Papers by Jennifer Blackford
Background: Choices requiring delay of gratification made during adolescence can have significant... more Background: Choices requiring delay of gratification made during adolescence can have significant impact on life trajectory. Willingness to delay gratification can be measured using delay discounting tasks that require a choice between a smaller immediate reward and a larger delayed reward. Individual differences in the subjective value of delayed rewards are associated with risk for development of psychopathology including substance abuse. The neurobiological underpinnings related to these individual differences early in life are not fully understood. Using functional magnetic resonance imaging (fMRI), we tested the hypothesis that individual differences in delay discounting behavior in healthy youth are related to differences in responsiveness to potential reward. Method: Nineteen 10-14 year-olds performed a monetary incentive delay task to assess neural sensitivity to potential reward and a questionnaire to measure discounting of future monetary rewards. Results: Left ventromedial caudate activation during anticipation of potential reward was negatively correlated with delay discounting behavior. There were no regions where brain responses during notification of reward outcome were associated with discounting behavior. Conclusions: Brain activation during anticipation of potential reward may serve as a marker for individual differences in ability or willingness to delay gratification in healthy youth.
Vanderbilt Law Review, May 1, 2006
Sex differences in psychophysical and neurophysiological responses to pain in older adults: a cross-sectional study
Biology of sex differences, 2015
Neuroimaging studies in younger adults have demonstrated sex differences in brain processing of p... more Neuroimaging studies in younger adults have demonstrated sex differences in brain processing of painful experimental stimuli. Such differences may contribute to findings that women suffer disproportionately from pain. It is not known whether sex-related differences in pain processing extend to older adults. This cross-sectional study investigated sex differences in pain reports and brain response to pain in 12 cognitively healthy older female adults and 12 cognitively healthy age-matched older male adults (age range 65-81, median = 67). Participants underwent psychophysical assessments of thermal pain responses, functional MRI, and psychosocial assessment. When compared to older males, older females reported experiencing mild and moderate pain at lower stimulus intensities (i.e., exhibited greater pain sensitivity; Cohen's d = 0.92 and 0.99, respectively, p < 0.01) yet did not report greater pain-associated unpleasantness. Imaging results indicated that, despite the lower sti...
Disgust proneness and associated neural substrates in obesity
Social Cognitive and Affective Neuroscience, 2015
Defects in experiencing disgust may contribute to obesity by allowing for the overconsumption of ... more Defects in experiencing disgust may contribute to obesity by allowing for the overconsumption of food. However, the relationship of disgust proneness and its associated neural locus has yet to be explored in the context of obesity. Thirty-three participants (17 obese; 16 lean) completed the Disgust Propensity and Sensitivity Scale-Revised (DPSS-R) and an fMRI paradigm where images from four categories (food, contaminates, contaminated food, or fixation) were randomly presented. Independent two-sample t-tests revealed significantly lower levels of Disgust Sensitivity for the obese group (mean score=14.7) compared to the lean group (mean score=17.6), p=0.026. The obese group had less activation in the right insula than the lean group when viewing contaminated food images. Multiple regression with interaction analysis revealed one left insula region where the association of Disgust Sensitivity scores with activation differed by group when viewing contaminated food images. These interaction effects were driven by the negative correlation of Disgust Sensitivity scores with beta values extracted from the left insula in the obese group (r=-0.59) compared to a positive correlation in the lean group (r=0.65). Given these BMI-dependent differences in Disgust Sensitivity and neural responsiveness to disgusting food images it is likely that altered Disgust Sensitivity may contribute to obesity.
Journal of the American Academy of Child & Adolescent Psychiatry, 2012
Objective-Behavioral inhibition (BI) has been associated with increased risk for developing socia... more Objective-Behavioral inhibition (BI) has been associated with increased risk for developing social anxiety disorder (SAD); however, the degree of risk associated with BI has yet to be systematically examined and quantified. The goal of the present study was to quantify the association between childhood BI and risk for developing SAD.
Health matrix (Cleveland, Ohio : 1991), 2007
MDMA use is associated with lower gray matter volume in widespread cortical regions
Drug and Alcohol Dependence, 2014
Journal of the American Academy of Child & Adolescent Psychiatry, 2013
Archives of general psychiatry, 2012
MDMA (3,4-methylenedioxymethamphetamine, also popularly known as "ecstasy") is a popula... more MDMA (3,4-methylenedioxymethamphetamine, also popularly known as "ecstasy") is a popular recreational drug that produces loss of serotonin axons in animal models. Whether MDMA produces chronic reductions in serotonin signaling in humans remains controversial. To determine whether MDMA use is associated with chronic reductions in serotonin signaling in the cerebral cortex of women as reflected by increased serotonin(2A) receptor levels. Cross-sectional case-control study comparing serotonin(2A) receptor levels in abstinent female MDMA polydrug users with those in women who did not use MDMA (within-group design assessing the association of lifetime MDMA use and serotonin(2A) receptors). Case participants were abstinent from MDMA use for at least 90 days as verified by analysis of hair samples. The serotonin(2A) receptor levels in the cerebral cortex were determined using serotonin(2A)-specific positron emission tomography with radioligand fluorine 18-labeled setoperone as th...
