RESUMEN
The serotonin transporter (5-HTT) is a key molecule of serotoninergic neurotransmission and target of many anxiolytics and antidepressants. In humans, 5-HTT gene variants resulting in lower expression levels are associated with behavioral traits of anxiety. Furthermore, functional magnetic resonance imaging (fMRI) studies reported increased cerebral blood flow (CBF) during resting state (RS) and amygdala hyperreactivity. 5-HTT deficient mice as an established animal model for anxiety disorders seem to be well suited for investigating amygdala (re-)activity in an fMRI study. We investigated wildtype (5-HTT+/+), heterozygous (5-HTT+/-), and homozygous 5-HTT-knockout mice (5-HTT-/-) of both sexes in an ultra-high-field 17.6 Tesla magnetic resonance scanner. CBF was measured with continuous arterial spin labeling during RS, stimulation state (SS; with odor of rats as aversive stimulus), and post-stimulation state (PS). Subsequently, post mortem c-Fos immunohistochemistry elucidated neural activation on cellular level. The results showed that in reaction to the aversive odor CBF in total brain and amygdala of all mice significantly increased. In male 5-HTT+/+ mice amygdala RS CBF levels were found to be significantly lower than in 5-HTT+/- mice. From RS to SS 5-HTT+/+ amygdala perfusion significantly increased compared to both 5-HTT+/- and 5-HTT-/- mice. Perfusion level changes of male mice correlated with the density of c-Fos-immunoreactive cells in the amygdaloid nuclei. In female mice the perfusion was not modulated by the 5-Htt-genotype, but by estrous cycle stages. We conclude that amygdala reactivity is modulated by the 5-Htt genotype in males. In females, gonadal hormones have an impact which might have obscured genotype effects. Furthermore, our results demonstrate experimental support for the tonic model of 5-HTTLPR function.
Asunto(s)
Amígdala del Cerebelo/irrigación sanguínea , Ansiedad/diagnóstico por imagen , Proteínas Proto-Oncogénicas c-fos/metabolismo , Proteínas de Transporte de Serotonina en la Membrana Plasmática/deficiencia , Amígdala del Cerebelo/metabolismo , Animales , Ansiedad/genética , Circulación Cerebrovascular , Modelos Animales de Enfermedad , Femenino , Hormonas Gonadales/metabolismo , Homocigoto , Imagen por Resonancia Magnética , Masculino , Ratones , Ratones Noqueados , Ratas , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genética , Caracteres SexualesRESUMEN
Hemorrhagic shock and resuscitation (HSR) may lead to long-term neurological dysfunction, such as depression and anxiety. Carbon monoxide (CO) has emerged as an excellent neuroprotective agent against caspase-1-associated pyroptosis, following HSR. We evaluated the effects and determined the mechanism through which CO protects against emotional changes in a model of HSR, in rats. We subjected rats to treatments with an exogenous, CO-releasing compound (CORM-3, 4 mg/kg), in vivo, after HSR. We measured sucrose preference and performed tail suspension and open field tests 7 days after HSR, assessed brain magnetic resonance imaging 12 h after HSR and evaluated pyroptosis, and neuronal and astrocyte death in the amygdala 12 h post-HSR. We also measured changes in behavior and pathology, following an injection of recombinant murine interleukin (IL)-18 into the amygdala. HSR-treated rats displayed increased depression-like and anxiety-like behaviors, increased amygdalar injury, as indicated by T2-weighted magnetic resonance imaging (MRI) and cerebral blood flow with arterial spin labeling (CBFASL), associated with both neuronal and astrocytic death and pyroptosis, and upregulated IL-18 expression was observed in astrocytes. CORM-3 administration after resuscitation, via a femoral vein injection, provided neuroprotection against HSR, and this neuroprotective effect could be partially reversed by the injection of recombinant murine IL-18 into the amygdala. Therefore, CORM-3 alleviated HSR-induced neuronal pyroptosis and emotional changes, through the downregulation of IL-18 in astrocytes.
