Jeffrey J. Borckardt

Clinical Practice as Natural Laboratory for Psychotherapy Research: A Guide to Case-Based Time-Series Analysis.

Both researchers and practitioners need to know more about how laboratory treatment protocols translate to real-world practice settings and how clinical innovations can be systematically tested and communicated to a skeptical scientific community. The single-case time-series study is well suited to opening a productive discourse between practice and laboratory. The appeal of case-based time-series studies, with multiple observations both before and after treatment, is that they enrich our design palette by providing the discipline another way to expand its empirical reach to practice settings and its subject matter to the contingencies of individual change. This article is a users guide to conducting empirically respectable case-based time-series studies in a clinical practice or laboratory setting.

A Pilot Study of the Tolerability and Effects of High-Definition Transcranial Direct Current Stimulation (HD-tDCS) on Pain Perception

UNLABELLED Several brain stimulation technologies are beginning to evidence promise as pain treatments. However, traditional versions of 1 specific technique, transcranial direct current stimulation (tDCS), stimulate broad regions of cortex with poor spatial precision. A new tDCS design, called high definition tDCS (HD-tDCS), allows for focal delivery of the charge to discrete regions of the cortex. We sought to preliminarily test the safety and tolerability of the HD-tDCS technique as well as to evaluate whether HD-tDCS over the motor cortex would decrease pain and sensory experience. Twenty-four healthy adult volunteers underwent quantitative sensory testing before and after 20 minutes of real (n = 13) or sham (n = 11) 2 mA HD-tDCS over the motor cortex. No adverse events occurred and no side effects were reported. Real HD-tDCS was associated with significantly decreased heat and cold sensory thresholds, decreased thermal wind-up pain, and a marginal analgesic effect for cold pain thresholds. No significant effects were observed for mechanical pain thresholds or heat pain thresholds. HD-tDCS appears well tolerated, and produced changes in underlying cortex that are associated with changes in pain perception. Future studies are warranted to investigate HD-tDCS in other applications, and to examine further its potential to affect pain perception. PERSPECTIVE This article presents preliminary tolerability and efficacy data for a new focal brain stimulation technique called high definition transcranial direct current stimulation. This technique may have applications in the management of pain.

Cloninger's temperament and character dimensions of personality in patients with major depressive disorder.

In this present study, we examined the relationship between the Cloningers dimensional psychobiologic model of personality and depression in an outpatient population with major depressive disorder. Eighty-one depressed outpatients (67 women, 14 men) and 51 healthy controls (35 women, 16 men) filled out the Turkish version of the Temperament and Character Inventory (TCI). Depression severity was evaluated by using the 17-item Hamilton Depression Rating Scale and the 21-item Beck Depression Inventory. Depressed patients exhibited statistically significant higher scores for harm avoidance and lower scores for self-directedness compared to healthy controls. Sentimentality (RD1) and dependence (RD4) subscale scores of reward dependence and spiritual acceptance (ST3) subscale of self-transcendence were significantly higher; attachment (RD3) subscale of reward dependence, responsibility (SD1), purposefulness (SD2), resourcefulness (SD3), and congruent second nature (SD5) subscales of self-directedness were significantly lower in the depressed group. In the depressed patient group, main effects of sex were significant for reward dependence and cooperativeness; the scores of both dimensions were higher for women. The Beck Inventory was positively correlated with harm avoidance and negatively correlated with novelty seeking and self-directedness dimensions (P < .05). The duration of depression (16.33 +/- 20.18 months) or the mean onset age of depression (28.68 +/- 8.11 years) did not show significant correlations with TCI scales. This study confirms the relationship between harm avoidance and depression and suggests a relationship between self-directedness and depression.

Prefrontal cortex transcranial direct current stimulation (tDCS) temporarily reduces food cravings and increases the self-reported ability to resist food in adults with frequent food craving.

This study examined whether a 20-min session of prefrontal transcranial direct current stimulation (tDCS) (anode over the right prefrontal cortex and cathode over the left prefrontal cortex) would reduce food cravings and increase the self-reported ability to resist foods in 19 healthy individuals who reported frequent food cravings. Participants viewed computerized images of food and used computerized visual analogue scales to rate food cravings and inability to resist foods before, during, and after receiving either real or sham tDCS. This study employed a randomized within-subject crossover design; participants received both real and sham tDCS and were blind to the condition. Food cravings ratings were reduced in both conditions, however, the percent change in cravings ratings from pre- to post-stimulation was significantly greater for real stimulation than for sham. The percent change in inability to resist food from pre- to post-stimulation also showed a greater decrease in the real condition than for sham. Post hoc analyses suggest that active prefrontal tDCS acutely and significantly decreased food cravings ratings for sweet foods and carbohydrates more so than sham tDCS. No significant differences were seen in the amount of food ingested between real and sham tDCS. These findings in healthy subjects indicate that tDCS is able to temporarily reduce food cravings and improve the self-reported ability to resist foods.

