The prefrontal cortex of the brain has been shown to play a crucial role in working memory, and age-related changes in prefrontal function may contribute to the improvements in working memory that are observed during childhood. We examined the developmental trajectory of working memory in school-age children with early-treated phenylketonuria (PKU), a metabolic disorder that results in prefrontal dysfunction. Using a recognition procedure, we evaluated working memory for letters, abstract objects, and spatial locations in 20 children with PKU and 20 typically developing control children. Children in both groups ranged from 6 to 17 years of age. Our findings revealed poorer performance across all three types of materials for children with PKU. In addition, there was a significant difference in the developmental trajectory of working memory for children with PKU as compared with controls. Specifically, deficits were not apparent in younger children with PKU. Instead, deficits were observed only in older children, suggesting the presence of a developmental deficit rather than a developmental delay in the working memory of children with PKU. (JINS, 2002, 8, 1–11.)

This study prospectively examined neuropsychological (NP) functioning associated with adolescent substance use and withdrawal. Participants were youths with histories of substance use disorders (n = 47) and demographically comparable youths with no such lifetime histories (n = 26). They were followed with NP testing and substance involvement interviews at 7 time points spanning 8 years, from ages 16 to 24, on average. After controlling for recent use, age, education, practice effects, and baseline NP functioning, substance use over the 8-year follow-up period significantly predicted performances on tests of memory and attention at Year 8. Additionally, withdrawal symptoms during the follow-up predicted visuospatial and attention scores at Year 8. Findings suggest that use and withdrawal may differentially impact neurocognitive functioning during youth, with heavy use leading to learning, retention, and attentional difficulties, and withdrawal leading to problems with visuospatial functioning. (JINS, 2002, 8, 873–883.)

Previous neuroimaging studies of the Stroop task have postulated that the anterior cingulate cortex (ACC) plays a critical role in resolution of the Stroop interference condition. However, activation of the ACC is not invariably seen and appears to depend on a variety of methodological factors, including the degree of response conflict and response expectancies. The present functional MRI study was designed to identify those brain areas critically involved in the interference condition. Healthy subjects underwent a blocked-trial design fMRI experiment while responding to 1 of 3 stimulus conditions: (1) incongruent color words, (2) congruent color words, and (3) color-neutral words. Subjects responded to the printed color of the word via a manual response. Compared to the congruent and neutral conditions, the incongruent condition produced significant activation within the left inferior precentral sulcus (IpreCS) located on the border between the inferior frontal gyrus, pars opercularis (BA 44) and the ventral premotor region (BA 6). Significant deactivations in the rostral component of the ACC and the posterior cingulate gyrus were also observed. Selective activation of the left IpreCS is compatible with findings from previous neuroimaging, lesion, electrophysiological, and behavioral studies and is presumably related to the mediation of competing articulatory demands during the interference condition. (JINS, 2002, 8, 735–742.)

The current study sought to determine if discrepancies in quality of education could explain differences in cognitive test scores between African American and White elders matched on years of education. A comprehensive neuropsychological battery was administered to a sample of African American and non-Hispanic White participants in an epidemiological study of normal aging and dementia in the Northern Manhattan community. All participants were diagnosed as nondemented by a neurologist, and had no history of Parkinson's disease, stroke, mental illness, or head injury. The Reading Recognition subtest from the Wide Range Achievement Test–Version 3 was used as an estimate of quality of education. A MANOVA revealed that African American elders obtained significantly lower scores than Whites on measures of word list learning and memory, figure memory, abstract reasoning, fluency, and visuospatial skill even though the groups were matched on years of education. However, after adjusting the scores for WRAT–3 reading score, the overall effect of race was greatly reduced and racial differences on all tests (except category fluency and a drawing measure) became nonsignificant. These findings suggest that years of education is an inadequate measure of the educational experience among multicultural elders, and that adjusting for quality of education may improve the specificity of certain neuropsychological measures. (JINS, 2002, 8, 341–348.)

