Performance on long delays of delayed response tasks is associated with medial temporal function, a region of the brain affected by severe hypoglycemia. A previous study showed that children with type 1 diabetes mellitus (T1DM) with higher risk for severe hypoglycemia performed worse than controls on long delays of a spatial delayed response (SDR) task. We tested the more specific hypothesis that frequency of severe hypoglycemia would relate to long delay SDR performance. Children with T1DM (n = 51) and controls (n = 32) performed the SDR task with short and long delays. Information was collected on children's past severe hypoglycemia. In children with T1DM, number of past severe hypoglycemic episodes accounted for a significant portion of the variance in long delay SDR after controlling for age and age of onset. This relationship was not seen with short delay SDR or with other tasks (verbal or object memory, attention, motor speed). These results support the hypothesis that severe hypoglycemia has specific, negative effects on memory skills in children. If this relationship is extrapolated to children with higher frequency of severe hypoglycemia, due to longer duration of disease or poorer glucose control, it may affect daily functioning and thus need to be considered in treatment decisions. (JINS, 2003, 9, 740–750.)

The present study investigated everyday numerical abilities in a group of 21 patients affected by mild to moderate dementia of Alzheimer's type (DAT). Though patients did not differ from a control group in standard laboratory tests tapping transcoding, number comparison, simple calculation, and estimation, they showed significant difficulties in numerical tasks embedded in an everyday context, such as handling money, a bus schedule, or a television program. Patients' difficulties were attributed to those multiple cognitive demands which are inherent to real situations as compared to well-structured abstract paper-and-pencil tasks. Overall, the study suggests that the examination of numerical abilities in DAT patients should go beyond abstract paper-and-pencil tasks which can only partially reflect the actual numerical skills in DAT and should therefore include also tasks simulating everyday life situations. Assessment of everyday numerical skills may be crucial in planning adequate support for patients, for example in handling money, but also in designing targeted training programs. (JINS, 2003, 9, 871–878.)

Previous studies by our group have demonstrated fMRI signal changes and synchronized gamma rhythm EEG oscillations between thalamus and cortical regions as subjects recall objects from visually presented features. Here, we extend this work by estimating the time course of fMRI signal changes in the cortical and subcortical regions found to exhibit evidence for task-related activation. Our results indicate that there are separate loci of signal changes in the thalamus (dorsomedial and pulvinar) that exhibit notable differences in times of onset, peak and return to baseline of signal changes. The signal changes in the pulvinar demonstrate the slowest transients of all the cortical and subcortical regions we examined. Evaluation of cortical regions demonstrated salient differences as well, with the signal changes in Brodmann area 6 (BA6) rising, peaking, and returning to baseline earlier than those detected in other regions. We conclude that BA6 mediates early designation or refinement of search criteria, and that the pulvinar may be involved in the binding of feature stimuli for an integrated object memory. (JINS, 2003, 9, 1031–1040.)

In recent years, interest in the use of computerized neuropsychological (NP) assessment measures has increased. However, there are limited data regarding how performance on these measures relates to performance on more traditional, clinical instruments. In the present study, 82 HIV+ men, who were all believed on clinical grounds to have neurobehavioral impairment, completed a traditional NP battery (TNB) and the California Computerized Assessment Package (CalCAP, a collection of computerized reaction time tests). Summary scores based on a TNB, as well as those based on the CalCAP, demonstrated significant associations with both degree of immunosuppression (CD4 count) and detectable viral load in cerebrospinal fluid, but not with detectable viral load in plasma. Established norms on the TNB and CalCAP batteries resulted in classifying 57% and 49% of the HIV+ sample as impaired, respectively. When using the TNB as the “gold standard,” impairment classifications based on CalCAP summary scores exhibited a sensitivity of 68% and a specificity of 77%. Overall agreement on impairment classifications between batteries was low (kappa = .44). Data from this study suggest that traditional NP batteries and computerized reaction time tests do not measure the same thing, and are not interchangeable in examining HIV-related NP impairments. (JINS, 2003, 9, 64–71.)

