICU stay and rated from immature retina (0) to grade 4. Motor abilities were assessed with the Peabody Developmental Motor Scales (PDMS-2). Cases with diagnosed perinatal brain pathology (moderate to severe) or cerebral palsy were excluded from analyses.

We used linear mixed regression analyses with multiple gestation as a random factor. Severity of ROP was our predictor of interest, whereas socioeconomic status, sex, gestational age, and birth-weight SD served as covariates. Separate analyses were conducted using the PDMS-2 Total Motor, Fine Motor, and Gross Motor Quotients as dependent variables. ROP severity explained a unique portion of the variance in the Total Motor Quotient (F[1, 89] = 5.59, p = .02). Examination of the relationship between ROP severity and motor skill domains yielded a significant association for the Fine Motor Quotient (F[1, 89] = 6.19, p = .015) and a trend for the Gross Motor Quotient (F[1, 89] = 3.64, p = .06).

The results of this study reveal that increase in ROP severity is linked to poorer motor skills in preterm-born preschoolers without major disabilities or perinatal diagnosis of moderate to severe brain pathology. This association was evident for both fine and gross motor skills, though only the relationship between ROP severity and the former motor index reached conventional statistical significance. Importantly, ROP severity accounted for a unique portion of the variance in motor performance, over and above the variance explained by other perinatal risk factors. This result is consistent with previous research findings indicating that ROP is linked to the occurrence of multiple, subtle hypoxemic events and 'exposure' to blood gas derangements during NICU stay in very preterm neonates who require respiratory support.

Infant motor development is a robust predictor of long-term developmental outcomes, especially in infants at high risk for neurodevelopmental impairments, such as those born preterm (PT, gestational age [GA] <37 weeks). Although direct assessments of motor development are available, they are infrequently applied by pediatricians in routine screening of the broader population of infants born preterm. Parent ratings, such as the Ages and Stages Questionnaire, 3rd Ed., can be used to screen for motor delays. However, this and other existing screening measures focus on whether children have reached milestones based on pre-established cutoffs, rather than on assessing development along a continuum of ability. The present study examined the validity of the Motor domain of the recently developed caregiver report screening tool, PediaTracTM, in distinguishing infants born PT from infants born full term (FT, GA ^37 weeks) across the first 6 months of life. The reliability and factor structure of this motor scale were also evaluated.

PediaTracTM is a web-based caregiver report assessing infant development across multiple domains, including motor functioning. This study reports on results from the PediaTracTM Motor domain for the study sample of 571 caregiver-infant dyads (240 PT, 331 FT). Caregivers rated their infants on age-targeted motor skills during the newborn period (NB, defined as term equivalent for the PT group) and at 2-, 4-, and 6-months after the NB period. Item Response Theory (IRT) methods were applied to assess the reliability (i.e., information) of caregiver-reported motor skills at each age. Using the IRT item parameters of discrimination and difficulty, items were selected for inclusion and to estimate theta, an index of the latent trait, motor ability, for each infant. Analyses conducted at each age assessed the effects of group, sex, and group x sex on the motor trait. Scale reliabilities and factor structure were also examined.

The PT group had significantly higher scores than the FT group on the motor trait at the NB period but significantly lower scores by 4 and 6 months, suggesting slower development of motor skills in the PT group. Means (SD) theta scores (similar to z scores) for the PT and FT groups, respectively, were .14 (.88) and -.05 (.91) for the NB period, -.01 (.90) and .01 (.91) for 2 months, .20 (.90) and .36 (88) for 4 months, and .46 (78) and .66 (.89) for 6 months. Effects for sex and group x sex interactions were not significant. Reliabilities, estimated at a point close to mean theta, were .94, .93, .96, and .98 at the NB, 2-, 4-, and 6-month periods, respectively. Exploratory factor analyses revealed evidence for a single primary motor factor and multiple second-order factors at each age.

Findings provide strong support for applications of the caregiver reported PediaTracTM motor scales in screening infants born PT and other at-risk populations for early delays or abnormalities in motor development. Advantages of this method include its ease of administration, sensitivity to developmental change, and promise in assessing subdomains of motor skill.

