Publications by authors named "Xingbao Li"

57 Publications

Sonication of the anterior thalamus with MRI-Guided transcranial focused ultrasound (tFUS) alters pain thresholds in healthy adults: A double-blind, sham-controlled study.

Brain Stimul 2020 Nov - Dec;13(6):1805-1812. Epub 2020 Oct 24.

Department of Psychiatry & Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA; Ralph H. Johnson VA Medical Center, Charleston, SC, USA.

Background: Transcranial focused ultrasound (tFUS) is a noninvasive brain stimulation method that may modulate deep brain structures. This study investigates whether sonication of the right anterior thalamus would modulate thermal pain thresholds in healthy individuals.

Methods: We enrolled 19 healthy individuals in this three-visit, double-blind, sham-controlled, crossover trial. Participants first underwent a structural MRI scan used solely for tFUS targeting. They then attended two identical experimental tFUS visits (counterbalanced by condition) at least one week apart. Within the MRI scanner, participants received two, 10-min sessions of either active or sham tFUS spread 10 min apart targeting the right anterior thalamus [fundamental frequency: 650 kHz, Pulse repetition frequency: 10 Hz, Pulse Width: 5 ms, Duty Cycle: 5%, Sonication Duration: 30s, Inter-Sonication Interval: 30 s, Number of Sonications: 10, ISPTA. 995 mW/cm2, ISPTA. 719 mW/cm2, Peak rarefactional pressure 0.72 MPa]. The primary outcome measure was quantitative sensory thresholding (QST), measuring sensory, pain, and tolerance thresholds to a thermal stimulus applied to the left forearm before and after right anterior thalamic tFUS.

Results: The right anterior thalamus was accurately sonicated in 17 of the 19 subjects. Thermal pain sensitivity was significantly attenuated after active tFUS. The pre-post x active-sham interaction was significant (F(1,245.95) = 4.03, p = .046). This interaction indicates that in the sham stimulation condition, thermal pain thresholds decreased 1.08 °C (SE = 0.28) pre-post session, but only decreased .51 °C (SE = 0.30) pre-post session in the active stimulation group.

Conclusions: Two 10-min sessions of anterior thalamic tFUS induces antinociceptive effects in healthy individuals. Future studies should optimize the parameter space, dose and duration of this effect which may lead to multi-session tFUS interventions for pain disorders.
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http://dx.doi.org/10.1016/j.brs.2020.10.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888561PMC
October 2020

Synchronized cervical VNS with accelerated theta burst TMS for treatment resistant depression.

Brain Stimul 2020 Sep - Oct;13(5):1449-1450. Epub 2020 Aug 7.

Brain Stimulation Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, CA, USA.

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http://dx.doi.org/10.1016/j.brs.2020.08.002DOI Listing
August 2020

Two weeks of image-guided left dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation improves smoking cessation: A double-blind, sham-controlled, randomized clinical trial.

Brain Stimul 2020 Sep - Oct;13(5):1271-1279. Epub 2020 Jun 10.

Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, 29425, USA; Ralph H. Johnson VA Medical Center, Charleston, SC, 29401, USA.

Background: Previous studies have found that repetitive transcranial magnetic stimulation (rTMS) to the left dorsal lateral prefrontal cortex (LDLPFC) transiently reduces smoking craving, decreases cigarette consumption, and increases abstinence rates.

Objective: We investigated whether 10 daily MRI-guided rTMS sessions over two weeks to the LDLPFC paired with craving cues could reduce cigarette consumption and induce smoking cessation.

Methods: We enrolled 42 treatment-seeking nicotine-dependent smokers (≥10 cigarettes per day) in a randomized, double-blind, sham-controlled trial. Participants received 10 daily sessions over 2 weeks of either active or sham MRI-guided rTMS (10Hz, 3000 pulses each session) to the LDLPFC concurrently with video smoking cues. The primary outcome was a reduction in biochemically confirmed cigarette consumption with a secondary outcome of abstinence on the target quit date. We also recorded cue-induced craving and withdrawal symptoms.

Results: Compared to sham (n = 17), participants receiving active rTMS (n = 21) smoked significantly fewer cigarettes per day during the 2-week treatment (mean [SD], 13.73[9.18] vs. 11.06[9.29], P < .005) and at 1-month follow-up (12.78[9.53] vs. 7.93[7.24], P < .001). Active rTMS participants were also more likely to quit by their target quit rate (23.81%vs. 0%, OR 11.67, 90% CL, 0.96-141.32, x = 4.66, P = .031). Furthermore, rTMS significantly reduced mean craving throughout the treatments and at follow-up (29.93[13.12] vs. 25.01[14.45], P < .001). Interestingly across the active treatment sample, more lateral coil location was associated with more success in quitting (-43.43[0.40] vs. -41.79[2.24], P < .013).

Conclusions: Daily MRI-guided rTMS to the LDLPFC for 10 days reduces cigarette consumption and cued craving for up to one month and also increases the likelihood of smoking cessation.

Trial Registration: ClinicalTrials.gov identifier: NCT02401672.
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http://dx.doi.org/10.1016/j.brs.2020.06.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494651PMC
June 2020

Can transcranial electrical stimulation motor threshold estimate individualized tDCS doses over the prefrontal cortex? Evidence from reverse-calculation electric field modeling.

Brain Stimul 2020 Jul - Aug;13(4):1150-1152. Epub 2020 May 19.

Brain Stimulation Laboratory, Department of Psychiatry, Medical University of South Carolina, Charleston, SC, USA; Ralph H. Johnson VA Medical Center, Charleston, SC, USA.

