Brain function relies on the ability of neural networks to maintain stable levels of activity, while experiences sculpt them. In neocortex, the balance between activity and stability relies on the co-regulation of excitatory and inhibitory inputs onto principal neurons. Shifts of excitation or inhibition result in altered excitability impaired processing of incoming information. In many neurodevelopmental and neuropsychiatric disorders, the excitability of local circuits is altered, suggesting that their pathophysiology may involve shifts in synaptic excitation, inhibition or both. Most studies focused on identifying the cellular and molecular mechanisms controlling network excitability to assess whether may be altered in animal models of disease. The impact of changes in excitation/inhibition (E/I) balance on local circuit and network computations is not clear. Here we report findings on the integration of excitatory and inhibitory inputs in healthy cortical circuits and discuss how shifts in E/I balance may relate to pathological phenotypes.

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Introduction The goal of cognitive enhancement is to improve mental functions using interventions including cognitive training, brain stimulation and pharmacology. Indeed, psychostimulants, commonly used for cognitive enhancement purposes, while preventing sleep, have been shown to increase working memory (WM) and attention. WM is widely believed play a core role in cognitive ability, and has been shown to correlate with broad measure of cognitive ability and fluid intelligence. Sleep, however, is also important for cognitive function; thus, understanding the interaction between stimulants, sleep and cognition may inform current approaches to cognitive enhancement. Methods We used a double-blind, placebo controlled, repeated-measure design to investigate the effect of morning administration (9am) of stimulant, dextroamphetamine (DEX, 20 mg), on within-day and overnight WM performance, and sleep in 46 (22 female) healthy young adults. We tested WM using an operation span task (OSPAN) as it engages and captures both the memory retention and online processing capacity of WM. WM was tested at 75 minutes post drug, 12 h post drug, and 24 h post drug over a night of sleep. Results Compared with placebo, DEX showed no changes to WM performance at 75min or 12-hr post-drug. After sleep, DEX performed worse than PBO and the overnight improvement in performance in the PBO condition was absent in the DEX condition. Moreover, sleep quality was negatively affected by DEX administration. Conclusion In summary, we found no cognitive boost from psychostimulants across a day of wake and a blockade of overnight WM increases with the stimulant, compared to PBO. Given the growing non-medical use of stimulants in young adults, these findings have important implications for assessing their benefit for cognitive enhancement. Support Office of Naval Research N00014-14-1-0513 (S.M.) and DoD Young Investigator Prize (S.M.)

Introduction There is a growing trend in the non-medical use of prescription psychostimulant (PStim) in healthy adults One of the main reasons of increased usage of PStim is due to their perceived benefits on the cognitive capacity. However, evidences from empirical studies on healthy adults point to an inconclusive answer. There are various factors which could have contributed to these overall mixed findings. These factors range from differences in drug dosages, individual baseline variability and use of different tasks. However, one of the important factors that previous studies have not considered is the presence possible selective bias of PStim towards a specific cognitive domain over others which may lead to its selective enhancement at the cost of others’ degradation. Methods To study this, we carried out a double blind, placebo-controlled study, with repeated measures design to investigate the differential influence of a stimulant drug (DEX vs PBO) on the cognitive skills of working memory (WM) and spatial selective attentive in the form multiple object tracking (MOT) across a period of a day. We compared the change in the performance of WM and MOT in DEX vs PBO conditions at 1) pre-drug baseline, 2) 75 minutes post-drug (peak concentration), 3) 12 hours post-drug intake (washout). Results First, we found that DEX did not have any overall significant effect on WM performance across a period of day compared to the placebo condition. We also found that MOT performance was rescued by DEX, unlike the placebo condition in which the MOT performance degraded over different testing periods across a wake day period. Importantly, we found that during the peak concentration of DEX in the body MOT performance was significantly superior to that of the WM performance. This superiority of MOT over WM was not present before the drug administration (baseline) and also returned to a level similar to baseline after a gap of 12hours. Conclusion Overall, our study findings suggest that DEX has a favorable bias towards MOT compared to WM and selectively enhances its performance when the brain is required to support both of these two cognitive domains concurrently. Support (If Any)