Polymorphic variation in choline transporter gene (CHT1) is associated with early, subclinical measures of carotid atherosclerosis in humans.

Atherosclerosis is a heritable trait with little known about specific genetic influences on preclinical measures of plaque formation. Based on relations of parasympathetic-cholinergic function to atherosclerosis and to a choline transporter gene [CHT1 (G/T)] polymorphism, we investigated whether the same allelic variant predicts variation in carotid intima-media thickness (IMT) and plaque formation. Carotid IMT and plaque occurrence as well as genotyping for the CHT1 (G/T) variant were measured in a sample (N = 264) of generally healthy adults (age 30-55) of European ancestry. CHT1 GG homozygotes had greater IMT (P < 0.005) and plaque occurrence (P < 0.020) than T allele carriers. This is the first study showing polymorphic variation in the CHT1 gene to predict early, subclinical measures of carotid atherosclerosis which may aid in understanding cholinergic-vagal processes potentially underlying atherosclerotic risk.

Focal electrically administered therapy: device parameter effects on stimulus perception in humans.

BACKGROUND: Focal electrically administered therapy is a new method of transcranial electrical stimulation capable of focal modulation of cerebral activity. Other than invasive studies in animals and examination of motor output in humans, there are limited possibilities for establishing basic principles about how variation in stimulus parameters impact on patterns of intracortical stimulation. This study used a simpler paradigm and evaluated the effects of different stimulation parameters on subjective perception of the quality and location of scalp pain. METHODS: In 2 studies, 19 subjects were randomly stimulated over the left forehead, varying the anode-cathode arrangement, the intensity of stimulation, the electrode size and placement, and whether the current flow was unidirectional or bidirectional. Subjects rated the location of the sensation and its quality. RESULTS: The perceived center of stimulation moved toward the cathode, regardless of placement. This shift in subjective sensation was more prominent when the electricity was unidirectional. In addition, more intense stimulation, as well as stimulation with a smaller electrode, caused greater perceived pain. Unidirectional stimulation was rated more painful when traveling from a large anode to a small cathode and less painful when traveling from a small anode to a large cathode. Finally, participants were more likely to perceive the electrical stimulation as moving toward a specific direction when the intensity was high than when it was low. CONCLUSIONS: The intensity and location of sensations can be manipulated by varying the intensity, current direction, or geometry of electrodes.

Focal electrical stimulation as a sham control for repetitive transcranial magnetic stimulation: Does it truly mimic the cutaneous sensation and pain of active prefrontal repetitive transcranial magnetic stimulation?

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a novel, noninvasive method of stimulating selected regions of the brain that has both research applications and potential clinical utility, particularly for depression. To conduct high-quality clinical studies of rTMS, it is necessary to have a convincing placebo (or sham) treatment. Prefrontal rTMS causes cutaneous discomfort and muscle twitching; therefore, an optimal control condition, ie, sham condition, would mimic the cutaneous sensation and muscular discomfort of rTMS without stimulating the brain. Ideally, the quality and intensity of the sham condition would feel identical to the quality and intensity of the rTMS condition, except that the sham would have no effect on cortical activity. We designed and built a focal electrical stimulation system as a sham rTMS condition. Although this electrical sham system is superior to methods used in previous studies, little is known about how the new electrical sham system compares with active rTMS in terms of the level of discomfort and type of sensation it produces. METHODS: We hypothesized that the electrical sham system may not mirror the experimental condition sufficiently. We studied this hypothesis under single-blind conditions in 15 healthy adults by administering either the real or sham rTMS at high and low intensities while subjects, who were unaware of condition, rated subjective qualities of the stimulation (such as tingling, pinching, and piercing), the scalp location of the perception, and the painfulness of the stimuli. RESULTS: At low-intensity stimulation, the two techniques (active and sham) differ with respect to the subjective quality of the sensation. The differences between real and sham rTMS were less dramatic at higher intensities. The best sham condition that most closely mimics real prefrontal rTMS requires individual titration of the intensity of electrical stimulation across a broad range. Performing this titration without unblinding patients is likely possible, but technically challenging. We propose a new approach to do this. CONCLUSION: We conclude that it is possible to create a truly indistinguishable sham condition (with appropriate acoustic masking as well), but more work is needed beyond these initial attempts.