James J. Prisciandaro

Volitional reduction of anterior cingulate cortex activity produces decreased cue craving in smoking cessation: a preliminary real-time fMRI study

Numerous research groups are now using analysis of blood oxygen level‐dependent (BOLD) functional magnetic resonance imaging (fMRI) results and relaying back information about regional activity in their brains to participants in the scanner in ‘real time’. In this study, we explored the feasibility of self‐regulation of frontal cortical activation using real‐time fMRI (rtfMRI) neurofeedback in nicotine‐dependent cigarette smokers during exposure to smoking cues. Ten cigarette smokers were shown smoking‐related visual cues in a 3 Tesla MRI scanner to induce their nicotine craving. Participants were instructed to modify their craving using rtfMRI feedback with two different approaches. In a ‘reduce craving’ paradigm, participants were instructed to ‘reduce’ their craving, and decrease the anterior cingulate cortex (ACC) activity. In a separate ‘increase resistance’ paradigm, participants were asked to increase their resistance to craving and to increase middle prefrontal cortex (mPFC) activity. We found that participants were able to significantly reduce the BOLD signal in the ACC during the ‘reduce craving’ task (P = 0.028). There was a significant correlation between decreased ACC activation and reduced craving ratings during the ‘reduce craving’ session (P = 0.011). In contrast, there was no modulation of the BOLD signal in mPFC during the ‘increase resistance’ session. These preliminary results suggest that some smokers may be able to use neurofeedback via rtfMRI to voluntarily regulate ACC activation and temporarily reduce smoking cue‐induced craving. Further research is needed to determine the optimal parameters of neurofeedback rtfMRI, and whether it might eventually become a therapeutic tool for nicotine dependence.

The structure of depression, anxiety and somatic symptoms in primary care.

BACKGROUND Observed co-morbidity among the mood and anxiety disorders has led to the development of increasingly sophisticated dimensional models to represent the common and unique features of these disorders. Patients often present to primary care settings with a complex mixture of anxiety, depression and somatic symptoms. However, relatively little is known about how somatic symptoms fit into existing dimensional models. METHOD We examined the structure of 91 anxiety, depression and somatic symptoms in a sample of 5433 primary care patients drawn from 14 countries. One-, two- and three-factor lower-order models were considered; higher-order and hierarchical variants were studied for the best-fitting lower-order model. RESULTS A hierarchical, bifactor model with all symptoms loading simultaneously on a general factor, along with one of three specific anxiety, depression and somatic factors, was the best-fitting model. The general factor accounted for the bulk of symptom variance and was associated with psychosocial dysfunction. Specific depression and somatic symptom factors accounted for meaningful incremental variance in diagnosis and dysfunction, whereas anxiety variance was associated primarily with the general factor. CONCLUSIONS The results (a) are consistent with previous studies showing the presence and importance of a broad internalizing or distress factor linking diverse emotional disorders, and (b) extend the bounds of internalizing to include somatic complaints with non-physical etiologies.

A randomized, double-blind, placebo-controlled clinical trial of acamprosate in alcohol-dependent individuals with bipolar disorder: a preliminary report

Tolliver BK, DeSantis SM, Brown DG, Prisciandaro JJ, Brady KT. A randomized, double‐blind, placebo‐controlled clinical trial of acamprosate in alcohol‐dependent individuals with bipolar disorder: a preliminary report. Bipolar Disord 2012: 14: 54–63.

Brain activation to cocaine cues and motivation/treatment status.

Motivation to change is believed to be a key factor in therapeutic success in substance use disorders; however, the neurobiological mechanisms through which motivation to change impacts decreased substance use remain unclear. Existing research is conflicting, with some investigations supporting decreased and others reporting increased frontal activation to drug cues in individuals seeking treatment for substance use disorders. The present study investigated the relationship between motivation to change cocaine use and cue‐elicited brain activity in cocaine‐dependent individuals using two conceptualizations of ‘motivation to change’: (1) current treatment status (i.e. currently receiving versus not receiving outpatient treatment for cocaine dependence) and (2) self‐reported motivation to change substance use, using the Stages of Change Readiness and Treatment Eagerness Scale. Thirty‐eight cocaine‐dependent individuals (14 currently in treatment) completed a diagnostic assessment and an fMRI cocaine cue‐reactivity task. Whole‐brain analyses demonstrated that both treatment‐seeking and motivated participants had lower activation to cocaine cues in a wide variety of brain regions in the frontal, occipital, temporal and cingulate cortices relative to non‐treatment–seeking and less motivated participants. Future research is needed to explain the mechanism by which treatment and/or motivation impacts neural cue reactivity, as such work could potentially aid in the development of more effective therapeutic techniques for substance‐dependent patients.

