Psychological distress and gender predict cognitive complaint after adult civilian mild traumatic brain injury in pre-morbidly healthy adults.

Subjective cognitive symptoms are common after mild traumatic brain injury (mTBI), and are associated with important outcome factors including return to work. This study examined self-reported cognitive symptoms in mTBI and trauma controls (TCs), and explored psychological distress and gender as predictors of these symptoms. Pre-morbidly healthy adults with mTBI (n = 68) and general trauma (n = 40) were prospectively recruited from inpatient hospital wards and assessed 6-10 weeks post-injury. Primary measures included self-reported cognitive symptoms, post-concussion symptoms, and psychological distress. Groups were matched on all background variables, including objective cognitive performance. Within this context, subjective cognitive symptoms were significantly elevated after mTBI relative to TCs (t = 3.396, p = .001). In contrast, there was no difference in post-concussion symptoms between groups (t = 1.275, p = .206). Psychological distress (ß = .536, p < .001) and gender (ß = .253, p = .012) predicted subjective cognitive symptoms in mTBI, with females and those with higher distress reporting greater symptoms. Unlike general post-concussion symptoms, subjective cognitive symptoms were elevated after mTBI relative to TCs, suggesting that mTBI-specific factors underly this elevation. Females and individuals with high psychological distress are important subgroups to consider for potential intervention following mTBI.

Hand preference is selectively related to common and internal carotid arterial asymmetry.

This study documents relationships between handedness and carotid arterial asymmetries. The article is divided into two sections, considering first geometric (n = 195) and then haemodynamic (n = 228) asymmetries. In the geometric study, diameters, lengths, and angles of the common carotid arteries in left and right-handed participants were measured using computed tomography angiography scans. Resistance to blood flow was calculated according to Poiseuille's formula. In the haemodynamic study, peak systolic and end-diastolic velocity, vessel diameter, and volume flow rate of the common, internal, and external carotid arteries were measured in left and right-handed participants, using Doppler ultrasonography. The findings reveal for the first time that the extracranial arteries supplying the cerebral hemispheres are asymmetrical in a direction that increases blood flow to the hemisphere dominant for handedness. Significant handedness interactions were identified in arterial length, diameter, resistance to blood flow, velocity and flow volume rate (p < .001). Arterial resistance and volume flow rates significantly predicted hand preference and proficiency. Our findings reveal a vascular correlate of handedness, but causality cannot be determined from this study alone. These asymmetries appear to be independent of aortic arch anomalies, suggesting a top-down, possibly demand-driven, pattern of development.

Differential Functional Connectivity Correlates of Cerebrospinal Fluid Biomarkers in Dementia of the Alzheimer's Type.

BACKGROUND: Alzheimer's disease (AD) is characterized by two cardinal pathologies, which have different topological distributions. The differential anatomical distributions of these pathologies raise the possibility that they exert differential effects on brain networks. OBJECTIVES: To investigate whether cerebrospinal fluid (CSF) biomarkers of the cardinal pathologies have differential relationships with functional connectivity networks in patients with dementia of the Alzheimer's type (DAT). METHODS: Thirty-nine participants underwent CSF sampling and resting-state functional magnetic resonance imaging. Functional connectivity networks were computed for each participant. CSF biomarker levels of p-tau and amyloid-ß (Aß) were regressed onto these networks to identify subnetworks associated with each biomarker. RESULTS: A subnetwork associated with tau-related pathology was identified with its hub in the right anterior entorhinal cortex. A separate subnetwork associated with Aß with its hub in the right dorsal anterior cingulate cortex was identified. CONCLUSION: These results demonstrate the differential effects of AD biomarkers on functional connectivity networks, supporting a possible division of labour between the cardinal pathologies.

Longitudinal Partial Volume Correction in 2-[18F]-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography Studies of Alzheimer Disease.

OBJECTIVE: To investigate partial volume correction (PVC) of 2-[F]-fluoro-2-deoxy-D-glucose positron emission tomography in Alzheimer disease in a longitudinal context. METHODS: A total of 115 participants were included, including 55 controls, 53 patients with mild cognitive impairment, and 7 patients with dementia of the Alzheimer type. Imaging was performed at baseline and 24 months. Partial volume corrected vs uncorrected rates of longitudinal change were compared for mesial temporal and cortical regions of interest. RESULTS: Partial volume correction increased apparent uptake, and this effect was greater at 24 months compared with baseline. Partial volume correction decreased the rate of decline, causing an apparent increase in uptake at 24 months compared with baseline. This effect was correlated with the structural atrophy. CONCLUSIONS: These findings suggest that applying PVC in a longitudinal context in Alzheimer disease might produce unpredictable results. Accordingly, both PVC corrected and uncorrected data should be reported to ensure that the results are physiologically plausible.

