Brain White Matter Correlates of Creativity in Schizophrenia: A Diffusion Tensor Imaging Study

The relationship between creativity and psychopathology has been a controversial research topic for decades. Specifically, it has been shown that people with schizophrenia have an impairment in creative performance. However, little is known about the brain correlates underlying this impairment. Therefore, the aim of this study was to analyze whole brain white matter (WM) correlates of several creativity dimensions in people with schizophrenia. Fifty-five patients with schizophrenia underwent diffusion-weighted imaging on a 3T magnetic resonance imaging machine as well as a clinical and a creativity assessment, including verbal and figural creativity measures. Tract-based spatial statistic, implemented in FMRIB Software Library (FSL), was used to assess whole brain WM correlates with different creativity dimensions, controlling for sex, age, premorbid IQ, and medication. Mean fractional anisotropy (FA) in frontal, temporal, subcortical, brain stem, and interhemispheric regions correlated positively with figural originality. The most significant clusters included the right corticospinal tract (cerebral peduncle part) and the right body of the corpus callosum. Verbal creativity did not show any significant correlation. As a whole, these findings suggest that widespread WM integrity is involved in creative performance of patients with schizophrenia. Many of these areas have also been related to creativity in healthy people. In addition, some of these regions have shown to be particularly impaired in schizophrenia, suggesting that these WM alterations could be underlying the worse creative performance found in this pathology.This study has been supported by 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 Fundacion Tatiana Perez de Guzman el Bueno. AG-G was supported by a fellowship from the Education, Language, Politics and Culture Department of the Basque Government (PRE_2015_1_0444). The funding agencies had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript

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

Brain connectivity and cognitive functioning in individuals six months after multiorgan failure

Multiorgan failure (MOF) is a life-threating condition that affects two or more systems of organs not involved in the disorder that motivates admission to an Intensive Care Unit (ICU). Patients who survive MOF frequently present long-term functional, neurological, cognitive, and psychiatric sequelae. However, the changes to the brain that explain such symptoms remain unclear. Objective: To determine brain connectivity and cognitive functioning differences between a group of MOF patients six months after ICU discharge and healthy controls (HC). Methods: 22 MOF patients and 22 HC matched by age, sex, and years of education were recruited. Both groups were administered a 3T magnetic resonance imaging (MRI), including structural T1 and functional BOLD, as well as a comprehensive neuropsychological evaluation that included tests of learning and memory, speed of information processing and attention, executive function, visual constructional abilities, and language. Voxel-based morphometry was used to analyses T1 images. For the functional data at rest, functional connectivity (FC) analyses were performed. Results: There were no significant differences in structural imaging and neuropsychological performance between groups, even though patients with MOF performed worse in all the cognitive tests. Functional neuroimaging in the default mode network (DMN) showed hyper-connectivity towards sensory-motor, cerebellum, and visual networks. DMN connectivity had a significant association with the severity of MOF during ICU stay and with the neuropsychological scores in tests of attention and visual constructional abilities. Conclusions: In MOF patients without structural brain injury, DMN connectivity six months after ICU discharge is associated with MOF severity and neuropsychological impairment, which supports the use of resting-state functional MRI as a potential tool to predict the onset of long-term cognitive deficits in these patients. Similar to what occurs at the onset of other pathologies, the observed hyper-connectivity might suggest network re-adaptation following MOF.This research was founded by Ministerio Economia, Industria y Competitividad, Spain and FEDER (grant no. DPI2016-79874-R) to JC and JCAL. ID's time was founded by the Department of Education of the Basque Country, postdoctoral program. JR's time was founded by the Ministry of Education, Language Policy and Culture (Basque Government). JMC's time was founded by Ikerbasque and the Department of Economic Development and Infrastructure of the Basque Country, Elkartek Program (grant no. KK-2018/00032). JCAL's time was founded by Ikerbasque and Fundacion Mutua Madrileña (grant no. AP169812018). IG's time was founded by the Instituto de Salud Carlos III for a Juan Rodes (grant no. JR15/00008 ) co-funded by the European Regional Development Fund/European Social Fund ‘Investing in Your Future’. AJM's time was partly founded by Euskampus Fundazioa

Brain connectivity and cognitive functioning in individuals six months after multiorgan failure

