Ethnic Differences in Physiological Responses to Fear Conditioned Stimuli

The idea that emotional expression varies with ethnicity is based largely on questionnaires and behavioral observations rather than physiological measures. We therefore compared the skin conductance responses (SCR) of Hispanic (Puerto Rican) and White non-Hispanic subjects in a fear conditioning and fear extinction task. Subjects were recruited from two sites: San Juan, Puerto Rico (PR), and Boston, Massachusetts (MA), using identical methods. A total of 78 healthy subjects (39 from PR, 39 from MA) were divided by sex and matched for age and educational level. Females from the two sites did not differ in their SCRs during any experimental phase of fear conditioning (habituation, conditioning, or extinction). In contrast, PR males responded significantly to the conditioned stimulus than MA males or PR females. Subtracting ethnic differences observed during the habituation phase (prior to conditioning) eliminated differences from subsequent phases, suggesting that PR males are elevated in their response to novelty rather than fear learning. Our findings suggest that, in addition to sex differences, there are ethnic differences in physiological responses to novel stimuli at least in males, which could be relevant for the assessment and treatment of anxiety disorders

Ethnic Differences in Physiological Responses to Fear Conditioned Stimuli

The idea that emotional expression varies with ethnicity is based largely on questionnaires and behavioral observations rather than physiological measures. We therefore compared the skin conductance responses (SCR) of Hispanic (Puerto Rican) and White non-Hispanic subjects in a fear conditioning and fear extinction task. Subjects were recruited from two sites: San Juan, Puerto Rico (PR), and Boston, Massachusetts (MA), using identical methods. A total of 78 healthy subjects (39 from PR, 39 from MA) were divided by sex and matched for age and educational level. Females from the two sites did not differ in their SCRs during any experimental phase of fear conditioning (habituation, conditioning, or extinction). In contrast, PR males responded significantly to the conditioned stimulus than MA males or PR females. Subtracting ethnic differences observed during the habituation phase (prior to conditioning) eliminated differences from subsequent phases, suggesting that PR males are elevated in their response to novelty rather than fear learning. Our findings suggest that, in addition to sex differences, there are ethnic differences in physiological responses to novel stimuli at least in males, which could be relevant for the assessment and treatment of anxiety disorders

Positive allosteric modulation as a potential therapeutic strategy in anti-NMDA receptor encephalitis

N-methyl-d-aspartate receptors (NMDARs) are ionotropic glutamate receptors important for synaptic plasticity, memory, and neuropsychiatric health. NMDAR hypofunction contributes to multiple disorders, including anti-NMDAR encephalitis (NMDARE), an autoimmune disease of the CNS associated with GluN1 antibody-mediated NMDAR internalization. Here we characterize the functional/pharmacological consequences of exposure to CSF from female human NMDARE patients on NMDAR function, and we characterize the effects of intervention with recently described positive allosteric modulators (PAMs) of NMDARs. Incubation (48 h) of rat hippocampal neurons of both sexes in confirmed NMDARE patient CSF, but not control CSF, attenuated NMDA-induced current. Residual NMDAR function was characterized by lack of change in channel open probability, indiscriminate loss of synaptic and extrasynaptic NMDARs, and indiscriminate loss of GluN2B-containing and GluN2B-lacking NMDARs. NMDARs tagged with N-terminal pHluorin fluorescence demonstrated loss of surface receptors. Thus, function of residual NMDARs following CSF exposure was indistinguishable from baseline, and deficits appear wholly accounted for by receptor loss. Coapplication of CSF and PAMs of NMDARs (SGE-301 or SGE-550, oxysterol-mimetic) for 24 h restored NMDAR function following 24 h incubation in patient CSF. Curiously, restoration of NMDAR function was observed despite washout of PAMs before electrophysiological recordings. Subsequent experiments suggested that residual allosteric potentiation of NMDAR function explained the persistent rescue. Further studies of the pathogenesis of NMDARE and intervention with PAMs may inform new treatments for NMDARE and other disorders associated with NMDAR hypofunction.SIGNIFICANCE STATEMENTAnti-N-methyl-d-aspartate receptor encephalitis (NMDARE) is increasingly recognized as an important cause of sudden-onset psychosis and other neuropsychiatric symptoms. Current treatment leaves unmet medical need. Here we demonstrate cellular evidence that newly identified positive allosteric modulators of NMDAR function may be a viable therapeutic strategy.</jats:p

Correlations between psychological tests and physiological responses during fear conditioning and renewal