Reading difficulty is associated with failure to lateralize temporooccipital function.

OBJECTIVE: Studies of focal epilepsy have revealed abnormalities of language organization; however, little attention has been paid to disorders of reading in this group. We hypothesized that language functional magnetic resonance imaging (fMRI) would reveal differences in language organization between focal epilepsy patients with and without reading difficulties. METHODS: We conducted language fMRI studies of 10 focal epilepsy patients with reading difficulties, 34 focal epilepsy patients without reading difficulties, and 42 healthy controls. RESULTS: We defined regions of interests on the basis of activation patterns on an orthographic lexical retrieval task. Comparison of activations within these ROIs on a second Noun-Verb task revealed epilepsy-related effects (relative to healthy controls: reduced activation in left inferior frontal cortex), as well as greater activation in the right temporooccipital cortex specific to the reading difficulty group. SIGNIFICANCE: These findings identify a focal epilepsy effect in the left frontal region (present in patients with and without reading difficulties), and a functional abnormality specific to the reading difficulty group localized to right temporooccipital cortex-a region implicated in lexicosemantic processing. Our observations suggest a failure of left hemisphere specialization among focal epilepsy patients with reading difficulties.

Autobiographical narratives relate to Alzheimer's disease biomarkers in older adults.

BACKGROUND: Autobiographical memory (ABM), personal semantic memory (PSM), and autonoetic consciousness are affected in individuals with mild cognitive impairment (MCI) but their relationship with Alzheimer's disease (AD) biomarkers are unclear. METHODS: Forty-five participants (healthy controls (HC) = 31, MCI = 14) completed the Episodic ABM Interview and a battery of memory tests. Thirty-one (HC = 22, MCI = 9) underwent ß-amyloid positron emission tomography (PET) and magnetic resonance (MR) imaging. Fourteen participants (HC = 9, MCI = 5) underwent one imaging modality. RESULTS: Unlike PSM, ABM differentiated between diagnostic categories but did not relate to AD biomarkers. Personal semantic memory was related to neocortical ß-amyloid burden after adjusting for age and apolipoprotein E (APOE) ɛ4. Autonoetic consciousness was not associated with AD biomarkers, and was not impaired in MCI. CONCLUSIONS: Autobiographical memory was impaired in MCI participants but was not related to neocortical amyloid burden, suggesting that personal memory systems are impacted by differing disease mechanisms, rather than being uniformly underpinned by ß-amyloid. Episodic and semantic ABM impairment represent an important AD prodrome.

Vague retellings of personal narratives in temporal lobe epilepsy.

PURPOSE: Aside from deficits identified in single-word level retrieval, individuals with temporal lobe epilepsy (TLE) exhibit clinical oddities, such as circumstantiality in their language production. Circumstantiality refers to the use of language which is pedantic, repetitive, and overly detailed. This becomes particularly evident when elicitation tasks impose minimal structure, or when impersonal narratives are retold over consecutive occasions. Personal reminiscence is highly specific and localised in time, placing unique demands on cognitive-linguistic systems. It is hypothesised that the nature of this elicitation paradigm will produce a unique psycholinguistic phenotype in those with TLE. Among controls there is a compression of output for impersonal narratives, meaning that they use fewer words over less time and are more fluent. The opposite effect is observed when personal narratives are retold. METHODS: To investigate the micro- and macrolinguistic processes underpinning personal discourse production in TLE, we examined the elicited language output of 15 surgically naïve individuals with TLE and 14 healthy controls. Participants were asked to recall and re-tell an autobiographical memory on four immediately consecutive occasions, representing an alternative unstructured elicitation. Following transcription and coding of output, a detailed multi-level discourse analysis of output volume, fluency, cohesion, and coherence was conducted. RESULTS: As anticipated, a distinctly different pattern emerged in TLE when compared with controls who did not compress their output volume across repetitions but instead produced greater novelty, and a more coherent and refined account over time. Individuals with TLE consistently told a less distinct story across repetitions, with disturbances in fluency, cohesion, and coherence. CONCLUSION: This reflects a reduced capacity to produce a coherent mental representation, in all likelihood related to the neurolinguistic demands of recalling and retelling specific personal events.

