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Background: Amnestic mild cognitive impairment (aMCI), considered as the prodromal stage of Alzheimer's disease, is characterized by isolated memory impairment and cerebral gray matter volume (GMV) alterations. Previous structural MRI studies in aMCI have been mainly based on univariate statistics using voxel-based morphometry. Objective: We investigated structural network differences between aMCI patients and cognitively normal older adults by using source-based morphometry, a multivariate approach that considers the relationship between voxels of various parts of the brain. Methods: Ninety-one aMCI patients and 80 cognitively normal controls underwent structural MRI and neuropsychological assessment. Spatially independent components (ICs) that covaried between participants were estimated and a multivariate analysis of covariance was performed with ICs as dependent variables, diagnosis as independent variable, and age, sex, education level, and site as covariates. Results: aMCI patients exhibited reduced GMV in the precentral, temporo-cerebellar, frontal, and temporal network, and increased GMV in the left superior parietal network compared to controls (pFWERâ<â0.05, Holm-Bonferroni correction). Moreover, we found that diagnosis, more specifically aMCI, moderated the positive relationship between occipital network and Mini-Mental State Examination scores (pFWERâ<â0.05, Holm-Bonferroni correction). Conclusions: Our results showed GMV alterations in temporo-fronto-parieto-cerebellar networks in aMCI, extending previous results obtained with univariate approaches.
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Major Depressive Disorder (MDD) often is a recurrent and chronic disorder. We investigated the neurocognitive underpinnings of the incremental risk for poor disease course by exploring relations between enduring depression and brain functioning during regulation of negative and positive emotions using cognitive reappraisal. We used fMRI-data from the longitudinal Netherlands Study of Depression and Anxiety acquired during an emotion regulation task in 77 individuals with MDD. Task-related brain activity was related to disease load, calculated from presence and severity of depression in the preceding nine years. Additionally, we explored task related brain-connectivity. Brain functioning in individuals with MDD was further compared to 35 controls to explore overlap between load-effects and general effects related to MDD history/presence. Disease load was not associated with changes in affect or with brain activity, but with connectivity between areas essential for processing, integrating and regulating emotional information during downregulation of negative emotions. Results did not overlap with general MDD-effects. Instead, MDD was generally associated with lower parietal activity during downregulation of negative emotions. During upregulation of positive emotions, disease load was related to connectivity between limbic regions (although driven by symptomatic state), and connectivity between frontal, insular and thalamic regions was lower in MDD (vs controls). Results suggest that previous depressive load relates to brain connectivity in relevant networks during downregulation of negative emotions. These abnormalities do not overlap with disease-general abnormalities and could foster an incremental vulnerability to recurrence or chronicity of MDD. Therefore, optimizing emotion regulation is a promising therapeutic target for improving long-term MDD course.
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Transtorno Depressivo Maior , Regulação Emocional , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Emoções/fisiologia , Imageamento por Ressonância Magnética/métodosRESUMO
BACKGROUND: The recurrent nature of Major Depressive Disorder (MDD) asks for a better understanding of mechanisms underlying relapse. Previously, self-referential processing abnormalities have been linked to vulnerability for relapse. We investigated whether abnormalities in self-referential cognitions and functioning of associated brain-networks persist upon remission and predict relapse. METHODS: Remitted recurrent MDD patients (n = 48) and never-depressed controls (n = 23) underwent resting-state fMRI scanning at baseline and were additionally assessed for their implicit depressed self-associations and ruminative behaviour. A template-based dual regression approach was used to investigate between-group differences in default mode, cingulo-opercular and frontoparietal network resting-state functional connectivity (RSFC). Additional prediction of relapse status at 18-month follow-up was investigated within patients using both regression analyses and machine learning classifiers. RESULTS: Remitted patients showed higher rumination, but no implicit depressed self-associations or RSFC abnormalities were observed between patients and controls. Nevertheless, relapse was related to i) baseline RSFC between the ventral default mode network and the precuneus, dorsomedial frontal gyrus, and inferior occipital lobe, ii) implicit self-associations, and iii) uncontrollability of ruminative thinking, when controlled for depressive symptomatology. Moreover, preliminary machine learning classifiers demonstrated that RSFC within the investigated networks predicted relapse on an individual basis. CONCLUSIONS: Remitted MDD patients seem to be commonly characterized by abnormal rumination, but not by implicit self-associations or abnormalities in relevant brain networks. Nevertheless, relapse was predicted by self-related cognitions and default mode RSFC during remission, suggesting that variations in self-relevant processing play a role in the complex dynamics associated with the vulnerability to developing recurrent depressive episodes. CLINICAL TRIAL REGISTRATION: Netherlands Trial Register, August 18, 2015, trial number NL53205.042.15.
