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BACKGROUND: Little is known about the neural substrates of suicide risk in mood disorders. Improving the identification of biomarkers of suicide risk, as indicated by a history of suicide-related behavior (SB), could lead to more targeted treatments to reduce risk. METHODS: Participants were 18 young adults with a mood disorder with a history of SB (as indicated by endorsing a past suicide attempt), 60 with a mood disorder with a history of suicidal ideation (SI) but not SB, 52 with a mood disorder with no history of SI or SB (MD), and 82 healthy comparison participants (HC). Resting-state functional connectivity within and between intrinsic neural networks, including cognitive control network (CCN), salience and emotion network (SEN), and default mode network (DMN), was compared between groups. RESULTS: Several fronto-parietal regions (k > 57, p < 0.005) were identified in which individuals with SB demonstrated distinct patterns of connectivity within (in the CCN) and across networks (CCN-SEN and CCN-DMN). Connectivity with some of these same regions also distinguished the SB group when participants were re-scanned after 1-4 months. Extracted data defined SB group membership with good accuracy, sensitivity, and specificity (79-88%). CONCLUSIONS: These results suggest that individuals with a history of SB in the context of mood disorders may show reliably distinct patterns of intrinsic network connectivity, even when compared to those with mood disorders without SB. Resting-state fMRI is a promising tool for identifying subtypes of patients with mood disorders who may be at risk for suicidal behavior.
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Corteza Cerebral/fisiopatología , Trastornos del Humor/fisiopatología , Vías Nerviosas/fisiopatología , Ideación Suicida , Intento de Suicidio , Adulto , Mapeo Encefálico , Estudios de Casos y Controles , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Trastornos del Humor/diagnóstico por imagen , Descanso , Adulto JovenRESUMEN
OBJECTIVES: Delays in the diagnosis and detection of bipolar disorder can lead to adverse consequences, including improper treatment and increased suicide risk. The Mood Spectrum Self-Report Measure (MOODS-SR) was designed to capture the full spectrum of lifetime mood symptomology with factor scores for depression and mania symptom constellations. The utility of the MOODS-SR as a tool to investigate homogeneous subgroups was examined, with particular focus on a possible bipolar risk subgroup. Moreover, potential patterns of differences in MOODS-SR subtypes were probed using cognitive vulnerabilities, neuropsychological functioning, and ventral striatum connectivity. METHODS: K-mean cluster analysis based on factor scores of MOODS-SR was used to determine homogeneous subgroupings within a healthy and remitted depressed young adult sample (N = 86). Between-group comparisons (based on cluster subgroupings) were conducted on measures of cognitive vulnerabilities, neuropsychological functioning, and ventral striatum rs-fMRI connectivity. RESULTS: Three groups of participants were identified: one with minimal symptomology, one with moderate primarily depressive symptomology, and one with more severe manic and depressive symptomology. Differences in impulsivity, neuroticism, conscientiousness, facial perception accuracy, and rs-fMRI connectivity exist between moderate and severe groups. CONCLUSIONS: Within a sample of people with and without depression histories, a severe subgroup was identified with potentially increased risk of developing bipolar disorder through use of the MOODS-SR. This small subgroup had higher levels of lifetime depression and mania symptoms. Additionally, differences in traits, affective processing, and connectivity exist between those with a more prototypic unipolar subgrouping and those with potential risk for developing bipolar disorder.
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Trastorno Bipolar/diagnóstico , Trastorno Depresivo Mayor/diagnóstico , Adulto , Afecto , Trastorno Bipolar/psicología , Análisis por Conglomerados , Trastorno Depresivo Mayor/psicología , Femenino , Humanos , Conducta Impulsiva , Masculino , Fenotipo , Psicometría/métodos , Autoinforme , Adulto JovenRESUMEN
Emotion perception deficits could be due to disrupted connectivity of key nodes in the salience and emotion network (SEN), including the amygdala, subgenual anterior cingulate cortex (sgACC), and insula. We examined SEN resting-state (rs-)fMRI connectivity in rMDD in relation to Facial Emotion Perception Test (FEPT) performance. Fifty-two medication-free people ages 18 to 23 years participated. Twenty-seven had major depressive disorder (MDD) in remission (rMDD, 10 males), as MDD is associated with emotion perception deficits and alterations in rsfMRI. Twenty-five healthy controls (10 males) also participated. Participants completed the FEPT during fMRI, in addition to an 8-minute eyes-open resting-state scan. Seed regions of interest were defined in the amygdala, anterior insula and sgACC. Multiple regression analyses co-varied diagnostic group, sex and movement parameters. Emotion perception accuracy was positively associated with connectivity between amygdala seeds and regions primarily in the SEN and cognitive control network (CCN), and also the default mode network (DMN). Accuracy was also positively associated with connectivity between the sgACC seeds and other SEN regions, and the DMN, particularly for the right sgACC. Connectivity negatively associated with emotion perception was mostly with regions outside of these three networks, other than the left insula and part of the DMN. This study is the first to our knowledge to demonstrate relationships between facial emotion processing and resting-state connectivity with SEN nodes and between SEN nodes and regions located within other neural networks.