Asunto(s)
Síntomas Afectivos/tratamiento farmacológico , Amígdala del Cerebelo/irrigación sanguínea , Amígdala del Cerebelo/efectos de los fármacos , Compuestos Organometálicos/uso terapéutico , Piroptosis/efectos de los fármacos , Choque Hemorrágico/tratamiento farmacológico , Síntomas Afectivos/etiología , Síntomas Afectivos/fisiopatología , Amígdala del Cerebelo/fisiología , Animales , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Circulación Cerebrovascular/efectos de los fármacos , Circulación Cerebrovascular/fisiología , Masculino , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Compuestos Organometálicos/farmacología , Piroptosis/fisiología , Ratas , Ratas Sprague-Dawley , Rutenio/farmacología , Rutenio/uso terapéutico , Choque Hemorrágico/complicaciones , Choque Hemorrágico/fisiopatologíaRESUMEN
Could nose-to-brain pathways mediate the effects of peptides such as oxytocin (OT) on brain physiology when delivered intranasally? We address this question by contrasting two methods of intranasal administration (a standard nasal spray, and a nebulizer expected to improve OT deposition in nasal areas putatively involved in direct nose-to-brain transport) to intravenous administration in terms of effects on regional cerebral blood flow during two hours post-dosing. We demonstrate that OT-induced decreases in amygdala perfusion, a key hub of the OT central circuitry, are explained entirely by OT increases in systemic circulation following both intranasal and intravenous OT administration. Yet we also provide robust evidence confirming the validity of the intranasal route to target specific brain regions. Our work has important translational implications and demonstrates the need to carefully consider the method of administration in our efforts to engage specific central oxytocinergic targets for the treatment of neuropsychiatric disorders.
Asunto(s)
Encéfalo/efectos de los fármacos , Circulación Cerebrovascular/efectos de los fármacos , Oxitocina/administración & dosificación , Administración Intranasal , Administración Intravenosa , Adulto , Amígdala del Cerebelo/irrigación sanguínea , Encéfalo/irrigación sanguínea , Método Doble Ciego , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Imagen por Resonancia Magnética , Masculino , Nebulizadores y Vaporizadores , Oxitocina/sangre , Oxitocina/farmacocinética , Placebos , Adulto JovenRESUMEN
Healthy first-degree relatives of patients with major depression are at an elevated risk of developing depression, and regional cerebral blood flow (CBF) alterations are observed in patients with depression. Therefore, in a 33-month follow-up study, we used arterial spin labeling-magnetic resonance imaging (ASL-MRI) to investigate quantitative CBF before and after the diagnosis of depression in healthy young adults with and without first-degree relatives with major depression (FH + and FH-, respectively). In cross-sectional and longitudinal CBF comparisons, CBF in the right amygdala was increased or decreased. Additionally, a significant correlation was observed between the altered CBF in the right amygdala and the scores on the 17-item Hamilton Depression Rating Scale (HDRS) in the FH + group. Furthermore, logistic regression and receiver operating characteristic curve analyses showed that increased CBF in the right amygdala at baseline predicted the subsequent onset of depression in the FH + group. Our results suggest that among healthy young adults with a familial risk of depression, those who exhibit increased CBF in the amygdala are susceptible to developing this disease.
Asunto(s)
Amígdala del Cerebelo/diagnóstico por imagen , Circulación Cerebrovascular/fisiología , Depresión/diagnóstico , Trastorno Depresivo Mayor , Amígdala del Cerebelo/irrigación sanguínea , Familia/psicología , Femenino , Estudios de Seguimiento , Humanos , Modelos Logísticos , Angiografía por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Factores de Riesgo , Adulto JovenRESUMEN
Reduced high-frequency heart rate variability (HF-HRV) is associated with a greater risk for cardiovascular disease (CVD). Although African Americans (AA) are at greater risk for CVD, they show greater HF-HRV compared to European Americans (EA). Previous studies suggest that differences in the association between regional cerebral blood flow (CBF) and HF-HRV in AA and EA may explain this surprising pattern of findings, termed the Cardiovascular Conundrum. Here we pooled data from a total of nâ¯=â¯452â¯EA and nâ¯=â¯102 AA, investigating differences in the association between CBF in 8 regions of interest (ROI), including the cingulate (anterior, mid, posterior), insula (anterior, posterior), and amygdala (basolateral, centromedial, superfical), with HF-HRV, mean heart rate (HR) and their Coefficient of Variation (CoV). Bayesian statistics illustrate that CBF - in particular in the anterior cingulate cortex (ACC) - is positively associated with HF-HRV and CoV in EA, but negatively associated in AA. Exploring the association between HF-HRV and CBF with self-reports of affect and affect regulation showed some differences as a function of ethnicity. The association between greater habitual use of reappraisal only showed a positive correlation with HF-HRV in AA. Similar, greater suppression or non-expression of angry emotions was associated with greater HF-HRV whereas greater outward direction of anger was associated with lower HF-HRV in AA only. Given the importance of the ACC in emotion and emotion regulation, we suggest that increased HF-HRV may serve a compensatory role in AA. Implications from these findings and suggestions for future studies are discussed.
