Longitudinal data on cortical thickness before and after working memory training

The data and supplementary information provided in this article relate to our research article “Task complexity and location specific changes of cortical thickness in executive and salience networks after working memory training.” [1]. We provide cortical thickness and subcortical volume data derived from parieto-frontal cortical regions and the basal ganglia with the FreeSurfer longitudinal analyses stream (http://surfer.nmr.mgh.harvard.edu [2]) before and after working memory training, “Cogmed and Cogmed Working Memory Training” [3]. This article also provides supplementary information to the research article, i.e., within-group comparisons between baseline and outcome cortical thickness and subcortical volume measures, between-group tests of performance changes in cognitive benchmark tests (www.cambridgebrainsciences.com[4]), correlation analyses between performance changes in benchmark tests and training-related structural changes, correlation analyses between the time spent training and structural changes, a scatterplot of the relationship between cortical thickness measures derived from the occipital lobe as control region and the chronological order of the MRI sessions to assess potential scanner drift effects and a post-hoc vertex-wise whole brain analysis with FreeSurfer Qdec (https://surfer.nmr.mgh.harvard.edu/fswiki/Qdec [5])

Connectivity differences between Gulf War Illness (GWI) phenotypes during a test of attention

One quarter of veterans returning from the 1990–1991 Persian Gulf War have developed Gulf War Illness (GWI) with chronic pain, fatigue, cognitive and gastrointestinal dysfunction. Exertion leads to characteristic, delayed onset exacerbations that are not relieved by sleep. We have modeled exertional exhaustion by comparing magnetic resonance images from before and after submaximal exercise. One third of the 27 GWI participants had brain stem atrophy and developed postural tachycardia after exercise (START: Stress Test Activated Reversible Tachycardia). The remainder activated basal ganglia and anterior insulae during a cognitive task (STOPP: Stress Test Originated Phantom Perception). Here, the role of attention in cognitive dysfunction was assessed by seed region correlations during a simple 0-back stimulus matching task (“see a letter, push a button”) performed before exercise. Analysis was analogous to resting state, but different from psychophysiological interactions (PPI). The patterns of correlations between nodes in task and default networks were significantly different for START (n = 9), STOPP (n = 18) and control (n = 8) subjects. Edges shared by the 3 groups may represent co-activation caused by the 0-back task. Controls had a task network of right dorsolateral and left ventrolateral prefrontal cortex, dorsal anterior cingulate cortex, posterior insulae and frontal eye fields (dorsal attention network). START had a large task module centered on the dorsal anterior cingulate cortex with direct links to basal ganglia, anterior insulae, and right dorsolateral prefrontal cortex nodes, and through dorsal attention network (intraparietal sulci and frontal eye fields) nodes to a default module. STOPP had 2 task submodules of basal ganglia–anterior insulae, and dorsolateral prefrontal executive control regions. Dorsal attention and posterior insulae nodes were embedded in the default module and were distant from the task networks. These three unique connectivity patterns during an attention task support the concept of Gulf War Disease with recognizable, objective patterns of cognitive dysfunction

Analyzing structural and functional brain changes related to an integrative cognitive remediation program for schizophrenia: A randomized controlled trial

Cognitive remediation has been shown to improve cognition in schizophrenia, but little is known about the specific functional and structural brain changes related to the implementation of an integrative cognitive remediation program. This study analyzed the functional and structural brain changes identified after implementing an integrative cognitive remediation program, REHACOP, in schizophrenia. The program combined cognitive remediation, social cognitive training, and functional and social skills training. The sample included 59 patients that were assigned to either the REHACOP group or an active control group for 20 weeks. In addition to a clinical and neuropsychological assessment, T1-weighted, diffusion-weighted and functional magnetic resonance images were acquired during a resting-state and during a memory paradigm, both at baseline and follow-up. Voxel-based morphometry, tract-based spatial statistics, resting-state functional connectivity, and brain activation analyses during the memory paradigm were performed. Brain changes were assessed with a 2 × 2 repeated-measure analysis of covariance for group x time interaction. Intragroup paired t-tests were also carried out. Repeated-measure analyses revealed improvements in cognition and functional outcome, but no significant brain changes associated with the integrative cognitive remediation program. Intragroup analyses showed greater gray matter volume and cortical thickness in right temporal regions at post-treatment in the REHACOP group. The absence of significant brain-level results associated with cognitive remediation may be partly due to the small sample size, which limited the statistical power of the study. Therefore, further research is needed to clarify whether the temporal lobe may be a key area involved in cognitive improvements following cognitive remediation.This study has been supported by the Carlos III Health Institute of the Spanish Ministry of Economy and Competitiveness (PI16/01022) and the Department of Education and Science of the Basque Government (Team A; IT946-16). AS was supported by a Fellowship from the Fundación Tatiana Pérez de Guzmán el Bueno. MTE was supported by a Fellowship from University of the Basque Country (UPV/EHU; PIF 19/40). The funding agencies had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript

Individual Differences In Value-Based Decision-Making: Learning And Time Preference

Human decisions are strongly influenced by past experience or by the subjective values attributed to available choice options. Although decision processes show some common trends across individuals, they also vary considerably between individuals. The research presented in this dissertation focuses on two domains of decision-making, related to learning and time preference, and examines factors that explain decision-making differences between individuals. First, we focus on a form of reinforcement learning in a dynamic environment. Across three experiments, we investigated whether individual differences in learning were associated with differences in cognitive abilities, personality, and age. Participants made sequential predictions about an on-screen location in a video game. Consistent with previous work, participants showed high variability in their ability to implement normative strategies related to surprise and uncertainty. We found that higher cognitive ability, but not personality, was associated with stronger reliance on the normative factors that should govern learning. Furthermore, learning in older adults (age 60+) was less influenced by uncertainty, but also less influenced by reward, a non-normative factor that has substantial effects on learning across the lifespan. Second, we focus on delay discounting, the tendency to prefer smaller rewards delivered soon over larger rewards delivered after a delay. Delay discounting has been used as a behavioral measure of impulsivity and is associated with many undesirable real-life outcomes. Specifically, we examined how neuroanatomy is associated with individual differences in delay discounting in a large adolescent sample. Using a novel multivariate method, we identified networks where cortical thickness varied consistently across individuals and brain regions. Cortical thickness in several of these networks, including regions such as ventromedial prefrontal cortex, orbitofrontal cortex, and temporal pole, was negatively associated with delay discounting. Furthermore, this brain data predicted differences beyond those typically accounted for by other cognitive variables related to delay discounting. These results suggest that cortical thickness may be a useful brain phenotype of delay discounting and carry unique information about impulsivity. Collectively, this research furthers our understanding of how cognitive abilities, brain structure and healthy aging relate to individual differences in value-based decision-making

Morphometric reorganization induced by working memory training: perspective from vertex and network levels

