Publications by authors named "André Aleman"

302 Publications

Anosognosia in Amnestic Mild Cognitive Impairment Is Related to Diminished Hippocampal Volume Comparable to Alzheimer's Disease Dementia: Preliminary MRI Findings.

Front Aging Neurosci 2021 28;13:739422. Epub 2021 Oct 28.

Programa de Maestría y Doctorado en Ciencias Médicas, Odontológicas y de la Salud, Universidad Nacional Autónoma de México, Mexico City, Mexico.

Although the presence of anosognosia in amnestic mild cognitive impairment (aMCI) may be predictive of conversion to Alzheimer's disease (AD), little is known about its neural correlates in AD and aMCI. Four different groups were compared using volumetric and diffusion magnetic resonance imaging metrics in regions of interest (hippocampus and cingulum cortex gray matter, cingulum bundle white matter): aMCI subjects with anosognosia ( = 6), aMCI subjects without anosognosia ( = 12), AD subjects with anosognosia ( = 6), and AD subjects without anosognosia ( = 9). aMCI subjects with anosognosia displayed a significantly lower gray matter density (GMD) in the bilateral hippocampus than aMCI subjects without anosognosia, which was accounted for by bilateral hippocampal differences. Furthermore, we identified that the mean hippocampal gray matter density of aMCI subjects with anosognosia was not statistically different than that of AD subjects. The groups of aMCI and AD subjects with anosognosia also displayed a lower GMD in the bilateral cingulum cortex compared to subjects without anosognosia, but these differences were not statistically significant. No statistically significant differences were found in the fractional anisotropy or mean diffusivity of the hippocampus or cingulum between subjects with and without anosognosia in aMCI or AD groups. While these findings are derived from a small population of subjects and are in need of replication, they suggest that anosognosia in aMCI might be a useful clinical marker to suspect brain changes associated with AD neuropathology.
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http://dx.doi.org/10.3389/fnagi.2021.739422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581404PMC
October 2021

Cortical and subcortical neuroanatomical signatures of schizotypy in 3004 individuals assessed in a worldwide ENIGMA study.

Mol Psychiatry 2021 Oct 27. Epub 2021 Oct 27.

Institute of Psychology, Chinese Academy of Sciences, Beijing, China.

Neuroanatomical abnormalities have been reported along a continuum from at-risk stages, including high schizotypy, to early and chronic psychosis. However, a comprehensive neuroanatomical mapping of schizotypy remains to be established. The authors conducted the first large-scale meta-analyses of cortical and subcortical morphometric patterns of schizotypy in healthy individuals, and compared these patterns with neuroanatomical abnormalities observed in major psychiatric disorders. The sample comprised 3004 unmedicated healthy individuals (12-68 years, 46.5% male) from 29 cohorts of the worldwide ENIGMA Schizotypy working group. Cortical and subcortical effect size maps with schizotypy scores were generated using standardized methods. Pattern similarities were assessed between the schizotypy-related cortical and subcortical maps and effect size maps from comparisons of schizophrenia (SZ), bipolar disorder (BD) and major depression (MDD) patients with controls. Thicker right medial orbitofrontal/ventromedial prefrontal cortex (mOFC/vmPFC) was associated with higher schizotypy scores (r = 0.067, p = 0.02). The cortical thickness profile in schizotypy was positively correlated with cortical abnormalities in SZ (r = 0.285, p = 0.024), but not BD (r = 0.166, p = 0.205) or MDD (r = -0.274, p = 0.073). The schizotypy-related subcortical volume pattern was negatively correlated with subcortical abnormalities in SZ (rho = -0.690, p = 0.006), BD (rho = -0.672, p = 0.009), and MDD (rho = -0.692, p = 0.004). Comprehensive mapping of schizotypy-related brain morphometry in the general population revealed a significant relationship between higher schizotypy and thicker mOFC/vmPFC, in the absence of confounding effects due to antipsychotic medication or disease chronicity. The cortical pattern similarity between schizotypy and schizophrenia yields new insights into a dimensional neurobiological continuity across the extended psychosis phenotype.
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http://dx.doi.org/10.1038/s41380-021-01359-9DOI Listing
October 2021

Training the attentional blink: subclinical depression decreases learning potential.

Psychol Res 2021 Oct 21. Epub 2021 Oct 21.

Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, Groningen, The Netherlands.

The attentional blink (AB) reflects a temporal restriction of selective attention and is generally regarded as a very robust phenomenon. However, previous studies have found large individual differences in AB performance, and under some training conditions the AB can be reduced significantly. One factor that may account for individual differences in AB magnitude is the ability to accurately time attention. In the current study, we focus on the sensitivity for temporal information on the ability to control attention. Following a visual AB task, a time estimation task was presented in either the visual or auditory modality, followed by another visual AB task. It was found that the time estimation training in both the auditory and visual modality reduced AB magnitude. Although a reduction in AB magnitude was also observed when individuals were trained on a control task (either an auditory frequency or visual line length estimation task), the effect was significantly larger following the time estimation tasks. In addition, it was found that individuals who showed most improvement on the visual time estimation task, also showed the largest reduction in AB magnitude, which was not the case for individuals who were trained on the control tasks. Finally, a negative correlation was observed between depression scores (tested by Beck Depression Inventory-Short Form (BDI-SF) scores and the improvement in the AB and time estimation tasks. Our findings demonstrate clear links between timing ability and mechanisms to control attention and emotion.
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http://dx.doi.org/10.1007/s00426-021-01603-5DOI Listing
October 2021

Interindividual variability of electric fields during transcranial temporal interference stimulation (tTIS).

Sci Rep 2021 Oct 13;11(1):20357. Epub 2021 Oct 13.

Experimental Psychology Lab, Department of Psychology, European Medical School, Cluster of Excellence "Hearing4All", Carl Von Ossietzky University, Ammerländer Heerstr. 114-118, 26129, Oldenburg, Germany.

