Daniel McCalley

All Publications

• The importance of overlap: A retrospective analysis of electrical field maps, alcohol cue-reactivity patterns, and treatment outcomes for alcohol use disorder. Brain stimulation McCalley, D. M., Hanlon, C. A. 2023

  View details for DOI 10.1016/j.brs.2023.04.015

  View details for PubMedID 37088452

• Sex/Gender as a Factor That Influences Transcranial Magnetic Stimulation Treatment Outcome: Three Potential Biological Explanations FRONTIERS IN PSYCHIATRY Hanlon, C. A., McCalley, D. M. 2022; 13: 869070

  Abstract

  Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique which is now being used in psychiatry clinics across the world as a therapeutic tool for a variety of neural-circuit based disorders (e.g., major depression, obsessive compulsive disorder, substance use disorders, post-traumatic stress disorder, headache, pain). The higher volume of use and publication of multiple large-scale clinical trials has provided researchers with a unique opportunity to retrospectively evaluate factors influencing TMS treatment responses in large samples of patients. While many studies have focused on TMS protocol parameters as moderators of treatment efficacy, sex/gender is another critical, often overlooked factor influencing TMS treatment outcome. Women, especially during periods of high estradiol, appear to be particularly sensitive to the therapeutic effects of rTMS. This manuscript makes a case for three potential biological explanations for these findings. Drawing on literature from cranio-facial anatomy, neuroimaging, and neuroendocrine fields, we posit that observed increases in response rates of women in clinical rTMS trials may be related to: (1) Closer proximity of the brain to the scalp at the prefrontal cortex, leading to larger TMS induced electric fields especially at the medial prefrontal cortex, (2) Greater gray matter density and gyrification in the prefrontal cortex, and (3) High levels of estradiol which facilitate cortical excitability. These biological explanations are empirical ideas which have been evaluated in laboratory studies and lend themselves to prospective evaluation in multisite clinical rTMS trials. The existing literature on this topic and these three potential biological explanations all indicate that the TMS field should routinely evaluate sex/gender (and associated biological metrics like scalp-to-cortex distance, gray matter density, estradiol/progesterone levels) as a factor that may influence treatment outcome.

  View details for DOI 10.3389/fpsyt.2022.869070

  View details for Web of Science ID 000795105600001

  View details for PubMedID 35573331

  View details for PubMedCentralID PMC9098922

• Targeting the Salience Network: A Mini-Review on a Novel Neuromodulation Approach for Treating Alcohol Use Disorder. Frontiers in psychiatry Padula, C. B., Tenekedjieva, L., McCalley, D. M., Al-Dasouqi, H., Hanlon, C. A., Williams, L. M., Kozel, F. A., Knutson, B., Durazzo, T. C., Yesavage, J. A., Madore, M. R. 2022; 13: 893833

  Abstract

  Alcohol use disorder (AUD) continues to be challenging to treat despite the best available interventions, with two-thirds of individuals going on to relapse by 1 year after treatment. Recent advances in the brain-based conceptual framework of addiction have allowed the field to pivot into a neuromodulation approach to intervention for these devastative disorders. Small trials of repetitive transcranial magnetic stimulation (rTMS) have used protocols developed for other psychiatric conditions and applied them to those with addiction with modest efficacy. Recent evidence suggests that a TMS approach focused on modulating the salience network (SN), a circuit at the crossroads of large-scale networks associated with AUD, may be a fruitful therapeutic strategy. The anterior insula or dorsal anterior cingulate cortex may be particularly effective stimulation sites given emerging evidence of their roles in processes associated with relapse.

