Search

For the treatment of mesial temporal lobe epilepsy on the language-dominant side in patients at high risk of memory decline, we propose a minimally invasive diagnostic and treatment technique, adopting the principles of multiple hippocampal transections (MHT) using stereo-electroencephalography-guided radiofrequency (SEEG-guided-RF-MHT). This new technique allows targeting of the longitudinal fibers in the hippocampus critical for seizure spreading, while sparing the transverse circuits which are considered important for memory processing and avoiding discomfort and longer post-operatory recovery time associated with craniotomies. We report the efficacy and safety of this procedure in a preliminary observational study of cases. Five patients at high risk of memory decline, including three with non-lesional hippocampi on MRI, had temporal lobe epilepsy (TLE) necessitating depth electrode implantation. A new strategy of SEEG electrode placement was used to mimic MHT. After confirming hippocampal seizure onset, all the patients had three linear ablations perpendicular to the amigdalohippocampal complex. The procedure was performed at the patient's bedside with the patient awake during the full length of the procedure. Four out of five patients were seizure-free (average follow up: 14-18 months). There were no associated complications. Visual inspection of brain MRI of patients at six months following SEEG-guided RF-MHT showed significant hippocampal volume preservation. Subjects who received the procedure in the dominant side reported no subjective memory complaints in the follow-up clinic assessments at six months. Our preliminary seizure outcome seems very promising since the majority of our patients (four out of five patients) were seizure-free. Since no lesions are made outside the amygdalo-hippocampal complex using this technique and the temporal stem remains intact, more favorable memory and language outcome is expected in patients at high risk of memory decline.

Prof. Hans Lüders organized the first International Electroencephalography (EEG)/Epilepsy course in Cleveland (Ohio, United States) in 1979. His vision was to impart a framework of basic knowledge in EEG and epilepsy. The course participants are assumed to have no prior knowledge of EEG or epilepsy. As such, the course is structured and paced to meet the expectations set forth by the organizing committee at the completion of the course. The curriculum has evolved over the years to reflect advancement of the field. There is an added emphasis on semiology (seizure semiology) and epileptic disorders. Also, the course content has expanded to include broader topics such as the intersection between epilepsy and sleep medicine for both adults and children. The course lasts 8 weeks and is offered twice a year, free of charge, in winter and summer at the University Hospital in Cleveland, Ohio, United States. The average class size ranges from 25 to 30, composed of individuals from around the world. The class hours are generally from 8 a.m. to 3:30 p.m. Daily attendance is expected as new concepts quickly build on previous ones. Midterm and final examinations are used for evaluations. Both written and verbal feedbacks on homework assignments are given daily. At the end of the course, a certificate of completion is awarded. The purpose of this article is to discuss the structural details of this intensive educational course that has been offered for 40 years.

Memory loss after brain injury can be a source of considerable morbidity, but there are presently few therapeutic options for restoring memory function. We have previously demonstrated that burst stimulation of the fornix is able to significantly improve memory in a rodent model of traumatic brain injury. The present study is a preliminary investigation with a small group of cases to explore whether theta burst stimulation of the fornix might improve memory in humans. Four individuals undergoing stereo-electroencephalography evaluation for drug-resistant epilepsy were enrolled. All participants were implanted with an electrode into the proximal fornix and dorsal hippocampal commissure on the language dominant (n = 3) or language non-dominant (n = 1) side, and stimulation of this electrode reliably produced a diffuse evoked potential in the head and body of the ipsilateral hippocampus. Each participant underwent testing of verbal memory (Rey Auditory-Verbal Learning Test), visual-spatial memory (Medical College of Georgia Complex Figure Test), and visual confrontational naming (Boston Naming Test Short Form) once per day over at least two consecutive days using novel test forms each day. For 50% of the trials, the fornix electrode was continuously stimulated using a burst pattern (200 Hz in 100 ms trains, five trains per second, 100 µs, 7 mA) and was compared with sham stimulation. Participants and examiners were blinded to whether stimulation was active or not, and the order of stimulation was randomized. The small sample size precluded use of inferential statistics; therefore, data were analysed using descriptive statistics and graphic analysis. Burst stimulation of the fornix was not perceived by any of the participants but was associated with a robust reversible improvement in immediate and delayed performance on the Medical College of Georgia Complex Figure Test. There were no apparent differences on either Rey Auditory-Verbal Learning Test or Boston Naming Test. There was no apparent relationship between performance and side of stimulation (language dominant or non-dominant). There were no complications. Preliminary evidence in this small sample of patients with drug-resistant epilepsy suggests that theta burst stimulation of the fornix may be associated with improvement in visual-spatial memory.

There are at least five types of alterations of consciousness that occur during epileptic seizures: auras with illusions or hallucinations, dyscognitive seizures, epileptic delirium, dialeptic seizures, and epileptic coma. Each of these types of alterations of consciousness has a specific semiology and a distinct pathophysiologic mechanism. In this proposal we emphasize the need to clearly define each of these alterations/loss of consciousness and to apply this terminology in semiologic descriptions and classifications of epileptic seizures. The proposal is a consensus opinion of experienced epileptologists, and it is hoped that it will lead to systematic studies that will allow a scientific characterization of the different types of alterations/loss of consciousness described in this article.

Purpose The purpose of this study is to determine if neuropsychological functioning and family protective factors are related to depressive symptoms in parents of adolescents with myelomeningocele (MMC). Methods Fifty adolescents (28 females, 22 males; predominately Caucasian; ages 12-21 years, M=15.7, SD=2.4) and their parents from a large Midwestern MMC Program participated in a cross-sectional descriptive mixed-methods study. Participants completed measures of adolescent clinical status (WeeFIM®, Demographic and Clinical Information Form), neuropsychological (NP) functioning, family protective factors and parents' depressive symptoms. Results Parents' depressive symptoms correlated significantly with NP functioning in the domains of Mental Processing Speed, Psychomotor Speed, Executive Functioning, Fine Motor Skills, and Language, and with each self-reported family protective factor. Multiple regression analysis revealed independent main effects for the NP variable, Executive Functioning and the Family Protective Factors Composite (p 0.10). Conclusion Clinicians are especially encouraged to include assessment of parental depressive symptoms if the adolescent has executive functioning impairments or if the parents have few family protective factors.

