Conventional two-photon microscopy (TPM) is capable of imaging neural dynamics with subcellular resolution, but it is limited to a field-of-view (FOV) diameter <1  mm. Although there has been recent progress in extending the FOV in TPM, a principled design approach for developing large FOV TPM (LF-TPM) with off-the-shelf components has yet to be established. Therefore, we present a design strategy that depends on analyzing the optical invariant of commercially available objectives, relay lenses, mirror scanners, and emission collection systems in isolation. Components are then selected to maximize the space-bandwidth product of the integrated microscope. In comparison with other LF-TPM systems, our strategy simplifies the sequence of design decisions and is applicable to extending the FOV in any microscope with an optical relay. The microscope we constructed with this design approach can image <1.7-μm lateral and <28-μm axial resolution over a 7-mm diameter FOV, which is a 100-fold increase in FOV compared with conventional TPM. As a demonstration of the potential that LF-TPM has on understanding the microarchitecture of the mouse brain across interhemispheric regions, we performed in vivo imaging of both the cerebral vasculature and microglia cell bodies over the mouse cortex.

Cortical circuit reorganization induced by anodal transcranial direct current stimulation (tDCS) over the Broca’s area of the dominant language hemisphere in 13 healthy adults was quantified by functional near-infrared spectroscopy (fNIRS). Transient cortical reorganization patterns in steady-state functional connectivity (seed-based and graph theory analysis) and temporal functional connectivity (sliding window correlation analysis) were recorded before, during, and after applying high current tDCS (1 mA, 8 min). fNIRS connectivity mapping showed that tDCS induced significantly (p  <  0.05) increased functional connectivity between Broca’s area and its neighboring cortical regions while it simultaneously decreased the connectivity to remote cortical regions. Furthermore, the anodal stimulation caused significant increases to the functional connectivity variability (FCV) of remote cortical regions related to language processing. In addition to the high current tDCS, low current tDCS (0.5 mA, 2 min 40 s) was also applied to test whether the transient effects of lower stimulation current could qualitatively predict cortical connectivity alterations induced by the higher currents. Interestingly, low current tDCS could qualitatively predict the increase in clustering coefficient and FCV but not the enhancement of local connectivity. Our findings indicate the possibility of combining future studies fNIRS with tDCS at lower currents to help guide therapeutic interventions.

Region and cell-type restricted expression of light-activated ion channels is the indispensable tool to study properties of synapses in specific circuits and to monitor synaptic alterations by various stimuli including neuromodulators and behaviors, both ex vivo and in vivo. These analyses require the light-activated proteins or viral vectors for their delivery that do not interfere with the phenomenon under study. Here, we report a case of such interference in which the high-level expression of channelrhodopsin-2 introduced in the somatostatin-positive GABAergic neurons of the dorsomedial prefrontal cortex by an adeno-associated virus vector weakens the presynaptic GABAb receptor-mediated suppression of GABA release.

Holographic speckle is a major impediment to computer-generated holographic (CGH) projections in applications ranging from display, optical tweezers, and machining to optogenetic neural control. We present an iterative phase retrieval algorithm that allows the projection of amplitude-controlled speckle-free one-dimensional patterns with a high degree of pattern uniformity. The algorithm, termed the weighted Gerchberg–Saxton with phase-control (GSW-PC), is shown to have the ability to simultaneously control both the phase and amplitude of projected patterns with high diffraction efficiencies. Furthermore, we show that the framework can address the challenge of projecting volumetric phase and amplitude-controlled patterns, by incorporating GSW-PC with the angular spectrum method. The algorithms’ performance is numerically and experimentally tested, and further compared with conventional and modern CGH techniques.