An efficient and accurate new method for locating the F3 position for prefrontal TMS applications

The International 10-20 system is a method for standardized placement of electroencephalogram (EEG) electrodes. The 10-20 system correlates external skull locations with the underlying cortical areas. This system accounts for variability in patient skull size by using certain percentages of the circumference and distances between four basic anatomical landmarks. This 10-20 system has recently been used in transcranial magnetic stimulation (TMS) research for locating specific cortical areas. In the treatment of depression (and some types of pain), the desired placement of the TMS coil is often above the left dorsalateral prefrontal cortex (DLPFC) which corresponds to the F3 location given by the 10-20 system. However, for an administrator with little experience with the 10-20 system, the numerous measurements and calculations can be excessively time-consuming. Additionally, with more measurements comes more opportunity for human error. For this reason we have developed a new, simpler and faster way to find the F3 position using only three skull measurements. In this paper, we describe and illustrate the application of the new F3 location system, provide the formulas used in the calculation of the F3 position, and summarize data from 10 healthy adults. After using both the International 10-20 system and this new method, it appears that the new method is sufficiently accurate; however, future investigations may be warranted to conduct more in dept analyses of the methods utility and potential limitations. This system requires less time and training to find the optimal position for prefrontal coil placement and it saves considerable time compared to the 10-20 EEG system.

Repetitive Transcranial Magnetic Stimulation of the Dorsolateral Prefrontal Cortex Reduces Nicotine Cue Craving

BACKGROUND Repetitive transcranial magnetic stimulation (rTMS) can noninvasively stimulate the brain and transiently amplify or block behaviors mediated through a region. We hypothesized that a single high-frequency rTMS session over the left dorsolateral prefrontal cortex (DLPFC) would reduce cue craving for cigarettes compared with a sham TMS session. METHODS Sixteen non-treatment-seeking, nicotine-dependent participants were randomized to receive either real high-frequency rTMS (10 Hz, 100% resting motor threshold, 5-sec on, 10-sec off for 15 min; 3000 pulses) or active sham (eSham) TMS over the DLPFC in two visits with 1 week between visits. The participants received cue exposure before and after rTMS and rated their craving after each block of cue presentation. RESULTS Stimulation of the left DLFPC with real, but not sham, rTMS reduced craving significantly from baseline (64.1±5.9 vs. 45.7±6.4, t = 2.69, p = .018). When compared with neutral cue craving, the effect of real TMS on cue craving was significantly greater than the effect of sham TMS (12.5±10.4 vs. -9.1±10.4; t = 2.07, p = .049). More decreases in subjective craving induced by TMS correlated positively with higher Fagerström Test for Nicotine Dependence score (r = .58, p = .031) and more cigarettes smoked per day (r = .57, p = .035). CONCLUSIONS One session of high-frequency rTMS (10 Hz) of the left DLPFC significantly reduced subjective craving induced by smoking cues in nicotine-dependent participants. Additional studies are needed to explore rTMS as an aid to smoking cessation.

Safety, tolerability, and effectiveness of high doses of adjunctive daily left prefrontal repetitive transcranial magnetic stimulation for treatment-resistant depression in a clinical setting.

Objective: Daily left prefrontal repetitive transcranial magnetic stimulation (rTMS) recently received Food and Drug Administration (FDA) approval for the treatment of depression and offers an alternative to traditional approaches. This approval was based on a study using 3000 stimuli per day (15,000 stimuli per week) in adults with unipolar depression not taking antidepressant medications. Several meta-analyses suggest a dose-response relationship with TMS. This study was carried out before US FDA approval to test the safety, tolerability, and effectiveness of adjunctive high-dose left prefrontal rTMS in a clinical setting with particular attention to safety of higher doses and potential interactions with antidepressant medications, speed of response, and effects on suicidality. Method: We enrolled 19 patients who were in a current major depressive episode with treatment-resistant unipolar or bipolar depression and treated them in their acute episode and in a maintenance fashion for 18 months. The patients received daily left prefrontal rTMS at 120% resting motor threshold, 10 Hz, 5 seconds on, and 10 seconds off and for a mean of 6800 stimuli per session (34,000 stimuli per week), more than twice the dose delivered in the pivotal FDA trial. All patients continued antidepressant medication throughout the rTMS treatment; thus rTMS was an adjunctive treatment. We measured adverse effects, depression, quality of life, suicidal ideation, and social and physical functioning. Results: These higher rTMS doses were well tolerated without significant adverse effects or adverse events. All measured dimensions showed improvement, with many showing improvement in 1 to 2 weeks. Of perhaps most importance, suicidal ideation diminished in 67% of the patients after just 1 week. Conclusions: These uncontrolled data suggest that higher doses of daily left prefrontal rTMS may safely be used in outpatients with major depressive episode even as an adjunctive treatment.

