Magnetoencephalography resting-state correlates of executive and language components of verbal fluency.

Verbal fluency (VF) is a heterogeneous cognitive function that requires executive as well as language abilities. The purpose of this study was to elucidate the specificity of the resting state MEG correlates of the executive and language components. To this end, we administered a VF test, another verbal test (Vocabulary), and another executive test (Trail Making Test), and we recorded 5-min eyes-open resting-state MEG data in 28 healthy participants. We used source-reconstructed spectral power estimates to compute correlation/anticorrelation MEG clusters with the performance at each test, as well as with the advantage in performance between tests, across individuals using cluster-level statistics in the standard frequency bands. By obtaining conjunction clusters between verbal fluency scores and factor loading obtained for verbal fluency and each of the two other tests, we showed a core of slow clusters (delta to beta) localized in the right hemisphere, in adjacent parts of the premotor, pre-central and post-central cortex in the mid-lateral regions related to executive monitoring. We also found slow parietal clusters bilaterally and a cluster in the gamma 2 and 3 bands in the left inferior frontal gyrus likely associated with phonological processing involved in verbal fluency.

Inconsistencies between measures of cognitive dysfunction in childhood acute lymphoblastic leukemia survivors: Description and understanding.

OBJECTIVES: The frequency of cognitive difficulties in childhood cancer survivors varies according to the measurement strategy. The goal of this research is to (a) describe agreements and differences between measures of working memory and attention (b) identify contributors of these differences, such as emotional distress, affects, and fatigue. METHODS: We used data available for 138 adults successfully treated for childhood acute lymphoblastic leukemia (ALL) (PETALE cohort). Working memory and attention were assessed using subtests from the WAIS-IV and self-reported questionnaires (BRIEF-SR and CAARS-S:L). Potential contributors included emotional distress, anxiety, depression (BSI-18), affects (PANAS), and fatigue (PedsQL-MFS). We explored measurement agreements and differences using diagnostic indices and multivariate regression models. RESULTS: The frequencies of working memory and attention deficits were higher when using cognitive tests (15%-21%) than with self-reports (10%-11%). Self-reported questionnaires showed high specificity (median 0.87) and low sensitivity (median 0.10), suggesting they did not reliably identify positive cases on cognitive tests. We identified negative affectivity as a possible contributor to inconsistencies between self-report and test results. CONCLUSIONS: When measuring working memory and attention in childhood ALL survivors, cognitive test results and self-reports should not be considered equivalent. At best, self-report may be used for screening (high specificity), but not to assess prevalence in large samples. Self-reported difficulties are also probably influenced by the negative mood in this population.

Visual short-term memory activation patterns in adult survivors of childhood acute lymphoblastic leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Treatments against ALL might lead to later cognitive effects and alterations in brain structure in survivors but to the authors' knowledge the observed variability in the severity of neurocognitive deficits is not fully understood. The objective of the current study was to investigate abnormalities in visual short-term memory (VSTM) brain activation in survivors of childhood ALL using magnetoencephalography. METHODS: A VSTM task was completed by 40 survivors of ALL and 26 controls. VSTM capacity (Cowan K) and brain activation were assessed during the retention period of the task (400-1400 milliseconds) using a standard minimum norm source localization method. RESULTS: Performance (Cowan K) was found to be similar between survivors of ALL and controls. Atypical brain activation was found in survivors of ALL during the task, including overactivation of regions usually involved in VSTM (lateral occipital, precentral gyrus, and postcentral gyrus), recruitment of regions that typically are not involved in VSTM (superior/middle temporal gyrus and supramarginal gyrus), and lower activation of frontal brain regions (inferior frontal gyrus). These patterns of activation were modulated by the age at the time of cancer onset (P = .01) because activity was found to be reduced in participants who were younger at diagnosis. CONCLUSIONS: The results of the current study suggest a pattern of neural inefficiency and compensatory activity during VSTM in survivors of ALL.

Influence of genetic factors on long-term treatment related neurocognitive complications, and on anxiety and depression in survivors of childhood acute lymphoblastic leukemia: The Petale study.

BACKGROUND: A substantial number of survivors of childhood acute lymphoblastic leukemia suffer from treatment-related late adverse effects including neurocognitive impairment. While multiple studies have described neurocognitive outcomes in childhood acute lymphoblastic leukemia (ALL) survivors, relatively few have investigated their association with individual genetic constitution. METHODS: To further address this issue, genetic variants located in 99 genes relevant to the effects of anticancer drugs and in 360 genes implicated in nervous system function and predicted to affect protein function, were pooled from whole exome sequencing data of childhood ALL survivors (PETALE cohort) and analyzed for an association with neurocognitive complications, as well as with anxiety and depression. Variants that sustained correction for multiple testing were genotyped in entire cohort (n = 236) and analyzed with same outcomes. RESULTS: Common variants in MTR, PPARA, ABCC3, CALML5, CACNB2 and PCDHB10 genes were associated with deficits in neurocognitive tests performance, whereas a variant in SLCO1B1 and EPHA5 genes was associated with anxiety and depression. Majority of associations were modulated by intensity of treatment. Associated variants were further analyzed in an independent SJLIFE cohort of 545 ALL survivors. Two variants, rs1805087 in methionine synthase, MTR and rs58225473 in voltage-dependent calcium channel protein encoding gene, CACNB2 are of particular interest, since associations of borderline significance were found in replication cohort and remain significant in combined discovery and replication groups (OR = 1.5, 95% CI, 1-2.3; p = 0.04 and; OR = 3.7, 95% CI, 1.25-11; p = 0.01, respectively). Variant rs4149056 in SLCO1B1 gene also deserves further attention since previously shown to affect methotrexate clearance and short-term toxicity in ALL patients. CONCLUSIONS: Current findings can help understanding of the influence of genetic component on long-term neurocognitive impairment. Further studies are needed to confirm whether identified variants may be useful in identifying survivors at increased risk of these complications.