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Encéfalo/fisiología , Trastorno Depresivo Mayor/fisiopatología , Emociones , Reconocimiento Facial , Adolescente , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Mapeo Encefálico , Trastorno Depresivo Mayor/diagnóstico por imagen , Emociones/fisiología , Reconocimiento Facial/fisiología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiología , Vías Nerviosas/fisiopatología , Pruebas Neuropsicológicas , Análisis de Regresión , Descanso , Adulto JovenRESUMEN
The recent epidemic of obesity corresponds closely with the decline in the average number of hours of sleep obtained nightly. While growing research suggests that sleep loss may affect hormonal and other physiological systems related to food intake, no studies have yet explored the role that sleepiness may play in reducing prefrontal inhibitory control over food intake. Because evidence suggests that women may be more prone to obesity and eating disorders, as well as more likely to suffer from sleep problems, we examined the relation between general daytime sleepiness, brain responses to food stimuli, and self-reported overeating separately for men and women. Thirty-eight healthy adults (16 women; 22 men) aged 18 to 45 underwent functional magnetic resonance imaging (fMRI) while viewing pictures of high- and low-calorie foods. Subjects completed the Epworth Sleepiness Scale (ESS) and provided a rating to the query "how often do you eat more than you intend to." Contrast images comparing brain activation derived from the high- versus low-calorie conditions were correlated voxel-wise with scores from the ESS in a second-level regression model, the output of which was used to predict self-reported overeating. As hypothesized, daytime sleepiness correlated with reduced activation in the ventromedial prefrontal cortex during perception of high- versus low-calorie food images. Moreover, activation within this cluster predicted overeating, but only for women. Findings suggest that normal fluctuations in sleepiness may be sufficient to affect brain regions important for regulating food intake, but that these effects may differ between men and women.
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Mapeo Encefálico , Ingestión de Alimentos/fisiología , Corteza Prefrontal/fisiología , Sueño/fisiología , Adolescente , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Caracteres Sexuales , Adulto JovenRESUMEN
In modern society, people often fail to obtain the amount of sleep that experts recommend for good health and performance. Insufficient sleep can lead to degraded cognitive performance and alterations in emotional functioning. However, most people also acknowledge that on a regular basis they obtain more sleep than they subjectively perceive they need at a minimum to stave off performance decrements, a construct we describe as subjective 'sleep credit'. Few people would contest the notion that getting more sleep is better, but data on both behavioural and neuroanatomical correlates of 'sleep credit' are surprisingly limited. We conducted a voxel-based morphometric study to assess cerebral grey matter correlates of habitually sleeping more than one's subjective requirements. We further tested whether these structural correlates are associated with perceived emotional intelligence and indices of psychopathology while controlling for age, gender, and total intracranial volume. In a sample of 55 healthy adults aged 18-45 years (28 males, 27 females), whole-brain multiple regression showed that habitual subjective 'sleep credit' was correlated positively with grey matter volume within regions of the left medial prefrontal cortex and right orbitofrontal gyrus. Volumes were extracted and regressed against self-report emotion and psychopathology indices. Only grey matter volume of the medial prefrontal cortex cluster correlated with greater emotional intelligence and lower scores on several indices of psychopathology. Findings converge with previous evidence of the role of the medial prefrontal cortex in the relationship between sleep and emotional functioning, and suggest that behaviour and brain structure vary with habitual 'sleep credit'.