Motor weaknesses are frequently observed in very preterm children (VPT; gestational age [GA] < 30 weeks) prior to school entry and may serve as markers of risk for school-age cognitive and behavioral deficits. The aims of the present study were to: (1) determine if weaknesses in preschool motor skills in children born VPT and a full-term comparison group (FT; GA > 37 weeks) are associated with lower scores on tests of cognition and caregiver ratings of behavior in early elementary school; (2) explore the possibility that weaknesses in preschool motor abilities predict less positive changes in cognition and behavior across follow-up; and (3) determine if associations between preschool motor skills and later cognitive and behavioral functioning differed for the two groups.

Thirty-eight children born VPT and thirty born FT completed measures of motor skills, global cognitive ability, and executive function and caregivers completed questionnaires assessing children's behavior at age 4 (T1; M = 4.71 years) and at ages 7 or 8 (T2; M = 7.87 years). ANCOVAs were used to examine group differences in cognitive and behavioral outcomes. Hierarchical regressions were conducted to examine the Movement Assessment Battery for Children, 2nd Ed. (MABC-2) total score at T1 as a predictor of T2 scores on cognitive tests and behavior ratings (step 1). Covariates included sex and socioeconomic status (step 1). Outcomes included the Differential Ability Scales-II (DAS-II), NIH Toolbox Dimensional Change Card Sort (DCCS), Behavior Rating Inventory of Executive Function Global Executive Composite (BRIEF GEC), Emotion Regulation Checklist, and Social Communications Questionnaire at T2. T1 status on the T2 cognitive and behavioral outcomes was included as a predictor to determine if T1 MABC-2 predicted change in these outcomes from T1 to T2 (step 2). In separate analyses, T1 MABC-2 x group interactions were included to determine if associations of the T1 MABC-2 with T2 outcomes differed by group.

The VPT group had significantly lower scores than the FT group on the DAS-II at T2. Lower scores on the T1 MABC-2 were significantly associated (p < .05) with lower scores on the DAS-II and DCCS and more executive dysfunction on the BRIEF-GEC. These associations were stronger for the VPT group than for the FT group for the T2 DAS-II Global Cognitive Ability and Verbal composites but not for the other outcomes. Lower scores on the T1 MABC-2 were associated with less positive change on the DAS-II Nonverbal composite and the DCCS and increased executive dysfunction on the BRIEF-GEC.

Weaknesses in motor abilities at 4 years of age were associated with cognitive and behavioral difficulties at early school age, both for children born VPT and those born FT. These weaknesses were also associated with less favorable changes in cognition and behavior across the transition from preschool to early school age. Findings suggest that early motor abilities provide a marker of generalized developmental impairment or that early motor impairments have cascading effects on development. These results support the need for early screening and intervention for motor deficits in preschoolers born either VPT or FT.

To examine associations between executive function (EF) domains (attentional control, information processing, cognitive flexibility, and goal setting) and math computation performance at 7 and 13 years in children born very preterm (VP; <30 weeks' gestation), and secondly, to investigate the associations of 7-year EF with change in math performance from 7 to 13 years.

In the prospective, longitudinal Victorian Infant Brain Studies (VIBeS) cohort of children born VP, assessment of EF and math performance was undertaken at 7 (n = 187) and 13 years (n = 174). Univariable and multivariable regression models (including all domains of EF) were used to examine associations between EF domains at both timepoints with math performance, as well as associations between EF at 7 years with change in math from 7 to 13 years.

At 7 and 13 years, all EF domains were positively associated with concurrent math performance, with multivariable models finding information processing, cognitive flexibility and goal setting independently contributed to math performance at both ages. All EF domains were positively associated with improvement in math performance from 7 to 13 years, with multivariable models finding that goal setting contributed unique variance to improvement in math over this period.

This study provides evidence for a strong, consistent association between EF and math performance in children born VP and emphasizes the importance of goal setting capacity for later improvement in math performance.

Preterm children with very low birthweight (VLBW) / extremely low birthweight (ELBW) with normal early development had been found poorer executive functions (EFs) at preschool-age (Ni, Huang & Guo, 2011). The previous study found that the risks of deficits in EFs at preschool-age of preterm children can be attenuated by more supportive home environment (Taylor & Clark, 2016). However, former studies didn't investigate the effect of birthweight and home environment on cognitive EFs of preterm children simultaneously, especially those with normal early development. The present study aims to investigate the predictive effect of birthweight and home environment on the cognitive EFs of VLBW / ELBW preterm children.