  View details for DOI 10.3389/fpsyt.2022.893833

  View details for PubMedID 35656355

• Medial prefrontal cortex theta burst stimulation improves treatment outcomes in Alcohol Use Disorder: a double-blind, sham-controlled neuroimaging study Biological Psychiatry: Global Open Science McCalley, D. M., Kaur, N., Wolf, J. P., Contreras, I. E., Book, S. W., Smith, J. P., Hanlon, C. A. 2022

  View details for DOI 10.1016/j.bpsgos.2022.03.002

• Regionally specific gray matter volume is lower in alcohol use disorder: Implications for noninvasive brain stimulation treatment ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH McCalley, D. M., Hanlon, C. A. 2021; 45 (8): 1672-1683

  Abstract

  There is growing interest in neuromodulation-based therapeutics as tools for individuals with alcohol use disorder (AUD). Through electromagnetic induction, techniques such as transcranial magnetic stimulation (TMS) can noninvasively depolarize cortical cells in the induced electrical field and monosynaptic afferents. The ability of TMS to modulate the brain is dependent upon two factors, which may be compromised in individuals with AUD: (1) gray matter volume (GMV) at the site of stimulation and (2) scalp-to-cortex (STC) distance. This study tested the hypotheses that these aspects of neural architecture are compromised in AUD patients, and thus AUD patients may need a higher TMS dose to depolarize the cortex.High-resolution magnetic resonance images were acquired from 44 individuals with AUD and 44 age-matched healthy controls (n = 88). Whole-brain voxel-based morphometry was conducted. Subsequent region-of-interest analysis was performed at three EEG 10-20 sites commonly used in TMS for AUD: FP1 (left frontal pole), F3 (left DLPFC), and C3 (left motor cortex). STC distance and TMS electric fields were assessed at these EEG sites.Individuals with AUD had significantly lower GMV in the bilateral orbitofrontal cortices, supramarginal gyri, and the left DLPFC (voxel-threshold p < 0.05, cluster-threshold p < 0.05) and within all 3 TMS target locations, F (1, 264) = 14.12, p = 0.0002. There was no significant difference in STC distance between the AUD and the healthy control group at any tested cortical location, F (3, 252) = 1.906, p = 0.129.Individuals with AUD had significantly lower GMV in multiple areas of interest for TMS treatment; however, these volumetric reductions did not impact STC distance. Given previous studies that have shown TMS-evoked changes in cortical and subcortical activity to be dependent on GMV, these data suggest that individuals with AUD may require higher doses of TMS to sufficiently modulate the neural circuits of interest.

  View details for DOI 10.1111/acer.14654

  View details for Web of Science ID 000680140600001

  View details for PubMedID 34120347

  View details for PubMedCentralID PMC8560006

• Determining the optimal pulse number for theta burst induced change in cortical excitability SCIENTIFIC REPORTS McCalley, D. M., Lench, D. H., Doolittle, J. D., Imperatore, J. P., Hoffman, M., Hanlon, C. A. 2021; 11 (1): 8726

  Abstract

  Theta-burst stimulation (TBS) is a form of non-invasive neuromodulation which is delivered in an intermittent (iTBS) or continuous (cTBS) manner. Although 600 pulses is the most common dose, the goal of these experiments was to evaluate the effect of higher per-dose pulse numbers on cortical excitability. Sixty individuals were recruited for 2 experiments. In Experiment 1, participants received 600, 1200, 1800, or sham (600) iTBS (4 visits, counterbalanced, left motor cortex, 80% active threshold). In Experiment 2, participants received 600, 1200, 1800, 3600, or sham (600) cTBS (5 visits, counterbalanced). Motor evoked potentials (MEP) were measured in 10-min increments for 60 min. For iTBS, there was a significant interaction between dose and time (F = 3.8296, p = 0.01), driven by iTBS (1200) which decreased excitability for up to 50 min (t = 3.1267, p = 0.001). For cTBS, there was no overall interaction between dose and time (F = 1.1513, p = 0.33). Relative to sham, cTBS (3600) increased excitability for up to 60 min (t = 2.0880, p = 0.04). There were no other significant effects of dose relative to sham in either experiment. Secondary analyses revealed high within and between subject variability. These results suggest that iTBS (1200) and cTBS (3600) are, respectively, the most effective doses for decreasing and increasing cortical excitability.