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Inteligencia Emocional/fisiología , Salud Mental , Fibras Nerviosas Amielínicas , Corteza Prefrontal/anatomía & histología , Corteza Prefrontal/fisiología , Sueño/fisiología , Adolescente , Adulto , Emociones/fisiología , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Fibras Nerviosas Amielínicas/fisiología , Tamaño de los Órganos , Corteza Prefrontal/citología , Pruebas Psicológicas , Autoinforme , Cráneo/anatomía & histología , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Mood disorders are associated with neurobiological disruptions in subliminal and supraliminal emotion processing. There may be additional variation based on sex and the presence of self-injurious thoughts and behaviors (SITBs). Examining individuals in remission allows us to understand trait-like emotion processing characteristics that persist in the absence of symptoms. This study investigates neural processing in response to supraliminal and subliminal emotional stimuli based upon mood disorder diagnosis, sex, and SITBs. METHODS: Seventy-five participants with a history of any mood disorder (AMD; 52 female) and 27 healthy controls (HC; 14 female) completed a fMRI task presenting subliminal and supraliminal facial stimuli. Within the AMD group, 20 had no history of SITBs, 26 had histories of suicidal ideation only, and 27 had histories of both SI and self-injurious behavior. We examined activation of salience network regions of interest including the amygdala, insula, and subgenual anterior cingulate cortex (sgACC) during the task. RESULTS: AMD showed greater insula activation in response to happy faces relative to sad faces, which was not seen in the HC group. Males exhibited lower insula activation in response to sad faces relative happy faces, a pattern not seen in females. Individuals with SITBs demonstrated a lack of sgACC blunting during supraliminal versus subliminal trials. CONCLUSIONS: We found different patterns of neural responses related to mood disorder status, sex, and SITBs. Findings highlight the importance of considering heterogeneity within diagnoses and examining neurobiological features in the context of remission.
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Trastornos del Humor , Conducta Autodestructiva , Adulto , Amígdala del Cerebelo/diagnóstico por imagen , Emociones/fisiología , Expresión Facial , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Trastornos del Humor/diagnóstico por imagen , Trastornos del Humor/etiología , Conducta Autodestructiva/diagnóstico por imagen , Estimulación SubliminalRESUMEN
Reward anticipation dysfunction is associated with major depressive disorder (MDD), but is not universally observed in individuals with MDD. Reward anticipation deficits have also been linked to childhood adversity (CA) and approach/avoidance traits. The present study evaluated whether severity of CA (as measured by the Childhood Trauma Questionnaire) and approach/avoidance traits predict individual differences in blood oxygen level dependent (BOLD) response to reward anticipation beyond MDD diagnosis alone. Participants were individuals with MDD (nâ¯=â¯23) and healthy controls (nâ¯=â¯27). Multiple regression was conducted using CTQ scores, trait approach/avoidance scores, and diagnosis to predict activation during reward anticipation in a monetary incentive delay fMRI task. Across groups, higher trait reward responsiveness predicted increased activation in the hippocampus, cingulate cortex, and medial frontal gyrus. Greater CTQ scores predicted increased reward network activation. Overall, CTQ and reward responsiveness scores predicted more variance in reward anticipation activation than diagnosis. These findings suggest that clinicians should assess history of childhood adversity and trait reward responsiveness when treating individuals with MDD.
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Adultos Sobrevivientes de Eventos Adversos Infantiles/psicología , Depresión/psicología , Motivación/fisiología , Recompensa , Adulto , Niño , Femenino , Giro del Cíngulo/diagnóstico por imagen , Hipocampo/diagnóstico por imagen , Humanos , Individualidad , Imagen por Resonancia Magnética , Masculino , Análisis Multivariante , Corteza Prefrontal/diagnóstico por imagen , Análisis de Regresión , Adulto JovenRESUMEN
INTRODUCTION: Neuropsychological tests are designed to assay brain function via performance measurements. Many tests corresponding to visual and motor cortex function have been validated. Tests probing reward circuitry, including the ventral striatum (VS), could benefit assessment of numerous neurological and psychiatric disorders in which reward or VS function is disturbed. The present study sought to examine convergent and divergent validity of our modified, titrated version of the Monetary Incentive Delay Task, such that it may in the future stand as a validated neuropsychological test for reward function. METHOD: Participants were 132 individuals with a history of mood disturbance (HMD) and 43 healthy comparisons, ages 18-30 years. In addition to a standard neuropsychological battery and symptom measures, participants completed a modified version of the Monetary Incentive Delay Task (T-MIDT) during functional magnetic resonance imaging (fMRI), which involved a multistage titration procedure to incrementally increase or decrease the response window time per each participant's psychomotor speed and optimize individual performance. RESULTS: Across groups after titration, performance on the T-MIDT diverged from measures of processing speed, attention, and spatial working memory, but not inhibitory control. Performance in the HMD group was differentially correlated with executive function measures before and after titration. The reward circuit (e.g., subcortical, insular, medial prefrontal) was activated during reward anticipation. CONCLUSION: The present findings provide preliminary evidence that the T-MIDT measures a construct distinct from many executive functions and that individualized titration of the task parameters is critical in parsing reward from executive function. The T-MIDT correlated with residual mood symptoms in individuals with remitted depression or bipolar disorder, implying that behavioral or brain activation group differences are only to be observed in the active state of illness.