Asunto(s)
Afecto/fisiología , Sistema Nervioso Autónomo/fisiología , Encéfalo/irrigación sanguínea , Encéfalo/fisiología , Circulación Cerebrovascular/fisiología , Regulación Emocional/fisiología , Frecuencia Cardíaca , Adulto , Negro o Afroamericano , Amígdala del Cerebelo/irrigación sanguínea , Amígdala del Cerebelo/fisiología , Mapeo Encefálico , Corteza Cerebral/irrigación sanguínea , Corteza Cerebral/fisiología , Femenino , Giro del Cíngulo/irrigación sanguínea , Giro del Cíngulo/fisiología , Humanos , Individualidad , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Autoinforme , Población BlancaRESUMEN
The experience of flow ensues when humans engage in a demanding task while task demands are balanced with the individual's level of skill or ability. Here, we further tested the hypothesis that the medial prefrontal cortex (MPFC) plays a causal role in mediating flow experience using transcranial direct current stimulation (tDCS) to interfere with MPFC's deactivation evoked by a flow paradigm and measured by magnetic resonance (MR)-based perfusion imaging. In a balanced, within-subjects repeated measure design, three treatments of tDCS (sham, anodal, cathodal) were applied in a sample of 22 healthy male participants. tDCS-modulatory effects on flow-specific regional cerebral blood flow (rCBF) and subjective flow experience significantly depended on participants' baseline level of flow experience during sham tDCS. Those participants with lower-flow experience during sham tDCS (LF) benefitted from tDCS, particularly from the anodal polarity, whereas both active treatments did not substantially affect subjects with relatively higher baseline flow experience (HF). Functionally, in LF subjects, relative deactivation of the right amygdala got more pronounced under anodal and cathodal tDCS, and changed inconsistently in HF subjects. Inter-individual regression analyses of rCBF data suggested that involvement of the subgenual anterior cingulate cortex appears crucial for affecting the response pattern in the right amygdala and can be modulated by tDCS. Present data support the notion that valuable insights into the neural mechanism of flow can be obtained using tDCS. However, a clearer understanding of tDCS' baseline dependency in terms of individual variations in brain connectivity states appears a necessary prerequisite to exploit this technique further.
Asunto(s)
Mapeo Encefálico , Circulación Cerebrovascular/fisiología , Corteza Prefrontal/fisiología , Estimulación Transcraneal de Corriente Directa , Adulto , Amígdala del Cerebelo/irrigación sanguínea , Amígdala del Cerebelo/fisiología , Electrodos , Humanos , Procesamiento de Imagen Asistido por Computador , Angiografía por Resonancia Magnética , Masculino , Corteza Prefrontal/diagnóstico por imagen , Análisis de Regresión , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Previous studies reported poor to fair test-retest reliability of amygdala BOLD responses to emotional stimuli. However, these findings are very heterogeneous across and within studies. The present study sought to systematically examine experimental and methodological factors that contribute to this heterogeneity. Forty-six young subjects were scanned twice with a mean test-retest interval of 7 weeks. We compared amygdala reliability across three tasks: A face-matching task, passive viewing of emotional faces, and passive viewing of emotional scenes. We also explored whether extraction of physiological noise can affect the stability of amygdala responses. We assessed test-retest reliability of amygdala mean amplitudes at the individual level and spatial repeatability (i.e., stability of the spatial distribution of activation) of the amygdala BOLD signal at the group and individual level. All three tasks evoked robust amygdala activation at the group level. At the individual level, amygdala spatial repeatability was poor during passive viewing of scenes and faces and fair or close to fair in the face-matching task. On the other hand, reliability of amygdala mean responses was very poor in the face-matching task while it was significantly higher during passive viewing of faces and scenes. Physiological noise correction changed reliability rates but not uniformly across the three tasks. The current work suggests that the presence of a concurrent task during emotion processing affects amygdala reliability. The dissociation between spatial repeatability and reliability of mean amplitudes highlights the importance of taking into account both measures for a multidimensional assessment of the reliability of BOLD responses.
