Rewiring the Addicted Brain: Circuits-Based Treatment for Addiction

Abstract

The advent of the noninvasive brain stimulation (NIBS) technique has paved the way for neural circuit-based treatments for addiction. Recently, evidence from both preclinical and clinical studies has evaluated the use of transcranial magnetic stimulation (TMS) as a safe and cost-effective therapeutic tool for substance use disorders (SUDs). Indeed, repetitive TMS impacts on neural activity inducing short-and long-term effects involving neuroplasticity mechanisms locally within the target area of stimulation and the network level throughout the brain. Here, we provide an integrated view of evidence highlighting the mechanisms of TMS-induced effects on modulating the maladaptive brain circuitry of addiction. We then review the preclinical and clinical findings suggesting rTMS as an effective interventional tool for the treatment of SUDs.

Summary: Order and Disorder in Brains and Behavior

“…His initial mouse study showed that prolonged cocaine self-administration decreases the intrinsic excitability of pyramidal neurons in the prelimbic cortex (Chen et al 2013). Through a series of fortuitous events, this research led to pilot studies in cocaine-addicted patients, revealing that transcranial magnetic stimulation (TMS) of dorsolateral prefrontal cortex reduces cocaine cravings and use (Madeo and Bonci 2019). Lui-hai Tsai presented a remarkable discovery that 40-Hz visual flicker reduces amyloid β in mouse models of Alzheimer's (Iaccarino et al 2016).…”

“…A less-invasive but also less-specific technique, transcranial magnetic stimulation, has also been gaining ground in treating major depression and anorexia. Antonello Bonci discussed how his group moved from a mouse model of compulsive drug use to TMS stimulation of dorsolateral cortex for ameliorating cocaine craving and drug use (Chen et al 2013;Madeo and Bonci 2019) and discussed several ongoing clinical trials building on their pilot studies. A continuing challenge for both DBS and TMS is the limited mechanistic understanding of their effects, a situation that is quickly changing.…”

rTMS-Induced Changes in Glutamatergic and Dopaminergic Systems: Relevance to Cocaine and Methamphetamine Use Disorders

“…Our current knowledge of the circuits involved in addiction comes from animal studies as the pathways and brain regions involved are similar in rodents and humans (Kalivas et al, 2006;Madeo and Bonci, 2019). Animal models of addiction are one of the most well-developed and validated models in neuropsychiatric research and are used by researchers and clinicians to gain insight into some of the mechanisms involved in addiction (Kalivas et al, 2006;Venniro et al, 2016).…”

“…In addition, because compulsive drug use has been associated with abnormal orbitofrontal-and mesolimbic-striatal circuits in subjects who are punishment resistant (i.e. even when faced with consequences, subjects continue to pursue the drug) (Hu et al, 2019), the possibility of using rTMS to stimulate hypoactive prefrontal cortical neurons, which can then modulate interconnected networks, is appealing (Diana et al, 2017;Madeo and Bonci, 2019;Song et al, 2019). An increasing number of studies have shown anticraving effects following rTMS treatment targeting the PFC (see Ma et al, 2019;Madeo and Bonci, 2019;Zhang et al, 2019), presumably through modulation of the efferent glutamatergic and afferent dopaminergic connections (Diana, 2011;Diana et al, 2017; Figure 1).…”

“…A recent meta-analysis that looked at single versus multiple sessions of neuromodulation across all addiction domains found that multiple sessions were more effective at reducing craving, with larger effect sizes compared to single sessions (Song et al, 2019). Recent systematic reviews have included several studies that demonstrate anticraving effects with chronic stimulation (Madeo and Bonci, 2019;Zhang et al, 2019). Moreover, in studies where there was no change in craving after the first session, there was a significant anticraving effect by the end of the treatment period (5 days of daily HF-rTMS) for active, but not sham, stimulation (Su et al, 2017).…”