BACKGROUND Multiple hippocampal transection (MHT) is a surgical treatment for mesial temporal lobe epilepsy associated with improved postoperative neuropsychological outcomes compared with lobectomy. OBJECTIVE To determine whether resection of the amygdala and anterior temporal neocortex during MHT affects postoperative seizure/memory outcome. METHODS Seventeen patients with normal magnetic resonance imaging and stereo-electroencephalogram-proven drug-resistant dominant mesial temporal lobe epilepsy were treated with MHT. Nine patients underwent MHT alone (MHT-) and 8 patients underwent MHT plus removal of the amygdala and anterior 4.5 cm of temporal neocortex lateral to the fusiform gyrus (MHT+). Verbal and visual-spatial memory were assessed in all patients preoperatively and in 14 patients postoperatively using the Wechsler Memory Scale. Postoperative seizure control was assessed at 12 months for all patients. RESULTS Overall, 11 of 17 patients (64.7%) were Engel class 1 at 1 year (6/9 MHT-, 5/8 MHT+, P = .38), and 10 of 14 patients (71.4%) had no significant postoperative decline in either verbal or visual memory (6/8 MHT-, 4/6 MHT+, P = .42). Verbal memory declined in 2 of 8 MHT- and 1 of 6 MHT+ patients, and visual memory declined in 1 of 8 MHT- and 2 of 6 MHT+ patients. Two patients had improved visual memory postoperatively, both in the MHT+ group. CONCLUSION MHT on the dominant side is associated with high rates of seizure freedom and favorable memory preservation outcomes regardless of the extent of neocortical resection. Preservation of the temporal neocortex and amygdala during MHT does not appear to decrease the risk of postoperative memory decline, nor does it alter seizure outcome.

In the study we describe adaptive functioning in children with epilepsy whose primary caregivers identified them as having learning problems. This was a cross-sectional study of 50 children with epilepsy and learning problems. Caregivers supplied information regarding the child’s adaptive functioning and behavior problems. Children rated their self-concept and completed a battery of neuropsychological tests. Mean estimated IQ (PPVT-III) in the participant children was 72.8 (SD = 18.3). On average, children scored 2 standard deviations below the norm on the Vineland Adaptive Behavior Scale–II and this was true even for children with epilepsy who had estimated IQ in the normal range. In conclusion, children with epilepsy and learning problems had relatively low adaptive functioning scores and substantial neuropsychological and mental health problems. In epilepsy, adaptive behavior screening can be very informative and guide further evaluation and intervention, even in those children whose IQ is in the normal range.

Objectives The purposes of this 36-month study of children with first recognized seizures were: (1) to describe baseline differences in behavior problems between children with and without prior unrecognized seizures; (2) to identify differences over time in behavior problems between children with seizures and their healthy siblings; (3) to identify the proportions of children with seizures and healthy siblings who were consistently at risk for behavior problems for 36 months; and (4) to identify risk factors for behavior problems 36 months following the first recognized seizure. Risk factors explored included demographic (child age and gender, caregiver education), neuropsychological (IQ, processing speed), seizure (epileptic syndrome, use of antiepileptic drug, seizure recurrence), and family (family mastery, satisfaction with family relationships, parent response) variables. Methods Participants were 300 children aged 6 through 14 years with a first recognized seizure and 196 healthy siblings. Data were collected from medical records, structured interviews, self-report questionnaires, and neuropsychological testing. Behavior problems were measured using the Child Behavior Checklist and the Teacher's Report Form. Data analyses included descriptive statistics and linear mixed models. Results Children with prior unrecognized seizures were at higher risk for behavior problems at baseline. As a group, children with seizures showed a steady reduction in behavior problems over time. Children with seizures were found to have significantly more behavior problems than their siblings over time, and significantly more children with seizures (11.3%) than siblings (4.6%) had consistent behavior problems over time. Key risk factors for child behavior problems based on both caregivers and teachers were: less caregiver education, slower initial processing speed, slowing of processing speed over the first 36 months, and a number of family variables including lower levels of family mastery or child satisfaction with family relationships, lower parent support of the child's autonomy, and lower parent confidence in their ability to discipline their child. Conclusions Children with new-onset seizures who are otherwise developing normally have higher rates of behavior problems than their healthy siblings; however, behavior problems are not consistently in the at-risk range in most children during the first 3 years after seizure onset. When children show behavior problems, family variables that might be targeted include family mastery, parent support of child autonomy, and parents’ confidence in their ability to handle their children's behavior.

Objectives Children with long-standing epilepsy have a significantly increased risk of academic underachievement compared with healthy controls. We prospectively followed children from seizure onset to assess the relationship between change in neuropsychological functioning and change in academic achievement and to explore the risk and protective moderating effects of demographic, seizure, and family variables. Methods As part of a larger study, neuropsychological and academic data were collected at both baseline and 36 months for 219 children 6–14 years of age with seizures. Prior factor analysis of results from a battery of well-standardized neuropsychological tests yielded four factors: language, processing speed, attention/executive/construction, and verbal memory/learning. Academic achievement was measured with the Woodcock–Johnson Revised Achievement Test Battery. Correlation coefficients and linear mixed models were used for analysis. Results The reading and math scores of children with seizures and siblings did not differ at baseline, but children with seizures had lower scores than siblings at 36 months. Writing scores were significantly lower for affected children than siblings at both times. Among children with seizures, there were positive correlations between neuropsychological functioning and academic achievement at baseline and 36 months. Changes in language and in verbal memory/learning were positively correlated with change in reading achievement ( r = 0.25 and r = 0.17, respectively). Age at onset moderated the association between change in neuropsychological functioning and change in reading and writing achievement ( P ≤ 0.006), with stronger relationships among younger children (β = 0.25–0.44). The association between change in language and change in writing achievement was moderated by caregiver anxiety ( P = 0.04; stronger for more anxious parents, β = 0.40), and the association between change in processing speed and change in math achievement was moderated by etiology ( P = 0.02; stronger for symptomatic/cryptogenic vs idiopathic, β = 0.29). Gender and other family variables did not have significant moderating effects. Conclusions Changes in neuropsychological function were associated with changes in academic achievement following onset of seizures, with risk factors being younger age at onset, lower caregiver education, high parental anxiety, and symptomatic/cryptogenic etiology. Academic performance should be closely monitored in children with early-onset seizures.