Der sich beschleunigende globale Alterungsprozess und die Tatsache, dass sich die kog-nitiven Fähigkeiten mit dem Alter verschlechtern, was sich erheblich auf die Lebensquali-tät älterer Erwachsener auswirkt, insbesondere bei altersbedingten Störungen (z. B. kogni-tiver Beeinträchtigung, Demenz), weisen auf einen dringenden Bedarf an Ansätzen zum Schutz und zur Verbesserung der kognitiven Fähigkeiten sowie an Untersuchungen der neuronalen Substrate altersbedingter Veränderungen und der Neuroplastizität hin. Da man davon ausgeht, dass das Arbeitsgedächtnis (WM) die grundlegende Ursache für altersbe-dingte kognitive Beeinträchtigungen bei einer Vielzahl von kognitiven Fähigkeiten dar-stellt, ist das Arbeitsgedächtnistraining (WMT) zu einem aktuellen Thema und einem be-liebten Ansatz geworden. Frühere Studien haben gezeigt, dass das Arbeitsgedächtnistrai-ning (WMT) die kognitive Leistung verbessert. Die spezifischen Auswirkungen sowie die zugrunde liegenden neurobiologischen Mechanismen sind jedoch nach wie vor um-stritten. Ziel dieser Arbeit ist es, die durch das WMT induzierte neuronale strukturelle Plastizität auf mehreren Ebenen sowie die Verhaltenseffekte des WMT zu untersuchen. In der ers-ten Studie untersuchten wir die topographischen Veränderungen der Morphologie der grauen Substanz durch WMT, indem wir vier strukturelle Metriken (d.h. die kortikale Dicke, das kortikale Volumen, die kortikale Oberfläche und den lokalen Gyrifikationsin-dex, LGI) sowie die subkortikalen Volumina explorierten. Konkret wurden 59 gesunde Probanden mittleren Alters nach dem Zufallsprinzip entweder einem adaptiven WMT oder einer nicht-adaptiven Intervention zugewiesen. Alle Teilnehmer unterzogen sich vor und nach der 8-wöchigen WMT-Phase einer Neurobildgebung sowie kognitiven Tests. Vor und nach dem WMT wurden vier kortikale Metriken auf Scheitelpunktniveau und sieben subkortikale Volumina sowie die globale mittlere kortikale Dicke berechnet. Das wich-tigste Ergebnis war, dass die WMT-Gruppe im Vergleich zur aktiven Kontrollgruppe eine größere Zunahme der kortikalen Faltung in den bilateralen parietalen Regionen zeigte. Die Ergebnisse deuten darauf hin, dass strukturelle Veränderungen durch WMT in WM-bezogenen Regionen, insbesondere in parietalen Regionen, die Verarbeitung einer höhe-ren WM-Belastung erleichtern können. Darüber hinaus könnte die kortikale Faltung das relevanteste und plastischste Merkmal von WM und Lernen sein und WMT-Effekte stär-ker widerspiegeln als andere Metriken. Basierend auf den Ergebnissen der ersten Studie haben wir darüber hinaus untersucht, ob die trainingsinduzierten Effekte des WMT in der kortikalen Faltung auf Vertex-Ebene von topologischen Veränderungen begleitet werden. Zu diesem Zweck untersuchten wir in Studie zwei die durch WMT verursachte Plastizität auf Netzwerkebene mit Hilfe eines strukturellen Kovarianzansatzes (SC), der auf denselben Stichproben basiert. Es wurden gyrifikationsbasierte SC-Matrizen für jede Gruppe vor und nach dem Training sowie lon-gitudinale gyrifikationsbasierte SC-Matrizen erstellt. Innerhalb jeder Gruppe ergab die LGI-basierte SC-Analyse keine Hinweise auf WMT-induzierte Veränderungen der kor-tiko-kortikalen Verbindungen, weder in der WMT- noch in der aktiven Kontrollgruppe. Die Ergebnisse der longitudinalen SC-Analyse (unkorrigiert p < 0,005) zeigten, dass die trainingsinduzierten Veränderungen der kortikalen Faltungsintensität signifikante Unter-schiede zwischen Paaren von parietalen Regionen sowie Paaren von frontalen Regionen aufwiesen. Insgesamt deuten die kombinierten Ergebnisse dieser beiden Studien darauf hin, dass ers-tens WMT neuronale strukturelle Plastizität hervorrufen kann; zweitens die kortikale Fal-tung das relevanteste und plastischste Merkmal von WM und Lernen sein könnte, das die Auswirkungen von WMT besser widerspiegelt als andere Indikatoren auf Vertex-Ebene; und drittens die trainingsinduzierten lokalisierten Veränderungen der kortikalen Faltung von einem ähnlichen Muster vergleichbarer struktureller Veränderungen zwischen ROIs innerhalb der Regionen