The combination of in vivo extracellular recording and genetic-engineering-assisted optical stimulation is a powerful tool for the study of neuronal circuits. Precise analysis of complex neural circuits requires high-density integration of multiple cellular-size light sources and recording electrodes. However, high-density integration inevitably introduces stimulation artifact. We present minimal-stimulation-artifact (miniSTAR) μLED optoelectrodes that enable effective elimination of stimulation artifact. A multi-metal-layer structure with a shielding layer effectively suppresses capacitive coupling of stimulation signals. A heavily boron-doped silicon substrate silences the photovoltaic effect induced from LED illumination. With transient stimulation pulse shaping, we reduced stimulation artifact on miniSTAR μLED optoelectrodes to below 50 μVpp, much smaller than a typical spike detection threshold, at optical stimulation of >50 mW mm–2irradiance. We demonstrated high-temporal resolution (<1 ms) opto-electrophysiology without any artifact-induced signal quality degradation during in vivo experiments. MiniSTAR μLED optoelectrodes will facilitate functional mapping of local circuits and discoveries in the brain.
Dynamic interactions within and across brain areas underlie behavioral and cognitive functions. To understand the basis of these processes, the activities of distributed local circuits inside the brain of a behaving animal must be synchronously recorded while the inputs to these circuits are precisely manipulated. Even though recent technological advances have enabled such large‐scale recording capabilities, the development of the high‐spatiotemporal‐resolution and large‐scale modulation techniques to accompany those recordings has lagged. A novel neural probe is presented in this work that enables simultaneous electrical monitoring and optogenetic manipulation of deep neuronal circuits at large scales with a high spatiotemporal resolution. The “hectoSTAR” micro‐light‐emitting‐diode (μLED) optoelectrode features 256 recording electrodes and 128 stimulation μLEDs monolithically integrated on the surface of its four 30‐µm thick silicon micro‐needle shanks, covering a large volume with 1.3‐mm × 0.9‐mm cross‐sectional area located as deep as 6 mm inside the brain. The use of this device in behaving mice for dissecting long‐distance network interactions across cortical layers and hippocampal regions is demonstrated. The recording‐and‐stimulation capabilities hectoSTAR μLED optoelectrodes enables will open up new possibilities for the cellular and circuit‐based investigation of brain functions in behaving animals.
more » « less- Award ID(s):
- 1707316
- NSF-PAR ID:
- 10446318
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Science
- Volume:
- 9
- Issue:
- 18
- ISSN:
- 2198-3844
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
more » « less
Abstract -
more » « less
Abstract Understanding the cytoarchitecture and wiring of the brain requires improved methods to record and stimulate large groups of neurons with cellular specificity. This requires miniaturized neural interfaces that integrate into brain tissue without altering its properties. Existing neural interface technologies have been shown to provide high-resolution electrophysiological recording with high signal-to-noise ratio. However, with single implantation, the physical properties of these devices limit their access to one, small brain region. To overcome this limitation, we developed a platform that provides three-dimensional coverage of brain tissue through multisite multifunctional fiber-based neural probes guided in a helical scaffold. Chronic recordings from the spatially expandable fiber probes demonstrate the ability of these fiber probes capturing brain activities with a single-unit resolution for long observation times. Furthermore, using
Thy1-ChR2-YFP mice we demonstrate the application of our probes in simultaneous recording and optical/chemical modulation of brain activities across distant regions. Similarly, varying electrographic brain activities from different brain regions were detected by our customizable probes in a mouse model of epilepsy, suggesting the potential of using these probes for the investigation of brain disorders such as epilepsy. Ultimately, this technique enables three-dimensional manipulation and mapping of brain activities across distant regions in the deep brain with minimal tissue damage, which can bring new insights for deciphering complex brain functions and dynamics in the near future. -
Abstract Functional magnetic resonance imaging (fMRI) has become an indispensable tool for investigating the human brain. However, the inherently poor signal-to-noise-ratio (SNR) of the fMRI measurement represents a major barrier to expanding its spatiotemporal scale as well as its utility and ultimate impact. Here we introduce a denoising technique that selectively suppresses the thermal noise contribution to the fMRI experiment. Using 7-Tesla, high-resolution human brain data, we demonstrate improvements in key metrics of functional mapping (temporal-SNR, the detection and reproducibility of stimulus-induced signal changes, and accuracy of functional maps) while leaving the amplitude of the stimulus-induced signal changes, spatial precision, and functional point-spread-function unaltered. We demonstrate that the method enables the acquisition of ultrahigh resolution (0.5 mm isotropic) functional maps but is also equally beneficial for a large variety of fMRI applications, including supra-millimeter resolution 3- and 7-Tesla data obtained over different cortical regions with different stimulation/task paradigms and acquisition strategies.more » « less
-
more » « less
Abstract Over the past decade, stereotactically placed electrodes have become the gold standard for deep brain recording and stimulation for a wide variety of neurological and psychiatric diseases. Current electrodes, however, are limited in their spatial resolution and ability to record from small populations of neurons, let alone individual neurons. Here, we report on an innovative, customizable, monolithically integrated human-grade flexible depth electrode capable of recording from up to 128 channels and able to record at a depth of 10 cm in brain tissue. This thin, stylet-guided depth electrode is capable of recording local field potentials and single unit neuronal activity (action potentials), validated across species. This device represents an advance in manufacturing and design approaches which extends the capabilities of a mainstay technology in clinical neurology.
-
Abstract Neural activity coordinated across different scales from neuronal circuits to large-scale brain networks gives rise to complex cognitive functions. Bridging the gap between micro- and macro-scale processes, we present a novel framework based on the maximum entropy model to infer a hybrid resting state structural connectome, representing functional interactions constrained by structural connectivity. We demonstrate that the structurally informed network outperforms the unconstrained model in simulating brain dynamics; wherein by constraining the inference model with the network structure we may improve the estimation of pairwise BOLD signal interactions. Further, we simulate brain network dynamics using Monte Carlo simulations with the new hybrid connectome to probe connectome-level differences in excitation-inhibition balance between apolipoprotein E (APOE)-ε4 carriers and noncarriers. Our results reveal sex differences among APOE-ε4 carriers in functional dynamics at criticality; specifically, female carriers appear to exhibit a lower tolerance to network disruptions resulting from increased excitatory interactions. In sum, the new multimodal network explored here enables analysis of brain dynamics through the integration of structure and function, providing insight into the complex interactions underlying neural activity such as the balance of excitation and inhibition.more » « less
