The expression of the distal dystrophin isoforms Dp140 and Dp71 in the human epileptic hippocampus in relation to cognitive functioning.

Dystrophin is an important protein within the central nervous system. The absence of dystrophin, characterizing Duchenne muscular dystrophy (DMD), is associated with brain related comorbidities such as neurodevelopmental (e.g., cognitive and behavioural) deficits and epilepsy. Especially mutations in the downstream part of the DMD gene affecting the dystrophin isoforms Dp140 and Dp71 are found to be associated with cognitive deficits. However, the function of Dp140 is currently not well understood and its expression pattern has previously been implicated to be developmentally regulated. Therefore, we evaluated Dp140 and Dp71 expression in human hippocampi in relation to cognitive functioning in patients with drug-resistant temporal lobe epilepsy (TLE) and post-mortem controls. Hippocampal samples obtained as part of epilepsy surgery were quantitatively analyzed by Western blot and correlations with neuropsychological test results (i.e., memory and intelligence) were examined. First, we demonstrated that the expression of Dp140 does not appear to differ across different ages throughout adulthood. Second, we identified an inverse correlation between memory loss (i.e., verbal and visual memory), but not intelligence (i.e., neither verbal nor performance), and hippocampal Dp140 expression. Finally, patients with TLE appeared to have similar Dp140 expression levels compared to post-mortem controls without neurological disease. Dp140 may thus have a function in normal cognitive (i.e., episodic memory) processes.

Pre- and postoperative verbal memory and executive functioning in frontal versus temporal lobe epilepsy.

There is accumulating evidence for considerable overlap in preoperatively affected cognitive functions in patients with temporal lobe epilepsy (TLE) and frontal lobe epilepsy (FLE). The current study investigated whether it is possible to differentiate between patients with FLE and TLE prior to surgery, based on measures of verbal memory and executive functioning. Furthermore, the postoperative cognitive development was compared. Pre- and postoperative data from 109 patients with FLE and 194 patients with TLE were retrospectively analyzed. Preoperatively, there were no differences in verbal memory, and postoperatively, no distinctive cognitive change was found between patients with FLE and TLE. However, patients with FLE performed worse on a cognitive switching task. Notably, irrespective of localization, patients with a presumed epileptogenic area in the language-dominant hemisphere performed worse than patients with seizures that originated in the nonlanguage-dominant hemisphere on measures of verbal memory, both pre- and postoperatively. In sum, the results suggest that verbal memory scores may be less valuable for differentiation between TLE and FLE, while measures of executive functioning may help identify patients with FLE. Additionally, rather than the localization, epilepsy lateralization critically impacts the evaluation of verbal memory functioning in both TLE and FLE. The results are discussed in light of the current frameworks of functional disturbances in epileptic networks.

The posterior parietal cortex and subjectively perceived confidence during memory retrieval.

Functional neuroimaging studies suggest a role for the left angular gyrus (AG) in processes related to memory recognition. However, results of neuropsychological and transcranial magnetic stimulation (TMS) studies have been inconclusive regarding the specific contribution of the AG in recollection, familiarity, and the subjective experience of memory. To obtain further insight into this issue, 20 healthy right-handed volunteers performed a memory task in a single-blind within-subject controlled TMS study. Neuronavigated inhibitory repetitive TMS (rTMS) was applied over the left AG and the vertex in a randomized and counterbalanced order. Prior to rTMS participants were presented with a list of words. After rTMS participants were shown a second list of words and instructed to indicate if the word was already shown prior to rTMS ("old") or was presented for the first time ("new"). In addition, subjectively perceived memory confidence was assessed. Results showed that recollection was unaffected following inhibitory left AG rTMS. In contrast, rTMS over the left AG improved both familiarity and the subjectively perceived confidence of participants that demonstrated low baseline memory recognition. Our study highlights the importance of taking into account individual differences in experimental designs involving noninvasive brain stimulation.

Working memory network alterations in high-functioning adolescents with an autism spectrum disorder.

