Gray matter volume deficits are associated with motor and attentional impairments in adolescents with schizophrenia.

Cognitive deficits have been well described in adolescents with schizophrenia, but little is known about the neuroanatomical basis of these abnormalities. The authors examined whether neuropsychological deficits observed in adolescents with schizophrenia were associated with cortical gray matter volume deficits. Volumes of the superior frontal gyrus, anterior cingulate gyrus and orbital frontal lobe were outlined manually from contiguous MR images and automatically segmented into gray and white matter in 52 patients and 48 healthy volunteers. Subjects received a comprehensive neuropsychological test battery, assessing five different functional domains: executive, attention, verbal memory, motor and sensory motor. Children and adolescents with schizophrenia were found to have lower total cortical and lower superior frontal gyrus gray matter volumes and lower test scores across all functional domains compared to healthy volunteers. Among patients, the lower total cortical gray matter volume was associated with worse functioning on the attention and motor domains. Our findings point to widespread, perhaps multifocal, pathology as contributing to cognitive dysfunction in adolescents with schizophrenia.

Increased anterior cingulate and temporal lobe activity during visuospatial working memory in children and adolescents with schizophrenia.

OBJECTIVE: Similar to adults, children and adolescents with schizophrenia present with significant working memory (WkM) deficits. However, unlike adults, findings of abnormal activity in the prefrontal cortex in early-onset schizophrenia (EOS) are not consistently reported. Since WkM continues to develop through adolescence and into early adulthood, patterns of activation in adolescents may be different than those found in adults. The goal of this study was to evaluate the functional neurobiology of WkM in patients with EOS. METHOD: Participants included 22 patients with EOS (mean age 15±2.8 years) and 24 controls (mean age 15.0±3.0 years). Diagnoses were confirmed using the KIDDIE-SADS-PL. All subjects underwent a functional MRI paradigm involving a visuospatial working memory task with three separate loads. RESULTS: The behavioral results demonstrated deficits in EOS patients at all three WkM loads. On functional imaging, EOS patients demonstrated increased activation in the anterior cingulate cortex (ACC), medial temporal lobe structures, the insula, and bilateral lateral temporal lobes. CONCLUSIONS: Patients with EOS demonstrate increased activity in limbic structures and regions involved in processing primary and secondary sensory information. In addition, EOS patients had load dependent decreased activity in the parietal lobe. Unlike studies in adults, we did not find that EOS patients had activation differences in the frontal cortical regions. One possibility is that abnormalities in PFC function are related to secondary downstream or developmental processes which are 'unmasked' during development. Finally, our findings support growing evidence that EOS patients have aberrations in the limbic and temporal lobe regions.

Limbic structures and networks in children and adolescents with schizophrenia.

Studies of adults with schizophrenia provide converging evidence for abnormalities in the limbic system. Limbic structures that show consistent patient/control differences in both postmortem and neuroimaging studies include the anterior cingulate and hippocampus, although differences in the amygdala, parahippocampal gyrus, and fornix have also been observed. Studies of white matter in children and adolescents with schizophrenia tend to show findings that are more focal than those seen in adults. Interestingly, these focal abnormalities in early-onset schizophrenia tend to be more localized to limbic regions. While it is unclear if these early limbic abnormalities are primary in the etiology of schizophrenia, there is evidence that supports a developmental progression with early limbic abnormalities evolving over time to match the neuroimaging profiles seen in adults with schizophrenia. Alternatively, the aberrations in limbic structures may be secondary to a more widespread or global pathological processes occurring with the brain that disrupt neural transmission. The goal of this article is to provide a review of the limbic system and limbic network abnormalities reported in children and adolescents with schizophrenia. These findings are compared with the adult literature and placed within a developmental context. These observations from neuroimaging studies enrich our current understanding of the neurodevelopmental model of schizophrenia and raise further questions about primary vs secondary processes. Additional research within a developmental framework is necessary to determine the putative etiologic roles for limbic and other brain abnormalities in early-onset schizophrenia.

The effect of age on memory for emotional faces.

Prior studies of emotion suggest that young adults should have enhanced memory for negative faces and that this enhancement should be reduced in older adults. Several studies have not shown these effects but were conducted with procedures different from those used with other emotional stimuli. In this study, researchers examined age differences in recognition of faces with emotional or neutral expressions, using trial-unique stimuli, as is typically done with other types of emotional stimuli. They also assessed the influence of personality traits and mood on memory. Enhanced recognition for negative faces was found in young adults but not in older adults. Recognition of faces was not influenced by mood or personality traits in young adults, but lower levels of extraversion and better emotional sensitivity predicted better negative face memory in older adults. These results suggest that negative expressions enhance memory for faces in young adults, as negative valence enhances memory for words and scenes. This enhancement is absent in older adults, but memory for emotional faces is modulated in older adults by personality traits that are relevant to emotional processing.

Age effects on social cognition: faces tell a different story.