Asunto(s)
Afecto/fisiología , Amígdala del Cerebelo/fisiología , Mapeo Encefálico/métodos , Imagen por Resonancia Magnética/métodos , Adulto , Amígdala del Cerebelo/irrigación sanguínea , Amígdala del Cerebelo/diagnóstico por imagen , Artefactos , Reconocimiento Facial/fisiología , Femenino , Humanos , Masculino , Reproducibilidad de los Resultados , Percepción Visual/fisiología , Adulto JovenRESUMEN
OBJECTIVE: Patients with depression show blunted amygdala hemodynamic activity to positive stimuli, including autobiographical memories. The authors examined the therapeutic efficacy of real-time functional MRI neurofeedback (rtfMRI-nf) training aimed at increasing the amygdala's hemodynamic response to positive memories in patients with depression. METHOD: In a double-blind, placebo-controlled, randomized clinical trial, unmedicated adults with depression (N=36) were randomly assigned to receive two sessions of rtfMRI-nf either from the amygdala (N=19) or from a parietal control region not involved in emotional processing (N=17). Clinical scores and autobiographical memory performance were assessed at baseline and 1 week after the final rtfMRI-nf session. The primary outcome measure was change in score on the Montgomery-Åsberg Depression Rating Scale (MADRS), and the main analytic approach consisted of a linear mixed-model analysis. RESULTS: In participants in the experimental group, the hemodynamic response in the amygdala increased relative to their own baseline and to the control group. Twelve participants in the amygdala rtfMRI-nf group, compared with only two in the control group, had a >50% decrease in MADRS score. Six participants in the experimental group, compared with one in the control group, met conventional criteria for remission at study end, resulting in a number needed to treat of 4. In participants receiving amygdala rtfMRI-nf, the percent of positive specific memories recalled increased relative to baseline and to the control group. CONCLUSIONS: rtfMRI-nf training to increase the amygdala hemodynamic response to positive memories significantly decreased depressive symptoms and increased the percent of specific memories recalled on an autobiographical memory test. These data support a role of the amygdala in recovery from depression.
Asunto(s)
Amígdala del Cerebelo/fisiopatología , Trastorno Depresivo Mayor/fisiopatología , Trastorno Depresivo Mayor/terapia , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/métodos , Memoria Episódica , Neurorretroalimentación/métodos , Adolescente , Adulto , Amígdala del Cerebelo/irrigación sanguínea , Trastorno Depresivo Mayor/psicología , Método Doble Ciego , Femenino , Hemodinámica/fisiología , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Prenatal stress has been linked to deficits in neurological function including deficient social behavior, alterations in learning and memory, impaired stress regulation, and susceptibility to adult disease. In addition, prenatal environment is known to alter cardiovascular health; however, limited information is available regarding the cerebrovascular consequences of prenatal stress exposure. Vascular disturbances late in life may lead to cerebral hypoperfusion which is linked to a variety of neurodegenerative and psychiatric diseases. The known impact of cerebrovascular compromise on neuronal function and behavior highlights the importance of characterizing the impact of stress on not just neurons and glia, but also cerebrovasculature. Von Willebrand factor has previously been shown to be impacted by prenatal stress and is predictive of cerebrovascular health. Here we assess the impact of prenatal stress on von Willebrand factor and related angiogenic factors. Furthermore, we assess the potential protective effects of concurrent anti-depressant treatment during in utero stress exposure on the assessed cerebrovascular endpoints. Prenatal stress augmented expression of von Willebrand factor which was prevented by concurrent in utero escitalopram treatment. The functional implications of this increase in von Willebrand factor remain elusive, but the presented data demonstrate that although prenatal stress did not independently impact total vascularization, exposure to chronic stress in adulthood decreased blood vessel length. In addition, the current study demonstrates that production of reactive oxygen species in the hippocampus is decreased by prenatal exposure to escitalopram. Collectively, these findings demonstrate that the prenatal experience can cause complex changes in adult cerebral vascular structure and function.