AIM: People with autism spectrum disorder (ASD) typically have deficits in the working memory (WM) system. WM is found to be an essential chain in successfully navigating in the social world. We hypothesize that brain networks for WM have an altered network integrity in ASD compared to controls. METHODS: Thirteen adolescents (one female) with autistic disorder (n = 1), Asperger's disorder (n = 7), or pervasive developmental disorder not otherwise specified (n = 5), and 13 typically developing healthy control adolescents (one female) participated in this study. Functional magnetic resonance imaging (MRI) was performed using an n-back task and in resting state. RESULTS: The analysis of the behavioral data revealed deficits in WM performance in ASD, but only when tested to the limit. Adolescents with ASD showed lower binary global efficiency in the WM network than the healthy control group with n-back and resting-state data. This correlated with diagnostic scores for total problems, reciprocity, and language. CONCLUSION: Adolescents with higher-functioning autism have difficulty with the WM system, which is typically compensated. Functional MRI markers of brain network organization in ASD are related to characteristics of autism as represented in diagnostic scores. Therefore, functional MRI provides neuronal correlates for memory difficulties in adolescents with ASD.

Social behaviour and social cognition in high-functioning adolescents with autism spectrum disorder (ASD): two sides of the same coin?

Of the triad of symptoms found in autism spectrum disorder (ASD), that is, social impairments, communication difficulties and repetitive interests and behaviour, the social impairments are the most stable and common throughout the lifespan. They typically manifest themselves in abnormalities as reciprocal interactions and difficulties in the expression and recognition of emotions. Although peer interactions become especially important during adolescence, little is known about the mentalizing abilities of high-functioning adolescents with ASD. Here, we compared the mentalizing skills and emotion recognition abilities of 21 high-functioning adolescents with ASD and 21 matched controls. All adolescents had estimated above-average verbal intelligence levels. Spontaneous social abilities and task-related social abilities were measured using questionnaires, tasks and the Autism Diagnostic Observation Schedule. Results confirm social impairment in daily life situations in adolescents with ASD, but were not found on experimental tasks of social cognition. The use of more explicit cognitive or verbally mediating reasoning techniques and a lesser tendency of high-functioning adolescents with ASD to search for and use social information in natural environments are further discussed.

Clinical utility of the Wechsler Memory Scale - Fourth Edition (WMS-IV) in patients with intractable temporal lobe epilepsy.

INTRODUCTION: The Wechsler Memory Scale (WMS) is one of the most widely used test batteries to assess memory functions in patients with brain dysfunctions of different etiologies. This study examined the clinical validation of the Dutch Wechsler Memory Scale - Fourth Edition (WMS-IV-NL) in patients with temporal lobe epilepsy (TLE). METHOD: The sample consisted of 75 patients with intractable TLE, who were eligible for epilepsy surgery, and 77 demographically matched healthy controls. All participants were examined with the WMS-IV-NL. RESULTS: Patients with TLE performed significantly worse than healthy controls on all WMS-IV-NL indices and subtests (p<.01), with the exception of the Visual Working Memory Index including its contributing subtests, as well as the subtests Logical Memory I, Verbal Paired Associates I, and Designs II. In addition, patients with mesiotemporal abnormalities performed significantly worse than patients with lateral temporal abnormalities on the subtests Logical Memory I and Designs II and all the indices (p<.05), with the exception of the Auditory Memory Index and Visual Working Memory Index. Patients with either a left or a right temporal focus performed equally on all WMS-IV-NL indices and subtests (F(15, 50)=.70, p=.78), as well as the Auditory-Visual discrepancy score (t(64)=-1.40, p=.17). CONCLUSION: The WMS-IV-NL is capable of detecting memory problems in patients with TLE, indicating that it is a sufficiently valid memory battery. Furthermore, the findings support previous research showing that the WMS-IV has limited value in identifying material-specific memory deficits in presurgical patients with TLE.

Parental education predicts change in intelligence quotient after childhood epilepsy surgery.

