Cue-induced reinstatement of extinguished drug seeking is a preclinical model of relapse. However, relapse typically occurs after abstinence rather than explicit extinction training. We show that inactivation of the dorsolateral caudate-putamen, but not other structures previously implicated in reinstatement, attenuates cocaine seeking after abstinence. This suggests that there is limited overlap in the substrates of cocaine seeking after abstinence versus extinction, and that habit learning exerts greater control over drug seeking than regions implicated in stimulus-reward associations.

rTMS over the left prefrontal cortex increases thermal pain thresholds in healthy adults. Results from the present study support the idea that the left prefrontal cortex may be a promising TMS cortical target for the management of pain. More research is needed to establish the reliability of these findings, maximize the effect, determine the length of effect and elucidate possible mechanisms of action.

Objective Stimulating the human cortex using transcranial magnetic stimulation (TMS) temporarily reduces clinical and experimental pain, however, it is unclear which cortical targets are the most effective. The motor cortex has been a popular target for managing neuropathic pain, while the prefrontal cortex has been investigated for an array of nociceptive pain conditions. It is unclear whether the motor cortex is the only effective cortical target for managing neuropathic pain, and no published studies to date have investigated the effects of prefrontal stimulation on neuropathic pain. Design This preliminary pilot trial employed a sham-controlled, within-subject, cross-over design to evaluate clinical pain as well as laboratory pain thresholds among four patients with chronic neuropathic pain. Each participant underwent three real and three sham 20-minute sessions of 10Hz left prefrontal rTMS. Daily pain diaries were collected for 3-weeks before and after each treatment phase along with a battery of self-report pain and mood questionnaires. Results Time-series analysis at the individual patient level indicated that real TMS was associated with significant improvements in average daily pain in 3 of the 4 participants. These effects were independent of changes in mood in 2 of the participants. At the group level, a decrease of 19% in daily pain on average, pain at its worst, and pain at its least was observed while controlling for changes in mood, activity-level and sleep. The effects of real TMS were significantly greater than sham. Real TMS was associated with increases in thermal and mechanical pain thresholds whereas sham was not. No statistically significant effects were observed across the questionnaire data. Conclusions The prefrontal cortex may be an important TMS cortical target for managing certain types of pain, including certain neuropathic pain syndromes.

Background-Transcranial magnetic stimulation (TMS) is a relatively noninvasive brain stimulation technology that can focally stimulate the human cortex. One significant limitation of much of the TMS research to date concerns the nature of the placebo or sham conditions employed. When TMS pulses are delivered repetitively (especially prefrontal TMS) it is often experienced as painful. Most sham TMS techniques produce identical sounds to active TMS, but they do not cause much, if any, scalp or facial sensation or discomfort. This is a serious problem when investigators are attempting to evaluate the effects of TMS using traditional sham techniques because of unintended systematic differences between real and sham TMS groups (i.e., confounds). As long as traditional approaches to sham TMS are employed, the validity of the inferences regarding the efficacy of TMS will be limited. While some other sophisticated systems have been developed to address these concerns, they tend to be expensive and lack portability. Portability will likely become more and more important as TMS applications expand into different clinical areas (e.g., TMS in the postanesthesia care unit following surgery)

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