Verbosity with retelling: Narrative discourse production in temporal lobe epilepsy.

To examine micro- and macrolinguistic underpinnings of circumstantiality in temporal lobe epilepsy (TLE), we examined the elicited narrative output of 15 individuals with TLE and 14 controls. To replicate and extend Field and colleagues' (2000) work, participants were asked to produce five immediately consecutive elicitations of an eight-frame cartoon "Cowboy Story" (Joanette et al., 1986). Following transcription and coding, detailed multi-level discourse analysis demonstrated a typical pattern of compression in controls. The narratives produced by individuals with TLE were less fluent, cohesive, and coherent across trials: producing fewer novel units and more repetitive and extraneous content. Significant group by trial interactions in sample length, spontaneous duration, and statements, were not explained by seizure burden, age, or lexical retrieval deficits. These findings suggest that they do not benefit from repeated engagement with a narrative in the same manner as controls. Disturbed social cognition and pragmatics in TLE might underpin communication inefficiencies.

Frequency and extent of cognitive complaint following adult civilian mild traumatic brain injury: a systematic review and meta-analysis.

OBJECTIVE: Cognitive symptoms are associated with return to work, healthcare use and quality of life after mild traumatic brain injury (mTBI). Additionally, while overall 'post-concussion' symptoms are often present at similar levels in mTBI and control groups, cognitive complaints may be specifically elevated in mTBI. A systematic review and meta-analysis was conducted to investigate the frequency and extent of cognitive complaints following adult civilian mTBI, and compare it to the frequency and extent of complaints in control populations (PROSPERO: CRD42020151284). METHOD: This review included studies published up to March 2022. Thirteen studies were included in the systematic review, and six were included in the meta-analysis. Data extraction and quality assessment were conducted by two independent reviewers. RESULTS: Cognitive complaints are common after mTBI, although reported rates differed greatly across studies. Results suggested that mTBI groups report cognitive complaints to a significantly greater extent than control groups (Hedges' g = 0.85, 95% CI 0.31-1.40, p = .0102). Heterogeneity between studies was high (τ2 = 0.20, 95% CI 0.04-1.58; I2 = 75.0%, 95% CI 43.4%-89.0%). Between-group differences in symptom reporting were most often found when healthy rather than injured controls were employed. CONCLUSIONS: Cognitive complaints are consistently reported after mTBI, and are present at greater levels in mTBI patients than in controls. Despite the importance of these complaints, including in regards to return to work, healthcare use and quality of life, there has been limited research in this area, and heterogeneity in research methodology is common.

Associations of Perceived Stress and Psychological Resilience With Cognition and a Modifiable Dementia Risk Score in Middle-Aged Adults.

OBJECTIVES: Psychological stress has been proposed as a risk factor for cognitive impairment and dementia. However, it remains unclear how an individual's stress-coping ability (i.e., psychological resilience) is related to cognition. This cross-sectional study investigated whether perceived stress and psychological resilience were associated with cognition and a modifiable dementia risk score in a large community-based sample of cognitively normal adults. The moderating effect of psychological resilience was also examined. METHODS: Participants (mean age = 57 ± 7 years) enrolled in the web-based Healthy Brain Project completed the Perceived Stress Scale and the Connor-Davidson Resilience Scale. Domains of attention and working memory were assessed using the Cogstate Brief Battery (n = 1,709), and associative memory was assessed using the Cambridge Neuropsychological Test Automated Battery (n = 1,522). Dementia risk was estimated for 1,913 participants using a modified version of the Cardiovascular Risk Factors, Aging, and Incidence of Dementia dementia risk score, calculated using only readily modifiable dementia risk factors. RESULTS: In separate linear regression analyses adjusted for age, sex, education, and race, greater levels of perceived stress and lower levels of psychological resilience were associated with poorer performance across all cognitive domains, as well as a higher modifiable dementia risk score. Psychological resilience did not moderate the effect of perceived stress on cognition or the dementia risk score. DISCUSSION: Higher perceived stress and lower resilience were associated with poorer cognition and a greater burden of modifiable dementia risk factors. Intervention studies are required to determine if lowering stress and building resilience can mitigate cognitive deficits and reduce dementia risk.