OBJECTIVE: To know whether change in the intelligence quotient (IQ) of children who undergo epilepsy surgery is associated with the educational level of their parents. METHODS: Retrospective analysis of data obtained from a cohort of children who underwent epilepsy surgery between January 1996 and September 2010. We performed simple and multiple regression analyses to identify predictors associated with IQ change after surgery. In addition to parental education, six variables previously demonstrated to be associated with IQ change after surgery were included as predictors: age at surgery, duration of epilepsy, etiology, presurgical IQ, reduction of antiepileptic drugs, and seizure freedom. We used delta IQ (IQ 2 years after surgery minus IQ shortly before surgery) as the primary outcome variable, but also performed analyses with pre- and postsurgical IQ as outcome variables to support our findings. To validate the results we performed simple regression analysis with parental education as the predictor in specific subgroups. RESULTS: The sample for regression analysis included 118 children (60 male; median age at surgery 9.73 years). Parental education was significantly associated with delta IQ in simple regression analysis (p = 0.004), and also contributed significantly to postsurgical IQ in multiple regression analysis (p = 0.008). Additional analyses demonstrated that parental education made a unique contribution to prediction of delta IQ, that is, it could not be replaced by the illness-related variables. Subgroup analyses confirmed the association of parental education with IQ change after surgery for most groups. SIGNIFICANCE: Children whose parents had higher education demonstrate on average a greater increase in IQ after surgery and a higher postsurgical--but not presurgical--IQ than children whose parents completed at most lower secondary education. Parental education--and perhaps other environmental variables--should be considered in the prognosis of cognitive function after childhood epilepsy surgery.

Parenting stress does not normalize after child's epilepsy surgery.

PURPOSE: This study aimed to investigate parenting stress expressed by parents before and two years after their children's epilepsy surgery. SUBJECTS: Parents of 31 consecutively included surgery patients with epilepsy and parents of 31 healthy sex- and age-matched control children were the subjects of this study. Materials and procedure: The questionnaire 'Parenting Stress Index', which distinguishes a Parent domain (stress leading parents to feel themselves inadequate) from a Child domain (child features felt by parent to cause stress) was completed before surgery of the patients and two years thereafter. At both time points, intelligence examination of the child was part of a comprehensive neuropsychological assessment, as were evaluations of recent stress-enhancing life events and epilepsy severity. RESULTS: Prior to surgery, total parenting stress was significantly higher in parents of patients than in parents of controls. Two years after surgery, total parenting stress had decreased significantly in parents of patients. The scores on parent-related subscales Role Restriction and Spouse and on the child-related subscale Distractibility/Hyperactivity, all relatively high before surgery, decreased significantly. Still, parents of patients experienced significantly more stress compared with parents of controls mainly because of persistently higher stress scores in parents of patients on the subscale Role Restriction (Parent domain) and on five of six subscales in the Child domain. Intelligence of the child was associated with parenting stress: the lower the child's intelligence, the higher the stress score on the subscale Distractibility/Hyperactivity and the lower the stress score on the subscale Mood. Stress decreased more in parents of patients who became seizure-free after surgery than in parents of patients with recurrent seizures. CONCLUSIONS: Parenting stress decreases but does not normalize in the first two years after epilepsy surgery. Parents should be offered counseling on epilepsy-related intricacies contributing to parenting stress, immediately after diagnosis as well as after epilepsy surgery, notwithstanding the resulting seizure status of the child.

Visual memory after epilepsy surgery in children: a standardized regression-based analysis of group and individual outcomes.

Visual memory is vulnerable to epilepsy surgery in adults, but studies in children suggest no change or small improvements. We investigated visual memory after epilepsy surgery, both group-wise and in individual children, using two techniques to assess change: 1) repeated measures analysis of variance (ANOVA) and 2) an empirically based technique for detecting cognitive change [standardized regression-based (SRB) analysis]. A prospective cohort consisting of 21 children completed comprehensive assessments of memory both before surgery (T0) and 6 (T1), 12 (T2), and 24 months (T3) after surgery. For each patient, two age- and gender-matched controls were assessed with the same tests at the same intervals. Repeated measures ANOVA replicated the results of previous studies reporting no change or minor improvements after surgery. However, group analysis of SRB results eliminated virtually all improvements, indicating that the ANOVA results were confounded by practice effects. Standardized regression-based group results showed that in fact patients scored lower after surgery than would be predicted based on their presurgical performance. Analysis of individual SRB results showed that per visual memory measure, an average of 18% of patients obtained a significantly negative SRB score, whereas, on average, only 2% obtained a significantly positive SRB score. At T3, the number of significantly negative SRB scores outweighed the number of significantly positive SRB scores in 62% of patients. There were no clear associations of clinical variables (including side and site of surgery and postsurgical seizure freedom) with memory outcome. The present analysis revealed that given their individual presurgical functioning, many children obtained disappointing results on some visual memory tests after epilepsy surgery. Comparison of the SRB analysis with ANOVA results emphasizes the importance of empirically based techniques for detecting cognitive effects of epilepsy surgery in childhood.

