Cortical thickness changes after computerized working memory training in patients with mild cognitive impairment

Background: Adaptive computerized working memory (WM) training has shown favorable effects on cerebral cortical thickness as compared to non-adaptive training in healthy individuals. However, knowledge of WM training-related morphological changes in mild cognitive impairment (MCI) is limited. Objective: The primary objective of this double-blind randomized study was to investigate differences in longitudinal cortical thickness trajectories after adaptive and non-adaptive WM training in patients with MCI. We also investigated the genotype effects on cortical thickness trajectories after WM training combining these two training groups using longitudinal structural magnetic resonance imaging (MRI) analysis in Freesurfer. Method: Magnetic resonance imaging acquisition at 1.5 T were performed at baseline, and after four- and 16-weeks post training. A total of 81 individuals with MCI accepted invitations to undergo 25 training sessions over 5 weeks. Longitudinal Linear Mixed effect models investigated the effect of adaptive vs. non-adaptive WM training. The LME model was fitted for each location (vertex). On all statistical analyzes, a threshold was applied to yield an expected false discovery rate (FDR) of 5%. A secondary LME model investigated the effects of LMX1A and APOE-ε4 on cortical thickness trajectories after WM training. Results: A total of 62 participants/patients completed the 25 training sessions. Structural MRI showed no group difference between the two training regimes in our MCI patients, contrary to previous reports in cognitively healthy adults. No significant structural cortical changes were found after training, regardless of training type, across all participants. However, LMX1A-AA carriers displayed increased cortical thickness trajectories or lack of decrease in two regions post-training compared to those with LMX1A-GG/GA. No training or training type effects were found in relation to the APOE-ε4 gene variants. Conclusion: The MCI patients in our study, did not have improved cortical thickness after WM training with either adaptive or non-adaptive training. These results were derived from a heterogeneous population of MCI participants. The lack of changes in the cortical thickness trajectory after WM training may also suggest the lack of atrophy during this follow-up period. Our promising results of increased cortical thickness trajectory, suggesting greater neuroplasticity, in those with LMX1A-AA genotype need to be validated in future trials.publishedVersio

Assessment of cognitive function, structural brain changes and fatigue 6 months after treatment of neuroborreliosis

publishedVersionPaid Open Acces

Adaptive Computerized Working Memory Training in Patients With Mild Cognitive Impairment. A Randomized Double-Blind Active Controlled Trial

ObjectiveWe investigated if a 5-week computerized adaptive working memory training program (Cogmed®) of 20 to 25 sessions would be effective in improving the working memory capacity and other neuropsychological functions compared to a non-adaptive working memory training program (active-controlled) in adult patients with mild cognitive impairment (MCI).MethodsThis randomized double-blinded active control trial included 68 individuals aged 43 to 88 years, 45 men and 23 women, who were diagnosed with MCI at four Memory clinics. The study sample was randomized by block randomization to either adaptive or non-adaptive computerized working memory training. All participants completed the training, and were assessed with a comprehensive neuropsychological test battery before the intervention, and at 1 and 4 months after training.ResultsCompared to the non-adaptive training group, the adaptive training group did not show significantly greater improvement on the main outcome of working memory performance at 1 and 4 months after training.ConclusionNo difference were found between the two types of training on the primary outcome of working memory, or on secondary outcomes of cognitive function domains, in this sample of MCI patients. Hence, the hypothesis that the adaptive training program would lead to greater improvements compared to the non-adaptive training program was not supported. Within group analyses was not performed due to the stringent RCT design

Cognitive Profiles and Atrophy Ratings on MRI in Senior Patients With Mild Cognitive Impairment