Psychological trajectories in the year after a newly diagnosed seizure.

PURPOSE: Underdiagnosed depression and anxiety are well-recognized issues in chronic epilepsy, but the evolution of these symptoms after diagnosis is not well understood. We aimed to identify mood trajectories after a first seizure, and to examine factors impacting these trajectories. METHODS: Seventy-four patients were evaluated at 1, 3, and 12 months with (1) the Hospital Anxiety and Depression Scale, and (2) a semistructured interview assessing patients' initial psychological reaction to the seizure at 1 month (limited vs. pervasive loss of control). The SAS Institute's TRAJ data modelling procedure was employed to delineate trajectories. KEY FINDINGS: Two depression and three anxiety trajectories were identified, with significant overlap. The majority of patients (≈ 74%) followed a trajectory with low depression throughout the study, and either low or moderate anxiety. A minority followed trajectories with high depression and anxiety from diagnosis (≈ 16%). Patients with high levels of distress were adversely affected by seizure recurrence and antiepileptic drugs (AEDs), whereas those with low levels were not. Trajectories were predicted by the patient's sense of loss of control early after diagnosis and were weakly related to demographic and medical variables (age, gender, education, relationship status, psychiatric history, and prior epileptic events). SIGNIFICANCE: Methods that account for heterogeneity in patient responses are critical for developing a clinically relevant understanding of adjustment after a newly diagnosed seizure. Most patients appear to be resilient in the face of early seizures, whereas those at risk of longer-term psychological difficulties may be evident from diagnosis. Early screening for depression and anxiety is warranted.

Memory Complaints in Healthy Middle-Aged Adults Are Not Associated with Memory or Sustained Attention Performance.

OBJECTIVE: To examine the associations between the number and type of memory complaints with memory and sustained attention performance in healthy middle-aged adults. METHOD: Sixty-six healthy individuals aged 35-64 years (Mage = 47.73 years) were administered the seven Questions, Rey Auditory Verbal Learning Test, Sustained Attention to Response Task, and Depression Anxiety Stress Scales 21. RESULTS: The number of memory complaints was not associated with memory or sustained attention performance but was associated with anxiety symptoms. The type of memory complaint was likewise not associated with memory or sustained attention performance. The complaints "recent change in ability to remember things" and "trouble remembering things from one second to the next" were associated with anxiety symptoms. CONCLUSION: Complaints about memory in otherwise healthy middle-aged adults do not reliably indicate memory or sustained attention performance. Rather, these complaints are more likely to be associated with heightened, but nevertheless subclinical, anxiety.

The Spatial Learning Task of Lhermitte and Signoret (1972): Normative Data in Adults Aged 18-45.

Objective: The Spatial Learning Task of Lhermitte and Signoret is an object-location arbitrary associative learning task. The task was originally developed to evaluate adults with severe amnesia. It is currently used in populations where the memory system either is not yet fully developed or where it has been compromised (e.g. epilepsy, traumatic brain injury, electroconvulsive therapy, cerebrovascular disease and dementia). Normative data have been published for paediatric cohorts and for older adults, however no data exist for the intervening adult years. Method: Here, we address this gap, collecting normative data from 101 adults aged 18-45. Results: Our data indicate that performance on the Spatial Learning Task is not influenced by age, gender, level of education or overall IQ. Less than 10% of the variance in learning scores is associated with variability in verbal memory. Ninety percent of participants achieved perfect scores on two successive trials (T2Cr) within five or fewer trials on the Spatial Learning Task. A T2Cr score of 6 is suggestive of impairment and a T2Cr score of 7 or more is statistically abnormal. Conclusion: These data expand the clinical utility of the Spatial Learning Task in the adult population. Future work should examine performance in lower IQ cohorts, including intellectual disability, and explore sensitivity to disease factors such as laterality of mesial temporal lobe damage.

