Biomedical subjects

Richard J Davidson

Publications and source records attributed to Richard J Davidson.

At least 19 recordsLinked to original sources

PubMed2025

A whole-brain voxel-based analysis of structural abnormalities in PTSD: An ENIGMA-PGC study.

BACKGROUND: Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group. METHODS: T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9). RESULTS: PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges' g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges' g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (p corrected  = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (p corrected  = .001). CONCLUSIONS: PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.

Humans↗

PubMed2006

Event-related functional magnetic resonance imaging measures of neural activity to positive social stimuli in pre- and post-treatment depression.

BACKGROUND: Relationships between aberrant social functioning and depression have been explored via behavioral, clinical, and survey methodologies, highlighting their importance in the etiology of depression. The neural underpinnings of these relationships, however, have not been explored. METHODS: Nine depressed participants and 14 never-depressed control subjects viewed emotional and neutral pictures at two functional magnetic resonance imaging (fMRI) scanning sessions approximately 22 weeks apart. In the interim, depressed patients received the antidepressant Venlafaxine. Positively rated images were parsed into three separate comparisons: social interaction, human faces, and sexual images; across scanning session, activation to these images was compared with other positively rated images. RESULTS: For each of the three social stimulus types (social interaction, faces, sexual images), a distinguishable circuitry was activated equally in non-depressed control subjects and post-treatment depressed subjects but showed a hypo-response in the depressed group pre-treatment. These structures include regions of prefrontal, temporal, and parietal cortices, insula, basal ganglia, and the hippocampus. CONCLUSIONS: The neural hypo-response to positively valenced social stimuli that is observed in depression remits as response to antidepressant medication occurs, suggesting a state-dependent deficiency in response to positive social incentives. These findings underscore the importance of addressing social dysfunction in research and treatment of depression.

Adult↗

PubMed2006

Amygdala and ventromedial prefrontal cortex are inversely coupled during regulation of negative affect and predict the diurnal pattern of cortisol secretion among older adults.

Among younger adults, the ability to willfully regulate negative affect, enabling effective responses to stressful experiences, engages regions of prefrontal cortex (PFC) and the amygdala. Because regions of PFC and the amygdala are known to influence the hypothalamic-pituitary-adrenal axis, here we test whether PFC and amygdala responses during emotion regulation predict the diurnal pattern of salivary cortisol secretion. We also test whether PFC and amygdala regions are engaged during emotion regulation in older (62- to 64-year-old) rather than younger individuals. We measured brain activity using functional magnetic resonance imaging as participants regulated (increased or decreased) their affective responses or attended to negative picture stimuli. We also collected saliva samples for 1 week at home for cortisol assay. Consistent with previous work in younger samples, increasing negative affect resulted in ventral lateral, dorsolateral, and dorsomedial regions of PFC and amygdala activation. In contrast to previous work, decreasing negative affect did not produce the predicted robust pattern of higher PFC and lower amygdala activation. Individuals demonstrating the predicted effect (decrease < attend in the amygdala), however, exhibited higher signal in ventromedial prefrontal cortex (VMPFC) for the same contrast. Furthermore, participants displaying higher VMPFC and lower amygdala signal when decreasing compared with the attention control condition evidenced steeper, more normative declines in cortisol over the course of the day. Individual differences yielded the predicted link between brain function while reducing negative affect in the laboratory and diurnal regulation of endocrine activity in the home environment.

Age Factors↗

PubMed2006

Altering expectancy dampens neural response to aversive taste in primary taste cortex.

The primary taste cortex consists of the insula and operculum. Previous work has indicated that neurons in the primary taste cortex respond solely to sensory input from taste receptors and lingual somatosensory receptors. Using functional magnetic resonance imaging, we show here that expectancy modulates these neural responses in humans. When subjects were led to believe that a highly aversive bitter taste would be less distasteful than it actually was, they reported it to be less aversive than when they had accurate information about the taste and, moreover, the primary taste cortex was less strongly activated. In addition, the activation of the right insula and operculum tracked online ratings of the aversiveness for each taste. Such expectancy-driven modulation of primary sensory cortex may affect perceptions of external events.