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http://dx.doi.org/10.1016/j.brs.2020.05.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891110PMC
May 2020

Transcranial electrical stimulation motor threshold can estimate individualized tDCS dosage from reverse-calculation electric-field modeling.

Brain Stimul 2020 Jul - Aug;13(4):961-969. Epub 2020 Apr 21.

Brain Stimulation Laboratory, Department of Psychiatry, Medical University of South Carolina, Charleston, SC, USA; Ralph H. Johnson VA Medical Center, Charleston, SC, USA.

Background: Unique amongst brain stimulation tools, transcranial direct current stimulation (tDCS) currently lacks an easy or widely implemented method for individualizing dosage.

Objective: We developed a method of reverse-calculating electric-field (E-field) models based on Magnetic Resonance Imaging (MRI) scans that can estimate individualized tDCS dose. We also evaluated an MRI-free method of individualizing tDCS dose by measuring transcranial magnetic stimulation (TMS) motor threshold (MT) and single pulse, suprathreshold transcranial electrical stimulation (TES) MT and regressing it against E-field modeling. Key assumptions of reverse-calculation E-field modeling, including the size of region of interest (ROI) analysis and the linearity of multiple E-field models were also tested.

Methods: In 29 healthy adults, we acquired TMS MT, TES MT, and anatomical T1-weighted MPRAGE MRI scans with a fiducial marking the motor hotspot. We then computed a "reverse-calculated tDCS dose" of tDCS applied at the scalp needed to cause a 1.00 V/m E-field at the cortex. Finally, we examined whether the predicted E-field values correlated with each participant's measured TMS MT or TES MT.

Results: We were able to determine a reverse-calculated tDCS dose for each participant using a 5 × 5 x 5 voxel grid region of interest (ROI) approach (average = 6.03 mA, SD = 1.44 mA, range = 3.75-9.74 mA). The Transcranial Electrical Stimulation MT, but not the Transcranial Magnetic Stimulation MT, significantly correlated with the ROI-based reverse-calculated tDCS dose determined by E-field modeling (R = 0.45, p < 0.001).

Conclusions: Reverse-calculation E-field modeling, alone or regressed against TES MT, shows promise as a method to individualize tDCS dose. The large range of the reverse-calculated tDCS doses between subjects underscores the likely need to individualize tDCS dose. Future research should further examine the use of TES MT to individually dose tDCS as an MRI-free method of dosing tDCS.
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http://dx.doi.org/10.1016/j.brs.2020.04.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906246PMC
December 2020

Tolerability and feasibility of accelerated repetitive transcranial stimulation for reduction of nicotine craving.

Brain Stimul 2019 Sep - Oct;12(5):1315-1316. Epub 2019 Jun 20.

Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA; Ralph H. Johnson Veterans Administration Medical Center, Charleston, SC, USA.

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http://dx.doi.org/10.1016/j.brs.2019.06.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263463PMC
June 2019

Cortical substrates of cue-reactivity in multiple substance dependent populations: transdiagnostic relevance of the medial prefrontal cortex.

Transl Psychiatry 2018 09 7;8(1):186. Epub 2018 Sep 7.

Department of Psychiatry and Behavioral Sciences Medical, University of South Carolina, Charleston, SC, 29425, USA.

Elevated drug-cue elicited brain activity is one of the most widely cited, transdiagnostically relevant traits of substance dependent populations. These populations, however, are typically studied in isolation. The goal of this study was to prospectively investigate the spatial topography of drug-cue reactivity in a large set of individuals dependent on either cocaine, alcohol, or nicotine. Functional MRI data was acquired from 156 substance dependent individuals (55 cocaine, 53 alcohol, and 48 nicotine) as they performed a standardized drug-cue exposure task. Clusters of significant activation to drug-cues relative to neutral cues ('hot spots') were isolated for each individual. K-means clustering was used to classify the spatial topography of the hotspots in the data set. The percentage of hotspots that would be reached at several distances (2-5 cm) of transcranial magnetic stimulation (TMS) were calculated. One hundred and three participants had at least one cluster of significant frontal cortex activity (66%). K-means revealed 3 distinct clusters within the medial prefrontal cortex (MPFC), left inferior frontal gyrus/insula, right premotor cortex. For the group as a whole (and for alcohol users and nicotine users independently), medial prefrontal cortex (BA 10) was the location of the greatest number of hotspots. The frontal pole was cortical location closest to the largest percentage of hotspots. While there is individual variability in the location of the cue-elicited 'hot spot' these data demonstrate that elevated BOLD signal to drug cues in the MPFC may be a transdiagnostic endophenotype of addiction which may also be a fruitful neuromodulation target.
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http://dx.doi.org/10.1038/s41398-018-0220-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128822PMC
September 2018

Cigarette smoking and schizophrenia independently and reversibly altered intrinsic brain activity.

Brain Imaging Behav 2018 Oct;12(5):1457-1465

Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.

