Mobilization of Medial and Lateral Frontal-Striatal Circuits in Cocaine Users and Controls: An Interleaved TMS/BOLD Functional Connectivity Study

Hanlon, Colleen A.; Dowdle, Logan T.; Moss, Hunter G.; Canterberry, Melanie; George, Mark S.

doi:10.1038/npp.2016.114

Cited by 59 publications

(57 citation statements)

References 57 publications

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“…They also demonstrated that activity in the DLPFC was inversely related to activity in the MPFC. However, our group has previously shown that the reciprocal relationship found between executive control and default mode networks in healthy controls is not present in cocaine users (Hanlon et al, 2016b). That is, stimulating the DLPFC did not have a significant attenuating effect on MPFC activity in cocaine users.…”

Section: Discussionmentioning

confidence: 95%

Left frontal pole theta burst stimulation decreases orbitofrontal and insula activity in cocaine users and alcohol users

Hanlon

Dowdle

Correia

et al. 2017

Drug and Alcohol Dependence

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Background Preclinical research has demonstrated a causal relationship between medial prefrontal cortex activity and cocaine self-administration. As a step towards translating those data to a neural circuit-based intervention for patients, this study sought to determine if continuous theta burst stimulation (cTBS) to the left frontal pole (FP), would attenuate frontal-striatal activity in two substance-dependent populations. Methods Forty-nine substance dependent individuals (25 cocaine, 24 alcohol) completed a single-blind, sham-controlled, crossover study wherein they received 6 trains of real or sham cTBS (110% resting motor threshold, FP1) each visit. Baseline evoked BOLD signal was measured immediately before and after real and sham cTBS (interleaved TMS/BOLD imaging: single pulses to left FP; scalp-to-cortex distance covariate, FWE correction p<0.05) Results Among cocaine users, real cTBS significantly decreased evoked BOLD signal in the caudate, accumbens, anterior cingulate, orbitofrontal (OFC) and parietal cortex relative to sham cTBS. Among alcohol users, real cTBS significantly decreased evoked BOLD signal in left OFC, insula, and lateral sensorimotor cortex. There was no significant difference between the groups. Conclusions These data suggest that 6 trains of left FP cTBS delivered in a single day decreases TMS-evoked BOLD signal in the OFC and several cortical nodes which regulate salience and are typically activated by drug cues. The reliability of this pattern across cocaine- and alcohol-dependent individuals suggests that cTBS may be an effective tool to dampen neural circuits typically engaged by salient drug cues. Multiday studies are required to determine it this has a sustainable effect on the brain or drug use behavior.

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Section: Discussionmentioning

confidence: 95%

Left frontal pole theta burst stimulation decreases orbitofrontal and insula activity in cocaine users and alcohol users

Hanlon

Dowdle

Correia

et al. 2017

Drug and Alcohol Dependence

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“…fMRI-rTMS studies in healthy controls have directly demonstrated that rTMS pulses to the frontopolar cortex caused BOLD activations in both the frontal pole and in the ventral striatum; rTMS pulses to the dlPFC, in contrast, caused BOLD activations in both the dlPFC and the dorsal caudate nucleus (Hanlon et al, 2013, 2016). A session of inhibitory, continuous theta-burst stimulation to the frontopolar cortex reduced the BOLD response to individual pulses at the same target, with the effect seen prominently in ventral striatum (Hanlon et al, 2015).…”

Section: Targeting the Sn-cstc With Therapeutic Brain Stimulationmentioning

confidence: 99%

“…Aside from the well-established example of SUD, pathology of this loop may be important in OCD, MDD (particularly for the symptom of anhedonia), schizophrenia, and other psychiatric disorders (as noted throughout the previous three sections of this review). In addition, interactions (such as mutual inhibition) between the activity of the dorsal striatal-SN loop and the ventral striatal reward loop may be important for understanding psychiatric pathology and its heterogeneity; such interactions between dorsal and ventral CSTC loops are an increasingly prevalent theme of study in recent work combining neuroimaging and neurostimulation in psychiatric illness (for example, Liston et al, 2014; Hanlon et al, 2016). …”

Section: Unresolved Questions and Future Directions For Studymentioning

confidence: 99%

Cortico-Striatal-Thalamic Loop Circuits of the Salience Network: A Central Pathway in Psychiatric Disease and Treatment

Peters

Dunlop

Downar³

2016

Front. Syst. Neurosci.