  View details for DOI 10.1038/s41598-021-87916-2

  View details for Web of Science ID 000642742500036

  View details for PubMedID 33888752

  View details for PubMedCentralID PMC8062542

• Non-invasive brain stimulation as a tool to decrease chronic pain in current opiate users: A parametric evaluation of two promising cortical targets DRUG AND ALCOHOL DEPENDENCE Imperatore, J. P., McCalley, D. M., Borckardt, J. J., Brady, K. T., Hanlon, C. A. 2021; 218: 108409

  Abstract

  Poorly controlled chronic pain can lead to non-prescription use of opiates, which is a growing crisis in our communities. Transcranial magnetic stimulation (TMS) is a non-invasive therapeutic tool which has emerged as a potential treatment option for these patients. It is still unclear, however, if the dorsolateral prefrontal cortex (DLPFC) or the motor cortex (MC) is a more effective treatment location. The purpose of this study was to directly compare the effects of DLPFC versus MC TMS on pain severity and the urge to use opiates among chronic pain patients.Twenty-two individuals with chronic pain currently using prescription opiates were randomized to receive 10, 3000 pulse sessions of 10 Hz repetitive TMS (rTMS) to the left DLPFC (110% resting motor threshold) or left MC (90% resting motor threshold). Multivariate linear models were used to evaluate the effect of TMS on pain and opiate use, including items from the Brief Pain Inventory (BPI) as well as subjective ratings of pain, distress, and the urge for opiates.Twenty participants (91%) completed all 10 treatment sessions and follow up visits. There was a main effect of stimulation site (F7,210 = 3.742, p = 0.001), wherein MC stimulation decreased pain interference significantly more than DLPFC stimulation (F1,216 = 8.447, p = 0.004). While both sites had comparable effect sizes on stress, pain, and discomfort, MC stimulation had larger effects on pain interference (Cohen's d: 0.7) and urge to use opiates (Cohen's d: 0.5) than DLPFC stimulation.These data suggest that the MC may be a promising target for decreasing opiate dependence and pain interference among chronic pain patients.

  View details for DOI 10.1016/j.drugalcdep.2020.108409

  View details for Web of Science ID 000600681400054

  View details for PubMedID 33250384

  View details for PubMedCentralID PMC8562904

• Non-invasive Brain Stimulation for Alcohol Use Disorders: State of the Art and Future Directions NEUROTHERAPEUTICS Philip, N. S., Sorensen, D. O., McCalley, D. M., Hanlon, C. A. 2020; 17 (1): 116-126

  Abstract

  Alcohol use disorders remain one of the leading causes of mortality and morbidity across the world, yet despite this impact, there are few treatment options for patients suffering from these disorders. To this end, non-invasive brain stimulation, most commonly utilizing technologies including transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), has recently emerged as promising potential treatments for alcohol use disorders. Enthusiasm for these interventions is fueled by their non-invasive nature, generally favorable safety profile, and ability to target and modulate brain regions implicated in substance use disorders. In this paper, we describe the underlying principles behind these commonly used stimulation technologies, summarize existing experiments and randomized controlled trials, and provide an integrative summary with suggestions for future areas of research. Currently available data generally supports the use of non-invasive brain stimulation as a near-term treatment for alcohol use disorder, with important caveats regarding the use of stimulation in this patient population.

  View details for DOI 10.1007/s13311-019-00780-x

  View details for Web of Science ID 000511657800010

  View details for PubMedID 31452080

  View details for PubMedCentralID PMC7007491

• Toward Inclusive, Evidence-Based rTMS Care for Patients With Co-Occurring Substance Use Disorders. The American journal of psychiatry Steele, V. R., Addicott, M. A., Addolorato, G., Baker, T., Biernacki, K., Bonci, A., Brady, K. T., Daughters, S. B., Diana, M., Durazzo, T. C., Ekhtiari, H., Fecteau, S., Fede, S. J., Froeliger, B., Gallimberti, L., Garza-Villarreal, E. A., George, T. P., Goudriaan, A. E., Heilig, M., Kang, D., Kearney-Ramos, T. E., Li, X., Lile, J. A., Madeo, G., Madore, M., Martinez, D., Maretinotti, G., McCalley, D. M., Moeller, S. J., Montemitro, C., Padula, C. B., Petersen, N., Pettorruso, M., Philip, N. S., Rakesh, G., Jo Salmeron, B., Sahlem, G. L., Sanna, A., Schütz, C. G., Schellekens, A., Sheffer, C. E., Soleimani, G., Spagnolo, P. A., Stein, E. A., Trivedi, M., Burrell Ward, H., Wesley, M. J., Young, J. R., Yuan, K., Yuan, T., Zangen, A., Zhao, D., Zhao, M., Hanlon, C. A. 2025; 182 (12): 1095-1096

