Implantable Micro-Light-Emitting Diode (µLED)-based optogenetic interfaces toward human applications.

Optogenetics has received wide attention in biomedical fields because of itsadvantages in temporal precision and spatial resolution. Beyond contributions to important advances in fundamental research, optogenetics is inspiring a shift towards new methods of improving human well-being and treating diseases. Soft, flexible and biocompatible systems using µLEDs as a light source have been introduced to realize brain-compatible optogenetic implants, but there are still many technical challenges to overcome before their human applications. In this review, we address progress in the development of implantable µLED probes and recent achievements in (i) device engineering design, (ii) driving power, (iii) multifunctionality and (iv) closed-loop systems. (v) Expanded optogenetic applications based on remarkable advances in µLED implants will also be discussed.

Molecular laterality encodes stress susceptibility in the medial prefrontal cortex.

Functional lateralization of the prefrontal cortex has been implicated in stress and emotional disorders, yet underlying gene expression changes remains unknown. Here, we report molecular signatures lateralized by chronic social defeats between the two medial prefrontal cortices (mPFCs). Stressed mice show 526 asymmetrically expressed genes between the mPFCs. This cortical asymmetry selectively occurs in stressed mice with depressed social activity, but not in resilient mice with normal behavior. We have isolated highly asymmetric genes including connective tissue growth factor (CTGF), a molecule that modulates wound healing at the periphery. Knockdown of CTGF gene in the right mPFC by shRNA led to a stress-resistant behavioral phenotype. Overexpression of CTGF in the right mPFC using viral transduction induces social avoidance while the left mPFC thereof prevent stress-induced social avoidance. Our study provides a molecular window into the mechanism of stress-induced socioemotional disorders, which can pave the way for new interventions by targeting cortical asymmetry.

Effect of Expectation on Pain Processing: A Psychophysics and Functional MRI Analysis.

Pain is a complex phenomenon that is highly modifiable by expectation. Whilst the intensity of incoming noxious information plays a key role in the intensity of perceived pain, this intensity can be profoundly shaped by an individual's expectations. Modern brain imaging investigations have begun to detail the brain regions responsible for placebo and nocebo related changes in pain, but less is known about the neural basis of stimulus-expectancy changes in pain processing. In this functional magnetic resonance imaging study, we administered two separate protocols of the same noxious thermal stimuli to 24 healthy subjects. However, different expectations were elicited by different explanations to subjects prior to each protocol. During one protocol, pain intensities were matched to expectation and in the other protocol they were not. Pain intensity was measured continuously via a manually operated computerized visual analogue scale. When individuals expected the stimulus intensity to remain constant, but in reality it was surreptitiously increased or decreased, pain intensity ratings were significantly lower than when expectation and pain intensities were matched. When the stimulus intensities did not match expectations, various areas in the brain such as the amygdala, anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (dlPFC), and the midbrain periaqueductal gray matter (PAG) displayed significantly different patterns of activity compared to instances when stimulus intensity and pain expectations were matched. These results show that stimulus-expectancy manipulation of pain intensity alters activity in both higher brain and brainstem centers which are known to modulate pain under various conditions.