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INTRODUCTION: Major depressive disorder (MDD) is associated with dysfunctional reward processing, which involves functional circuitry of the habenula (Hb) and nucleus accumbens (NAc). Since ketamine elicits rapid antidepressant and antianhedonic effects in MDD, this study sought to investigate how serial ketamine infusion (SKI) treatment modulates static and dynamic functional connectivity (FC) in Hb and NAc functional networks. METHODS: MDD participants (n = 58, mean age = 40.7 years, female = 28) received four ketamine infusions (0.5 mg/kg) 2-3 times weekly. Resting-state functional magnetic resonance imaging (fMRI) scans and clinical assessments were collected at baseline and 24 h post-SKI. Static FC (sFC) and dynamic FC variability (dFCv) were calculated from left and right Hb and NAc seeds to all other brain regions. Changes in FC pre-to-post SKI, and correlations with changes with mood and anhedonia were examined. Comparisons of FC between patients and healthy controls (HC) at baseline (n = 55, mean age = 32.6, female = 31), and between HC assessed twice (n = 16) were conducted as follow-up analyses. RESULTS: Following SKI, significant increases in left Hb-bilateral visual cortex FC, decreases in left Hb-left inferior parietal cortex FC, and decreases in left NAc-right cerebellum FC occurred. Decreased dFCv between left Hb and right precuneus and visual cortex, and decreased dFCv between right NAc and right visual cortex both significantly correlated with improvements in mood ratings. Decreased FC between left Hb and bilateral visual/parietal cortices as well as increased FC between left NAc and right visual/parietal cortices both significantly correlated with improvements in anhedonia. No differences were observed between HC at baseline or over time. CONCLUSION: Subanesthetic ketamine modulates functional pathways linking the Hb and NAc with visual, parietal, and cerebellar regions in MDD. Overlapping effects between Hb and NAc functional systems were associated with ketamine's therapeutic response.
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Trastorno Depresivo Mayor , Habénula , Ketamina , Imagen por Resonancia Magnética , Núcleo Accumbens , Humanos , Ketamina/farmacología , Ketamina/administración & dosificación , Masculino , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/fisiopatología , Trastorno Depresivo Mayor/diagnóstico por imagen , Núcleo Accumbens/efectos de los fármacos , Núcleo Accumbens/diagnóstico por imagen , Núcleo Accumbens/fisiopatología , Adulto , Femenino , Habénula/efectos de los fármacos , Habénula/fisiopatología , Habénula/diagnóstico por imagen , Persona de Mediana Edad , Antidepresivos/farmacología , Antidepresivos/administración & dosificación , Anhedonia/efectos de los fármacos , Anhedonia/fisiologíaRESUMEN
OBJECTIVE: Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by motor and early non-motor symptoms. The habenula is implicated in the pathophysiology of depression. This study investigates habenular volume in PD patients without clinical depression to show the changes in PD unrelated to depression. METHODS: The study used high-resolution 7 Tesla MRI data from the TRACK-PD study involving 104 PD patients and 44 healthy controls (HCs). The habenula was manually segmented, and volumes were measured, considering demographic data and depression scores via the Beck Depression Inventory (BDI). RESULTS: No significant correlation was found between habenular volume and BDI scores in PD patients or HCs. However, the PD group exhibited a significantly larger mean and right habenular volume than HCs. Although PD patients showed higher BDI scores, indicating more subthreshold depression, these did not correlate with the habenular volume. CONCLUSION: The results suggest that while the habenula may be involved in the symptoms of PD, its role in depression within this cohort is unclear. The changes might be related to the role of the habenula in motor symptoms. This study provides a new perspective on the role of the habenula in PD, but future research could lead to a greater understanding of the neuroanatomical features of the habenula in PD.
