BACKGROUND Abnormalities of reward sensitivity and impulsivity are known to be correlated with ea... more BACKGROUND Abnormalities of reward sensitivity and impulsivity are known to be correlated with each other and alcohol use disorder (AUD) risk, but the underlying aberrant neural circuitry involved is not clearly defined. We sought to extend the current knowledge of AUD pathophysiology by studying incentive processing in persons with AUD using functional neuroimaging data. METHODS We utilized functional MRI data from the Human Connectome Project Database (HCP) obtained during performance of a number-guessing incentive processing task with win, loss, and neutral feedback conditions in N=78 participants with either DSM-IV alcohol abuse or dependence (combined as the AUD group) and N=78 age and sex-matched control (CON) participants. Within a network consisting of anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), insula, ventral striatum (VS) and dorsal striatum (DS) in the right hemisphere, we performed dynamic causal modeling (DCM) analysis to test group-level differences (AUD vs. CON) in effective directional connectivity (EC) as modulated by "win" and "loss" conditions. We performed linear regression analyses to characterize relationships between each EC outcome and measures of cumulative alcohol exposure and impulsivity. RESULTS During wins, AUD participants had lower ECs from ACC to the other four nodes, greater ECs from insula to the other four nodes, greater ECs from DLPFC to the other four nodes, and greater DS to DS self-connection EC compared to CON participants. In the total sample, EC from the insula to the DLPFC (insulaDLPFC) during wins was positively correlated with both impulsivity (as measured by the Delay Discounting Task) and cumulative alcohol exposure; the DS to DS self-connection EC during wins was positively correlated with impulsivity. Many of the altered ECs from ACC and insula to other nodes were correlated with cumulative alcohol exposure. CONCLUSIONS Individuals with AUD have disrupted EC in both instrumentally-driven and automatized cortico-striatal reward circuits during non-alcohol reward feedback. These results point to disrupted corticostriatal EC in both "top-down" and "bottom-up" pathways among individuals with AUD.
Cannabis use continues to be a public health concern and has become a major clinical and nonclini... more Cannabis use continues to be a public health concern and has become a major clinical and nonclinical research construct in numerous fields for numerous reasons. First, the slight alterations in the criteria for cannabis use disorder (CUD) diagnosis required validation and prevalence statistics. Second, the shift in social perceptions of cannabis use and its legalization by various states have led to significant increases in cannabis use, abuse, and individuals meeting the criteria for CUD. Additionally, understanding the psychological and neural mechanisms associated with CUD will allow for innovative and tailored intervention and treatment methods for those suffering from the condition. This chapter provides a brief overview of the central, peripheral, and autonomic processes associated with CUD. It then considers the current treatments for CUD that are informed by pharmacological and epidemiological information. Finally, the authors contrast CUD with cardiovascular dysfunction, pr...
4. Subjects (Page 4): After checking Table 1, I found that there were left-hand subjects although... more 4. Subjects (Page 4): After checking Table 1, I found that there were left-hand subjects although the major of the subjects were right-handed. It is known that there is laterality in motor activation, which is very important for brain connectivity studies. The left-handed subjects may be a confounding factor for the data. Therefore I urge the authors to remove these left-handed subjects from the analysis.
BackgroundChronic substance use and its effects on brain function and structure has long been of ... more BackgroundChronic substance use and its effects on brain function and structure has long been of interest to clinicians and researchers. Prior cross-sectional comparisons of diffusion tensor imaging (DTI) metrics have suggested deleterious effects of chronic substance use (i.e., cocaine use) on white matter integrity (WM). However, it is unclear how these effects may replicate with improving DTI technologies to enhance detection of substance use-related WM decrements. In this study, we sought to conduct a replication of previous work in this area and determine whether there are any patterns of persistent differences in WM microstructure between individuals with a history of Cocaine Use Disorder (CocUD, according to DSM-IV) and healthy controls. Method46 participants (21 healthy controls, 25 chronic cocaine users) were recruited from the Richmond, Virginia metropolitan area. Information regarding past and current substance use was collected from all participants. Participants also co...