  View details for DOI 10.1176/appi.ajp.20250407

  View details for PubMedID 41320823

• Developing a reverse translational model of low-intensity rTMS in alcohol use disorder: The influence of theta burst stimulation protocols on binge alcohol drinking in mice. Transcranial magnetic stimulation (2024) Dhungana, A., McCalley, D. M., Heath, A. M., Kraybill, E. P., Mojabi, F. S., Morales, J. M., Morningstar, A. R., Davis, A. K., Padula, C. B., Giardino, W. J., McNerney, M. W. 2025; 4

  Abstract

  Repetitive Transcranial Magnetic Stimulation (rTMS) is a promising treatment tool for Alcohol Use Disorder (AUD). A challenge facing the field is that the optimal TMS parameters to reduce drinking are unknown. There are now rodent TMS coils which can be adapted to evaluate rTMS-induced changes in alcohol consumption in a rapid, cost-effective manner.Develop a preclinical model of rTMS in alcohol consuming rodents and collect pilot data to evaluate the influence rTMS parameters (here, theta burst pattern) on change in alcohol consumption and biochemistry.66 C57BL/6 J mice (32 F) received sham, intermittent Theta Burst Stimulation (iTBS), or continuous Theta Burst Stimulation (cTBS) (14 sessions, 2 sessions/day, low intensity 16mT stimulation). Alcohol consumption and preference were evaluated before and after rTMS using a two-bottle choice, Drinking in the Dark (DID) paradigm. Cortical brain tissue was assayed for BDNF gene expression via qPCR. During DID sessions, control mice (n = 31) were given access to water only.Relative to sham, iTBS increased alcohol consumption (d=0.72) and preference (d=0.44), however these results were not statistically significant. Female mice receiving iTBS, experienced a significant, large increase in alcohol consumption (p = 0.02, d=1.5). Among water only mice, iTBS (d=-1.01) and cTBS (d=-1.03) significantly reduced BDNF expression.This preclinical model is a feasible method to evaluate rTMS-induced changes in alcohol consumption. This pilot analysis warrants future work evaluating the influence of rTMS parameters and sex on changes in drinking or drug-seeking behaviors.

  View details for DOI 10.1016/j.transm.2025.100098

  View details for PubMedID 40585525

  View details for PubMedCentralID PMC12201979

• Illuminating posterior targets for transcranial magnetic stimulation beyond the prefrontal cortex NATURE MENTAL HEALTH McCalley, D. M., Sanderson, L. L., Dowdle, L. T., Padula, C. B., Siddiqi, S. H., Ellard, K. K., Taylor, J. J. 2025

  View details for DOI 10.1038/s44220-025-00433-3

  View details for Web of Science ID 001528303000001

• A Randomized Controlled Trial of Medial Prefrontal Cortex Theta Burst Stimulation for Cocaine Use Disorder: A Three-Month Feasibility and Brain Target Engagement Study BIOLOGICAL PSYCHIATRY-COGNITIVE NEUROSCIENCE AND NEUROIMAGING Mccalley, D. M., Kinney, K. R., Kaur, N., Wolf, J. P., Contreras, I. E., Smith, J. P., Book, S. W., Hanlon, C. A. 2025; 10 (6): 616-625