Adolescent↗

PubMed2006

Resting anterior cingulate activity and abnormal responses to errors in subjects with elevated depressive symptoms: a 128-channel EEG study.

Depression has been associated with dysfunctional executive functions and abnormal activity within the anterior cingulate cortex (ACC), a region critically involved in action regulation. Prior research invites the possibility that executive deficits in depression may arise from abnormal responses to negative feedback or errors, but the underlying neural substrates remain unknown. We hypothesized that abnormal reactions to error would be associated with dysfunctional rostral ACC activity, a region previously implicated in error detection and evaluation of the emotional significance of events. To test this hypothesis, subjects with low and high Beck Depression Inventory (BDI) scores performed an Eriksen Flanker task. To assess whether tonic activity within the rostral ACC predicted post-error adjustments, 128-channel resting EEG data were collected before the task and analyzed with low-resolution electromagnetic tomography (LORETA) using a region-of-interest approach. High BDI subjects were uniquely characterized by significantly lower accuracy after incorrect than correct trials. Mirroring the behavioral findings, high BDI subjects had significantly reduced pretask gamma (36.5-44 Hz) current density within the affective (rostral; BA24, BA25, BA32) but not cognitive (dorsal; BA24', BA32') ACC subdivision. For low, but not high, BDI subjects pretask gamma within the affective ACC subdivision predicted post-error adjustments even after controlling for activity within the cognitive ACC subdivision. Abnormal responses to errors may thus arise due to lower activity within regions subserving affective and/or motivational responses to salient cues. Because rostral ACC regions have been implicated in treatment response in depression, our findings provide initial insight into putative mechanisms fostering treatment response.

Adolescent↗

PubMed2006

Motion correction and the use of motion covariates in multiple-subject fMRI analysis.

The impact of using motion estimates as covariates of no interest was examined in general linear modeling (GLM) of both block design and rapid event-related functional magnetic resonance imaging (fMRI) data. The purpose of motion correction is to identify and eliminate artifacts caused by task-correlated motion while maximizing sensitivity to true activations. To optimize this process, a combination of motion correction approaches was applied to data from 33 subjects performing both a block-design and an event-related fMRI experiment, including analysis: (1) without motion correction; (2) with motion correction alone; (3) with motion-corrected data and motion covariates included in the GLM; and (4) with non-motion-corrected data and motion covariates included in the GLM. Inclusion of covariates was found to be generally useful for increasing the sensitivity of GLM results in the analysis of event-related data. When motion parameters were included in the GLM for event-related data, it made little difference if motion correction was actually applied to the data. For the block design, inclusion of motion covariates had a deleterious impact on GLM sensitivity when even moderate correlation existed between motion and the experimental design. Based on these results, we present a general strategy for block designs, event-related designs, and hybrid designs to identify and eliminate probable motion artifacts while maximizing sensitivity to true activations.

Adolescent↗

PubMed2006

Brain mechanisms of expectation associated with insula and amygdala response to aversive taste: implications for placebo.

The experience of aversion is shaped by multiple physiological and psychological factors including one's expectations. Recent work has shown that expectancy manipulation can alter perceptions of aversive events and concomitant brain activation. Accruing evidence indicates a primary role of altered expectancies in the placebo effect. Here, we probed the mechanism by which expectation attenuates sensory taste transmission by examining how brain areas activated by misleading information during an expectancy period modulate insula and amygdala activation to a highly aversive bitter taste. In a rapid event-related fMRI design, we showed that activations in the rostral anterior cingulate cortex (rACC), orbitofrontal cortex (OFC), and dorsolateral prefrontal cortex to a misleading cue that the taste would be mildly aversive predicted decreases in insula and amygdala activation to the highly aversive taste. OFC and rACC activation to the misleading cue were also associated with less aversive ratings of that taste. Additional analyses revealed consistent results demonstrating functional connectivity among the OFC, rACC, and insula. Altering expectancies of upcoming aversive events are shown here to depend on robust functional associations among brain regions implicated in prior work on the placebo effect.