The preterm children were recruited from the Premature Baby Foundation of Taiwan. Inclusion criteria were their scores of Bayley Scales of Infant and Toddler Development, second or third edition at 12 and 24 months, and Wechsler Preschool and Primary Scale of Intelligence, Revised Edition at 5 years old were higher than 70. Exclusion criteria were visual impairment, hearing impairment, and cerebral palsy. There was a total of 287 preterm children with age 6 recruited in the present study. Preterm children were then divided into VLBW group (n=202, birthweight between 1001-1500g) and ELBW group (n=85, birthweight less than 1000g). The typical children included 89 term-born healthy and typically developing children with age 6, who were recruited from comparable social status families in the community. Four types of cognitive EFs including 22 indicators were assessed. Inhibition ability including 8 indicators was assessed through Comprehensive Nonverbal Attention Test Battery (CNAT), cognitive flexibility including 6 indicators was assessed through Wisconsin Card Sorting Test (WCST), working memory including 2 indicators was assessed through Digit Span Subtest of Wechsler Intelligence Scale for Children-IV (WISC-IV) and Knox's Cube Test (KCT), planning ability including 6 indicators was assessed through Tower of London (ToL). The home environment was assessed through Home Observation for Measurement of the Environment (HOME), Revised edition. Data were analyzed with Stepwise Regression.

Results showed that the regression model with birthweight significantly predicted 83.3% of planning ability indicators, 83.3% of cognitive flexibility indicators, and 50% of working memory indicators. Among indicators mentioned above, birthweight has been found the greatest predictive effect on summation-of score of ToL (R2=.04, p<.001). The regression model with HOME significantly predicted 66.7% of planning ability indicators, 16.7% of cognitive flexibility indicators, and 12.5% of inhibition ability indicators. Among the indicators mentioned above, HOME has been found the greatest predictive effect on rule-1 of ToL (R2=.027, p=.001). The regression model with birthweight and HOME significantly predicted 50% of planning ability indicators. Among indicators mentioned above, the regression model has been found the greatest predictive effect on summation-of-score of ToL (R2=.061, p<.001).

Both birthweight and home environment have been found significantly predicted different types of cognitive EFs at preschool-age of VLBW / ELBW preterm children with normal early development. Though the home environment doesn't have such a great predictive effect as birthweight is, both birthweight and home environment are significant predictors of planning ability.

Previous studies had shown that even with normal early development, preterm children at age six still have executive function deficits, including planning, cognitive flexibility, and nonverbal working memory. The present study aims to discuss further the correlation between IQ and EF of preterm children with different birthweight in order to clarify the potential influence of birthweight.

The preterm children were recruited from the Regional Cohort Network for premature infants who were admitted to neonatal intensive care units. Inclusion criteria were their scores of Bayley Scales of Infant and Toddler Development, second or third edition at 12 and 24 months, and Wechsler Preschool and Primary Scale of Intelligence, Revised Edition at 5 years old were higher than 70. Meanwhile, their FSIQ of Wechsler Intelligence Scale for Children, Fourth Edition were higher than 85 at age 6. Exclusion criteria were visual impairment, hearing impairment, and cerebral palsy. There was a total of 251 preterm children recruited in the present study. Preterm children were then divided into very low birthweight (VLBW) and extremely low birth weight (ELBW) groups. The VLBW group included 183 preterm children, whose birthweight is between 1000-1500g, and gestational age is less than 37 weeks. The ELBW group included 68 preterm children, whose birthweight is less than 1000g and gestational age is less than 37 weeks. Four types of executive function were assessed. Inhibition was assessed through Comprehensive Nonverbal Attention Test Battery (CNAT), cognitive flexibility was assessed through Wisconsin Card Sorting Test (WCST), verbal working memory was assessed through the Longest Digit Span Forward (LDSB) index of Digit Span Subtest of Wechsler Intelligence Scale for Children-IV (WISC-IV), and nonverbal working memory was assessed through Knox's Cube Test (KCT), and planning ability was assessed through Tower of London (ToL). Data were analyzed with independent T-test and Pearson Correlation.