  Abstract

  Cue-induced craving precipitates relapse in drug and alcohol use disorders. Theta burst stimulation (TBS) to the left frontal pole of the medial prefrontal cortex (MPFC) has previously been shown to reduce drinking and brain reactivity to alcohol cues. In this randomized, double-blind, sham-controlled target engagement study, we aimed to assess whether TBS has similar effects in individuals with cocaine use disorder.Thirty-three participants in intensive outpatient treatment received either real or sham TBS over 10 sessions across 3 weeks (36,000 pulses total; continuous TBS, 110% resting motor threshold, 3600 pulses/session). TBS was administered on days of behavioral counseling. Twenty-five individuals completed all 10 TBS sessions. Brain reactivity to cocaine cues was measured using functional magnetic resonance imaging at baseline, 1 month, 2 months, and 3 months.Cocaine abstinence during the 3-month follow-up period was greater in the real TBS group (1-month: 92.0%, 2-month: 100.0%, 3-month: 85.0%) than sham (1-month: 66.6%, 2-month: 66.6%, 3-month: 66.6%), although the difference was not statistically significant (1-month odds ratio [OR] = 6.00, p = .14; 2-month OR = 14.30, p = .09; and 3-month OR = 2.75, p = .30). However, there was a significant effect on cocaine cue reactivity (treatment effect: F1,365 = 8.92, p = .003; time × treatment interaction: F3,365 = 12.88, p < .001). Real TBS reduced cocaine cue reactivity in the MPFC (F3,72 = 5.46, p = .02), the anterior cingulate (F3,72 = 3.03, p = .04), and the insula (F3,72 = 3.60, p = .02).This early-stage trial demonstrates that TBS to the MPFC reduces brain reactivity to cocaine cues in key nodes of the salience network in treatment-seeking cocaine users. Future, well-powered trials are warranted to evaluate clinical efficacy outcomes.

  View details for DOI 10.1016/j.bpsc.2024.11.022

  View details for Web of Science ID 001512044100001

  View details for PubMedID 39667495

• Intermittent theta burst to the left dorsolateral prefrontal cortex promoted decreased alcohol consumption and improved outcomes in those with alcohol use disorder: A randomized, double-blind, placebo-controlled clinical trial. Drug and alcohol dependence Durazzo, T. C., Kraybill, E. P., Stephens, L. H., McCalley, D. M., Humphreys, K., May, A. C., Padula, C. B. 2025; 270: 112641

  Abstract

  Over 60 % of individuals with alcohol use disorder (AUD) resume hazardous drinking within 6 months post-treatment, necessitating the development of more efficacious interventions. Accumulating evidence suggests transcranial magnetic stimulation (TMS) is a promising intervention for AUD. This randomized, double-blind, placebo-controlled trial assessed the efficacy of intermittent theta burst (iTBS), a form of TMS, as an adjunct treatment for AUD.Forty-nine Veterans with AUD (48 males, 1 female) were recruited from residential AUD and substance use disorder treatment. Participants were randomized to 20 sessions of Active (n = 25) or Sham (n = 24) iTBS (1200 pulses/session), targeting the left dorsolateral prefrontal cortex (DLPFC) administered over 14 days or less. Five participants were withdrawn unrelated to iTBS procedure adverse events. Participant alcohol/substance use was monitored for 6-months following final iTBS session.Relative to participants who received Sham iTBS, those who received Active iTBS showed a significantly greater reduction in percent heavy drinking days and a trend for higher rate of continuous abstinence over 6-months. Among participants who resumed alcohol consumption, those in the Active group demonstrated significantly lower quantity and duration of alcohol consumption than Sham. Pre-study alcohol consumption variables were not related to post-iTBS treatment outcomes.Findings indicated that Active left DLPFC iTBS, delivered over approximately 2-weeks, was a safe and efficient intervention for AUD that promoted significantly reduced heavy drinking and improved clinical outcomes compared to Sham over 6-months post-iTBS. This study provides novel data to inform and power future larger-scale, multi-site clinical trials employing iTBS for AUD.