Asunto(s)
Citalopram/farmacología , Efectos Tardíos de la Exposición Prenatal/prevención & control , Estrés Psicológico/metabolismo , Factor de von Willebrand/biosíntesis , Factores de Edad , Amígdala del Cerebelo/irrigación sanguínea , Proteínas Angiogénicas/biosíntesis , Animales , Citalopram/administración & dosificación , Femenino , Hipocampo/irrigación sanguínea , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Masculino , Corteza Prefrontal/irrigación sanguínea , Embarazo , Ratas , Especies Reactivas de Oxígeno/metabolismo , Estrés Psicológico/patologíaRESUMEN
OBJECTIVES: Autobiographical memory (AM) recall is impaired in both bipolar depression (BD) and major depressive disorder (MDD). The current study used functional magnetic resonance imaging (fMRI) to investigate differences between healthy controls (HCs) and depressed participants with either BD or MDD as they recalled AMs that varied in emotional valence. METHODS: Unmedicated adults in a current major depressive episode who met criteria for either MDD or BD and HCs (n=16/group) underwent fMRI while recalling AMs in response to emotionally valenced cue words. Control tasks involved generating examples from a given category and counting the number of risers in a letter string. RESULTS: Both participants with BD and those with MDD recalled fewer specific and more categorical memories than HC participants. During specific AM recall of positive memories, participants with BD showed increased hemodynamic activity in the ventrolateral prefrontal cortex, posterior cingulate cortex, anterior insula, middle temporal gyrus, parahippocampus, and amygdala relative to MDD and HC participants, as well as decreased dorsolateral prefrontal (DLPFC) activity relative to MDD participants. During specific AM recall of negative memories, participants with BD manifested decreased activity in the precuneus, amygdala, anterior cingulate, and DLPFC along with increased activity in the dorsomedial PFC relative to MDD participants. CONCLUSIONS: While depressed participants with BD and MDD exhibited similar depression ratings and memory deficits, the brain regions underlying successful AM recall significantly differentiated these patient groups. Differential amygdala activity during emotional memory recall (particularly increased activity in participants with BD for positive AMs) may prove useful in the differentiation of individuals with MDD and BD experiencing a depressive episode.
Asunto(s)
Amígdala del Cerebelo , Trastorno Bipolar , Trastorno Depresivo Mayor , Emociones/fisiología , Memoria Episódica , Corteza Prefrontal , Adulto , Amígdala del Cerebelo/irrigación sanguínea , Amígdala del Cerebelo/diagnóstico por imagen , Amígdala del Cerebelo/fisiopatología , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/psicología , Señales (Psicología) , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/psicología , Femenino , Hemodinámica , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Trastornos de la Memoria/fisiopatología , Recuerdo Mental/fisiología , Corteza Prefrontal/irrigación sanguínea , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiopatologíaRESUMEN
Real-time fMRI neurofeedback (rtfMRI-nf) is an emerging approach for studies and novel treatments of major depressive disorder (MDD). EEG performed simultaneously with an rtfMRI-nf procedure allows an independent evaluation of rtfMRI-nf brain modulation effects. Frontal EEG asymmetry in the alpha band is a widely used measure of emotion and motivation that shows profound changes in depression. However, it has never been directly related to simultaneously acquired fMRI data. We report the first study investigating electrophysiological correlates of the rtfMRI-nf procedure, by combining the rtfMRI-nf with simultaneous and passive EEG recordings. In this pilot study, MDD patients in the experimental group (n = 13) learned to upregulate BOLD activity of the left amygdala using an rtfMRI-nf during a happy emotion induction task. MDD patients in the control group (n = 11) were provided with a sham rtfMRI-nf. Correlations between frontal EEG asymmetry in the upper alpha band and BOLD activity across the brain were examined. Average individual changes in frontal EEG asymmetry during the rtfMRI-nf task for the experimental group showed a significant positive correlation with the MDD patients' depression severity ratings, consistent with an inverse correlation between the depression severity and frontal EEG asymmetry at rest. The average asymmetry changes also significantly correlated with the amygdala BOLD laterality. Temporal correlations between frontal EEG asymmetry and BOLD activity were significantly enhanced, during the rtfMRI-nf task, for the amygdala and many regions associated with emotion regulation. Our findings demonstrate an important link between amygdala BOLD activity and frontal EEG asymmetry during emotion regulation. Our EEG asymmetry results indicate that the rtfMRI-nf training targeting the amygdala is beneficial to MDD patients. They further suggest that EEG-nf based on frontal EEG asymmetry in the alpha band would be compatible with the amygdala-based rtfMRI-nf. Combination of the two could enhance emotion regulation training and benefit MDD patients.
Asunto(s)
Amígdala del Cerebelo/irrigación sanguínea , Trastorno Depresivo Mayor/patología , Trastorno Depresivo Mayor/rehabilitación , Lóbulo Frontal/fisiopatología , Neurorretroalimentación/métodos , Adulto , Amígdala del Cerebelo/diagnóstico por imagen , Análisis de Varianza , Electroencefalografía , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Vías Nerviosas/fisiología , Oxígeno/sangre , Proyectos Piloto , Escalas de Valoración Psiquiátrica , Estadística como Asunto , Escala Visual AnalógicaRESUMEN
Conventional structural imaging is often normal after mild traumatic brain injury (mTBI). There is a need for structural neuroimaging biomarkers that facilitate detection of milder injuries, allow recovery trajectory monitoring, and identify those at risk for poor functional outcome and disability. We present a novel approach to quantifying volumes of candidate brain regions at risk for injury. Compared to controls, patients with mTBI had significantly smaller volumes in several regions including the caudate, putamen, and thalamus when assessed 2 months after injury. These differences persisted but were reduced in magnitude 1 year after injury, suggesting the possibility of normalization over time in the affected regions. More pronounced differences, however, were found in the amygdala and hippocampus, suggesting the possibility of regionally specific responses to injury.