In VLBW preterm group, results showed that there were significant correlations (p<.05) between FSIQ and EF indexes in five out of six indexes of WCST, LDSB of Digit Span of WISC-IV, Backward score of Knox's Cube Test, and three out of six indexes of ToL. As to the CNAT, there was no index of CNAT that was significantly correlated with FSIQ in the VLBW preterm group. In ELBW preterm group, results showed that there were significant correlations (p<.05) between FSIQ and EF indexes in one out of five indexes of CNAT, one out of six indexes of WCST, Backward score of Knox's Cube Test, and two out of six indexes of ToL. And the LDSB of Digit Span of WISC-IV was not significantly correlated with FSIQ in ELBW preterm group.

There were fewer EF indexes significantly correlated with FSIQ in ELBW preterm children with normal early development than VLBW preterm children with normal early development, suggesting that even with an IQ higher than 85, lower the birthweight, especially lower than 1000g, higher the EF performance should be concerned. Therefore, in the clinical setting, it is very important to assess the EF independently. And birthweight may be a crucial factor in preterm children's prefrontal cortex maturity.

Previous studies had shown that very low birth weight(VLBW) preterm children with normal early development had poorer cognitive executive functions(CEFs) and emotional executive functions(EEFs) at preschool-aged. There were still about 73% of children with deficits of CEFs and 74% of them with deficits of EEFs at school-aged. (Ni et al., 2011; Chiang et al., 2019; Lee et al., 2022). Besides, former studies less discuss the core neuropsychological ability related to the EFs development. In this study, meta-attention was chosen as the core ability. This study applied longitudinal design aimed to discuss the predictive power of meta-attention at preschool-aged on the CEFs and EEFs at school-aged for VLBW preterm and typically developing children.

The VLBW group was referred by Premature Baby Foundation of Taiwan. These children have been followed up with Bayley Scales of Infant Development(BSID) II or III administered at the age of 12 months and 24 months and Wechsler Preschool and Primary Scale of Intelligence-Revised(WPPSI-R) at the age of 5-year-old. Children with visual impairment, auditory impairment, cerebral palsy developmental indices of BSID-II or III less than 70, or full-scale IQ of WPPSI-R less than 70 were excluded.

The typical group was recruited from the community and included 30 children whose development was typical. Both preterm and typically developing children completed the CEFs and EEFs test at 6 and 8. Four types of CEFs including 33 indicators were assessed: Meta-attention including 18 indicators through Comprehensive Nonverbal Attention Test Battery(CNAT), working memory including 2 indicators through Digit Span Subtest of Wechsler Intelligence Scale for Children-IV(WISC-IV) and Knox’s Cube Test(KCT), planning ability including 6 indicators through Tower of London(ToL), and cognitive flexibility including 7 indicators through Wisconsin Card Sorting Test(WCST).

Two types of EEFs including 5 indicators were assessed. We designed Emotional EF Ecological Assessment Battery for Children in Taiwan to assess EEFs, including 3 indicators of theory of mind and 2 indicators of emotion regulation. Data were analyzed with correlation analysis and independent sample t-test.

Meta-attention at 6 among the VLBW group significantly correlated with 73.3% of CEFs and 80% of EEFs indicators at 8 and had significant predictive power on working memory, planning ability, cognitive flexibility, emotion regulation, and theory of mind. (p<.05) When the significance level was 0.01, meta-attention still correlated with 33% of CEFs and 80% of EEFs indicators and can predict those CEFs and EEFs among the VLBW group. Meta-attention at 6 among the typical group significantly correlated with 26.7% of CEFs and 80% of EEFs indicators at 8 and had significant predictive power on working memory, planning ability, emotion regulation, and theory of mind. (p<.05)

When the significance level was 0.01, meta-attention only correlated with 80% of EEFs indicators and can’t predict any CEFs and EEFs among the typical group.

Meta-attention at 6 can predict CEFs and EEFs among VLBW preterm children at 8, while the effect didn’t be found among typically developing children. Thus, meta-attention can be served as a clinical cut-point for VLBW preterm children to find the deficits and intervene early.