  View details for DOI 10.1016/j.drugalcdep.2025.112641

  View details for PubMedID 40048832

• Two Faces of Reward: Alcohol-Cue and Monetary Assessment of Reward Circuit Functioning Reveals Neural Predictors of Relapse in Alcohol Use Disorder Padula, C., MacNiven, K., Tenekedjieva, L., McCalley, D., Knutson, B., Williams, L. SPRINGERNATURE. 2024: 217-218

  View details for Web of Science ID 001421429700430

• Females Experience Greater Clinical Benefit from TMS for AUD: A Translational Analysis of Sex-Differences in Preclinical and Clinical Treatment Outcomes McCalley, D., Hanlon, C., Giardino, W. J., McNerney, M., Padula, C. SPRINGERNATURE. 2024: 230-231

  View details for Web of Science ID 001421429700454

• Accelerated Deep TMS in Alcohol Use Disorder: A Preliminary Pilot Trial Targeting the Dorsal Anterior Cingulate Cortex Increases Neural Target Engagement and Abstinence. Brain stimulation Padula, C. L., Tenekedjieva, L. E., McCalley, D. A., Morales, J. A., Madore, M. I. 2024

  View details for DOI 10.1016/j.brs.2024.09.002

  View details for PubMedID 39265786

• Transdiagnostic Mood, Anxiety and Trauma Symptom Factors in Alcohol Use Disorder: Neural Correlates Across Three Brain Networks. Biological psychiatry. Cognitive neuroscience and neuroimaging Tenekedjieva, L. T., McCalley, D. M., Goldstein-Piekarski, A. N., Williams, L. M., Padula, C. B. 2024

  Abstract

  Alcohol use disorder (AUD) is associated with high rates of trauma, mood, and anxiety disorders. Individual symptoms highly overlap across diagnoses, highlighting the need for a transdiagnostic approach. Further, there is limited research on how transdiagnostic psychopathology impacts the neural correlates of AUD. Thus, we aimed to identify symptom factors spanning diagnoses and how they relate to the neurocircuitry of addiction.Eighty-six Veterans with AUD completed self-report measures and reward, incentive salience and cognitive control fMRI tasks. Factor analysis was performed on self-reported trauma, depression, anxiety, and stress symptoms to obtain transdiagnostic symptom compositions. Neural correlates with a-priori-defined regions of interest in the three networks were assessed. Independent samples t-tests compared the same nodes by DSM-5 diagnosis.Four symptom factors were identified: trauma distress, negative affect, hyperarousal, and somatic anxiety. Trauma distress score was associated with increased cognitive control activity regions during response inhibition (dACC). Negative affect related to lower activation in reward regions (R.Caudate) but higher activation in cognitive control regions during response inhibition (L.dlPFC). Hyperarousal related to lower reward activity during monetary reward anticipation (L.Caudate, R.Caudate) Somatic anxiety was not significantly associated with brain activation. No difference in neural activity was found by PTSD, MDD or GAD diagnosis CONCLUSION: These preliminary, hypothesis-generating findings offer transdiagnostic symptom factors that are differentially associated with neural function and could guide us towards a brain-based classification of psychiatric dysfunction in AUD. Results warrant further investigation of transdiagnostic approaches to symptoms in addiction.

  View details for DOI 10.1016/j.bpsc.2024.01.013

  View details for PubMedID 38432622

• A pilot, randomized clinical trial: Left dorsolateral prefrontal cortex intermittent theta burst stimulation improves treatment outcomes in veterans with alcohol use disorder. Alcohol, clinical & experimental research Padula, C. B., McCalley, D. M., Tenekedjieva, L., MacNiven, K., Rauch, A., Morales, J. M., Knutson, B., Humphreys, K., Williams, L. M., Durazzo, T. C. 2024; 48 (1): 164-177