Summary Purpose: To test over time the relationships of neuropsychological functioning to mental health in children following a first recognized seizure and, of primary importance, to determine if the strength of these relationships differs based on risk and protective factors. Methods: In a larger prospective study, 135 children with a first seizure (ages 8–14 years) and 73 healthy sibling controls completed neuropsychological testing at baseline and 36 months. Structured telephone interviews were used to obtain data from children on mental health and family environment; major caregiving parents provided data on demographic and family variables. Data analyses included correlation coefficients and linear regression models. Results: Children with seizures showed an overall trend for improvement in mental health. More children with seizures than siblings had declines in processing speed. Declines in neuropsychological functioning were correlated with worse mental health. With regard to risk and protective factors, higher parent education protected against decline in self-esteem related to decline in processing speed. Better family functioning and greater parental support protected against decline in self-esteem related to decrease in verbal memory and learning. Older child age protected against increase in depressive symptoms related to decline in processing speed. Discussion: Seizure onset had a negative impact on mental health in children with declines in cognitive functioning except for older children and those with more family resources. Children should be assessed for declines in processing speed and, if found, those subgroups of children with less educated or more anxious parents and those in less supportive families should be targeted for interventions.

This study characterized structural abnormalities associated with onset of seizures in children, using magnetic resonance imaging and a standardized classification system in a large prospective cohort. Two hundred eighty-one children aged 6-14 years completed magnetic resonance imaging within 6 months of their first recognized seizure. Most examinations were performed with a standardized, dedicated seizure protocol; all were scored using a standard scoring system. At least one magnetic resonance imaging abnormality was identified in 87 of 281 (31%) children with a first recognized seizure. Two or more abnormalities were identified in 34 (12%). The commonest abnormalities were ventricular enlargement (51%), leukomalacia/gliosis (23%), gray-matter lesions such as heterotopias and cortical dysplasia (12%), volume loss (12%), other white-matter lesions (9%), and encephalomalacia (6%). Abnormalities defined as significant, or potentially related to seizures, occurred in 40 (14%). Temporal lobe and hippocampal abnormalities were detected at a higher frequency than in previous studies (13/87). Magnetic resonance imaging and a standardized, reliable, valid scoring system demonstrated a higher rate of abnormal findings than previously reported, including findings formerly considered incidental. Practice parameters may need revision, to expand the definition of significant abnormalities and support wider use of magnetic resonance imaging in children with newly diagnosed seizures.

Structural brain abnormalities of various types can lead to epilepsy, and many are associated with delays in cognitive development or specific cognitive deficits. Genetic cortical malformations (e.g., lissencephaly, schizencephaly, heterotopias, and polymicrogyria) are often characterized by seizure disorders, typically with significant delays in broad cognitive development (Guerrini, 2005). Similarly, tuberous sclerosis is characteristically associated with seizures and developmental delays. More importantly, the degree of intellectual deficit appears to be related to the degree of structural abnormality (i.e., the number of tubers) (Jambaque et al., 1991). Hippocampal sclerosis, a common finding in temporal lobe epilepsy in adults, has been associated with specific deficits in verbal memory and language or spatial memory in a manner consistent with the hemisphere affected (e.g., Baxendale et al., 1998); intelligence and other functions are relatively spared (e.g., Bourgeois et al., 1983; Ellenberg et al., 1986; Martin et al., 1999; Rodin et al., 1986). The degree of neuropsychological deficit is related to hippocampal volumes in adulthood (Baxendale et al., 1998; Hermann et al., 2002). The nature and extent of these neuropsychological deficits appear to be related to age of seizure onset, with lower memory scores and smaller hippocampal volumes observed among individuals with childhood onset (Baxendale et al., 1998). Furthermore, these effects might even be moderated by age of onset, with earlier age of onset being associated with not only hippocampal volume loss but an additional reduction in total brain volume, together with broader neuropsychological deficits that extend outside of the memory domain (Hermann et al., 2002). These findings support an association between the presence of structural brain abnormalities and cognitive deficits in children with epilepsy. For some conditions (e.g. tuberous sclerosis complex), the extent of the structural abnormalities is related to the severity of neuropsychological dysfunction (Jambaque et al., 1991; O’Callaghan et al., 2003; Weber et al., 2000). Moreover, the type and location of the structural abnormalities can be related to the nature of neuropsychological deficits affecting specific cognitive domains (e.g., Hermann et al., 2002). Shinnar and colleagues followed 411 children in New York City after their first unprovoked afebrile seizure (Shinnar et al., 2001). That study helped to characterize a new onset sample with regard to structural brain abnormalities; however, there are potential limitations that could affect the conclusions and generalizability of those findings. First, although the sample was large, only 27% (n = 59) of the children had MRIs; the majority (73%) had CT scans. As would be expected, abnormalities were detected in higher proportions of children using MRI (34%) compared to CT (22%). Therefore, that study likely underestimated the extent of structural brain abnormalities in this population. Second, there was no differentiation between abnormalities that seemed to be related to the seizure disorder versus those that were not related. In addition, imaging data were collected over the course of the children’s disorder in order to use the most sensitive imaging study for each participant that was available at the time of the 2001 publication (Shinnar, 2006). Consequently, many of the children in that sample completed their imaging studies many years after onset. In a subsequent and parallel study, Berg and colleagues followed 613 children in Connecticut following a second unprovoked seizure (Berg et al., 2000). The Connecticut study improved on many of the limitations in the New York City study. The majority of children in the Connecticut study completed MRI studies (vs. CT), and the imaging was obtained in conjunction with the initial evaluation at onset. Consequently, the lower proportion of children showing abnormalities in the Connecticut sample (12.7%, using more sensitive imaging but closer to onset) versus the New York City sample (21%, using less sensitive imaging but more chronic seizures) raises the possibility that some of these abnormalities might develop or become more detectable over the course of the disorder. However, it is possible that differences in exclusion criteria and/or definitions of onset also contributed to the differences in rates of abnormalities. In an effort to start addressing these differences, it would be beneficial to replicate these findings in a new sample with many of the strengths of the Connecticut study. All of these imaging studies have documented the potential for structural abnormalities at the onset of seizures in children. However, it is unclear if these abnormalities are related to cognitive function. Neuropsychological data were not reported for any of these studies. Neuropsychological deficits have been well documented in children with epilepsy (see Fastenau et al., 2003, for brief review), but there have been mixed findings in children at the onset of the disorder. Williams and colleagues (Williams et al., 1998) examined a small cohort (n = 37) of children newly diagnosed with epilepsy prior to initiation of antiepileptic drug therapy and found no differences in neuropsychological performance compared to children newly diagnosed with diabetes. However, others have documented subtle deficits at onset in children. Oostrom and colleagues (Oostrom et al., 2003) compared 51 children with new onset of epilepsy (i.e., at least two seizures) to a group of 48 healthy same age classmates with nearly identical IQ. At baseline they found that children with epilepsy showed deficits in attention and learning compared to the control group. None of these studies examined the relationship between structural abnormalities and neuropsychological deficits at the onset of the disorder. In this study, we explored the relationships between MRI abnormalities of the brain and neuropsychological functioning in children who were evaluated following their first recognized seizure. In the analyses we separated the MRI abnormalities into those that seemed to be related to the seizure disorder and into those that were not related.