Asunto(s)
Amígdala del Cerebelo/irrigación sanguínea , Lesiones Encefálicas/fisiopatología , Circulación Cerebrovascular/fisiología , Hipocampo/irrigación sanguínea , Neostriado/irrigación sanguínea , Flujo Sanguíneo Regional/fisiología , Tálamo/irrigación sanguínea , Adulto , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Factores de TiempoRESUMEN
Prenatal cocaine exposure (PCE) is associated with long-term and negative effect on arousal regulation. Recent neuroimaging studies have examined brain mechanisms related to arousal dysregulation with cross-sectional experimental designs; but longitudinal changes in the brain, reflecting group differences in neurodevelopment, have never been directly examined. To directly assess the interaction of PCE and neurodevelopment, the present study used a longitudinal design to analyze functional magnetic resonance imaging (fMRI) data collected from 33 adolescents (21 with PCE and 12 non-exposed controls) while they performed the same working memory task with emotional distracters at two points in time. The mean age of participants was 14.3 years at time_1 and 16.7 years at time_2. With confounding factors statistically controlled, the fMRI data revealed significant exposure-by-time interaction in the activations of the amygdala and default mode network (DMN). For the control adolescents, brain activations associated with emotional arousal (amygdala) and cognitive effort (DMN) were both reduced at time_2 as compared to that at time_1. However, these activation reductions were not observed in the PCE group, indicating persistently high levels of emotional arousal and cognitive effort. In addition, correlations between longitudinal changes in the brain and in behavior have shown that adolescents with persistently high emotional arousal were more likely in need of high cognitive effort; and their cognitive performance was more likely to be affected by distractive challenges. The present results complement and extend previous findings from cross-sectional studies with further evidence supporting the view of PCE associated long-term teratogenic effects on arousal regulation.
Asunto(s)
Amígdala del Cerebelo/patología , Cocaína/efectos adversos , Inhibidores de Captación de Dopamina/efectos adversos , Trastornos Mentales/etiología , Trastornos del Humor/etiología , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/patología , Adolescente , Amígdala del Cerebelo/irrigación sanguínea , Ciencias Bioconductuales , Reacción de Cicloadición , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Memoria a Corto Plazo/fisiología , Pruebas Neuropsicológicas , Oxígeno , Embarazo , Estadística como AsuntoRESUMEN
Prior work suggests that there may be two distinct pathways of alcohol use disorder (AUD) risk: one associated with positive emotion enhancement and behavioral impulsivity, and another associated with negative emotion relief and coping. We sought to map these two pathways onto individual differences in neural reward and threat processing assessed using blood-oxygen-level-dependent functional magnetic resonance imaging in a sample of 759 undergraduate students (426 women, mean age 19.65±1.24 years) participating in the Duke Neurogenetics Study. We demonstrate that problem drinking is highest in the context of stress and in those with one of two distinct neural phenotypes: (1) a combination of relatively low reward-related activity of the ventral striatum (VS) and high threat-related reactivity of the amygdala; or (2) a combination of relatively high VS activity and low amygdala reactivity. In addition, we demonstrate that the relationship between stress and problem alcohol use is mediated by impulsivity, as reflected in monetary delay discounting rates, for those with high VS-low amygdala reactivity, and by anxious/depressive symptomatology for those with the opposite neural risk phenotype. Across both neural phenotypes, we found that greater divergence between VS and amygdala reactivity predicted greater risk for problem drinking. Finally, for those individuals with the low VS-high amygdala risk phenotype we found that stress not only predicted the presence of AUD diagnosis at the time of neuroimaging but also subsequent problem drinking reported 3 months following study completion. These results offer new insight into the neural basis of AUD risk and suggest novel biological targets for early individualized treatment or prevention.
