Deficits in executive functions and motor coordination in children with frontal lobe epilepsy

Abstract

Frontal lobe dysfunction in adults has been associated with impairments of planning abilities, working memory, impulse control, attention and certain aspects of motor coordination. However, very few studies have attempted to assess these functions in children suffering from frontal lobe epilepsy. The aim of the present study was to determine whether some or all of the components of the frontal lobe syndrome are present in children with this disorder. For this purpose, a neuropsychological test battery was administered to 32 unresected epileptic children, aged 8–16 years: 16 with frontal lobe epilepsy (FLE), eight with temporal lobe epilepsy (TLE) and eight with generalized epilepsy whose principal manifestations were typical absences (GEA). The performances of the three epileptic groups were further compared to normative data derived from 200 French-speaking, healthy children aged 7–16 years, except for standardized tests for which the norms provided in the manual were used. The three epilepsy groups did not differ with respect to conceptual shift and recency memory. However, the FLE children showed deficits in planning and impulse control. Furthermore, they had significantly more coordination problems and exhibited greater rigidity than the other epilepsy groups on the motor tests. These problems were more marked in younger FLE children (8–12 years). The latter were also more impaired on verbal fluency measures. No differences were observed with respect to gender, localization of the epileptic abnormality (unilateral versus bilateral) or medication (monotherapy versus polytherapy). The findings reveal similarities between the neuropsychological profiles of FLE children and adults with frontal lobe lesions.

Introduction

Experimental and clinical evidence points to the importance of the frontal lobes, especially the prefrontal areas, in the mediation of executive functions and motor coordination [8], [27], [65], [67]. Executive functions represent a cognitive construct which refers to the ability to maintain an appropriate problem-solving set for the attainment of future goals [13], [14], [32], [61], [71]. They include planning, self-monitoring, organized search, concept formation, attention and impulse control [72] as well as working memory [7], [52], [53].

Data documenting the role of prefrontal cortex in the organization of executive functions have been derived from a variety of sources such as studies in adult patients with frontal lobe damage [2], [4], [8], [34], [61], [65], lesion studies in non-human primates [11], [13], [19], single-cell recordings [16] and, more recently, neuroradiological studies using regional cerebral blood flow [23], positron emission tomography (PET) [52], [53], single photon emission computed tomography (SPECT) [57] and functional magnetic resonance imaging (fMRI) in patients and healthy subjects [7], [30], [55]. The common finding is that the prefrontal areas are involved in various aspects of executive functions. Furthermore, cerebral imaging procedures have shown that the prefrontal cortex is functionally heterogeneous. For instance, there is evidence that the mid-dorsolateral frontal cortex is associated with working memory whereas the posterior dorsolateral region is crucial for visual associative learning [52], [53]. With regard to motor functions, results of fMRI studies [27] in normal subjects point to the important role of the dorsolateral and medial premotor regions in the programming of trains of repetitive tapping movements.

Most of the research in patients with frontal lobe epilepsy has been carried out on adults who have undergone frontal lobectomy [22], [39], [41], [43]. These patients display deficits on spatial, non-spatial and sensory delay tasks, sorting tasks, tests requiring the monitoring of sequences of external events [15], [29], [41], [42], [43], concept formation and response inhibition tasks [40], [63], associative learning tasks [51], [54], as well as on a variety of attention and memory tasks [25], [63], [67]. In a recent neuropsychological study, Helmstaedter et al. [22] compared the performance of unresected temporal lobe epilepsy and frontal lobe epilepsy adults. The latter performed more poorly on Luria's unimanual and bimanual motor sequencing tasks. They were also inferior to patients with temporal lobe epilepsy with regard to response maintenance and response inhibition on the Stroop Test. Furthermore, they were impaired on tests designed to assess visuo-perceptual speed (rapid discrimination of symbols) and interference (reverse reading of a letter sequence). Finally, they showed impairments with respect to concept formation, planning behaviour and response inhibition on the Wisconsin Card Sorting Test (WCST) and on a Maze test which were similar to those previously observed in patients with various types of frontal lobe lesions [32], [33]. In contrast, the two epilepsy groups did not differ on the Verbal Fluency Test and on a letter cancellation test measuring sustained visual attention.

Studies in children have to take into account developmental aspects of frontal lobe functioning [10]. There is evidence that executive functions emerge in the first year of life, begin to mature between the ages of 4 and 7 years [47], undergo major changes between 8 and 12 years [5], [47] and continue to develop in certain aspects at least until puberty (12–15 years and beyond) [18], [72]. The maturational stages are demonstrable in the children's increasing proficiency on various neuropsychological measures. This is exemplified in a study by Levin et al. [28]. These authors used the WCST, the Verbal Fluency and Graphic Fluency Test, the Tower of London, a Delayed Alternation task and a go–no-go task in healthy children who were divided into three groups along age lines. Children aged 7–8 and 9–12 years demonstrated increasing skills in concept formation and conceptual shift on the WCST and the go–no go task, while the 13- to 14-year-old children showed important gains in the areas of response generation, planning ability and performance speed, as evidenced by an enhanced performance on the Graphic Fluency Test and the Tower of London.