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Anticipación Psicológica/fisiología , Encéfalo/diagnóstico por imagen , Función Ejecutiva/fisiología , Motivación/fisiología , Adolescente , Adulto , Mapeo Encefálico , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Memoria a Corto Plazo/fisiología , Pruebas Neuropsicológicas , Tiempo de Reacción/fisiología , Recompensa , Adulto JovenRESUMEN
A large number of studies have attempted to use neuroimaging tools to aid in treatment prediction models for major depressive disorder (MDD). Most such studies have reported on only one dimension of function and prediction at a time. In this study, we used three different tasks across domains of function (emotion processing, reward anticipation, and cognitive control, plus resting state connectivity completed prior to start of medication to predict treatment response in 13-36 adults with MDD. For each experiment, adults with MDD were prescribed only label duloxetine (all experiments), whereas another subset were prescribed escitalopram. We used a KeyNet (both Task derived masks and Key intrinsic Network derived masks) approach to targeting brain systems in a specific match to tasks. The most robust predictors were (Dichter et al., 2010) positive response to anger and (Gong et al., 2011) negative response to fear within relevant anger and fear TaskNets and Salience and Emotion KeyNet (Langenecker et al., 2018) cognitive control (correct rejections) within Inhibition TaskNet (negative) and Cognitive Control KeyNet (positive). Resting state analyses were most robust for Cognitive control Network (positive) and Salience and Emotion Network (negative). Results differed by whether an -fwhm or -acf (more conservative) adjustment for multiple comparisons was used. Together, these results implicate the importance of future studies with larger sample sizes, multidimensional predictive models, and the importance of using empirically derived masks for search areas.
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Antidepresivos/uso terapéutico , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/tratamiento farmacológico , Emociones/fisiología , Imagen por Resonancia Magnética/métodos , Estimulación Luminosa/métodos , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/efectos de los fármacos , Citalopram/uso terapéutico , Trastorno Depresivo Mayor/psicología , Clorhidrato de Duloxetina/uso terapéutico , Emociones/efectos de los fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuroimagen/métodos , Valor Predictivo de las Pruebas , Desempeño Psicomotor/efectos de los fármacos , Desempeño Psicomotor/fisiología , Resultado del TratamientoRESUMEN
Perturbation-based balance training has shown to induce adaptation of reactive balance responses that can significantly reduce longer-term fall risk in older adults. While specific cortical and subcortical areas in control of posture and locomotion have been identified, little is known about the training-induced plasticity occurring in neural substrates for challenging tasks involving reactive balance control. The purpose of this study was to use functional neuroimaging to examine and determine the neural substrates, if any, involved in inducing adaptation to slip-like perturbations experienced during walking over 3 consecutive training days. We used a mental imagery task to examine the neural changes accompanied by treadmill-slip perturbation training. Ten healthy young adults were exposed to increasing magnitude of displacements during slip-like perturbations while walking, with an acceleration of 6 m/s2 on a motorized treadmill for 3 consecutive days. Brain activity was recorded through MRI while performing imagined slipping and imagined walking tasks before and after the perturbation training. The number of compensatory steps and center of mass state stability at compensatory step touchdown were recorded. As compared with day 1 (first trial), on day 3 (last trial) there was a significant reduction in number of compensatory steps and increase in stability at compensatory step touchdown on the mid and highest perturbation intensities. Before perturbation training, imagined slipping showed increased activity in the SMA, parietal regions, parahippocampal gyrus, and cingulate gyrus compared with rest. After perturbation training, imagined slipping showed increased activation in DLPFC, superior parietal lobule, inferior occipital gyrus, and lingual gyrus. Perturbation training was not associated with decline in activity in any of the brain regions. This study provides evidence for learning-related changes in cortical structures while adapting to slip-like perturbations while walking. The findings reflect that higher-level processing is required for timing and sequencing of movements to execute an effective balance response to perturbations. Specifically, the CNS relies on DLPFC along with motor, parietal, and occipital cortices for adapting to postural tasks posing a significant threat to balance.