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Depresión , Habénula , Imagen por Resonancia Magnética , Enfermedad de Parkinson , Humanos , Habénula/diagnóstico por imagen , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Imagen por Resonancia Magnética/métodos , Anciano , Depresión/diagnóstico por imagenRESUMEN
BACKGROUND: Habenula, a hub brain region controlling monoaminergic brain center, has been implicated in major depressive disorder (MDD) and as a possible target of antidepressant response. Nevertheless, the effect of antidepressant drug treatment on habenular volumes remains unknown. The objective of the present research was to study habenular volume change after antidepressant treatment in patients with MDD, and assess whether it is associated with clinical improvement. METHODS: Fifty patients with a current major depressive episode (MDE) in the context of MDD, and antidepressant-free for at least 1 month, were assessed for habenula volume (3T MRI with manual segmentation) before and after a 3 months sequence of venlafaxine antidepressant treatment. RESULTS: A 2.3% significant increase in total habenular volume (absolute volume: P = 0.0013; relative volume: P = 0.0055) and a 3.3% significant increase in left habenular volume (absolute volume: P = 0.00080; relative volume: P = 0.0028) were observed. A significant greater variation was observed in male patients (4.8%) compared to female patients. No association was observed between habenular volume changes and response and remission. Some habenula volume changes were associated with improvement of olfactory pleasantness. CONCLUSION: Habenular volumes increased after 3 months of venlafaxine treatment in depressed patients. Further studies should assess whether cell proliferation and density or dendritic structure variations are implied in these volume changes.
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Trastorno Depresivo Mayor , Habénula , Imagen por Resonancia Magnética , Clorhidrato de Venlafaxina , Humanos , Clorhidrato de Venlafaxina/farmacología , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/patología , Femenino , Masculino , Habénula/efectos de los fármacos , Habénula/diagnóstico por imagen , Habénula/patología , Adulto , Persona de Mediana Edad , Antidepresivos de Segunda Generación/farmacologíaRESUMEN
BACKGROUND AND PURPOSE: The habenula is a key node in the regulation of emotion-related behavior. Accurate visualization of the habenula and its reliable quantitative analysis is vital for the assessment of psychiatric disorders. To obtain high-contrast habenula images and allow them to be compatible with clinical applications, this preliminary study compared 3T MP2RAGE and quantitative susceptibility mapping with MPRAGE by evaluating the habenula segmentation performance. MATERIALS AND METHODS: Ten healthy volunteers were scanned twice with 3T MPRAGE and MP2RAGE and once with quantitative susceptibility mapping. Image quality and visibility of habenula anatomic features were analyzed by 3 radiologists using a 5-point scale. Contrast assessments of the habenula and thalamus were also performed. The reproducibility of the habenula volume from MPRAGE and MP2RAGE was evaluated by manual segmentation and the Multiple Automatically Generated Template brain segmentation algorithm (MAGeTbrain). T1 values and susceptibility were measured in the whole habenula and habenula geometric subregion using MP2RAGE T1-mapping and quantitative susceptibility mapping. RESULTS: The 3T MP2RAGE and quantitative susceptibility mapping demonstrated clear boundaries and anatomic features of the habenula compared with MPRAGE, with a higher SNR and contrast-to-noise ratio (all P < .05). Additionally, 3T MP2RAGE provided reliable habenula manual and MAGeTbrain segmentation volume estimates with greater reproducibility. T1-mapping derived from MP2RAGE was highly reliable, and susceptibility contrast was highly nonuniform within the habenula. CONCLUSIONS: We identified an optimized sequence combination (3T MP2RAGE combined with quantitative susceptibility mapping) that may be useful for enhancing habenula visualization and yielding more reliable quantitative data.
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Habénula , Humanos , Habénula/diagnóstico por imagen , Reproducibilidad de los Resultados , Algoritmos , Imagen por Resonancia Magnética/métodos , Voluntarios Sanos , EncéfaloRESUMEN
Introduction: The habenula, a brain region involved in aversion, might negatively modulate caloric intake. Functional magnetic resonance imaging (fMRI) studies reported associations between weight loss and habenula functional connectivity. However, whether habenula resting-state functional connectivity (rsFC) and reward-related activity are altered in obesity is yet unknown. Methods: Using data from the Human Connectome Project, we included 300 subjects with various body mass indexes (BMIs) and a healthy long-term blood glucose (hemoglobin A1c [HbA1c]). In addition, we investigated a potential BMI × HbA1c interaction in a separate cohort including subjects with prediabetes (n = 72). Habenula rsFC was assessed using a region of interest (ROI)-to-ROI analysis. Furthermore, a separate analysis using gambling task fMRI data focused on reward-related habenula activity. Results: We did not find an association between BMI and habenula rsFC for any of the ROIs. For the exploratory analysis of the BMI × HbA1c effect, a significant interaction effect was found for the habenula-ventral tegmental area (VTA) connection, but this did not survive multiple comparisons correction. Monetary punishment compared with reward activated the bilateral habenula in the BMI sample, but this activity was not associated with BMI. Discussion: In conclusion, we did not find evidence for an association between BMI and habenula rsFC or reward-related activity. However, there might be an interaction between BMI and HbA1c for the habenula-VTA rsFC, suggestive of a role of the habenula in glucose regulation. Future studies should focus on metabolic parameters in their experimental design to confirm our findings and explore the precise role of the habenula in metabolism.