The present study examined how knowledge of children’s seizure condition was related to teachers’ assessment of the children’s academic ability. Children with epilepsy were divided into two groups based on teacher awareness of the child’s seizure condition (Label). The children’s achievement was assessed using the Woodcock Johnson Tests of Achievement-Revised (WJ-R), and the teacher’s ratings were obtained from the Child Behavior Checklist Teacher Report Form (TRF) (Source). A 2 (Source) × 2 (Label) mixed-design analysis of covariance (controlling for IQ and how well the teacher knew the child) found a significant interaction, F (1, 121) = 4.22, p = 0.04. For the WJ-R there was no effect of Label on Achievement, but on the TRF lower scores were observed for children who were labeled. These results support the hypothesis that some teachers might underestimate the academic abilities of children with epilepsy.

Sir, We thank Drs van den Noort et al. (2015) and Fried (2015) for their interest in our study (Miller et al. , 2015) reporting improvement in visual-spatial memory during theta burst deep brain stimulation of the fornix in four individuals with temporal lobe epilepsy, a translational study previously tested in rodents by our team (Sweet et al. , 2014). While echoing our cautionary statements regarding interpretation, Dr Fried (2015) applauded the use of a unique clinical opportunity to provide intriguing preliminary data. Dr van den Noort et al. (2015) describe the study as being ‘highly innovative’, ‘a promising direction for various disorders’ and ‘a pioneering study’, adding that ‘it is a strength that the authors of the present study use neuropsychological tests’. Their group also raised some concerns, so we appreciate this opportunity to respond. Dr van den Noort et al. (2015) stated that ‘stimulation settings were different from previous studies, making comparisons … impossible.’ It would have been ideal to directly …

OBJECT Temporal lobe epilepsy (TLE) in the absence of MRI abnormalities and memory deficits is often presumed to have an extramesial or even extratemporal source. In this paper the authors report the results of a comprehensive stereoelectroencephalography (SEEG) analysis in patients with TLE with normal MRI images and memory scores. METHODS Eighteen patients with medically refractory epilepsy who also had unremarkable MR images and normal verbal and visual memory scores on neuropsychological testing were included in the study. All patients had seizure semiology and video electroencephalography (EEG) findings suggestive of TLE. A standardized SEEG investigation was performed for each patient with electrodes implanted into the mesial and lateral temporal lobe, temporal tip, posterior temporal neocortex, orbitomesiobasal frontal lobe, posterior cingulate gyrus, and insula. This information was used to plan subsequent surgical management. RESULTS Interictal SEEG abnormalities were observed in the mesial temporal structures in 17 patients (94%) and in the temporal tip in 6 (33%). Seizure onset was exclusively from mesial structures in 13 (72%), exclusively from lateral temporal cortex and/or temporal tip structures in 2 (11%), and independently from mesial and neocortical foci in 3 (17%). No seizure activity was observed arising from any extratemporal location. All patients underwent surgical intervention targeting the temporal lobe and tailored to the SEEG findings, and all experienced significant improvement in seizure frequency with a postoperative follow-up observation period of at least 1 year. CONCLUSIONS This study demonstrates 3 important findings: 1) normal memory does not preclude mesial temporal seizure onset; 2) onset of seizures exclusively from mesial temporal structures without early neocortical involvement is common, even in the absence of memory deficits; and 3) extratemporal seizure onset is rare when video EEG and semiology are consistent with focal TLE.

This study examined the degree to which neurophysiological activity on routine clinical EEG is associated with neuropsychological deficiencies in children with epilepsy.Ninety-five children with epilepsy (58 chronic, 37 recent-onset; mean age = 10.41 years, S.D. = 2.87 years; mean age at onset = 5.86 years, S.D. = 3.46 years) completed a neuropsychological battery. Neurophysiological data were collected from the most recent EEG.In the recent-onset sample, no neuropsychological scores were related to any EEG variable. In the chronic sample, however, presence of slow-wave activity was related to memory impairment (p0.01). Post-hoc analyses on other neuropsychological measures showed localization of epileptiform activity (EA) might be related to verbal learning.Children with slow-wave activity on EEG might be at increased risk for developing neuropsychological deficits. When these abnormalities are observed on a child's EEG, closer monitoring of cognitive and academic functioning seems warranted. Differences between these findings and past research suggest that conclusions drawn from adult surgical studies cannot be generalized to pediatric patients, especially recent-onset samples, without qualification. Differences between the recent-onset and chronic samples in this cross-sectional study raise the possibility that neurophysiological abnormalities have a cumulative effect on cognitive development.

