Cigarette smokers and substance users discount the value of delayed outcomes more steeply than non-users. Higher discounting rates are associated with relapse and poorer treatment outcomes. The left dorsolateral prefontal cortex (DLPFC) exerts an inhibitory influence on impulsive or seductive choices and greater activity in the prefrontal cortex is associated with lower discounting rates. We hypothesized that increasing activity in the left DLPFC with high frequency repetitive transcranial magnetic stimulation (HF rTMS) would decrease delay discounting and decrease impulsive decision-making in a gambling task as well as decrease cigarette consumption, similar to other studies. In this single-blind, within-subjects design, smokers with no intention to quit (n=47) and nonsmokers (n=19) underwent three counterbalanced sessions of HF rTMS (20Hz, 10Hz, sham) delivered over the left DLPFC. Tasks were administered at baseline and after each stimulation session. Stimulation decreased discounting of monetary gains (F[3,250]=4.46, p<.01), but increased discounting of monetary losses (F[3,246]=4.30, p<.01), producing a reflection effect, normally absent in delay discounting. Stimulation had no effect on cigarette consumption. These findings provide new insights into cognitive processes involved with decision-making and cigarette consumption and suggest that like all medications for substance dependence, HF rTMS is likely to be most effective when paired with cognitive-behavioral interventions.

Objective/Hypothesis Determine whether low-frequency rTMS improves tinnitus by decreasing neural activity in auditory processing regions of the temporal cortex and the utility of PET for targeting treatment. Study Design Randomized, sham-controlled crossover. Methods Patients received a 5-day course of active and sham 1-Hz rTMS (1800 pulses at 110% of motor threshold) to the temporal cortex, with a week separating active and sham treatment. Visual analogue ratings of tinnitus loudness (VARL) were assessed at baseline and the end of each treatment week; regional brain blood flow (rBBF) and glucose metabolism (via PET) were measured before and after treatment in regions of interest (ROI) beneath the stimulating coil and control sites. Results The VARL for both ears significantly decreased after active but not sham treatment. Responders comprised 43% of patients, experiencing at least a 33% drop in tinnitus loudness. The site most consistently associated with a positive response was the secondary auditory cortex (Brodmann Area 22) in either hemisphere. PET asymmetries were variable across patients and not always accessible to rTMS. Whereas PET activity decreased significantly beneath the stimulating coil following active treatment, similar changes occurred at control sites and after sham stimulation. Change in tinnitus perception did not correlate significantly with change in PET activity at the treatment site ROI. Conclusions Active TMS led to a significant reduction in tinnitus loudness, but PET scans failed to support the hypothesis that low-frequency rTMS improves tinnitus by reducing cortical activation at the stimulation site, questioning the utility of PET for targeting rTMS.

One technique for the controlled delivery of ethanol to neonatal rat pups is intragastric intubation. Often, the vehicle used for delivery of ethanol is composed of a nutrient mixture to compensate for decreased suckling or other possible nutritional compromise. This study analyzed the selection of nutrient vehicle, the combination of experimental treatment groups within a litter, and the overall litter size on the growth rate of ethanol-intubated and intubated-control pups, compared with mother-raised control pups. Sprague-Dawley rat pups were raised in litters of 8 or 10, and administered ethanol by intragastric intubation with 20% (v/v) Sustacal or 80% (v/v) Intralipid-II nutrient vehicle. Pups were treated between postnatal days 2 and 10, and body weight was analyzed on day 10. Pups were assigned to a treatment group as either intubated ethanol, intubated control, or nonintubated mother-raised controls. Experimental comparison by statistical analyses was performed to identify the optimal treatment design (mixed treatment groups in a single litter or a single treatment group per litter), the optimal vehicle (Sustacal or Intralipid-II), and the optimal number of pups per litter (8 vs. 10). The analyses demonstrate that the mixing of intubated control, intubated ethanol, and nonintubated mother-raised control treatment groups within a single litter introduced an uncontrolled variable that confounded measurement of ethanol-specific alterations. The sensitivity of treatment groups to inclusion in mixed litters was dependent on the nutrient vehicle and thus nutritional adequacy. Our results suggest that an optimal design was achieved with eight pups per litter. Furthermore, ethanol intubated and intubated control pups grow at a rate identical to parallel litters of eight mother-raised control pups when Intralipid-II is used as nutrient vehicle, and a single treatment group is present in a litter. Optimization of these experimental parameters has provided an excellent neonatal rat model for analysis of specific ethanol effects on brain development during the third trimester.