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Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Depressão , Encéfalo/diagnóstico por imagem , Lobo Frontal , Imageamento por Ressonância Magnética , Recidiva , Mapeamento EncefálicoRESUMO
BACKGROUND: It has been theorized that hallucinations, a common symptom of schizophrenia, are caused by failures in reality monitoring. The paracingulate sulcus (PCS) has been implicated as a brain structure supporting reality monitoring with the absence or shorter length of PCS associated with an occurrence of hallucinations in schizophrenia. The absence or shorter length of PCS has been associated with an occurrence of hallucinations. There are inconsistent findings in the literature regarding the role of the asymmetry of this structure for hallucinations. Here, we investigated the length of the PCS and cortical thickness of surrounding structures in patients with a lifetime history of auditory verbal hallucinations (AVH). DESIGN: Seventy-seven patients and twenty-eight healthy controls (HC) underwent an anatomical MRI scan. PCS length and cortical thickness were estimated using Mango brain visualization and FreeSurfer, respectively. Patients with AVH (n = 45) and patients without AVH were compared (n = 32) to the controls. RESULTS: PCS length significantly differed between HC and patient groups (F(2,102) = 3.57, P = .032) in the left but not in the right sulcus. We found significantly longer PCS between HC and AVH group but no difference between patient groups. Similarly, we found significant thinning of cortical structures including structures surrounding anterior parts of PCS between HC and patients either in general or per group, but no significant differences were observed between patient groups. CONCLUSIONS: PCS length in the left hemisphere is shorter in schizophrenia patients with hallucinations as compared to HC subjects. The patient group without hallucinations was in between those 2 groups. Cortical thickness of neighboring areas of PCS is diminished in patient groups relative to the healthy comparison subjects. The role of lateralization and functional involvement of the PCS region in processes underlying hallucinations, such as reality monitoring, needs further clarification.
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Esquizofrenia , Humanos , Alucinações , Encéfalo , Imageamento por Ressonância Magnética , NeuroimagemRESUMO
Older age is associated with worsened outcome after mild traumatic brain injury (mTBI) and a higher risk of developing persistent post-traumatic complaints. However, the effects of mTBI sequelae on brain connectivity at older age and their association with post-traumatic complaints remain understudied.We analyzed multi-echo resting-state functional magnetic resonance imaging data from 25 older adults with mTBI (mean age: 68 years, SD: 5 years) in the subacute phase (mean injury to scan interval: 38 days, SD: 9 days) and 20 age-matched controls. Severity of complaints (e.g. fatigue, dizziness) was assessed using self-reported questionnaires. Group independent component analysis was used to identify intrinsic connectivity networks (ICNs). The effects of group and severity of complaints on ICNs were assessed using spatial maps intensity (SMI) as a measure of within-network connectivity, and (static) functional network connectivity (FNC) as a measure of between-network connectivity.Patients indicated a higher total severity of complaints than controls. Regarding SMI measures, we observed hyperconnectivity in left-mid temporal gyrus (cognitive-language network) and hypoconnectivity in the right-fusiform gyrus (visual-cerebellar network) that were associated with group. Additionally, we found interaction effects for SMI between severity of complaints and group in the visual(-cerebellar) domain. Regarding FNC measures, no significant effects were found.In older adults, changes in cognitive-language and visual(-cerebellar) networks are related to mTBI. Additionally, group-dependent associations between connectivity within visual(-cerebellar) networks and severity of complaints might indicate post-injury (mal)adaptive mechanisms, which could partly explain post-traumatic complaints (such as dizziness and balance disorders) that are common in older adults during the subacute phase.