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Conectoma , Habénula , Humanos , Conectoma/métodos , Habénula/diagnóstico por imagen , Habénula/fisiología , Hemoglobina Glucada , Imagen por Resonancia Magnética , Obesidad/diagnóstico por imagen , RecompensaRESUMEN
The habenula has been implicated in the pathogenesis of pain and analgesia, while evidence concerning its function in chronic low back pain (cLBP) is sparse. This study aims to investigate the resting-state functional connectivity (rsFC) and effective connectivity of the habenula in 52 patients with cLBP and 52 healthy controls (HCs) and assess the feasibility of distinguishing cLBP from HCs based on connectivity by machine learning methods. Our results indicated significantly enhanced rsFC of the habenula-left superior frontal cortex (SFC), habenula-right thalamus, and habenula-bilateral insular pathways as well as decreased rsFC of the habenula-pons pathway in cLBP patients compared to HCs. Dynamic causal modelling revealed significantly enhanced effective connectivity from the right thalamus to right habenula in cLBP patients compared with HCs. RsFC of the habenula-SFC was positively correlated with pain intensities and Hamilton Depression scores in the cLBP group. RsFC of the habenula-right insula was negatively correlated with pain duration in the cLBP group. Additionally, the combination of the rsFC of the habenula-SFC, habenula-thalamus, and habenula-pons pathways could reliably distinguish cLBP patients from HCs with an accuracy of 75.9% by support vector machine, which was validated in an independent cohort (N = 68, accuracy = 68.8%, p = .001). Linear regression and random forest could also distinguish cLBP and HCs in the independent cohort (accuracy = 73.9 and 55.9%, respectively). Overall, these findings provide evidence that cLBP may be associated with abnormal rsFC and effective connectivity of the habenula, and highlight the promise of machine learning in chronic pain discrimination.
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Dolor Crónico , Habénula , Dolor de la Región Lumbar , Humanos , Dolor de la Región Lumbar/diagnóstico por imagen , Dolor de la Región Lumbar/patología , Imagen por Resonancia Magnética/métodos , Habénula/diagnóstico por imagen , Dolor Crónico/diagnóstico por imagen , Aprendizaje AutomáticoRESUMEN
Understanding the evolutionarily conserved feature of functional laterality in the habenula has been attracting attention due to its potential role in human cognition and neuropsychiatric disorders. Deciphering the structure of the human habenula remains to be challenging, which resulted in inconsistent findings for brain disorders. Here, we present a large-scale meta-analysis of the left-right differences in the habenular volume in the human brain to provide a clearer picture of the habenular asymmetry. We searched PubMed, Web of Science, and Google Scholar for articles that reported volume data of the bilateral habenula in the human brain, and assessed the left-right differences. We also assessed the potential effects of several moderating variables including the mean age of the participants, magnetic field strengths of the scanners and different disorders by using meta-regression and subgroup analysis. In total 52 datasets (N = 1427) were identified and showed significant heterogeneity in the left-right differences and the unilateral volume per se. Moderator analyses suggested that such heterogeneity was mainly due to different MRI scanners and segmentation approaches used. While inversed asymmetry patterns were suggested in patients with depression (leftward) and schizophrenia (rightward), no significant disorder-related differences relative to healthy controls were found in either the left-right asymmetry or the unilateral volume. This study provides useful data for future studies of brain imaging and methodological developments related to precision habenula measurements, and also helps to further understand potential roles of the habenula in various disorders.