Previous studies showed that cortex in the anterior portions of the left frontal and temporal lobes participates in generating words with emotional connotations and processing pictures with emotional content. If these cortices process the semantic attribute of emotional connotation, they should be active whenever processing emotional connotation, without respect to modality of input or mode of output. Thus, we hypothesized that they would activate during monitoring of words with emotional connotations. Sixteen normal subjects performed semantic monitoring of words with emotional connotations, animal names, and implement names during fMRI. Cortex in the anterior left frontal lobe demonstrated significant activity for monitoring words with emotional connotations compared to monitoring tone sequences, animal names, or implement names. Together, the current and previous results implicate cortex in the anterior left frontal lobe in semantic processing of emotional connotation, consistent with connections of this cortex to paralimbic association areas. Current findings also indicate that neural substrates for processing emotional connotation are independent of substrates for processing the categories of living and nonliving things.

Subtypes of working memory performance were examined in a cohort of 50 HIV-infected adults and 23 uninfected controls using an n-back paradigm (2-back) in which alphabetic stimuli were quasi-randomly presented to a quadrant of a computer monitor. In the verbal working memory condition, participants determined whether each successive letter matched the letter that appeared two previously in the series, regardless of spatial location. In the spatial working memory condition, participants determined whether each letter matched the spatial location of the letter that had appeared two previously, regardless of letter identity. The dependent variable was percent accuracy in each condition. Results of mixed model ANOVA revealed that the HIV-infected participants performed significantly worse than controls on both the verbal and spatial working memory tasks. A significant main effect for working memory condition was also present with both participant groups performing better on the spatial working memory task. These results, the first study of HIV-infected adults to directly compare verbal versus spatial working memory performance using the identical test stimuli across task conditions, suggests that HIV infection is associated with a decrement in working memory efficiency that is equally apparent for both verbal and spatial processing. These findings implicate central executive dysfunction as a likely substrate and provide the basis for hypothesizing that decline in working memory may contribute to other HIV-associated neuropsychological deficits. (JINS, 2002, 8, 532–538.)

Healthy dextrals underwent fMRI during a task of graphesthesia requiring detection of any number written consecutively from an otherwise random number sequence. Test conditions included (1) focus on unilateral right hand stimuli, (2) focus on unilateral left hand stimuli, (3) focus on right hand only during bilateral hand stimulation, (4) focus on left hand only during bilateral hand stimulation, and (5) rest. Attention to unilateral hand stimulation produced bihemispheric activation with minimal or no activation of ipsilateral primary sensorimotor region. Attention to unilateral left hand stimuli resulted in more activation than attention to unilateral right hand stimuli. Stimulation of the nonattended hand activated the contralateral somatosensory area, but to a lesser spatial extent than attended stimuli. Comparing focused attention to the left versus right side during identical sensory inputs (i.e., bilateral hand stimulation), focused attention to the right hand increased activation in the left somatosensory region, but focused attention to the left hand increased activation in both cerebral hemispheres. Thus, focused attention to unilateral somatosensory stimuli produces bilateral cerebral activation, but the increase in blood flow is greater in the contralateral hemisphere. Unattended stimuli activate the contralateral primary somatosensory area. Left/right asymmetries were demonstrated consistent with cerebral lateralization. (JINS, 2002, 8, 349–359.)

The presence of cocaine during the prenatal period disrupts the development of neural systems involved in mediating visual attention; therefore, it is possible that prenatal cocaine exposure results in impairments in visual attention in early childhood. In the current study we hypothesized that preschool children with prenatal cocaine exposure would exhibit difficulties in the disengagement operation of visual attention and in sustaining attention, particularly for targets presented in the right visual field. Fourteen cocaine-exposed children and 20 control children between 14 and 60 months of age were assessed on measures of visual attention, cognition, and behavior. Cocaine-exposed children had slower reaction times on disengagement trials in the second half of our attention task, supporting our hypotheses that impairments in disengagement and sustained attention are associated with prenatal cocaine exposure. There was a trend for slower reaction times to targets presented in the right visual field, but not to targets presented in the left visual field. Cocaine-exposed children also exhibited greater difficulties in behavioral regulation. Overall, our findings suggest that children with prenatal cocaine exposure demonstrate specific impairments in visual attention and behavioral regulation. (JINS, 2002, 8, 12–21.)