Transcranial temporal interference stimulation (tTIS) is a novel non-invasive brain stimulation technique for electrical stimulation of neurons at depth. Deep brain regions are generally small in size, making precise targeting a necessity. The variability of electric fields across individual subjects resulting from the same tTIS montages is unknown so far and may be of major concern for precise tTIS targeting. Therefore, the aim of the current study is to investigate the variability of the electric fields due to tTIS across 25 subjects. To this end, the electric fields of different electrode montages consisting of two electrode pairs with different center frequencies were simulated in order to target selected regions-of-interest (ROIs) with tTIS. Moreover, we set out to compare the electric fields of tTIS with the electric fields of conventional tACS. The latter were also based on two electrode pairs, which, however, were driven in phase at a common frequency. Our results showed that the electric field strengths inside the ROIs (left hippocampus, left motor area and thalamus) during tTIS are variable on single subject level. In addition, tTIS stimulates more focally as compared to tACS with much weaker co-stimulation of cortical areas close to the stimulation electrodes. Electric fields inside the ROI were, however, comparable for both methods. Overall, our results emphasize the potential benefits of tTIS for the stimulation of deep targets, over conventional tACS. However, they also indicate a need for individualized stimulation montages to leverage the method to its fullest potential.
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http://dx.doi.org/10.1038/s41598-021-99749-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514596PMC
October 2021

Social-Specific Impairment of Negative Emotion Perception in Alexithymia.

Soc Cogn Affect Neurosci 2021 Aug 18. Epub 2021 Aug 18.

Shenzhen Key Laboratory of Affective and Social Neuroscience, Center for Brain Disorders and Cognitive Sciences, Shenzhen University, Shenzhen 518060, China.

Alexithymia has been characterized as an impaired ability of emotion processing and regulation. The definition of alexithymia does not include a social component. However, there is some evidence that social cognition may be compromised in individuals with alexithymia. Hence, emotional impairments associated with alexithymia may extend to socially relevant information. Here, we recorded electrophysiological responses of individuals meeting the clinically relevant cut-off for alexithymia (ALEX; n=24) and individuals without alexithymia (NonALEX; n=23) while they viewed affective scenes that varied on the dimensions of sociality and emotional valence during a rapid serial visual presentation task. We found that ALEX exhibited lower accuracy and larger N2 than NonALEX in the perception of social negative scenes. Source reconstruction revealed that the group difference in N2 was localized at the dorsal anterior cingulate cortex. Irrespective of emotional valence, ALEX showed stronger alpha power than NonALEX in social but not nonsocial conditions. Our findings support the hypothesis of social processing being selectively affected by alexithymia, especially for stimuli with negative valence. Electrophysiological evidence suggests altered deployment of attentional resources in the perception of social-specific emotional information in alexithymia. This work sheds light on the neuropsychopathology of alexithymia and alexithymia-related disorders.
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http://dx.doi.org/10.1093/scan/nsab099DOI Listing
August 2021

No antidepressant effects of low intensity transcranial pulsed electromagnetic fields for treatment resistant depression.

J Affect Disord 2021 11 22;294:679-685. Epub 2021 Jul 22.

University of Groningen, University Medical Center Groningen, Department of Psychiatry, Research School of Behavioral and Cognitive Neurosciences (BCN), Interdisciplinary Center Psychopathology of Emotion regulation (ICPE), the Netherlands.

Background: Noninvasive neurostimulation with transcranial Pulsed Electromagnetic Fields (tPEMF) may be a promising method for treatment resistant depression (TRD). Studies shown substantial improvement of depressive symptoms in patients with TRD, but there is no information on long-term antidepressant effects. The aim of this study was to investigate the short- and long-term efficacy of tPEMF in participants with TRD.

Methods: Eligible participants with TRD in this sham-controlled double-blind multicenter trial were randomly assigned to five weeks either daily active or sham tPEMF. Severity of depression and anxiety was assessed pre- and directly post-treatment and five and fifteen weeks post-treatment. Primary outcome was change on the 17-item Hamilton depression rating scale directly post-treatment. Secondary outcome was change on the Hamilton-17 during follow-up and change on the Inventory of Depressive Symptomatology Self-Report and the Beck Anxiety Index.

Results: Of the 55 included participants, 50 completed the treatment protocol. Depressive symptoms improved over time in both groups. The improvement continued until the last follow-up measure. There was no difference in outcome between the active and the sham group on change in depression post-treatment or on any secondary measure.

Conclusion: Treatment with this type of active tPEMF was not superior to sham in patients with TRD. This is in contrast to a previous study using a similar design and power calculation, but a higher magnetic field strength, that reported improvement of depression after treatment with tPEMF compared to sham. An important limitation of our study was the fact that no different dosing regimens were tried.
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http://dx.doi.org/10.1016/j.jad.2021.07.087DOI Listing
November 2021

Neurobiological substrates of the positive formal thought disorder in schizophrenia revealed by seed connectome-based predictive modeling.

Neuroimage Clin 2021 30;30:102666. Epub 2021 Apr 30.

Iowa Neuroscience Institute, Carver College of Medicine, University of Iowa, Iowa City, IA, United States; Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, United States. Electronic address:

Formal thought disorder (FTD) is a core symptom cluster of schizophrenia, but its neurobiological substrates remain poorly understood. Here we collected resting-state fMRI data from 276 subjects at seven sites and employed machine-learning to investigate the neurobiological correlates of FTD along positive and negative symptom dimensions in schizophrenia. Three a priori, meta-analytically defined FTD-related brain regions were used as seeds to generate whole-brain resting-state functional connectivity (rsFC) maps, which were then compared between schizophrenia patients and controls. A repeated cross-validation procedure was realized within the patient group to identify clusters whose rsFC patterns to the seeds were repeatedly observed as significantly associated with specific FTD dimensions. These repeatedly identified clusters (i.e., robust clusters) were functionally characterized and the rsFC patterns were used for predictive modeling to investigate predictive capacities for individual FTD dimensional-scores. Compared with controls, differential rsFC was found in patients in fronto-temporo-thalamic regions. Our cross-validation procedure revealed significant clusters only when assessing the seed-to-whole-brain rsFC patterns associated with positive-FTD. RsFC patterns of three fronto-temporal clusters, associated with higher-order cognitive processes (e.g., executive functions), specifically predicted individual positive-FTD scores (p = 0.005), but not other positive symptoms, and the PANSS general psychopathology subscale (p > 0.05). The prediction of positive-FTD was moreover generalized to an independent dataset (p = 0.013). Our study has identified neurobiological correlates of positive FTD in schizophrenia in a network associated with higher-order cognitive functions, suggesting a dysexecutive contribution to FTD in schizophrenia. We regard our findings as robust, as they allow a prediction of individual-level symptom severity.
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http://dx.doi.org/10.1016/j.nicl.2021.102666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105296PMC
July 2021

Correlates of Hallucinatory Experiences in the General Population: An International Multisite Replication Study.