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Habénula , Humanos , Habénula/diagnóstico por imagen , Cognición , Imagen por Resonancia Magnética , Lateralidad FuncionalRESUMEN
BACKGROUND: Increasing evidence has suggested the significant relationships between major depressive disorder (MDD) and the neural abnormalities of the Habenula (Hb). Yet, previous research on the relationships between Hb and MDD mainly focuses on the static descriptions of their functional connectivity. However, recent work suggests that the connectivity patterns are indeed dynamic, though related analysis and interpretation remain scarce. METHODS: Using seed-based resting-state fMRI, the static (sFC) and dynamic functional connectivity (dFC) between the Hb and whole-brain were calculated, including 51 clinical participants (MDDs) and 45 healthy controls (HCs). Association between the aberrant connectivity patterns and depressive symptomatology was also analyzed. RESULTS: Compared with the HCs, MDDs exhibited increased sFC from the left Hb to the right inferior temporal gyrus and left superior frontal gyrus (SFG), while sFC to the right calcarine gyrus decreased. Notably, we observed that dFC between the left Hb and the right supplementary motor area, right postcentral gyrus (PoCG), left inferior frontal gyrus as well as left occipital gyrus was weak in MDDs. Furthermore, sFC between the Hb and SFG correlated positively with the measured attention-related cognitive deficits. Importantly, there was a positive correlation between dFC between the Hb and PoCG and depressive severity. CONCLUSIONS: The findings indicate that the anomalous neural circuitry of Hb may underpin impaired attention disengagement, emotional modulation and motor inhibition associated with depressive symptoms such as rumination disposition and psychomotor retardation. This may open new avenues for studying the neuropathology mechanisms and guiding new treatment strategies for MDD.
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Trastorno Depresivo Mayor , Habénula , Humanos , Trastorno Depresivo Mayor/diagnóstico por imagen , Depresión , Habénula/diagnóstico por imagen , Encéfalo , Corteza Prefrontal , Imagen por Resonancia Magnética , Gravedad del PacienteRESUMEN
BACKGROUND: Major depressive disorder (MDD) is a common cause of disability and morbidity, affecting about 10% of the population worldwide. Subclinical depression (SD) can be understood as a precursor of MDD, and therefore provides an MDD risk indicator. The pathogenesis of MDD and SD in humans is still unclear, and the current diagnosis lacks accurate biomarkers and gold standards. METHODS: A total of 40 MDD, 34 SD, and 40 healthy control (HC) participants matched by age, gender, and education were included in this study. Resting-state functional magnetic resonance images (rs-fMRI) were used to analyze the functional connectivity (FC) of the posterior parietal thalamus (PPtha), which includes the lateral habenula, as the region of interest. Analysis of variance with the post hoc t-test test was performed to find significant differences in FC and clarify the variations in FC among the HC, SD, and MDD groups. RESULTS: Increased FC was observed between PPtha and the left inferior temporal gyrus (ITG) for MDD versus SD, and between PPtha and the right ITG for SD versus HC. Conversely, decreased FC was observed between PPtha and the right middle temporal gyrus (MTG) for MDD versus SD and MDD versus HC. The FC between PPtha and the middle frontal gyrus (MFG) in SD was higher than that in MDD and HC. Compared with the HC group, the FC of PPtha-ITG (left and right) increased in both the SD and MDD groups, PPtha-MTG (right) decreased in both the SD and MDD groups and PPtha-MFG (right) increased in the SD group and decreased in the MDD group. CONCLUSION: Through analysis of FC measured by rs-fMRI, the altered FC between PPtha and several brain regions (right and left ITG, right MTG, and right MFG) has been identified in participants with SD and MDD. Different alterations in FC between PPtha and these regions were identified for patients with depression. These findings might provide insights into the potential pathophysiological mechanisms of SD and MDD, especially related to PPtha and the lateral habenula.