begleitet wurden. In Zukunft sind weitere Forschungen erforder-lich, um diese Ergebnisse zu wiederholen und zu validieren sowie um trainingsinduzierte topologische und topografische Veränderungen anhand einer breiteren Palette von Metri-ken und Eigenschaften zu untersuchen.The accelerating global aging process and the fact that cognitive abilities deteriorate with age, which has a significant impact on the quality of life of older adults, particularly those with age-related disorders (e.g., cognitive impairment, dementia), all point to an urgent need for approaches to protect and enhance cognitive abilities, as well as studies of the neural substrates of aging-related changes and neuroplasticity. Since working memory (WM) has been assumed to be the fundamental source of age-related cognitive impair-ments in a variety of cognitive abilities, working memory training (WMT) has become a hot topic as well as a popular approach. Previous studies have established that working memory training (WMT) improves cognitive performance. However, the specific effects, as well as the underlying neurobiological mechanisms, remain a matter of controversy. The purpose of this thesis is to investigate WMT-induced neural structural plasticity at multiple levels together with the behavioral effects of WMT. In study one, we investigated the topographic changes of grey matter morphology due to WMT by combining four structural metrics (i.e., cortical thickness (CT), cortical volume (CV), cortical surface area (CSA), and local gyrification index (LGI)) as well as subcortical volumes. Specifically, 59 healthy volunteers between the ages of 50 and 65 were randomly assigned to either an adaptive or a non-adaptive intervention. All participants underwent neuroimaging as well as cognitive testing before and after the 8-week intervention. Four cortical metrics at ver-tex level and seven subcortical volumes, as well as global mean cortical thickness, were calculated before and after the intervention. The most important finding was that the adap-tive WMT group showed greater increases in cortical folding in bilateral parietal regions in comparison to the active control group who performed the non-adaptive intervention. The results indicate that structural changes due to adaptive WMT in WM related regions, particularly parietal regions, may facilitate the processing of a higher WM load. In addi-tion, the cortical folding might be the most relevant and plastic feature of WM and learn-ing, reflecting WMT effects more than other metrics. Based on the findings of study one, we further asked whether the training-induced effects of WMT in cortical folding at vertex-level are accompanied by topological changes. To this end, study two investigated network-level plasticity due to WMT by using the struc-tural covariance (SC) approach based on the same samples. Gyrification based SC matri-ces for each group before and after training, together with longitudinal gyrification SC matrices, were constructed. Within each group, the LGI-based SC analysis revealed no evidence of WMT-induced changes in cortical-cortical connections, either in the WMT or the active control groups. The results of the longitudinal SC analysis (uncorrected p < 0.005) revealed that the training induced changes of cortical folding intensity showed sig-nificant difference between pairs of parietal regions as well as pairs of frontal regions. Overall, the combined findings of these two studies indicate that: firstly, WMT can pro-duce neural structural plasticity; secondly, cortical folding might be the most relevant and plastic feature of WM and learning, better reflecting the effects of WMT than other vertex-level indicators; and thirdly, the training induced localized changes in cortical folding were accompanied by the pattern of similar structural changes between ROIs within the regions. In the future, more research is required to replicate and validate these findings, as well as to investigate training-induced topological and topographic changes using a broader set of metrics and properties