Schizophrenia patients are at high risk for cigarette smoking, but the neurobiological mechanisms of this comorbid association are relatively unknown. Long-term nicotine intake may impact brain that are independently and additively associated with schizophrenia. We investigated whether altered intrinsic brain activity (iBA) related to schizophrenia pathology is also associated with nicotine addiction. Forty-two schizophrenia patients (21 smokers and 21 nonsmokers) and 21 sex- and age-matched healthy nonsmokers underwent task-free functional MRI. Whole brain iBA was measured by the amplitude of spontaneous low frequency fluctuation. Furthermore, correlation analyses between iBA, symptom severity and nicotine addiction severity were performed. We found that prefrontal cortex, right caudate, and right postcentral gyrus were related to both disease and nicotine addiction effects. More importantly, schizophrenia smokers, compared to schizophrenia nonsmokers showed reversed iBA in the above brain regions. In addition, schizophrenia smokers, relative to nonsmokers, altered iBA in the left striatal and motor cortices. The iBA of the right caudate was negatively correlated with symptom severity. The iBA of the right postcentral gyrus negatively correlated with nicotine addiction severity. The striatal and motor cortices could potentially increase the vulnerability of smoking in schizophrenia. More importantly, smoking reversed iBA in the right striatal and prefrontal cortices, consistent with the self-medication theory in schizophrenia. Smoking altered left striatal and motor cortices activity, suggesting that the nicotine addiction effect was independent of disease. These results provide a local property of intrinsic brain activity mechanism that contributes to cigarette smoking and schizophrenia.
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http://dx.doi.org/10.1007/s11682-017-9806-8DOI Listing
October 2018

Transcranial magnetic stimulation of the dorsal lateral prefrontal cortex inhibits medial orbitofrontal activity in smokers.

Am J Addict 2017 Dec 12;26(8):788-794. Epub 2017 Sep 12.

Brain Stimulation Division, Department of Psychiatry, Medical University of South Carolina, Charleston, South Carolina.

Background And Objective: Several studies have shown that repetitive transcranial magnetic stimulation (rTMS), applied to the dorsolateral prefrontal cortex (DLPFC), can reduce cue-elicited craving in smokers. Currently, the mechanism of this effect is unknown. We used functional magnetic resonance imaging (fMRI) to explore the effect of a single treatment of rTMS on cortical and sub-cortical neural activity in non-treatment seeking nicotine-dependent participants.

Methods: We conducted a randomized, counterbalanced, crossover trial in which participants attended two experimental visits separated by at least 1 week. On the first visit, participants received either active, or sham rTMS (10 Hz, 5 s-on, 10 s-off, 100% motor threshold, 3,000 pulses) over the left DLPFC, and on the second visit they received the opposite condition (active or sham). Cue craving fMRI scans were completed before and after each rTMS session.

Results: A total of 11 non-treatment seeking nicotine-dependent cigarette smokers were enrolled in the study [six female, average age 39.7 ± 13.2, average cigarettes per day 17.3 ± 5.9]. Active rTMS decreased activity in the contralateral medial orbitofrontal cortex (mOFC) and ipsilateral nucleus accumbens (NAc) compared to sham rTMS.

Conclusions: This preliminary data suggests that one session of rTMS applied to the DLPFC decreases brain activity in the NAc and mOFC in smokers.

Scientific Significance: rTMS may exert its anti-craving effect by decreasing activity in the NAc and mOFC in smokers. Despite a small sample size, these findings warrant future rTMS/fMRI studies in addictions. (Am J Addict 2017;26:788-794).
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http://dx.doi.org/10.1111/ajad.12621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5699931PMC
December 2017

Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex reduces resting-state insula activity and modulates functional connectivity of the orbitofrontal cortex in cigarette smokers.

Drug Alcohol Depend 2017 05 28;174:98-105. Epub 2017 Feb 28.

Brain Stimulation Division, Department of Psychiatry, Medical University of South Carolina, Charleston, SC, 29425, USA; Center for Biomedical Imaging, Medical University of South Carolina, Charleston, SC, 29425, USA; Ralph H. Johnson VA Medical Center, Charleston, SC, 29425, USA.

Background: Previous studies reported that repetitive transcranial magnetic stimulation (rTMS) can reduce cue-elicited craving and decrease cigarette consumption in smokers. The mechanism of this effect however, remains unclear. We used resting-state functional magnetic resonance imaging (rsfMRI) to test the effect of rTMS in non-treatment seeking smokers.

Methods: We used a single blinded, sham-controlled, randomized counterbalanced crossover design where participants underwent two visits separated by at least 1 week. Participants received active rTMS over the left dorsolateral prefrontal cortex (DLPFC) during one of their visits, and sham rTMS during their other visit. They had two rsFMRI scans before and after each rTMS session. We used the same rTMS stimulation parameters as in a previous study (10Hz, 5s-on, 10s-off, 100% resting motor threshold, 3000 pulses).

Results: Ten non-treatment-seeking, nicotine-dependent, cigarette smokers (6 women, an average age of 39.72 and an average cigarette per day of 17.30) finished the study. rsFMRI results demonstrate that as compared to a single session of sham rTMS, a single session of active rTMS inhibits brain activity in the right insula and thalamus in fractional amplitude of low frequency fluctuation (fALFF). For intrinsic brain connectivity comparisons, active TMS resulted in significantly decreased connectivity from the site of rTMS to the left orbitomedial prefrontal cortex.

Conclusions: This data suggests that one session of rTMS can reduce activity in the right insula and right thalamus as measured by fALFF. The data also demonstrates that rTMS can reduce rsFC between the left DLPFC and the medial orbitofrontal cortex.
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http://dx.doi.org/10.1016/j.drugalcdep.2017.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5400684PMC
May 2017

Regional Brain Activity in Abstinent Methamphetamine Dependent Males Following Cue Exposure.

J Drug Abuse 2016;2(1). Epub 2016 Feb 19.

Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA.

Background: Neuroimaging of drug-associated cue presentations has aided in understanding the neurobiological substrates of craving and relapse for cocaine, alcohol, and nicotine. However, imaging of cue-reactivity in methamphetamine addiction has been much less studied.

Method: Nine caucasian male methamphetamine-dependent subjects and nine healthy controls were scanned in a Phillips 3.0T MRI scan when they viewed a randomized presentation of visual cues of methamphetamine, neutral objects, and rest conditions. Functional Imaging data were analyzed with Statistical Parametric Mapping software 5 (SPM 5).

