Effects of stress-related neuromodulators on amygdala and hippocampus resting state functional connectivity.

BACKGROUND: The human stress response is characterized by increases in neuromodulators, including norepinephrine (NE) and cortisol. Both neuromodulators can enter the brain and affect neurofunctional responses. Two brain areas associated with stress are the amygdala and the hippocampus. The precise influence of NE and cortisol on the amygdala and hippocampal resting state functional connectivity (RSFC) is poorly understood. AIMS: To investigate the influence of NE and cortisol on the amygdala and hippocampal RSFC. METHODS: We recruited 165 participants who received 10 mg yohimbine and/or 10 mg hydrocortisone in a randomized, placebo-controlled design. With seed-based analyses, we compared RSFC of the hippocampus and amygdala separately between the three groups that received medication versus placebo. RESULTS: We found no differences between yohimbine and placebo condition or between hydrocortisone and placebo condition regarding amygdala or hippocampal FC. Compared with placebo, the yohimbine/hydrocortisone condition showed increased amygdala and hippocampal RSFC with the cerebellum. Also, they had increased hippocampal RSFC with the amygdala and cerebral white matter. DISCUSSION: The group with elevated NE and cortisol showed significantly increased RSFC between the amygdala, hippocampus, and cerebellum compared to placebo. These three brain areas are involved in associative learning and emotional memory, suggesting a critical role for this network in the human stress response. Our results show that NE and cortisol together may influence the strength of this association. Compared to placebo, we found no differences in the groups receiving only one medication, suggesting that increasing one neuromodulator alone may not induce differences in neurofunctional responses. The study procedure has been registered at clinicaltrials.gov (ID: NCT04359147).

The effects of yohimbine and hydrocortisone on selective attention to fearful faces: An fMRI study.

INTRODUCTION: Selective attention to salient emotional information can enable an advantage in the face of danger. The present study aims to investigate the influence of the stress neuromodulators, norepinephrine and cortisol, on selective attention processes to fearful faces and its neuronal activation. METHODS AND MATERIALS: We used a randomized, double-blind, placebo-controlled design. 167 healthy men between 18 and 35 years (mean [SD] age: 25.23 [4.24] years) participated in the study. Participants received either: (A) yohimbine (n= 41), (B) hydrocortisone (n = 41), (C) yohimbine and hydrocortisone (n = 42) or (D) placebo only (n= 43) and participated in a dot-probe task with fearful and neutral faces in an fMRI scanner. RESULTS: We found an attentional bias toward fearful faces across all groups and related neuronal activation in the left cuneus. We did not find any differences between experimental treatment groups in selective attention and its neuronal activation. DISCUSSION: Our results provide evidence that fearful faces lead to an attentional bias with related neuronal activation in the left cuneus. We did not replicate formerly reported activation in the amygdala, intraparietal sulcus, dorsal anterior cingulate cortex, and thalamus. Suitability of the dot-probe task for fMRI studies and insignificant treatment effects are discussed.

No changes in triple network engagement following (combined) noradrenergic and glucocorticoid stimulation in healthy men.

Successful recovery from stress is integral for adaptive responding to the environment. At a cellular level, this involves (slow genomic) actions of cortisol, which alter or reverse rapid effects of noradrenaline and cortisol associated with acute stress. At the network scale, stress recovery is less well understood but assumed to involve changes within salience-, executive control-, and default mode networks. To date, few studies have investigated this phase and directly tested these assumptions. Here, we present results from a double-blind, placebo-controlled, between-group paradigm (N = 165 healthy males) administering 10 mg oral yohimbine and/or 10 mg oral hydrocortisone two hours prior to resting state scanning. We found no changes in within-network connectivity of the three networks, both after single and combined drug administration. We further report the results of Bayesian parameter inference to provide evidence for the null hypothesis. Our results contrast with previous findings, which may be attributable to systematic differences between paradigms, highlighting the need to isolate paradigm-specific effects from those related to stress.

Childhood trauma and cortical thickness in healthy women, women with post-traumatic stress disorder, and women with borderline personality disorder.

BACKGROUND: Structural brain changes have been associated with childhood trauma (CT) and several trauma-associated mental disorders. It is not known whether specific brain alterations are rather associated with CT as such or with disorders that are common sequelae of CT. In this study, we characterized cortical thickness in three distinct groups with CT: healthy women (HC/CT), women with posttraumatic stress disorder (PTSD/CT) and women with borderline personality disorder (BPD/CT). These three CT-exposed groups were compared with healthy controls not exposed to CT (HC). METHODS: We recruited 129 women (n = 70 HC, n = 25 HC/CT, n = 14 PTSD/CT, and n = 20 BPD/CT) and acquired T1-weighted anatomical images. FreeSurfer was used for conducting whole-brain cortical thickness between-group comparisons, applying separate generalized linear models to compare cortical thickness of each CT-exposed group with HC. RESULTS: The HC/CT group had lower cortical thickness in occipital lobe areas (right lingual gyrus, left lateral occipital lobe) than the HC group. The BPD/CT group showed a broader pattern of reduced cortical thickness compared to the HC group, including the bilateral superior frontal gyrus, and bilateral isthmus, the right posterior, and left caudal anterior of the cingulate cortex as well as the right lingual gyrus of the occipital lobe. We found no differences between PTSD/CT and HC. CONCLUSIONS: Cortical thickness reduction in the right lingual gyrus of the occipital lobe seem to be related to CT but is also present in BPD patients even after adjusting for severity of CT. Possibly, reduced cortical thickness in the lingual gyrus presents a CT-related vulnerability factor for CT-related adult psychopathologies such as BPD. Reduced cortical thickness in the frontal and cingulate cortex may represent unique neuroanatomical markers of BPD possibly related to difficulties in emotion regulation.