To explore possible neurotoxic sequelae of Gulf War (GW) participation, olfactory identification performance, neurocognitive functioning, health perceptions, and emotional distress were assessed in 72 veterans deployed to the GW and 33 military personnel activated during the GW but not deployed to the war zone. Findings revealed that war-zone-exposed veterans reported more concerns about health, cognitive functioning, and depression than did their counterparts who did not see war-zone duty. There was no evidence that performances on olfactory or neurocognitive measures were related to war-zone duty or to self-reported exposure to GW toxicants. However, symptoms of emotional distress were positively correlated with self-report of health and cognitive complaints. Results do not provide support for the hypothesis that objectively-measured sensory (i.e., olfactory) or cognitive deficits are related to war-zone participation but do underscore the increasingly demonstrated association between self-reported health concerns and symptoms of emotional distress. (JINS, 2003, 9, 407–418.)

The relationship between apolipoprotein E (apoE) genotype and cognitive performance was examined in 200 patients with probable Alzheimer's disease (AD). Differences between composite measures of verbal and nonverbal functioning were used to define asymmetric patterns of cognition. Patients who were homozygous for apoE ε4 demonstrated relatively worse nonverbal as compared to verbal cognitive ability. In contrast, participants who were heterozygous for apoE ε4 or who possessed no ε4 allele demonstrated relatively equivalent verbal and nonverbal cognitive abilities. Although age and dementia severity also contributed to these patterns, apoE genotype appears to have a significant unique contribution to cognitive performance in these individuals. The ε4 allele may thus be associated with a specific neurocognitive phenotype among patients with AD, with the overall pattern of cognitive asymmetry dependent upon ε4 dose. (JINS, 2003, 9, 751–759.)

The impact of basal ganglia dysfunction on semantic processing was investigated by comparing the performance of individuals with nonthalamic subcortical (NS) vascular lesions, Parkinson's disease (PD), cortical lesions, and matched controls on a semantic priming task. Unequibiased lexical ambiguity primes were used in auditory prime-target pairs comprising 4 critical conditions; dominant related (e.g., bank–money), subordinate related (e.g., bank–river), dominant unrelated (e.g., foot–money) and subordinate unrelated (e.g., bat–river). Participants made speeded lexical decisions (word/nonword) on targets using a go–no-go response. When a short prime–target interstimulus interval (ISI) of 200 ms was employed, all groups demonstrated priming for dominant and subordinate conditions, indicating nonselective meaning facilitation and intact automatic lexical processing. Differences emerged at the long ISI (1250 ms), where control and cortical lesion participants evidenced selective facilitation of the dominant meaning, whereas NS and PD groups demonstrated a protracted period of nonselective meaning facilitation. This finding suggests a circumscribed deficit in the selective attentional engagement of the semantic network on the basis of meaning frequency, possibly implicating a disturbance of frontal–subcortical systems influencing inhibitory semantic mechanisms. (JINS, 2003, 9, 1041–1052.)

Psychophysical functions are used to characterize both normal perception and altered perception among patients with neglect, yet the reliability of these functions is rarely examined. The present study examined two-week, test-retest reliability for power functions derived from line bisection data among 58 normal, young and old, male and female subjects. Power function exponents and constants were, at best, moderately reliable over time. The size of the exponent tended to decrease at retesting. Reliability coefficients varied by age and gender; they were highly significant for young men, marginally significant for older men, and non-significant for women. Race influenced reliability as coefficients were significant for Caucasian subjects but not for African American subjects. Age and gender effects in this study parallel those in the literature on pseudoneglect, and they may reflect hemispheric differences in visuo-spatial processing, magnitude estimation, or both. (JINS, 2003, 9, 72–78.)

Prior studies have found no adverse effects of pediatric epilepsy surgery on IQ. However, empirical techniques such as regression models, designed to account for confounding factors such as practice effects and test–retest reliability and able to provide a standardized method for evaluating outcome, have not been used in studying change after pediatric epilepsy. The goal of this study was to demonstrate the regression technique while empirically measuring the effect of epilepsy surgery on IQ in a group of pediatric patients. Predictors of retest IQ (e.g., baseline IQ, retest interval, demographics, epilepsy severity) were evaluated in a control group with intractable seizures (N = 23) assessed twice with the WISC–III. The resulting equation was used to evaluate IQ changes in a second group of children who underwent epilepsy surgery (N = 22). In controls, baseline IQ was a strong predictor of retest IQ. Number of AEDs was inversely related to retest IQ. Based on the control regression, four children (18%) in the surgical sample obtained significantly higher than expected postsurgical IQ scores and one child (5%) obtained a lower than expected IQ score. This study demonstrates that regression-based techniques yield informative estimates on outcome and may be an improvement over prior methods of measuring change after pediatric epilepsy surgery. (JINS, 2003, 9, 879–886.)