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Background: Behavioral evidence for cortical involvement in reactive balance control in response to environmental perturbation is established, however, the neural correlates are not known. This study aimed to examine the neural mechanisms involved in reactive balance control for recovery from slip-like perturbations using mental imagery and to evaluate the difference in activation patterns between imagined and observed slipping. Methods: Ten healthy young participants after an exposure to regular walking and slip-perturbation trial on a treadmill, performed mental imagery and observation tasks in the MR scanner. Participants received verbal instructions to imagine walking (IW), observe walking (OW), imagine slipping (IS) and observe slipping (OS) while walking. Results: Analysis using general linear model showed increased activation during IS versus IW condition in precentral gyrus, middle frontal gyrus, superior, middle and transverse temporal gyrus, parahippocampal gyrus, cingulate gyrus, insula, pulvinar nucleus of the thalamus, pons, anterior and posterior cerebellar lobes. During IS versus OS condition, there was additional activation in parahippocampus, cingulate gyrus, inferior parietal lobule, superior temporal, middle and inferior frontal gyrus. Conclusion: The findings of the current study support involvement of higher cortical and subcortical structures in reactive balance control. Greater activation during slipping could be attributed to the complexity of the sensorimotor task and increased demands to maintain postural stability during slipping as compared with regular walking. Furthermore, our findings suggest that mental imagery of slipping recruited greater neural substrates rather than observation of slipping, possibly due to increased sensory, cognitive and perceptual processing demands. New and Noteworthy: The behavioral factors contributing to falls from external perturbations while walking are better understood than neural mechanisms underlying the behavioral response. This study examines the neural activation pattern associated with reactive balance control during slip-like perturbations while walking through an fMRI paradigm. This study identified specific neural mechanisms involved in complex postural movements during sudden perturbations, to particularly determine the role of cortical structures in reactive balance control. It further highlights the specific differences in neural structures involved in regular unperturbed versus perturbed walking.
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BACKGROUND: Major Depressive Disorder (MDD) is a prevalent, disruptive illness. A majority of those with MDD are at high risk for recurrence and increased risk for morbidity and mortality. This study examined whether multimodal baseline (and retest) Cognitive Control performance and neuroimaging markers (task activation and neural connectivity between key brain nodes) could differentiate between those with and without future recurrence of a major depressive (MD) episode within one year. We hypothesized that performance and neuroimaging measures of Cognitive Control would identify markers that differ between these two groups. METHODS: A prospective cohort study of young adults (ages 18-23) with history (h) of early-onset MDD (Nâ¯=â¯60), now remitted, and healthy young adults (Nâ¯=â¯49). Baseline Cognitive Control measures of performance, task fMRI and resting state connectivity (and reliability retest 4-12â¯weeks later) were used to compare those with future recurrence of MDD (Nâ¯=â¯21) relative to those without future recurrence of MDD (Nâ¯=â¯34 with resilience). The measures tested were (1) Parametric Go/No-Go (PGNG) performance, and task activation for (2) PGNG Correct Rejections, (3) PGNG Commission errors, and (4 & 5), resting state connectivity analyses of Cognitive Control Network to and from subgenual anterior cingulate. RESULTS: Relative to other groups at baseline, the group with MDD Recurrence had less bilateral middle frontal gyrus activation during commission errors. MDD Recurrence exhibited greater connectivity of right middle frontal gyrus to subgenual anterior cingulate (SGAC). SGAC connectivity was also elevated in this group to numerous regions in the Cognitive Control Network. Moderate to strong ICCs were present from test to retest, and highest for rs-fMRI markers. There were modest, significant correlations between task, connectivity and behavioral markers that distinguished between groups. CONCLUSION: Markers of Cognitive Control function could identify those with early course MD who are at risk for depression recurrence. Those at high risk for recurrence would benefit from maintenance or preventative treatments. Future studies could test and validate these markers as potential predictors, accounting for sample selection and bias in feature detection.