Different types of working memory binding in epilepsy patients with unilateral anterior temporal lobectomy.

The medial temporal lobe is an important structure for long-term memory formation, but its role in working memory is less clear. Recent studies have shown hippocampal involvement during working memory tasks requiring binding of information. It is yet unclear whether this is limited to tasks containing spatial features. The present study contrasted three binding conditions and one single-item condition in patients with unilateral anterior temporal lobectomy. A group of 43 patients with temporal lobectomy (23 left; 20 right) and 20 matched controls were examined with a working memory task assessing spatial relational binding (object-location), non-spatial relational binding (object-object), conjunctive binding (object-colour) and working memory for single items. We varied the delay period (3 or 6s), as there is evidence showing that delay length may modulate working memory performance. The results indicate that performance was worse for patients than for controls in both relational binding conditions, whereas patients were unimpaired in conjunctive binding. Single-item memory was found to be marginally impaired, due to a deficit on long-delay trials only. In conclusion, working memory binding deficits are found in patients with unilateral anterior temporal lobectomy. The role of the medial temporal lobe in working memory is not limited to tasks containing spatial features. Rather, it seems to be involved in relational binding, but not in conjunctive binding. The medial temporal lobe gets involved when working memory capacity does not suffice, for example when relations have to be maintained or when the delay period is long.

Clinical validation of the WMS-IV-NL brief cognitive status exam (BCSE) in older adults with MCI or dementia.

ABSTRACT Background: The Brief Cognitive Status Exam (BCSE) is a new, optional subtest of the Wechsler Memory Scale-IV (WMS-IV) developed for rapid detection of cognitive deficits. We examined the clinical validation of the Dutch version of the BCSE in older adults with mild cognitive impairment (MCI) or dementia, comparing it to the Mini-Mental State Examination (MMSE). Method: BCSE and MMSE were administered in 39 older adults with MCI, 51 with dementia and 96 matched healthy controls. Results: Our results show that the BCSE is a valid screening instrument, with psychometric properties similar to the widely used MMSE. High correlations were found between the BCSE and MMSE (r = 0.79, n = 183, p < 0.001). Furthermore, a BCSE cut-off score ≤ 42 revealed a sensitivity of 96% a specificity of 92%, a positive predictive value of 86% and a negative predictive value of 97%, whereas the MMSE cut-off score of ≤ 24 showed values of 84%, 96%, 91%, and 92%, respectively. Sensitivity, specificity, positive and negative predictive values to detect MCI compared to controls was 81%, 80%, 61%, and 92%, respectively, on the BCSE, with a cut-off score of ≤ 46, and 84%, 76%, 57%, and 92%, respectively, on the MMSE, with a cut-off score of ≤ 27. Conclusions: The Dutch version of the BCSE is a clinically valid screening instrument for the detection of cognitive impairment in patients with dementia. Nevertheless, for distinguishing older adults with MCI from healthy controls both the BCSE and MMSE have limitations.

The Development of a Short Form of the Indonesian Version of the Wechsler Adult Intelligence Scale-Fourth Edition.