Journal of Neurodevelopmental Disorders, 2014
Background: Individuals with Down Syndrome (DS) are reported to experience early onset of brain a... more Background: Individuals with Down Syndrome (DS) are reported to experience early onset of brain aging. However, it is not well understood how pre-existing neurodevelopmental effects versus neurodegenerative processes might be contributing to the observed pattern of brain atrophy in younger adults with DS. The aims of the current study were to: (1) to confirm previous findings of age-related changes in DS compared to adults with typical development (TD), (2) to test for an effect of these age-related changes in a second neurodevelopmental disorder, Williams syndrome (WS), and (3) to identify a pattern of regional age-related effects that are unique to DS.
Developmental cognitive neuroscience, 2014
Choices requiring delay of gratification made during adolescence can have significant impact on l... more Choices requiring delay of gratification made during adolescence can have significant impact on life trajectory. Willingness to delay gratification can be measured using delay discounting tasks that require a choice between a smaller immediate reward and a larger delayed reward. Individual differences in the subjective value of delayed rewards are associated with risk for development of psychopathology including substance abuse. The neurobiological underpinnings related to these individual differences early in life are not fully understood. Using functional magnetic resonance imaging (fMRI), we tested the hypothesis that individual differences in delay discounting behavior in healthy youth are related to differences in responsiveness to potential reward. Nineteen 10-14 year-olds performed a monetary incentive delay task to assess neural sensitivity to potential reward and a questionnaire to measure discounting of future monetary rewards. Left ventromedial caudate activation during a...
Patient Complaints and Malpractice Risk in a Regional Healthcare Center
Southern Medical Journal, 2007
To study the association between physicians&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;a... more To study the association between physicians&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; complaint records and their risk management experiences in a regional healthcare center. Patient complaints about physicians in a large border state medical center&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s hospital and outpatient clinics were recorded and coded. The study period was from January 2001 through December 2003. These records were linked to the counterpart physicians&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; data covered by the institutions&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; risk management plan through June 2004. All physicians at the institution who had contact with patients during the study period were identified as surgeons or non-surgeons. Complaints for these physicians were recorded by the institution&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Office of Patient Relations (OPR) and independently coded using a standardized protocol to characterize the nature of the problem and to uniquely identify the person complained about. The complaint records were then linked to the risk management files (RMFs) for the defined physician cohort. In addition, these data were supplemented with clinical service values (RVUs) which were available for 338 members (76%) of the 445 member cohort. Both patient complaints and risk management events were higher for surgeons than for non-surgeons. This was true for the number of RMFs, those involving expenditures, and for lawsuits. Logistic regression was used to assess the effects of complaint counts, practice type and volume of clinical activity. All were statistically significant in predicting the number of RMF openings, RMF openings with expenditures and lawsuits. Predictive concordance was 75% or greater for each of the three risk management outcomes. Expressions of patient dissatisfaction and practice type are significantly related to risk management experiences in a regional medical center. Associations of risk management experiences with volume of clinical activity (RVUs) for surgeons in the regional medical center environment were not as strong as those found in a similar study reported from an academic medical center.
Social Cognitive and Affective Neuroscience, 2013
Habituation is a basic form of learning that reflects the adaptive reduction in responses to a st... more Habituation is a basic form of learning that reflects the adaptive reduction in responses to a stimulus that is neither threatening nor rewarding. Extremely shy, or inhibited individuals, are typically slow to acclimate to new people, a behavioral pattern that may reflect slower habituation to novelty. To test this hypothesis, we used functional magnetic resonance imaging to examine habituation to neutral faces in 39 young adults with either an extreme inhibited or extreme uninhibited temperament. Our investigation focused on two key brain regions involved in response to noveltythe amygdala and the hippocampus. Habituation to neutral faces in the amygdala and hippocampus differed significantly by temperament group. Individuals with an uninhibited temperament demonstrated habituation in both the amygdala and hippocampus, as expected. In contrast, in individuals with an inhibited temperament, the amygdala and hippocampus failed to habituate across repeated presentations of faces. The failure of the amygdala and hippocampus to habituate to faces represents a novel neural substrate mediating the behavioral differences seen in individuals with an inhibited temperament. We propose that this failure to habituate reflects a social learning deficit in individuals with an inhibited temperament and provides a possible mechanism for increased risk for social anxiety.