Children with epilepsy are at great risk for academic difficulties (1–7) and for underemployment as adults (6,8). Fastenau et al. (9) described a model to explain how various risk factors might contribute to academic problems. In that model, neuropsychological functioning appears to play an integral role, possibly mediating the effects of structural and electrophysiologic abnormalities (10–14). Other risk factors in the model include seizure, demographic, and psychosocial variables (9). Studies to date have not been consistent in identifying seizure variables (e.g., seizure type, age at onset, seizure severity) that might influence the relation between neuropsychological functioning and academic achievement in children with epilepsy. For example, some studies have shown academic underachievement to be associated with absence epilepsy more so than with juvenile rheumatoid arthritis (15), and children with generalized seizures demonstrated worse outcomes than did those with partial seizures (5,16,17). Still, others found no association between seizure type and academic achievement (4,18,19), and no studies of academic achievement examined the interaction between seizure type and neuropsychological functioning. An early age at onset for seizures was associated with worse cognitive function in many studies (e.g., 5,20–22); yet others failed to find a relation (18,23). Persistent seizures and greater seizure severity also have been associated with greater academic underachievement in children (1,15), but others have failed to find a relation between seizure severity and achievement (e.g., 4). The lack of consistency in this literature suggests a need for further evaluation of seizure variables in academic functioning, particularly as they might interact with other variables (i.e., moderate other relations). In addition to seizure variables, demographic and psychosocial variables might serve as moderators in the relation between neuropsychological functioning and academic achievement. Past studies suggest that gender, family environment, and children’s perceptions influence academic achievement in children with epilepsy. With regard to gender, a study of children with epilepsy found males to be more at risk for academic underachievement than females (1). In contrast, Howe et al. (24) found male adolescents, including those with neurologic conditions, had higher achievement scores than did adolescent females. In addition, low stimulation and support in the family environment were related to poorer academic achievement in children with seizures (4). Negative child attitudes and perceptions have been associated with poorer academic performance in children with epilepsy (1). Negative attributions have been observed in epilepsy for both adults (25) and teens (26), and such attributions have been associated with poor academic achievement in school-age children (27). Despite the support for the roles of these psychosocial factors on classroom success, no studies have examined the extent to which psychosocial variables might interact with neuropsychological functioning to influence academic achievement in this population. Past studies focusing on seizure and psychosocial predictors of achievement in childhood epilepsy have been limited in several ways. They tended to rely on group tests of achievement or parent report or both, rather than using well-validated individual achievement tests (e.g., 1). In addition, neuropsychological functioning in many of those studies was assessed with limited measures, or a large battery of tests was used with no attempt to reduce the data into fewer and more relevant constructs (e.g., 28). We identified only one study of neuropsychology and academic achievement with this population that included a factor analysis to reduce the test battery into fewer, more salient neuropsychological constructs (29). Most important, no study to date has modeled the complex moderating roles of demographic, seizure, and psychosocial variables on the relation between neuropsychological functioning and academic achievement. The present study builds on past studies by (1) recruiting a large sample of school-age children with diverse seizure types, (2) using a more comprehensive battery of neuropsychological and achievement tests, (3) exploring the factor structure of that battery, (4) modeling the relative contributions of each of these cognitive deficits to specific outcomes in each major academic domain, and (5) testing whether demographic, seizure, and psychosocial variables serve as moderators of the relation between neuropsychological functioning and academic achievement.

Background: Complaints of persistent cognitive deficits following mild head trauma are often uncorroborated by structural brain imaging and neuropsychological examination. Objective: To investigate, using positron emission tomography (PET), the in vivo changes in regional cerebral uptake of 2-[ 18 F]fluoro-2-deoxy-D-glucose (FDG) and regional cerebral blood flow (rCBF) in patients with persistent symptoms following mild head trauma. Methods: Five patients with mild head trauma and five age and education matched healthy controls were imaged using FDG-PET to measure differences in resting regional cerebral glucose metabolism. Oxygen-15 labelled water (H 2 15 O)-PET was also used to measure group differences in rCBF changes during a spatial working memory task. In addition, neuropsychological testing and self report of dysexecutive function and post-concussion symptoms were acquired to characterise the sample. Results: There was no difference between patients and controls in normalised regional cerebral FDG uptake in the resting state in frontal and temporal regions selected a priori. However, during the spatial working memory task, patients had a smaller increase in rCBF than controls in the right prefrontal cortex. Conclusions: Persistent post-concussive symptoms may not be associated with resting state hypometabolism. A cognitive challenge may be necessary to detect cerebral changes associated with mild head trauma.

Adolescents with complex neurological conditions such as spina bifida require a holistic approach to their health care. Quality of Life (QOL) and the factors associated with QOL are important and understudied variables for these adolescents. A sample of 60 adolescents and their parents was interviewed to determine a) the adolescent’s and family’s QOL, b) condition/adolescent/family factors associated with QOL measures, and c) the relationship between adolescent and parent ratings on QOL measures. QOL was moderately high in these families. Few condition measures were related to QOL. However, several adolescent and family factors were significantly related to both overall QOL and health-related quality of life. There was no difference between adolescents and their parents on overall adolescent and family QOL items. Holistic practitioners need to be aware of areas perceived positively and negatively by these adolescents and their families as well as factors associated with outcomes.

Substantial progress in the medical treatment of individuals with spina bifida (SB) has increased the numbers who survive into adolescence and adulthood. However, sexual health in this population has not received much attention. This study explored the knowledge (SB Sexuality Knowledge Scale), worries (SB Worries Scale), romantic appeal (from Harter’s Self-Perception Scale), and access to sexuality information of a sample of 60 adolescents from a midwestern state. Study participants reported having sexual feelings like their peers, and they knew they could contract sexually transmitted diseases (STDs) if they were sexually active. However, only a moderate percentage was aware that women with SB are fertile, that adolescent women with SB should take a multivitamin with folic acid, and that latex-free condoms should be used by most adolescents with SB. They did not worry about their ability to make friends; however, these adolescents reported low levels of perceived romantic appeal and they worried about sexuality issues. These sexuality issues were not correlated to measures of SB neurological severity. Although over 50% reported having discussed sexuality with a health professional, 29% reported no one discussed sexuality and SB with them. Data from this study can affect the way health care providers and educators conduct sexuality education in health care and school settings.

The Self-Appraisal of Illness Questionnaire (SAIQ) is a self-report instrument designed to assess attitudes toward mental illness among persons receiving psychiatric treatment. This instrument was developed for use in community settings, adapted closely from the Patient's Experience of Hospitalization questionnaire. In order to examine the validity of the SAIQ, a factor analysis was first conducted on the items of this instrument in a sample of 59 outpatients with schizophrenia or schizoaffective illness. Three factors emerged: Need for Treatment, Worry, and Presence/Outcome of Illness. Next, to examine the concurrent validity of these three SAIQ subscales, they were correlated with researcher rated insight scales and neuropsychological tests. Results indicated that the Need for Treatment and Presence/Outcome subscales were significantly correlated with both researcher-rated insight scales and with neuropsychological tests of executive functioning. The Worry subscale was not associated with either researcher-rated insight scales or neuropsychological tests. It was concluded that the Need for Treatment and Presence/Outcome subscales may be used in combination as a brief screening instrument for clients with schizophrenia receiving outpatient psychiatric treatment who may be at risk for treatment non-compliance due to a lack of insight into illness.