Novel pharmacological strategies to treat cognitive dysfunction in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a major incurable global health burden and currently the 3rd largest cause of death in the world, with approximately 3.23 million deaths per year. Globally, the financial burden of COPD is approximately €82 billion per year and causes substantial morbidity and mortality. Importantly, much of the disease burden and health care utilisation in COPD is associated with the management of its comorbidities and viral and bacterial-induced acute exacerbations (AECOPD). Recent clinical studies have shown that cognitive dysfunction is present in up to 60% of people with COPD, with impairments in executive function, memory, and attention, impacting on important outcomes such as quality of life, hospitalisation and survival. The high prevalence of cognitive dysfunction in COPD may also help explain the insufficient adherence to therapeutic plans and strategies, thus worsening disease progression in people with COPD. However, the mechanisms underlying the impaired neuropathology and cognition in COPD remain largely unknown. In this review, we propose that the observed pulmonary oxidative burden and inflammatory response of people with COPD 'spills over' into the systemic circulation, resulting in damage to the brain and leading to cognitive dysfunction. As such, drugs targeting the lungs and comorbidities concurrently represent an exciting and unique therapeutic opportunity to treat COPD and cognitive impairments, which may lead to the production of novel targets to prevent and reverse the debilitating and life-threatening effects of cognitive dysfunction in COPD.

Association of Stress with Risk of Dementia and Mild Cognitive Impairment: A Systematic Review and Meta-Analysis.

BACKGROUND: Although many studies have investigated the association between stress and risk of dementia, findings are inconsistent due to the variation in the measures used to assess stress. OBJECTIVE: We conducted a systematic review and meta-analysis to investigate the association between psychological stress (including neuroticism, stressful life events, and perceived stress) and the risk of incident dementia and mild cognitive impairment in adults. METHODS: PsycINFO, Embase, and MEDLINE were searched to October 2020 for eligible observational, prospective studies. Of the 1,607 studies screened, 26 (24 unique cohorts) were included in the qualitative analysis and 16 (15 unique cohorts) were included in the quantitative analysis. RESULTS: Across studies, higher perceived stress was significantly associated with an increased risk of mild cognitive impairment (Cases/Total N = 207/860: hazard ratio [HR] = 1.19, 95% confidence interval [CI] = 1.03-1.38) and all-cause dementia (Cases/Total N = 203/1,882: HR = 1.44, 95% CI = 1.07-1.95). Exposure to two or more stressful life events (versus none) was significantly associated with an increased risk of all-cause dementia (Cases/Total N = 3,354/11,597: HR = 1.72, 95% CI = 1.14-2.60), while one or more stressful life events was not. Higher neuroticism was significantly associated with an increased risk of Alzheimer's disease dementia (Cases/Total N = 497/4,771: HR = 1.07, 95% CI = 1.01-1.12), but not all-cause dementia. CONCLUSION: This review suggests that psychological stress in adulthood is associated with an increased risk of dementia. Further research is needed to clarify the mechanisms underlying these associations.

Verbal memory in mesial temporal lobe epilepsy: beyond material specificity.

The idea that verbal and non-verbal forms of memory are segregated in their entirety, and localized to the left and right hippocampi, is arguably the most influential concept in the neuropsychology of temporal lobe epilepsy, forming a cornerstone of pre-surgical decision making, and a frame for interpreting postoperative outcome. This critical review begins by examining some of the unexpressed but inescapable assumptions of the material-specificity model: (i) verbal and non-verbal memory are unitary and internally homogenous constructs; and (ii) left and right memory systems are assumed to be independent, self-contained modules. The next section traces the origins of an alternative view, emanating largely from three challenges to these assumptions: (i) verbal memory is systematically fractionated by left mesial temporal foci; (ii) the resulting components are differentially localized within the left temporal lobe; and (iii) verbal and non-verbal memory functions are not entirely lateralized. It is argued here that the perirhinal cortex is a key node in a more extensive network mediating protosemantic associative memory. Impairment of this fundamental memory system is a proximal neurocognitive marker of mesial temporal epileptogenesis.

Neuropsychological function in patients with a single gene mutation associated with autosomal dominant nocturnal frontal lobe epilepsy.

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a nonlesional condition associated with mutation of the gene coding for the alpha4 nicotinic acetylcholine receptor (nAChR). The nAChR modulates aspects of memory and attention. We examined the neuropsychological phenotype of ADNFLE, with a particular emphasis on understanding the impact on frontal lobe functions. We used standard clinical tests as well as focused measures of frontal lobe function in a well-defined group of patients with ADNFLE. Their performance was compared with that of a group of age-, sex-, and education-matched control participants. Patients with ADNFLE showed impairments on tasks requiring cognitive flexibility against a background of well-preserved intellectual abilities. In accord with existing research, verbal memory impairments were identified in the patient group; the level of impairment on these tasks correlated with disease-related factors. In our study of ADNFLE associated with one mutation, cognitive flexibility appears to be the core cognitive deficit.