Results: Methamphetamine subjects had significant brain activation in the ventral striatum and medial frontal cortex in comparison to meth pictures and neutral pictures in healthy controls (p<0.005, threshold 15 voxels). Interestingly the ventral striatum activation significantly correlated with the days since the last use of meth (r=-0.76, p=0.017). No significant activity was found in healthy control group.

Conclusion: The preliminary data suggest that methamphetamine dependent subjects, when exposed to methamphetamine-associated visual cues, have increased brain activity in ventral striatum, caudate nucleus and medial frontal cortex which subserve craving, drug-seeking, and drug use.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907368PMC
http://dx.doi.org/10.21767/2471-853x.100016DOI Listing
February 2016

Antidepressant Effects of Electroconvulsive Therapy Correlate With Subgenual Anterior Cingulate Activity and Connectivity in Depression.

Medicine (Baltimore) 2015 Nov;94(45):e2033

From the Department of Radiology (YL, YL); Department of Psychiatry, the First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China (LD, WZ, DL, JZ, YF, HQ, XL, TQ, HH, HM, QL); Department of Psychiatry Brain Stimulation Laboratory, Medical University of South Carolina, Charleston, SC (LD, XL); and Medical Psychology Department, the Third Military Medical University third hospital, Chongqing, P.R. China (HL).

The mechanisms underlying the effects of electroconvulsive therapy (ECT) in major depressive disorder (MDD) are not fully understood. Resting-state functional magnetic resonance imaging (rs-fMRI) is a new tool to study the effects of brain stimulation interventions, particularly ECT. The authors aim to investigate the mechanisms of ECT in MDD by rs-fMRI.They used rs-fMRI to measure functional changes in the brain of first-episode, treatment-naive MDD patients (n = 23) immediately before and then following 8 ECT sessions (brief-pulse square-wave apparatus, bitemporal). They also computed voxel-wise amplitude of low-frequency fluctuation (ALFF) as a measure of regional brain activity and selected the left subgenual anterior cingulate cortex (sgACC) to evaluate functional connectivity between the sgACC and other brain regions.Increased regional brain activity measured by ALFF mainly in the left sgACC following ECT. Functional connectivity of the left sgACC increased in the ipsilateral parahippocampal gyrus, pregenual ACC, contralateral middle temporal pole, and orbitofrontal cortex. Importantly, reduction in depressive symptoms were negatively correlated with increased ALFF in the left sgACC and left hippocampus, and with distant functional connectivity between the left sgACC and contralateral middle temporal pole. That is, across subjects, as depression improved, regional brain activity in sgACC and its functional connectivity increased in the brain.Eight ECT sessions in MDD patients modulated activity in the sgACC and its networks. The antidepressant effects of ECT were negatively correlated with sgACC brain activity and connectivity. These findings suggest that sgACC-associated prefrontal-limbic structures are associated with the therapeutic effects of ECT in MDD.
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http://dx.doi.org/10.1097/MD.0000000000002033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912303PMC
November 2015

A comprehensive study of sensorimotor cortex excitability in chronic cocaine users: Integrating TMS and functional MRI data.

Drug Alcohol Depend 2015 Dec 26;157:28-35. Epub 2015 Sep 26.

Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, United States; Ralph H. Johnson VA Medical Center, Charleston, SC, United States.

Background: Disruptions in motor control are often overlooked features of chronic cocaine users. During a simple sensorimotor integration task, for example, cocaine users activate a larger area of cortex than controls but have lower functional connectivity between the cortex and dorsal striatum, which is further correlated with poor performance. The purpose of this study was to determine whether abnormal cortical excitability in cocaine users was related to disrupted inhibitory or excitatory mechanisms, as measured by transcranial magnetic stimulation (TMS).

Methods: A battery of TMS measures were acquired from 87 individuals (50 cocaine dependent, 37 controls). Functional MRI data were acquired from a subset of 28 individuals who performed a block-design finger tapping task.

Results: TMS measures revealed that cocaine users had significantly higher resting motor thresholds and higher intracortical cortical facilitation (ICF) than controls. There was no between-group difference in either measure of cortical inhibition. Task-evoked BOLD signal in the motor cortex was significantly correlated with ICF in the cocaine users. There was no significant difference in brain-skull distance between groups.

Conclusion: These data demonstrated that cocaine users have disrupted cortical facilitation (as measured with TMS), which is related to elevated BOLD signal. Cortical inhibition, however, is largely intact. Given the relationship between ICF and glutamatergic agents, this may be a potentially fruitful and treatable target in addiction. Finally, among controls the distance from the scalp to the cortex was correlated with the motor threshold which may be a useful parameter to integrate into therapeutic TMS protocols in the future.
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http://dx.doi.org/10.1016/j.drugalcdep.2015.07.1196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4899825PMC
December 2015

Individualized real-time fMRI neurofeedback to attenuate craving in nicotine-dependent smokers.

J Psychiatry Neurosci 2016 Jan;41(1):48-55

From the Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC (Hartwell, Hanlon, Li, Borckardt, Canterberry, Priscriandaro, Maria, LeMatty, George, Brady); and the Ralph H. Johnson VA Medical Center, Charleston, SC (Hartwell, George, Brady).

Background: Cue-induced craving plays an important role in relapse, and the neural correlates of cue-induced craving have been elucidated using fMRI. This study examined the utility of real-time fMRI (rtfMRI) neurofeedback to strengthen self-regulation of craving-related neural activation and cue-reactivity in cigarette smokers.