The Rey-Osterrieth Complex Figure Test ("the Rey"; Osterrieth, 1944; Rey, 1941) has accumulated a considerable literature as a test of visual-spatial perception/construction and memory. The Extended Complex Figure Test (ECFT; Fastenau, 1996a, in press-a; Fastenau & Manning, 1992) supplements the Rey with Recognition and Matching trials that follow Copy, Immediate Recall, and Delayed Recall. The Rey and ECFT were administered to 211 healthy adults. Age ranged from 30 years to 85 years (M = 62.9, SD = 14.2), education ranged from 12 years to 25 years (M = 14.9, SD = 2.6), 55% were women, and over 95% were Caucasian. Age and education effects were evident on all trials (Multiple R ranged .23 to .50, p < .05), but education explained minimal variance (usually 2-3%) on copy and memory trials. Gender effects were negligible, if present. Age-appropriate norms are presented using Osterrieth's 36-point scoring, overlapping cells, and convenient tables for converting raw scores to scaled scores.

Four 15-item and two 30-item short forms for the Boston Naming Test were validated using 108 non-neurological community-dwelling adults, ages 57-85. All forms were administered to all participants (counterbalanced), with no effect of administration sequence on any score. An age effect emerged (Multiple R = .28, por =.01). No effects for education or gender were found, nor were there any interactions (por = .10). Descriptive data are stratified by age group. Reliability and validity for each form were demonstrated in several ways. These short forms should be very useful as screening instruments and/or as alternate forms for the BNT in test-retest clinical protocols, pre-post experimental designs, and longitudinal research.

This study empirically tested Fastenau and Adams' (1996) concerns about using regression-based norms (RBN) to statistically correct for demographic influences. A widely used RBN system (Heaton, Grant, & Matthews, 1991) was applied to scores from 63 healthy older adults for the Trail Making Test, Boston Naming Test, and Wisconsin Card Sorting Test (WCST). Age influences on all tests were virtually eliminated by the RBNs, whereas education influences were created by the RBN (better educated older adults penalized by the norms). Using RBNs from the Revised WCST Manual also created distortions, far overcorrecting for age. These findings cast considerable suspicion on norms that are generated by statistical regression when there are not adequate numbers of people supporting each demographic cell. Clinically, these norms can lead to higher rates of false negatives (or missed diagnoses) in older adults, especially those with less education and especially women in their 60s.

Digit span (DS) and visual–spatial memory span (VMS) tasks have been considered indices of auditory and visual–spatial processing, respectively, often classified as ‘‘primary memory’’ or ‘‘attention’’. There has been limited evidence for their modality specificity, however. We present two children who showed visual–spatial processing deficiencies (including VMS) and non-dominant manual inefficiency with normal visual–spatial perception, auditory–verbal processing and dominant fine manual skills. These children support a distinction between auditory and visual–spatial memory span. These findings are discussed with regard to a hypothesis that the unique expression of VMS is time-limited, that visual–spatial processing becomes more verbalized as children learn to read and that these behavioral changes produce a lateral shift in cortical processing of visual–spatial information.

Standard parametric tests generate p values and effect sizes, but often these are difficult to translate into real-world outcomes. In this study, the odds ratio was applied to neuropsychological testing and was compared to parametric approaches. Participants were 26 community-dwelling adults with possible or probable Alzheimer's disease and 25 matched healthy community-dwelling volunteers. Odds ratios were computed to estimate the probability of concurrent diagnosis given neuropsychological performance level. Odds ratios discriminated the groups at magnitudes that could not be discerned from t-test significance tables. These values were compared to sensitivity, specificity, and overall accuracy. Clinical and research applications and implications were addressed.

The Wechsler Memory Scale-Revised (Wechsler, 1987) was elaborated by adding 20 recognition items for Logical Memory (LM) and by adding recognition, matching, and copy trials for Visual Reproductions (VR). Reliability was very good for VR copy (α = .77, interrater agreement, 100% within 1 point). Reliability was modest for LM recognition (α = .42) and for VR recognition (α = .58), but reasonable given the small number of items on each measure. The reliability coefficient was very weak for VR matching (a = .10), limited considerably by the ease of the task for this healthy sample and by the small number of items. After statistically correcting for imperfect reliability, validity coefficients (correlations with similar tests that are well standardized) were good for all of the new trials (r = .60 to r = 1.00). Age- and education-appropriate reference data are provided using 81 healthy adults. Further validation using theoretically and clinically meaningful patient groups would be very valuable. In t...

Comprehensive Norms for an Expanded Halstead-Reitan Battery: Demographic Corrections, Research Findings, and Clinical Applications. Odessa, Florida: Psychological Assessment Resources, Inc., 344 pp. (No ISBN printed in the volume or in the catalog) $69.00 (U.S.)

Psychometric guidelines are suggested that expand the evaluation of scoring systems beyond the most frequently (and often singly) considered criterion, that of interrater reliability. Principles of reliability and validity are elaborated and discussed with regard to scoring systems. Also addressed are assays for efficiency in applying a new system, the effects of rater proficiency on outcome scores, the comparison of costs and benefits of new scoring systems, and the comparison of a new scoring system to an existing system to demonstrate its advantage. As a timely example to illustrate these principles, a new scoring system is introduced for the Rey-Osterrieth Complex Figure Test and is compared to the most popular scoring system for this test (Lezak, 1983, p. 400). The proposed principles would be relevant to any scoring system that codes subjective behavioral data into objective values.

Recognition and matching trials were designed for the Rey-Osterrieth Complex Figure Test (ROCFT). Following pilot testing and expert review, they were standardized using 90 community-dwelling adults (58% female, ages 30 to 88). Recognition has 30 multiple-choice items for different figural elements; scores distributed normally with strong item-total correlations and with normally distributed item difficulties. Cronbach alphas were .84,.61, and .81 for the Total, Global, and Detail Scales. Recognition correlated .81 with ROCFT recall and .65 with Visual Reproductions. Matching has 10 multiple-choice items; scores were negatively skewed with a substantial ceiling effect. Alpha for Matching was .58, limited in part by few items. Matching correlated .68 with Judgment of Line Orientation and .74 to .90 with copy trials. Both Recognition and Matching discriminated 34 patients with intractable epilepsy from 34 matched controls. Overall, Recognition appeared to be reliable and showed evidence of validity. By comparison, Matching reliability and validity were less impressive and warrant further examination.

