Functional Magnetic Resonance Imaging of Language in Epilepsy

Functional magnetic resonance imaging (fMRI) has revolutionized our understanding of functional networks and cerebral organization in both normal and pathological brains. In the present review, we describe the use of fMRI for mapping language in epilepsy patients prior to surgical intervention including a discussion of methodological issues and task design, comparisons between fMRI and the intracarotid sodium amobarbital test, fMRI studies of language reorganization, and the use of fMRI laterality indexes to predict outcome after anterior temporal lobectomy.     

Memory deficits before and after temporal lobectomy: Effect of laterality and age of onset

Laterality and age of onset effects on semantic and figural memory were evaluated in 30 right-handed, left speech dominant (amobarbital test) patients with epilepsy before and after temporal lobectomy. There were no effects of focus on WAIS-R IQ scores. Early onset (less than or equal to 5 years) was associated with lower IQ and memory (WMS). Left Temporal (LT) patients showed worse semantic than figural memory preoperatively. Unexpectedly, early onset LT had marked postoperative decline of figural memory, whereas late onset LT patients showed the previously reported worsening of semantic memory. Right Temporal (RT) lobectomy patients, in contrast, improved in both semantic and figural memory regardless of age of onset. A "crowding effect" was suggested by the decline in figural memory following surgery in the early onset LT patients who remained stable or improved in semantic memory. Results indicate the need to incorporate age of onset of seizures into laterality models of memory function following unilateral temporal-hippocampal resection.     

Interhemispheric dissociation of expressive and receptive language functions in patients with complex-partial seizures: An amobarbital study

Bilateral intracarotid amobarbital procedures (IAP) were performed in 144 patients with medically intractable complex-partial seizures. As a result of language testing, 29 patients (20.1%) were found to have bilateral language representation to different degrees. In four (2.8%) of these patients--all right-handers with early onset of epilepsy and/or evidence of early brain damage--there was strong evidence of an interhemispheric dissociation of expressive and receptive language functions. Two of these patients had circumscribed temporal foci (one left, one right), and receptive language functions were represented in the hemisphere contralateral to the focus. One patient with a right frontal focus showed left-hemisphere dominance for expressive functions, while the fourth patient exhibited left-hemisphere dominance for receptive functions associated with a right temporo-parietal focus. It is argued that in these four cases the circumscribed functional and/or structural impairments have led to a shift of the anatomically associated language functions to the opposite hemisphere (rather than to neighboring regions of the same hemisphere). These findings substantiate the hypothesis that in special circumstances the anterior (expressive) language area can be located in one hemisphere and the posterior (receptive) area in the other.     

Effects of barbiturates and other sedative hypnotics in pigeons trained to discriminate phencyclidine from saline.

Pigeons were trained to peck the center key (lighted white) of three response keys to turn off the center keylight and to light one of the side keys with a red keylight and the other side key with a green keylight. Five responses (fixed-ratio component) on either side key relighted the center key. Food was delivered following 10 fixed-ratio components on the red key if 1.5 mg/kg phencyclidine had been given before the session. The position of the red and green keylights on the side keys varied randomly each time they were lighted by a peck on the center key. Subsequently, increasing doses of phencyclidine, barbital, amobarbital, phenobarbital, methaqualone, methyprylon, diazepam, oxazepam, and d-amphetamine were substituted for the training dose of phencyclidine, using a cumulative dosing procedure. At low doses of the sedative hypnotics, birds pecked the keylight color associated with saline. At higher doses, birds pecked both key colors. At the highest doses of pentobarbital and amobarbital, some birds responded almost exclusively On he color associated with phencyclidine. When responding on keys of both colors occurred following administration of phencyclidine or other sedative hypnotics, this responding was controlled by key position rather than by key color.     