Fifteen minutes of left prefrontal repetitive transcranial magnetic stimulation acutely increases thermal pain thresholds in healthy adults

BACKGROUND Transcranial magnetic stimulation (TMS) of the motor cortex appears to alter pain perception in healthy adults and in patients with chronic neuropathic pain. There is, however, emerging brain imaging evidence that the left prefrontal cortex is involved in pain inhibition in humans. OBJECTIVE Because the prefrontal cortex may be involved in descending pain inhibitory systems, the present pilot study was conducted to investigate whether stimulation of the left prefrontal cortex via TMS might affect pain perception in healthy adults. METHODS Twenty healthy adults with no history of depression or chronic pain conditions volunteered to participate in a pilot laboratory study in which thermal pain thresholds were assessed before and after 15 min of repetitive TMS (rTMS) over the left prefrontal cortex (10 Hz, 100% resting motor threshold, 2 s on, 60 s off, 300 pulses total). Subjects were randomly assigned to receive either real or sham rTMS and were blind to condition. RESULTS Subjects who received real rTMS demonstrated a significant increase in thermal pain thresholds following TMS. Subjects receiving sham TMS experienced no change in pain threshold. CONCLUSIONS rTMS over the left prefrontal cortex increases thermal pain thresholds in healthy adults. Results from the present study support the idea that the left prefrontal cortex may be a promising TMS cortical target for the management of pain. More research is needed to establish the reliability of these findings, maximize the effect, determine the length of effect and elucidate possible mechanisms of action.

Postoperative left prefrontal repetitive transcranial magnetic stimulation reduces patient-controlled analgesia use.

Background:Several recent studies suggest that repetitive transcranial magnetic stimulation can temporarily reduce pain perception in neuropathic pain patients and in healthy adults using laboratory pain models. No studies have investigated the effects of prefrontal cortex stimulation using transcranial magnetic stimulation on postoperative pain. Methods:Twenty gastric bypass surgery patients were randomly assigned to receive 20 min of either active or sham left prefrontal repetitive transcranial magnetic stimulation immediately after surgery. Patient-controlled analgesia pump use was tracked, and patients also rated pain and mood twice per day using visual analog scales. Results:Groups were similar at baseline in terms of body mass index, age, mood ratings, pain ratings, surgery duration, time under anesthesia, and surgical anesthesia methods. Significant effects were observed for surgery type (open vs. laparoscopic) and condition (active vs. sham transcranial magnetic stimulation) on the cumulative amount of patient-delivered morphine during the 44 h after surgery. Active prefrontal repetitive transcranial magnetic stimulation was associated with a 40% reduction in total morphine use compared with sham during the 44 h after surgery. The effect seemed to be most prominent during the first 24 h after cortical stimulation delivery. No effects were observed for repetitive transcranial magnetic stimulation on mood ratings. Conclusions:A single session of postoperative prefrontal repetitive transcranial magnetic stimulation was associated with a reduction in patient-controlled analgesia pump use in gastric bypass surgery patients. This is important because the risks associated with postoperative morphine use are high, especially among obese patients who frequently have obstructive sleep apnea, right ventricular dysfunction, and pulmonary hypertension. These preliminary findings suggest a potential new noninvasive method for managing postoperative morphine use.

Intermittent "real-time" fMRI feedback is superior to continuous presentation for a motor imagery task: a pilot study.

Real‐time functional MRI feedback (RTfMRIf) is a developing technique, with unanswered methodological questions. Given a delay of seconds between neural activity and the measurable hemodynamic response, one issue is the optimal method for presentation of neurofeedback to subjects. The primary objective of this preliminary study was to compare the methods of continuous and intermittent presentation of neural feedback on targeted brain activity.