Simultaneous recording of optical and electrophysiological signals from multiple cortical areas may provide crucial information to expand our understanding of cortical function. However, the insertion of multiple electrodes into the brain may compromise optical imaging by both restricting the field of view and interfering with the approaches used to stabilize the specimen. Existing methods that combine electrophysiological recording and optical imaging in vivo implement either multiple surface electrodes, silicon probes, or a single electrode for deeper recordings. To address such limitation, we built a microelectrode array (hyperdrive, patent US5928143 A) compatible with wide-field imaging that allows insertion of up to 12 probes into a large brain area (8 mm diameter). The hyperdrive is comprised of a circle of individual microdrives where probes are positioned at an angle leaving a large brain area unobstructed for wide-field imaging. Multiple tetrodes and voltage-sensitive dye imaging were used for acute simultaneous registration of spontaneous and evoked cortical activity in anesthetized mice. The electrophysiological signals were used to extract local field potential (LFP) traces, multiunit, and single-unit spiking activity. To demonstrate our approach, we compared LFP and VSD signals over multiple regions of the cortex and analyzed the relationship between single-unit and global cortical population activities. The study of the interactions between cortical activity at local and global scales, such as the one presented in this work, can help to expand our knowledge of brain function.

Fiber photometry uses genetically encoded optical reporters to link specific cellular activity in stereotaxically targeted brain structures to specific behaviors. There are still a number of barriers that have hindered the widespread adoption of this approach. This includes cost, but also the high-levels of light required to excite the fluorophore, limiting commercial systems to the investigation of short-term transients in neuronal activity to avoid damage of tissue by light. Here, we present a cost-effective optoelectronic system for in vivo fiber photometry that achieves high-sensitivity to changes in fluorescence intensity, enabling detection of optical transients of a popular calcium reporter with excitation powers as low as 100 nW. By realizing a coherent detection scheme and by using a photomultiplier tube as a detector, the system demonstrates reliable study of in vivo neuronal activity, positioning it for future use in the experiments inquiring into learning and memory processes. The system was applied to study stress-evoked calcium transients in corticotropin-releasing hormone neurons in the mouse hypothalamus.

Time-domain diffuse correlation spectroscopy (TD-DCS) has been recently proposed to improve detection of deep blood flow dynamics in a biological tissue, such as human brain. To obtain a high sensitive measurement, several experimental parameters such as the source–detector (SD) distance, gate opening time, and width need to be considered and optimized. We use a simulation approach to optimize these parameters based on Monte Carlo computations using a realistic human head model. Two cortical regions are investigated including the frontal and temporal lobes. SD distance ranging from 0 to 45 mm, gate opening time from 400 to 1000 ps, and gate width from 50 to 3000 ps are considered. The goal is to find out the optimal combinations of these parameters by which the higher contrast measurement on the cortical dynamics can be achieved. The simulations show that with an acceptable input power of light, the combinations of SD distance ranging from 0 to 15 mm, gate opening time at 700 to 800 ps, and gate width of 800 ps are optimal for achieving higher contrast measurement on the cortical dynamics. The simulation approach and results are helpful for the optimization of TD-DCS experimental design focused on brain functional detection.

Motion artifacts are often a significant component of the measured signal in functional near-infrared spectroscopy (fNIRS) experiments. A variety of methods have been proposed to address this issue, including principal components analysis (PCA), correlation-based signal improvement (CBSI), wavelet filtering, and spline interpolation. The efficacy of these techniques has been compared using simulated data; however, our understanding of how these techniques fare when dealing with task-based cognitive data is limited. Brigadoi et al. compared motion correction techniques in a sample of adult data measured during a simple cognitive task. Wavelet filtering showed the most promise as an optimal technique for motion correction. Given that fNIRS is often used with infants and young children, it is critical to evaluate the effectiveness of motion correction techniques directly with data from these age groups. This study addresses that problem by evaluating motion correction algorithms implemented in HomER2. The efficacy of each technique was compared quantitatively using objective metrics related to the physiological properties of the hemodynamic response. Results showed that targeted PCA (tPCA), spline, and CBSI retained a higher number of trials. These techniques also performed well in direct head-to-head comparisons with the other approaches using quantitative metrics. The CBSI method corrected many of the artifacts present in our data; however, this approach produced sometimes unstable HRFs. The targeted PCA and spline methods proved to be the most robust, performing well across all comparison metrics. When compared head to head, tPCA consistently outperformed spline. We conclude, therefore, that tPCA is an effective technique for correcting motion artifacts in fNIRS data from young children.