Social Cognitive and Affective Neuroscience, 2011
Previous theories have proposed that the amygdala is hyper-responsive to novel stimuli in persons... more Previous theories have proposed that the amygdala is hyper-responsive to novel stimuli in persons with an inhibited temperamenta biologically based predisposition to respond to novelty with wariness or avoidance behavior. In the current study, we used functional magnetic resonance imaging (fMRI) to assess amygdala blood oxygenation level-dependent (BOLD) response when viewing novel or recently familiarized faces in persons with an extreme inhibited or uninhibited temperament. In persons with an inhibited temperament, the amygdala showed increased BOLD response when viewing both novel and recently familiarized faces. In contrast, in persons with an uninhibited temperament, BOLD response in the amygdala was increased only when viewing novel faces. These findings suggest that inhibited temperament is characterized not by a simple exaggerated response to novel faces, but rather by a sustained increase in amygdala response to faces even after the faces have become familiarized. In individuals with an inhibited temperament, this sustained response may be related to the wariness of social situations that persists beyond initial exposure.
Quality and Safety in Health Care, 2006
Background: Patient complaints are associated with increased malpractice risk but it is unclear i... more Background: Patient complaints are associated with increased malpractice risk but it is unclear if complaints might be associated with medical complications. The purpose of this study was to determine whether an association exists between patient complaints and surgical complications. Methods: A retrospective analysis of 16 713 surgical admissions was conducted over a 54 month period at a single academic medical center. Surgical complications were identified using administrative data. The primary outcome measure was unsolicited patient complaints. Results: During the study period 0.9% of surgical admissions were associated with a patient complaint. 19% of admissions associated with a patient complaint included a postoperative complication compared with 12.5% of admissions without a patient complaint (p = 0.01). After adjusting for surgical specialty, comorbid illnesses and length of stay, admissions with complications had an odds ratio of 1.74 (95% confidence interval 1.01 to 2.98) of being associated with a complaint compared with admissions without complications. Conclusions: Admissions with surgical complications are more likely to be associated with a complaint than surgical admissions without complications. Further research is necessary to determine if patient complaints might serve as markers for poor clinical outcomes.
Processing speed impairment in schizophrenia is mediated by white matter integrity
Psychological Medicine, 2014
Processing speed predicts functional outcome and is a potential endophenotype for schizophrenia. ... more Processing speed predicts functional outcome and is a potential endophenotype for schizophrenia. Establishing the neural basis of processing speed impairment may inform the treatment and etiology of schizophrenia. Neuroimaging investigations in healthy subjects have linked processing speed to brain anatomical connectivity. However, the relationship between processing speed impairment and white matter (WM) integrity in schizophrenia is unclear. Individuals with schizophrenia and healthy subjects underwent diffusion tensor imaging (DTI) and completed a brief neuropsychological assessment that included measures of processing speed, verbal learning, working memory and executive functioning. Group differences in WM integrity, inferred from fractional anisotropy (FA), were examined throughout the brain and the hypothesis that processing speed impairment in schizophrenia is mediated by diminished WM integrity was tested. WM integrity of the corpus callosum, cingulum, superior and inferior frontal gyri, and precuneus was reduced in schizophrenia. Average FA in these regions mediated group differences in processing speed but not in other cognitive domains. Diminished WM integrity in schizophrenia was accounted for, in large part, by individual differences in processing speed. Cognitive impairment in schizophrenia was mediated by reduced WM integrity. This relationship was strongest for processing speed because deficits in working memory, verbal learning and executive functioning were not mediated by WM integrity. Larger sample sizes may be required to detect more subtle mediation effects in these domains. Interventions that preserve WM integrity or ameliorate WM disruption may enhance processing speed and functional outcome in schizophrenia.
Cannabis cue-induced brain activation correlates with drug craving in limbic and visual salience regions: Preliminary results
Psychiatry Research: Neuroimaging, 2013
Craving is a major motivator underlying drug use and relapse but the neural correlates of cannabi... more Craving is a major motivator underlying drug use and relapse but the neural correlates of cannabis craving are not well understood. This study sought to determine whether visual cannabis cues increase cannabis craving and whether cue-induced craving is associated with regional brain activation in cannabis-dependent individuals. Cannabis craving was assessed in 16 cannabis-dependent adult volunteers while they viewed cannabis cues during a functional MRI (fMRI) scan. The Marijuana Craving Questionnaire was administered immediately before and after each of three cannabis cue-exposure fMRI runs. FMRI blood-oxygenation-level-dependent (BOLD) signal intensity was determined in regions activated by cannabis cues to examine the relationship of regional brain activation to cannabis craving. Craving scores increased significantly following exposure to visual cannabis cues. Visual cues activated multiple brain regions, including inferior orbital frontal cortex, posterior cingulate gyrus, parahippocampal gyrus, hippocampus, amygdala, superior temporal pole, and occipital cortex. Craving scores at baseline and at the end of all three runs were significantly correlated with brain activation during the first fMRI run only, in the limbic system (including amygdala and hippocampus) and paralimbic system (superior temporal pole), and visual regions (occipital cortex). Cannabis cues increased craving in cannabis-dependent individuals and this increase was associated with activation in the limbic, paralimbic, and visual systems during the first fMRI run, but not subsequent fMRI runs. These results suggest that these regions may mediate visually cued aspects of drug craving. This study provides preliminary evidence for the neural basis of cue-induced cannabis craving and suggests possible neural targets for interventions targeted at treating cannabis dependence.