To test over time the relationships of neuropsychological functioning to mental health in children following a first recognized seizure and, of primary importance, to determine if the strength of these relationships differs based on risk and protective factors.In a larger prospective study, 135 children with a first seizure (ages 8-14 years) and 73 healthy sibling controls completed neuropsychological testing at baseline and 36 months. Structured telephone interviews were used to obtain data from children on mental health and family environment; major caregiving parents provided data on demographic and family variables. Data analyses included correlation coefficients and linear regression models.Children with seizures showed an overall trend for improvement in mental health. More children with seizures than siblings had declines in processing speed. Declines in neuropsychological functioning were correlated with worse mental health. With regard to risk and protective factors, higher parent education protected against decline in self-esteem related to decline in processing speed. Better family functioning and greater parental support protected against decline in self-esteem related to decrease in verbal memory and learning. Older child age protected against increase in depressive symptoms related to decline in processing speed.Seizure onset had a negative impact on mental health in children with declines in cognitive functioning except for older children and those with more family resources. Children should be assessed for declines in processing speed and, if found, those subgroups of children with less educated or more anxious parents and those in less supportive families should be targeted for interventions.

Objective: This large, prospective, community-based study characterized neuropsychological functioning and academic achievement at the time of the first recognized seizure and identified risk factors for cognitive deficits. Methods: We compared 282 children (ages 6–14 years, IQ ≥70) with a first recognized seizure to 147 healthy siblings on a battery of well-standardized and widely used neuropsychological and academic achievement tests and examined relationships with demographic and clinical variables. Results: In this intellectually normal cohort, 27% with just one seizure and up to 40% of those with risk factors exhibited neuropsychological deficits at or near onset. Risk factors associated with neuropsychological deficits included multiple seizures (i.e., second unprovoked seizure; odds ratio [OR] = 1.96), use of antiepileptic drugs (OR = 2.27), symptomatic/cryptogenic etiology (OR = 2.15), and epileptiform activity on the initial EEG (OR = 1.90); a child with all 4 risks is 3.00 times more likely than healthy siblings to experience neuropsychological deficits by the first clinic visit. Absence epilepsy carried increased odds for neuropsychological impairment (OR = 2.00). Conclusions: A subgroup of intellectually normal children with seizures showed neuropsychological deficits at onset. Academic achievement was unaffected, suggesting that there is a window early in the disorder for intervention to ameliorate the impact on school performance. Therefore, the risk factors identified here (especially if multiple risks are present) warrant swift referral for neuropsychological evaluation early in the course of the condition.

Adolescents with spina bifida (SB) vary in their ability to adapt to the disease, and it is likely that numerous risk and protective factors affect adaptation outcomes. The primary aim was to test neuropsychological impairment, exemplified herein by executive dysfunction, as a risk factor in the Ecological Model of Adaptation for Adolescents with SB. Specific hypotheses were that: (1) executive functioning predicts the adaptation outcome of functional independence in adolescents with SB; (2) executive functioning mediates the impact of neurological severity on functional independence; and (3) family and adolescent protective factors are related to functional independence and moderate the relationship between executive functioning and functional independence. Forty-three adolescents aged 12–21 years completed neuropsychological measures and an interview that assessed risk, adolescent and family protective factors, and functional independence. Age, level of lesion, executive functioning, and the protective factor adolescent activities were significantly correlated with the functional independence outcome. In hierarchical regression analysis, the model accounted for 61% of the variance in functional independence outcomes. Executive functioning mediated the impact of neurological severity on functional independence. (JINS, 2008, 14, 793–804.)

Epilepsy is associated with sleep disturbance, but little is known about how early this relationship develops and how it affects neuropsychological functioning. This study documented the frequency and types of sleep problems and examined how sleep problems are associated with seizures and neuropsychological functioning in 332 children following their first recognized seizure (ages 6–14) and in 225 sibling controls. Formal neuropsychological batteries were administered to all subjects. Sleep was measured using the Sleep Behavior Questionnaire and the Child Behavior Checklist. Sleep problems were more frequent in the seizure sample relative to siblings and previously published norms; bedtime difficulties, daytime somnolence, and parasomnias were the most frequently occurring sleep problems. In the seizure group, sleep problems were related to seizure parameters and to neuropsychological functioning. Seizure patients with significant sleep problems had worse neuropsychological functioning on all measures. Findings demonstrate the significant impact of sleep disturbance on children with newly recognized seizures.

The Extended Complex Figure Test (ECFT; Fastenau, 1996b, 2003a), adds recognition and matching trials to the Rey-Osterrieth Complex Figure Test (ROCFT). An alternate administration of the ECFT, the ECFT-Motor Independent version (ECFT-MI; Fastenau, 2003a) measures visuospatial memory without the motoric demands of the ROCFT. ECFT-MI test-retest reliabilities were examined in 55 healthy adults tested two times separated by one week. The Recognition Trial showed strong reliability for the Total Score (r = .80, p < .0001). Reliabilities for Recognition Detail Scale and Subscales (r = .62-.74, p < .0001) and for the Global Scale (r = .51, p < or = .005) were attenuated by fewer items per subscale but were comparable to other memory tests. Matching Trial reliability coefficients were attenuated by extreme ceiling effects and restriction of range, but scores were very consistent between the two administrations. This study supports the temporal stability of the ECFT-MI.

The Carnegie Council on Adolescent Development, USA has identified activities, beliefs, and perceptions critical for healthy development. The aim of this study was to measure the activities, beliefs and expectations, and perceived outcomes of adolescents with myelomeningocele. In this descriptive study, 66 adolescents with myelomeningocele, aged 12 to 21 years and functioning at grade level, completed a structured interview. Thirty-eight (58%) of the participants were female. The level of lesion was distributed as follows: 30% had thoracic level lesions, 32% had lumbar level lesions, 15% had lumbosacral level lesions, and 23% of the sample had sacral level lesions. Instruments used had both established reliability and validity (WeeFIM, Harter's Self-Perception Profile, Austin's Child Attitude Toward Illness Scale, and Snyder's Hope Scale, Adolescent Decision-Making Inventory, Adolescent Coping Scale) or were scales developed for this study (Adolescent Activities Inventory, Future Expectations Scale, Communication Efficacy, and Adolescent Self-Management and Independence Scale). Scale reliabilities ranged from 0.70 to 0.88. These participants, though hopeful and positive in their attitudes toward myelomeningocele and generally able to perform activities of daily living independently, are not engaging in the full range of adolescent activities (decision making, friendship activities, and household responsibilities) and achieving positive outcomes (self-management and job) necessary to make a successful transition to adulthood. This might explain why so many individuals with myelomeningocele are underemployed and are not living independently as young adults.