Psychol Sci 2021 07 4;32(7):1024-1037. Epub 2021 Jun 4.

Department of Psychology, Durham University.

Hallucinatory experiences can occur in both clinical and nonclinical groups. However, in previous studies of the general population, investigations of the cognitive mechanisms underlying hallucinatory experiences have yielded inconsistent results. We ran a large-scale preregistered multisite study, in which general-population participants ( = 1,394 across 11 data-collection sites and online) completed assessments of hallucinatory experiences, a measure of adverse childhood experiences, and four tasks: source memory, dichotic listening, backward digit span, and auditory signal detection. We found that hallucinatory experiences were associated with a higher false-alarm rate on the signal detection task and a greater number of reported adverse childhood experiences but not with any of the other cognitive measures employed. These findings are an important step in improving reproducibility in hallucinations research and suggest that the replicability of some findings regarding cognition in clinical samples needs to be investigated.
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http://dx.doi.org/10.1177/0956797620985832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8641136PMC
July 2021

Correlates of Hallucinatory Experiences in the General Population: An International Multisite Replication Study.

Psychol Sci 2021 07 4;32(7):1024-1037. Epub 2021 Jun 4.

Department of Psychology, Durham University.

Hallucinatory experiences can occur in both clinical and nonclinical groups. However, in previous studies of the general population, investigations of the cognitive mechanisms underlying hallucinatory experiences have yielded inconsistent results. We ran a large-scale preregistered multisite study, in which general-population participants ( = 1,394 across 11 data-collection sites and online) completed assessments of hallucinatory experiences, a measure of adverse childhood experiences, and four tasks: source memory, dichotic listening, backward digit span, and auditory signal detection. We found that hallucinatory experiences were associated with a higher false-alarm rate on the signal detection task and a greater number of reported adverse childhood experiences but not with any of the other cognitive measures employed. These findings are an important step in improving reproducibility in hallucinations research and suggest that the replicability of some findings regarding cognition in clinical samples needs to be investigated.
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http://dx.doi.org/10.1177/0956797620985832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8641136PMC
July 2021

Foreign Language Learning as Cognitive Training to Prevent Old Age Disorders? Protocol of a Randomized Controlled Trial of Language Training vs. Musical Training and Social Interaction in Elderly With Subjective Cognitive Decline.

Front Aging Neurosci 2021 27;13:550180. Epub 2021 Apr 27.

English Linguistics and English as a Second Language, Bilingualism and Aging Lab, University of Groningen, Groningen, Netherlands.

: With aging comes a reduction of cognitive flexibility, which has been related to the development of late-life depression and progression of general cognitive decline. Several factors have been linked to attenuating such decline in cognitive flexibility, such as education, physical exercise and stimulating leisure activities. Speaking two or more languages has recently received abundant attention as another factor that may build up cognitive reserve, thereby limiting the functional implications of compromised cognition that accompany old age. With the number of older adults reaching record levels, it is important to attenuate the development of old-age disorders. Learning to speak a foreign language might offer a powerful tool in promoting healthy aging, but up to date effect studies are sparse. Here, the protocol that forms the foundation of the current study is presented. The present study aims to: (1) examine the effects of a foreign language training on cognitive flexibility and its neural underpinnings, and on mental health; and (2) assess the unique role of foreign language training vs. other cognitive or social programs. : One-hundred and ninety-eight Dutch elderly participants reporting subjective cognitive decline are included and randomized to either a language intervention, a music intervention, or a social control intervention. During 3 to 6 months, the language group learns English, the music group learns to play the guitar and the social group participates in social meetings where art workshops are offered. At baseline, at a 3-month follow-up, and at 6 months after termination of the training program, clinical, cognitive and brain activity measurements (combined EEG and fNIRS methods) are taken to assess cognitive flexibility and mental health. : This is the first trial addressing combined effects of language learning in elderly on cognition, language proficiency, socio-affective measures, and brain activity in the context of a randomized controlled trial. If successful, this study can provide insights into how foreign language training can contribute to more cognitively and mentally healthy years in older adulthood. : The trial is registered at the Netherlands Trial Register, July 2, 2018, trial number NL7137. https://www.trialregister.nl/trial/7137.
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http://dx.doi.org/10.3389/fnagi.2021.550180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111015PMC
April 2021

ENIGMA-Sleep: Challenges, opportunities, and the road map.

J Sleep Res 2021 12 28;30(6):e13347. Epub 2021 Apr 28.

Department of Sleep and Cognition, Netherlands Institute for Neuroscience (NIN), an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.

Neuroimaging and genetics studies have advanced our understanding of the neurobiology of sleep and its disorders. However, individual studies usually have limitations to identifying consistent and reproducible effects, including modest sample sizes, heterogeneous clinical characteristics and varied methodologies. These issues call for a large-scale multi-centre effort in sleep research, in order to increase the number of samples, and harmonize the methods of data collection, preprocessing and analysis using pre-registered well-established protocols. The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium provides a powerful collaborative framework for combining datasets across individual sites. Recently, we have launched the ENIGMA-Sleep working group with the collaboration of several institutes from 15 countries to perform large-scale worldwide neuroimaging and genetics studies for better understanding the neurobiology of impaired sleep quality in population-based healthy individuals, the neural consequences of sleep deprivation, pathophysiology of sleep disorders, as well as neural correlates of sleep disturbances across various neuropsychiatric disorders. In this introductory review, we describe the details of our currently available datasets and our ongoing projects in the ENIGMA-Sleep group, and discuss both the potential challenges and opportunities of a collaborative initiative in sleep medicine.
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http://dx.doi.org/10.1111/jsr.13347DOI Listing
December 2021

Association of Age, Antipsychotic Medication, and Symptom Severity in Schizophrenia With Proton Magnetic Resonance Spectroscopy Brain Glutamate Level: A Mega-analysis of Individual Participant-Level Data.

JAMA Psychiatry 2021 Jun;78(6):667-681

Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York.

Importance: Proton magnetic resonance spectroscopy (1H-MRS) studies indicate that altered brain glutamatergic function may be associated with the pathophysiology of schizophrenia and the response to antipsychotic treatment. However, the association of altered glutamatergic function with clinical and demographic factors is unclear.

Objective: To assess the associations of age, symptom severity, level of functioning, and antipsychotic treatment with brain glutamatergic metabolites.