(1) Background: The Wechsler intelligence scales are very popular in clinical practice and for research purposes. However, they are time consuming to administer. Therefore, researchers and psychologists have explored the possibility of shorter test battery compositions. (2) Methods: In this study, we investigated 13 potential short forms of the Indonesian version of the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV-ID). An existing standardization data set of 1745 Indonesian participants collected for the validation of the WAIS-IV-ID was used to examine the short forms' validity. These ranged from 2-subtest versions to 7-subtest versions. Regression analyses with goodness-of-fit measures were performed, and regression equations were determined for each short form to estimate the Full Scale IQ (FSIQ) score. Discrepancies between the FSIQ and the estimated FSIQ (FSIQEst) scores were examined and classification accuracies were calculated for each short form (% agreement of intelligence classification between the FSIQEst and FSIQ). (3) Results: None of the 13 short form FSIQEst values significantly differed from the FSIQ scores based on the full WAIS-IV-ID, and strong correlations were observed between each of these values. The classification accuracies of the short forms were between 56.8% and 81.0%. The 4-subtest short form of the WAIS-IV-ID consisting of the subtests Matrix Reasoning, Information, Arithmetic, and Coding had the optimal balance between best classification values and a short administration duration. The validity of this short form was demonstrated in a second study in an independent sample (N = 20). (4) Conclusions: Based on the results presented here, the WAIS-IV-ID short forms are able to reliably estimate the FSIQ, with a significant shorter administration duration. The WAIS-IV-ID short form consisting of four subtests, Matrix Reasoning, Information, Arithmetic, and Coding, was the best version according to our criteria.

Development and external validation of a new PTA assessment scale.

BACKGROUND: Post-traumatic amnesia (PTA) is a key symptom of traumatic brain injury (TBI). Accurate assessment of PTA is imperative in guiding clinical decision making. Our aim was to develop and externally validate a short, examiner independent and practical PTA scale, by selecting the most discriminative items from existing scales and using a three-word memory test. METHODS: Mild, moderate and severe TBI patients and control subjects were assessed in two separate cohorts, one for derivation and one for validation, using a questionnaire comprised of items from existing PTA scales. We tested which individual items best discriminated between TBI patients and controls, represented by sensitivity and specificity. We then created our PTA scale based on these results. This new scale was externally evaluated for its discriminative value using Receiver Operating Characteristic (ROC) analysis and compared to existing PTA scales. RESULTS: The derivation cohort included 126 TBI patients and 31 control subjects; the validation cohort consisted of 132 patients and 30 controls. A set of seven items was eventually selected to comprise the new PTA scale: age, name of hospital, time, day of week, month, mode of transport and recall of three words. This scale demonstrated adequate discriminative values compared to existing PTA scales on three consecutive administrations in the validation cohort. CONCLUSION: We introduce a valid, practical and examiner independent PTA scale, which is suitable for mild TBI patients at the emergency department and yet still valuable for the follow-up of more severely injured TBI patients.

The Aftercare Survey: Assessment and intervention practices after brain tumor surgery in Europe.

Background: People with gliomas need specialized neurosurgical, neuro-oncological, psycho-oncological, and neuropsychological care. The role of language and cognitive recovery and rehabilitation in patients' well-being and resumption of work is crucial, but there are no clear guidelines for the ideal timing and character of assessments and interventions. The goal of the present work was to describe representative (neuro)psychological practices implemented after brain surgery in Europe. Methods: An online survey was addressed to professionals working with individuals after brain surgery. We inquired about the assessments and interventions and the involvement of caregivers. Additionally, we asked about recommendations for an ideal assessment and intervention plan. Results: Thirty-eight European centers completed the survey. Thirty of them offered at least one postsurgical (neuro)psychological assessment, mainly for language and cognition, especially during the early recovery stage and at long term. Twenty-eight of the participating centers offered postsurgical therapies. Patients who stand the highest chances of being included in evaluation and therapy postsurgically are those who underwent awake brain surgery, harbored a low-grade glioma, or showed poor recovery. Nearly half of the respondents offer support programs to caregivers, and all teams recommend them. Treatments differed between those offered to individuals with low-grade glioma vs those with high-grade glioma. The figure of caregiver is not yet fully recognized in the recovery phase. Conclusion: We stress the need for more complete rehabilitation plans, including the emotional and health-related aspects of recovery. In respondents' opinions, assessment and rehabilitation plans should also be individually tailored and goal-directed (eg, professional reinsertion).

Combining Gamma With Alpha and Beta Power Modulation for Enhanced Cortical Mapping in Patients With Focal Epilepsy.