Anterior cingulate cortex abnormalities associated with a first psychotic episode in bipolar disorder.

BACKGROUND: The anterior cingulate cortex is frequently implicated in the pathophysiology of bipolar disorder, but magnetic resonance imaging (MRI) studies have reported variable findings owing to a reliance on patient samples with chronic illness and to limited appreciation of the region's heterogeneity. AIMS: To characterise anterior cingulate cortex abnormalities in patients with bipolar disorder experiencing their first episode of psychosis while accounting for regional anatomical variability. METHOD: Grey matter volume, surface area and cortical thickness were measured in six anterior cingulate cortex subregions per hemisphere using MRI scans acquired from 26 patients with bipolar I disorder experiencing first-episode psychosis and 26 healthy controls matched for age, gender and regional morphological variability. RESULTS: Relative to controls, male patients displayed increased thickness in the right subcallosal limbic anterior cingulate cortex. No significant differences were identified in females for grey matter volume or surface area measures. The findings were not attributable to medication effects. CONCLUSIONS: These data suggest that first-episode psychosis in bipolar disorder is associated with a gender-specific, right-lateralised thickness increase in anterior cingulate cortex subregions known to play a role in regulating physiological stress responses.

Cognitive complaints after a first seizure in adulthood: Influence of psychological adjustment.

PURPOSE: To examine the nature and determinants (biologic and psychological) of cognitive complaints in first-seizure patients. We analyzed this in the context of our previous findings that a sense of loss of control after a newly diagnosed seizure (limited or pervasive) predicts subsequent psychological adjustment trajectories. METHODS: Eighty-five consecutive First Seizure Clinic patients were assessed at 1 and 3 months. Cognitive complaints were evaluated qualitatively, with a semistructured interview, and quantitatively, with the A-B Neuropsychological Assessment Schedule (ABNAS). Objective attentional processing was assessed with reaction time tasks and the Wechsler Adult Intelligence Scale-3rd edition (WAIS-III) Processing Speed Index. Mood was assessed with the Hospital Anxiety and Depression Scale (HADS). Psychological adjustment trajectories were represented by previous classification of patients into limited and pervasive groups, as derived from semistructured interview. RESULTS: Cognitive complaints at 1 and 3 months were strongly associated with mood, and unrelated to objective attentional processing. Psychological adjustment trajectories influenced the longitudinal course of cognitive complaints, and these effects were partially mediated by mood differences between the limited and pervasive groups. The course of cognitive complaints was also altered by commencing antiepileptic drugs. Patients experiencing seizure recurrence reported greater cognitive complaints, even before their seizure recurred. Mediation analyses showed this effect was likely attributable to increased mood disturbance in the seizure recurrence group, and was unrelated to objective attentional processing. DISCUSSION: Understanding cognitive complaints in first-seizure patients requires a longitudinal perspective that takes into account the patients' changing psychological and medical contexts. Patients presenting with extensive cognitive complaints may warrant assessment for mood and adjustment issues.

Neuropsychological and functional MRI studies provide converging evidence of anterior language dysfunction in BECTS.

PURPOSE: Benign childhood epilepsy with centrotemporal spikes (BECTS) is the most common epilepsy syndrome of childhood and can be associated with language difficulties. The exact profile of these difficulties and their neurofunctional underpinnings, however, are not yet clear. METHODS: To further understand the impact of the BECTS syndrome on language, we assessed language performance using standard neuropsychological measures, and patterns of language lateralization using functional magnetic resonance imaging (fMRI) in children with typical BECTS (n = 20) and healthy controls (n = 20). RESULTS: The fMRI analyses revealed that language-related activation was less lateralized to the left hemisphere in anterior brain regions in the patients relative to the control group. This finding was consistent with decreased performance in the BECTS group compared to the control group on the neuropsychological measure most dependent on the integrity of anterior aspects of the language axis, namely, sentence production. DISCUSSION: The converging lines of evidence from the neuropsychological and activation methodologies support the view that BECTS is associated with language difficulties that are regional, and anterior, in nature.