Data Sources: The MEDLINE database was searched to identify journal articles published between January 1, 1980, and June 3, 2020, using the following search terms: MRS or magnetic resonance spectroscopy and (1) schizophrenia or (2) psychosis or (3) UHR or (4) ARMS or (5) ultra-high risk or (6) clinical high risk or (7) genetic high risk or (8) prodrome* or (9) schizoaffective. Authors of 114 1H-MRS studies measuring glutamate (Glu) levels in patients with schizophrenia were contacted between January 2014 and June 2020 and asked to provide individual participant data.

Study Selection: In total, 45 1H-MRS studies contributed data.

Data Extraction And Synthesis: Associations of Glu, Glu plus glutamine (Glx), or total creatine plus phosphocreatine levels with age, antipsychotic medication dose, symptom severity, and functioning were assessed using linear mixed models, with study as a random factor.

Main Outcomes And Measures: Glu, Glx, and Cr values in the medial frontal cortex (MFC) and medial temporal lobe (MTL).

Results: In total, 42 studies were included, with data for 1251 patients with schizophrenia (mean [SD] age, 30.3 [10.4] years) and 1197 healthy volunteers (mean [SD] age, 27.5 [8.8] years). The MFC Glu (F1,1211.9 = 4.311, P = .04) and Glx (F1,1079.2 = 5.287, P = .02) levels were lower in patients than in healthy volunteers, and although creatine levels appeared lower in patients, the difference was not significant (F1,1395.9 = 3.622, P = .06). In both patients and volunteers, the MFC Glu level was negatively associated with age (Glu to Cr ratio, F1,1522.4 = 47.533, P < .001; cerebrospinal fluid-corrected Glu, F1,1216.7 = 5.610, P = .02), showing a 0.2-unit reduction per decade. In patients, antipsychotic dose (in chlorpromazine equivalents) was negatively associated with MFC Glu (estimate, 0.10 reduction per 100 mg; SE, 0.03) and MFC Glx (estimate, -0.11; SE, 0.04) levels. The MFC Glu to Cr ratio was positively associated with total symptom severity (estimate, 0.01 per 10 points; SE, 0.005) and positive symptom severity (estimate, 0.04; SE, 0.02) and was negatively associated with level of global functioning (estimate, 0.04; SE, 0.01). In the MTL, the Glx to Cr ratio was positively associated with total symptom severity (estimate, 0.06; SE, 0.03), negative symptoms (estimate, 0.2; SE, 0.07), and worse Clinical Global Impression score (estimate, 0.2 per point; SE, 0.06). The MFC creatine level increased with age (estimate, 0.2; SE, 0.05) but was not associated with either symptom severity or antipsychotic medication dose.

Conclusions And Relevance: Findings from this mega-analysis suggest that lower brain Glu levels in patients with schizophrenia may be associated with antipsychotic medication exposure rather than with greater age-related decline. Higher brain Glu levels may act as a biomarker of illness severity in schizophrenia.
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http://dx.doi.org/10.1001/jamapsychiatry.2021.0380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060889PMC
June 2021

Similar EEG Activity Patterns During Experimentally-Induced Auditory Illusions and Veridical Perceptions.

Front Neurosci 2021 1;15:602437. Epub 2021 Apr 1.

Experimental Psychology Lab, Department of Psychology, European Medical School, Cluster of Excellence "Hearing4All," Carl von Ossietzky University, Oldenburg, Germany.

Hallucinations and illusions are two instances of perceptual experiences illustrating how perception might diverge from external sensory stimulations and be generated or altered based on internal brain states. The occurrence of these phenomena is not constrained to patient populations. Similar experiences can be elicited in healthy subjects by means of suitable experimental procedures. Studying the neural mechanisms underlying these experiences not only has the potential to expand our understanding of the brain's perceptual machinery but also of how it might get impaired. In the current study, we employed an auditory signal detection task to induce auditory illusions by presenting speech snippets at near detection threshold intensity embedded in noise. We investigated the neural correlates of auditory false perceptions by examining the EEG activity preceding the responses in speech absent (false alarm, FA) trials and comparing them to speech present (hit) trials. The results of the comparison of event-related potentials (ERPs) in the activation period vs. baseline revealed the presence of an early negativity (EN) and a late positivity (LP) similar in both hits and FAs, which were absent in misses, correct rejections (CR) and control button presses (BPs). We postulate that the EN and the LP might represent the auditory awareness negativity (AAN) and centro-parietal positivity (CPP) or P300, respectively. The event-related spectral perturbations (ERSPs) exhibited a common power enhancement in low frequencies (<4 Hz) in hits and FAs. The low-frequency power enhancement has been frequently shown to be accompanied with P300 as well as separately being a marker of perceptual awareness, referred to as slow cortical potentials (SCP). Furthermore, the comparison of hits vs. FAs showed a significantly higher LP amplitude and low frequency power in hits compared to FAs. Generally, the observed patterns in the present results resembled some of the major neural correlates associated with perceptual awareness in previous studies. Our findings provide evidence that the neural correlates associated with conscious perception, can be elicited in similar ways in both presence and absence of externally presented sensory stimuli. The present findings did not reveal any pre-stimulus alpha and beta modulations distinguishing conscious vs. unconscious perceptions.
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http://dx.doi.org/10.3389/fnins.2021.602437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047478PMC
April 2021

Functional parcellation of human and macaque striatum reveals human-specific connectivity in the dorsal caudate.

Neuroimage 2021 07 2;235:118006. Epub 2021 Apr 2.

Institute of Neuroscience and Medicine (INM-7), Heinrich Heine University Düsseldorf, Düsseldorf, Germany; Institute of Systems Neuroscience, Research Centre Jülich, Jülich, Germany. Electronic address:

