Jeffery J. Borckardt

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.

Regional Brain Activation during Meditation Shows Time and Practice Effects: An Exploratory FMRI Study

Meditation involves attentional regulation and may lead to increased activity in brain regions associated with attention such as dorsal lateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). Using functional magnetic resonance imaging, we examined whether DLPFC and ACC were activated during meditation. Subjects who meditate were recruited and scanned on a 3.0 Tesla scanner. Subjects meditated for four sessions of 12 min and performed four sessions of a 6 min control task. Individual and group t-maps were generated of overall meditation response versus control response and late meditation response versus early meditation response for each subject and time courses were plotted. For the overall group (n = 13), and using an overall brain analysis, there were no statistically significant regional activations of interest using conservative thresholds. A region of interest analysis of the entire group time courses of DLPFC and ACC were statistically more active throughout meditation in comparison to the control task. Moreover, dividing the cohort into short (n = 8) and long-term (n = 5) practitioners (>10 years) revealed that the time courses of long-term practitioners had significantly more consistent and sustained activation in the DLPFC and the ACC during meditation versus control in comparison to short-term practitioners. The regional brain activations in the more practised subjects may correlate with better sustained attention and attentional error monitoring. In summary, brain regions associated with attention vary over the time of a meditation session and may differ between long- and short-term meditation practitioners.

Focal electrical stimulation as a sham control for repetitive transcranial magnetic stimulation: Does it truly mimic the cutaneous sensation and pain of active prefrontal repetitive transcranial magnetic stimulation?

BACKGROUND Repetitive transcranial magnetic stimulation (rTMS) is a novel, noninvasive method of stimulating selected regions of the brain that has both research applications and potential clinical utility, particularly for depression. To conduct high-quality clinical studies of rTMS, it is necessary to have a convincing placebo (or sham) treatment. Prefrontal rTMS causes cutaneous discomfort and muscle twitching; therefore, an optimal control condition, ie, sham condition, would mimic the cutaneous sensation and muscular discomfort of rTMS without stimulating the brain. Ideally, the quality and intensity of the sham condition would feel identical to the quality and intensity of the rTMS condition, except that the sham would have no effect on cortical activity. We designed and built a focal electrical stimulation system as a sham rTMS condition. Although this electrical sham system is superior to methods used in previous studies, little is known about how the new electrical sham system compares with active rTMS in terms of the level of discomfort and type of sensation it produces. METHODS We hypothesized that the electrical sham system may not mirror the experimental condition sufficiently. We studied this hypothesis under single-blind conditions in 15 healthy adults by administering either the real or sham rTMS at high and low intensities while subjects, who were unaware of condition, rated subjective qualities of the stimulation (such as tingling, pinching, and piercing), the scalp location of the perception, and the painfulness of the stimuli. RESULTS At low-intensity stimulation, the two techniques (active and sham) differ with respect to the subjective quality of the sensation. The differences between real and sham rTMS were less dramatic at higher intensities. The best sham condition that most closely mimics real prefrontal rTMS requires individual titration of the intensity of electrical stimulation across a broad range. Performing this titration without unblinding patients is likely possible, but technically challenging. We propose a new approach to do this. CONCLUSION We conclude that it is possible to create a truly indistinguishable sham condition (with appropriate acoustic masking as well), but more work is needed beyond these initial attempts.

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.

Oscillating Square Wave Transcranial Direct Current Stimulation (tDCS) Delivered During Slow Wave Sleep Does Not Improve Declarative Memory More Than Sham: A Randomized Sham Controlled Crossover Study.