In this cross-sectional study, we sought to describe cognitive and neuroimaging profiles of Memory clinic patients with Mild Cognitive Impairment (MCI). 51 MCI patients and 51 controls, matched on age, sex, and socio-economic status (SES), were assessed with an extensive neuropsychological test battery that included a measure of intelligence (General Ability Index, “GAI,” from WAIS-IV), and structural magnetic resonance imaging (MRI). MCI subtypes were determined after inclusion, and z-scores normalized to our control group were generated for each cognitive domain in each MCI participant. MR-images were scored by visual rating scales. MCI patients performed significantly worse than controls on 23 of 31 cognitive measures (Bonferroni corrected p = 0.001), and on 8 of 31 measures after covarying for intelligence (GAI). Compared to nonamnestic MCI patients, amnestic MCI patients had lower test results in 13 of 31 measures, and 5 of 31 measures after co-varying for GAI. Compared to controls, the MCI patients had greater atrophy on Schelten's Medial temporal lobe atrophy score (MTA), especially in those with amnestic MCI. The only structure-function correlation that remained significant after correction for multiple comparisons was the MTA—long delay recall domain. Intelligence operationalized as GAI appears to be an important moderator of the neuropsychological outcomes. Atrophy of the medial temporal lobe, based on MTA scores, may be a sensitive biomarker for the functional episodic memory deficits associated with MCI

Trajectories of brain development in school-age children born preterm with very low birth weight

Preterm birth (gestational age < 37 weeks) with very low birth weight (VLBW, birth weight ≤ 1500 g) is associated with lifelong cognitive deficits, including in executive function, and persistent alterations in cortical and subcortical structures. However, it remains unclear whether “catch-up” growth is possible in the preterm/VLBW brain. Longitudinal structural MRI was conducted with children born preterm with VLBW (n = 41) and term-born peers participating in the Norwegian Mother and Child Cohort Study (MoBa) (n = 128) at two timepoints in early school age (mean ages 8.0 and 9.3 years). Images were analyzed with the FreeSurfer 5.3.0 longitudinal stream to assess differences in development of cortical thickness, surface area, and brain structure volumes, as well as associations with executive function development (NEPSY Statue and WMS-III Spatial Span scores) and perinatal health markers. No longitudinal group × time effects in cortical thickness, surface area, or subcortical volumes were seen, indicating similar brain growth trajectories in the groups over an approximately 16-month period in middle childhood. Higher IQ scores within the VLBW group were associated with greater surface area in left parieto-occipital and inferior temporal regions. Among VLBW preterm-born children, cortical surface area was smaller across the cortical mantle, and cortical thickness was thicker occipitally and frontally and thinner in lateral parietal and posterior temporal areas. Smaller volumes of corpus callosum, right globus pallidus, and right thalamus persisted in the VLBW group from timepoint 1 to 2. VLBW children had on average IQ 1 SD below term-born MoBa peers and significantly worse scores on WMS-III Spatial Span. Executive function scores did not show differential associations with morphometry between groups cross-sectionally or longitudinally. This study investigated divergent or “catch-up” growth in terms of cortical thickness, surface area, and volumes of subcortical gray matter structures and corpus callosum in children born preterm/VLBW and did not find group × time interactions. Greater surface area at mean age 9.3 in left parieto-occipital and inferior temporal cortex was associated with higher IQ in the VLBW group. These results suggest that preterm VLBW children may have altered cognitive networks, yet have structural growth trajectories that appear generally similar to their term-born peers in this early school age window.publishedVersion© The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/

Joint Analysis of Cortical Area and Thickness as a Replacement for the Analysis of the Volume of the Cerebral Cortex

Cortical surface area is an increasingly used brain morphology metric that is ontogenetically and phylogenetically distinct from cortical thickness and offers a separate index of neurodevelopment and disease. However, the various existing methods for assessment of cortical surface area from magnetic resonance images have never been systematically compared. We show that the surface area method implemented in FreeSurfer corresponds closely to the exact, but computationally more demanding, mass-conservative (pycnophylactic) method, provided that images are smoothed. Thus, the data produced by this method can be interpreted as estimates of cortical surface area, as opposed to areal expansion. In addition, focusing on the joint analysis of thickness and area, we compare an improved, analytic method for measuring cortical volume to a permutation-based nonparametric combination (NPC) method. We use the methods to analyze area, thickness and volume in young adults born preterm with very low birth weight, and show that NPC analysis is a more sensitive option for studying joint effects on area and thickness, giving equal weight to variation in both of these 2 morphological features

A longitudinal study of associations between psychiatric symptoms and disorders and cerebral gray matter volumes in adolescents born very preterm