Intelligence profiles in children and adolescents with left temporal lobe epilepsy: relationship to language laterality

Pre- and postoperative IQ profiles were examined in children and adolescents with left temporal-lobe epilepsy. Participants were grouped according to their pattern of speech dominance, as indicated by the intracarotid sodium amobarbital procedure. Seven participants with typical (left hemisphere) speech representation were matched for age and sex to seven participants with atypical (bilateral or right hemisphere) speech representation. The group with atypical speech representation tended to perform worse pre- and postoperatively on several verbal and nonverbal subtests. Unlike Strauss et al.'s (1990) sample, however, the groups did not differ significantly on pre- or postoperative Performance IQ. The results suggest that when individuals are matched closely for age and sex, there may only be limited support for a nonverbal "crowding" hypothesis. Atypical speech representation in children and adolescents with early temporal-lobe epilepsy appears to be associated with lowered performance on both verbal and nonverbal IQ subtests.     

Memory performance in abstinent 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") users

Research with animals and humans has suggested that acute and subacute use of 3,4-methylenedioxymethamphetamine (MDMA "ecstasy") may lead to memory impairment. However, research is limited by (1) low power due to small sample sizes, (2) the possible confound of polydrug use, and (3) the failure to consider intelligence as a covariate. The present study compared the memory performance on the Wechsler Memory Scale-III of 26 abstinent (2-wk. minimum) recreational MDMA users with 26 abstinent (2-wk. minimum) recreational polydrug users. Despite significantly greater polydrug use amongst these MDMA users, no significant group differences in memory were observed. Regression of total lifetime amount of MDMA use also did not predict memory performance after accounting for intelligence. In addition, the length of time since abstinence (at least 2 wk.) was not associated with an increase in memory performance. Greater total lifetime cocaine use, rather than total lifetime MDMA use, was significantly associated with greater decrements in General Memory and Delayed Verbal Memory performance.     

Measuring recollection and familiarity: Improving the remember/know procedure

The remember/know (RK) procedure is the most widely used method to investigate recollection and familiarity. It uses trial-by-trial reports to determine how much recollection and familiarity contribute to different kinds of recognition. Few other methods provide information about individual memory judgements and no alternative allows such direct indications of recollection and familiarity influences. Here we review how the RK procedure has been and should be used to help resolve theoretical disagreements about the processing and neural bases of components of recognition memory. Emphasis is placed on procedural weaknesses and a possible confound of recollection and familiarity with recognition memory strength. Recommendations are made about how to minimise these problems including using modified versions of the procedure. The proposals here are important for improving behavioural and lesion research, and vital for brain imaging work.     

Assessment of executive functioning in childhood epilepsy: the Tower of London and BRIEF

Children and adolescents with epilepsy are known to demonstrate executive function dysfunction, including working memory deficits and planning deficits. Accordingly, assessing specific executive function skills is important when evaluating these individuals. The present investigation examined the utility of two measures of executive functions-the Tower of London and the Behavioral Rating Inventory of Executive Functioning (BRIEF)-in a pediatric epilepsy sample. Ninety clinically referred children and adolescents with seizures were included. Both the Tower of London and BRIEF identified executive dysfunction in these individuals, but only the Tower of London variables showed significant relations with epilepsy severity variables such as age of epilepsy onset, seizure frequency, number of antiepileptic medications, etc. Further, the Tower of London and BRIEF variables were uncorrelated. Results indicate that objective measures of executive function deficits are more closely related to epilepsy severity but may not predict observable deficits, as reported by parents. Comprehensive evaluation of such deficits, therefore, should include both objective measures as well as subjective ratings from caregivers.     

Quantitative and Qualitative Evaluation of Patterns of Cerebral Language Dominance : An Amobarbital Study