  Abstract

  BACKGROUND: Transcranial magnetic stimulation (TMS) offers a promising treatment avenue to modulate brain function in alcohol use disorder (AUD). To the best of our knowledge, this pilot study is the first randomized, double-blind, sham-controlled trial to deliver intermittent theta burst stimulation to the left dorsolateral prefrontal cortex (DLPFC) among US veterans with AUD. We hypothesized that 20 sessions of real TMS are tolerable and feasible. As a secondary line of inquiry, we hypothesized that, relative to sham TMS, individuals receiving real TMS would experience greater reductions in 6-month relapse rates, anhedonia, and alcohol cue-reactivity.METHODS: Veterans (n=17, one woman) were enrolled in a double-blind, sham-controlled trial (2-3 sessions/day; 7-10days; 600 pulses/session; 20 sessions). Pre- and posttreatment assessments included responses to self-report questionnaires and functional magnetic resonance imaging measures of alcohol cue-reactivity. Alcohol consumption was assessed for 6months. Linear mixed-effects models were constructed to predict posttreatment craving, mood, and cue-reactivity.RESULTS: Individuals who received active iTBS (n=8) were less likely to relapse within 3months after treatment than the sham-treated group (n=9) (OR=12.0). Greater reductions in anhedonia were observed following active iTBS (Cohen's d=-0.59), relative to sham (d=-0.25). Alcohol cue-reactivity was reduced following active iTBS and increased following sham within the left insula (d=-0.19 vs. 0.51), left thalamus (d=-0.28 vs. 0.77), right insula (d=0.18 vs. 0.52), and right thalamus (d=-0.06 vs. 0.62).CONCLUSIONS: Relative to sham, we demonstrate that 20 sessions of real left DLPFC iTBS reduced the likelihood of relapse for at least 3months. The potential utility of this approach is underscored by observed decreases in anhedonia and alcohol cue-reactivity-strong predictors of relapse among veterans. These initial data offer a valuable set of effect sizes to inform future clinical trials in this patient population.

  View details for DOI 10.1111/acer.15224

  View details for PubMedID 38197808

• Preliminary Results of Deep Transcranial Magnetic Stimulation to the Dorsal Anterior Cingulate Cortex Reveal Increased Neural Target Function and Abstinence in Veterans with Alcohol Use Disorder Padula, C., McCalley, D., Tenekedjieva, L., Morales, J., Madore, M. SPRINGERNATURE. 2023: 448

  View details for Web of Science ID 001126640300418

• Left Dorsolateral Prefrontal Cortex Intermittent Theta Burst Stimulation Improves Treatment Outcomes in Veterans With Alcohol Use Disorder: A Randomized, Sham-Controlled Clinical Pilot Trial McCalley, D., Tenekedjieva, L., MacNiven, K., Rauch, A., Morales, J., Knutson, B., Humphreys, K., Williams, L., Durazzo, T., Padula, C. SPRINGERNATURE. 2023: 449

  View details for Web of Science ID 001126640300420

• Evaluating a novelMR-compatiblefoot pedal device for unipedal and bipedal motion:Test-retestreliability of evoked brain activity HUMAN BRAIN MAPPING Doolittle, J. D., Downey, R. J., Imperatore, J. P., Dowdle, L. T., Lench, D. H., McLeod, J., McCalley, D. M., Gregory, C. M., Hanlon, C. A. 2021; 42 (1): 128-138

  Abstract

  The purpose of this study was to develop and evaluate a new, open-source MR-compatible device capable of assessing unipedal and bipedal lower extremity movement with minimal head motion and high test-retest reliability. To evaluate the prototype, 20 healthy adults participated in two magnetic resonance imaging (MRI) visits, separated by 2-6 months, in which they performed a visually guided dorsiflexion/plantar flexion task with their left foot, right foot, and alternating feet. Dependent measures included: evoked blood oxygen level-dependent (BOLD) signal in the motor network, head movement associated with dorsiflexion/plantar flexion, the test-retest reliability of these measurements. Left and right unipedal movement led to a significant increase in BOLD signal compared to rest in the medial portion of the right and left primary motor cortex (respectively), and the ipsilateral cerebellum (FWE corrected, p < .001). Average head motion was 0.10 ± 0.02 mm. The test-retest reliability was high for the functional MRI data (intraclass correlation coefficients [ICCs]: >0.75) and the angular displacement of the ankle joint (ICC: 0.842). This bipedal device can robustly isolate activity in the motor network during alternating plantarflexion and dorsiflexion with minimal head movement, while providing high test-retest reliability. Ultimately, these data and open-source building instructions will provide a new, economical tool for investigators interested in evaluating brain function resulting from lower extremity movement.

