Detection of common EEG phenomena using individual electrodes placed outside the hair.

Many studies over the past decades have provided exciting evidence that electrical signals recorded from the scalp (electroencephalogram, EEG) hold meaningful information about the brain's function or dysfunction. This information is used routinely in research laboratories to test specific hypotheses and in clinical settings to aid in diagnoses (such as during polysomnography evaluations). Unfortunately, with very few exceptions, such meaningful information about brain function has not yet led to valuable solutions that can address the needs of many people outside such research laboratories or clinics. One of the major hurdles to practical application of EEG-based neurotechnologies is the current predominant requirement to use electrodes that are placed in the hair, which greatly reduces practicality and cosmesis. While several studies reported results using one specific combination of signal/reference electrode outside the hair in one specific context (such as a brain-computer interface experiment), it has been unclear what information about brain function can be acquired using different signal/referencing locations placed outside the hair. To address this issue, in this study, we set out to determine to what extent EEG phenomena related to auditory, visual, cognitive, motor, and sleep function can be detected from different combinations of individual signal/referencing electrodes that are placed outside the hair. The results of our study from 15 subjects suggest that only a few EEG electrodes placed in locations on the forehead or around the ear can provide substantial task-related information in 6 of 7 tasks. Thus, the results of our study provide encouraging evidence and guidance that should invigorate and facilitate the translation of laboratory experiments into practical, useful, and valuable EEG-based neurotechnology solutions.

Neural Mechanism Underlying Task-Specific Enhancement of Motor Learning by Concurrent Transcranial Direct Current Stimulation.

The optimal protocol for neuromodulation by transcranial direct current stimulation (tDCS) remains unclear. Using the rotarod paradigm, we found that mouse motor learning was enhanced by anodal tDCS (3.2 mA/cm2) during but not before or after the performance of a task. Dual-task experiments showed that motor learning enhancement was specific to the task accompanied by anodal tDCS. Studies using a mouse model of stroke induced by middle cerebral artery occlusion showed that concurrent anodal tDCS restored motor learning capability in a task-specific manner. Transcranial in vivo Ca2+ imaging further showed that anodal tDCS elevated and cathodal tDCS suppressed neuronal activity in the primary motor cortex (M1). Anodal tDCS specifically promoted the activity of task-related M1 neurons during task performance, suggesting that elevated Hebbian synaptic potentiation in task-activated circuits accounts for the motor learning enhancement. Thus, application of tDCS concurrent with the targeted behavioral dysfunction could be an effective approach to treating brain disorders.

Ghrelin signaling in dCA1 suppresses neuronal excitability and impairs memory acquisition via PI3K/Akt/GSK-3ß cascades.

Ghrelin is a circulating peptide hormone that promotes feeding and regulates metabolism in humans and rodents. The action of ghrelin is mediated by the growth hormone secretagogue receptor type 1a (GHSR-1a) that is widely distributed in the brain, including the hippocampus. Studies have demonstrated the critical role of hippocampal ghrelin/GHS-R1a signaling in synaptic physiology and memory. However, those findings are controversial, and the mechanism underlying ghrelin modulation of learning and memory is uncertain. Here, we report that micro-infusion of ghrelin in the CA1 region of the dorsal hippocampus during training specifically impairs memory acquisition. The activation of GHS-R1a and the subsequent PI3K/Akt/GSK3ß signaling cascades are involved in this process. Moreover, we report that bath application of ghrelin suppresses the intrinsic excitability of dCA1 pyramidal neurons through activating GHS-R1a, and PI3K inhibitor LY294002 blocks ghrelin's effect. However, LY294002 fails to rescue ghrelin-induced LTP impairment. Our findings support an adverse effect of ghrelin-dependent activation of GHS-R1a on memory acquisition, and suggest that PI3K/Akt/GSK3ß signaling-dependent repression of neuronal intrinsic excitability is an important novel mechanism underlying memory inhibition of ghrelin in the hippocampus.

Ghrelin but not nesfatin-1 affects certain forms of learning and memory in both rats and mice.

Ghrelin and nesfatin-1 are two recently discovered peptide hormones that play opposite roles in the food intake, body-weight control and energy homeostasis in both human and rodents. Beyond its appetite-control function, increasing evidence has shown that ghrelin affects multiple advanced activities in the central nervous system, including memory and emotion. Nesfatin-1 was also widely expressed in extra-hypothalamic brain regions including hippocampus and amygdala. However, the possible actions of nesfatin-1 in those important brain regions are largely unknown. In this study, we micro-infused ghrelin or nesfatin-1 into the lateral amygdala (LA) or area CA1 of the dorsal hippocampus (CA1) and investigated the immediate effects of those two peptide hormones on cognitive and affective behaviors. We found that the micro infusion of ghrelin into the LA or the CA1 interfered with certain types of learning and memory in both rats and mice, while nesfatin-1 had no effect. Our data thus suggested that although nesfatin-1 works as a functional antagonist of ghrelin in the feeding control, only ghrelin affects learning and memory.

Ghrelin modulates lateral amygdala neuronal firing and blocks acquisition for conditioned taste aversion.

Ghrelin is an orexigenic brain-gut hormone promoting feeding and regulating energy metabolism in human and rodents. An increasing number of studies have reported that ghrelin and its identified receptor, the growth hormone secretagogue receptor 1a (GHS-R1a), produces remarkably wide and complex functions and biological effects on specific populations of neurons in central nervous system. In this study, we sought to explore the in vivo effects of acute ghrelin exposure on lateral amygdala (LA) neurons at the physiological and behavioral levels. In vivo extracellular single-unit recordings showed that ghrelin with the concentration of several nanomolars (nM) stimulated spontaneous firing of the LA neurons, an effect that was dose-dependent and could be blocked by co-application of a GHS-R1a antagonist D-Lys3-GHRP-6. We also found that D-Lys3-GHRP-6 inhibited spontaneous firing of the LA neurons in a dose-dependent manner, revealing that tonic GHS-R1a activity contributes to orchestrate the basal activity of the LA neurons. Behaviorally, we found that microinfusion of ghrelin (12 ng) into LA before training interfered with the acquisition of conditioned taste aversion (CTA) as tested at 24 h after conditioning. Pre-treatment with either purified IgG against GHS-R1a or GHS-R1a antagonist blocked ghrelin's effect on CTA memory acquisition. Ghrelin (12 ng) had no effect on CTA memory consolidation or the expression of acquired CTA memory; neither did it affect the total liquid consumption of tested rats. Altogether, our data indicated that ghrelin locally infused into LA blocks acquisition of CTA and its modulation effects on neuronal firing may be involved in this process.