Adolescent↗

PubMed2006

Anxiety selectively disrupts visuospatial working memory.

On the basis of a review of the extant literature describing emotion-cognition interactions, the authors propose 4 methodological desiderata for studying how task-irrelevant affect modulates cognition and present data from an experiment satisfying them. Consistent with accounts of the hemispheric asymmetries characterizing withdrawal-related negative affect and visuospatial working memory (WM) in prefrontal and parietal cortices, threat-induced anxiety selectively disrupted accuracy of spatial but not verbal WM performance. Furthermore, individual differences in physiological measures of anxiety statistically mediated the degree of disruption. A second experiment revealed that individuals characterized by high levels of behavioral inhibition exhibited more intense anxiety and relatively worse spatial WM performance in the absence of threat, solidifying the authors' inference that anxiety causally mediates disruption. These observations suggest a revision of extant models of how anxiety sculpts cognition and underscore the utility of the desiderata.

Anxiety↗

PubMed2006

Psychological well-being and ill-being: do they have distinct or mirrored biological correlates?

BACKGROUND: Increasingly, researchers attend to both positive and negative aspects of mental health. Such distinctions call for clarification of whether psychological well-being and ill-being comprise opposite ends of a bipolar continuum, or are best construed as separate, independent dimensions of mental health. Biology can help resolve this query--bipolarity predicts 'mirrored' biological correlates (i.e. well-being and ill-being correlate similarly with biomarkers, but show opposite directional signs), whereas independence predicts 'distinct' biological correlates (i.e. well-being and ill-being have different biological signatures). METHODS: Multiple aspects of psychological well-being (eudaimonic, hedonic) and ill-being (depression, anxiety, anger) were assessed in a sample of aging women (n = 135, mean age = 74) on whom diverse neuroendocrine (salivary cortisol, epinephrine, norepinephrine, DHEA-S) and cardiovascular factors (weight, waist-hip ratio, systolic and diastolic blood pressure, HDL cholesterol, total/HDL cholesterol, glycosylated hemoglobin) were also measured. RESULTS: Measures of psychological well-being and ill-being were significantly linked with numerous biomarkers, with some associations being more strongly evident for respondents aged 75+. Outcomes for seven biomarkers supported the distinct hypothesis, while findings for only two biomarkers supported the mirrored hypothesis. CONCLUSION: This research adds to the growing literature on how psychological well-being and mental maladjustment are instantiated in biology. Population-based inquiries and challenge studies constitute important future directions.

Aged↗

PubMed2005

Social relationships, sleep quality, and interleukin-6 in aging women.

This study examined the interplay of social engagement, sleep quality, and plasma levels of interleukin-6 (IL-6) in a sample of aging women (n = 74, aged 61-90, M age = 73.4). Social engagement was assessed by questionnaire, sleep was assessed by using the NightCap in-home sleep monitoring system and the Pittsburgh Sleep Quality Index, and blood samples were obtained for analysis of plasma levels of IL-6. Regarding subjective assessment, poorer sleep (higher scores on the Pittsburgh Sleep Quality Index) was associated with lower positive social relations scores. Multivariate regression analyses showed that lower levels of plasma IL-6 were predicted by greater sleep efficiency (P < 0.001), measured objectively and by more positive social relations (P < 0.05). A significant interaction showed that women with the highest IL-6 levels were those with both poor sleep efficiency and poor social relations (P < 0.05). However, those with low sleep efficiency but compensating good relationships as well as women with poor relationships but compensating high sleep efficiency had IL-6 levels comparable to those with the protective influences of both good social ties and good sleep.

Aged↗

PubMed2005

Functional neuroanatomy of aversion and its anticipation.