A wide homology between human and macaque striatum is often assumed as in both the striatum is involved in cognition, emotion and executive functions. However, differences in functional and structural organization between human and macaque striatum may reveal evolutionary divergence and shed light on human vulnerability to neuropsychiatric diseases. For instance, dopaminergic dysfunction of the human striatum is considered to be a pathophysiological underpinning of different disorders, such as Parkinson's disease (PD) and schizophrenia (SCZ). Previous investigations have found a wide similarity in structural connectivity of the striatum between human and macaque, leaving the cross-species comparison of its functional organization unknown. In this study, resting-state functional connectivity (RSFC) derived striatal parcels were compared based on their homologous cortico-striatal connectivity. The goal here was to identify striatal parcels whose connectivity is human-specific compared to macaque parcels. Functional parcellation revealed that the human striatum was split into dorsal, dorsomedial, and rostral caudate and ventral, central, and caudal putamen, while the macaque striatum was divided into dorsal, and rostral caudate and rostral, and caudal putamen. Cross-species comparison indicated dissimilar cortico-striatal RSFC of the topographically similar dorsal caudate. We probed clinical relevance of the striatal clusters by examining differences in their cortico-striatal RSFC and gray matter (GM) volume between patients (with PD and SCZ) and healthy controls. We found abnormal RSFC not only between dorsal caudate, but also between rostral caudate, ventral, central and caudal putamen and widespread cortical regions for both PD and SCZ patients. Also, we observed significant structural atrophy in rostral caudate, ventral and central putamen for both PD and SCZ while atrophy in the dorsal caudate was specific to PD. Taken together, our cross-species comparative results revealed shared and human-specific RSFC of different striatal clusters reinforcing the complex organization and function of the striatum. In addition, we provided a testable hypothesis that abnormalities in a region with human-specific connectivity, i.e., dorsal caudate, might be associated with neuropsychiatric disorders.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214073PMC
July 2021

Diminished Feedback Evaluation and Knowledge Updating Underlying Age-Related Differences in Choice Behavior During Feedback Learning.

Front Hum Neurosci 2021 5;15:635996. Epub 2021 Mar 5.

Department of Experimental Psychology, University of Groningen, Groningen, Netherlands.

In our daily lives, we continuously evaluate feedback information, update our knowledge, and adapt our behavior in order to reach desired goals. This ability to learn from feedback information, however, declines with age. Previous research has indicated that certain higher-level learning processes, such as feedback evaluation, integration of feedback information, and updating of knowledge, seem to be affected by age, and recent studies have shown how the adaption of choice behavior following feedback can differ with age. The neural mechanisms underlying this age-related change in choice behavior during learning, however, remain unclear. The aim of this study is therefore to investigate the relation between learning-related neural processes and choice behavior during feedback learning in two age groups. Behavioral and fMRI data were collected, while a group of young (age 18-30) and older (age 60-75) adults performed a probabilistic learning task consisting of 10 blocks of 20 trials each. On each trial, the participants chose between a house and a face, after which they received visual feedback (loss vs. gain). In each block, either the house or the face image had a higher probability of yielding a reward (62.5 vs. 37.5%). Participants were instructed to try to maximize their gains. Our results showed that less successful learning in older adults, as indicated by a lower learning rate, corresponded with a higher tendency to switch to the other stimulus option, and with a reduced adaptation of this switch choice behavior following positive feedback. At the neural level, activation following positive and negative feedback was found to be less distinctive in the older adults, due to a smaller feedback-evaluation response to positive feedback in this group. Furthermore, whereas young adults displayed increased levels of knowledge updating prior to adapting choice behavior, we did not find this effect in older adults. Together, our results suggest that diminished learning performance with age corresponds with diminished evaluation of positive feedback and reduced knowledge updating related to changes in choice behavior, indicating how such differences in feedback processing at the trial level in older adults might lead to reduced learning performance across trials.
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http://dx.doi.org/10.3389/fnhum.2021.635996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973460PMC
March 2021

Deficient auditory emotion processing but intact emotional multisensory integration in alexithymia.

Psychophysiology 2021 06 20;58(6):e13806. Epub 2021 Mar 20.

Shenzhen Key Laboratory of Affective and Social Neuroscience, Magnetic Resonance Imaging, Center for Brain Disorders and Cognitive Sciences, Shenzhen University, Shenzhen, China.

Alexithymia has been associated with emotion recognition deficits in both auditory and visual domains. Although emotions are inherently multimodal in daily life, little is known regarding abnormalities of emotional multisensory integration (eMSI) in relation to alexithymia. Here, we employed an emotional Stroop-like audiovisual task while recording event-related potentials (ERPs) in individuals with high alexithymia levels (HA) and low alexithymia levels (LA). During the task, participants had to indicate whether a voice was spoken in a sad or angry prosody while ignoring the simultaneously presented static face which could be either emotionally congruent or incongruent to the human voice. We found that HA performed worse and showed higher P2 amplitudes than LA independent of emotion congruency. Furthermore, difficulties in identifying and describing feelings were positively correlated with the P2 component, and P2 correlated negatively with behavioral performance. Bayesian statistics showed no group differences in eMSI and classical integration-related ERP components (N1 and N2). Although individuals with alexithymia indeed showed deficits in auditory emotion recognition as indexed by decreased performance and higher P2 amplitudes, the present findings suggest an intact capacity to integrate emotional information from multiple channels in alexithymia. Our work provides valuable insights into the relationship between alexithymia and neuropsychological mechanisms of emotional multisensory integration.
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http://dx.doi.org/10.1111/psyp.13806DOI Listing
June 2021

Widespread white matter aberration is associated with the severity of apathy in amnestic Mild Cognitive Impairment: Tract-based spatial statistics analysis.

Neuroimage Clin 2021 19;29:102567. Epub 2021 Jan 19.

Cognitive Neuroscience Center, Department of Biomedical Sciences of Cells & Systems, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Apathy is recognized as a prevalent behavioral symptom of amnestic Mild Cognitive Impairment (aMCI). In aMCI, apathy is associated with an increased risk and increases the risk of progression to Alzheimer's Disease (AD). Previous DTI study in aMCI showed that apathy has been associated with white matter alterations in the cingulum, middle and inferior longitudinal fasciculus, fornix, and uncinate fasciculus. However, the underlying white matter correlates associated with apathy in aMCI are still unclear. We investigated this relationship using whole-brain diffusion tensor imaging (DTI). Twenty-nine aMCI patients and 20 matched cognitively healthy controls were included. Apathy severity was assessed using the Apathy Evaluation Scale Clinician version. We applied the tract-based spatial statistics analyses to DTI parameters: fractional anisotropy (FA), mean diffusivity, axial diffusivity, and radial diffusivity to investigate changes in white matter pathways associated with the severity of apathy. No significant difference was found in any of the DTI parameters between aMCI and the control group. In aMCI, higher severity of apathy was associated with lower FA in various white matter pathways including the left anterior part of inferior fronto-occipital fasciculus/uncinate fasciculus, genu and body of the corpus callosum, superior and anterior corona radiata, anterior thalamic radiation of both hemispheres and in the right superior longitudinal fasciculus/anterior segment of arcuate fasciculus (p < .05, TFCE-corrected) after controlling for age, gender and GDS non-apathy. A trend association was observed in the right posterior corona radiata and corticospinal tract/internal capsule, and bilateral forceps minor (p < .065, TFCE-corrected). In conclusion, in aMCI, severity of apathy is associated with aberrant white matter integrity in widely distributed pathways, within and between hemispheres.
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http://dx.doi.org/10.1016/j.nicl.2021.102567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856325PMC
June 2021

Connectome-Based Predictive Modeling of Individual Anxiety.