About one third of patients with epilepsy have seizures refractory to the medical treatment. Electrical stimulation mapping (ESM) is the gold standard for the identification of "eloquent" areas prior to resection of epileptogenic tissue. However, it is time-consuming and may cause undesired side effects. Broadband gamma activity (55-200 Hz) recorded with extraoperative electrocorticography (ECoG) during cognitive tasks may be an alternative to ESM but until now has not proven of definitive clinical value. Considering their role in cognition, the alpha (8-12 Hz) and beta (15-25 Hz) bands could further improve the identification of eloquent cortex. We compared gamma, alpha and beta activity, and their combinations for the identification of eloquent cortical areas defined by ESM. Ten patients with intractable focal epilepsy (age: 35.9 ± 9.1 years, range: 22-48, 8 females, 9 right handed) participated in a delayed-match-to-sample task, where syllable sounds were compared to visually presented letters. We used a generalized linear model (GLM) approach to find the optimal weighting of each band for predicting ESM-defined categories and estimated the diagnostic ability by calculating the area under the receiver operating characteristic (ROC) curve. Gamma activity increased more in eloquent than in non-eloquent areas, whereas alpha and beta power decreased more in eloquent areas. Diagnostic ability of each band was close to 0.7 for all bands but depended on multiple factors including the time period of the cognitive task, the location of the electrodes and the patient's degree of attention to the stimulus. We show that diagnostic ability can be increased by 3-5% by combining gamma and alpha and by 7.5-11% when gamma and beta were combined. We then show how ECoG power modulation from cognitive testing can be used to map the probability of eloquence in individual patients and how this probability map can be used in clinical settings to optimize ESM planning. We conclude that the combination of gamma and beta power modulation during cognitive testing can contribute to the identification of eloquent areas prior to ESM in patients with refractory focal epilepsy.

Do importance instructions improve time-based prospective remembering in autism spectrum conditions?

This study explored the impact of motivation on the memory for delayed intentions (so-called, prospective memory, PM) in autistic individuals. Specifically, we were interested in the effects of personal (i.e., receiving a reward) as compared to social motivation (i.e., performing a favour for someone). Given the well-established theory of mind deficits in autism, we expected autistic individuals to benefit more strongly from personal than social importance manipulations, whereas the opposite pattern was predicted for controls. Sixty-one adolescents with autism and 61 typically developing adolescents participated, with each group distributed equally to one of the three motivation conditions of standard, social and personal reward. Participants worked on a 2-back picture-based ongoing task in which a time-based PM task was embedded. A mixed 2 (Group) x 3 (Motivation condition) analysis of covariance with age, verbal and non-verbal abilities as covariates and correct PM responses as dependent variable indicated solely a main effect of group, with controls outperforming the autism group. In contrast to our expectations, there was no main effect of condition, no significant interaction, and none of the covariates had any significant impact. However, further planned analyses revealed that controls only outperformed autistic individuals in the personal reward condition. Controls performed significantly best when a personal reward was promised, whereas there were no significant differences between the motivation conditions for autistic individuals. Findings are discussed in terms of underlying processes.

Emotion perception and interpersonal behavior in epilepsy patients after unilateral amygdalohippocampectomy.

Aim of this study was to examine the relation between perception of facial expressions and interpersonal behavior in epilepsy patients after unilateral amygdalohippocampectomy (AH). Nine patients with unilateral amygdalohippocampectomy and 14 controls completed a forced-choice emotional recognition task, in which morphed facial emotional expressions were shown at different emotional intensities, and a self-report questionnaire of interpersonal behavior. Face perception and depressive symptoms were also taken into account. Compared to normal controls, patients were less sensitive in the recognition of fearful and disgusted facial expressions, in line with previous reports. These impairments were only minimally correlated with self-report interpersonal behavior. In all, unilateral damage to the amygdala and medial temporal lobe results in subtle emotion recognition impairments, but these deficits do not appear to extend to self-reported impairments in everyday interpersonal behavior. Further studies need to explore in more detail the effects of these subtle recognition problems on daily social intercourse.

Brain resting-state networks in adolescents with high-functioning autism: Analysis of spatial connectivity and temporal neurodynamics.

