Neurophotonics最新文献

Significance: Prefrontal cortex (PFC) hemodynamics are regulated by numerous underlying neurophysiological components over multiple temporal scales. The pattern of output signals, such as functional near-infrared spectroscopy fluctuations (i.e., fNIRS), is thus complex. We demonstrate first-of-its-kind evidence that this fNIRS complexity is a marker that captures the influence of endurance capacity and the effects of hydrogen gas ($H_2$) on PFC regulation.

Aim: We aim to explore the effects of different physical loads of exercise as well as the intaking of hydrogen gas on the fNIRS complexity of the PFC.

Approach: Twenty-four healthy young men completed endurance cycling exercise from 0 (i.e., baseline) to 100% of their physical loads after intaking 20 min of either $H_2$ or placebo gas (i.e., control) on each of two separate visits. The fNIRS measuring the PFC hemodynamics and heart rate (HR) was continuously recorded throughout the exercise. The fNIRS complexity was quantified using multiscale entropy.

Results: The fNIRS complexity was significantly greater in the conditions from 25% to 100% of the physical load ($p<0.0005$) compared with the baseline and after intaking $H_2$ before exercise; this increase of fNIRS complexity was significantly greater compared with the control ($p=0.001\sim 0.01$). At the baseline, participants with a greater fNIRS complexity had a lower HR ($\beta =-0.35\sim -0.33$, $p=0.008\sim 0.02$). Those with a greater increase of complexity had a lower increase of the HR ($\beta =-0.30\sim -0.28$, $p=0.001\sim 0.002$) during exercise.

Conclusions: These observations suggest that fNIRS complexity would be a marker that captures the adaptive capacity of PFC to endurance exercise and to the effects of interventions on PFC hemodynamics.

Significance: Diffuse correlation spectroscopy (DCS) is an optical method to measure relative changes in cerebral blood flow (rCBF) in the microvasculature. Each heartbeat generates a pulsatile signal with distinct morphological features that we hypothesized to be related to intracranial compliance (ICC).

Aim: We aim to study how three features of the pulsatile rCBF waveforms: the augmentation index (AIx), the pulsatility index, and the area under the curve, change with respect to ICC. We describe ICC as a combination of vascular compliance and extravascular compliance.

Approach: Since patients with Chiari malformations (CM) ($n=30$) have been shown to have altered extravascular compliance, we compare the morphology of rCBF waveforms in CM patients with age-matched healthy control ($n=30$).

Results: AIx measured in the supine position was significantly less in patients with CM compared to healthy controls ($p<0.05$). Since physiologic aging also leads to changes in vessel stiffness and intravascular compliance, we evaluate how the rCBF waveform changes with respect to age and find that the AIx feature was strongly correlated with age ($R_{\text{healthy subjects}}=-0.63$, $R_{\text{preoperative}\mathrm{CM}\text{patient}}=-0.70$, and $R_{\text{postoperative}\mathrm{CM}\text{patients}}=-0.62$, $p<0.01$).

Conclusions: These results suggest that the AIx measured in the cerebral microvasculature using DCS may be correlated to changes in ICC.

Significance: Comorbidities such as mood and cognitive disorders are often found in individuals with epilepsy after seizures. Cortex processes sensory, motor, and cognitive information. Brain circuit changes can be studied by observing functional network changes in epileptic mice's cortex.

Aim: The cortex is easily accessible for non-invasive brain imaging and electroencephalogram recording (EEG). However, the impact of seizures on cortical activity and functional connectivity has been rarely studied in vivo.

Approach: Intrinsic optical signal and EEG were used to monitor cortical activity in awake mice within 4 h after pilocarpine induction. It was divided into three periods according to the behavior and EEG of the mice: baseline, onset of seizures (onset, including seizures and resting in between seizure events), and after seizures (post, without seizures). Changes in cortical activity were compared between the baseline and after seizures.

Results: Hemoglobin levels increased significantly, particularly in the parietal association cortex (PT), retrosplenial cortex (RS), primary visual cortex (V1), and secondary visual cortex (V2). The network-wide functional connectivity changed post seizures, e.g., hypoconnectivity between PT and visual-associated cortex (e.g., V1 and V2). In contrast, connectivity between the motor-associated cortex and most other regions increased. In addition, the default mode network (DMN) also changed after seizures, with decreased connectivity between primary somatosensory region (SSp) and visual region (VIS), but increased connectivity involving anterior cingulate cortex (AC) and RS.

Conclusions: Our results provide references for understanding the mechanisms behind changes in brain circuits, which may explain the profound effects of seizures on comorbid health conditions.

Imaging neuronal architecture has been a recurrent challenge over the years, and the localization of synaptic proteins is a frequent challenge in neuroscience. To quantitatively detect and analyze the structure of synapses, we recently developed free SODA software to detect the association of pre and postsynaptic proteins. To fully take advantage of spatial distribution analysis in complex cells, such as neurons, we also selected some new dyes for plasma membrane labeling. Using Icy SODA plugin, we could detect and analyze synaptic association in both conventional and single molecule localization microscopy, giving access to a molecular map at the nanoscale level. To replace those molecular distributions within the neuronal three-dimensional (3D) shape, we used MemBright probes and 3D STORM analysis to decipher the entire 3D shape of various dendritic spine types at the single-molecule resolution level. We report here the example of synaptic proteins within neuronal mask, but these tools have a broader spectrum of interest since they can be used whatever the proteins or the cellular type. Altogether with SODA plugin, MemBright probes thus provide the perfect toolkit to decipher a nanometric molecular map of proteins within a 3D cellular context.