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Cognición/fisiología , Depresión/fisiopatología , Trastorno Depresivo Mayor/fisiopatología , Neuroimagen , Adolescente , Adulto , Encéfalo/patología , Encéfalo/fisiopatología , Mapeo Encefálico , Femenino , Humanos , Masculino , Vías Nerviosas/fisiopatología , Neuroimagen/métodos , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
Individuals in a major depressive episode often display impairment in cognitive control, and this impairment exists outside of the acute phase of illness. Impairment in cognitive control also has been associated with exposure to childhood adversity (CA). The current study examined whether exposure to CA can explain variance in a component of cognitive control-inhibitory control-independent of diagnostic status in young adults with and without a history of depression. Healthy control individuals (n = 40) and individuals with remitted major depressive disorder (n = 53) completed a task measuring inhibitory control, reported level of CA and completed a scanning session to assess gray matter volume and resting state connectivity in regions associated with cognitive control. The results demonstrate that higher levels of CA were associated with poorer inhibitory control, reduced right middle frontal gyrus gray matter, decreased connectivity of salience and emotion networks and increased connectivity in cognitive control networks, even after controlling for diagnostic status, residual depression symptoms and current stressors. Together, the results suggest that inhibitory control impairment and intrinsic connectivity changes may be characterized as developmental sequelae of early stress exposure.
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Encéfalo/diagnóstico por imagen , Cognición/fisiología , Trastorno Depresivo Mayor/diagnóstico por imagen , Función Ejecutiva/fisiología , Sustancia Gris/diagnóstico por imagen , Adolescente , Trastorno Depresivo Mayor/psicología , Emociones , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Pruebas Neuropsicológicas , Adulto JovenRESUMEN
We investigated the ability of preferred classical music to activate the nucleus accumbens in patients with Major depressive disorder (MDD). Twelve males with MDD and 10 never mentally ill male healthy controls (HC) completed measures of anhedonia and depression severity, and listened to 90-second segments of preferred classical music during fMRI. Compared to HCs, individuals with MDD showed less activation of the left nucleus accumbens (NAcc). Individuals with MDD showed attenuation of the left NAcc response in later compared to earlier parts of the experiment, supporting theories that MDD involves an inability to sustain reward network activation. Counter intuitively, we found that NAcc activity during early music listening was associated with greater depression severity. In whole-brain analyses, anhedonia scores predicted activity in regions within the default mode network, supporting previous findings. Our results support theories that MDD involves an inability to sustain reward network activation. It also highlights that pleasant classical music can engage critical neural reward circuitry in MDD.
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Anhedonia/fisiología , Percepción Auditiva/fisiología , Trastorno Depresivo Mayor/fisiopatología , Neuroimagen Funcional/métodos , Música , Núcleo Accumbens/fisiopatología , Adolescente , Adulto , Trastorno Depresivo Mayor/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Núcleo Accumbens/diagnóstico por imagen , Adulto JovenRESUMEN
There is substantial variability across studies of default mode network (DMN) connectivity in major depressive disorder, and reliability and time-invariance are not reported. This study evaluates whether DMN dysconnectivity in remitted depression (rMDD) is reliable over time and symptom-independent, and explores convergent relationships with cognitive features of depression. A longitudinal study was conducted with 82 young adults free of psychotropic medications (47 rMDD, 35 healthy controls) who completed clinical structured interviews, neuropsychological assessments, and 2 resting-state fMRI scans across 2 study sites. Functional connectivity analyses from bilateral posterior cingulate and anterior hippocampal formation seeds in DMN were conducted at both time points within a repeated-measures analysis of variance to compare groups and evaluate reliability of group-level connectivity findings. Eleven hyper- (from posterior cingulate) and 6 hypo- (from hippocampal formation) connectivity clusters in rMDD were obtained with moderate to adequate reliability in all but one cluster (ICC's range = 0.50 to 0.76 for 16 of 17). The significant clusters were reduced with a principle component analysis (5 components obtained) to explore these connectivity components, and were then correlated with cognitive features (rumination, cognitive control, learning and memory, and explicit emotion identification). At the exploratory level, for convergent validity, components consisting of posterior cingulate with cognitive control network hyperconnectivity in rMDD were related to cognitive control (inverse) and rumination (positive). Components consisting of anterior hippocampal formation with social emotional network and DMN hypoconnectivity were related to memory (inverse) and happy emotion identification (positive). Thus, time-invariant DMN connectivity differences exist early in the lifespan course of depression and are reliable. The nuanced results suggest a ventral within-network hypoconnectivity associated with poor memory and a dorsal cross-network hyperconnectivity linked to poorer cognitive control and elevated rumination. Study of early course remitted depression with attention to reliability and symptom independence could lead to more readily translatable clinical assessment tools for biomarkers.