As a part of presurgical evaluation, 173 patients received bilateral intracarotid amobarbital tests for determination of cerebral language dominance. Language testing during intracarotid amobarbital procedures (IAP) consisted of the following tasks: automatic speech, sentence comprehension, body commands, naming, repetition, reading, and spontaneous speech. Patterns of cerebral language dominance were evaluated and discussed on five levels of analysis: (1) quantification of language dominance on the basis of a lateralization index derived from the total language scores in each IAP; (2) determination of five dominance subpatterns (left or right dominant, strongly bilateral, and incomplete left or right dominant) according to quantification performed on level (I) and clinical judgment; (3) qualitative differentiation of three kinds of bilaterality (positive, negative, and general) according to total language performance in left and right IAP; (4) analysis of grouped linguistic subfunctions extracted from performance in specific IAP subtests; (5) extraordinary individual case histories. The distribution of lateralization indices revealed only partially continuous degrees of lateralization, especially between the left-dominant and bilateral subgroups. As for the clinically oriented classification, incomplete left dominance is frequent (16.2%), while incomplete right dominance does not occur at all. Atypical dominance patterns are mostly correlated to bilateral and/or extratemporal foci. Concerning grouped subfunctions, a rotated factor matrix statistic yields an analysis of clusters of IAP subtests, where functions involving expressive language capacities are separated from those that are purely receptive. Further analyses of bilaterality subpatterns suggest that there are mainly four bilaterality phenomena, namely interhemispheric dissociation, double representation, unilateal representation of subfunctions, and partial representation of subfunctions in either hemisphere. Application of these differentiations to individual cases yields additional evidence that can be used in patient selection for operation in order to avoid postoperative neuropsychological deficits, especially in candidates for extratemporal surgery. In conclusion, a multilevel analysis of LAP language data is recommended since it permits a detailed account of varieties of language dominance patterns and contributes to more adequate presurgical decision-making in planned operations in cognitively relevant brain areas.     

Sources of variability and systematic error in mouse timing behavior

In the peak procedure, starts and stops in responding bracket the target time at which food is expected. The variability in start and stop times is proportional to the target time (scalar variability), as is the systematic error in the mean center (scalar error). The authors investigated the source of the error and the variability, using head poking in the mouse, with target intervals of 5 s, 15 s, and 45 s, in the standard procedure, and in a variant with 3 different target intervals at 3 different locations in a single trial. The authors conclude that the systematic error is due to the asymmetric location of start and stop decision criteria, and the scalar variability derives primarily from sources other than memory.     

Childhood Epilepsy and Autism Spectrum Disorders: Psychiatric Problems, Phenotypic Expression, and Anticonvulsants

Epilepsy and autism spectrum disorders (ASDs) frequently co-occur during childhood, however, the characteristics of psychiatric or behavioural problems in these children remains largely unknown. This article contributes to these discussions by reporting on the prevalence and presentation of psychiatric or behavioural problems in children with epilepsy and ASDs, as well as on the use of anticonvulsants in these children. The current evidence suggests that children with epilepsy and ASDs may present with a distinct clinical profile, with a greater number of developmental difficulties, and a more severe expression of the ASD phenotype that can not solely be accounted for by level of intellectual functioning. Positive effects of anticonvulsants on behavioural symptoms associated with ASDs were also reported, though pharmacoresistance and a lack of clear treatment guidelines may contribute to an elevated risk of adverse side effects. In relation to clinical presentation and management there is a need for careful consideration of potential interaction effects between disorder specific factors (e.g., age of seizure onset/ASD diagnosis), cognitive characteristics (e.g., intellectual functioning, memory), and psychosocial variables (e.g., coping strategies). Ultimately however, many conclusions are tentative and this review highlights the need for more empirically validated research on children with epilepsy and ASDs.     

Differences in memory functioning between children with attention-deficit/hyperactivity disorder and/or focal epilepsy