Prospective associations between brain activation to cocaine and no-go cues and cocaine relapse

BACKGROUND The ability to predict potential for relapse to substance use following treatment could be very useful in targeting aftercare strategies. Recently, a number of investigators have focused on using neural activity measured by fMRI to predict relapse propensity. The purpose of the present study was to use fMRI to investigate prospective associations between brain reactivity to cocaine and response inhibition cues and relapse to cocaine use. METHODS Thirty cocaine-dependent participants with clean cocaine urine drug screens (UDS) completed a baseline fMRI scan, including a cocaine-cue reactivity task and a go no-go response inhibition task. After participating in a brief clinical trial of d-cycloserine for the facilitation of cocaine-cue extinction, they returned for a one-week follow-up UDS. Associations between baseline activation to cocaine and inhibition cues and relapse to cocaine use were explored. RESULTS Positive cocaine UDS was significantly associated with cocaine-cue activation in the right putamen and insula, as well as bilateral occipital regions. Associations between positive cocaine UDS and activation to no-go cues were concentrated in the postcentral gyri, a region involved in response execution. CONCLUSIONS Although preliminary, these results suggest that brain imaging may be a useful tool for predicting risk for relapse in cocaine-dependent individuals. Further, larger-scale naturalistic studies are needed to corroborate and extend these findings.

Real-time fMRI in the treatment of nicotine dependence: a conceptual review and pilot studies.

Technical advances allowing for the analysis of functional MRI (fMRI) results in real time have led to studies exploring the ability of individuals to use neural feedback signals to modify behavior and regional brain activation. The use of real-time fMRI (rtfMRI) feedback has been explored for therapeutic benefit in a number of disease states, but to our knowledge, the potential therapeutic benefit of rtfMRI feedback in the treatment of addictive disorders has not been explored. This article will provide an overview of the development of rtfMRI and discussion of its potential uses in the treatment of addictions. We also describe a series of pilot studies that highlight some of the technical challenges in developing a rtfMRI feedback paradigm for use in addictions, specifically in nicotine dependence. Because the use of rtfMRI feedback is in its infancy, the work described is focused on establishing some of the basic parameters in optimizing the rtfMRI feedback, such as the type of feedback signal, region of interest for feedback and predicting which subjects are most likely to respond well to training. While rtfMRI feedback remains an intriguing possibility for the treatment of addictions, much work remains to be done in establishing its efficacy.

Impact of Depressive Symptoms on Future Alcohol Use in Patients with Co-Occurring Bipolar Disorder and Alcohol Dependence: A Prospective Analysis in an 8-Week Randomized Controlled Trial of Acamprosate

BACKGROUND Bipolar disorders and alcohol use disorders commonly co-occur, yet little is known about the proximal impact of bipolar symptoms on alcohol use in patients with this comorbidity. The present study examined the impact of depressive symptoms and alcohol craving on proximal alcohol use in patients with co-occurring bipolar disorder and alcohol dependence. METHODS Data were collected during an 8-week randomized controlled trial of acamprosate for individuals with co-occurring bipolar disorder and alcohol dependence (n = 30). Depressive symptoms and alcohol craving were assessed biweekly using the Montgomery Asberg Depression Rating Scale (MADRS) and the Obsessive Compulsive Drinking Scale (OCDS), respectively. Daily alcohol use data were available via administration of the Time-line Follow-back interview at baseline and at subsequent weekly study visits. Correlational analyses and hidden Markov modeling were used to examine the prospective relationships between depressive symptoms, alcohol craving, and alcohol use. RESULTS Depressive symptoms and alcohol craving were significantly correlated with proximal (i.e., 1 week later) alcohol use across a variety of alcohol consumption summary measures. In hidden Markov models, depressive symptoms (OR = 1.3, 95% credible interval = [1.1, 1.5]) and alcohol craving (OR = 1.6, 95% credible interval = [1.4, 1.9]) significantly predicted transitioning from a light to a heavy drinking state, or remaining in a heavy drinking state. CONCLUSIONS The results from the present study suggest that depressive symptoms and alcohol craving increase proximal risk for alcohol use in individuals with co-occurring bipolar and alcohol use disorders.