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BACKGROUND: Major depressive disorder (MDD) is characterized by dysfunction in cognitive and emotional systems. However, the neural network correlates of cognitive control (cold cognition) and emotion processing (hot cognition) during the remitted state of MDD (rMDD) remain unclear and not fully probed, which has important implications for identifying intermediate phenotypes of depression risk. METHODS: 43 young adults with rMDD and 33 healthy controls (HCs) underwent fMRI while completing separate tasks of cold cognition (Parametric Go/No-Go test) and hot cognition (Facial Emotion Processing Test). Two 2 group (rMDD, HC) × 2 event (sad/fearful faces, correct rejections) factorial models of activation were calculated in SPM8. Functional activation was evaluated in the salience and emotional network (SEN) and the cognitive control network (CCN), including hypothesized interaction between group and task within the CCN. RESULTS: Individuals with rMDD demonstrated greater spatial extent of suprathreshold activation within the SEN during sad faces relative to HCs. There were several regions within the CCN in which HCs showed greater activation than rMDD during correct rejections of lures, whereas individuals with rMDD showed greater activation than HCs during sad or fearful faces. LIMITATIONS: Results were not directly compared with active MDD. CONCLUSIONS: These results provide evidence of deficient CCN engagement during cognitive control in rMDD (dysfunctional cold cognition). Elevated SEN activation during sad faces could represent heightened salience of negative emotional faces in rMDD; elevated CCN activation during emotional faces in rMDD could represent compensatory regulatory control. These group differences may represent vulnerability factors, scars of prior depressive episodes, or processes maintaining wellness.
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Cognición/fisiología , Trastorno Depresivo Mayor/fisiopatología , Emociones/fisiología , Mapeo Encefálico , Estudios de Casos y Controles , Expresión Facial , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Estimulación Luminosa , Inducción de Remisión , Adulto JovenRESUMEN
INTRODUCTION: Studying remitted Major Depressive Disorder (rMDD) facilitates a better understanding of neural mechanisms for risk, given that confounding effects of active symptoms are removed. Disrupted functional connectivity has been reported in multiple networks in MDD. However, no study to date of rMDD has specifically examined connectivity of the ventral striatum (VS), a region highly implicated in reward and motivation. We investigated functional connectivity of the VS in individuals with and without a history of MDD, and in relation to affective personality traits. METHODS: Forty-two individuals with rMDD and 28 healthy controls across two sites completed resting-state fMRI and the Behavioral Inhibition System/Behavioral Activation System Scale. Voxel-wise, whole-brain comparisons were conducted across and between groups for four seeds: left and right inferior VS (VSi), left and right superior VS (VSs). RESULTS: VSs connectivity to temporal and subcortical regions including the putamen and amygdala was positive and greater in HCs compared to rMDD individuals. Across groups, VSi connectivity was positively correlated with trait reward-responsiveness in somatomotor regions. Across groups, VSs connectivity was positively correlated with trait drive, particularly in the putamen, parahippocampal, and inferior temporal gyrus, and was negatively associated with trait behavioral inhibition in the anterior cingulate, frontal gyri, and insula. LIMITATIONS: Limitations include scanning at two sites and using multiple comparisons. DISCUSSION: Group connectivity differences emerged from the VSs rather than VSi. VSs showed associations with trait drive and behavioral inhibition, whereas VSi corrrelated with reward-responsiveness. Depression history and affective traits contribute meaningful and specific information about VS connectivity in understanding risk for MDD.
