Late Functional Changes Post-Severe Traumatic Brain Injury Are Related to Community Reentry Support: Results From the PariS-TBI Cohort.

OBJECTIVES: To explore late functional changes after a traumatic brain injury and their relation to patients' characteristics and reentry support. DESIGN: Prospective follow-up of an inception cohort of adults with severe traumatic brain injury recruited in 2005-2007 in the Parisian area, France. One and 4-year assessments were performed by trained neuropsychologists. One-to-4-year change in the Glasgow Outcome Scale-Extended defined 3 groups: "improvement," "stability," and "worsening." Relationships between these groups and patients' characteristics were analyzed. RESULTS: Among 504 recruited patients and 245 four-year survivors, 93 participated in both evaluations. Overall Glasgow Outcome Scale-Extended improved by 0.4. Forty percent of the sample improved, 44% were stable, and 16% worsened. Being in a more unfavorable group was related to preinjury alcohol abuse and to higher anxiety and depression at 4 years. Attendance to a specialized community reentry unit was related to higher chances of being in the "improvement" group in univariate analyses and after adjustment for age, time to follow command, preinjury alcohol and occupation, and mood disorders (adjusted odds ratio [OR] = 4.6 [1.1-20]). CONCLUSION: Late functional changes were related to psychosocial variables and to reentry support. The effect of reentry support on late recovery needs to be confirmed by further investigations.

Prevalence of traumatic brain injury and epilepsy among prisoners in France: Results of the Fleury TBI study.

OBJECTIVE: The first aim of this study was to estimate the prevalence of TBI and epilepsy in a French prison population and to study variables known to be associated with TBI. The second aim was to compare prisoners with and without a history of TBI. PARTICIPANTS: All offenders (females, males and juveniles) admitted consecutively to Fleury-Mérogis prison over a period of 3 months were included in the study. DESIGN: During the admission procedure, offenders were interviewed by healthcare staff using a self-reported questionnaire. RESULTS: In all, 1221 prisoners were included. The rates of TBI and epilepsy were high, with a prevalence of 30.6% and 5.9%, respectively. Psychiatric care, anxiolytic and antidepressant treatment, use of alcohol and cannabis were all significantly higher among offenders with a history of TBI. Moreover, the number of times in custody and the total time spent in jail over the preceding 5 years were significantly higher among offenders with a history of TBI. CONCLUSIONS: These results provide further evidence that specific measures need to be developed such as, first of all, screening for TBI upon arrival in prison.

Predictive factors for 1-year outcome of a cohort of patients with severe traumatic brain injury (TBI): results from the PariS-TBI study.

OBJECTIVES: To assess outcome and predicting factors 1 year after a severe traumatic brain injury (TBI). METHODS: Multi-centre prospective inception cohort study of patients aged 15 or older with a severe TBI in the Parisian area, France. Data were collected prospectively starting the day of injury. One-year evaluation included the relatives-rating of the Dysexecutive Questionnaire (DEX-R), the Glasgow Outcome Scale-Extended (GOSE) and employment. Univariate and multivariate tests were computed. RESULTS: Among 257 survivors, 134 were included (mean age 36 years, 84% men). Good recovery concerned 19%, moderate disability 43% and severe disability 38%. Among patients employed pre-injury, 42% were working, 28% with no job change. DEX-R score was significantly associated with length of education only. Among initial severity measures, only the IMPACT prognostic score was significantly related to GOSE in univariate analyses, while measures relating to early evolution were more significant predictors. In multivariate analyses, independent predictors of GOSE were length of stay in intensive care (LOS), age and education. Independent predictors of employment were LOS and age. CONCLUSIONS: Age, education and injury severity are independent predictors of global disability and return to work 1 year after a severe TBI.

Neurological sequelae after cerebral anoxia.