Asunto(s)
Alcoholismo/complicaciones , Alcoholismo/diagnóstico , Amígdala del Cerebelo/patología , Estrés Psicológico/etiología , Estrés Psicológico/patología , Estriado Ventral/patología , Adolescente , Consumo de Bebidas Alcohólicas/fisiopatología , Amígdala del Cerebelo/irrigación sanguínea , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Oxígeno/sangre , Escalas de Valoración Psiquiátrica , Autoinforme , Estriado Ventral/irrigación sanguínea , Adulto JovenRESUMEN
Depression, anxiety, and posttraumatic stress disorder are linked to altered limbic morphology, dysregulated neuroendocrine function, and heightened amygdala responses to salient social cues. Oxytocin appears to be a potent modulator of amygdala reactivity and neuroendocrine responses to psychosocial stress. Given these stress regulatory effects, there is increasing interest in understanding the role of oxytocin in vulnerability to stress-related clinical disorders. The present study examines the impact of a common functional variant within the oxytocin receptor (OXTR) gene (rs2254298) on structure and function of the amygdala in a high-risk sample of urban, low-income, minority youth with a high incidence of early life stress (ELS). Compared to G/G homozygotes, youth carrying the OXTR A-allele showed increased amygdala volume, reduced behavioral performance, and heightened amygdala response during two functional magnetic resonance imaging (fMRI) tasks that involved viewing socially-relevant face stimuli. Higher amygdala response was related to ELS in A-allele carriers but not G/G homozygotes. These findings underscore a series of relations among a common oxytocin system gene variant, ELS exposure, and structure and function of the amygdala in early life. Heightened amygdala response to salient social cues in OXTR A-allele carriers may elevate risk for emotional psychopathology by increasing amygdala involvement in disambiguating environmental cues, particularly for individuals with ELS.
Asunto(s)
Amígdala del Cerebelo/fisiopatología , Señales (Psicología) , Polimorfismo de Nucleótido Simple/genética , Receptores de Oxitocina/genética , Estrés Psicológico/genética , Estrés Psicológico/patología , Adolescente , Amígdala del Cerebelo/irrigación sanguínea , Amígdala del Cerebelo/patología , Niño , Emociones/fisiología , Femenino , Lateralidad Funcional , Genotipo , Sustancia Gris/irrigación sanguínea , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Grupos Minoritarios , Oxígeno/sangre , Reconocimiento Visual de Modelos , Estimulación Luminosa , Pobreza , Escalas de Valoración PsiquiátricaRESUMEN
Previous studies reported an association of depressive disorder and structural alteration of frontolimbic brain regions in subjects with emotional abuse experiences during childhood and adolescence. The results suggest that aberrant function of the frontolimbic circuit and its relation with psychiatric symptoms can be found in adolescents with preclinical status. We investigated functional changes of frontolimbic networks during implicit negative emotional face processing and their relationships with depressive symptoms in adolescents with previous verbal abuse experiences. We designed a gender discrimination task using emotional faces to induce an implicit level of emotional exposure, and was completed by 31 preclinical male adolescents during an fMRI scan. The right amygdala activity and its functional connectivity with the rostral anterior cingulate cortex (ACC) during implicit processing of negative emotional faces showed a significant relationship with previous verbal abuse experiences. The hierarchical regression analyses showed that their current depressive symptoms were associated with aberrant functional interaction between the right amygdala activity and right amygdala-rostral ACC connectivity. Our findings of verbal abuse-related functional changes in the right frontoamygdala circuit may be related to vulnerability to future mood disorder.
Asunto(s)
Amígdala del Cerebelo/fisiopatología , Depresión/patología , Violencia Doméstica/psicología , Emociones/fisiología , Corteza Prefrontal/fisiopatología , Adolescente , Amígdala del Cerebelo/irrigación sanguínea , Análisis de Varianza , Mapeo Encefálico , Depresión/psicología , Humanos , Procesamiento de Imagen Asistido por Computador , Pruebas de Inteligencia , Imagen por Resonancia Magnética , Masculino , Oxígeno/sangre , Estimulación Luminosa , Corteza Prefrontal/irrigación sanguínea , Escalas de Valoración Psiquiátrica , Análisis de Regresión , Encuestas y CuestionariosRESUMEN
Recent studies have challenged the view that orbitofrontal cortex (OFC) and amygdala mediate flexible reward-guided behavior. We trained macaques to perform an object discrimination reversal task during fMRI sessions and identified a lateral OFC (lOFC) region in which activity predicted adaptive win-stay/lose-shift behavior. Amygdala and lOFC activity was more strongly coupled on lose-shift trials. However, lOFC-amygdala coupling was also modulated by the relevance of reward information in a manner consistent with a role in establishing how credit for reward should be assigned. Day-to-day fluctuations in signals and signal coupling were correlated with day-to-day fluctuation in performance. A second experiment confirmed the existence of signals for adaptive stay/shift behavior in lOFC and reflecting irrelevant reward in the amygdala in a probabilistic learning task. Our data demonstrate that OFC and amygdala each make unique contributions to flexible behavior and credit assignment.