Work on implicit memory in normal subjects has demonstrated the influence of stimulus modality on the retrieval of semantic information. The present study examined the effects of auditory and visual semantic priming on the recognition of visual words using a lexical decision task. Performance was studied in a group of 20 patients with DSM–IV schizophrenia and 26 normal volunteers of similar age and sex. There were two versions of the task: ipsimodal, in which the word or nonword visual target followed 400 ms after the onset of a visual word prime which may or may not be semantically related to the target; and cross-modal, in which the visual target followed 400 ms after the onset of an auditory word prime. Both groups showed significant priming in both modality conditions, although the schizophrenia patients exhibited significantly greater priming in the cross-modal condition. Priming effects in the ipsimodal condition did not differ substantially between patients and controls. The priming effects in the two conditions correlated with each other in the schizophrenia patients only. The results suggest that priming may occur through amodal semantic representations. In schizophrenia, there appears to be increased cross-modal connectivity (reduced modality modularity and informational encapsulation) between lexical representations that could result in impaired language, particularly speech, processing. (JINS, 2002, 8, 884–892.)

The relationship between MRI findings (i.e., subcortical hyperintensities; SH, whole brain volume) and the cognitive dysfunction of vascular dementia (VaD) was examined. Participants included 24 persons that met NINDS-AIREN criteria for VaD (MMSE = 19.9 ± 4.2) and underwent comprehensive neuropsychological assessment and MRI brain imaging. The volume of subcortical hyperintensities (SH) was strongly associated with executive–psychomotor performance, but not with performance across other cognitive domains or global cognitive functional level. Conversely, WBV was strongly associated with global cognitive functioning and performance across most cognitive domains (memory, language, visual integration), but not with executive–psychomotor functioning. The failure of SH to account for either the global dementia evident in these VaD patients or impairments across most cognitive domains suggests that deep subcortical white matter disease may only indirectly contribute to the global cognitive dysfunction of VaD. That WBV emerged as a stronger correlate of dementia raises further questions regarding the cerebral mechanisms that contribute to the development of VaD. (JINS, 2002, 8, 743–752.)

Even though frontal lobe epilepsy (FLE) is a relatively common seizure type, no formal psychometric studies of children with FLE have been reported. We compared 12 children with FLE and 15 children with temporal lobe epilepsy (TLE) on neuropsychological tests of attention, memory, executive functioning, and adaptive functioning. The results of these tests indicated that the children with FLE had deficits in planning and executive functions, whereas their verbal and nonverbal memory was intact. The opposite pattern was observed in children with TLE. Measures of executive functioning and impulse control were the best predictors of adaptive functioning. The findings suggest that children with FLE have a pattern of cognitive deficits that differs markedly from the pattern seen in children with TLE. Children with FLE have prominent deficits in executive functioning that appear to be related to poor behavioral adaptation.

Unawareness of deficit is a common feature of degenerative dementia. The present study explored awareness and correction of naturalistic action errors in 54 dementia participants and 10 healthy controls while they performed a series of everyday tasks, such as toast preparation and gift-wrapping. Awareness for everyday task performance and cognitive functioning was also assessed with questionnaire discrepancy scores, and a neuropsychological test protocol was administered. Dementia participants were aware of and corrected a significantly smaller proportion of errors compared to controls (z = 4.59, p < 001). Awareness and correction of action errors was not significantly correlated with the number of naturalistic errors committed, questionnaire discrepancy scores, or neuropsychological test data. Within-group analyses showed awareness differed across error types, such that participants were aware of a greater proportion of substitution and sequence errors compared to omissions, perseverations, and action addition (i.e., utilization behavior) errors (z ≤ −3.2,p≤.002 for all analyses). Taken together these data suggest that error awareness and correction during the course of action is not related to error production or awareness measured via questionnaire discrepancy scores. Rather, direct assessment of error detection and correction may provide novel information about behavioral monitoring that can not be extrapolated from measures of dementia severity or traditional neuropsychological assessment.

Areas of the brain affected in the early stages of Alzheimer's disease are also areas heavily involved in the processing of olfactory information. Olfactory event-related potentials (OERPs) and auditory ERPs were recorded from the Fz, Cz, and Pz electrode sites in 12 Alzheimer's disease (AD) patients and 12 age and gender matched normal controls (NC) in a single-stimulus paradigm with a 45 s inter-trial interval, using amyl acetate as the olfactory stimulus, and in a separate session a 500 Hz tone as the auditory stimulus. Odor identification (ID) was also used to assess ability to identify odors. The results indicate that (1) OERP P2 and P3 latencies were significantly longer in AD patients than normal controls; (2) olfactory ERP latency measures correlated significantly with dementia status as measured by the Dementia Rating Scale (DRS), indicating that as participants performed more poorly on the DRS, reflecting increased dementia, OERP latencies increased; (3) olfactory ERP latency measures better differentiated AD patients from normal controls than auditory ERP latency measures; (4) olfactory ERP measures alone correctly classified up to 92% of participants; (5) odor ID measures, namely the UPSIT and San Diego-Odor-ID tests also classified participants at a high rate. Combining scores for odor identification with olfactory P3 latency measures resulted in a correct classification rate of 100%. The results strongly support the use of olfactory measures in the assessment of AD. (JINS, 2002, 8, 753–763.)

