An approach for identifying brainstem dopaminergic pathways using resting state functional MRI.

Here, we present an approach for identifying brainstem dopaminergic pathways using resting state functional MRI. In a group of healthy individuals, we searched for significant functional connectivity between dopamine-rich midbrain areas (substantia nigra; ventral tegmental area) and a striatal region (caudate) that was modulated by both a pharmacological challenge (the administration of the dopaminergic agonist bromocriptine) and a dopamine-sensitive cognitive trait (an individual's working memory capacity). A significant inverted-U shaped connectivity pattern was found in a subset of midbrain-striatal connections, demonstrating that resting state fMRI data is sufficiently powerful to identify brainstem neuromodulatory brain networks

Individual differences in neural responses to social rejection: The joint effect of self-esteem and attentional control

Individuals with low self-esteem have been found to react more negatively to signs of interpersonal rejection than those with high self-esteem. However, previous research has found that individual differences in attentional control can attenuate negative reactions to social rejection among vulnerable, low self-esteem individuals. The current fMRI study sought to elucidate the neurobiological substrate of this buffering effect. We hypothesized and found that while looking at scenes of social rejection (vs negative scenes) low self-esteem high attentional control individuals engaged the rostral anterior cingulate cortex (rACC), an area of the brain associated with emotional control, more than their low self-esteem low attentional control peers. Furthermore, we found that low self-esteem high attentional control individuals evaluated social rejection as less arousing and less rejecting in a separate behavioral task. Importantly, activation in the rACC fully mediated the relationship between the interaction of self-esteem and attentional control and emotional evaluations, suggesting that the rACC activation underlies the buffering effects of attentional control. Results are discussed in terms of individual differences in emotional vulnerability and protection and by highlighting the role of rACC in emotion regulation

Plasticity in the Auditory Pathway

The auditory pathway has a remarkable ability to change its response based on sound experiences. Plasticity also occurs as an adaptive response following injury to the auditory pathway, such as in hearing loss. My doctoral work aims to improve our understanding of plasticity in the auditory system during normal development, and in cases of trauma or disease.First, I studied the tonotopic map of the primary auditory cortex and inferior colliculus in juvenile rats that underwent passive exposure to a single frequency pure tone pip during the auditory critical period. Previously it has been shown that such acoustic exposure leads to an enlarged representation of the exposure frequency in primary auditory cortex. However, whether this change originated in cortex or also present in an upstream auditory nucleus remained unclear. I addressed this question by comparing the tonotopic representations of inferior colliculus and primary auditory cortex and showed that enlarged frequency representation is observed only in the primary auditory cortex but not in the inferior colliculus. Second, I investigated adult plasticity following hearing loss. It has been hypothesized that a reorganization of auditory cortex underlies perceptual problems that develop after hearing loss. In particular, perception of a phantom sound, or tinnitus, has been associated with abnormal tonotopic representation in the auditory cortex. Using a mouse behavioral model of tinnitus, I have shown that tonotopic map reorganization is likely a consequence of hearing loss, and is not sufficient to induce tinnitus by itself. Further, I have provided evidence that changes in the Glutamate Decarboxylase 65 expression level may be involved in the etiology of tinnitus

Neural Activity to a Partner's Facial Expression Predicts Self-Regulation After Conflict

Introduction: Failure to self-regulate after an interpersonal conflict can result in persistent negative mood and maladaptive behaviors. Research indicates that lateral prefrontal cortex (LPFC) activity is related to the regulation of emotional experience in response to lab-based affective challenges, such as viewing emotional pictures. This suggests that compromised LPFC function may be a risk-factor for mood and behavior problems after an interpersonal stressor. However, it remains unclear whether LPFC activity to a lab-based affective challenge predicts self-regulation in real-life. Method: We investigated whether LPFC activity to a lab-based affective challenge (negative facial expressions of a partner) predicts self-regulation after a real-life affective challenge (interpersonal conflict). During an fMRI scan, healthy, adult participants in committed, dating relationships (N = 27) viewed positive, negative, and neutral facial expressions of their partners. In an online daily-diary, participants reported conflict occurrence, level of negative mood, rumination, and substance-use. Results: LPFC activity in response to the lab-based affective challenge predicted self- regulation after an interpersonal conflict in daily life. When there was no interpersonal conflict, LPFC activity was not related to the change in mood or behavior the next day. However, when an interpersonal conflict did occur, ventral LPFC (VLPFC) activity predicted the change in mood and behavior the next day, such that lower VLPFC activity was related to higher levels of negative mood, rumination, and substance-use. Conclusions: Low LPFC function may be a vulnerability and high LPFC function may be a protective factor for the development of mood and behavior problems after an interpersonal stressor.Psycholog

The Influence of Personality on Neural Mechanisms of Observational Fear and Reward Learning