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Concussão Encefálica , Idoso , Encéfalo/diagnóstico por imagem , Concussão Encefálica/diagnóstico por imagem , Tontura/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Rede Nervosa/diagnóstico por imagemRESUMO
The recurrent nature of Major Depressive Disorder (MDD) necessitates a better understanding of mechanisms facilitating relapse. MDD has often been associated with abnormal emotion regulation, underpinned by aberrant interactions between the prefrontal cortex and subcortical areas. We assessed whether neural regulation abnormalities remain after remission and relate to emotion regulation problems in daily life. At the baseline measurement of a randomized controlled trial, an emotion regulation task was performed during fMRI scanning by 46 remitted recurrent (rrMDD) patients and 24 healthy controls. We assessed both fMRI peak activity and the temporal dynamics of the neural response during passive attendance and explicit regulation of positive and negative emotions. Furthermore, we assessed regulation strategy use in daily life using questionnaires, and attentional biases using a modified attentional dot-probe task. RrMDD patients showed lower activation and different temporal dynamics in occipital, parietal, and prefrontal brain regions during passive attendance of emotional material compared to healthy controls. During explicit downregulation of negative emotions, no group differences were found. However, during explicit upregulation of positive emotions, rrMDD patients showed a different neural response over time in the insula. Behaviourally, rrMDD patients were characterized by dysfunctional regulation strategies in daily life. Within rrMDD patients, rumination was associated with activation within a limbic- prefrontal network. After remission, immediate emotional processing seems unaffected, but regulatory abnormalities remain, especially uninstructed and in daily life. Abnormal insula activation during positive upregulation suggests decreased monitoring of positive emotions. The relation between inadequate rumination and brain activity during emotion regulation suggests that regulation of both positive and negative affect is important in understanding neurocognitive underpinnings of resilience.
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Transtorno Depressivo Maior , Regulação Emocional , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Depressão , Emoções/fisiologia , Humanos , Imageamento por Ressonância MagnéticaRESUMO
INTRODUCTION: The memory impairment that is characteristic of amnestic mild cognitive impairment (aMCI) is often accompanied by difficulties in executive functioning, including planning. Though planning deficits in aMCI are well documented, their neural correlates are largely unknown, and have not yet been investigated with functional magnetic resonance imaging (fMRI). OBJECTIVES: The aim of this study was to: (1) identify differences in brain activity and connectivity during planning between people with aMCI and cognitively healthy older adults, and (2) find whether planning-related activity and connectivity are associated with cognitive performance and symptoms of apathy. METHODS: Twenty-five people with aMCI and 15 cognitively healthy older adults performed a visuospatial planning task (Tower of London; ToL) during fMRI. Task-related brain activation, spatial maps of task-related independent components, and seed-to-voxel functional connectivity were compared between the two groups and regressed against measures of executive functions (Trail Making Test difference score, TMT B-A; Digit Symbol Substitution Test, DSST), delayed recall (Rey Auditory Verbal Learning Test), and apathy (Apathy Evaluation Scale). RESULTS: People with aMCI scored lower on task-switching (TMT B-A), working memory (DSST), and planning (ToL). During planning, people with aMCI had less activation in the bilateral anterior calcarine sulcus/cuneus, the bilateral temporal cortices, the left precentral gyrus, the thalamus, and the right cerebellum. Across all participants, higher planning-related activity in the supplementary motor area, the retrosplenial cortex and surrounding areas, and the right temporal cortex was related to better delayed recall. There were no between-group differences in functional connectivity, nor were there any associations between connectivity and cognition. We also did not find any associations between brain activity or connectivity and apathy. CONCLUSION: Impaired planning in people with aMCI appears to be accompanied by lower activation in a diffuse cortico-thalamic network. Across all participants, higher planning-related activity in parieto-occipital, temporal, and frontal areas was related to better memory performance. The results point to the relevance of planning deficits for understanding aMCI and extend its clinical and neurobiological signature.