BACKGROUND A 2006 trial in healthy medical students found that anodal slow oscillating tDCS delivered bi-frontally during slow wave sleep had an enhancing effect in declarative, but not procedural memory. Although there have been supporting animal studies, and similar findings in pathological groups, this study has not been replicated, or refuted, in the intervening years. We therefore tested these earlier results for replication using similar methods with the exception of current waveform (square in our study, nearly sinusoidal in the original). OBJECTIVE/HYPOTHESIS Our objective was to test the findings of a 2006 trial suggesting bi-frontal anodal tDCS during slow wave sleep enhances declarative memory. METHODS Twelve students (mean age 25, 9 women) free of medical problems underwent two testing conditions (active, sham) in a randomized counterbalanced fashion. Active stimulation consisted of oscillating square wave tDCS delivered during early Non-Rapid Eye Movement (NREM) sleep. The sham condition consisted of setting-up the tDCS device and electrodes, but not turning it on during sleep. tDCS was delivered bi-frontally with anodes placed at F3/F4, and cathodes placed at mastoids. Current density was 0.517 mA/cm(2), and oscillated between zero and maximal current at a frequency of 0.75 Hz. Stimulation occurred during five-five minute blocks with 1-min inter-block intervals (25 min total stimulation). The primary outcomes were both declarative memory consolidation measured by a paired word association test (PWA), and non-declarative memory, measured by a non-dominant finger-tapping test (FTT). We also recorded and analyzed sleep EEG. RESULTS There was no difference in the number of paired word associations remembered before compared to after sleep [(active = 3.1 ± 3.0 SD more associations) (sham = 3.8 ± 3.1 SD more associations)]. Finger tapping improved, (non-significantly) following active stimulation [(3.6 ± 2.7 SD correctly typed sequences) compared to sham stimulation (2.3 ± 2.2 SD correctly typed sequences)]. CONCLUSION In this study, we failed to find improvements in declarative or performance memory and could not replicate an earlier study using nearly identical settings. Specifically we failed to find a beneficial effect on either overnight declarative or non-declarative memory consolidation via square-wave oscillating tDCS intervention applied bi-frontally during early NREM sleep. It is unclear if the morphology of the tDCS pulse is critical in any memory related improvements.

A closer look at the nature of anxiety in weight loss surgery candidates.

Objective: Depression among weight loss surgery (WLS) candidates is common. Anxiety in this population is less studied. Untreated anxiety persists post-surgery and is associated with poor surgical outcomes. The current study sought to explore the nature of anxiety in WLS candidates. Given shared symptoms of anxiety and obesity, we hypothesized that physiological symptoms of anxiety would be most common. Methods: In this retrospective study, the medical records of 174 pre-WLS candidates at a large medical center were reviewed. Each completed a comprehensive medical, surgical, and psychological evaluation as part of standard of care. Data from these evaluations were abstracted. One hundred forty-three candidates completed the Beck Anxiety Inventory (BAI). A Principal Components Analysis (PCA) with varimax rotation was used to identify the factor structure of the BAI. Results: The sample consisted of primarily middle-aged (46.0 ± 13.24 years), married (60.8%), Caucasian (65.7%), females (79%) with Class III obesity (Body Mass Index = 50.1 ± 10.68) and mild anxiety (8.86 ± 8.70). Forty-four percent of the sample endorsed clinically significant anxiety. PCA revealed a four-factor structure that explained 56.28% of the variance in the BAI. The four factors were: 1) cognitive-emotional distress, 2) autonomic hyperarousal, 3) neurophysiologic concerns, and 4) body temperature. Conclusions: Clinically significant anxiety is common among WLS candidates. Cognitive-emotional clustering of anxiety symptoms was more common than hypothesized. This is notable given the overlap of physiological symptoms of anxiety and obesity. Findings lend support for the utility of psychotherapeutic approaches tailored to address maladaptive thoughts to address anxiety and potentially improve WLS outcomes.

More than black and white: differences in predictors of obesity among Native Hawaiian/Pacific Islanders and European Americans.