Parents of adolescents with spina bifida (SB) face unique challenges of which they may not be aware. The purpose of this study was to heighten awareness of the challenge of parenting such adolescents. This enhanced understanding can help rehabilitation professionals optimize their interventions with families. In this qualitative study, which was part of a larger mixed-method descriptive investigation exploring adaptation by adolescents with SB, we used content analysis to evaluate 20 parent interviews for common domain, themes, and subthemes. The analysis yielded four major domains: (a) daily life experiences, (b) the dance of individuation, (c) reflections on parenting, and (d) practice suggestions for healthcare professionals. Overall, experiences of the parents were positive. Parents described meeting daily demands and balancing independence-dependence needs with the adolescent as major challenges. Rehabilitation professionals must provide guidance to foster autonomy, decision making, cognitive skill building, and coping skills to help parents and adolescents manage independence-dependence issues and multiple life demands.

Adolescents with spina bifida (SB), a congenital spinal cord impairment, are at high risk for negative outcomes. Even those with favorable cognitive status often fail to achieve independence, exhibiting poor functional and psychosocial outcomes. The purpose of this study was to examine the relationship between adaptation outcomes (functional status, self-management, and developmental competence) and SB condition-specific, adolescent protective factors, and family protective factors in a sample of adolescents with SB. Individual, interpersonal, and social developmental competence were explored. Sixty-six adolescent/parent pairs were interviewed. Data analysis included descriptive statistics, Cronbach alpha coefficients, and partial correlations controlling for age. All instruments had acceptable reliabilities. Factors associated with outcomes generally fell into two patterns. SB condition-specific variables and adolescent activities (e.g., decision-making, household responsibilities) were related to functional status, self-management, and social competence. In contrast, adolescent beliefs (hope, attitude, and communication efficacy) were predominantly related to individual, interpersonal, and overall developmental competence.

Although research examining Auditory-Verbal and Visual Memory Span in adults has failed to provide compelling evidence for the modality specificity of such tasks, Fastenau, Conant, and Lauer (1998) suggested that these processes may be dissociable in children until around the age of 8 years when visuospatial memory span appears to become more verbally mediated perhaps as a function of formal reading training. A subsequent cross-cultural study in Zaire (now Democratic Republic of Congo) by Conant and colleagues (1999) supported that hypothesis. However, other differences in the sociocultural environments of American and rural Zairian children such as nutritional and health care factors could potentially account for the findings. The present study examines the relationships among Auditory-Verbal, Visual, and Cross-Modal Memory Span tasks with 46 Lao and 56 American children. Both samples were divided into younger and older groups, and separate partial correlational analyses were performed on Kaufman Assessment Battery for Children (K-ABC) data from each group. In younger Lao and American children, Auditory-Verbal Memory Span was not significantly correlated with Visual Memory Span or Cross-Modal Memory Span, whereas significant correlations were found between Auditory-Verbal Memory Span and these other tasks in older children from both countries. The similar pattern in both cultures, together with findings from Zaire, supports the hypothesis that the relationship between Auditory-Verbal and Visual Memory Span may change with reading training.

The purpose of this cross-sectional descriptive study was to describe the particular types of behavioral problems, self-concept, and symptoms of depression experienced by children with both low IQ and epilepsy. Three groups of children (83 males, 81 females; mean age 11 years 10 months, SD 1 year 10 months; age range 9 to 14 years) with epilepsy were compared: (Group 1) Low IQ (100), n=58, 34 males, 24 females. The Child Behavior Checklist, Piers–Harris Self-Concept Scale, and Children’s Depression Inventory were used to measure behavior, self-concept, and depression respectively. Results indicated that children in the Low IQ group had the most behavioral and mental health problems. Additionally, there were IQ group-by-sex interactions, with females in the Low IQ group being at the highest risk for poor self-concept. Findings suggest that children with both epilepsy and low IQ should be carefully assessed for mental health problems in the clinical setting.

Accurate understanding of practice characteristics, performance stability, and error on neuropsychological tests is essential to both valid clinical assessment and maximization of signal detection for clinical trials of cognitive enhancing drugs. We examined practice effects in 28 healthy adults. As part of a larger study using donepezil and simulating a Phase I trial, participants were randomized into: placebo, no-treatment and donepezil. Donepezil results are presented elsewhere. Neuropsychological tests were administered in a fixed order for 6 weeks, with alternate forms available for most tests. Despite alternate forms, ANOVAs revealed significant improvements for the pooled control group (placebo and no-treatment) on all tests except Letter Number Sequencing and Trails B. Learning occurred principally in the first three to four sessions. PASAT and Stroop interference showed the greatest learning. Thus, serial assessment with alternate forms may attenuate retest effects on some tests, but continued learning occurs on novel tests or those in which an advantageous test-taking strategy can be identified. Alternate forms and baseline practice sessions may help control early, rapid improvements in clinical trials.

Executive function deficits are seen in both schizophrenia and obsessive-compulsive disorder (OCD), but research suggests that dorsolateral prefrontal (DLPF) dysfunction is associated with schizophrenia and orbitofrontal (OBF) dysfunction is associated with OCD. As part of a comprehensive europsychological assessment, the Bechara Gambling Task (BGT) was used to assess OBF function and the Wisconsin Card Sorting Test (WCST) was used to assess DLPF function among three groups: 26 individuals with schizophrenia/schizoaffective disorder with obsessive-compulsive symptoms (SCZ+), 28 individuals with schizophrenia/schizoaffective disorder without obsessive-compulsive symptoms (SCZ−), and, 11 individuals with OCD. It was predicted that the SCZ+ group and the OCD group would show impairments in OBF function, as compared to the SCZ− group, and that the SCZ+ and SCZ− groups would show impairments in DLPF function, as compared to the OCD group. It was also predicted that the SCZ+ group would perform more poorly than the SCZ− and OCD groups in a number of other cognitive domains. Contrary to expectation, no divergence between groups was seen on tests of executive function. Instead, there was a statistical trend for the SCZ+ and SCZ− groups, when combined, to perform worse than individuals with OCD on the measure of OBF. Although not significant at the designated alpha level, the profile results showed that the SCZ+ group performed slightly below the OCD and SCZ− groups across nearly all neuropsychological domains.