A developmental trend was also observed by Chelune and Baer [5] who found that skills in concept formation, planning and problem-solving, measured on the WCST, developed progressively in children between 6 and 10 years. Around the age of 11 years most of the children were performing the task at adult level.

In another study, conducted by Welsh et al. [72] healthy children aged 3–12 years were submitted to a battery of ‘frontal’ tests in order to determine the point in development at which adult-level performance was achieved. Planning ability, assessed on a simple version of the Tower of Hanoi (TOH), was efficient at the age of 6 years. Children between 3 and 4 years of age showed significant steps towards achievement of this task. Conceptual shift was mastered around the age of 10 years, whereas the development of motor sequencing, verbal search and more complex planning skills (involving the manipulation of four or more disks on the TOH) appear to continue beyond the age of 12, since the 12-year-olds in the study were unable to attain adult level performance in these functions. Evidently, any insult at a given stage in development would be expected to interfere with the emergence of age-appropriate executive functions and motor skills.

Studies in pediatric patient populations have shown that impairments in executive functions can result from a variety of neurological conditions such as closed head injury [29], [30], [37], meningitis [68], brain hemorrhage [20] and exposure to environmental toxins [44], to name but a few. Some of these deficits can be directly related to frontal lobe dysfunction [29], [30], [37]. For instance, using fMRI in children with traumatic head injury, Levin et al [30] observed that frontal lobe damage, but not extrafrontal damage, was associated with impaired performance on the Tower of London.

Distinct patterns of frontal lobe dysfunctions have also been described in four frontally-injured children, studied by Mateer and Williams [38]. The children showed cognitive and behavioural changes marked by impaired attention, academic deficits, irritability and social problems in the absence of apparent intellectual, linguistic or perceptual problems. Two children exhibited difficulties in planning and organization on the Mazes and the Block Design subtests of the revised Wechsler Intelligence Scale for Children (WISC-R). A reduction in verbal fluency (animal names) was observed in another case. Furthermore, all four children showed reduced speed on the interference part of the Stroop Test.

Similar impairments have been reported by Grattan and Esslinger [20] for a patient who suffered a subarachnoid hemorrhage in the left frontal region at the age of 7 years. A 26-year follow-up of this patient further indicated important long-term deficits in psychosocial development and adaptive behaviour which could be attributed to poor auto-regulation. Deficits in self-regulatory and self-monitoring control also dominated the neurobehavioural tableau of a young boy, described by Marlowe [37] who sustained traumatic injury to the right prefrontal cortex. The patient was unable to elaborate and maintain efficient problem-solving strategies in spite of normally developed, even superior, verbal and non-verbal reasoning abilities.

Studies investigating executive functions in children with frontal lobe epilepsy are still scarce. Boone et al. [3], in a single case study, reported a frontal lobe syndrome in conjunction with a focus in the left frontal lobe in a 13-year-old girl. Neuropsychological testing revealed impaired performance on tasks measuring motor speed (Finger Tapping Test), attention and concentration (Digit Span of the WISC-R), alternation between two concepts (Trail Making Test, part B), planning ability (Mazes of the WISC-R) and response inhibition (Stroop Test). The motor performance on the Finger Tapping Test was depressed, particularly for the non-dominant left hand. No deficits were observed on tasks requiring categorization, abstract reasoning and concept formation (WCST). Similarly, Jambaqué and Dulac [24] observed frontal lobe deficits in an 8-year-old boy of normal intelligence who presented with an epileptic focus in the right fronto-temporal region. The child showed marked behavioural and affective changes which abated when adequate seizure control was achieved. On neuropsychological tests, he manifested deficits in motor speed and planning ability on the WISC-R subtests Coding and Mazes. Manual dexterity was also affected as evidenced by a deterioration of his handwriting. Furthermore, he had difficulties reproducing a sequence of hand movements. His verbal fluency was reduced as was his attention span.

To our knowledge, no group studies have been conducted to date that have attempted to distinguish children with frontal lobe epilepsy (FLE) from children with other types of epilepsy. The purpose of the present study was to determine whether some or all characteristics of frontal lobe dysfunction are present in children with FLE as compared to children with temporal lobe epilepsy (TLE) or generalized epilepsy (GEA). Based on the few single case studies reviewed above, we expected that the FLE children would do more poorly on measures of motor coordination, mental flexibility, response initiation, impulse control and planning than the TLE and GEA children. We were also interested to know which of the tests employed to assess these functions would be most sensitive to frontal lobe dysfunction in children. The performance of the epileptic children was further compared to normative data derived from healthy children. Finally, the effects of the patients’ age and the localization of the epileptic abnormality (unilateral versus bilateral) were analyzed in order to assess maturation factors and possible effects of the extent of the pathology.