Background:Being born preterm with very low birthweight (VLBW≤1500 g) poses a risk for cortical andsubcortical gray matter (GM) abnormalities, as well as for having more psychiatric problems during childhood andadolescence than term-born individuals. The aim of this study was to investigate the relationship between corticaland subcortical GM volumes and the course of psychiatric disorders during adolescence in VLBW individuals.Methods:We followed VLBW individuals and term-born controls (birth weight≥10th percentile) from 15 (VLBW;controlsn=40;56)to19(n= 44;60) years of age. Of these, 30;37 individuals were examined longitudinally. Cortical andsubcortical GM volumes were extracted from MRPRAGE images obtained with the same 1.5 T MRI scanner at both timepoints and analyzed at each time point with the longitudinal stream of the FreeSurfer software package 5.3.0. Allparticipants underwent clinical interviews and were assessed for psychiatric symptoms and diagnosis (Schedule forAffective Disorders and Schizophrenia for School-age Children, Children’s Global Assessment Scale, Attention-Deficit/Hyperactivity Disorder Rating Scale-IV). VLBW adolescents were divided into two groups according to diagnostic statusfrom 15 to 19 years of age: persisting/developing psychiatric diagnosis or healthy/becoming healthy.Results:Reduction in subcortical GM volume at 15 and 19 years, not including the thalamus, was limited to VLBWadolescents with persisting/developing diagnosis during adolescence, whereas VLBW adolescents in the healthy/becoming healthy group had similar subcortical GM volumes to controls. Moreover, across the entire VLBW group,poorer psychosocial functioning was predicted by smaller subcortical GM volumes at both time points and withreduced GM volume in the thalamus and the parietal and occipital cortex at 15 years. Inattention problems werepredicted by smaller GM volumes in the parietal and occipital cortex.Conclusions:GM volume reductions in the parietal and occipital cortex as well as smaller thalamic and subcortical GMvolumes were associated with the higher rates of psychiatric symptoms found across the entire VLBW group.Significantly smaller subcortical GM volumes in VLBW individuals compared with term-born peers might pose a risk fordeveloping and maintaining psychiatric diagnoses during adolescence. Future research should explore the possiblerole of reduced cortical and subcortical GM volumes in the pathogenesis of psychiatric illness in VLBW adolescents

Relationship between hippocampal subfield volumes and memory function in adults born preterm with very low birth weight (VLBW)

Background:Being born preterm with very low birth weight (VLBW) is related to aberrant brain development. Hippocampus is a brain region particularly vulnerable to injury, for instance from consequences following preterm birth. The hippocampus is a complex structure with distinct subfields related to specific memory functions which are differently affected by neuropathological conditions. The relationship between deviations in hippocampal subfields and memory function has not been studied in adults born preterm with VLBW previously. Aims: In this long-term follow-up study of a geographically based cohort (birth years 1986-88) of VLBW individuals and term born controls with normal birth weight, the main aim was to examine group differences in memory function and hippocampal volumes at age 26 years. We also explored hippocampal structurefunction relationships in the VLBW group. Methods: Fifty-two VLBW and 82 control individuals aged 26 years were examined clinically of whom 44 VLBW and 70 controls had high-quality structural cerebral MRI at 3T. The participants were assessed with subtests from Wechsler Memory Scale and Cambridge Neuropsychological Test Automated Battery on verbal, visual and working memory. From the T1 weighted 3D images, hippocampal subfield volumes were estimated in FreeSurfer 6.0. In addition to group comparisons, partial correlations were performed in the VLBW group between hippocampal subfields’ volumes and neonatal risk factors, and between reduced hippocampal subfields’ volumes and performance on the memory tests. Results: Adults with VLBW had lower verbal, visual and working memory scores compared with term born control adults. Absolute hippocampal total and most subfield volumes were smaller in the VLBW group than in the control group, but with different findings in men and women. When adjusting for intracranial volume, left and right cornu ammonis fields and left dentate gyrus were smaller in VLBW women, while the right subiculum was smaller in VLBW men compared with control women and men, respectively. There was a negative correlation between days on mechanical ventilation and volume of the left subiculum in the VLBW group. Smaller left dentate gyrus volume was associated with lower visual memory performance in the VLBW group. Conclusions: Adults born preterm with VLBW had lower performance on memory tests and smaller hippocampi compared with term born controls, and volume of dentate gyrus was associated with visual memory. Hippocampal subfield volumes seem to be differently affected following preterm birth in VLBW men and women