A detailed theoretical analysis of low-power, fast optogenetic control of firing of Chronos-expressing neurons has been presented. A three-state model for the Chronos photocycle has been formulated and incorporated in a fast-spiking interneuron circuit model. The effect of excitation wavelength, pulse irradiance, pulse width, and pulse frequency has been studied in detail and compared with ChR2. Theoretical simulations are in excellent agreement with recently reported experimental results and bring out additional interesting features. At very low irradiances (0.005  mW  /  mm²), the plateau current in Chronos exhibits a maximum. At 0.05  mW  /  mm², the plateau current is 2 orders of magnitude smaller and saturates at longer pulse widths (∼700  ms) compared to ChR2 (∼350  ms). I_peak in Chronos saturates at much shorter pulse widths (1775 pA at 1.5 ms and 5  mW  /  mm²) than in ChR2. Spiking fidelity is also higher at lower irradiances and longer pulse widths compared to ChR2. Chronos exhibits an average maximal driven rate of over 200  spikes  /  s in response to 100  pulses  /  s stimuli, each of 1-ms pulse-width, in the intensity range 0 to 200  mW  /  mm². The analysis is important to not only understand the photodynamics of Chronos and Chronos-expressing neurons but also to design opsins with optimized properties and perform precision experiments with required spatiotemporal resolution.

This study examined the neural mechanism underlying two translation strategies associated with Chinese to English simultaneous interpreting (SI) targeting the left prefrontal cortex (PFC), which is generally involved in the control of interference and conflict resolution and has been identified as the brain area that plays a pivotal role in SI. Brain activation associated with the two strategies including “pairing” and “transphrasing” were compared with that from “nontranslation,” which keeps the source language item unchanged in the target language production and is considered as a tactic that does not require complex cognitive operation associated with bilingual processing effort. Our findings revealed that “pairing” elicited the strongest and almost immediate brain activation in the Broca’s area, and “transphrasing” resulted in the most extensive and strongest activation overall in the left PFC. By contrast, “nontranslation” induced very little brain activation in these regions. This work, which represents one of the first efforts in investigating brain activation related to translation strategies involving different levels of cognitive control, will not only pave a new avenue for better understanding of the cognitive mechanism underlying SI but also provide further insight into the role that the Broca’s region plays in domain-general cognitive control.

Many patients with substance use disorders (SUDs) live in a stressful environment, and comorbidity is not uncommon. Understanding the neural mechanisms underlying heroin and nicotine dependences and their relationships to social cognition could facilitate behavioral therapy efficacy. We aimed to provide a translational approach that leads to identifying potential biomarkers for opioid use disorder (OUD) susceptibility during recovery. We examined the clinical characters and the relationships between theory of mind (ToM) and executive functions in three groups: heroin plus nicotine-dependent (HND) patients who had remained heroin abstinent (≥3 months), nicotine-dependent (ND) subjects, and healthy controls (C). The domains included emotion recognition, inhibition, shifting, updating, access, and processing speed. Resting-state functional connectivity (rsFC), ToM task-induced functional connectivity, and brain networks were then explored among 21 matched subjects using functional near-infrared spectroscopy. HND enhanced the severities of anxiety, depression, and hyperactivity. Inhibition domain was impaired in both HND and ND. No impairment in domains of emotion recognition, access, and update was observed. HND demonstrated enhanced rsFC in the medial prefrontal cortex and orbitofrontal cortex (OFC) and decreased ToM-induced connectivity across the PFC. The right superior frontal gyrus in the OFC (oSFG; x  =  22, y  =  77, and z  =  6) was associated with working memory and emotion recognition in HND. Using a neuroimaging tool, these results supported the prominent reward-deficit-and-stress-surfeit hypothesis in SUDs, especially OUD, after protracted withdrawal. This may provide an insight in identifying potential biomarkers related to a dynamic environment.