PRIMARY OBJECTIVE: Cardiac arrest can cause neurological impairment. The aim of this study is to confirm the disability and the predominant part of executive and behavioural impairments after cardiac arrest. RESEARCH DESIGN: A retrospective study is proposed. METHODS AND PROCEDURES: All consecutive patients admitted to the Department of Rehabilitation for Neurological Impairments following cerebral anoxia after cardiac arrest between 1995-2007 were included. Clinical and neuropsychological assessment was proposed. MAIN OUTCOMES AND RESULTS: Thirty patients, 19 men, were examined. Ages ranged from 16-58 (mean = 39.5). Fourteen patients presented with severe disability and 16 patients presented with moderate disability. In the first group (severe disability) no patients were autonomous for daily life activities. They presented with dysexecutive syndrome and behavioural disorders associated with amnesia syndrome; 64% of them presented with motor disorders. In the second group, patients with moderate disability were autonomous in daily life but not for the complex activities or functioning. They had no motor impairment but suffered from executive and memory impairments. Behavioural changes were noted. Medical history or demographic data did not differ between the two groups. CONCLUSION: The study confirms the predominant part of executive, memory and behavioural impairments after cardiac arrest. This retrospective study cannot provide prognosis factors and further prognosis studies are needed.

[Cognitive rehabilitation]. / La rééducation cognitive.

During these last 30 years, cognitive rehabilitation has accomplished dramatic improvement. In this paper, we review progress in four main domains: the development of pragmatic and ecological approaches in neuropsychological rehabilitation; the development of computerised rehabilitation; rehabilitation of executive functions; cognitive rehabilitation in degenerative dementia. Finally, we present a single-case study, recently published elsewhere, showing the effectiveness of rehabilitation of verbal working memory in a patient with left hemisphere stroke. In addition, future issues for rehabilitation research are presented. The development of bottom-up rehabilitation strategies as well as the use of inter-hemispheric interactions appears as future promising tracks for clinical rehabilitation.

[Sensory syndrome and aphasia after left insular infarct]. / L'insula, une île oubliée? Troubles sensitifs et troubles du langage après infarctus insulaire gauche.

INTRODUCTION: Sensorial impairment without hemiplegia is usually caused by a thalamic lesion. CASE REPORT: A 28-year-old woman presented with hemianesthesia associated with aphasia following a left insular lesion, subsequent to subarachnoid hemorrhage. Brain MRI Flair sequence revealed a high intensity signal in the left insular and frontal subcortical regions. Insular infarct was diagnosed, associated with hemorrhagic sequelae. DISCUSSION/CONCLUSION: Study of the normal and pathologic insular cortex suggest several implications of the region in somatosensory and language functions. However, the insular cortex has been mainly associated with central pain. Lasting objective hypoesthesia has been very rarely documented. The left insular cortex has also been implicated in speech apraxia but our patient presented with fluent aphasia mostly affecting the rhythm of speech, as it has been observed in thalamic aphasia.

[The effect of age on executive functioning after acquired brain injury in adults]. / Effet de l'âge sur le fonctionnement exécutif après lésion cérébrale chez l'adulte.

INTRODUCTION: Executive functioning deficits have often been described in normal aging. They are also known to be a frequent sequel of traumatic brain injury, where patients may exhibit severe long-standing impairments in instrumental activities of daily living. One could therefore expect that cerebral lesions affecting executive functioning would result in more severe impairments in older patients. We previously developed an ecological assessment of executive functions, consisting of a cooking task, requiring multitasking abilities and known to be sensitive to a dysexecutive syndrome [Cortex 36 (2000) 649-669]. The aim of this study was to analyze the effect of age on the cognitive and ecological assessments of executive functions in a group of patients with acquired brain injury (ABI) resulting in a dysexecutive syndrome. Studies in this area usually focus on patients older than 60 or 65, but we chose to analyze the effect of age in a younger population. We hypothesized that older patients would have poorer performances on the cognitive and ecological tests of executive functioning, when compared to younger patients. METHODS: Forty-five patients with ABI resulting in frontal lesions and a dysexecutive syndrome participated in this study. Patients underwent a comprehensive battery of cognitive tests assessing executive functioning, as well as the cooking task. We also studied a group of 12 control subjects who performed the cooking task. RESULTS: No effect of age was found on performance in the cooking task in the control group. Age was not related to demographic parameters or injury severity in the ABI group. Although the ABI group was relatively young (mean age: 40.3 years (S.D.=12.5), ranging from 17 to 63), results indicated a significant deleterious effect of age on the cognitive tests of executive functioning in the ABI group. We also highlighted a significant worsening of patients' performance in the cooking task with age, and this effect was found on several variables of task analysis: the number of errors and occurrence of dangerous behaviors. CONCLUSION: Our study demonstrates the deleterious effect of aging on cognitive and ecological assessment of executive functioning after ABI. The strength of this study is that it deviated from the traditional age considered in studies of elderly populations and focused on younger patients. It is therefore important to consider the implication that this may have on a patient's rehabilitation program and postinjury discharge.

