Mapping lesion, structural disconnection, and functional disconnection to symptoms in semantic aphasia

Patients with semantic aphasia have impaired control of semantic retrieval, often accompanied by executive dysfunction following left hemisphere stroke. Many but not all of these patients have damage to the left inferior frontal gyrus, important for semantic and cognitive control. Yet semantic and cognitive control networks are highly distributed, including posterior as well as anterior components. Accordingly, semantic aphasia might not only reflect local damage but also white matter structural and functional disconnection. Here we characterise the lesions and predicted patterns of structural and functional disconnection in individuals with semantic aphasia and relate these effects to semantic and executive impairment. Impaired semantic cognition was associated with infarction in distributed left- hemisphere regions, including in the left anterior inferior frontal and posterior temporal cortex. Lesions were associated with executive dysfunction within a set of adjacent but distinct left frontoparietal clusters. Performance on executive tasks was also associated with interhemispheric structural disconnection across the corpus callosum. Poor semantic cognition was associated with small left-lateralized structurally disconnected clusters, including in the left posterior temporal cortex. These results demonstrate that while left- lateralized semantic and executive control regions are often damaged together in stroke aphasia, these deficits are associated with distinct patterns of structural disconnection, consistent with the bilateral nature of executive control and the left-lateralized yet distributed semantic control network.

Efficacy of Online Goal Management Training for Age-Associated Executive Impairment

Goal Management Training® (GMT) is a standardized cognitive rehabilitation program that enhances individuals’ awareness of executive function impairments and trains them to regularly monitor and manage their goals. In-person GMT is well-validated among numerous subpopulations, including people experiencing age-related cognitive impairment or acquired brain injury, and people with psychiatric disorders. The goal of this study was to evaluate the efficacy and usability of online GMT relative to computerized “brain training” in a registered randomized controlled trial (protocol NCT03602768 at Trials.gov). Both interventions were administered in a self-paced format, with background therapist support provided for GMT. Primary outcomes were measured as self-reported executive impairment on standardized measures (the Dysexecutive Questionnaire and the Cognitive Failures Questionnaire) at pre-, immediate post-, and 6 weeks post-intervention. 62 older adults without psychiatric or neurological diagnoses completed the trial (online GMT: n = 37, age[mean] = 69 years; computerized brain training: n = 25, age[mean] = 64 years; both groups: 76% female). Improvements on the primary outcomes were observed post-intervention and were maintained at follow-up. GMT and computerized brain training groups could not be differentiated statistically, possibly due to restriction of range in the outcome measures at baseline. Additionally, the self-paced format prolonged the intervention beyond the recommended duration, which may have diluted efficacy. GMT was well-received, with participants reporting frequent use of the trained metacognitive strategies. Future studies will examine online GMT’s effectiveness in samples with documented executive impairment and with additional supports to promote engagement for this virtual program.

Brain correlates of impaired goal management in bipolar mania

Background Although executive impairment has been reported in mania, its brain functional correlates have been relatively little studied. This study examined goal management, believed to be more closely related to executive impairment in daily life than other executive tasks, using a novel functional magnetic resonance imaging (fMRI) paradigm in patients in this illness phase. Methods Twenty-one currently manic patients with bipolar disorder and 30 matched healthy controls were scanned while performing the Computerized Multiple Elements Test (CMET). This requires participants to sequentially play four simple games, with transition between games being made either voluntarily (executive condition) or automatically (control condition). Results CMET performance was impaired in the manic patients compared to the healthy controls. Manic patients failed to increase activation in the lateral frontal, cingulate and inferior parietal cortex when the executive demands of the task increased, while this increase was observed in the healthy controls. Activity in these regions was associated with task performance. Conclusions Manic patients show evidence of impaired goal management, which is associated with a pattern of reduced medial and lateral frontal and parietal activity.

Design Fluency in Children with ADHD and Comorbid Disorders

Background: Attention deficit/hyperactivity disorder (ADHD) is often associated with frontal executive impairment in children. Oppositional defiant disorder (ODD) and anxiety disorders (AD) frequently accompany ADHD, but the impact of these comorbid disorders on cognition remains elusive. The five-point test (FPT), a design fluency task, has been shown to be sensitive to neurological damage, specifically to frontal lobe lesions in patients with brain injuries. The purpose of this study was to compare the performances of neurotypical children with that of children with ADHD, ADHD-ODD, and ADHD-AD on the FPT in order to examine whether these groups could be distinguished from one another based on their cognitive profile. Methods: A total of 111 children aged 8 to 11 years old participated in the study. Six measures from the FPT were used to characterize their performance. Results: Statistically significant differences between groups were observed for five of the six FPT measures. Essentially, children with ADHD-ODD made more repeated designs than the three other groups (control p > 0.001, ADHD p = 0.008, ADHD-AD p = 0.008), while children with ADHD-AD produced fewer total and correct designs than the control and ADHD groups (p = 0.009). Conclusions: This suggests that comorbidities have an additive impact on the cognitive profile of children with ADHD. Design fluency may be a sensitive measure for capturing the subtle cognitive deficits that are likely to be involved in these disorders.

Study investigating executive function in schizophrenia patients and their unaffected siblings

Background: Schizophrenia (SCZ) is a serious genetic mental illness. Most research indicates that executive impairment has a certain genetic predisposition. The shared neuropathological characteristics of patients with schizophrenia and their siblings might reveal intermediate phenotypes in behavior that could be used to further characterize the illness. Methods: Our study involved 32 schizophrenia patients, 32 unaffected siblings,and 33 healthy controls. The three groups underwent a computerized version of the Wisconsin Card Sorting Test (WCST) and a battery of cognitive neuropsychological assessments. These tests evaluated executive function and several cognitive domains. Results: In this study, the WCST results demonstrate that the total correct (TC), total error (TE), perseverative response (PR) and perseverative error (PE) scores in the SZ group were significantly lower than those in the HC group (TC (p=0.011), TE (p<0.001), PR (p=0.007) and PE (p=0.002)), and compared to the unaffected siblings, we found significant differences in TE (p=0.003). Moreover, significant differences were observed between the unaffected siblings and healthy controls as follows: TC (p=0.034), TE (p=0.008), PR (p=0.016) and PE (p=0.013). Conclusion: The schizophrenia patients and their siblings performed worse in the WCST test than the healthy controls. This result supports the claim that the development of functional impairment is not unique to schizophrenia patients and that unaffected siblings may have a certain level of abnormal brain function.Neurological abnormalities lead to abnormal functioning in siblings and patients,suggesting that genetics plays a considerable role in such results.

Neuropsychological Profile of Children with Early and Continuously Treated Phenylketonuria: Systematic Review and Future Approaches

Objective: To provide a comprehensive systematic review of the literature by examining studies published on all cognitive aspects of children with early and continuously treated phenylketonuria (ECT-PKU) included in the databases Medline, PsycINFO, and PsycARTICLE. Method: In addition to a classical approach, we summarized methodology and results of each study in order to discuss current theoretical and methodological issues. We also examined recent advances in biochemical markers and treatments of PKU, with implications for future research on metabolic control and its role as a determinant of neuropsychological outcome. Results: Consistent with previous reviews, the hypothesis of a specific and central executive impairment in children with ECT-PKU was suggested. However, findings are inconclusive regarding the nature of executive impairments as well as their specificity, impact on everyday life, persistence over time, and etiology. Conclusion: Given the current state of the science, we suggest future directions for research that utilizes a developmental and integrative approach to examine the effects of recent advances in biochemical markers and treatment of PKU. (JINS, 2019, 25, 624–643)