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Trastorno Depresivo Mayor , Habénula , Encéfalo , Mapeo Encefálico , Depresión , Habénula/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética/métodosRESUMEN
BACKGROUND: A significant proportion of patients with major depressive disorder are resistant to antidepressant medication and psychological treatments. A core symptom of treatment-resistant depression (TRD) is anhedonia, or the inability to feel pleasure, which has been attributed to disrupted habenula function - a component of the reward network. This study aimed to map detailed neural circuitry architecture related to the habenula to identify neural mechanisms of TRD. METHODS: 35 TRD patients, 35 patients with treatment-sensitive depression (TSD), and 38 healthy controls (HC) underwent resting-state functional magnetic resonance imaging. Functional connectivity analyses were performed using the left and right habenula as seed regions of interest, and the three groups were compared using whole-brain voxel-wise comparisons. RESULTS: The TRD group demonstrated hyperconnectivity of the left habenula to the left precuneus cortex and the right precentral gyrus, compared to the TSD group, and to the right precuneus cortex, compared to the TSD and HC groups. In contrast, TSD demonstrated hypoconnectivity than HC for both connectivity measures. These connectivity values were significantly higher in patients with a history of suicidal ideation. CONCLUSIONS: This study provides evidence that, unlike TSD, TRD is characterized by hyperconnectivity of the left habenula particularly with regions of the default mode network. An increased interplay between reward and default mode networks is linked to suicidality and could be a possible mechanism for anhedonia in hard to treat depression.
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Trastorno Depresivo Mayor/terapia , Trastorno Depresivo Resistente al Tratamiento/patología , Habénula/fisiopatología , Anhedonia/fisiología , Estudios de Casos y Controles , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Resistente al Tratamiento/diagnóstico por imagen , Trastorno Depresivo Resistente al Tratamiento/terapia , Habénula/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Ideación SuicidaRESUMEN
The decision that it is worth doing something rather than nothing is a core yet understudied feature of voluntary behaviour. Here we study "willingness to act", the probability of making a response given the context. Human volunteers encountered opportunities to make effortful actions in order to receive rewards, while watching a movie inside a 7 T MRI scanner. Reward and other context features determined willingness-to-act. Activity in the habenula tracked trial-by-trial variation in participants' willingness-to-act. The anterior insula encoded individual environment features that determined this willingness. We identify a multi-layered network in which contextual information is encoded in the anterior insula, converges on the habenula, and is then transmitted to the supplementary motor area, where the decision is made to either act or refrain from acting via the nigrostriatal pathway.
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Encéfalo/patología , Toma de Decisiones/fisiología , Habénula/fisiología , Adolescente , Adulto , Animales , Conducta , Encéfalo/diagnóstico por imagen , Corteza Cerebral , Femenino , Habénula/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Probabilidad , Recompensa , Adulto JovenRESUMEN
The habenula is a small epithalamic structure with widespread connections to multiple cortical, subcortical and brainstem regions. It has been identified as the central structure modulating the reward value of social interactions, behavioral adaptation, sensory integration and circadian rhythm. Autism spectrum disorder (ASD) is characterized by social communication deficits, restricted interests, repetitive behaviors, and is frequently associated with altered sensory perception and mood and sleep disorders. The habenula is implicated in all these behaviors and results of preclinical studies suggest a possible involvement of the habenula in the pathophysiology of this disorder. Using anatomical magnetic resonance imaging and automated segmentation we show that the habenula is significantly enlarged in ASD subjects compared to controls across the entire age range studied (6-30 years). No differences were observed between sexes. Furthermore, support-vector machine modeling classified ASD with 85% accuracy (model using habenula volume, age and sex) and 64% accuracy in cross validation. The Social Responsiveness Scale (SRS) significantly differed between groups, however, it was not related to individual habenula volume. The present study is the first to provide evidence in human subjects of an involvement of the habenula in the pathophysiology of ASD.
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Trastorno del Espectro Autista/diagnóstico por imagen , Habénula/diagnóstico por imagen , Adolescente , Adulto , Trastorno del Espectro Autista/patología , Niño , Femenino , Habénula/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Conducta Social , Máquina de Vectores de SoporteRESUMEN
The habenula (Hb) has been hypothesized to play an essential role in major depressive disorder (MDD) as it is considered to be an important node between fronto-limbic areas and midbrain monoaminergic structures based on animal studies. In this study, we aimed to investigate the differences in volume and T1 value of the Hb between patients with MDD and healthy control (HC) subjects. Analysis for the Hb volumes was performed using high-resolution 7-T magnetic resonance (MR) image data from 33 MDD patients and 36 healthy subjects. Two researchers blinded to the clinical data manually delineated the habenular nuclei and Hb volume, and T1 values were calculated based on overlapping voxels. We compared the Hb volume and T1 value between the MDD and HC groups and compared the volume and T1 values between the left and right Hbs in each group. Compared to HC subjects, MDD patients had a smaller right Hb volume; however, there was no significant volume difference in the left Hb between groups. In the MDD group, the right Hb was smaller in volume and lower in T1 value than the left Hb. The present findings suggest a smaller right Hb volume and left-right asymmetry of Hb volume in MDD. Future high-resolution 7-T MR imaging studies with larger sample sizes will be needed to derive a more definitive conclusion.