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Disfunção Cognitiva , Imageamento por Ressonância Magnética , Idoso , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Disfunção Cognitiva/diagnóstico por imagem , Função Executiva , Humanos , Imageamento por Ressonância Magnética/métodos , Testes NeuropsicológicosRESUMO
Studying individuals who recently experienced a romantic reltionship breakup allows us to investigate mood disturbances in otherwise healthy individuals. In our study, we aimed to identify distinct depressive symptom trajectories following breakup and investigate whether these trajectories relate to personality traits and cognitive control. Subjects (n = 87) filled out questionnaires (RRS-NL-EXT trait rumination and NEO-FFI neuroticism) and performed cognitive tasks (trail making test, Stroop task) during a period of 30 weeks. To identify distinct depressive symptom trajectories ('trajectory groups'), we performed K-means clustering on the consecutive (assessed every 2 weeks) Major Depression Inventory scores. This resulted in four trajectory groups; 'resilience', 'fast recovery', 'slow recovery' and 'chronic distress'. The 'slow recovery group' and the 'chronic distress group' were found to have higher neuroticism and trait rumination levels compared to the 'resilience group', and the 'chronic distress group' also had higher neuroticism levels than the 'fast recovery group'. Moreover, the 'chronic distress group' showed worse overall trail making test performance than the 'resilience group'. Taken together, our findings show that distinct patterns of depressive symptom severity can be observed following breakup and that personality traits and cognitive flexibility seem to play a role in these depressive symptom patterns.
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Depressão , Transtorno Depressivo Maior , Cognição , Depressão/psicologia , Humanos , Neuroticismo , Personalidade , Inquéritos e QuestionáriosRESUMO
Incomplete spinal cord injury (SCI) may result in muscle weakness and difficulties with force gradation. Although these impairments arise from the injury and subsequent changes at spinal levels, changes have also been demonstrated in the brain. Blood-oxygen-level dependent (BOLD) imaging was used to investigate these changes in brain activation in the context of unimanual contractions with the first dorsal interosseous muscle. BOLD- and force data were obtained in 19 individuals with SCI (AISA Impairment Scale [AIS] C/D, level C4-C8) and 24 able-bodied controls during maximal voluntary contractions (MVCs). To assess force modulation, participants performed 12 submaximal contractions with each hand (at 10, 30, 50, and 70% MVC) by matching their force level to a visual target. MVCs were weaker in the SCI group (both hands p < 0.001), but BOLD activation did not differ between SCI and control groups. For the submaximal contractions, force (as %MVC) was similar across groups. However, SCI participants showed increased activity of the ipsilateral motor cortex and contralateral cerebellum across all contractions, with no differential effect of force level. Activity of ipsilateral M1 was best explained by force of the target hand (vs. the non-target hand). In conclusion, the data suggest that after incomplete cervical SCI, individuals remain capable of producing maximal supraspinal drive and are able to modulate this drive adequately. Activity of the ipsilateral motor network appears to be task related, although it remains uncertain how this activity contributes to task performance and whether this effect could potentially be harnessed to improve motor functioning.
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Atividade Motora/fisiologia , Contração Muscular/fisiologia , Músculo Esquelético/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , Adulto , Idoso , Estudos de Casos e Controles , Cerebelo/diagnóstico por imagem , Cerebelo/fisiopatologia , Vértebras Cervicais , Feminino , Mãos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Motor/diagnóstico por imagem , Córtex Motor/fisiopatologia , Traumatismos da Medula Espinal/diagnóstico por imagemRESUMO
INTRODUCTION: Following mild traumatic brain injury (mTBI), a substantial number of patients experience disabling fatigue for months after the initial injury. To date, the underlying mechanisms of fatigue remain unclear. Recently, it was shown that mTBI patients with persistent fatigue do not demonstrate increased performance fatigability (i.e., objective performance decline) during a sustained motor task. However, it is not known whether the neural activation required to sustain this performance is altered after mTBI. METHODS: Blood oxygen level-dependent (BOLD) fMRI data were acquired from 19 mTBI patients (>3 months post-injury) and 19 control participants during two motor tasks. Force was recorded from the index finger abductors of both hands during submaximal contractions and a 2-minute maximal voluntary contraction (MVC) with the right hand. Voluntary muscle activation (i.e., CNS drive) was indexed during the sustained MVC using peripheral nerve stimulation. Fatigue was quantified using the Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS). Questionnaire, task, and BOLD data were compared across groups, and linear regression was used to evaluate the relationship between BOLD-activity and fatigue in the mTBI group. RESULTS: The mTBI patients reported significantly higher levels of fatigue (FSS: 5.3 vs. 2.6, p < 0.001). Both mTBI- and control groups demonstrated significant performance fatigability during the sustained MVC, but no significant differences in task performance or BOLD-activity were observed between groups. However, mTBI patients reporting higher FSS scores showed increased BOLD-activity in the bilateral visual cortices (mainly extrastriate) and the left midcingulate gyrus. Furthermore, across all participants mean voluntary muscle activation during the sustained MVC correlated with long lasting post-contraction BOLD-activation in the right insula and midcingulate cortex. CONCLUSION: The fMRI findings suggest that self-reported fatigue in mTBI may relate to visual processing and effort perception. Long lasting activation associated with high levels of CNS drive might be related to changes in cortical homeostasis in the context of high effort.