Performance on many cognitive and neuropsychological tests may be improved by prior exposure to testing stimuli and procedures. These beneficial practice effects can have a significant impact on test performance when conventional neuropsychological tests are administered at test–retest intervals of weeks, months or years. Many recent investigations have sought to determine changes in cognitive function over periods of minutes or hours (e.g., before and after anesthesia) using computerized tests. However, the effects of practice at such brief test–retest intervals has not been reported. The current study sought to determine the magnitude of practice effects in a group of 113 individuals assessed with an automated cognitive test battery on 4 occasions in 1 day. Practice effects were evident both between and within assessments, and also within individual tests. However, these effects occurred mostly between the 1st and 2nd administration of the test battery, with smaller, nonsignificant improvements observed between the 2nd, 3rd, and 4th administrations. On the basis of these results, methodological and statistical strategies that may aid in the differentiation of practice effects from drug-induced cognitive changes are proposed. (JINS, 2003, 9, 419–428.)

This study identified subtypes of psychosocial functioning in children who had sustained traumatic brain injury (TBI). Child Behavior Checklist (CBCL) profiles for 92 participants, aged 12 to 18 years, who had sustained a mild, moderate, or severe TBI were subjected to Q-Factor analysis. Sixty-four of the participants (75%) were classified into a four-category psychosocial typology labelled Normal (n = 32), Attention (n = 14), Delinquent (n = 10), and Withdrawn–Somatic (n = 8). This typology was found to overlap in part with previous TBI psychosocial typology (Butler et al., 1997), and with three of the clinical profile types derived by Achenbach (1993) for the CBCL. The majority of participants, including those who sustained severe TBI, were assigned to the Normal subtype and the overall level of psychosocial deviance was relatively mild in the other three subtypes. The results of this study support previous typology efforts and confirm the heterogeneous presentation of social and emotional functioning following TBI. (JINS, 2003, 9, 887–898.)

Phonemic and semantic fluency involve the capacity to generate words beginning with particular letters or belonging to particular categories, respectively. The former has been associated with frontal lobe function and the latter with temporoparietal function, but neuroimaging studies indicate overlap of underlying neural networks. Schizophrenia patients may experience disproportionate semantic fluency impairment owing to abnormal semantic organization; however, executive dysfunction in schizophrenia suggests possible disproportionate phonemic fluency impairment. Moreover, little is known about the diagnostic specificity of either verbal fluency deficit to schizophrenia or their stability over time. We examined 83 schizophrenia patients, 15 bipolar disorder patients, and 83 normal controls. Both fluency types were impaired in schizophrenia patients. Schizophrenia patients as a whole manifested disproportionate semantic fluency impairment relative to bipolar disorder patients, but only a subset of schizophrenia patients manifested disproportionate semantic fluency impairment relative to controls. Few characteristics, except to some extent paranoid-nonparanoid subtype, meaningfully differentiated schizophrenia patients with and without this disproportionate impairment. Verbal fluency measures were moderately stable over a 4-year period in schizophrenia patients and controls (.48 < rs < .79). These results mirror a literature that overall suggests a small degree of disproportionate semantic fluency impairment in schizophrenia, but also some heterogeneity in fluency deficits. (JINS, 2003, 9, 79–88.)

The role of the basal ganglia in syntactic language processing was investigated with event-related brain potentials in fourteen neurologically impaired patients. Seven of these patients had basal ganglia lesions while 7 other patients primarily had lesions of the left temporo–parietal region excluding the basal ganglia. All patients listened to sentences that were either correct or included a verb argument structure violation. In previous experiments this type of violation elicited a biphasic pattern of an N400–P600 complex in young healthy participants. While the N400 may result from incorrect semantic-thematic role assignment, the P600 reflects the fact that verb information does not license the syntactic structure at present. Results of the patient experiment revealed a double dissociation: patients with left temporo–parietal lesions only show a P600, whereas patients with lesions of the basal ganglia showed no P600, but a negativity with extended duration that resembled an N400. The latter pattern not only confirms previous reports that the basal ganglia modulate the P600 but extends these results by showing that the N400 as a late semantic–thematic integration process appears partially modulated by the basal ganglia. (JINS, 2003, 9, 1053–1060.)