Past investigations utilizing diffusion tensor imaging (DTI) have demonstrated that cocaine use d... more Past investigations utilizing diffusion tensor imaging (DTI) have demonstrated that cocaine use disorder (CUD) yields white matter changes, primarily in the corpus callosum. By applying Bayesian model averaging using multiple linear regression in DTI, we demonstrate there may exist relationships between the impaired white matter and glutamic acid decarboxylase (GAD) polymorphisms. This work explored the two-way and three-way interactions between GAD1a (SNP: rs1978340) and GAD1b (SNP: rs769390) polymorphisms and years of cocaine use (YCU). GAD1a was associated with more frontal white matter changes on its own but GAD1b was associated with more midbrain and cerebellar changes as well as a greater increase in white matter changes in the context of chronic cocaine use. The three-way interaction GAD1a|GAD1b|YCU appeared to be roughly an average of the polymorphism two-way interactions GAD1a|YCU and GAD1b|YCU. The three-way interaction demonstrated multiple regions including corpus callos...
BACKGROUND Takotsubo syndrome (TS) is an acute, reversible form of heart failure, often mimicking... more BACKGROUND Takotsubo syndrome (TS) is an acute, reversible form of heart failure, often mimicking an acute coronary syndrome (ACS). Data regarding racial differences in TS are inconsistent. The aim is to assess clinical features associated with unfavorable in-hospital outcomes between African American (AA) and Caucasian (CAU) patients. METHODS A retrospective electronic health record query identified 44 AA patients and 110 CAU patients with a diagnosis of TS. Our primary outcome was a composite of death, stroke, and cardiogenic shock during hospitalization. Variables associated with an increased risk of the primary composite outcomes were included in a logistic regression model. RESULTS Compared to CAU patients, AA patients were a more comorbid population, and presented a higher prevalence of history of illicit drug use (27.3% vs 13.6% p=0.044). There were no significant differences regarding in-hospital complication rates between AA and CAU patients. In the logistic regression model, infection was associated with greater risk of developing the primary outcome in AA patients (OR=7.26 95% CI [1.22-43.17], p=0.029), whereas angina was a protective factor (OR=0.11 95% CI [0.02-0.65], p=0.015). In CAU patients, severely depressed ejection fraction and worse peak creatinine during hospitalization increased risk of developing the primary outcome (OR=5.88 95% CI [2.01-17.17], p<0.001 and OR=1.64 95% CI [1.15-2.58], p=0.031, respectively). Meanwhile, emotional stressors were protective (OR=0.16 95% CI [0.03-0.88], p=0.004). CONCLUSIONS Despite experiencing the same rate of in-hospital complications, the clinical profiles of AA patients are distinct from CAU patients admitted for TS, and clinical variables correlated with worse in-hospital outcomes also differ by race.
Dynamic causal modeling (DCM) is a method for analyzing functional magnetic resonance imaging (fM... more Dynamic causal modeling (DCM) is a method for analyzing functional magnetic resonance imaging (fMRI) and other functional neuroimaging data that provides information about directionality of connectivity between brain regions. A review of the neuropsychiatric fMRI DCM literature suggests that there may be a historical trend to under-report self-connectivity (within brain regions) compared to between brain region connectivity findings. These findings are an integral part of the neurologic model represented by DCM and serve an important neurobiological function in regulating excitatory and inhibitory activity between regions. We reviewed the literature on the topic as well as the past 13 years of available neuropsychiatric DCM literature to find an increasing (but still, perhaps, and inadequate) trend in reporting these results. The focus of this review is fMRI as the majority of published DCM studies utilized fMRI and the interpretation of the self-connectivity findings may vary acros...
Recently, an association between cannabis use and Takotsubo (stress) cardiomyopathy (TTC) has bee... more Recently, an association between cannabis use and Takotsubo (stress) cardiomyopathy (TTC) has been shown. With the current trend of legalization of cannabis, it is important to understand brain effects of cannabis use that could lead to cardiac disease, such as TTC. Here we review recent brain imaging studies in order to search for the evidence supporting the association between cannabis use, stress, and TTC. There exist brain imaging studies showing similar findings across TTC, stress, and cannabis use. These similar findings are mainly centered on a key central autonomic network region amygdala, i.e., amygdala hyperactivity/hyperconnectivity when exposed to challenge, stress, or negative stimuli. This similarity supports a close association among cannabis use, stress, and TTC. Amygdala-centered neuronal circuits could underlie cannabis use as risk factor to TTC. Based on the findings, several directions for future studies are proposed.