The primary health care version of ICD-11: the detection of common mental disorders in general medical settings☆☆☆★

BACKGROUND The primary health care version of the ICD-11 is currently being revised. AIM To test two brief sets of symptoms for depression and anxiety in primary care settings, and validate them against diagnoses of major depression and current generalised anxiety made by the CIDI. METHOD The study took place in general medical or primary care clinics in 14 different countries, using the Composite International Diagnostic Interview adapted for primary care (CIDI-PC) in 5,438 patients. The latent structure of common symptoms was explored, and two symptom scales were derived from item response theory (IRT), these were then investigated against research diagnoses. RESULTS Correlations between dimensions of anxious, depressive and somatic symptoms were found to be high. For major depression the 5 item depression scale has marked superiority over the usual 2 item scales used by both the ICD and DSM systems, and for anxiety there is some superiority. If the questions are used with patients that the clinician suspects may have a psychological disorder, the positive predictive value of the scale is between 78 and 90%. CONCLUSION The two scales allow clinicians to make diagnostic assessments of depression and anxiety with a high positive predictive value, provided they use them only when they suspect that a psychological disorder is present.

Associations between behavioral disinhibition and cocaine use history in individuals with cocaine dependence

BACKGROUND Behavioral disinhibition has been suggested as both a cause and consequence of substance use disorders. Many studies examining associations between behavioral disinhibition and substance use history have focused on individuals with alcohol dependence or non-dependent college students. In the present study, the relationship between behavioral disinhibition and cocaine use history in individuals with cocaine dependence is examined. METHODS Forty-six non-treatment-seeking cocaine-dependent men and women completed impulsivity (Barratt impulsiveness scale; BIS) and novelty seeking (temperament and character inventory; TCI) questionnaires at the baseline visit of an ongoing study. Unadjusted, and adjusted for gender and age, Pearson correlations were calculated between BIS, TCI, and cocaine use variables from the structured clinical interview for DSM-IV and timeline follow-back (age of onset, quantity/frequency of past 30 day cocaine use). RESULTS As expected, elevated motor impulsivity and novelty seeking were each associated with younger age of dependence onset. Also, individuals with lower levels of persistence on the TCI reported more days of cocaine use over the previous month. Unexpectedly, increased novelty seeking and attentional impulsivity were associated with fewer days of cocaine use and less money spent on cocaine, respectively. Controlling for age and gender did not substantially change the pattern of observed associations. CONCLUSIONS The present study provides preliminary evidence for associations between behavioral disinhibition and cocaine use history in cocaine-dependent individuals. Given our relatively small sample size and the correlational nature of our findings, further research is needed to replicate and extend our results.

The relationship between years of cocaine use and brain activation to cocaine and response inhibition cues

AIMS Functional magnetic resonance imaging research has attempted to elucidate the neurobehavioral underpinnings of cocaine dependence by evaluating differences in brain activation to cocaine and response inhibition cues between cocaine-dependent individuals and controls. This study investigated associations between task-related brain activation and cocaine use characteristics. DESIGN Cross-sectional. SETTING The Center for Biomedical Imaging at the Medical University of South Carolina, USA. PARTICIPANTS Fifty-one cocaine users (41 dependent). MEASUREMENTS Brain activation to cocaine-cue exposure and Go No-Go tasks in six a priori selected brain regions of interest and cocaine use characteristics (i.e. cocaine dependence status, years of cocaine use, cocaine use in the past 90 days) assessed via standardized interviews. FINDINGS Participants demonstrated elevated activation to cocaine (bilateral ventral striatum, dorsal caudate, amygdala) and response inhibition (bilateral anterior cingulate, insula, inferior frontal gyrus) cues in all hypothesized brain regions. Years of cocaine use was associated with task-related brain activation, with more years of cocaine use associated with greater activation to cocaine cues in right (F = 7.97, P = 0.01) and left (F = 5.47, P = 0.02) ventral striatum and greater activation to response inhibition cues in left insula (F = 5.10, P = 0.03) and inferior frontal gyrus (F = 4.12, P = 0.05) controlling for age, cocaine dependence status and cocaine use in the past 90 days. CONCLUSIONS Years of cocaine use may be more centrally related to cocaine cue and response inhibition brain activation than cocaine dependence diagnosis or amount of recent use.