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Trastorno Depresivo Mayor/diagnóstico por imagen , Habénula/patología , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Adulto , Estudios de Casos y Controles , Trastorno Depresivo Mayor/patología , Femenino , Habénula/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Adulto JovenRESUMEN
The habenula is one of the most important brain regions for investigating the etiology of psychiatric diseases such as major depressive disorder (MDD). However, the habenula is challenging to delineate with the naked human eye in brain imaging due to its low contrast and tiny size, and the manual segmentation results vary greatly depending on the observer. Therefore, there is a great need for automatic quantitative analytic methods of the habenula for psychiatric research purposes. Here we propose an automated segmentation and volume estimation method for the habenula in 7 Tesla magnetic resonance imaging based on a deep learning-based semantic segmentation network. The proposed method, using the data of 69 participants (33 patients with MDD and 36 normal controls), achieved an average precision, recall, and dice similarity coefficient of 0.869, 0.865, and 0.852, respectively, in the automated segmentation task. Moreover, the intra-class correlation coefficient reached 0.870 in the volume estimation task. This study demonstrates that this deep learning-based method can provide accurate and quantitative analytic results of the habenula. By providing rapid and quantitative information on the habenula, we expect our proposed method will aid future psychiatric disease studies.
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Aprendizaje Profundo , Trastorno Depresivo Mayor/diagnóstico por imagen , Habénula/diagnóstico por imagen , Imagen por Resonancia Magnética , Adulto , Femenino , Humanos , Masculino , Reproducibilidad de los ResultadosRESUMEN
Fear generalization - the tendency to interpret ambiguous stimuli as threatening due to perceptual similarity to a learned threat - is an adaptive process. Overgeneralization, however, is maladaptive and has been implicated in a number of anxiety disorders. Neuroimaging research has indicated several regions sensitive to effects of generalization, including regions involved in fear excitation (e.g., amygdala, insula) and inhibition (e.g., ventromedial prefrontal cortex). Research has suggested several other small brain regions may play an important role in this process (e.g., hippocampal subfields, bed nucleus of the stria terminalis [BNST], habenula), but, to date, these regions have not been examined during fear generalization due to limited spatial resolution of standard human neuroimaging. To this end, we utilized the high spatial resolution of 7T fMRI to characterize the neural circuits involved in threat discrimination and generalization. Additionally, we examined potential modulating effects of trait anxiety and intolerance of uncertainty on neural activation during threat generalization. In a sample of 31 healthy undergraduate students, significant positive generalization effects (i.e., greater activation for stimuli with increasing perceptual similarity to a learned threat cue) were observed in the visual cortex, thalamus, habenula and BNST, while negative generalization effects were observed in the dentate gyrus, CA1, and CA3. Associations with individual differences were underpowered, though preliminary findings suggested greater generalization in the insula and primary somatosensory cortex may be correlated with self-reported anxiety. Overall, findings largely support previous neuroimaging work on fear generalization and provide additional insight into the contributions of several previously unexplored brain regions.