  View details for DOI 10.1002/hbm.25209

  View details for Web of Science ID 000580597500001

  View details for PubMedID 33089953

  View details for PubMedCentralID PMC7721228

• Activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) regulates anxiety- and novelty-related behaviors GENES BRAIN AND BEHAVIOR Penrod, R. D., Kumar, J., Smith, L. N., McCalley, D., Nentwig, T. B., Hughes, B. W., Barry, G. M., Glover, K., Taniguchi, M., Cowan, C. W. 2019; 18 (7): e12561

  Abstract

  The activity-regulated cytoskeleton-associated protein (Arc, also known as Arg3.1) regulates glutamatergic synapse plasticity and has been linked to neuropsychiatric illness; however, its role in behaviors associated with mood and anxiety disorders remains unclear. We find that stress upregulates Arc expression in the adult mouse nucleus accumbens (NAc)-a brain region implicated in mood and anxiety behaviors. Global Arc knockout mice have altered AMPAR-subunit surface levels in the adult NAc, and the Arc-deficient mice show reductions in anxiety-like behavior, deficits in social novelty preference, and antidepressive-like behavior. Viral-mediated expression of Arc in the adult NAc of male, global Arc KO mice restores normal levels of anxiety-like behavior in the elevated plus maze (EPM). Consistent with this finding, viral-mediated reduction of Arc in the adult NAc reduces anxiety-like behavior in male, but not female, mice in the EPM. NAc-specific reduction of Arc also produced significant deficits in both object and social novelty preference tasks. Together our findings indicate that Arc is essential for regulating normal mood- and anxiety-related behaviors and novelty discrimination, and that Arc's function within the adult NAc contributes to these behavioral effects.

  View details for DOI 10.1111/gbb.12561

  View details for Web of Science ID 000483672700005

  View details for PubMedID 30761730

• Consequences of Adolescent Exposure to the Cannabinoid Receptor Agonist WIN55,212-2 on Working Memory in Female Rats FRONTIERS IN BEHAVIORAL NEUROSCIENCE Kirschmann, E. K., McCalley, D. M., Edwards, C. M., Torregrossa, M. M. 2017; 11: 137

  Abstract

  Marijuana is a prevalent illicit substance used by adolescents, and several studies have indicated that adolescent use can lead to long-term cognitive deficits including problems with attention and memory. However, preclinical animal studies that observe cognitive deficits after cannabinoid exposure during adolescence utilize experimenter administration of doses of cannabinoids that may exceed what an organism would choose to take, suggesting that contingency and dose are critical factors that need to be addressed in translational models of consequences of cannabinoid exposure. Indeed, we recently developed an adolescent cannabinoid self-administration paradigm in male rats, and found that prior adolescent self-administration of the cannabinoid receptor agonist WIN55,212-2 (WIN) resulted in improved working memory performance in adulthood. In addition, the doses self-administered were not as high as those that are found to produce memory deficits. However, given known sex differences in both drug self-administration and learning and memory processes, it is possible that cannabinoid self-administration could have different cognitive consequences in females. Therefore, we aimed to explore the effects of self-administered vs. experimenter-administered WIN in adolescent female rats on adult cognitive function. Female rats were trained to self-administer WIN daily throughout adolescence (postnatal day 34-59). A control group self-administered vehicle solution. The acute effects of adolescent WIN self-administration on memory were determined using a short-term spatial memory test 24 h after final SA session; and the long-term effects on cognitive performance were assessed during protracted abstinence in adulthood using a delayed-match-to-sample working memory task. In a separate experiment, females were given daily intraperitoneal (IP) injections of a low or high dose of WIN, corresponding to self-administered and typical experimenter-administered doses, respectively, or its vehicle during adolescence and working memory was assessed under drug-free conditions in adulthood. While self-administration of WIN in adolescence had no significant effects on short-term spatial memory or adult working memory, experimenter administration of WIN resulted in improved adult working memory performance that was more pronounced in the low dose group. Thus, low-dose adolescent WIN exposure, whether self-administered or experimenter-administered, results in either improvements or no change in adult working memory performance in female rats, similar to previous results found in males.

  View details for DOI 10.3389/fnbeh.2017.00137

  View details for Web of Science ID 000406468500001

  View details for PubMedID 28785210

  View details for PubMedCentralID PMC5519521