Fear and reward learning can occur through direct experience or observation. Both channels can enhance survival or create maladaptive behavior. We used fMRI to isolate neural mechanisms of observational fear and reward learning and investigate whether neural response varied according to individual differences in neuroticism and extraversion. Participants learned object-emotion associations by observing a woman respond with fearful (or neutral) and happy (or neutral) facial expressions to novel objects. The amygdala-hippocampal complex was active when learning the object-fear association, and the hippocampus was active when learning the object-happy association. After learning, objects were presented alone; amygdala activity was greater for the fear (vs. neutral) and happy (vs. neutral) associated object. Importantly, greater amygdala-hippocampal activity during fear (vs. neutral) learning predicted better recognition of learned objects on a subsequent memory test. Furthermore, personality modulated neural mechanisms of learning. Neuroticism positively correlated with neural activity in the amygdala and hippocampus during fear (vs. neutral) learning. Low extraversion/high introversion was related to faster behavioral predictions of the fearful and neutral expressions during fear learning. In addition, low extraversion/high introversion was related to greater amygdala activity during happy (vs. neutral) learning, happy (vs. neutral) object recognition, and faster reaction times for predicting happy and neutral expressions during reward learning. These findings suggest that neuroticism is associated with an increased sensitivity in the neural mechanism for fear learning which leads to enhanced encoding of fear associations, and that low extraversion/high introversion is related to enhanced conditionability for both fear and reward learning.Psycholog

Tinnitus Correlates with Downregulation of Cortical Glutamate Decarboxylase 65 Expression But Not Auditory Cortical Map Reorganization

Hearing loss is the biggest risk factor for tinnitus, and hearing-loss-related pathological changes in the auditory pathway have been hypothesized as the mechanism underlying tinnitus. However, due to the comorbidity of tinnitus and hearing loss, it has been difficult to differentiate between neural correlates of tinnitus and consequences of hearing loss. In this study, we dissociated tinnitus and hearing loss in FVB mice, which exhibit robust resistance to tinnitus following monaural noise-induced hearing loss. Furthermore, knock-down of glutamate decarboxylase 65 (GAD65) expression in auditory cortex (AI) by RNA interference gave rise to tinnitus in normal-hearing FVB mice. We found that tinnitus was significantly correlated with downregulation of GAD65 in the AI. By contrast, cortical map distortions, which have been hypothesized as a mechanism underlying tinnitus, were correlated with hearing loss but not tinnitus. Our findings suggest new strategies for the rehabilitation of tinnitus and other phantom sensation, such as phantom pain.SIGNIFICANCE STATEMENT Hearing loss is the biggest risk factor for tinnitus in humans. Most animal models of tinnitus also exhibit comorbid hearing loss, making it difficult to dissociate the mechanisms underlying tinnitus from mere consequences of hearing loss. Here we show that, although both C57BL/6 and FVB mice exhibited similar noise-induced hearing threshold increase, only C57BL/6, but not FVB, mice developed tinnitus following noise exposure. Although both strains showed frequency map reorganization following noise-induced hearing loss, only C57BL/6 mice had reduced glutamate decarboxylase 65 (GAD65) expression in the auditory cortex (AI). Knocking down GAD65 expression in the AI resulted in tinnitus in normal-hearing FVB mice. Our results suggest that reduced inhibitory neuronal function, but not sensory map reorganization, underlies noise-induced tinnitus.American Tinnitus Association; National Institute on Deafness and Other Communicative DisordersUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Deafness & Other Communication Disorders (NIDCD) [DC009259]6 month embargo; published online: 11 December 2019This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Whole-brain correlation maps with midbrain seeds across all subjects and across both placebo and bromocriptine sessions.

<p>Maps are thresholded at p < .05 FDR corrected with a minimum cluster size of 20 voxels. The color bar indicates t values.</p

Division of the caudate into a head/body and tail regions is displayed at the top of the figure.

<p>Venn diagrams illustrate the degree of overlap between caudate voxels (middle figure – head/body; bottom figure – tail) identified as correlated with the midbrain (p < .05, FDR and small-volume corrected) collapsed across span and drug condition (left circle) and caudate voxels identified as having an inverted-U shaped relationship with the midbrain (p < 0.05, uncorrected; right circle). A significantly greater percentage of overlapping voxels are present in the tail than the head/body of the caudate.</p

Venn diagrams illustrating degree of overlap.

<p><b>Left.</b> Venn diagram illustrates the degree of overlap between caudate voxels identified as correlated with the midbrain (p < 0.05, FDR and small-volume corrected) collapsed across span and drug condition (left circle) and caudate voxels identified as having an inverted-U shaped relationship with the midbrain (p < 0.05, uncorrected; right circle). Only 122/(122+833) voxels (13%) exhibiting significant midbrain-caudate connectivity also exhibit an inverted –U shaped response dependent on span and drug. <b>Right.</b> Venn diagram illustrates the degree of overlap between caudate voxels identified as having greater connectivity with the midbrain in higher span subjects in the placebo sessions (left circle) and caudate voxels identified as having an inverted-U shaped relationship with the midbrain (p < 0.05, uncorrected). Only 61/(61+61) voxels (50%) exhibiting a significant increase in midbrain-caudate connectivity based on span also exhibit an inverted-U shaped response dependent on span and drug. The number of voxels is presented within the circles.</p

Representative bilateral midbrain ROI (red) on a co-registered T1 image in one participant.

<p>Representative bilateral midbrain ROI (red) on a co-registered T1 image in one participant.</p