Numerous studies have suggested that frontal cortex plays a strategic, rather than an absolute, role in memory performance. Typically, frontal patients are reported to have impaired recall but normal recognition memory. A recent meta-analysis, however, has questioned this conclusion. To further investigate the role of frontal cortex in long-term memory, patients with focal frontal lesions and age- and education-matched controls were tested on a new version of the California Verbal Learning Test (CVLT–II). Frontal patients exhibited a number of deficits on this test, including overall poorer recall, an increased tendency to make intrusions, reduced semantic clustering, and impaired yes/no recognition performance. Further analysis of the error rates in the yes/no recognition task revealed that frontal patients were most likely to mistakenly endorse 2 types of distractors: semantically related words and words from an interference list. These findings are discussed with respect to the role of frontal dysfunction in false recollections and poor source memory, as well as the distinction between the roles of frontal and temporal cortex in long-term memory. (JINS, 2002, 8, 539–546.)

Performance variability on neuropsychological measures is not a unitary phenomenon, and different measures (consistency, dispersion, diversity) evaluate separate elements of variability. It has been suggested that increased variability may be a specific attribute of frontal lobe pathology. This hypothesis was tested in 2 matched groups of demented subjects, 8 with dementia of the Alzheimer type (DAT), 5 with frontal lobe dementia (FLD), compared with 10 elderly normal controls (ENC). A Stroop test and Reaction Time measures were administered weekly for 5 weeks to all subjects. Both measures contained three subtests varying in degree of complexity. The results from the Stroop task indicated that the FLD group showed significantly greater variability on measures of consistency (fluctuations over time) and diversity (between participant variability) regardless of the complexity of the subtest. For the Reaction Time subtests, measures of consistency and diversity showed significantly greater variability in FLD, but were affected in a different pattern. Greater variability in terms of consistency of performance was manifested only in the more attentionally demanding of the Reaction Time subtests (Choice Reaction Time, CRT). On the measure of diversity, variable performance was found to be greater on the Simple Reaction Time (SRT) subtest than on the more effortful CRT. Dispersion (within participant variability) was only assessed on the reaction time subtests. The results indicate no significant evidence for an increase in dispersion for the FLD patients. The hypothesis that variability will be increased in frontal lobe dementia is thus confirmed, and the independence of the three forms of variability measurement is demonstrated in dementia subjects. (JINS, 2002, 8, 360–372.)

The planum temporale is clearly involved in language processing, for it serves as the auditory association cortex. Research has consistently demonstrated that 60 to 70% of the population has leftward asymmetry of the planum temporale. Research has also suggested that dyslexic individuals tend to have either rightward asymmetry or symmetrical plana. Moreover, many studies have found a relationship between the presence of dyslexia and/or language impairment and deficits in the normal right ear advantage found in dichotic listening paradigms. In this context, this study examined the relationship between planum temporale asymmetry and ear preference in dichotic listening performance in children with Developmental Dyslexia and Attention-Deficit/Hyperactivity Disorder (ADHD). Subjects included 19 children with dyslexia (10 of whom had a comorbid diagnosis of ADHD), 23 children with ADHD, and 12 diagnosed normal control children. Dichotic listening data were not collected for 8 of the 12 normal control children and for 3 of the 23 ADHD children. Results revealed no significant difference between ADHD and dyslexic subjects in regard to ear advantage on the free recall dichotic listening task. In addition, although the directed dichotic listening tasks were not related to degree of planum asymmetry, as predicted, results indicated that subjects who consistently displayed an atypical left ear advantage tended to have larger right bank lengths than those who consistently displayed a typical right ear advantage. These findings support the notion that some individuals with dyslexia or language deficits tend to have a larger right planum temporale and that performance on dichotic listening tasks may reflect this relatively unusual pattern. (JINS, 2002, 8, 22–36.)