Prior research has shown that attention-deficit/hyperactivity disorder (ADHD) and epilepsy are frequently comorbid and that both disorders are associated with various attention and memory problems. Nonetheless, limited research has been conducted comparing the two disorders in one sample to determine unique versus shared deficits. Hence, we investigated differences in working memory (WM) and short-term and delayed recall between children with ADHD, focal epilepsy of mixed foci, comorbid ADHD/epilepsy and controls. Participants were compared on the Core subtests and the Picture Locations subtest of the Children’s Memory Scale (CMS). Results indicated that children with ADHD displayed intact verbal WM and long-term memory (LTM), as well as intact performance on most aspects of short-term memory (STM). They performed worse than controls on Numbers Forward and Picture Locations, suggesting problems with focused attention and simple span for visual-spatial material. Conversely, children with epilepsy displayed poor focused attention and STM regardless of the modality assessed, which affected encoding into LTM. The only loss over time was found for passages (Stories). WM was intact. Children with comorbid ADHD/epilepsy displayed focused attention and STM/LTM problems consistent with both disorders, having the lowest scores across the four groups. Hence, focused attention and visual-spatial span appear to be affected in both disorders, whereas additional STM/encoding problems are specific to epilepsy. Children with comorbid ADHD/epilepsy have deficits consistent with both disorders, with slight additive effects. This study suggests that attention and memory testing should be a regular part of the evaluation of children with epilepsy and ADHD.     

Controlling for stimulus dominance effects in the Fused Dichotic Words Test when predicting speech lateralization in children

A log-linear analysis (Grimshaw et al., 1994) of Fused Dichotic Words Test data was examined in a sample of 28 children with epilepsy who had undergone the intracarotid amobarbital procedure to determine the nature of speech representation. The analysis yields a measure of ear dominance (lambda*) that controls for stimulus dominance confounds. Most patients with unilateral speech obtained statistically significant ear advantages, whereas most with bilateral speech displayed no significant ear advantage. Despite controlling for stimulus dominance confounds, some of the scores from patients with left-hemisphere speech overlapped with those from patients with bilateral speech representation.     

Memory Rehabilitation in Patients with Epilepsy: a Systematic Review

Memory failure is a common clinical concern of patients with epilepsy and is associated with significant functional impairments. Thus, memory rehabilitation is of critical clinical importance. In this article, we aimed to systematically evaluate the efficacy of memory rehabilitation in patients with epilepsy. The Preferred Items for Systematic Reviews and Meta-Analyses (PRISMA) was used to guide searches, extraction and reporting of data in this review. PsycINFO, Medline and PsychBITE searches yielded 95 studies. Twelve papers met inclusion criteria, reporting outcomes of cognitive or behavioural interventions that specifically targeted the rehabilitation of memory in patients with epilepsy. Methodological rigour was rated using the Single-Case Experimental Design (SCED) scale for single-case studies and a modified version of the Downs and Black checklist for group studies. Twelve prospective studies, nine group (six pre-post design, one waitlist crossover, two randomised controlled trials) and three single-case studies were identified. Eleven of the studies included adults, eight of which involved adults with temporal lobe epilepsy (TLE). One paediatric study was identified. The quality of group studies ranged from 36% (poor) to 72% (good), using the modified Downs and Black checklist. Single-case studies were assessed using the SCED scale and assessed to range in quality from four to seven out to 11. Overall, memory rehabilitation was associated with improved memory function in all studies. Verbal memory outcomes were most commonly examined and associated with improvements. This review found that the level of evidence available to support rehabilitation of memory in patients with epilepsy was generally weak and inconsistent. Nevertheless, studies conducted to date, albeit of limited methodological quality, offer preliminary evidence that memory rehabilitation is associated with improvements in verbal memory in patients with temporal lobe epilepsy. Little is known about the efficacy of memory rehabilitation in patients with non-TLE, children, and other aspects of memory difficulties. Guidelines for future research are proposed.     

Assessment of executive functioning in childhood epilepsy: The Tower of London and BRIEF

Children and adolescents with epilepsy are known to demonstrate executive function dysfunction, including working memory deficits and planning deficits. Accordingly, assessing specific executive function skills is important when evaluating these individuals. The present investigation examined the utility of two measures of executive functions—the Tower of London and the Behavioral Rating Inventory of Executive Functioning (BRIEF)—in a pediatric epilepsy sample. Ninety clinically referred children and adolescents with seizures were included. Both the Tower of London and BRIEF identified executive dysfunction in these individuals, but only the Tower of London variables showed significant relations with epilepsy severity variables such as age of epilepsy onset, seizure frequency, number of antiepileptic medications, etc. Further, the Tower of London and BRIEF variables were uncorrelated. Results indicate that objective measures of executive function deficits are more closely related to epilepsy severity but may not predict observable deficits, as reported by parents. Comprehensive evaluation of such deficits, therefore, should include both objective measures as well as subjective ratings from caregivers.     