Association between childhood trauma and brain anatomy in women with post-traumatic stress disorder, women with borderline personality disorder, and healthy women.

Background: Childhood trauma (CT) is associated with altered brain anatomy. These neuroanatomical changes might be more pronounced in individuals with a psychiatric disorder. Post-traumatic stress disorder (PTSD) and borderline personality disorder (BPD) are more prevalent in individuals with a history of CT. Objective: In this study, we examined limbic and total brain volumes in healthy women with and without a history of CT and in females with PTSD or BPD and a history of CT to see whether neuroanatomical changes are a function of psychopathology or CT. Method: In total, 128 women (N = 70 healthy controls without CT, N = 25 healthy controls with CT, N = 14 individuals with PTSD, and N = 19 individuals with BPD) were recruited. A T1-weighted anatomical MRI was acquired from all participants for Freesurfer-based assessment of total brain, hippocampus, and amygdala volumes. Severity of CT was assessed with a clinical interview and the Childhood Trauma Questionnaire. Group differences in hippocampal and amygdala volumes (adjusted for total brain volume) and total brain volume (adjusted for height) were characterized by analysis of covariance. Results: Volume of the total brain, hippocampus, and amygdala did not differ between the four groups (p > .05). CT severity correlated negatively with total brain volume across groups (r = -0.20; p = .029). Conclusions: CT was associated with reduced brain volume but PTSD or BPD was not. The association between CT and reduced brain volume as a global measure of brain integrity suggests a common origin for vulnerability to psychiatric disorders later in life.

Antecedentes: El trauma infantil (TI) se asocia con alteraciones en la anatomía cerebral. Estos cambios neuroanatómicos pueden ser más pronunciados en individuos con trastornos psiquiátricos. El trastorno de estrés postraumático (TEPT) y el trastorno de personalidad limítrofe (TPL) son más prevalentes en individuos con historia de TI.Objetivo: En este estudio, examinamos los volúmenes límbico y cerebral total en mujeres sanas con y sin historia de TI y mujeres con TEPT o TPL e historia de TI para ver si los cambios neuroanatómicos son una función de la psicopatología o del TI.Método: En total, 128 mujeres (N= 70 controles sanas sin TI, N= 25 controles sanas con TI, N= 14 individuos con TEPT y N= 19 individuos con TPL) fueron reclutadas. Se obtuvo una RNM anatómica ponderada en T1 de todas las participantes para la evaluación basada en Freesurfer de los volúmenes totales del cerebro, hipocampo y amígdala. La severidad del TI fue evaluada con una entrevista clínica y con el Cuestionario de Trauma Infantil. Las diferencias grupales en los volúmenes del hipocampo y amígdala (ajustadas por el volumen cerebral total) y el volumen cerebral total (ajustadas por altura) se caracterizaron mediante análisis de covarianza.Resultados: El volumen total del cerebro, hipocampo y amígdala no difirieron entre los cuatro grupos (p > .05). La severidad del TI se correlacionó negativamente con el volumen cerebral total en todos los grupos (r = −0.20; p =.29).Conclusiones: El TI estuvo asociado a un volumen cerebral reducido, pero el TEPT o TPL no se asociaron. La asociación entre TI y volumen cerebral disminuido como una medida global de la integridad cerebral sugiere un origen común de vulnerabilidad a los trastornos psiquiátricos más adelante en la vida.

Validity of the Empatica E4 Wristband to Measure Heart Rate Variability (HRV) Parameters: a Comparison to Electrocardiography (ECG).

Wearable monitoring devices are an innovative way to measure heart rate (HR) and heart rate variability (HRV), however, there is still debate about the validity of these wearables. This study aimed to validate the accuracy and predictive value of the Empatica E4 wristband against the VU University Ambulatory Monitoring System (VU-AMS) in a clinical population of traumatized adolescents in residential care. A sample of 345 recordings of both the Empatica E4 wristband and the VU-AMS was derived from a feasibility study that included fifteen participants. They wore both devices during two experimental testing and twelve intervention sessions. We used correlations, cross-correlations, Mann-Whitney tests, difference factors, Bland-Altman plots, and Limits of Agreement to evaluate differences in outcomes between devices. Significant correlations were found between Empatica E4 and VU-AMS recordings for HR, SDNN, RMSSD, and HF recordings. There was a significant difference between the devices for all parameters but HR, although effect sizes were small for SDNN, LF, and HF. For all parameters but RMSSD, testing outcomes of the two devices led to the same conclusions regarding significance. The Empatica E4 wristband provides a new opportunity to measure HRV in an unobtrusive way. Results of this study indicate the potential of the Empatica E4 as a practical and valid tool for research on HR and HRV under non-movement conditions. While more research needs to be conducted, this study could be considered as a first step to support the use of HRV recordings provided by wearables.