Cereb Cortex 2021 05;31(6):3006-3020

Beijing Key Laboratory of Applied Experimental Psychology, Faculty of Psychology, Beijing Normal University, Beijing 100875, China.

Anxiety-related illnesses are highly prevalent in human society. Being able to identify neurobiological markers signaling high trait anxiety could aid the assessment of individuals with high risk for mental illness. Here, we applied connectome-based predictive modeling (CPM) to whole-brain resting-state functional connectivity (rsFC) data to predict the degree of trait anxiety in 76 healthy participants. Using a computational "lesion" approach in CPM, we then examined the weights of the identified main brain areas as well as their connectivity. Results showed that the CPM successfully predicted individual anxiety based on whole-brain rsFC, especially the rsFC between limbic areas and prefrontal cortex. The prediction power of the model significantly decreased from simulated lesions of limbic areas, lesions of the connectivity within limbic areas, and lesions of the connectivity between limbic areas and prefrontal cortex. Importantly, this neural model generalized to an independent large sample (n = 501). These findings highlight important roles of the limbic system and prefrontal cortex in anxiety prediction. Our work provides evidence for the usefulness of connectome-based modeling in predicting individual personality differences and indicates its potential for identifying personality factors at risk for psychopathology.
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http://dx.doi.org/10.1093/cercor/bhaa407DOI Listing
May 2021

Insight does not come at random: Individual gray matter networks relate to clinical and cognitive insight in schizophrenia.

Prog Neuropsychopharmacol Biol Psychiatry 2021 07 23;109:110251. Epub 2021 Jan 23.

Department of Biomedical Sciences of Cells and Systems, Cognitive Neuroscience Center, University of Groningen, University Medical Center Groningen, Antonius Deusinglaan 2, 9713 AW Groningen, the Netherlands.

Background: Impaired clinical and cognitive insight are prevalent in schizophrenia and relate to poorer outcome. Good insight has been suggested to depend on social cognitive and metacognitive abilities requiring global integration of brain signals. Impaired insight has been related to numerous focal gray matter (GM) abnormalities distributed across the brain suggesting dysconnectivity at the global level. In this study, we test whether global integration deficiencies reflected in gray matter network connectivity underlie individual variations in insight.

Methods: We used graph theory to examine whether individual GM-network metrics relate to insight in patients with a psychotic disorder (n = 114). Clinical insight was measured with the Schedule for the Assessment of Insight-Expanded and item G12 of the Positive and Negative Syndrome Scale, and cognitive insight with the Beck Cognitive Insight Scale. Individual GM-similarity networks were created from GM-segmentations of T1-weighted MRI-scans. Graph metrics were calculated using the Brain Connectivity Toolbox.

Results: Networks of schizophrenia patients with poorer clinical insight showed less segregation (i.e. clustering coefficient) into specialized subnetworks at the global level. Schizophrenia patients with poorer cognitive insight showed both less segregation and higher connectedness (i.e. lower path length) of their brain networks, making their network topology more "random".

Conclusions: Our findings suggest less segregated processing of information in patients with poorer cognitive and clinical insight, in addition to higher connectedness in patients with poorer cognitive insight. The ability to take a critical perspective on one's symptoms (clinical insight) or views (cognitive insight) might depend especially on segregated specialized processing within distinct subnetworks.
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http://dx.doi.org/10.1016/j.pnpbp.2021.110251DOI Listing
July 2021

Intrinsic Connectivity Patterns of Task-Defined Brain Networks Allow Individual Prediction of Cognitive Symptom Dimension of Schizophrenia and Are Linked to Molecular Architecture.

Biol Psychiatry 2021 02 3;89(3):308-319. Epub 2020 Oct 3.

Institute of Neuroscience and Medicine: Brain and Behavior (INM-7), Research Center Jülich, Jülich, Germany; Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.

Background: Despite the marked interindividual variability in the clinical presentation of schizophrenia, the extent to which individual dimensions of psychopathology relate to the functional variability in brain networks among patients remains unclear. Here, we address this question using network-based predictive modeling of individual psychopathology along 4 data-driven symptom dimensions. Follow-up analyses assess the molecular underpinnings of predictive networks by relating them to neurotransmitter-receptor distribution patterns.

Methods: We investigated resting-state functional magnetic resonance imaging data from 147 patients with schizophrenia recruited at 7 sites. Individual expression along negative, positive, affective, and cognitive symptom dimensions was predicted using a relevance vector machine based on functional connectivity within 17 meta-analytic task networks following repeated 10-fold cross-validation and leave-one-site-out analyses. Results were validated in an independent sample. Networks robustly predicting individual symptom dimensions were spatially correlated with density maps of 9 receptors/transporters from prior molecular imaging in healthy populations.

Results: Tenfold and leave-one-site-out analyses revealed 5 predictive network-symptom associations. Connectivity within theory of mind, cognitive reappraisal, and mirror neuron networks predicted negative, positive, and affective symptom dimensions, respectively. Cognitive dimension was predicted by theory of mind and socioaffective default networks. Importantly, these predictions generalized to the independent sample. Intriguingly, these two networks were positively associated with D receptor and serotonin reuptake transporter densities as well as dopamine synthesis capacity.

Conclusions: We revealed a robust association between intrinsic functional connectivity within networks for socioaffective processes and the cognitive dimension of psychopathology. By investigating the molecular architecture, this work links dopaminergic and serotonergic systems with the functional topography of brain networks underlying cognitive symptoms in schizophrenia.
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http://dx.doi.org/10.1016/j.biopsych.2020.09.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770333PMC
February 2021

Alpha Power and Functional Connectivity in Cognitive Decline: A Systematic Review and Meta-Analysis.

J Alzheimers Dis 2020 ;78(3):1047-1088

University of Groningen, University Medical Center Groningen, Department of Biomedical Sciences of Cells & Systems, Cognitive Neuroscience Center, Groningen, The Netherlands.