Although Native Hawaiians and Pacific Islanders exhibit the highest rates of obesity and associated chronic diseases of any racial/ethnic group, they remain vastly underrepresented in health research. In a cross‐sectional survey of college students (N = 402) we examined BMI and health outcomes in an ethno‐racially diverse rural sample of Native Hawaiian/Pacific Islanders (25.1%), Asian Americans (39.8%), and European Americans (35.1%). Measures assessed BMI, health status, health behaviors, frequency of exercise, and symptoms of psychiatric disorders (i.e., depression, anxiety, posttraumatic stress, and substance abuse and dependence). Regression analyses revealed that an overall model of five predictors (gender, race, regular exercise, difficulty sleeping, and anxiety) was significantly associated with obesity (P < 0.001) and correctly classified 84.2% of cases. A 30.7% of Native Hawaiians/Pacific Islanders were obese as compared with 9.2% of European Americans and 10.6% of Asian Americans. These findings suggest that Native Hawaiian/ Pacific Islanders are at high risk for obesity and associated medical comorbidities, but that regular physical activity may ameliorate this risk. Further, these results support the consideration of Native Hawaiians/Pacific Islanders as a distinct racial/ethnic subgroup separate from other Asian populations.

Cathodal and anodal left prefrontal tDCS and the perception of control over pain.

Objectives:The prefrontal cortex may be a promising target for the use of transcranial direct current stimulation (tDCS) in the management of pain symptoms. The present study explored the effects of anodal and cathodal tDCS over the left dorsolateral prefrontal cortex on the effects of perceived pain controllability. Materials and Methods:Forty-one participants received continuous anodal or cathodal tDCS and underwent a laboratory pain task designed to manipulate the perception of pain control. Participants were told that they would be completing a reaction-time task (press keyboard button of corresponding arrow shown on computer screen with either green or red background). A thermal pain stimulus was delivered following each trial by a thermode placed on the participant’s left forearm. Although pain stimuli were pseudorandomally ordered and matched for total duration between control (green) and noncontrol (red) trials, participants were told that if they responded correctly and more quickly on green trials than their average reaction times, the thermal pain stimulus duration would be decreased (ie, perceived control). Participants were told they had no control of pain stimulus duration over trials presented with the red background. Results:There was a significant main effect for tDCS condition (anode vs. cathode) on pain unpleasantness ratings (P<0.04). Specifically, individuals receiving cathodal tDCS reported higher pain unpleasantness ratings (least squares mean=69.40, SE=3.72), whereas those receiving anodal tDCS reported lower pain unpleasantness ratings (least squares mean=58.05, SE=3.81). Exploratory analysis revealed a simple main effect for tDCS group at the level of perceived controllability (P<0.02). In addition, participants receiving cathodal tDCS subjectively reported feeling less control of the painful stimuli than those receiving anodal tDCS. Discussion:Left dorsolateral prefrontal cortex tDCS may play a role in modulating the neurocircuitry involved with the perception of control over pain.

Interprofessional Collaborative Care Reduces Excess Service Utilization Among Individuals With Chronic Pancreatitis

Background: Pain is common and multifactorial among patients with chronic pancreatitis. Underrecognized and undertreated psychosocial comorbidity can exacerbate pain experience. Excess inpatient service utilization within this patient population prompted a performance improvement initiative at a large academic medical center. Methods: An interprofessional treatment approach with programmatic medical, surgical, and psychological and psychiatric interventions was rolled‐out in January 2007 and length of stay (LOS) was measured on a quarterly basis for a 2‐year period. Trends in resource utilization (LOS, estimated opportunity costs) were assessed with a novel modified bootstrapping technique, Simulation Modeling Analysis (SMA). Results: From January 1, 2007, through December 31, 2008, SMA revealed a linear downward trend in LOS (&rgr; = −0.857, p = .0170), and the interprofessional treatment approach was associated with estimated opportunity cost savings of

Beyond rose colored glasses: the adaptive role of depressive and anxious symptoms among individuals with heart failure who were evaluated for transplantation

670,750.27. There were no associated changes in 7‐, 14‐, and 30‐day readmission rates, p > .05. Conclusion: Interprofessional care that combines behavioral approaches to pain management; behavioral contingency management for opioid medication management; psychological and psychotropic treatments for depression, anxiety, and addiction in addition to standard medical and surgical treatments for pancreatitis appears to be associated with lower healthcare costs. Future research should examine patient reported outcomes of this model.