The capacity to anticipate aversive circumstances is central not only to successful adaptation but also to understanding the abnormalities that contribute to excessive worry and anxiety disorders. Forecasting and reacting to aversive events mobilize a host of affective and cognitive capacities and corresponding brain processes. Rapid event-related functional magnetic resonance imaging (fMRI) in 21 healthy volunteers assessed the overlap and divergence in the neural instantiation of anticipating and being exposed to aversive pictures. Brain areas jointly activated by the anticipation of and exposure to aversive pictures included the dorsal amygdala, anterior insula, dorsal anterior cingulate cortex (ACC), right dorsolateral prefrontal cortex (DLPFC), and right posterior orbitofrontal cortex (OFC). Anticipatory processes were uniquely associated with activations in rostral ACC, a more superior sector of the right DLPFC, and more medial sectors of the bilateral OFC. Activation of the right DLPFC in anticipation of aversion was associated with self-reports of increased negative affect, whereas OFC activation was associated with increases in both positive and negative affect. These results show that anticipation of aversion recruits key brain regions that respond to aversion, thereby potentially enhancing adaptive responses to aversive events.

Adult↗

PubMed2005

Neural circuitry underlying the interaction between emotion and asthma symptom exacerbation.

Asthma, like many inflammatory disorders, is affected by psychological stress, suggesting that reciprocal modulation may occur between peripheral factors regulating inflammation and central neural circuitry underlying emotion and stress reactivity. Despite suggestions that emotional factors may modulate processes of inflammation in asthma and, conversely, that peripheral inflammatory signals influence the brain, the neural circuitry involved remains elusive. Here we show, using functional magnetic resonance imaging, that activity in the anterior cingulate cortex and insula to asthma-relevant emotional, compared with valence-neutral stimuli, is associated with markers of inflammation and airway obstruction in asthmatic subjects exposed to antigen. This activation accounts for > or =40% of the variance in the peripheral markers and suggests a neural basis for emotion-induced modulation of airway disease in asthma. The anterior cingulate cortex and insula have been implicated in the affective evaluation of sensory stimulation, regulation of homeostatic responses, and visceral perception. In individuals with asthma and other stress-related conditions, these brain regions may be hyperresponsive to disease-specific emotional and afferent physiological signals, which may contribute to the dysregulation of peripheral processes, such as inflammation.

Airway Obstruction↗

PubMed2005

Brain regions associated with the expression and contextual regulation of anxiety in primates.

BACKGROUND: A key to successful adaptation is the ability to regulate emotional responses in relation to changing environmental demands or contexts. METHODS: High-resolution PET 18fluoro-deoxyglucose (FDG) scanning in rhesus monkeys was performed during two contexts (alone, and human intruder with no eye contact) during which the duration of anxiety related freezing behavior was assessed. Correlations between individual differences in freezing duration and brain activity were performed for each of the two conditions, as well as for the contextual regulation between the two conditions. RESULTS: In both conditions, activity in the basal forebrain, including the bed nucleus of the stria terminalis and the nucleus accumbens were correlated with individual differences in freezing duration. In contrast, individual differences in the ability to regulate freezing behavior between contexts were correlated with activity in the dorsal anterior cingulate cortex, the thalamus and the dorsal raphe nucleus. CONCLUSIONS: These findings demonstrate differences in the neural circuitry mediating the expression compared to the contextual regulation of freezing behavior. These findings are relevant since altered regulatory processes may underlie anxiety disorders.

Amygdala↗

PubMed2005

Stability of amygdala BOLD response to fearful faces over multiple scan sessions.

