Honors & Awards
Outstanding Scholar in Neuroscience Award (OSNAP), National Institute of Mental Health (NIMH) and National Institute of Drug Abuse (NIDA) (2022)
Distinguished Graduate, Medical University of South Carolina, College of Graduate Studies (2022)
Ruth L. Kirschtein National Service in Research Award; F31, National Institute of Alcohol Abuse and Alcoholism (2020-2022)
Doctor of Philosophy, Medical University Of South Carolina (2022)
Bachelor of Science, University of Pittsburgh (2017)
Ph.D., Medical University of South Carolina, Neuroscience (2022)
B.S., University of Pittsburgh, Neuroscience (2017)
Claudia Padula, Postdoctoral Faculty Sponsor
Sex/Gender as a Factor That Influences Transcranial Magnetic Stimulation Treatment Outcome: Three Potential Biological Explanations
FRONTIERS IN PSYCHIATRY
2022; 13: 869070
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
2022; 13: 893833
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
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
2021; 45 (8): 1672-1683
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
2021; 11 (1): 8726
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
2021; 218: 108409
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
2020; 17 (1): 116-126
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
Evaluating a novelMR-compatiblefoot pedal device for unipedal and bipedal motion:Test-retestreliability of evoked brain activity
HUMAN BRAIN MAPPING
2021; 42 (1): 128-138
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
2019; 18 (7): e12561
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
2017; 11: 137
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