Background: Anxiety disorders are characterized by specific emotions, thoughts and physiological responses. Little is known, however, about the relationship between psychological/personality indices of anxiety responses to fear stimuli. Methods: We studied this relationship in healthy subjects by comparing scores on psychological and personality questionnaires with results of an experimental fear conditioning paradigm using a visual conditioned stimulus (CS). We measured skin conductance response (SCR) during habituation, conditioning, and extinction; subsequently testing for recall and renewal of fear 24 hours later. Results: We found that multiple regression models explained 45% of the variance during conditioning to the CS+, and 24% of the variance during renewal of fear to the CS+. Factors that explained conditioning included lower levels of conscientiousness, increased baseline reactivity (SCL), and response to the shock (UCR). Low levels of extraversion correlated with greater renewal. No model could be found to explain extinction learning or extinction recall to the CS+. Conclusions: The lack of correlation of fear extinction with personality and neuropsychological indices suggests that extinction may be less determined by trait variables and cognitive state, and may depend more on the subject’s current emotional state. The negative correlation between fear renewal and extraversion suggests that this personality characteristic may protect against post-treatment relapse of symptoms of anxiety disorders

Building a diverse workforce and thinkforce to reduce health disparities

The Research Centers in Minority Institutions (RCMI) Program was congressionally man-dated in 1985 to build research capacity at institutions that currently and historically recruit, train, and award doctorate degrees in the health professions and health-related sciences, primarily to individuals from underrepresented and minority populations. RCMI grantees share similar infrastructure needs and institutional goals. Of particular importance is the professional development of multidisciplinary teams of academic and community scholars (the “workforce”) and the harnessing of the heterogeneity of thought (the “thinkforce”) to reduce health disparities. The purpose of this report is to summarize the presentations and discussion at the RCMI Investigator Development Core (IDC) Workshop, held in conjunction with the RCMI Program National Conference in Bethesda, Maryland, in December 2019. The RCMI IDC Directors provided information about their professional development activities and Pilot Projects Programs and discussed barriers identified by new and early-stage investigators that limit effective career development, as well as potential solutions to overcome such obstacles. This report also proposes potential alignments of professional development activities, targeted goals and common metrics to track productivity and success

Sleep-amount differentially affects fear-processing neural circuitry in pediatric anxiety: A preliminary fMRI investigation

Insufficient sleep, as well as the incidence of anxiety disorders, both peak during adolescence. While both conditions present perturbations in fear-processing-related neurocircuitry, it is unknown whether these neurofunctional alterations directly link anxiety and compromised sleep in adolescents. Fourteen anxious adolescents (AAs) and 19 healthy adolescents (HAs) were compared on a measure of sleep amount and neural responses to negatively valenced faces during fMRI. Group differences in neural response to negative faces emerged in the dorsal anterior cingulate cortex (dACC) and the hippocampus. In both regions, correlation of sleep amount with BOLD activation was positive in AAs, but negative in HAs. Follow-up psychophysiological interaction (PPI) analyses indicated positive connectivity between dACC and dorsomedial prefrontal cortex, and between hippocampus and insula. This connectivity was correlated negatively with sleep amount in AAs, but positively in HAs. In conclusion, the presence of clinical anxiety modulated the effects of sleep-amount on neural reactivity to negative faces differently among this group of adolescents, which may contribute to different clinical significance and outcomes of sleep disturbances in healthy adolescents and patients with anxiety disorders

Less fear, more diversity.

Fear is an instinctual response that's adaptive and critical for survival when it is short-lived but can lead to anxiety disorders when chronic. Studying how the brain controls our fears helps us understand the mechanisms required to recover from traumatic experiences and what goes wrong when we don't. Research in rodents has identified neural circuits and molecular mechanisms regulating fear expression. Rodent work has been amenable to translation to humans and has led to improvements in clinical therapies for anxiety disorders. The societal benefit of this type of research is magnified when performed in minority-serving institutions, offering high-caliber training opportunities to increase ethnic diversity in science

Neuronal signalling of fear memory

The learning and remembering of fearful events depends on the integrity of the amygdala, but how are fear memories represented in the activity of amygdala neurons? Here, we review recent electrophysiological studies indicating that neurons in the lateral amygdala encode aversive memories during the acquisition and extinction of Pavlovian fear conditioning. Studies that combine unit recording with brain lesions and pharmacological inactivation provide evidence that the lateral amygdala is a crucial locus of fear memory. Extinction of fear memory reduces associative plasticity in the lateral amygdala and involves the hippocampus and prefrontal cortex. Understanding the signalling of aversive memory by amygdala neurons opens new avenues for research into the neural systems that support fear behaviour.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/61954/1/marenNRN04.pd