DIVERGT screening procedure predicts general cognitive functioning in adult long-term survivors of pediatric acute lymphoblastic leukemia: A PETALE study.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Because of major improvements in treatment protocols, the survival rate now exceeds 80%. However, ALL treatments can cause long-term neurocognitive sequelae, which negatively impact academic achievement and quality of life. Therefore, cognitive sequelae need to be carefully evaluated. The DIVERGT is a battery of tests proposed as a screening tool, sensitive to executive function impairments in children and adolescent cancer survivors. Our study aimed at verifying the predictive value of the DIVERGT on general cognitive functioning in adult long-term survivors of ALL. METHODS: ALL survivors completed the DIVERGT 13.4 years, on average, after remission (N = 247). In addition, 49 of these survivors (equally selected amongst those with low, average, and high DIVERGT scores) as well as 29 controls completed a more comprehensive neuropsychological evaluation within a 3-year period from DIVERGT administration. Multivariate regression analysis was used to assess the predictive value of the DIVERGT on general intelligence, mathematics, verbal memory, and working memory. As a follow-up analysis, three performance groups were created based on the DIVERGT results. Multivariate analysis of variance (MANOVA) assessed neuropsychological differences between groups. RESULTS: The DIVERGT accurately predicted General Ability Index (GAI) (P < 0.0001), mathematics (P < 0.0001) and verbal memory (P = 0.045). Moreover, the low-performance group consistently had poorer performance than the high-performance and control groups on the neuropsychological tests. CONCLUSION: The DIVERGT is a useful, time-effective screening battery for broader neurocognitive impairments identification in long-term adult ALL survivors. It could be implemented as routine examination in cancer follow-up clinics.

Spontaneous brain oscillations as neural fingerprints of working memory capacities: A resting-state MEG study.

Short-term storage and mental information manipulation capacities in the human brain are key to healthy cognition. These brain processes collectively known as working memory (WM) are associated with modulations of rhythmic brain activity across multiple brain areas and frequencies. Yet, it is not clear whether - and, if so, how-intrinsic resting-state neuronal oscillations are related to individual WM capacities, as measured by standard neuropsychological tests. We addressed this question by probing the correlation between resting-state brain activity, recorded with magnetoencephalography (MEG), and verbal and visuo-spatial WM indices obtained from the standardized Wechsler Adult Intelligence Scale (WAIS-IV) and the Wechsler Memory Scale (WMS-IV). To this end, 5-min eyes-open resting-state MEG data were acquired in 28 healthy participants. Source-reconstructed spectral power estimates were then computed in standard frequency bands and their correlation with neuropsychological indices across individuals was assessed using Pearson correlation and cluster-level statistics. We found statistically significant positive correlations between spectral amplitudes measured at rest and standardized scores on both verbal and visuo-spatial WM performance. The correlation clusters primarily involved key medial and dorsolateral components within the parietal and prefrontal regions. In addition, while the correlation in some clusters was frequency selective (e.g., alpha-band oscillations), other areas showed correlations with WM across a wide range of frequencies reflecting a broadband effect. These results provide the first evidence for a positive correlation between neuromagnetic signals measured at rest and WM performance separately assessed by standardized neuropsychological tests. Our results advance our understanding of the link between WM capacities and intrinsic oscillatory dynamics networks. They also suggest that individual differences in baseline spectral power might need to be taken into account when probing differences in brain responses during the execution of WM tasks.

Visual short term memory related brain activity predicts mathematical abilities.

OBJECTIVE: Previous research suggests visual short-term memory (VSTM) capacity and mathematical abilities are significantly related. Moreover, both processes activate similar brain regions within the parietal cortex, in particular, the intraparietal sulcus; however, it is still unclear whether the neuronal underpinnings of VSTM directly correlate with mathematical operation and reasoning abilities. The main objective was to investigate the association between parieto-occipital brain activity during the retention period of a VSTM task and performance in mathematics. METHOD: The authors measured mathematical abilities and VSTM capacity as well as brain activity during memory maintenance using magnetoencephalography (MEG) in 19 healthy adult participants. Event-related magnetic fields (ERFs) were computed on the MEG data. Linear regressions were used to estimate the strength of the relation between VSTM related brain activity and mathematical abilities. RESULTS: The amplitude of parieto-occipital cerebral activity during the retention of visual information was related to performance in 2 standardized mathematical tasks: mathematical reasoning and calculation fluency. CONCLUSIONS: The findings show that brain activity during retention period of a VSTM task is associated with mathematical abilities. Contributions of VSTM processes to numerical cognition should be considered in cognitive interventions. (PsycINFO Database Record