BACKGROUND Abnormalities of reward sensitivity and impulsivity are known to be correlated with ea... more BACKGROUND Abnormalities of reward sensitivity and impulsivity are known to be correlated with each other and alcohol use disorder (AUD) risk, but the underlying aberrant neural circuitry involved is not clearly defined. We sought to extend the current knowledge of AUD pathophysiology by studying incentive processing in persons with AUD using functional neuroimaging data. METHODS We utilized functional MRI data from the Human Connectome Project Database (HCP) obtained during performance of a number-guessing incentive processing task with win, loss, and neutral feedback conditions in N=78 participants with either DSM-IV alcohol abuse or dependence (combined as the AUD group) and N=78 age and sex-matched control (CON) participants. Within a network consisting of anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), insula, ventral striatum (VS) and dorsal striatum (DS) in the right hemisphere, we performed dynamic causal modeling (DCM) analysis to test group-level differences (AUD vs. CON) in effective directional connectivity (EC) as modulated by "win" and "loss" conditions. We performed linear regression analyses to characterize relationships between each EC outcome and measures of cumulative alcohol exposure and impulsivity. RESULTS During wins, AUD participants had lower ECs from ACC to the other four nodes, greater ECs from insula to the other four nodes, greater ECs from DLPFC to the other four nodes, and greater DS to DS self-connection EC compared to CON participants. In the total sample, EC from the insula to the DLPFC (insulaDLPFC) during wins was positively correlated with both impulsivity (as measured by the Delay Discounting Task) and cumulative alcohol exposure; the DS to DS self-connection EC during wins was positively correlated with impulsivity. Many of the altered ECs from ACC and insula to other nodes were correlated with cumulative alcohol exposure. CONCLUSIONS Individuals with AUD have disrupted EC in both instrumentally-driven and automatized cortico-striatal reward circuits during non-alcohol reward feedback. These results point to disrupted corticostriatal EC in both "top-down" and "bottom-up" pathways among individuals with AUD.
Cannabis use continues to be a public health concern and has become a major clinical and nonclini... more Cannabis use continues to be a public health concern and has become a major clinical and nonclinical research construct in numerous fields for numerous reasons. First, the slight alterations in the criteria for cannabis use disorder (CUD) diagnosis required validation and prevalence statistics. Second, the shift in social perceptions of cannabis use and its legalization by various states have led to significant increases in cannabis use, abuse, and individuals meeting the criteria for CUD. Additionally, understanding the psychological and neural mechanisms associated with CUD will allow for innovative and tailored intervention and treatment methods for those suffering from the condition. This chapter provides a brief overview of the central, peripheral, and autonomic processes associated with CUD. It then considers the current treatments for CUD that are informed by pharmacological and epidemiological information. Finally, the authors contrast CUD with cardiovascular dysfunction, pr...
4. Subjects (Page 4): After checking Table 1, I found that there were left-hand subjects although... more 4. Subjects (Page 4): After checking Table 1, I found that there were left-hand subjects although the major of the subjects were right-handed. It is known that there is laterality in motor activation, which is very important for brain connectivity studies. The left-handed subjects may be a confounding factor for the data. Therefore I urge the authors to remove these left-handed subjects from the analysis.
BackgroundChronic substance use and its effects on brain function and structure has long been of ... more BackgroundChronic substance use and its effects on brain function and structure has long been of interest to clinicians and researchers. Prior cross-sectional comparisons of diffusion tensor imaging (DTI) metrics have suggested deleterious effects of chronic substance use (i.e., cocaine use) on white matter integrity (WM). However, it is unclear how these effects may replicate with improving DTI technologies to enhance detection of substance use-related WM decrements. In this study, we sought to conduct a replication of previous work in this area and determine whether there are any patterns of persistent differences in WM microstructure between individuals with a history of Cocaine Use Disorder (CocUD, according to DSM-IV) and healthy controls. Method46 participants (21 healthy controls, 25 chronic cocaine users) were recruited from the Richmond, Virginia metropolitan area. Information regarding past and current substance use was collected from all participants. Participants also co...