Introduction: Autism spectrum disorder (ASD) is mainly characterized by functional and communication impairments as well as restrictive and repetitive behavior. The leading hypothesis for the neural basis of autism postulates globally abnormal brain connectivity, which can be assessed using functional magnetic resonance imaging (fMRI). Even in the absence of a task, the brain exhibits a high degree of functional connectivity, known as intrinsic, or resting-state, connectivity. Global default connectivity in individuals with autism versus controls is not well characterized, especially for a high-functioning young population. The aim of this study is to test whether high-functioning adolescents with ASD (HFA) have an abnormal resting-state functional connectivity. Materials and Methods: We performed spatial and temporal analyses on resting-state networks (RSNs) in 13 HFA adolescents and 13 IQ- and age-matched controls. For the spatial analysis, we used probabilistic independent component analysis (ICA) and a permutation statistical method to reveal the RSN differences between the groups. For the temporal analysis, we applied Granger causality to find differences in temporal neurodynamics. Results: Controls and HFA display very similar patterns and strengths of resting-state connectivity. We do not find any significant differences between HFA adolescents and controls in the spatial resting-state connectivity. However, in the temporal dynamics of this connectivity, we did find differences in the causal effect properties of RSNs originating in temporal and prefrontal cortices. Conclusion: The results show a difference between HFA and controls in the temporal neurodynamics from the ventral attention network to the salience-executive network: a pathway involving cognitive, executive, and emotion-related cortices. We hypothesized that this weaker dynamic pathway is due to a subtle trigger challenging the cognitive state prior to the resting state.

Spatial and non-spatial contextual working memory in patients with diencephalic or hippocampal dysfunction.

Damage to the medial temporal lobe (MTL) and diencephalon results in impaired long-term memory, which relies on the binding of multiple, mostly contextual, features. Recent neuroimaging and patient studies have suggested that impairments may also be present in working memory after MTL or diencephalic damage. To examine whether patients with damage to these brain structures have impairments in working memory for contextual information, 15 patients with damage to the diencephalon due to Korsakoff's syndrome and 12 patients with unilateral MTL lesions, and 30 age-matched healthy controls performed a delayed match-to-sample (DMS) task in which they had to maintain either object-location associations, color-number associations, single colors or single locations. Compared to their age-matched controls, performance on the DMS task was generally impaired in both patient groups, whereas no deficits were found on standard neuropsychological span tasks that do not rely on maintenance aspects of working memory. The patients did not show disproportionate impairments on the binding condition. In all, the results clearly show that impairments in working memory maintenance are present in patients with MTL or diencephalic lesions. However, we did not find a disproportionate inability in maintaining spatial or non-spatial associations within working memory as previously demonstrated in long-term memory.

Evaluating WAIS-IV structure through a different psychometric lens: structural causal model discovery as an alternative to confirmatory factor analysis.

OBJECTIVE: Since the publication of the WAIS-IV in the U.S. in 2008, efforts have been made to explore the structural validity by applying factor analysis to various samples. This study aims to achieve a more fine-grained understanding of the structure of the Dutch language version of the WAIS-IV (WAIS-IV-NL) by applying an alternative analysis based on causal modeling in addition to confirmatory factor analysis (CFA). The Bayesian Constraint-based Causal Discovery (BCCD) algorithm learns underlying network structures directly from data and assesses more complex structures than is possible with factor analysis. METHOD: WAIS-IV-NL profiles of two clinical samples of 202 patients (i.e. patients with temporal lobe epilepsy and a mixed psychiatric outpatient group) were analyzed and contrasted with a matched control group (N = 202) selected from the Dutch standardization sample of the WAIS-IV-NL to investigate internal structure by means of CFA and BCCD. RESULTS: With CFA, the four-factor structure as proposed by Wechsler demonstrates acceptable fit in all three subsamples. However, BCCD revealed three consistent clusters (verbal comprehension, visual processing, and processing speed) in all three subsamples. The combination of Arithmetic and Digit Span as a coherent working memory factor could not be verified, and Matrix Reasoning appeared to be isolated. CONCLUSIONS: With BCCD, some discrepancies from the proposed four-factor structure are exemplified. Furthermore, these results fit CHC theory of intelligence more clearly. Consistent clustering patterns indicate these results are robust. The structural causal discovery approach may be helpful in better interpreting existing tests, the development of new tests, and aid in diagnostic instruments.