[Ecological assessment of executive functions in a patient with acquired brain injury]. / Evaluation écologique des fonctions exécutives chez un patient traumatisé crânien.

UNLABELLED: Dysexecutive syndrome is one of the most frequent sequel of severe traumatic brain injury. It causes severe disabilities and it is incompletely assessed by the classical "paper and pencil" neuropsychological tests. We developed an ecological assessment conducted in a naturalistic situation, consisting of a cooking task, and we described a classification of errors. This assessment is very sensitive, even to a mild dysexecutive syndrome. OBJECTIVE: To describe the disabilities in activities of daily living of a traumatic brain-injured patient and to demonstrate the sensitivity of an ill-structured ecological assessment. METHOD: We report a single case study illustrating how the ecological assessment by the cooking task helped better understand and characterize the patient's disabilities. RESULTS: The patient presented severe disabilities in daily life activities, which were well described by his family. His cognitive disorders were mild in the cognitive tests, even those supposed to be more ecological, such as the Six Elements Task or script generation. He exhibited very severe disorders in the cooking task, with a very high number of errors. Moreover, duration of the cooking task was very long; he did not achieve the goal and exhibited dangerous behaviour. DISCUSSION AND CONCLUSION: The cooking task involves abilities to deal with multitasking, which particularly involve executive functions. The most severe disorders were observed during the patient's interaction with the environment while conducting a complex goal-directed action plan, indicating control disorders. This type of naturalistic assessment provides very useful information to help patients organise their familial, social or professional reintegration.

[Fantastic confabulations or delusion?]. / Confabulations fantastiques ou délire ?

INTRODUCTION: Confabulations are inaccurate narratives purporting to convey information about the world or the self. Fantastic utterances from brain-injured patients are difficult to interpret as confabulation or delusion. METHODS: Starting from two clinical observations, we analyse the terms "spontaneous confabulations" and "delusion". RESULTS: Two brain-injured patients presented with fantastic utterances; the adhesion was complete for both patients. They also suffered from amnesic and executive disorders. Clinical interviews with neuropsychologist and psychopathologist could not distinct between spontaneaous confabulations and delusion. DISCUSSION: Neuropsychological interpretations of spontaneous confabulations are (1) the deficient strategic retrieval process arising from executive failures and (2) confusion of the temporal order of information within memory. These hypotheses cannot explain the fantastic utterances described. Are spontaneous fantastic confabulations a specific entity or did these patients present a morbid association of neurological and psychiatric disorders? Fantastic confabulations are very scarcely described and the association of neurological and psychiatric impairments enables us to better describe the clinical observations. Spontaneous confabulations reported after amnesic and executive disorders are indeed typically composed of the patient's past experiences and do not usually comprehend fantastic utterances. CONCLUSION: Neurological and psychological analyses of the fantastic utterances from two brain-injured patients do not respond to the definition of spontaneous confabulation. Fantastic confabulations are a rare entity and we propose another explanation consisting of the association of neurological and psychiatric disorders.

[Cognitive rehabilitation of amusia]. / Vers une rééducation cognitive de l'amusie.

INTRODUCTION: The cognitive model of music processing has a modular architecture with two main pathways (a melody pathway and a time pathway) for processing the musical "message" and thus enabling music recognition. It also features a music-specific module for tonal encoding of pitch which stands apart from all other known cognitive systems (including language processing). To the best of our knowledge, rehabilitation therapy for amusia has not yet been reported. OBJECTIVE: We developed a therapeutic method (inspired by work on word deafness) in order to determine whether specific rehabilitation based on melody discrimination could prompt the regression of amusia. METHOD: We report the case of a patient having developed receptive, acquired amusia four years previously. His tone deafness disorder was assessed using the Montreal Battery of Evaluation of Amusia (MBEA), which revealed impairment of the melody pathway but no deficiency in the time pathway. A computer-assisted rehabilitation method was implemented; it used melody discrimination tasks and an errorless learning paradigm with progressively fading visual cues. RESULTS: After therapy, we noted an improvement in the overall MBEA score and its component subscores which could not be explained by spontaneous recovery (in view of the number of years since the neurological accident). The improvement was maintained at seven months post-therapy. Although post-therapy improvement in daily life was not systematically assessed, the patient started listening to his favourite music again. CONCLUSION: Specific amusia therapy has shown efficacy.