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Concussão Encefálica , Concussão Encefálica/complicações , Concussão Encefálica/diagnóstico por imagem , Eletromiografia , Fadiga/etiologia , Humanos , Fadiga Muscular , Saturação de Oxigênio , Percepção VisualRESUMO
Experiencing stress can have a disadvantageous effect on mental well-being. Additional to the relation between suffering from chronic stress and depression, both stress (acute and chronic) and depression are associated with cognitive alterations, including working memory. The breakup of a relationship is considered to be a stressful event that can lead to symptoms of depression in otherwise healthy people. Additional to elevated depression scores, stress-related cognitive alterations may occur in this population as well. Therefore, in the present fMRI study we investigated whether experiencing a relationship breakup is associated with working memory alterations and whether this is related to depressive symptom severity. A three workload version of the n-back task (0-back, 1-back, 2-back) was used to measure working memory in subjects who experienced a breakup in the preceding 6 months ("heartbreak group", n = 70) and subjects in a romantic relationship ("relationship group", n = 46). Behavioral task performance was compared between the two groups. Functional MRI scans were analyzed using General Linear Model (GLM) activation analyses. Workload conditions were contrasted to each other and to baseline and group differences were assessed. To investigate whether brain networks are associated with depressive symptom severity within the heartbreak group specifically, a post hoc feature-based Independent Component Analysis was performed on the 2-back > 0-back contrast images to identify brain regions that covaried across subjects. Behaviorally, the heartbreak group performed similar at high workload (i.e., 2-back) and better at moderate workload (i.e., 1-back) than the relationship group. GLM analysis revealed an interaction between group and 2-back > 0-back, 2-back > 1-back and 2-back > baseline; the heartbreak group showed less precuneus activation compared to the relationship group. Furthermore, within the heartbreak group, we found a negative association between depressive symptom severity and a brain network representing mostly the precuneus, anterior cingulate gyrus and supplementary motor cortex. Our findings suggest that the effect of a breakup is accompanied by workload-dependent working memory alterations. Therefore, we propose that this population can potentially be used to investigate the interplay between stress, cognitive functioning and depression.
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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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Apatia , Disfunção Cognitiva , Substância Branca , Anisotropia , Encéfalo , Disfunção Cognitiva/diagnóstico por imagem , Imagem de Tensor de Difusão , Humanos , Substância Branca/diagnóstico por imagemRESUMO
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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Encéfalo/diagnóstico por imagem , Cognição/fisiologia , Substância Cinzenta/diagnóstico por imagem , Rede Nervosa/diagnóstico por imagem , Esquizofrenia/diagnóstico por imagem , Psicologia do Esquizofrênico , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Individuals with a psychotic disorder are at an increased risk of becoming the victim of a crime. A body-oriented resilience therapy (BEATVIC) aimed at preventing victimization by addressing putatively underlying factors was developed. One of these factors is social cognition, particularly facial affect processing. The current study investigated neural effects of BEATVIC on facial affect processing using two face processing tasks. Participants were randomized to either BEATVIC or a 'Befriending' control group. Twenty-seven patients completed an Emotional Faces task and the Wall of Faces task during fMRI, pre- and post-intervention. General linear model analyses yielded no differences between groups over time. Independent component analyses revealed increased activation of the salience network to angry and fearful faces in BEATVIC compared to Befriending. Increased activation of the salience network may suggest an increased alertness for potentially dangerous faces.