Significance: Bedside cerebral blood flow (CBF) monitoring has the potential to inform and improve care for acute neurologic diseases, but technical challenges limit the use of existing techniques in clinical practice.

Aim: Here, we validate the Openwater optical system, a novel wearable headset that uses laser speckle contrast to monitor microvascular hemodynamics.

Approach: We monitored 25 healthy adults with the Openwater system and concurrent transcranial Doppler (TCD) while performing a breath-hold maneuver to increase CBF. Relative blood flow (rBF) was derived from changes in speckle contrast, and relative blood volume (rBV) was derived from changes in speckle average intensity.

Results: A strong correlation was observed between beat-to-beat optical rBF and TCD-measured cerebral blood flow velocity (CBFv), $R=0.79$; the slope of the linear fit indicates good agreement, 0.87 (95% CI: 0.83 $-0.92$). Beat-to-beat rBV and CBFv were also strongly correlated, $R=0.72$, but as expected the two variables were not proportional; changes in rBV were smaller than CBFv changes, with linear fit slope of 0.18 (95% CI: 0.17 to 0.19). Further, strong agreement was found between rBF and CBFv waveform morphology and related metrics.

Conclusions: This first in vivo validation of the Openwater optical system highlights its potential as a cerebral hemodynamic monitor, but additional validation is needed in disease states.

Significance: The development of imaging systems that are cost-efficient and modular is essential for modern neuroscience research.

Aim: In the current study, we designed, developed, and characterized a low-cost reversible tandem lens mesoscope for brain imaging in rodents.

Approach: Using readily available components, we assembled a robust imaging system that is highly efficient and cost-effective. We developed a mesoscope that offers high-resolution structural and functional imaging with cost-effective lenses and CMOS camera.

Results: The reversible tandem lens configuration of the mesoscope offers two fields of view (FOVs), which can be achieved by swapping the objective and imaging lenses. The large FOV configuration of $12.6\times 10.5\mathrm{mm}$ provides a spatial resolution up to $4.92\mu m$, and the small FOV configuration of $6\times 5\mathrm{mm}$ provides a resolution of up to $2.46\mu m$. We demonstrate the efficiency of our system for imaging neuronal calcium activity in both rat and mouse brains in vivo.

Conclusions: The careful selection of the mesoscope components ensured its compactness, portability, and versatility, meaning that different types of samples and sample holders can be easily accommodated, enabling a range of different experiments both in vivo and in vitro. The custom-built reversible FOV mesoscope is cost-effective and was developed for under US$10,000 with excellent performance.

Significance: fNIRS-based neuroenhancement depends on the feasible detection of hemodynamic responses in target brain regions. Using the lateral occipital complex (LOC) and the fusiform face area (FFA) in the ventral visual pathway as neurofeedback targets boosts performance in visual recognition. However, the feasibility of utilizing fNIRS to detect LOC and FFA activity in adults remains to be validated as the depth of these regions may exceed the detection limit of fNIRS.

Aim: This study aims to investigate the feasibility of using fNIRS to measure hemodynamic responses in the ventral visual pathway, specifically in the LOC and FFA, in adults.

Approach: We recorded the hemodynamic activities of the LOC and FFA regions in 35 subjects using a portable eight-channel fNIRS instrument. A standard one-back object and face recognition task was employed to elicit selective brain responses in the LOC and FFA regions. The placement of fNIRS optodes for LOC and FFA detection was guided by our group's transcranial brain atlas (TBA).

Results: Our findings revealed selective activation of the LOC target channel (CH2) in response to objects, whereas the FFA target channel (CH7) did not exhibit selective activation in response to faces.

Conclusions: Our findings indicate that, although fNIRS detection has limitations in capturing FFA activity, the LOC region emerges as a viable target for fNIRS-based detection. Furthermore, our results advocate for the adoption of the TBA-based method for setting the LOC target channel, offering a promising solution for optrode placement. This feasibility study stands as the inaugural validation of fNIRS for detecting cortical activity in the ventral visual pathway, underscoring its ecological validity. We suggest that our findings establish a pivotal technical groundwork for prospective real-life applications of fNIRS-based research.

Serge Charpak (Institut de la Vision) discusses his pioneering work in imaging of sensory processing and neurovascular coupling, in an interview with former trainee and fellow Neurophotonics Editorial Board Member Jérôme Lecoq (Allen Institute).

Significance: An array of techniques for targeted neuromodulation is emerging, with high potential in brain research and therapy. Calcium imaging or other forms of functional fluorescence imaging are central solutions for monitoring cortical neural responses to targeted neuromodulation, but often are confounded by thermal effects that are inter-mixed with neural responses.

Aim: Here, we develop and demonstrate a method for effectively suppressing fluorescent thermal transients from calcium responses.

Approach: We use high precision phased-array 3 MHz focused ultrasound delivery integrated with fiberscope-based widefield fluorescence to monitor cortex-wide calcium changes. Our approach for detecting the neural activation first takes advantage of the high inter-hemispheric correlation of resting state ${\mathrm{Ca}}^{2+}$ dynamics and then removes the ultrasound-induced thermal effect by subtracting its simulated spatio-temporal signature from the processed profile.

Results: The focused $350\mu m$-sized ultrasound stimulus triggered rapid localized activation events dominated by transient thermal responses produced by ultrasound. By employing bioheat equation to model the ultrasound heat deposition, we can recover putative neural responses to ultrasound.

Conclusions: The developed method for canceling transient thermal fluorescence quenching could also find applications with optical stimulation techniques to monitor thermal effects and disentangle them from neural responses. This approach may help deepen our understanding of the mechanisms and macroscopic effects of ultrasound neuromodulation, further paving the way for tailoring the stimulation regimes toward specific applications.