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Adaptación Psicológica/fisiología , Miedo/fisiología , Neuroimagen Funcional/métodos , Generalización del Estimulo/fisiología , Imagen por Resonancia Magnética/métodos , Red Nerviosa/diagnóstico por imagen , Adolescente , Adulto , Ansiedad/fisiopatología , Corteza Cerebral/diagnóstico por imagen , Femenino , Habénula/diagnóstico por imagen , Hipocampo/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Red Nerviosa/fisiología , Núcleos Septales/diagnóstico por imagen , Corteza Somatosensorial/diagnóstico por imagen , Tálamo/diagnóstico por imagen , Incertidumbre , Corteza Visual/diagnóstico por imagen , Adulto JovenRESUMEN
BACKGROUND: Ketamine's potent and rapid antidepressant properties have shown great promise to treat severe forms of major depressive disorder (MDD). A recently hypothesized antidepressant mechanism of action of ketamine is the inhibition of N-methyl-D-aspartate receptor-dependent bursting activity of the habenula (Hb), a small brain structure that modulates reward and affective states. METHODS: Resting-state functional magnetic resonance imaging was conducted in 35 patients with MDD at baseline and 24 hours following treatment with i.v. ketamine. A seed-to-voxel functional connectivity (FC) analysis was performed with the Hb as a seed-of-interest. Pre-post changes in FC and the associations between changes in FC of the Hb and depressive symptom severity were examined. RESULTS: A reduction in Montgomery-Åsberg Depression Rating Scale scores from baseline to 24 hours after ketamine infusion was associated with increased FC between the right Hb and a cluster in the right frontal pole (t = 4.65, P = .03, false discovery rate [FDR]-corrected). A reduction in Quick Inventory of Depressive Symptomatology-Self Report score following ketamine was associated with increased FC between the right Hb and clusters in the right occipital pole (t = 5.18, P < .0001, FDR-corrected), right temporal pole (t = 4.97, P < .0001, FDR-corrected), right parahippocampal gyrus (t = 5.80, P = .001, FDR-corrected), and left lateral occipital cortex (t = 4.73, P = .03, FDR-corrected). Given the small size of the Hb, it is possible that peri-habenular regions contributed to the results. CONCLUSIONS: These preliminary results suggest that the Hb might be involved in ketamine's antidepressant action in patients with MDD, although these findings are limited by the lack of a control group.
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Antidepresivos/farmacología , Corteza Cerebral/fisiopatología , Conectoma , Trastorno Depresivo Mayor/fisiopatología , Trastorno Depresivo Resistente al Tratamiento/tratamiento farmacológico , Trastorno Depresivo Resistente al Tratamiento/fisiopatología , Habénula/fisiopatología , Ketamina/farmacología , Administración Intravenosa , Adulto , Antidepresivos/administración & dosificación , Corteza Cerebral/diagnóstico por imagen , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Resistente al Tratamiento/diagnóstico por imagen , Femenino , Habénula/diagnóstico por imagen , Humanos , Ketamina/administración & dosificación , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de SaludRESUMEN
The habenula plays an important role in brain reward circuitry and psychiatric conditions. While much work has been done on the function and structure of the habenula in animal models, in vivo imaging studies of the human habenula have been relatively scarce due to its small size, deep brain location, and lack of clear biomarkers for its heterogeneous substructure. In this paper, we report high-resolution (0.5 × 0.5 × 0.8 mm3) MRI of the human habenula with quantitative susceptibility mapping (QSM) at 3 T. By analyzing 48 scan datasets collected from 21 healthy subjects, we found that magnetic susceptibility contrast is highly non-uniform within the habenula and across the subjects. In particular, we observed high prevalence of elevated susceptibility in the posterior subregion of the habenula. Correlation analysis between the susceptibility and the effective transverse relaxation rate (R2*) indicated that localized susceptibility enhancement in the habenula is more associated with increased paramagnetic (such as iron) rather than decreased diamagnetic (such as myelin) sources. Our results suggest that high-resolution QSM could make a potentially useful tool for substructure-resolved in vivo habenula imaging, and provide a groundwork for the future development of magnetic susceptibility as a quantitative biomarker for human habenula studies.