Previous studies of depression after stroke have reported widely variable findings, possibly due to differences between studies in patient characteristics and methods for the assessment of depression, small sample sizes, and the failure to examine stroke-free reference groups to determine the base rate of depression in the general population. In an effort to address certain of those methodologic issues and further investigate the frequency and clinical determinants of depression after stroke, we administered the Structured Interview Guide for the Hamilton Depression Rating Scale (SIGH–D) and neurological, neuropsychological, and functional assessments to 421 patients (age = 71.5 ± 8.0 years) 3 months after ischemic stroke and 249 stroke-free control subjects (age = 70.8 ± 6.7 years). We required a SIGH–D total score > 11 for the identification of depression. We found that depression was less frequent (47/421 patients, or 11.2%, and 13/249 control subjects, or 5.2%), less severe, and less persistent in our stroke cohort than previously reported, possibly due to the underrepresentation of patients with a premorbid history of affective illness. Depression was associated with more severe stroke, particularly in vascular territories that supply limbic structures; dementia; and female sex. SIGH–D item analyses suggested that a reliance on nonsomatic rather than somatic symptoms would result in the most accurate diagnoses of depression after ischemic stroke. (JINS, 2003, 9, 429–439.)

While neurobiological factors are known to play a role in human aggression, relatively few studies have examined neuropsychological contributions to propensity for violence. We previously demonstrated cognitive deficits among men who committed domestic violence (batterers) compared to non-violent controls. Batterers had deficits in verbal ability, learning and executive problem-solving ability. These findings led us to examine whether executive control problems involving impulsivity contribute to problems with behavioral control among batterers, and to further examine their deficits in verbal functioning. Batterers (n = 41) enrolled in a domestic violence program were compared to 20 non-violent men of similar age, education, and socioeconomic background on neuropsychological tests of executive functioning, including impulsivity. Questionnaires and structured clinical interviews were used to assess emotional distress, aggression and self-reported impulsivity. Batterers showed greater impulsivity compared to non-batterers on several neuropsychological measures. Yet, the severity of these deficits was relatively mild and not evident in all batterers. Consistent with our previous findings, significant verbal deficits were again observed among the batterers. These findings suggest that while impulsivity may be a factor associated with domestic violence, it probably is not the sole determinant of the strong relationship between cognitive functioning and batterer status that we previously observed. Both verbal expressive deficits and behavioral impulsivity appear to be relevant variables in predisposing men to domestic violence. (JINS, 2003, 9, 760–770.)

fMRI was used to determine the frontal, basal ganglia, and thalamic structures engaged by three facets of language generation: lexical status of generated items, the use of semantic vs. phonological information during language generation, and rate of generation. During fMRI, 21 neurologically normal subjects performed four tasks: generation of nonsense syllables given beginning and ending consonant blends, generation of words given a rhyming word, generation of words given a semantic category at a fast rate (matched to the rate of nonsense syllable generation), and generation of words given a semantic category at a slow rate (matched to the rate of generating of rhyming words). Components of a left pre-SMA–dorsal caudate nucleus–ventral anterior thalamic loop were active during word generation from rhyming or category cues but not during nonsense syllable generation. Findings indicate that this loop is involved in retrieving words from pre-existing lexical stores. Relatively diffuse activity in the right basal ganglia (caudate nucleus and putamen) also was found during word-generation tasks but not during nonsense syllable generation. Given the relative absence of right frontal activity during the word generation tasks, we suggest that the right basal ganglia activity serves to suppress right frontal activity, preventing right frontal structures from interfering with language production. Current findings establish roles for the left and the right basal ganglia in word generation. Hypotheses are discussed for future research to help refine our understanding of basal ganglia functions in language generation. (JINS, 2003, 9, 1061–1077.)

