Age group and sex differences in performance on a computerized neurocognitive battery in children age 8-21.

Studies have examined the developmental course of specific behavioral domains ranging from auditory processing (Keith, 2000) to executive-control functions, such as attention and working memory (e.g., Conklin, Luciana, Hooper, & Yarger, 2007; Goldberg, Maurer, & Lewis, 2001; Pickering, 2001), language and reasoning (e.g., Friederici & Wartenburger, 2010; Kuhl, 2010) and, more recently, social cognition (e.g., Burnett, Sebastian, Cohen-Kadosh, & Blakemore, 2010; Shaw et al., 2011). General intelligence measures have been reported as stable across development (Salthouse, 2004), but improved performance from childhood to young adulthood has been especially pronounced for executive domains of attention and working memory (Ang 2008, 2010; Gao et al., 2011). Neural substrates for these age-related changes have been examined with structural and functional neuroimaging and several consistent findings have emerged. These findings highlight childhood and adolescence, periods during which important changes occur in neural substrates associated with functional age-related changes (Casey, Duhoux & Malter, 2010; Giedd, et al., 1999; Matsuzawa et al., 2001; Shaw et al., 2008, 2011). Integrating neuroimaging with behavioral findings, Jung and Haier (2007) identified a central role for frontal and parietal regions in the neurodevelopment of cognition, and this hypothesis has received support in large-scale studies (Deary, Penke & Johnson, 2010). Sex differences have been extensively documented in behavioral measures (e.g., Halpern, Benbow, Geary, Gur, Hyde, & Gernsbacher, 2007; Hines, 2010). Males perform better than females on spatial (Voyer, Voyer & Bryden, 1995; Linn & Petersen, 1985) and motor tasks (e.g., Moreno-Briseno, Diaz, Campos-Romo, & Fernandez-Ruiz, 2010; Thomas & French, 1985), while females perform better than males on some verbal and memory tasks (e.g., Hedges & Nowell, 1995; Hyde & Linn, 1988; Saykin et al., 1995) and measures of social cognition (Erwin et al., 1992, Williams et al., 2008). Some sex differences have been related to structural neuroimaging (e.g., De Bellis et al., 2001; Goldstein et al., 2001; Gur et al., 1999; Lenroot, et al., 2007) and functional imaging measures (e.g., Gur et al., 1982; 1995; 2000; Lenroot & Giedd, 2010), including volumetric differences in executive and memory-related areas, supporting neural substrates for sex differences in cognition. However, the developmental course of sex differences in brain-behavior relationship is still relatively unexamined. Several shortcomings of most cognitive measures used in studies to date limit their applicability in establishing further links between brain function and behavioral domains. They tend to be broadly defined and load heavily on the “g factor” (Salthouse, 2004) and they do not separate accuracy from speed, which would preclude rigorous testing of hypotheses on the effects of brain connectivity on performance. Furthermore, the paper-and-pencil administration format precludes their use in studies that are scaled to the size required for neuroimaging genomics. More narrowly defined behavioral tasks, used in functional neuroimaging studies, have been adapted for use as computerized tests to obtain rapid and efficient quantification of individual differences (Gur, Erwin & Gur, 1992, Gur et al., 2001, 2010). No available studies have applied an identical neurocognitive test battery across a population ranging from childhood to adulthood in a prospective study aiming to integrate behavior with neuroimaging and genomics. The present study is a collaboration between the Center for Applied Genomics (CAG) at Children’s Hospital of Philadelphia (CHOP) and the Brain Behavior Laboratory at the University of Pennsylvania (Penn). The target sample consists of 10,000 youths ages 8–21 who consulted the CHOP network and volunteered to participate in genomic studies of complex pediatric disorders. All research participants undergo clinical assessment, including a neuropsychiatric structured interview, and review of electronic medical records. They are also administered a neuroscience based computerized neurocognitive battery (CNB) (Gur et al., 2001, 2010) and a subsample (1000) undergoes neuroimaging. The CNB, developed for large-scale studies, yields measures of accuracy and speed for domains of executive-control functions (abstraction, attention, working memory), episodic memory (verbal, facial, spatial), complex cognitive processing (language reasoning, nonverbal reasoning, spatial processing), social cognition (emotion identification, emotion intensity differentiation, age differentiation) and sensorimotor and motor speed. Here we present CNB testing results for the first 3,500 participants to evaluate its sensitivity and specificity for developmental age effects and sex differences. Importantly, establishing both age effects and sex differences in this age range required some adaptation of instructions and stimuli compared to earlier versions of the CNB. In the standardization sample for the computerized battery (Gur et al., 2010), where the age range was 18–84, we found negative correlations between age and performance reflecting the sensitivity of the tests to senescence. Based on the available literature and the age range of 8 to 21 in this new sample, we hypothesized that performance will improve with increased age group, and that age effects are more pronounced for executive domains (e.g., Gao et al., 2011). Given the evidence of increased white matter volume and connectivity with age (e.g., Matsuzawa et al., 2001; Shaw et al., 2011; Deary, Penke & Johnson, 2010), we hypothesized that the age group effect will be pronounced for speed of sensory-motor response. We also hypothesized sex differences, with better performance in females on memory and social cognition tests and better performance for males on spatial and motor tests (Halpern et al., 2007). We did not have a basis to hypothesize age group × sex interaction effects on specific cognitive development, but since females mature earlier physically we expected to see earlier apex performance in females.