Past investigations utilizing diffusion tensor imaging (DTI) have demonstrated that cocaine use d... more Past investigations utilizing diffusion tensor imaging (DTI) have demonstrated that cocaine use disorder (CUD) yields white matter changes, primarily in the corpus callosum. By applying Bayesian model averaging using multiple linear regression in DTI, we demonstrate there may exist relationships between the impaired white matter and glutamic acid decarboxylase (GAD) polymorphisms. This work explored the two-way and three-way interactions between GAD1a (SNP: rs1978340) and GAD1b (SNP: rs769390) polymorphisms and years of cocaine use (YCU). GAD1a was associated with more frontal white matter changes on its own but GAD1b was associated with more midbrain and cerebellar changes as well as a greater increase in white matter changes in the context of chronic cocaine use. The three-way interaction GAD1a|GAD1b|YCU appeared to be roughly an average of the polymorphism two-way interactions GAD1a|YCU and GAD1b|YCU. The three-way interaction demonstrated multiple regions including corpus callos...
BACKGROUND Takotsubo syndrome (TS) is an acute, reversible form of heart failure, often mimicking... more BACKGROUND Takotsubo syndrome (TS) is an acute, reversible form of heart failure, often mimicking an acute coronary syndrome (ACS). Data regarding racial differences in TS are inconsistent. The aim is to assess clinical features associated with unfavorable in-hospital outcomes between African American (AA) and Caucasian (CAU) patients. METHODS A retrospective electronic health record query identified 44 AA patients and 110 CAU patients with a diagnosis of TS. Our primary outcome was a composite of death, stroke, and cardiogenic shock during hospitalization. Variables associated with an increased risk of the primary composite outcomes were included in a logistic regression model. RESULTS Compared to CAU patients, AA patients were a more comorbid population, and presented a higher prevalence of history of illicit drug use (27.3% vs 13.6% p=0.044). There were no significant differences regarding in-hospital complication rates between AA and CAU patients. In the logistic regression model, infection was associated with greater risk of developing the primary outcome in AA patients (OR=7.26 95% CI [1.22-43.17], p=0.029), whereas angina was a protective factor (OR=0.11 95% CI [0.02-0.65], p=0.015). In CAU patients, severely depressed ejection fraction and worse peak creatinine during hospitalization increased risk of developing the primary outcome (OR=5.88 95% CI [2.01-17.17], p<0.001 and OR=1.64 95% CI [1.15-2.58], p=0.031, respectively). Meanwhile, emotional stressors were protective (OR=0.16 95% CI [0.03-0.88], p=0.004). CONCLUSIONS Despite experiencing the same rate of in-hospital complications, the clinical profiles of AA patients are distinct from CAU patients admitted for TS, and clinical variables correlated with worse in-hospital outcomes also differ by race.
Dynamic causal modeling (DCM) is a method for analyzing functional magnetic resonance imaging (fM... more Dynamic causal modeling (DCM) is a method for analyzing functional magnetic resonance imaging (fMRI) and other functional neuroimaging data that provides information about directionality of connectivity between brain regions. A review of the neuropsychiatric fMRI DCM literature suggests that there may be a historical trend to under-report self-connectivity (within brain regions) compared to between brain region connectivity findings. These findings are an integral part of the neurologic model represented by DCM and serve an important neurobiological function in regulating excitatory and inhibitory activity between regions. We reviewed the literature on the topic as well as the past 13 years of available neuropsychiatric DCM literature to find an increasing (but still, perhaps, and inadequate) trend in reporting these results. The focus of this review is fMRI as the majority of published DCM studies utilized fMRI and the interpretation of the self-connectivity findings may vary acros...
Recently, an association between cannabis use and Takotsubo (stress) cardiomyopathy (TTC) has bee... more Recently, an association between cannabis use and Takotsubo (stress) cardiomyopathy (TTC) has been shown. With the current trend of legalization of cannabis, it is important to understand brain effects of cannabis use that could lead to cardiac disease, such as TTC. Here we review recent brain imaging studies in order to search for the evidence supporting the association between cannabis use, stress, and TTC. There exist brain imaging studies showing similar findings across TTC, stress, and cannabis use. These similar findings are mainly centered on a key central autonomic network region amygdala, i.e., amygdala hyperactivity/hyperconnectivity when exposed to challenge, stress, or negative stimuli. This similarity supports a close association among cannabis use, stress, and TTC. Amygdala-centered neuronal circuits could underlie cannabis use as risk factor to TTC. Based on the findings, several directions for future studies are proposed.
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