462

298

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The salience network (SN) plays a central role in cognitive control by integrating sensory input to guide attention, attend to motivationally salient stimuli and recruit appropriate functional brain-behavior networks to modulate behavior. Mounting evidence suggests that disturbances in SN function underlie abnormalities in cognitive control and may be a common etiology underlying many psychiatric disorders. Such functional and anatomical abnormalities have been recently apparent in studies and meta-analyses of psychiatric illness using functional magnetic resonance imaging (fMRI) and voxel-based morphometry (VBM). Of particular importance, abnormal structure and function in major cortical nodes of the SN, the dorsal anterior cingulate cortex (dACC) and anterior insula (AI), have been observed as a common neurobiological substrate across a broad spectrum of psychiatric disorders. In addition to cortical nodes of the SN, the network’s associated subcortical structures, including the dorsal striatum, mediodorsal thalamus and dopaminergic brainstem nuclei, comprise a discrete regulatory loop circuit. The SN’s cortico-striato-thalamo-cortical loop increasingly appears to be central to mechanisms of cognitive control, as well as to a broad spectrum of psychiatric illnesses and their available treatments. Functional imbalances within the SN loop appear to impair cognitive control, and specifically may impair self-regulation of cognition, behavior and emotion, thereby leading to symptoms of psychiatric illness. Furthermore, treating such psychiatric illnesses using invasive or non-invasive brain stimulation techniques appears to modulate SN cortical-subcortical loop integrity, and these effects may be central to the therapeutic mechanisms of brain stimulation treatments in many psychiatric illnesses. Here, we review clinical and experimental evidence for abnormalities in SN cortico-striatal-thalamic loop circuits in major depression, substance use disorders (SUD), anxiety disorders, schizophrenia and eating disorders (ED). We also review emergent therapeutic evidence that novel invasive and non-invasive brain stimulation treatments may exert therapeutic effects by normalizing abnormalities in the SN loop, thereby restoring the capacity for cognitive control. Finally, we consider a series of promising directions for future investigations on the role of SN cortico-striatal-thalamic loop circuits in the pathophysiology and treatment of psychiatric disorders.

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“…Having demonstrated that it was possible to differentiate these circuits in controls, the next step was to evaluate the integrity of these circuits in cocaine users [36]. Eighteen cocaine-dependent individuals with a history of failed quit attempts and 18 age-matched controls were recruited from the community.…”

Section: Study 2: Which Circuit Is More Disrupted In Cocaine Users?mentioning

confidence: 99%

Developing Repetitive Transcranial Magnetic Stimulation (rTMS) as a Treatment Tool for Cocaine Use Disorder: a Series of Six Translational Studies

Hanlon

Kearney-Ramos

Dowdle

et al. 2017

Curr Behav Neurosci Rep

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Purpose of the Review Cocaine dependence is a chronic and relapsing disorder which is particularly resistant to behavioral or pharmacologic treatment, and likely involves multiple dysfunctional frontal-striatal circuits. Through advances in preclinical research in the last decade, we now have an unprecedented understanding of the neural control of drug-taking behavior. In both rodent models and human clinical neuroimaging studies, it is apparent that medial frontal-striatal limbic circuits regulate drug cue-triggered behavior. While non-human preclinical studies can use invasive stimulation techniques to inhibit drug cue-evoked behavior, in human clinical neuroscience, we are pursuing non-invasive theta burst stimulation (TBS) as a novel therapeutic tool to inhibit drug cue-associated behavior. Recent Findings Our laboratory and others have spent the last 7 years systematically and empirically developing a non-invasive, neural circuit-based intervention for cocaine use disorder. Utilizing a multimodal approach of functional brain imaging and brain stimulation, we have attempted to design and optimize a repetitive transcranial magnetic stimulation treatment protocol for cocaine use disorder. This manuscript will briefly review the data largely from our own lab that motivated our selection of candidate neural circuits, and then summarize the results of six studies, culminating in the first double-blinded, sham-controlled clinical trial of TMS as a treatment adjuvant for treatment-engaged cocaine users (10 sessions, medial prefrontal cortex, 110% resting motor threshold, continuous theta burst stimulation, 3600 pulses/session). Summary The intent of this review is to highlight one example of a systematic path for TMS treatment development in patients. This path is not necessarily optimal, exclusive, or appropriate for every neurologic or psychiatric disease. Rather, it is one example of a reasoned, empirically derived pathway which we hope will serve as scaffolding for future investigators seeking to develop TMS treatment protocols.

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Mobilization of Medial and Lateral Frontal-Striatal Circuits in Cocaine Users and Controls: An Interleaved TMS/BOLD Functional Connectivity Study

Cited by 59 publications

References 57 publications

Left frontal pole theta burst stimulation decreases orbitofrontal and insula activity in cocaine users and alcohol users

Left frontal pole theta burst stimulation decreases orbitofrontal and insula activity in cocaine users and alcohol users

Cortico-Striatal-Thalamic Loop Circuits of the Salience Network: A Central Pathway in Psychiatric Disease and Treatment

Developing Repetitive Transcranial Magnetic Stimulation (rTMS) as a Treatment Tool for Cocaine Use Disorder: a Series of Six Translational Studies

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