Abstract Multiorgan failure (MOF) is a life-threating condition that affects two or more systems of organs not involved in the disorder that motivates admission to an Intensive Care Unit (ICU). Patients who survive MOF frequently present long-term functional, neurological, cognitive, and psychiatric sequelae. However, the changes to the brain that explain such symptoms remain unclear. OBJECTIVE: To determine brain connectivity and cognitive functioning differences between a group of MOF patients six months after ICU discharge and healthy controls (HC). METHODS: 22 MOF patients and 22 HC matched by age, sex, and years of education were recruited. Both groups were administered a 3T magnetic resonance imaging (MRI), including structural T1 and functional BOLD, as well as a comprehensive neuropsychological evaluation that included tests of learning and memory, speed of information processing and attention, executive function, visual constructional abilities, and language. Voxel-based morphometry was used to analyses T1 images. For the functional data at rest, functional connectivity (FC) analyses were performed. RESULTS: There were no significant differences in structural imaging and neuropsychological performance between groups, even though patients with MOF performed worse in all the cognitive tests. Functional neuroimaging in the default mode network (DMN) showed hyper-connectivity towards sensory-motor, cerebellum, and visual networks. DMN connectivity had a significant association with the severity of MOF during ICU stay and with the neuropsychological scores in tests of attention and visual constructional abilities. CONCLUSIONS: In MOF patients without structural brain injury, DMN connectivity six months after ICU discharge is associated with MOF severity and neuropsychological impairment, which supports the use of resting-state functional MRI as a potential tool to predict the onset of long-term cognitive deficits in these patients.Similar to what occurs at the onset of other pathologies, the observed hyper-connectivity might suggest network re-adaptation following MOF.This research was founded by Ministerio Economia, Industria y Competitividad, Spain and FEDER (grant no. DPI2016-79874-R) to JC and JCAL. ID's time was founded by the Department of Education of the Basque Country, postdoctoral program. JR's time was founded by the Ministry of Education, Language Policy and Culture (Basque Government). JMC's time was founded by Ikerbasque and the Department of Economic Development and Infrastructure of the Basque Country, Elkartek Program (grant no. KK-2018/00032). JCAL's time was founded by Ikerbasque and Fundacion Mutua Madrilena (grant no. AP169812018). IG's time was founded by the Instituto de Salud Carlos III for a Juan Rodes (grant no. JR15/00008) co-funded by the European Regional Development Fund/European Social Fund 'Investing in Your Future'. AJM's time was partly founded by Euskampus Fundazioa

Heart-brain synchronization breakdown in Parkinson's disease

Heart rate variability (HRV) abnormalities are potential early biomarkers in Parkinson's disease (PD) but their relationship with central autonomic network (CAN) activity is not fully understood. We analyzed the synchronization between HRV and brain activity in 31 PD patients and 21 age-matched healthy controls using blood-oxygen-level-dependent (BOLD) signals from resting-state functional brain MRI and HRV metrics from finger plethysmography recorded for 7.40 min. We additionally quantified autonomic symptoms (SCOPA-AUT) and objective autonomic cardiovascular parameters (blood pressure and heart rate) during deep breathing, Valsalva, and head-up tilt, which were used to classify the clinical severity of dysautonomia. We evaluated HRV and BOLD signals synchronization (HRV-BOLD-sync) with Pearson lagged cross-correlations and Fisher's statistics for combining window-length-dependent HRV-BOLD-Sync Maps and assessed their association with clinical dysautonomia. HRV-BOLD-sync was lower significantly in PD than in controls in various brain regions within CAN or in networks involved in autonomic modulation. Moreover, heart-brain synchronization index (HBSI), which quantifies heart-brain synchronization at a single-subject level, showed an inverse exposure-response relationship with dysautonomia severity, finding the lowest HBSI in patients with severe dysautonomia, followed by moderate, mild, and, lastly, controls. Importantly, HBSI was associated in PD, but not in controls, with Valsalva pressure recovery time (sympathetic), deep breathing E/I ratio (cardiovagal), and SCOPA-AUT. Our findings support the existence of heart-brain de-synchronization in PD with an impact on clinically relevant autonomic outcomes.We want to thank all the patients and participants involved in the study. This study was partially co-funded by Michael J. Fox Foundation [RRIA 2014 (Rapid Response Innovation Awards) Program (Grant ID: 10189)], by the Carlos III Health Institute, and the European Union (ERDF/ESF, "A Way to Make Europe"/"Investing in Your Future") through the projects PI14/00679 and PI16/00005, the Juan Rodes grant "JR15/00008" (I.G.), and by the Department of Health of the Basque Government through the project "2016111009" and "2020333033". A.J.M. was supported by a predoctoral grant from the Basque Government (PRE_2019_1_0070). M.I. acknowledges financial support from"La Caixa" Foundation (ID 100010434, fellowship LCF/BQ/EU20/11810065). The Edmond and Lily Safra Center for Brain Sciences and the Basque Government (POS_2019_2_0020) to A.E. J.M.C. is funded by Ikerbasque: The Basque Foundation for Science and from the Ministerial de Economia, Industria y Competitividad (Spain) and FEDER (grant DPI2016-79874-R), and from the Department of Economic and Infrastructure Development of the Basque Country (Elkartek Program, KK-2018/00032, KK-2018/00090, and KK-2021/00009/BCB)