Methods: Nicotine-dependent smokers were randomized to rtfMRI neurofeedback or to a no-feedback control group. Participants completed 3 neuroimaging visits. Within each visit, an initial run during which smoking-related cues were used to provoke craving, an individualized craving-related region of interest (ROI) in the prefrontal cortex or anterior cingulate cortex was identified. In the rtfMRI group, activity from the ROI was fed back via a visual display during 3 subsequent runs while participants were instructed to reduce craving during cue exposure. The control group had an identical experience with no feedback provided.

Results: Forty-four nicotine-dependent smokers were recruited to participate in our study; data from the 33 participants who completed a 1-week follow-up visit were included in the analysis. Subjective craving ratings and cue-induced brain activation were lower in the rtfMRI group than in the control group.

Limitations: As participants were not seeking treatment, clinical outcomes are lacking.

Conclusion: Nicotine-dependent smokers receiving rtfMRI feedback from an individualized ROI attenuated smoking cue-elicited neural activation and craving, relative to a control group. Further studies are needed in treatment-seeking smokers to determine if this intervention can translate into a clinically meaningful treatment modality.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688028PMC
http://dx.doi.org/10.1503/jpn.140200DOI Listing
January 2016

Safe management of a bipolar depressed patient with prefrontal repetitive transcranial magnetic stimulation (rTMS) Over 7 years and >2 million stimuli.

Brain Stimul 2014 Nov-Dec;7(6):919-21. Epub 2014 Oct 7.

Brain Stimulation Division, Department of Psychiatry, Medical University of South Carolina, Charleston, SC, USA; Department of Radiology, Medical University of South Carolina, Charleston, SC, USA; Ralph H. Johnson VA Medical Center, Charleston, SC, USA.

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http://dx.doi.org/10.1016/j.brs.2014.09.005DOI Listing
September 2015

Varenicline effects on drinking, craving and neural reward processing among non-treatment-seeking alcohol-dependent individuals.

Psychopharmacology (Berl) 2014 Sep 20;231(18):3799-807. Epub 2014 Mar 20.

Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, 29425, USA,

Rationale: The α4β2 nicotinic acetylcholine receptor partial agonist varenicline has been reported to reduce drinking among both heavy-drinking smokers and primary alcoholics, and this effect may be related to varenicline-mediated reduction of alcohol craving. Among smokers, varenicline has been reported to modulate cigarette cue-elicited brain activation in several reward-related areas.

Objectives: This pilot study tested varenicline's effects on drinking, alcohol craving, and alcohol cue-elicited activation of reward-related brain areas among non-treatment-seeking alcohol-dependent individuals.

Methods: Thirty-five such individuals (mean age = 30, 57 % male, 76 % heavy drinking days in the past month, 15 smokers) were randomized to either varenicline (titrated to 2 mg) or placebo for 14 days, and were administered an alcohol cue reactivity fMRI task on day 14. A priori regions of interest (ROIs) were bilateral and medial orbitofrontal cortex (OFC), right ventral striatum (VS), and medial prefrontal cortex (mPFC).

Results: Despite good medication adherence, varenicline did not reduce heavy drinking days or other drinking parameters. It did, however, increase self-reported control over alcohol-related thoughts and reduced cue-elicited activation bilaterally in the OFC, but not in other brain areas.

Conclusions: These data indicate that varenicline reduces alcohol craving and some of the neural substrates of alcohol cue reactivity. However, varenicline effects on drinking mediated by cue-elicited brain activation and craving might be best observed among treatment-seekers motivated to reduce their alcohol consumption.
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http://dx.doi.org/10.1007/s00213-014-3518-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4146648PMC
September 2014

Suzuki-Miyaura cross-coupling of bulky anthracenyl carboxylates by using pincer nickel N-heterocyclic carbene complexes: an efficient protocol to access fluorescent anthracene derivatives.

Chem Commun (Camb) 2013 Dec;49(98):11539-41

Department of Chemistry, Fudan University, 220 Handan Road, 200433, Shanghai, China.

A series of fluorescent (hetero)-aryl substituted anthracene derivatives were readily accessible from the corresponding bulky anthracen-9-yl carboxylates via Suzuki-Miyaura cross-coupling reactions by using pincer nickel N-heterocyclic carbene complex even at the catalyst loading as low as 0.1 mol% in the presence of catalytic amounts of PCy3.
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http://dx.doi.org/10.1039/c3cc46663aDOI Listing
December 2013

Low frequency repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex transiently increases cue-induced craving for methamphetamine: a preliminary study.

Drug Alcohol Depend 2013 Dec 26;133(2):641-6. Epub 2013 Aug 26.

Medical University of South Carolina, United States. Electronic address:

Background: Repetitive transcranial magnetic stimulation (rTMS) can temporarily interrupt or facilitate activity in a focal brain region. Several lines of evidence suggest that rTMS of the dorsolateral prefrontal cortex (DLPFC) can affect processes involved in drug addiction. We hypothesized that a single session of low-frequency rTMS of the left DLPFC would modulate cue-induced craving for methamphetamine (MA) when compared to a sham rTMS session.

Methods: In this single-blind, sham-controlled crossover study, 10 non-treatment seeking MA-dependent users and 8 healthy controls were randomized to receive 15 min of sham and real (1 Hz) DLPFC rTMS in two experimental sessions separated by 1h. During each rTMS session, participants were exposed to blocks of neutral cues and MA-associated cues. Participants rated their craving after each cue block.

Results: In MA users, real rTMS over the left DLPFC increased self-reported craving as compared to sham stimulation (17.86 ± 1.46 vs. 24.85 ± 1.57, p=0.001). rTMS had no effect on craving in healthy controls. One Hertz rTMS of the left DLPFC was safe and tolerable for all participants.