Asunto(s)
Adaptación Psicológica/fisiología , Amígdala del Cerebelo/fisiología , Conducta de Elección/fisiología , Aprendizaje/fisiología , Corteza Prefrontal/fisiología , Recompensa , Amígdala del Cerebelo/irrigación sanguínea , Amígdala del Cerebelo/citología , Animales , Mapeo Encefálico , Procesamiento de Imagen Asistido por Computador , Macaca mulatta , Imagen por Resonancia Magnética , Masculino , Vías Nerviosas/fisiología , Neuronas/fisiología , Oxígeno/sangre , Corteza Prefrontal/irrigación sanguínea , Refuerzo en Psicología , Temperatura , Factores de TiempoRESUMEN
Although the initiation of sexual behavior is common among adolescents and young adults, some individuals express this behavior in a manner that significantly increases their risk for negative outcomes including sexually transmitted infections. Based on accumulating evidence, we have hypothesized that increased sexual risk behavior reflects, in part, an imbalance between neural circuits mediating approach and avoidance in particular as manifest by relatively increased ventral striatum (VS) activity and relatively decreased amygdala activity. Here, we test our hypothesis using data from seventy 18- to 22-year-old university students participating in the Duke Neurogenetics Study. We found a significant three-way interaction between amygdala activation, VS activation, and gender predicting changes in the number of sexual partners over time. Although relatively increased VS activation predicted greater increases in sexual partners for both men and women, the effect in men was contingent on the presence of relatively decreased amygdala activation and the effect in women was contingent on the presence of relatively increased amygdala activation. These findings suggest unique gender differences in how complex interactions between neural circuit function contributing to approach and avoidance may be expressed as sexual risk behavior in young adults. As such, our findings have the potential to inform the development of novel, gender-specific strategies that may be more effective at curtailing sexual risk behavior.
Asunto(s)
Amígdala del Cerebelo/irrigación sanguínea , Asunción de Riesgos , Caracteres Sexuales , Conducta Sexual/fisiología , Estriado Ventral/irrigación sanguínea , Adolescente , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Oxígeno/sangre , Valor Predictivo de las Pruebas , Análisis de Regresión , Adulto JovenRESUMEN
This study aimed to identify neuroimaging measures associated with risk for, or protection against, bipolar disorder by comparing youth offspring of parents with bipolar disorder versus youth offspring of non-bipolar parents versus offspring of healthy parents in (i) the magnitude of activation within emotional face processing circuitry; and (ii) functional connectivity between this circuitry and frontal emotion regulation regions. The study was conducted at the University of Pittsburgh Medical Centre. Participants included 29 offspring of parents with bipolar disorder (mean age = 13.8 years; 14 females), 29 offspring of non-bipolar parents (mean age = 13.8 years; 12 females) and 23 healthy controls (mean age = 13.7 years; 11 females). Participants were scanned during implicit processing of emerging happy, sad, fearful and angry faces and shapes. The activation analyses revealed greater right amygdala activation to emotional faces versus shapes in offspring of parents with bipolar disorder and offspring of non-bipolar parents than healthy controls. Given that abnormally increased amygdala activation during emotion processing characterized offspring of both patient groups, and that abnormally increased amygdala activation has often been reported in individuals with already developed bipolar disorder and those with major depressive disorder, these neuroimaging findings may represent markers of increased risk for affective disorders in general. The analysis of psychophysiological interaction revealed that offspring of parents with bipolar disorder showed significantly more negative right amygdala-anterior cingulate cortex functional connectivity to emotional faces versus shapes, but significantly more positive right amygdala-left ventrolateral prefrontal cortex functional connectivity to happy faces (all P-values corrected for multiple tests) than offspring of non-bipolar parents and healthy controls. Taken together with findings of increased amygdala-ventrolateral prefrontal cortex functional connectivity, and decreased amygdala-anterior cingulate cortex functional connectivity previously shown in individuals with bipolar disorder, these connectivity patterns in offspring of parents with bipolar disorder may be risk markers for, rather than markers conferring protection against, bipolar disorder in youth. The patterns of activation and functional connectivity remained unchanged after removing medicated participants and those with current psychopathology from analyses. This is the first study to demonstrate that abnormal functional connectivity patterns within face emotion processing circuitry distinguish offspring of parents with bipolar disorder from those of non-bipolar parents and healthy controls.