Dynamic functional connectivity in Parkinson's disease patients with mild cognitive impairment and normal cognition

The objective was to assess dynamic functional connectivity (FC) and local/global connectivity in Parkinson's disease (PD) patients with mild cognitive impairment (PD-MCI) and with normal cognition (PD-NC).The sample included 35 PD patients and 26 healthy controls (HC). Cognitive assessment followed an extensive neuropsychological battery. For resting-state functional MRI (rs-fMRI) analysis, independent component analysis (ICA) was performed and components were located in 7 networks: Subcortical (SC), Auditory (AUD), Somatomotor (SM), visual (VI), cognitive-control (CC), default-mode (DMN), and cerebellar (CB). Dynamic FC analysis was performed using the GIFT toolbox. FC differences between groups in each FC state were analysed with the network-based statistic (NBS) approach. Finally, a graph-theoretical analysis for local/global parameters was performed.The whole sample showed 2 dynamic FC states during the rs-fMRI. PD-MCI patients showed decreased mean dwell time in the hypo-connectivity state (p=0.030) and showed increased number of state transitions (p=0.007) compared with the HC. In addition, in the hypo-connectivity state, PD-MCI patients showed reduced inter-network FC between the SM-CC, SM-VI, SM-AUD, CC-VI and SC-DMN compared with the HC (p<0.05-FDR). These FC alterations in PD-MCI were accompanied by graph-topological alterations in nodes located in the SM network (p<0.001). In contrast, no differences were found between the PD-NC and HC.Findings suggest the presence of dynamic functional brain deteriorations in PD-MCI that are not present in PD-NC, showing the PD-MCI group dynamic FC dysfunctions, reduced FC mostly between SM-CC networks and graph-topological deteriorations in the SM network. A dynamic FC approach could be helpful to understand cognitive deterioration in PD. Keywords: Dynamic functional connectivity, Graph theory, Parkinson's disease, Mild cognitive impairment, PD-MCI, Network

Neuroanatomical Correlates of Theory of Mind Deficit in Parkinson's Disease: A Multimodal Imaging Study.

Parkinson's disease (PD) patients show theory of mind (ToM) deficit since the early stages of the disease, and this deficit has been associated with working memory, executive functions and quality of life impairment. To date, neuroanatomical correlates of ToM have not been assessed with magnetic resonance imaging in PD. The main objective of this study was to assess cerebral correlates of ToM deficit in PD. The second objective was to explore the relationships between ToM, working memory and executive functions, and to analyse the neural correlates of ToM, controlling for both working memory and executive functions.Thirty-seven PD patients (Hoehn and Yahr median = 2.0) and 15 healthy controls underwent a neuropsychological assessment and magnetic resonance images in a 3T-scanner were acquired. T1-weighted images were analysed with voxel-based morphometry, and white matter integrity and diffusivity measures were obtained from diffusion weighted images and analysed using tract-based spatial statistics.PD patients showed impairments in ToM, working memory and executive functions; grey matter loss and white matter reduction compared to healthy controls. Grey matter volume decrease in the precentral and postcentral gyrus, middle and inferior frontal gyrus correlated with ToM deficit in PD. White matter in the superior longitudinal fasciculus (adjacent to the parietal lobe) and white matter adjacent to the frontal lobe correlated with ToM impairment in PD. After controlling for executive functions, the relationship between ToM deficit and white matter remained significant for white matter areas adjacent to the precuneus and the parietal lobe.Findings reinforce the existence of ToM impairment from the early Hoehn and Yahr stages in PD, and the findings suggest associations with white matter and grey matter volume decrease. This study contributes to better understand ToM deficit and its neural correlates in PD, which is a basic skill for development of healthy social relationships

Correlations between ToM deficit and WM MD controlling for executive functions in PD.

<p>Significant WM regions are shown in red-yellow; the WM skeleton is shown in green. S = superior; I = inferior; A = anterior; P = posterior. Coordinates are shown in MNI space (Montreal Neurological Institute).</p

Group differences in GM volume.

<p>GM areas showing volume decrease in PD compared to healthy controls are shown in red-yellow. S = superior; I = inferior; A = anterior; P = posterior. Coordinates are shown in MNI space (Montreal Neurological Institute).</p

Sociodemographic, clinical and neuropsychological characteristics of the sample.

<p>Values are expressed as mean (S.D) unless otherwise noted. PD = Parkinson’s disease; HC = Healthy controls; UPDRS = Unified Parkinson Disease Rating Scale; LEDD = Levodopa Equivalent Daily dose; ToM = Theory of Mind.</p><p>*Ambidextrous understood as people who were originally left handed and who learned to be right handed during childhood.</p><p>Sociodemographic, clinical and neuropsychological characteristics of the sample.</p