Neuropsychopharmacology, 2011
The serotonergic neurotoxin, 3,4-methylenedioxymethamphetamine (MDMA/Ecstasy), is a highly popula... more The serotonergic neurotoxin, 3,4-methylenedioxymethamphetamine (MDMA/Ecstasy), is a highly popular recreational drug. Human recreational MDMA users have neurocognitive and neuropsychiatric impairments, and human neuroimaging data are consistent with animal reports of serotonin neurotoxicity. However, functional neuroimaging studies have not found consistent effects of MDMA on brain neurophysiology in human users. Several lines of evidence suggest that studying MDMA effects in visual system might reveal the general cortical and subcortical neurophysiological consequences of MDMA use. We used 3 T functional magnetic resonance imaging during visual stimulation to compare visual system lateral geniculate nucleus (LGN) and Brodmann Area (BA) 17 and BA 18 activation in 20 long abstinent (479.95±580.65 days) MDMA users and 20 non-MDMA user controls. Lifetime quantity of MDMA use was strongly positively correlated with blood oxygenation level-dependent (BOLD) signal intensity in bilateral LGN (r s ¼ 0.59; p ¼ 0.007), BA 17 (r s ¼ 0.50; p ¼ 0.027), and BA 18 (r s ¼ 0.48; p ¼ 0.031), and with the spatial extent of activation in BA 17 (r s ¼ 0.059; p ¼ 0.007) and BA 18 (r s ¼ 0.55; p ¼ 0.013). There were no between-group differences in brain activation in any region, but the heaviest MDMA users showed a significantly greater spatial extent of activation than controls in BA 17 (p ¼ 0.031) and BA 18 (p ¼ 0.049). These results suggest that human recreational MDMA use may be associated with a long-lasting increase in cortical excitability, possibly through loss of serotonin input to cortical and subcortical regions. When considered in the context of previous results, cortical hyper-excitability may be a biomarker for MDMA-induced serotonin neurotoxicity.
Neuropsychopharmacology, 2005
Unipolar and bipolar depressions show abnormal behavioral manifestations of ultradian (less than ... more Unipolar and bipolar depressions show abnormal behavioral manifestations of ultradian (less than 24 h) rhythms, but abnormal rhythms of the central neurotransmitters thought to be important for depression pathophysiology (eg dopamine (DA) and serotonin (5-HT)) have not been shown in this time frame. Since antidepressant treatments normalize disrupted rhythms in depression (eg rapid-eyemovement sleep and hormonal rhythms), we hypothesized that depression-related changes in ultradian oscillations of DA and 5-HT might be revealed during antidepressant treatment. Cerebrospinal fluid (CSF) samples collected q10 min for 24 h in 13 patients experiencing major depressive episodes (MDE) before and after treatment for 5 weeks with sertraline or bupropion were assayed for levels of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), and their ratio was calculated. Data were analyzed in the frequency domain using Fourier transforms and multivariate permutation testing. Antidepressant treatments were associated with decreased variance for 5-HIAA, increased variance for HVA, and markedly increased variance for the HVA : 5-HIAA ratio (po0.05, po0.02, and po0.003, respectively). With treatment, the correlations between 5-HIAA and HVA weakened (p ¼ 0.06). Power spectral density (PSDFthe Fourier magnitude squared) of the 5-HIAA signals at periods of 1.75 and 3.7 h (both po0.05) decreased, while circadian cycling of HVA levels (po0.05) and of the ratio (po0.005) increased after treatment. The PSD of the full-length HVA : 5-HIAA ratio series after treatment increased in rapid variability (20-103 min periods, po0.05). Spectrographic windowing demonstrated a focal span of enhanced HVA : 5-HIAA ratio variability following antidepressant treatment, in an approximately 84-min period through the evening (po0.05). Periodic neurotransmitter relationships in depressed patients were altered by treatment in this analysis of a small data set. This may represent a baseline abnormality in the regulation of periodic functions involved in the depression pathophysiology, but it could also be due to an unrelated antidepressant effect. Further studies including comparisons with healthy subject data are in progress.
Uploads
Papers by Jennifer Blackford