Background: Mild cognitive impairment (MCI) is a stage between expected age-related cognitive decline and dementia. Dementias have been associated with changes in neural oscillations across the frequency spectrum, including the alpha range. Alpha is the most prominent rhythm in human EEG and is best detected during awake resting state (RS). Though several studies measured alpha power and synchronization in MCI, findings have not yet been integrated.

Objective: To consolidate findings on power and synchronization of alpha oscillations across stages of cognitive decline.

Methods: We included studies published until January 2020 that compared power or functional connectivity between 1) people with MCI and cognitively healthy older adults (OA) or people with a neurodegenerative dementia, and 2) people with progressive and stable MCI. Random-effects meta-analyses were performed when enough data was available.

Results: Sixty-eight studies were included in the review. Global RS alpha power was lower in AD than in MCI (ES = -0.30; 95% CI = -0.51, -0.10; k = 6), and in MCI than in OA (ES = -1.49; 95% CI = -2.69, -0.29; k = 5). However, the latter meta-analysis should be interpreted cautiously due to high heterogeneity. The review showed lower RS alpha power in progressive than in stable MCI, and lower task-related alpha reactivity in MCI than in OA. People with MCI had both lower and higher functional connectivity than OA. Publications lacked consistency in MCI diagnosis and EEG measures.

Conclusion: Research indicates that RS alpha power decreases with increasing impairment, and could-combined with measures from other frequency bands-become a biomarker of early cognitive decline.
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http://dx.doi.org/10.3233/JAD-200962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739973PMC
September 2021

Efficacy of non-invasive brain stimulation on cognitive functioning in brain disorders: a meta-analysis.

Psychol Med 2020 11 19;50(15):2465-2486. Epub 2020 Oct 19.

Department of Biomedical Sciences of Cells & Systems, Section Cognitive Neurosciences, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Background: Cognition is commonly affected in brain disorders. Non-invasive brain stimulation (NIBS) may have procognitive effects, with high tolerability. This meta-analysis evaluates the efficacy of transcranial magnetic stimulation (TMS) and transcranial Direct Current Stimulation (tDCS) in improving cognition, in schizophrenia, depression, dementia, Parkinson's disease, stroke, traumatic brain injury, and multiple sclerosis.

Methods: A PRISMA systematic search was conducted for randomized controlled trials. Hedges' g was used to quantify effect sizes (ES) for changes in cognition after TMS/tDCS v. sham. As different cognitive functions may have unequal susceptibility to TMS/tDCS, we separately evaluated the effects on: attention/vigilance, working memory, executive functioning, processing speed, verbal fluency, verbal learning, and social cognition.

Results: We included 82 studies (n = 2784). For working memory, both TMS (ES = 0.17, p = 0.015) and tDCS (ES = 0.17, p = 0.021) showed small but significant effects. Age positively moderated the effect of TMS. TDCS was superior to sham for attention/vigilance (ES = 0.20, p = 0.020). These significant effects did not differ across the type of brain disorder. Results were not significant for the other five cognitive domains.

Conclusions: Our results revealed that both TMS and tDCS elicit a small trans-diagnostic effect on working memory, tDCS also improved attention/vigilance across diagnoses. Effects on the other domains were not significant. Observed ES were small, yet even slight cognitive improvements may facilitate daily functioning. While NIBS can be a well-tolerated treatment, its effects appear domain specific and should be applied only for realistic indications (i.e. to induce a small improvement in working memory or attention).
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http://dx.doi.org/10.1017/S0033291720003670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737055PMC
November 2020

Thinking fast or slow? Functional magnetic resonance imaging reveals stronger connectivity when experienced neurologists diagnose ambiguous cases.

Brain Commun 2020 2;2(1):fcaa023. Epub 2020 Mar 2.

Center for Education Development and Research in Health Professions, University of Groningen and University Medical Center Groningen, P.O. Box 196, 9700 AD Groningen, The Netherlands.

For ∼40 years, thinking about reasoning has been dominated by dual-process theories. This model, consisting of two distinct types of human reasoning, one fast and effortless and the other slow and deliberate, has also been applied to medical diagnosis. Medical experts are trained to diagnose patients based on their symptoms. When symptoms are prototypical for a certain diagnosis, practitioners may rely on fast, recognition-based reasoning. However, if they are confronted with ambiguous clinical information slower, analytical reasoning is required. To examine the neural underpinnings of these two hypothesized forms of reasoning, 16 highly experienced clinical neurologists were asked to diagnose two types of medical cases, straightforward and ambiguous cases, while functional magnetic resonance imaging was being recorded. Compared with reading control sentences, diagnosing cases resulted in increased activation in brain areas typically found to be active during reasoning such as the caudate nucleus and frontal and parietal cortical regions. In addition, we found vast increased activity in the cerebellum. Regarding the activation differences between the two types of reasoning, no pronounced differences were observed in terms of regional activation. Notable differences were observed, though, in functional connectivity: cases containing ambiguous information showed stronger connectivity between specific regions in the frontal, parietal and temporal cortex in addition to the cerebellum. Based on these results, we propose that the higher demands in terms of controlled cognitive processing during analytical medical reasoning may be subserved by stronger communication between key regions for detecting and resolving uncertainty.
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http://dx.doi.org/10.1093/braincomms/fcaa023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425520PMC
March 2020

Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders.

JAMA Psychiatry 2021 Jan;78(1):47-63

Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Maastricht University, the Netherlands.

Importance: Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood.

Objective: To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia.

Design, Setting, And Participants: Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244.

Main Outcomes And Measures: Interregional profiles of group difference in cortical thickness between cases and controls.

Results: A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (except for OCD); collectively, gene-expression profiles of the 3 cell types explain between 25% and 54% of variance in interregional profiles of group differences in cortical thickness. Principal component analysis revealed a shared profile of difference in cortical thickness across the 6 disorders (48% variance explained); interregional profile of this principal component 1 was associated with that of the pyramidal-cell gene expression (explaining 56% of interregional variation). Coexpression analyses of these genes revealed 2 clusters: (1) a prenatal cluster enriched with genes involved in neurodevelopmental (axon guidance) processes and (2) a postnatal cluster enriched with genes involved in synaptic activity and plasticity-related processes. These clusters were enriched with genes associated with all 6 psychiatric disorders.

Conclusions And Relevance: In this study, shared neurobiologic processes were associated with differences in cortical thickness across multiple psychiatric disorders. These processes implicate a common role of prenatal development and postnatal functioning of the cerebral cortex in these disorders.
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http://dx.doi.org/10.1001/jamapsychiatry.2020.2694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450410PMC
January 2021

Abnormal dynamic resting-state brain network organization in auditory verbal hallucination.