History of traumatic brain injury in prison populations: A systematic review.

Traumatic brain injury (TBI) can lead to cognitive, behavioural and social impairments. The relationship between criminality and a history of TBI has been addressed on several occasions. OBJECTIVE: The objective of this review was to present an update on current knowledge concerning the existence of a history of TBI in prison populations. METHODS: PubMed and PsycINFO databases were searched for relevant papers, using the PRISMA guidelines. We selected papers describing TBI prevalence among incarcerated individuals and some that also discussed the validity of such studies. RESULTS: Thirty-three papers were selected. The majority of the papers were on prison populations in Australia (3/33), Europe (5/33) and the USA (22/33). The selected studies found prevalence rates of the history of TBI ranging from 9.7% and 100%, with an average of 46% (calculated on a total population of 9342). However, the level of evidence provided by the literature was poor according to the French national health authority scale. The majority of the prisoners were males with an average age of 37. In most of the papers (25/33), prevalence was evaluated using a questionnaire. The influence of TBI severity on criminality could not be analysed because of a lack of data in the majority of papers. Twelve papers mentioned that several comorbidities (mental health problems, use of alcohol…) were frequently found among prisoners with a history of TBI. Two papers established the validity of the use of questionnaires to screen for a history of TBI. CONCLUSION: These results confirmed the high prevalence of a history of TBI in prison populations. However, they do not allow conclusions to be drawn about a possible link between criminality and TBI. Specific surveys need to be performed to study this issue. The authors suggest ways of improving the screening and healthcare made available to these patients.

Behavioral and affective disorders after brain injury: French guidelines for prevention and community supports.

OBJECTIVE: The purpose of this study was to elaborate practice guidelines for the prevention of behavioral and affective disorders in adult outpatients after traumatic brain injury (TBI); but also to identify the support systems available for family, caregivers of patients with TBI within the community. METHODS: The elaboration of these guidelines followed the procedure validated by the French health authority for good practice recommendations, close to the Prisma statement. This involved a systematic and critical review of the literature looking for studies that investigated the impact of programs in community settings directed to behavioral and affective disorders post-TBI. Recommendations were than elaborated by a group of professionals and family representatives. RESULTS: Only six articles were found comprising 4 studies with a control group. Two studies showed a beneficial effect of personalized behavior management program delivered within natural community settings for persons with brain injury and their caregivers. Two other studies showed the relevance of scheduled telephone interventions to improve depressive symptoms and one study emphasized the usefulness of physical training. One study investigated the relevance of an outreach program; this study showed an improvement of the patients' independence but did not yield any conclusions regarding anxiety and depression. DISCUSSION AND RECOMMENDATIONS: In addition to the application of care pathways already established by the SOFMER, prevention of behavioral and affective disorders for brain-injured outpatients should involve pain management, as well as development of therapeutic partnerships. It is recommended to inform patients, their family and caregivers regarding the local organization and facilities involved in the management of traumatic brain injury. The relevance of therapeutic education for implementing coping strategies, educating caregivers on behavioral disorder management, follow-up telephone interventions, and holistic therapy seems established. The level of evidence is low and preliminary studies should be confirmed with larger controlled trials.

A comprehensive picture of 4-year outcome of severe brain injuries. Results from the PariS-TBI study.

OBJECTIVES: Survivors of severe traumatic brain injury have a great variety of impairments and participation restrictions. Detailed descriptions of their long-term outcome are critical. We aimed to assess brain injury outcome for subjects with traumatic brain injury in terms of the International classification of functioning, disability and health. MATERIALS AND METHODS: Four-year follow-up of an inception cohort of adults with severe traumatic brain injury by using face-to-face interviews with patients and proxies. RESULTS: Among 245 survivors at 4 years, 147 were evaluated (80% male, mean age: 32.5±14.2 years at injury); 46 (32%) presented severe disability, 58 (40%) moderate disability, and 40 (28%) good recovery. Most frequent somatic problems were fatigue, headaches, other pain, and balance. One quarter of subjects had motor impairments. Rates of cognitive complaints ranged from 25 to 68%, the most frequent being memory, irritability, slowness and concentration. With the Hospital Anxiety and Depression Scale, 43% had anxiety and 25% depression. Overall, 79% were independent in daily living activities and 40 to 50% needed help for outdoor or organizational activities on the BICRO-39. Most had regular contacts with relatives or close friends but few contacts with colleagues or new acquaintances. Subjects spent little time in productive activities such as working, studying, looking after children or voluntary work. Quality of life on the QOLIBRI scale was associated with disability level (P<0.0001). CONCLUSION: Management of late brain injury needs to focus on cognitive difficulties, particularly social skills, to enhance patient participation in life.