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Afecto/fisiología , Trastorno Depresivo Mayor/fisiopatología , Motivación/fisiología , Recompensa , Estriado Ventral/fisiopatología , Adolescente , Amígdala del Cerebelo/fisiopatología , Encéfalo/fisiopatología , Estudios de Casos y Controles , Corteza Cerebral/fisiopatología , Trastorno Depresivo Mayor/psicología , Femenino , Giro del Cíngulo/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Adulto JovenRESUMEN
Anhedonia, the diminished anticipation and pursuit of reward, is a core symptom of major depressive disorder (MDD). Trait behavioral activation (BA), as a proxy for anhedonia, and behavioral inhibition (BI) may moderate the relationship between MDD and reward-seeking. The present studies probed for reward learning deficits, potentially due to aberrant BA and/or BI, in active or remitted MDD individuals compared to healthy controls (HC). Active MDD (Study 1) and remitted MDD (Study 2) participants completed the modified monetary incentive delay task (mMIDT), a behavioral reward-seeking task whose response window parameters were individually titrated to theoretically elicit equivalent accuracy between groups. Participants completed the BI Scale and BA Reward-Responsiveness and Drive Scales. Despite individual titration, active MDD participants won significantly less money than HCs. Higher Reward-Responsiveness scores predicted more won; Drive and BI were not predictive. Remitted MDD participants' performance did not differ from controls', and trait BA and BI measures did not predict r-MDD performance. These results suggest that diminished reward-responsiveness may contribute to decreased motivation and reward pursuit during active MDD, but that reward learning is intact in remission. Understanding individual reward processing deficits in MDD may inform personalized intervention addressing anhedonia and motivation deficits in select MDD patients.
Asunto(s)
Anhedonia , Trastorno Depresivo Mayor/psicología , Aprendizaje , Personalidad , Recompensa , Adulto , Anhedonia/fisiología , Trastorno Depresivo Mayor/diagnóstico , Femenino , Humanos , Aprendizaje/fisiología , Masculino , Persona de Mediana Edad , Trastornos del Humor/diagnóstico , Trastornos del Humor/psicología , Motivación , Personalidad/fisiología , Valor Predictivo de las Pruebas , Tiempo de Reacción/fisiología , Adulto JovenRESUMEN
According to the hyperarousal theory of insomnia, difficulty in initiating or maintaining sleep occurs as a result of increased cognitive and physiological arousal caused by acute stressors and associated cognitive rumination, placing the individual in a perpetual cycle of hyperarousal and increased sensitivity to sensory stimulation. We tested the hypothesis that difficulty in initiating or maintaining sleep would be associated with increased functional connectivity between primary sensory processing and motor planning regions. Fifty-eight healthy adults (29 men, 29 women) completed a self-report inventory about sleep onset and maintenance problems and underwent a 6-min resting-state functional MRI scan. Bilateral regions of interest (ROIs) were placed in primary visual cortex, auditory cortex, olfactory cortex, and the supplementary motor cortex, and the mean processed signal time course was extracted and correlated with each of the other ROIs. Difficulty in falling asleep was associated with increased functional connectivity between the primary visual cortex and other sensory regions such as the primary auditory cortex, olfactory cortex, and the supplementary motor cortex. The primary auditory cortex also showed greater connectivity with the supplementary motor cortex in those with sleep initiation problems. Problems with sleep maintenance were associated with greater connectivity between the primary visual cortex and the olfactory cortex. Consistent with the predictions of the hyperarousal model, difficulty in falling asleep was associated with greater functional connectivity between primary sensory and supplementary motor regions. Such augmented functional connectivity may contribute to the sustained sensory processing of environmental stimuli, potentially prolonging the latency to sleep.
Asunto(s)
Corteza Cerebral/patología , Red Nerviosa/patología , Trastornos del Inicio y del Mantenimiento del Sueño/patología , Adolescente , Adulto , Corteza Cerebral/irrigación sanguínea , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Red Nerviosa/irrigación sanguínea , Oxígeno/sangre , Trastornos del Inicio y del Mantenimiento del Sueño/psicología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Emotional intelligence (EI) refers to a constellation of traits, competencies, or abilities that allow individuals to understand emotional information and successfully navigate and solve social/emotional problems. While little is known about the neurobiological substrates that underlie EI, some evidence suggests that these capacities may involve a core neurocircuitry involved in emotional decision-making that includes the ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC), insula, and amygdala. In a sample of 39 healthy volunteers (22 men; 17 women), scores on the Bar-On EQ-i (a trait/mixed model of EI) and Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT; an ability model of EI) were correlated with functional magnetic resonance imaging responses during brief presentations of moving facial expressions that changed in the level of perceived trustworthiness. Core emotion neurocircuitry was responsive to dynamic changes in facial features, regardless of whether they reflected increases or decreases in apparent trustworthiness. In response to facial movements indicating decreasing trustworthiness, MSCEIT correlated positively with functional responses of the vmPFC and rostral ACC, whereas the EQ-i was unrelated to regional activation. Systematic differences in EI ability appear to be significantly related to the responsiveness of the vmPFC and rostral ACC to facial movements suggesting potential trustworthiness.