Hemispheric specialization for emotional expression: a reexamination of results from intracarotid administration of sodium amobarbital

Emotional and behavioral responses to sodium amobarbital injection were examined in 44 epilepsy surgery candidates. Thirty-three emotional reactions occurred in 26 patients, 44% of the reactions following right hemisphere injection and 32% after injection of the left hemisphere. Among all patients examined, laughter/elated mood was statistically more frequent following right hemisphere injection while crying was statistically associated with left hemisphere injections. These observed effects were not related to amobarbital dose, sex, bilateral hemispheric inactivation (angiographic crossflow), general cognitive status, or side of seizure onset. These results support differing specialization of emotional expression in the right and left cerebral hemispheres and their subcortical connections.     

Whichever way you choose to categorize, working memory helps you learn

There has been growing interest in the relationship between the capacity of a person's working memory and their ability to learn to categorize stimuli. While there is evidence that working memory capacity (WMC) is related to the speed of category learning, it is unknown whether WMC predicts which strategies people use when there are multiple possible solutions to a categorization problem. To explore the relationship between WMC, category learning, and categorization strategy use, 173 participants completed two categorization tasks and a battery of WMC tasks. WMC predicted the speed of category learning, but it did not predict which strategies participants chose to perform categorization. Thus, WMC does not predict which categorization strategies people use but it predicts how well they will use the strategy they select.     

Whichever way you choose to categorize,working memory helps you learn

There has been growing interest in the relationship between the capacity of a person's working memory and their ability to learn to categorize stimuli. While there is evidence that working memory capacity (WMC) is related to the speed of category learning, it is unknown whether WMC predicts which strategies people use when there are multiple possible solutions to a categorization problem. To explore the relationship between WMC, category learning, and categorization strategy use, 173 participants completed two categorization tasks and a battery of WMC tasks. WMC predicted the speed of category learning, but it did not predict which strategies participants chose to perform categorization. Thus, WMC does not predict which categorization strategies people use but it predicts how well they will use the strategy they select.     

Operant variability: evidence,functions, and theory

Although responses are sometimes easy to predict, at other times responding seems highly variable, unpredictable, or even random. The inability to predict is generally attributed to ignorance of controlling variables, but this article is a review of research showing that the highest levels of behavioral variability may result from identifiable reinforcers contingent on such variability. That is, variability is an operant. Discriminative stimuli and reinforcers control it, resulting in low or high variability, depending on the contingencies. Schedule-of-reinforcement effects are orderly, and choosing to vary or repeat is lawfully governed by relative reinforcement frequencies. The operant nature of variability has important implications. For example, learning, exploring, creating, and problem solving may partly depend on it. Abnormal levels of variability, including those found in psychopathologies such as autism, depression, and attention deficit hyperactivity disorder, may be modified through reinforcement. Operant variability may also help to explain some of the unique attributes of voluntary action.     

A Comparison of Children with Epilepsy to an Age- and IQ-Matched Control Group on the Children's Memory Scale

Past research has found that children with epilepsy exhibit decreased memory skills. In addition, some studies have found that children with epilepsy obtain significantly lower IQ scores than controls. In an effort to examine whether children with epilepsy have specific memory weaknesses versus global cognitive difficulties, the present study compared the performance of 62 children (age range = 6–16 years). Thirty-one children with epilepsy were compared to 31 age- and IQ-matched controls on the Children's Memory Scale (CMS) to determine whether differences in memory skills persist when IQ is matched. An independent t-test comparing index and scaled scores was performed. The results indicated that with the exception of the Word Pairs subtest (p < .01), children with epilepsy did not differ significantly on the CMS subtests when IQ was matched. This suggests that list-learning paradigms may be particularly sensitive to memory impairments in children with epilepsy and/or that children with epilepsy have more global cognitive impairments.