Ecological Assessment Battery for Numbers (EABN) for brain-damaged patients: standardization and validity study.

OBJECTIVES: Number-processing may be altered following brain injury and might affect the everyday life of patients. We developed the first ecological tool to assess number-processing disorders in brain-injured patients, the Ecological Assessment Battery for Numbers (EABN; in French, the BENQ). The aim of the present study was to standardize and validate this new tool. MATERIAL AND METHODS: Standardization included 126 healthy controls equally distributed by age, sex and sociocultural level. First, 17 patients were evaluated by the EABN; then scores for a subgroup of 10 were compared with those from a French analytical calculation test, the Évaluation Clinique des Aptitudes Numériques (ECAN). The concordance between the EABN and the ECAN was analyzed to determine construct validity. Discrimination indexes were calculated to assess the sensitivity of the subtests. RESULTS: Standardization highlighted a major effect of sociocultural level. In total, 9 of 17 patients had a pathological EABN score, with difficulties in telling time, making appointments and reading numerical data. The results of both the EABN and ECAN tests were concordant (Kendall's w=0.97). Finally, the discriminatory power was good, particularly for going to the movies, cheque-writing and following a recipe: scores were>0.4. CONCLUSION: The EABN is a new tool to assess number-processing disorders in adults. This tool has been standardized and has good psychometric properties for patients with brain injury.

Patterns of Objective and Subjective Burden of Informal Caregivers in Multiple Sclerosis.

BACKGROUND: Home care for patients with Multiple Sclerosis (MS) relies largely on informal caregivers (ICs). Methods. We assessed ICs objective burden (Resource Utilization in Dementia measuring informal care time (ICT)) and ICs subjective burden (Zarit Burden Inventory (ZBI)). RESULTS: ICs (N = 99) were spouses (70%), mean age 52 years, assisting disabled patients with a mean EDSS (Expanded Disability Status Scale) of 5.5, with executive dysfunction (mean DEX (Dysexecutive questionnaire) of 25) and a duration of MS ranging from 1 to 44 years. OBJECTIVE: burden was high (mean ICT = 6.5 hours/day), mostly consisting of supervision time. Subjective burden was moderate (mean ZBI = 27.3). Multivariate analyses showed that both burdens were positively correlated with higher levels of EDSS and DEX, whereas coresidency and IC's female gender correlated with objective burden only and IC's poor mental health status with subjective burden only. When considering MS aggressiveness, it appeared that both burdens were not correlated with a higher duration of MS but rather increased for patients with severe and early dysexecutive function and for patients classified as fast progressors according to the Multiple Sclerosis Severity Score. CONCLUSION: Evaluation of MS disability course and IC's personal situation is crucial to understand the burden process and to implement adequate interventions in MS.

Repetitive transcranial magnetic stimulation and transcranial direct current stimulation in motor rehabilitation after stroke: an update.

Stroke is a leading cause of adult motor disability. The number of stroke survivors is increasing in industrialized countries, and despite available treatments used in rehabilitation, the recovery of motor functions after stroke is often incomplete. Studies in the 1980s showed that non-invasive brain stimulation (mainly repetitive transcranial magnetic stimulation [rTMS] and transcranial direct current stimulation [tDCS]) could modulate cortical excitability and induce plasticity in healthy humans. These findings have opened the way to the therapeutic use of the 2 techniques for stroke. The mechanisms underlying the cortical effect of rTMS and tDCS differ. This paper summarizes data obtained in healthy subjects and gives a general review of the use of rTMS and tDCS in stroke patients with altered motor functions. From 1988 to 2012, approximately 1400 publications were devoted to the study of non-invasive brain stimulation in humans. However, for stroke patients with limb motor deficit, only 141 publications have been devoted to the effects of rTMS and 132 to those of tDCS. The Cochrane review devoted to the effects of rTMS found 19 randomized controlled trials involving 588 patients, and that devoted to tDCS found 18 randomized controlled trials involving 450 patients. Without doubt, rTMS and tDCS contribute to physiological and pathophysiological studies in motor control. However, despite the increasing number of studies devoted to the possible therapeutic use of non-invasive brain stimulation to improve motor recovery after stroke, further studies will be necessary to specify their use in rehabilitation.