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Terapia Comportamental , Terapia por Exercício , Reconhecimento Facial , Reabilitação Psiquiátrica , Transtornos Psicóticos/fisiopatologia , Transtornos Psicóticos/reabilitação , Cognição Social , Adulto , Terapia Combinada , Reconhecimento Facial/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/diagnóstico por imagem , Resiliência Psicológica , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: Tourette syndrome (TS) is characterised by the presence of sudden, rapid movements and vocalizations (tics). The nature of tics suggests impairments in inhibitory control. However, findings of impaired inhibitory control have so far been inconsistent, possibly due to small sample sizes, wide age ranges, or not taking medication use or attention-deficit/hyperactivity disorder (ADHD) comorbidity into account. METHODS: We investigated group differences in response inhibition using an fMRI-based stop-signal task in 103 8 to 12-year-old children (n = 51 with TS, of whom n = 28 without comorbid ADHD [TS - ADHD] and n = 23 with comorbid ADHD [TS + ADHD]; and n = 52 healthy controls), and related these measures to tic and ADHD severity. RESULTS: We observed an impaired response inhibition performance in children with TS + ADHD, but not in those with TS - ADHD, relative to healthy controls, as evidenced by a slower stop-signal reaction time, slower mean reaction times, and larger variability of reaction times. Dimensional analyses implicated ADHD severity as the driving force in these findings. Neural activation during failed inhibition was stronger in the inferior frontal gyrus and temporal and parietal areas in TS + ADHD compared to healthy controls. CONCLUSIONS: Impaired inhibitory performance and increased neural activity in TS appear to manifest predominantly in relation to ADHD symptomatology.
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Transtorno do Deficit de Atenção com Hiperatividade , Tiques , Síndrome de Tourette , Criança , Humanos , Inibição Psicológica , Imageamento por Ressonância Magnética , Síndrome de Tourette/diagnóstico por imagemRESUMO
For â¼40 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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There is a need for simple and effective ways to screen for visual field defects (VFD). Watching a movie is a simple task most humans are familiar with. Therefore we assessed whether it is possible to detect and reconstruct visual field defects based on free viewing eye movements, recorded while watching movie clips. Participants watched 90 movie clips of one minute, with and without simulated visual field defects (sVFD), while their eye movements were tracked. We simulated homonymous hemianopia (HH) (left and right sided) and glaucoma (small nasal arc, large nasal arc, and tunnel vision). We generated fixation density maps of the visual field and trained a linear support vector machine to predict the viewing conditions of each trial of each participant based on these maps. To reconstruct the visual field defect, we computed "viewing priority" maps and maps of differences in fixation density of the visual field of each participant. We were able to classify the simulated visual field condition with more than 85% accuracy. In simulated HH, the viewing priority distribution over the visual field indicated the location of the sVFD in the simulated HH condition. In simulated glaucoma the difference in fixation density to the control condition indicated the location of the sVFD. It is feasible to use natural viewing behavior to screen for and reconstruct (simulated) visual field defects. Movie clip viewing in combination with eye tracking may thus provide an alternative to or supplement standard automated perimetry, in particular in patients who cannot perform the latter technique.
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Movimentos Oculares/fisiologia , Testes de Campo Visual/métodos , Adulto , Feminino , Glaucoma/diagnóstico , Hemianopsia/diagnóstico , Humanos , MasculinoRESUMO
Maladaptive aggression, as present in conduct disorder (CD) and, to a lesser extent, oppositional defiant disorder (ODD), has been associated with structural alterations in various brain regions, such as ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC), amygdala, insula and ventral striatum. Although aggression can be subdivided into reactive and proactive subtypes, no neuroimaging studies have yet investigated if any structural brain alterations are associated with either of the subtypes specifically. Here we investigated associations between aggression subtypes, CU traits and ADHD symptoms in predefined regions of interest. T1-weighted magnetic resonance images were acquired from 158 children and adolescents with disruptive behavior (ODD/CD) and 96 controls in a multi-center study (aged 8-18). Aggression subtypes were assessed by questionnaires filled in by participants and their parents. Cortical volume and subcortical volumes and shape were determined using Freesurfer and the FMRIB integrated registration and segmentation tool. Associations between volumes and continuous measures of aggression were established using multilevel linear mixed effects models. Proactive aggression was negatively associated with amygdala volume (b = -10.7, p = 0.02), while reactive aggression was negatively associated with insula volume (b = -21.7, p = 0.01). No associations were found with CU traits or ADHD symptomatology. Classical group comparison showed that children and adolescents with disruptive behavior had smaller volumes than controls in (bilateral) vmPFC (p = 0.003) with modest effect size and a reduced shape in the anterior part of the left ventral striatum (p = 0.005). Our study showed negative associations between reactive aggression and volumes in a region involved in threat responsivity and between proactive aggression and a region linked to empathy. This provides evidence for aggression subtype-specific alterations in brain structure which may provide useful insights for clinical practice.