Conclusions: Low frequency rTMS of the left DLPFC transiently increased cue-induced craving in MA participants. These preliminary results suggest that 1 Hz rTMS of the left DLPFC may increase craving by inhibiting the prefrontal cortex or indirectly activating subcortical regions involved in craving.
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http://dx.doi.org/10.1016/j.drugalcdep.2013.08.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196687PMC
December 2013

Sustained reduction of nicotine craving with real-time neurofeedback: exploring the role of severity of dependence.

Nicotine Tob Res 2013 Dec 9;15(12):2120-4. Epub 2013 Aug 9.

Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC;

Background: Neurofeedback delivered via real-time functional magnetic resonance imaging (rtfMRI) is a promising therapeutic technique being explored to facilitate self-regulation of craving in nicotine-dependent cigarette smokers. The current study examined the role of nicotine-dependence severity and the efficacy of multiple visits of neurofeedback from a single region of interest (ROI) in the anterior cingulate cortex (ACC) on craving reduction.

Methods: Nine nicotine-dependent cigarette smokers participated in three rtfMRI visits that examined cue-induced craving and brain activation. Severity of nicotine dependence was assessed with the Fagerström Test for Nicotine Dependence. When viewing smoking-related images with instructions to "crave," patient-tailored ROIs were generated in the vicinity of the ACC. Activity levels from the ROI were fed back while participants viewed smoking cues with the instruction to reduce craving.

Results: Neurofeedback from a single ROI in the ACC led to consistent decreases in self-reported craving and activation in the ACC across the three visits. Dependence severity predicted response to neurofeedback at Visit 3.

Conclusions: This study builds upon previous rtfMRI studies on the regulation of nicotine craving in demonstrating that feedback from the ACC can reduce activation to smoking cues across three separate visits. Individuals with lower nicotine-dependence severity were more successful in reducing ACC activation over time. These data highlight the need to consider dependence severity in developing more individualized neurofeedback methods.
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http://dx.doi.org/10.1093/ntr/ntt122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3819983PMC
December 2013

Probing the frontostriatal loops involved in executive and limbic processing via interleaved TMS and functional MRI at two prefrontal locations: a pilot study.

PLoS One 2013 9;8(7):e67917. Epub 2013 Jul 9.

Department of Psychiatry, Medical University of South Carolina, Charleston, South Carolina, United States of America.

Background: The prefrontal cortex (PFC) is an anatomically and functionally heterogeneous area which influences cognitive and limbic processing through connectivity to subcortical targets. As proposed by Alexander et al. (1986) the lateral and medial aspects of the PFC project to distinct areas of the striatum in parallel but functionally distinct circuits. The purpose of this preliminary study was to determine if we could differentially and consistently activate these lateral and medial cortical-subcortical circuits involved in executive and limbic processing though interleaved transcranial magnetic stimulation (TMS) in the MR environment.

Methods: Seventeen healthy individuals received interleaved TMS-BOLD imaging with the coil positioned over the dorsolateral (EEG: F3) and ventromedial PFC (EEG: FP1). BOLD signal change was calculated in the areas directly stimulated by the coil and in subcortical regions with afferent and efferent connectivity to the TMS target areas. Additionally, five individuals were tested on two occasions to determine test-retest reliability.

Results: Region of interest analysis revealed that TMS at both prefrontal sites led to significant BOLD signal increases in the cortex under the coil, in the striatum, and the thalamus, but not in the visual cortex (negative control region). There was a significantly larger BOLD signal change in the caudate following medial PFC TMS, relative to lateral TMS. The hippocampus in contrast was significantly more activated by lateral TMS. Post-hoc voxel-based analysis revealed that within the caudate the location of peak activity was in the ventral caudate following medial TMS and the dorsal caudate following lateral TMS. Test-retest reliability data revealed consistent BOLD responses to TMS within each individual but a large variation between individuals.

Conclusion: These data demonstrate that, through an optimized TMS/BOLD sequence over two unique prefrontal targets, it is possible to selectively interrogate the patency of these established cortical-subcortical networks in healthy individuals, and potentially patient populations.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0067917PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3706588PMC
February 2014

Reduction of cue-induced craving through realtime neurofeedback in nicotine users: the role of region of interest selection and multiple visits.

Psychiatry Res 2013 Jul 15;213(1):79-81. Epub 2013 May 15.

Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC 29425, USA.

This multi-visit, real-time functional magnetic resonance imaging feedback study demonstrates that treatment-seeking smokers can effectively modulate their behavioral and brain responses to smoking cues. They are more effective at decreasing activity in functionally defined regions involved in "craving" (e.g. ventral anterior cingulate cortex (vACC)) rather than increasing activity in regions involved in "resisting" (e.g. dorsal medial prefrontal cortex (dmPFC)).
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http://dx.doi.org/10.1016/j.pscychresns.2013.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4093788PMC
July 2013

Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex reduces nicotine cue craving.

Biol Psychiatry 2013 Apr 26;73(8):714-20. Epub 2013 Feb 26.

Medical University of South Carolina, Charleston, SC 29425, USA.

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.
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http://dx.doi.org/10.1016/j.biopsych.2013.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3615051PMC
April 2013

Effects of a GABA-ergic medication combination and initial alcohol withdrawal severity on cue-elicited brain activation among treatment-seeking alcoholics.

Psychopharmacology (Berl) 2013 Jun 7;227(4):627-37. Epub 2013 Feb 7.

Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC 29425, USA.