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Encéfalo/diagnóstico por imagen , Habénula/diagnóstico por imagen , Habénula/fisiología , Adulto , Anciano , Biomarcadores , Química Encefálica , Mapeo Encefálico/métodos , Femenino , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Vaina de Mielina/metabolismo , Tamaño de los Órganos , Factores Sexuales , Adulto JovenRESUMEN
Irritable bowel syndrome (IBS) is a disorder involving dysfunctional brain-gut interactions characterized by chronic recurrent abdominal pain, altered bowel habits, and negative emotion. Previous studies have linked the habenula to the pathophysiology of negative emotion and pain. However, no studies to date have investigated habenular function in IBS patients. In this study, we investigated the resting-state functional connectivity (rsFC) and effective connectivity of the habenula in 34 subjects with IBS and 34 healthy controls and assessed the feasibility of differentiating IBS patients from healthy controls using a machine learning method. Our results showed significantly enhanced rsFC of the habenula-left dorsolateral prefrontal cortex (dlPFC) and habenula-periaqueductal grey (PAG, dorsomedial part), as well as decreased rsFC of the habenula-right thalamus (dorsolateral part), in the IBS patients compared with the healthy controls. Habenula-thalamus rsFC was positively correlated with pain intensity (r = .467, p = .005). Dynamic causal modeling (DCM) revealed significantly decreased effective connectivity from the right habenula to the right thalamus in the IBS patients compared to the healthy controls that was negatively correlated with disease duration (r = -.407, p = .017). In addition, IBS was classified with an accuracy of 71.5% based on the rsFC of the habenula-dlPFC, habenula-thalamus, and habenula-PAG in a support vector machine (SVM), which was further validated in an independent cohort of subjects (N = 44, accuracy = 65.2%, p = .026). Taken together, these findings establish altered habenular rsFC and effective connectivity in IBS, which extends our mechanistic understanding of the habenula's role in IBS.
Asunto(s)
Conectoma , Corteza Prefontal Dorsolateral/fisiopatología , Habénula/fisiopatología , Síndrome del Colon Irritable/diagnóstico por imagen , Síndrome del Colon Irritable/fisiopatología , Imagen por Resonancia Magnética , Dolor/fisiopatología , Sustancia Gris Periacueductal/fisiopatología , Máquina de Vectores de Soporte , Tálamo/fisiopatología , Adulto , Estudios Transversales , Corteza Prefontal Dorsolateral/diagnóstico por imagen , Estudios de Factibilidad , Femenino , Habénula/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Dolor/diagnóstico por imagen , Sustancia Gris Periacueductal/diagnóstico por imagen , Tálamo/diagnóstico por imagen , Adulto JovenRESUMEN
Studies of habenula (Hb) function and structure provided evidence of its involvement in psychiatric disorders, including schizophrenia and bipolar disorder. Previous studies using magnetic resonance imaging (manual/semiautomated segmentation) have reported conflicting results. Aiming to improve Hb segmentation reliability and the study of large datasets, we describe a fully automated protocol that was validated against manual segmentations and applied to 3 datasets (childhood/adolescence and adult bipolar disorder and schizophrenia). It achieved reliable Hb segmentation, providing robust volume estimations across a large age range and varying image acquisition parameters. Applying it to clinically relevant datasets, we found smaller Hb volumes in the adult bipolar disorder dataset and larger volumes in the adult schizophrenia dataset compared with healthy control subjects. There are indications that Hb volume in both groups shows deviating developmental trajectories early in life. This technique sets a precedent for future studies, as it allows for fast and reliable Hb segmentation and will be publicly available.
Asunto(s)
Habénula , Trastornos Mentales , Adolescente , Adulto , Niño , Habénula/diagnóstico por imagen , Habénula/fisiopatología , Humanos , Imagen por Resonancia Magnética , Trastornos Mentales/diagnóstico por imagen , Trastornos Mentales/fisiopatología , Reproducibilidad de los ResultadosRESUMEN
This study aimed to examine habenular resting state functional connectivity (RSFC) abnormalities in tobacco-smoking veterans. The authors explored RSFC in sated smokers (n = 3D 18), overnight deprived smokers (n = 3D 13), and nonsmoker controls (n = 3D 26). Seed-to-voxel analysis was used to explore RSFC in the habenula. Compared to sated smokers, deprived smokers demonstrated higher RSFC between the right habenula and two clusters of voxels: one in the right fusiform gyrus, and one in the left lingual gyrus. To study nicotine withdrawal, the authors used the Shiffman-Jarvik Withdrawal Questionnaire (SJWQ) score as a regressor and found higher RSFC between the right habenula and the left frontal pole in deprived compared to sated smokers. Right habenula RSFC distinguished between sated and deprived smokers and differentiated between sated and deprived smokers when using SJWQ as a regressor, suggesting a habenular role in tobacco withdrawal.