Among children born at extremely low birthweight (ELBW: <1000 g at birth) there is an association between the presence of periventricular brain injury (PVBI) and lowered performance on tests of reading and spelling ability. The present study was designed to determine if this association might be related to underlying dysfunction in the subcortical magnocellular visual pathway or its cortical targets in the dorsal stream, a prediction motivated by the magnocellular theory of dyslexia. Thirty-five ELBW children were divided into two groups based upon the presence or absence of PVBI (no PVBI, n = 11; PVBI, n = 24). The performance of these two groups was compared to that of a group of healthy full term children (n = 12) on a motion-defined form recognition task believed to tap into the functioning of the magnocellular pathway and/or the dorsal stream. ELBW children did, in fact, show a striking impairment on this task, with 71% of the sample performing at a level more than three standard deviations below the mean of full term controls. Surprisingly, their difficulties were not found to be related to either the presence of brain injury (verified by neonatal cranial ultrasound) or to problems with reading or spelling. An association was documented, however, between difficulties with motion processing and performance on several subtests of the Performance IQ scale of the Wechsler Intelligence Scale for Children–Third Edition. This latter finding is consistent with our earlier suggestion that magnocellular pathway/dorsal stream dysfunction may underlie problems with visuospatial and visuomotor performance in this population. (JINS, 2003, 9, 440–449.)

The effect of the degree of illiteracy (complete or incomplete) on phonological skills, verbal and visual memory and visuospatial skills is examined in 97 normal Brazilian adults who considered themselves illiterate, and 41 Brazilian school children aged 7 to 8 years, either nonreaders or beginning readers. Similar literacy effects were observed in children and in adults. Tasks involving phonological awareness and visual recognition memory of nonsense figures distinguish the best nonreaders and beginning readers. Children performed better than adults at oral repetition of short items and figure recall, and adults better than children at semantic verbal fluency, digit span, and word list recall. A principal component analysis of the correlations between tasks showed that phonological awareness/ reading, phonological memory/oral repetition, and semantic verbal memory/fluency tasks, generated different components. The respective role of culturally based preschool activities and literacy on the cognitive functions that are explored in this study is discussed. (JINS, 2003, 9, 771–782.)

The standardization sample from the WMS–III (N = 1250), which varied in age from 16 to 89, was used to determine whether encoding, retrieval, or storage of verbal and spatial information was most affected by normal aging. Immediate and delayed recall and recognition of Logical Memory and Visual Reproduction were examined. Immediate verbal and spatial recall significantly deteriorated with increasing age, and the age-associated deterioration in delayed recall and recognition was largely explained by poorer immediate memory. These findings, in concert with the smaller aging effects for percent retention after a delay, suggest that the aging effect is due to deterioration in encoding more than retrieval or storage of new information. While Visual Reproduction deteriorated more rapidly with age than Logical Memory, the pattern of performance decrements as a function of age were comparable across both tests. Decreases in performance were first seen in the fifth decade with gradual deterioration until the eighth decade when there was another precipitous drop. These results suggest that functions that are more dependent on the frontal lobes are more vulnerable to aging than those that are more dependent on the temporal lobes. (JINS, 2003, 9, 89–96.)

Calculation and number-processing abilities were studied in 49 patients with chronic single vascular brain lesions by means of a standardized multitask assessment battery (EC301), as well as through other tasks, testing functions thought to be implicated in calculation such as language, visuo-perceptive abilities, verbal and spatial working memory, planning, and attention. The results show that (1) lesions involving parietal areas—particularly left parietal lesions—are prone to alter calculation processing. A more detailed analysis showed that patients with lesions involving left parietal areas were impaired in both digital (i.e., comprehension and production of numbers written in Arabic code) and oral (i.e., comprehension and production of numbers heard or expressed orally) processing while lesions involving right parietal areas lead to an impairment in digital processing only. However, linguistically related alphanumerical processing (i.e., comprehension and production of numbers written orthographically) was not influenced by parietal lesions. (2) Semantic representations (knowledge of the magnitude related to a given number) as well as rote arithmetical knowledge are also impaired following damage to parietal and particularly left parietal lesions, suggesting that these areas are also implicated in magnitude comparisons and in the retrieval of arithmetical facts. (3) Performance in calculation is highly correlated with language. (4) Moreover, we found a highly significant correlation between performances in oral calculation and verbal working memory, and between written-digit calculation and visuospatial working memory. Performances in regard to visuo-perceptive abilities, planning, and attention were less consistently correlated with calculation. These results stress the close correlation, but relative independence between calculation and language, as well as a dissociated sensitivity of oral and digital processing to brain lesions. (JINS, 2003, 9, 899–912.)