Rationale: Many studies have reported medication effects on alcohol cue-elicited brain activation or associations between such activation and subsequent drinking. However, few have combined the methodological rigor of a randomized clinical trial (RCT) with follow-up assessments to determine whether cue-elicited activation predicts relapse during treatment, the crux of alcoholism.

Objectives: This study analyzed functional magnetic resonance imaging (fMRI) data from 48 alcohol-dependent subjects enrolled in a 6-week RCT of an investigational pharmacotherapy.

Methods: Subjects were randomized, based on their level of alcohol withdrawal (AW) at study entry, to receive either a combination of gabapentin (GBP; up to 1,200 mg for 39 days) and flumazenil (FMZ) infusions (2 days) or two placebos. Midway through the RCT, subjects were administered an fMRI alcohol cue reactivity task.

Results: There were no main effects of medication or initial AW status on cue-elicited activation, but these factors interacted, such that the GBP/FMZ/higher AW and placebo/lower AW groups, which had previously been shown to have relatively reduced drinking, demonstrated greater dorsal anterior cingulate cortex (dACC) activation to alcohol cues. Further analysis suggested that this finding represented differences in task-related deactivation and was associated with greater control over alcohol-related thoughts. Among study completers, regardless of medication or AW status, greater left dorsolateral prefrontal cortex (DLPFC) activation predicted more post-scan heavy drinking.

Conclusions: These data suggest that alterations in task-related deactivation of dACC, a component of the default mode network, may predict better alcohol treatment response, while activation of DLPFC, an area associated with selective attention, may predict relapse drinking.
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http://dx.doi.org/10.1007/s00213-013-2996-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664140PMC
June 2013

Naloxone-reversible modulation of pain circuitry by left prefrontal rTMS.

Neuropsychopharmacology 2013 Jun 11;38(7):1189-97. Epub 2013 Jan 11.

Brain Stimulation Laboratory, Department of Psychiatry, Medical University of South Carolina, Charleston, SC 29414, USA.

A 20-minute session of 10 Hz repetitive transcranial magnetic stimulation (rTMS) of Brodmann Area (BA) nine of the left dorsolateral prefrontal cortex (DLPFC) can produce analgesic effects on postoperative and laboratory-induced pain. This analgesia is blocked by pretreatment with naloxone, a μ-opioid antagonist. The purpose of this sham-controlled, double-blind, crossover study was to identify the neural circuitry that underlies the analgesic effects of left DLPFC rTMS, and to examine how the function of this circuit, including midbrain and medulla, changes during opioid blockade. Fourteen healthy volunteers were randomized to receive intravenous saline or naloxone immediately before sham and real left DLPFC rTMS on the same experimental visit. One week later, each participant received the novel pretreatment but the same stimulation paradigm. Using short sessions of heat on capsaicin-sensitized skin, hot allodynia was assessed during 3 Tesla functional magnetic resonance imaging (fMRI) scanning at baseline, post-sham rTMS, and post-real rTMS. Data were analyzed using whole-brain voxel-based analysis, as well as time series extractions from anatomically-defined regions of interest representing midbrain and medulla. Consistent with previous findings, real rTMS significantly reduced hot allodynia pain ratings. This analgesia was associated with elevated blood oxygenation-level dependent (BOLD) signal in BAs 9 and 10, and diminished BOLD signal in the anterior cingulate, thalamus, midbrain, and medulla during pain. Naloxone pretreatment largely abolished rTMS-induced analgesia, as well as rTMS-induced attenuation of BOLD signal response to painful stimuli throughout pain processing regions, including midbrain and medulla. These preliminary results suggest that left DLPFC rTMS drives top-down opioidergic analgesia.
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http://dx.doi.org/10.1038/npp.2013.13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3656361PMC
June 2013

Imaging the neural mechanisms of TMS neglect-like bias in healthy volunteers with the interleaved TMS/fMRI technique: preliminary evidence.

Front Hum Neurosci 2012 17;6:326. Epub 2012 Dec 17.

Brain Stimulation Laboratory, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina Charleston, SC, USA ; Department of Psychology and Neuroscience Institute of Turin, University of Turin Turin, Italy.

Applying a precisely timed pulse of transcranial magnetic stimulation (TMS) over the right posterior parietal cortex (PPC) can produce temporary visuo-spatial neglect-like effects. Although the TMS is applied over PPC, it is not clear what other brain regions are involved. We applied TMS within a functional magnetic resonance imaging (fMRI) scanner to investigate brain activity during TMS induction of neglect-like bias in three healthy volunteers, while they performed a line bisection judgment task (i.e., the landmark task). Single-pulse TMS at 115% of motor threshold was applied 150 ms after the visual stimulus onset. Participants completed two different TMS/fMRI sessions while performing this task: one session while single-pulse TMS was intermittently and time-locked applied to the right PPC and a control session with TMS positioned over the vertex. Perceptual rightward bias was observed when TMS was delivered over the right PPC. During neglect-like behavior, the fMRI maps showed decreased neural activity within parieto-frontal areas, which are often lesioned or dysfunctional in patients with left neglect. Vertex TMS induced behavioral effects compatible with leftward response bias and increased BOLD signal in the left caudate (a site which has been linked to response bias). These results are discussed in relation to recent findings on neural networks subserving attention in space.
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http://dx.doi.org/10.3389/fnhum.2012.00326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3523259PMC
December 2012

Interacting effects of naltrexone and OPRM1 and DAT1 variation on the neural response to alcohol cues.

Neuropsychopharmacology 2013 Feb 3;38(3):414-22. Epub 2012 Oct 3.

Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC 29425, USA.