Neurological complications of primary Sjögren's syndrome.

OBJECTIVE: To better delineate the spectrum of neurological complications of primary Sjögren's syndrome (PSS). METHODS: A detailed neurological investigation was prospectively performed in a group of 25 consecutive patients with PSS followed in an internal medicine department between June 1996 and December 1997 (Internal Medicine group). In addition, eleven patients with neurological complications of PSS were identified in the Neurological Department of the same institution during the same period (Neurological group). RESULTS: In the Internal Medicine group, neurological complications were discovered in 10/25 (40%) patients. Peripheral nervous system involvement was present in 4/25 patients from the Internal Medicine group and in 10/11 patients from the Neurological group and consisted mainly of axonal sensorimotor/sensory polyneuropathy. A motor neuron syndrome was identified in two patients. CNS involvement occurred in 7/25 patients from the Internal Medicine group and in 4/11 patients from the Neurological group. Three patients had spinal cord involvement. Cognitive dysfunction was the most frequent finding (5/25 in the Internal Medicine group, 3/11 in the Neurological group) characterized either by subcortical or corticosubcortical dysfunction. Cognitive impairment was not attributed to mood disturbance and was not associated with specific laboratory or radiological abnormalities. CONCLUSION: Neurological complications of PSS are frequent since they were present in 40% (10/25) of patients in a consecutive series of patients from a department of Internal Medicine. Although PNS involvement predominates, complications of PSS affecting the brain or spinal cord are not rare, with subcortical dysfunction as the main finding.

An ecological approach to planning dysfunction: script execution.

Planning, which concerns many activities in everyday life, is a two-stage process. The first one predetermines a course of actions aimed at achieving some specific goals. It is founded on managerial knowledge or overlearned sequences of events and may be tested by script generation. The second stage entails monitoring and guiding the execution of the plan to a successful conclusion. It must take into account environmental contingencies and may be tested by script execution. If the frontal lobes intervene not only in managerial knowledge (Grafman, 1989) but also in binding the plan with contextual environment (Damasio, Tranel and Damasio, 1991; Shallice and Burgess, 1991), script execution would be more sensitive than script generation to planning deficits. To test this hypothesis, script execution and script generation were compared in 11 patients with a dysexecutive syndrome and 10 matched controls, using three scripts of daily life activities: (1) 'shopping for groceries'; (2) 'cooking'; (3) 'answering a letter and finding the way to post the reply'. Two way ANOVAs showed more errors in execution than in generation, more errors in patients than in controls, and a greater difference between execution and generation in patients than in controls. Furthermore, 'context neglect' and 'environmental adherence' were the two types of errors that best differentiated patients from controls. Finally, the total number of errors in execution correlated with the score on behavioral questionnaires answered by occupational therapists. These results confirm our hypothesis and suggest that script execution may be a valid ecological approach to estimate the severity of deficits in daily life activities.

Distinct frontal regions for processing sentence syntax and story grammar.

Time is a fundamental dimension of cognition. It is expressed in the sequential ordering of individual elements in a wide variety of activities such as language, motor control or in the broader domain of long range goal-directed actions. Several studies have shown the importance of the frontal lobes in sequencing information. The question addressed in this study is whether this brain region hosts a single supramodal sequence processor, or whether separate mechanisms are required for different kinds of temporally organised knowledge structures such as syntax and action knowledge. Here we show that so-called agrammatic patients, with lesions in Broca's area, ordered word groups correctly to form a logical sequence of actions but they were severely impaired when similar word groups had to be ordered as a syntactically well-formed sentence. The opposite performance was observed in patients with dorsolateral prefrontal lesions, that is, while their syntactic processing was intact at the sentence level, they demonstrated a pronounced deficit in producing temporally coherent sequences of actions. Anatomical reconstruction of lesions from brain scans revealed that the sentence and action grammar deficits involved distinct, non-overlapping sites within the frontal lobes. Finally, in a third group of patients whose lesions encompassed both Broca's area and the prefrontal cortex, the two types of deficits were found. We conclude that sequence processing is specific to knowledge domains and involves different networks within the frontal lobes.