Brain Struct Funct 2020 Nov 19;225(8):2315-2330. Epub 2020 Aug 19.

Department of Biomedical Sciences of Cells and Systems, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Auditory-verbal hallucinations (AVH) are a key symptom of schizophrenia. Recent neuroimaging studies examining dynamic functional connectivity suggest that disrupted dynamic interactions between brain networks characterize complex symptoms in mental illness including schizophrenia. Studying dynamic connectivity may be especially relevant for hallucinations, given their fluctuating phenomenology. Indeed, it remains unknown whether AVH in schizophrenia are directly related to altered dynamic connectivity within and between key brain networks involved in auditory perception and language, emotion processing, and top-down control. In this study, we used dynamic connectivity approaches including sliding window and k-means to examine dynamic interactions among brain networks in schizophrenia patients with and without a recent history of AVH. Dynamic brain network analysis revealed that patients with AVH spent less time in a 'network-antagonistic' brain state where the default mode network (DMN) and the language network were anti-correlated, and had lower probability to switch into this brain state. Moreover, patients with AVH showed a lower connectivity within the language network and the auditory network, and lower connectivity was observed between the executive control and the language networks in certain dynamic states. Our study provides the first neuroimaging evidence of altered dynamic brain networks for understanding neural mechanisms of AVH in schizophrenia. The findings may inform and further strengthen cognitive models of AVH that aid the development of new coping strategies for patients.
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http://dx.doi.org/10.1007/s00429-020-02119-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544708PMC
November 2020

Real-Time Functional Magnetic Resonance Imaging Neurofeedback for the Relief of Distressing Auditory-Verbal Hallucinations: Methodological and Empirical Advances.

Schizophr Bull 2020 12;46(6):1409-1417

Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Auditory-verbal hallucinations (AVH) are often associated with high levels of distress and disability in individuals with schizophrenia-spectrum disorders. In around 30% of individuals with distressing AVH and diagnosed with schizophrenia, traditional antipsychotic drugs have little or no effect. Thus, it is important to develop mechanistic models of AVH to inform new treatments. Recently a small number of studies have begun to explore the use of real-time functional magnetic resonance imaging neurofeedback (rtfMRI-NF) for the treatment of AVH in individuals with schizophrenia. rtfMRI-NF protocols have been developed to provide feedback about brain activation in real time to enable participants to progressively achieve voluntary control over their brain activity. We offer a conceptual review of the background and general features of neurofeedback procedures before summarizing and evaluating existing mechanistic models of AVH to identify feasible neural targets for the application of rtfMRI-NF as a potential treatment. We consider methodological issues, including the choice of localizers and practicalities in logistics when setting up neurofeedback procedures in a clinical setting. We discuss clinical considerations relating to the use of rtfMRI-NF for AVH in individuals distressed by their experiences and put forward a number of questions and recommendations about best practice. Lastly, we conclude by offering suggestions for new avenues for neurofeedback methodology and mechanistic targets in relation to the research and treatment of AVH.
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http://dx.doi.org/10.1093/schbul/sbaa103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707074PMC
December 2020

Joint Multi-modal Parcellation of the Human Striatum: Functions and Clinical Relevance.

Neurosci Bull 2020 Oct 23;36(10):1123-1136. Epub 2020 Jul 23.

Institute of Neuroscience and Medicine (INM-7, Brain and Behaviour), Research Centre Jülich, Jülich, Germany.

The human striatum is essential for both low- and high-level functions and has been implicated in the pathophysiology of various prevalent disorders, including Parkinson's disease (PD) and schizophrenia (SCZ). It is known to consist of structurally and functionally divergent subdivisions. However, previous parcellations are based on a single neuroimaging modality, leaving the extent of the multi-modal organization of the striatum unknown. Here, we investigated the organization of the striatum across three modalities-resting-state functional connectivity, probabilistic diffusion tractography, and structural covariance-to provide a holistic convergent view of its structure and function. We found convergent clusters in the dorsal, dorsolateral, rostral, ventral, and caudal striatum. Functional characterization revealed the anterior striatum to be mainly associated with cognitive and emotional functions, while the caudal striatum was related to action execution. Interestingly, significant structural atrophy in the rostral and ventral striatum was common to both PD and SCZ, but atrophy in the dorsolateral striatum was specifically attributable to PD. Our study revealed a cross-modal convergent organization of the striatum, representing a fundamental topographical model that can be useful for investigating structural and functional variability in aging and in clinical conditions.
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http://dx.doi.org/10.1007/s12264-020-00543-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532244PMC
October 2020

The silent danger of social distancing.

Psychol Med 2020 Jul 6:1-2. Epub 2020 Jul 6.

Department of Biomedical Sciences of Cells and Systems, University of Groningen, University Medical Center Groningen, Netherlands.

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http://dx.doi.org/10.1017/S0033291720002597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360942PMC
July 2020

ENIGMA MDD: seven years of global neuroimaging studies of major depression through worldwide data sharing.

Transl Psychiatry 2020 05 29;10(1):172. Epub 2020 May 29.

Illinois Institute of Technology, Chicago, IL, USA.

A key objective in the field of translational psychiatry over the past few decades has been to identify the brain correlates of major depressive disorder (MDD). Identifying measurable indicators of brain processes associated with MDD could facilitate the detection of individuals at risk, and the development of novel treatments, the monitoring of treatment effects, and predicting who might benefit most from treatments that target specific brain mechanisms. However, despite intensive neuroimaging research towards this effort, underpowered studies and a lack of reproducible findings have hindered progress. Here, we discuss the work of the ENIGMA Major Depressive Disorder (MDD) Consortium, which was established to address issues of poor replication, unreliable results, and overestimation of effect sizes in previous studies. The ENIGMA MDD Consortium currently includes data from 45 MDD study cohorts from 14 countries across six continents. The primary aim of ENIGMA MDD is to identify structural and functional brain alterations associated with MDD that can be reliably detected and replicated across cohorts worldwide. A secondary goal is to investigate how demographic, genetic, clinical, psychological, and environmental factors affect these associations. In this review, we summarize findings of the ENIGMA MDD disease working group to date and discuss future directions. We also highlight the challenges and benefits of large-scale data sharing for mental health research.
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http://dx.doi.org/10.1038/s41398-020-0842-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260219PMC
May 2020
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