We used fMRI to examine amygdala activation in response to fearful facial expressions, measured over multiple scanning sessions. 15 human subjects underwent three scanning sessions, at 0, 2 and 8 weeks. During each session, functional brain images centered about the amygdala were acquired continuously while participants were shown alternating blocks of fearful, neutral and happy facial expressions. Intraclass correlation coefficients calculated across the sessions indicated stability of response in left amygdala to fearful faces (as a change from baseline), but considerably less left amygdala stability in responses to neutral expressions and for fear versus neutral contrasts. The results demonstrate that the measurement of fMRI BOLD responses in amygdala to fearful facial expressions might be usefully employed as an index of amygdala reactivity over extended periods. While signal change to fearful facial expressions appears robust, the experimental design employed here has yielded variable responsivity within baseline or comparison conditions. Future studies might manipulate the experimental design to either amplify or attenuate this variability, according to the goals of the research.

Adult↗

PubMed2005

Cortical thickness analysis in autism with heat kernel smoothing.

We present a novel data smoothing and analysis framework for cortical thickness data defined on the brain cortical manifold. Gaussian kernel smoothing, which weights neighboring observations according to their 3D Euclidean distance, has been widely used in 3D brain images to increase the signal-to-noise ratio. When the observations lie on a convoluted brain surface, however, it is more natural to assign the weights based on the geodesic distance along the surface. We therefore develop a framework for geodesic distance-based kernel smoothing and statistical analysis on the cortical manifolds. As an illustration, we apply our methods in detecting the regions of abnormal cortical thickness in 16 high functioning autistic children via random field based multiple comparison correction that utilizes the new smoothing technique.

Adolescent↗

PubMed2005

Calling for help is independently modulated by brain systems underlying goal-directed behavior and threat perception.

In primates, during times of need, calling for help is a universal experience. Calling for help recruits social support and promotes survival. However, calling for help also can attract predators, and it is adaptive to inhibit calls for help when a potential threat is perceived. Based on this, we hypothesized that individual differences in calling for help would be related to the activity of brain systems that mediate goal-directed behavior and the detection of threat. By using high-resolution positron emission tomography in rhesus monkeys undergoing social separation, we demonstrate that increased [18F]-fluoro-2-deoxy-D-glucose uptake in the right dorsolateral prefrontal cortex and decreased uptake in the amygdala independently predict individual differences in calling for help. When taken together, these two regions account for 76% of the variance in calling for help. This result suggests that the drive for affiliation and the perception of threat determine the intensity of an individual's behavior during separation. These findings in monkeys are relevant to humans and provide a conceptual neural framework to understand individual differences in how primates behave when in need of social support.

Animal Communication↗

PubMed2005

Gaze fixation and the neural circuitry of face processing in autism.

Diminished gaze fixation is one of the core features of autism and has been proposed to be associated with abnormalities in the neural circuitry of affect. We tested this hypothesis in two separate studies using eye tracking while measuring functional brain activity during facial discrimination tasks in individuals with autism and in typically developing individuals. Activation in the fusiform gyrus and amygdala was strongly and positively correlated with the time spent fixating the eyes in the autistic group in both studies, suggesting that diminished gaze fixation may account for the fusiform hypoactivation to faces commonly reported in autism. In addition, variation in eye fixation within autistic individuals was strongly and positively associated with amygdala activation across both studies, suggesting a heightened emotional response associated with gaze fixation in autism.

Adolescent↗

PubMed2005

Cardiac reactivity is associated with changes in negative emotion in 24-month-olds.

Despite the call for multilevel observation of negative affect, including multiple physiological systems, too little empirical research has been conducted in infants and young children, and physiology-affect associations are not consistently reported. We examined changes in heart rate, respiratory sinus arrhythmia, and preejection period in 24-month-olds across four increasingly challenging, emotion-eliciting tasks. We predicted that changes in cardiac reactivity would be systematically related to changes in negative affect. Results largely support the predictions with one important exception. With increasing distress across the tasks, HR increased and RSA decreased. However, no significant changes in PEP were observed. HR was associated with negative affect during all tasks, and changes in HR were related to changes in negative affect. PEP and negative affect were associated, but only marginally so. Within-subject analyses confirmed the predicted associations. Finally, the associations between physiology and negative affect were different for boys and girls. We discuss these results in the context of implications for future research on cardiac-affect associations in young children.

Affect↗