The authors administered social cognition tasks to younger and older adults to investigate age-related differences in social and emotional processing. Although slower, older adults were as accurate as younger adults in identifying the emotional valence (i.e., positive, negative, or neutral) of facial expressions. However, the age difference in reaction time was largest for negative faces. Older adults were significantly less accurate at identifying specific facial expressions of fear and sadness. No age differences specific to social function were found on tasks of self-reference, identifying emotional words, or theory of mind. Performance on the social tasks in older adults was independent of performance on general cognitive tasks (e.g., working memory) but was related to personality traits and emotional awareness. Older adults also showed more intercorrelations among the social tasks than did the younger adults. These findings suggest that age differences in social cognition are limited to the processing of facial emotion. Nevertheless, with age there appears to be increasing reliance on a common resource to perform social tasks, but one that is not shared with other cognitive domains.

Age-related changes in brain activity across the adult lifespan.

A number of theories have emerged to explain the well-studied changes in memory that occur with age. Many of these theories invoke mechanisms that have the potential to affect multiple cognitive domains, in addition to memory. Such mechanisms include alterations in attentional or inhibitory function, or dysfunction of specific brain areas, such as the frontal lobes. To gain insight into these mechanisms, we used functional magnetic resonance imaging to examine brain activity during encoding and recognition tasks in young, middle-aged, and older adults to identify correlations between age and brain activity across the various tasks. The goal was to see whether these correlations were task-specific or common across tasks, and to determine whether age differences emerged in a linear fashion over the adult years. Across all memory tasks, at both encoding and recognition, linear increases of activity with age were found in areas normally decreased during task performance (e.g., medial frontal and parietal regions), whereas activity in regions with task-related activation (e.g., dorsolateral prefrontal cortex) decreased with age. These results suggest that there is a gradual, age-related reduction in the ability to suspend non-task-related or "default-mode" activity and engage areas for carrying out memory tasks. Such an alteration in the balance between default-mode and task-related activity could account for increased vulnerability to distraction from irrelevant information, and thereby affect multiple cognitive domains.

Assessment of hot and cool executive function in young children: age-related changes and individual differences.

Although executive function (EF) is often considered a domain-general cognitive function, a distinction has been made between the "cool" cognitive aspects of EF more associated with dorsolateral regions of prefrontal cortex and the "hot" affective aspects more associated with ventral and medial regions (Zelazo and Mller, 2002). Assessments of EF in children have focused almost exclusively on cool EF. In this study, EF was assessed in 3- to 5-year-old children using 2 putative measures of cool EF (Self-Ordered Pointing and Dimensional Change Card Sort) and 2 putative measures of hot EF (Children's Gambling Task and Delay of Gratification). Findings confirmed that performance on both types of task develops during the preschool period. However, the measures of hot and cool EF showed different patterns of relations with each other and with measures of general intellectual function and temperament. These differences provide preliminary evidence that hot and cool EF are indeed distinct, and they encourage further research on the development of hot EF.

The development of executive function in early childhood.

According to the Cognitive Complexity and Control (CCC) theory, the development of executive function can be understood in terms of age-related increases in the maximum complexity of the rules children can formulate and use when solving problems. This Monograph describes four studies (9 experiments) designed to test hypotheses derived from the CCC theory and from alternative theoretical perspectives on the development of executive function (memory accounts, inhibition accounts, and redescription accounts). Each study employed a version of the Dimensional Change Card Sort (DCCS), in which children are required first to sort cards by one pair of rules (e.g., color rules: "If red then here, if blue then there"), and then sort the same cards by another, incompatible pair of rules (e.g., shape rules). Study 1 found that although most 3- to 4-year-olds failed the standard version of this task (i.e., they perseverated on the preswitch rules during the postswitch phase), they usually performed well when they were required to use four rules (including bidimensional rules) and those rules were not in conflict (i.e., they did not require children to respond in two different ways to the same test card). These findings indicate that children's perseveration cannot be attributed in a straightforward fashion to limitations in children's memory capacity. Study 2 examined the circumstances in which children can use conflicting rules. Three experiments demonstrated effects of rule dimensionality (uni- vs. bidimensional rules) but no effects of stimulus characteristics (1 vs. 2 test cards; spatially integrated vs. separated stimuli). Taken together, these studies suggest that conflict among rules is a key determinant of difficulty, but that conflict interacts with dimensionality. Study 3 examined what types of conflict pose problems for 3- to 4-year-olds by comparing performance on standard, Partial Change, and Total Change versions of the DCCS. Results revealed effects of conflict at the level of specific rules (e.g., "If red, then there"), rather than specific stimulus configurations or dimensions per se, indicating that activation of the preswitch rules persists into the postswitch phase. Study 4 examined whether negative priming also contributes to difficulty on the DCCS. Two experiments suggested that the active selection of preswitch rules against a competing alternative results in the lasting suppression of the alternative. Taken together, the results of these studies provide the basis for a revision of the CCC theory (CCC-r) that specifies more clearly the circumstances in which children will have difficulty using rules at various levels of complexity, provides a more detailed account of how to determine the complexity of rules required in a task, takes account of both the activation and inhibition of rules as a function of experience, and highlights the importance of taking intentionality seriously in the study of executive function.