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Transtorno da Conduta , Comportamento Problema , Adolescente , Agressão , Tonsila do Cerebelo , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/diagnóstico por imagem , Criança , Transtorno da Conduta/diagnóstico por imagem , Humanos , Imageamento por Ressonância MagnéticaRESUMO
Depressive symptoms following a stressful life event, such as a relationship breakup, are common, and constitute a potent risk factor for the onset of a major depressive episode. Resting-state neuroimaging studies have increasingly identified abnormal whole-brain communication in patients with depression, but it is currently unclear whether depressive symptoms in individuals without a clinical diagnosis have reliable neural underpinnings. We investigated to what extent the severity of depressive symptoms in a non-clinical sample was associated with imbalances in the complex dynamics of the brain during rest. To this end, a novel intrinsic ignition approach was applied to resting-state neuroimaging data from sixty-nine participants with varying degrees of depressive symptoms following a relationship breakup. Ignition-based measures of integration, hierarchy, and metastability were calculated for each participant, revealing a negative correlation between these measures and depressive ratings. We found that the severity of depressive symptoms was associated with deficits in the brain's capacity to globally integrate and process information over time. Furthermore, we found that increased depressive symptoms were associated with reduced spatial diversity (i.e., hierarchy) and reduced temporal variability (i.e., metastability) in the functional organization of the brain. These findings suggest the merit of investigating constrained dynamical complexity as it is sensitive to the level of depressive symptoms even in a non-clinical sample.
Assuntos
Encéfalo/fisiopatologia , Depressão/fisiopatologia , Depressão/psicologia , Transtorno Depressivo Maior/fisiopatologia , Adolescente , Adulto , Mapeamento Encefálico/métodos , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Neuroimagem/métodos , Descanso/psicologia , Adulto JovemRESUMO
BACKGROUND: Cognitive insight is defined as the ability to reflect upon oneself (i.e. self-reflectiveness), and to not be overly confident of one's own (incorrect) beliefs (i.e. self-certainty). These abilities are impaired in several disorders, while they are essential for the evaluation and regulation of one's behavior. We hypothesized that cognitive insight is a dynamic process, and therefore examined how it relates to temporal dynamics of resting state functional connectivity (FC) and underlying structural network characteristics in 58 healthy individuals. METHODS: Cognitive insight was measured with the Beck Cognitive Insight Scale. FC characteristics were calculated after obtaining four FC states with leading eigenvector dynamics analysis. Gray matter (GM) and DTI connectomes were based on GM similarity and probabilistic tractography. Structural graph characteristics, such as path length, clustering coefficient, and small-world coefficient, were calculated with the Brain Connectivity Toolbox. FC and structural graph characteristics were correlated with cognitive insight. RESULTS: Individuals with lower cognitive insight switched more and spent less time in a globally synchronized state. Additionally, individuals with lower self-reflectiveness spent more time in, had a higher probability of, and had a higher chance of switching to a state entailing default mode network (DMN) areas. With lower self-reflectiveness, DTI-connectomes were segregated less (i.e. lower global clustering coefficient) with lower embeddedness of the left angular gyrus specifically (i.e. lower local clustering coefficient). CONCLUSIONS: Our results suggest less stable functional and structural networks in individuals with poorer cognitive insight, specifically self-reflectiveness. An overly present DMN appears to play a key role in poorer self-reflectiveness.