Effects of Hyperdirect Pathway Theta Burst Transcranial Magnetic Stimulation on Inhibitory Control, Craving, and Smoking in Adults With Nicotine Dependence: A Double-Blind, Randomized Crossover Trial.

BACKGROUND: Nicotine dependence is associated with dysregulated hyperdirect pathway (HDP)-mediated inhibitory control (IC). However, there are currently no evidence-based treatments that have been shown to target the HDP to improve IC and reduce cigarette cravings and smoking. METHODS: Following a baseline nonstimulation control session, this study (N = 37; female: n = 17) used a double-blind, randomized crossover design to examine the behavioral and neural effects of intermittent theta burst stimulation (iTBS) and continuous TBS (cTBS) to the right inferior frontal gyrus (rIFG)-a key cortical node of the HDP. Associations between treatment effects were also explored. RESULTS: At baseline, HDP IC task-state functional connectivity was positively associated with IC task performance, which confirmed the association between HDP circuit function and IC. Compared with iTBS, rIFG cTBS improved IC task performance. Compared with the baseline nonstimulation control session, both TBS conditions reduced cigarette craving and smoking; however, although craving and smoking were lower for cTBS, no differences were found between the two active conditions. In addition, although HDP IC task-state functional connectivity was greater following cTBS than iTBS, there was no significant difference between conditions. Finally, cTBS-induced improvement in IC task performance was associated with reduced craving, and cTBS-induced reduction in craving was associated with reduced smoking. CONCLUSIONS: These findings warrant further investigation into the effects of rIFG cTBS for increasing IC and reducing craving and smoking among individuals with nicotine dependence. Future sham-controlled cTBS studies may help further elucidate the mechanisms by which rIFG cTBS mediates IC and smoking behavior.

Neuroversion: using electroconvulsive therapy as a bridge to deep brain stimulation implantation.

Parkinson's disease (PD) is a movement disorder with significant neuropsychiatric comorbidities. Electroconvulsive therapy (ECT) is effective in treating these neuropsychiatric symptoms; however, clinicians are reluctant to use ECT in patients with deep brain stimulation (DBS) implantations for fear of damaging the device, as well as potential cognitive side effects. Right unilateral ultra-brief pulse (RUL UBP) ECT has a more favorable cognitive side-effect profile yet has never been reported in PD patients with DBS implants. We present a case series of three patients with a history of PD that all presented with psychiatric decompensation immediately prior to planned DBS surgery. All three patients had DBS electrode(s) in place at the time and an acute course of ECT was utilized in a novel method to "bridge" these individuals to neurosurgery. The patients all experienced symptom resolution (psychosis and/or depression and/or anxiety) without apparent cognitive side effects. This case series not only illustrates that right unilateral ultra-brief pulse can be utilized in patients with DBS electrodes but also illustrates that this intervention can be utilized as a neuromodulatory "bridge", where nonoperative surgical candidates with unstable psychiatric symptoms can be converted to operative candidates in a manner similar to electrical cardioversion.

Five-Year Follow-Up of Bilateral Epidural Prefrontal Cortical Stimulation for Treatment-Resistant Depression.

BACKGROUND: Epidural prefrontal cortical stimulation (EpCS) represents a novel therapeutic approach with many unique benefits that can be used for treatment-resistant depression (TRD). OBJECTIVE: To examine the long-term safety and efficacy of EpCS of the frontopolar cortex (FPC) and dorsolateral prefrontal cortex (DLPFC) for treatment of TRD. METHODS: Adults (N = 5) who were 21-80 years old with severe TRD [failure to respond to adequate courses of at least 4 antidepressant medications, psychotherapy and ≥20 on the Hamilton Rating Scale for Depression (HRSD24)] were recruited. Participants were implanted with bilateral EpCS over the FPC and DLPFC and received constant, chronic stimulation throughout the five years with Medtronic IPGs. They were followed for 5 years (2/1/2008-10/14/2013). Efficacy of EpCS was assessed with the HRSD24 in an open-label design as the primary outcome measure at five years. RESULTS: All 5 patients continued to tolerate the therapy. The mean improvements from pre-implant baseline on the HRSD24 were [7 months] 54.9% (±37.7), [1 year] 41.2% (±36.6), [2 years] 53.8% (±21.7), and [5 years] 45% (±47). Three of 5 (60%) subjects continued to be in remission at 5 years. There were 5 serious adverse events: 1 electrode 'paddle' infection and 4 device malfunctions, all resulting in suicidal ideation and/or hospitalization. CONCLUSION: These results suggest that chronic bilateral EpCS over the FPC and DLPFC is a promising and potentially durable new technology for treating TRD, both acutely and over 5 years.