Variation at a single nucleotide polymorphism in the μ-opioid receptor gene (OPRM1), A118G (Asn40Asp), may moderate naltrexone (NTX) effects in alcohol dependence. Both NTX and A118G variation have also been reported to affect alcohol cue-elicited brain activation. This study investigated whether sub-acute NTX treatment and A118G genotype interacted in their effects on cue-elicited activation of the ventral striatum (VS), medial prefrontal cortex (mPFC), and orbitofrontal cortex (OFC). Secondarily, variation at a variable number tandem repeat polymorphism in the dopamine transporter gene (DAT1/SLC6A3), which has been associated with increased reward-related activation in VS, was analyzed as a moderator of medication and A118G effects. Seventy-four non-treatment-seeking alcohol-dependent individuals, half preselected to carry at least one copy of the A118G G (Asp) allele, were randomized to NTX (50 mg) or placebo for 7 days, and performed an fMRI alcohol cue reactivity task on day 6. Region-of-interest analyses indicated no main effects of medication or A118G genotype. However, these factors interacted in their effects on OFC activation, such that, among NTX-treated individuals, G-allele carriers had less activation than A-allele homozygotes. DAT1 variation also moderated medication/A118G effects. There was a three-way interaction between medication and A118G and DAT1 genotypes on VS activation, such that, among G-allele carriers who received NTX, DAT1 10-repeat-allele (10R) homozygotes had less activation than 9-repeat-allele (9R) carriers. Further, 10R homozygotes who received NTX had less mPFC activation than 9R carriers. Polymorphic variation in OPRM1 and DAT1 should be considered in future studies of NTX, particularly regarding its effects on reward processing.
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http://dx.doi.org/10.1038/npp.2012.195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3547192PMC
February 2013

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

Psychol Addict Behav 2013 Jun 7;27(2):501-9. Epub 2012 May 7.

Department of Psychiatry, Medical University of South Carolina, Charleston, SC 29425, USA.

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.
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http://dx.doi.org/10.1037/a0028215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646943PMC
June 2013

Prefrontal rTMS for treating depression: location and intensity results from the OPT-TMS multi-site clinical trial.

Brain Stimul 2013 Mar 14;6(2):108-17. Epub 2012 Mar 14.

Medical University of South Carolina, USA.

Background: Motor cortex localization and motor threshold determination often guide Transcranial Magnetic Stimulation (TMS) placement and intensity settings for non-motor brain stimulation. However, anatomic variability results in variability of placement and effective intensity.

Objective: Post-study analysis of the OPT-TMS Study reviewed both the final positioning and the effective intensity of stimulation (accounting for relative prefrontal scalp-cortex distances).

Methods: We acquired MRI scans of 185 patients in a multi-site trial of left prefrontal TMS for depression. Scans had marked motor sites (localized with TMS) and marked prefrontal sites (5 cm anterior of motor cortex by the "5 cm rule"). Based on a visual determination made before the first treatment, TMS therapy occurred either at the 5 cm location or was adjusted 1 cm forward. Stimulation intensity was 120% of resting motor threshold.

Results: The "5 cm rule" would have placed stimulation in premotor cortex for 9% of patients, which was reduced to 4% with adjustments. We did not find a statistically significant effect of positioning on remission, but no patients with premotor stimulation achieved remission (0/7). Effective stimulation ranged from 93 to 156% of motor threshold, and no seizures were induced across this range. Patients experienced remission with effective stimulation intensity ranging from 93 to 146% of motor threshold, and we did not find a significant effect of effective intensity on remission.

Conclusions: Our data indicates that individualized positioning methods are useful to reduce variability in placement. Stimulation at 120% of motor threshold, unadjusted for scalp-cortex distances, appears safe for a broad range of patients.
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http://dx.doi.org/10.1016/j.brs.2012.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3573221PMC
March 2013

Individual variability in the locus of prefrontal craving for nicotine: implications for brain stimulation studies and treatments.

Drug Alcohol Depend 2012 Oct 28;125(3):239-43. Epub 2012 Mar 28.

Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC 29425, USA.

Background: Attenuation of cue-elicited craving with brain stimulation techniques is a growing area of attention in addiction research. This investigation aims to guide these studies by assessing individual variability in the location of peak cortical activity during cue-elicited craving.

Method: Twenty-six nicotine-dependent individuals performed a cue-elicited craving task in a 3T MRI scanner while BOLD signal data was collected. The task included epochs of smoking cues, neutral cues, and rest. The location of peak activity during smoking cues relative to neutral cues ('hot spot') was isolated for each individual. The spatial dispersion of the 26 cue-elicited hot spots (1 per participant) was quantified via hierarchical clustering.

Results: When viewing nicotine cues all 26 participants had at least one cluster of significant prefrontal cortex activity (p<0.05, cluster corrected). Only 62% had peak activity in the medial prefrontal cortex cluster (including 100% of the men). In 15% of the participants peak activity was located in either the left lateral prefrontal cortex or left insula cluster. Peak activity in the remaining 23% was dispersed throughout the prefrontal cortex.

Conclusion: There is considerable individual variability in the location of the cue-elicited 'hot spot' as measured by BOLD activity. Men appear to have a more uniform location of peak BOLD response to cues than women. Consequently, acquiring individual functional imaging data may be advantageous for either tailoring treatment to the individual or filtering participants before enrollment in treatment.
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http://dx.doi.org/10.1016/j.drugalcdep.2012.02.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3499028PMC
October 2012

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

Addict Biol 2013 Jul 28;18(4):739-48. Epub 2012 Mar 28.

Department of Psychiatry, Medical University of South Carolina, Charleston, SC 29425, USA.

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.
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http://dx.doi.org/10.1111/j.1369-1600.2012.00449.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3389595PMC
July 2013