Role of brain imaging in disorders of brain-gut interaction: a Rome Working Team Report.

Imaging of the living human brain is a powerful tool to probe the interactions between brain, gut and microbiome in health and in disorders of brain-gut interactions, in particular IBS. While altered signals from the viscera contribute to clinical symptoms, the brain integrates these interoceptive signals with emotional, cognitive and memory related inputs in a non-linear fashion to produce symptoms. Tremendous progress has occurred in the development of new imaging techniques that look at structural, functional and metabolic properties of brain regions and networks. Standardisation in image acquisition and advances in computational approaches has made it possible to study large data sets of imaging studies, identify network properties and integrate them with non-imaging data. These approaches are beginning to generate brain signatures in IBS that share some features with those obtained in other often overlapping chronic pain disorders such as urological pelvic pain syndromes and vulvodynia, suggesting shared mechanisms. Despite this progress, the identification of preclinical vulnerability factors and outcome predictors has been slow. To overcome current obstacles, the creation of consortia and the generation of standardised multisite repositories for brain imaging and metadata from multisite studies are required

Neurobiological mechanisms of hallucinations in schizophrenia

All perception is a construct of the brain. Yet occasionally, sensory constructions emerge without origin in the physical world and are experienced as hallucinations. Hallucinations occur transdiagnostically, cross-culturally, and in all sensory modalities. They are common in people with schizophrenia, presenting in 60-80% of patients. Despite over 20 years of active neuroimaging research on hallucinations, the neural systems supporting these anomalous perceptual experiences remain disputed. This dissertation investigates the neurobiology of hallucinations, integrating research across structural and functional magnetic resonance imaging (MRI) to elucidate how hallucinations, chiefly in the context of schizophrenia, are supported by the brain, drawing on MRI indices of neurodevelopment. I introduce the phenomenon of hallucinations and motivate the utility of MRI for studying hallucinations. Considering their prevalence in other medical conditions, I conduct a meta-analysis and systematic review of the structural brain basis of hallucinations across diagnoses, primarily schizophrenia spectrum disorders and Parkinson’s disease. This illustrated distinct neuroanatomical organizations of grey matter associated with hallucinations that occur in neurodevelopmental compared to neurodegenerative disorders, which I hypothesise constitute at least two distinct mechanisms. Focussing on the neurodevelopmental mechanism characterized by fronto-temporal and insular grey matter reductions, I turn to the contribution of cortical sulcation, a product of second and third trimester neurodevelopmental processes, which has been robustly implicated in schizophrenia pathology, and, more recently, in hallucinations. Sulcal patterns derived from structural MRI provide a proxy in adulthood for early brain development. I studied two independent datasets of patients with schizophrenia who underwent clinical assessment and 3T MRI from the United Kingdom and Shanghai, China, stratified into those with and without hallucinations, and healthy controls from Shanghai. I first replicate the finding that left hemisphere paracingulate sulcus (PCS) length is reduced in patients who experience hallucinations, then demonstrate similar associations for superior temporal sulcus depth. Length and depth alterations occurred with focal deviations in sulcal geometry. The interindividual and interhemispheric variability of the PCS necessitated the development of semi-automated methods to characterize its morphology and validation to a manual protocol. I used structural covariance networks of the local gyrification index to investigate how specific sulcal deviations relate to global neurodevelopmental coordination, demonstrating that hallucinations correspond to increased covariance within and between salience and auditory networks. Hypothesizing structure-function relationships, I analyse resting-state functional MRI data from the same datasets described, finding significant interactions between PCS length and hallucinations status, but no main effects. There were no effects of hallucination status on salience and auditory network connectivity or in graph theoretical measures of connectivity, suggesting that resting-state connectivity is not a trait marker for hallucinations. Together, the discovery of neurodevelopmental alterations contributing to hallucinations provides mechanistic insight into the pathological consequences of prenatal origins. The interaction of sulcal alterations and hallucination status are associated with connectivity, which may have a role in the pathophysiology of hallucinations. I provide clear predictions and recommendations for future research.Gates Cambridge Scholarshi

Principles of Integrated Cognitive Training for Executive Attention: Application to an Instrumental Skill

One effective cognitive treatment is the rehabilitation of working memory (WM) using an integrated approach that targets the “executive attention” system. Recent neuroscientific literature has revealed that treatment efficacy depends on the presence of various features, such as adaptivity, empathy, customization, avoidance of automatism and stereotypies, and alertness activation. Over the last two decades, an Integrated Cognitive Training (ICT) protocol has been proposed and developed; ICT takes the above-mentioned features and existing literature into account, and has been used to promote the development of reading skills. ICT has been employed in several clinical settings and involves stimulation of a specific deteriorated system (e.g., reading) and the improvement of executive attention components, thus also increasing working memory capacity. In this context, we present two experiments. In Experiment 1, participants diagnosed with dyslexia (aged between 8 and 14 years) underwent two ICT sessions a week, with home supplements, for a duration of 7 months. The participants showed a significant improvement in the reading speed of text, words, and non-words, and in the reading accuracy of text and non-words. In Experiment 2, we replicated Experiment 1, but included a comparison between two groups (experimental group vs. control group) of young participants with diagnosis of dyslexia. The experimental group was subjected to 18 ICT sessions twice a week and with home supplements, using the same protocol as in Experiment 1. The control group was entrusted to the protocol of compensatory tools and dispense/helping procedures provided by the scholastic Personalized Educational Plan. After training, the experimental group gained about 0.5 syllables per second in text reading, and a marked decrease in error rate. The control group showed no significant improvement in reading skills after the same period. Moreover, the improvement observed in the experimental group remained stable 4 months after ICT had ended. The results of these two experiments support the efficacy of the integrated ICT protocol in improving reading skills in children with dyslexia and its sustained effect