Name: brain mapping using a graphene electrode array
Uploaded: 2023-10-20T14:45:00
Description: Watch this Scientific Journal Video about Brain Mapping Using a Graphene Electrode Array at JoVE.com

This work was supported by Incheon National University (International Cooperative) for Sunggu Yang.

All animal-handling procedures were approved by the Institutional Animal Care and Use Committee of the Incheon National University (INU-ANIM-2017-08).
1. Animal preparation for surgery
NOTE: Use Sprague Dawley Rat (8-10 weeks old) without the sex bias for this experiment.
<ol>
	<li>Anesthetize the rat with 90 mg/kg ketamine and 10 mg/kg xylazine cocktail intraperitoneally. To maintain the desired depth of anesthesia throughout the surgery, provide...

<ol>
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The presented protocol provides an in-depth, step-by-step process that explains how to access and map the somatosensory responses of rats using a graphene electrode array. The protocol-acquired data are SEPs that provide somatosensory information that is synaptically linked to each body part.
Several aspects of this protocol should be considered. When extracting cerebrospinal fluid to prevent brain edema and mitigate inflammation, it is crucial for the experimenter not to damage the brainstem ...

A cortical map is a set of local patches representing response properties to sensorimotor stimuli in the cerebral cortex. They are a spatial formation of neural networks and enable prediction for perception and cognition. Therefore, cortical maps are useful in evaluating neural responses to external stimuli and processing sensorimotor information1,2,3,4. Invasive and noninvasive methods are available for cortical mapping. One of the most common invasive methods involves the use of intracortical (or penetrating) electrodes for mapping5,6,7,8.
Assessing the on-demand high-resolution cortical maps using penetrating electrodes has faced several obstacles. The method is too laborious to obtain a decent map and too invasive to implement for clinical use, prohibiting further development. More recent technologies such as electroencephalography (EEG), positron emission tomography (PET), magnetoencephalography (MEG), and functional magnetic resonance imaging (fMRI) have gained popularity because these are less invasive and reproducible. However, given their prohibitive costs and poor resolution, they are used in a limited number of cases9,10,11. Recently, flexible surface electrodes with superior signal reliability have attracted considerable attention. Graphene-based surface electrodes demonstrate long-term biocompatibility and mechanical flexibility, providing stable recordings in a convoluted brain12,13,14,15,16. Our group has recently developed a graphene-based multichannel array for high-resolution recording and site-specific neurostimulation on the cortical surface. This technology allows us to keep track of the cortical representations of sensory information for an extended period.
This article describes the steps involved in acquiring a brain map of the somatosensory cortex using a 30-channel graphene multielectrode array. To measure brain activity, a graphene electrode array is placed on the subdural area of the cortex, while the forepaw, forelimb, hind paw, hindlimb, trunk, and whiskers are stimulated with a wooden stick. The somatosensory-evoked-potentials (SEPs) are recorded for somatosensory areas. This protocol can also be applied to other brain areas, such as the auditory, visual, and motor cortex.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>1mL syringe</td>
			<td>KOREAVACCINE CORPORATION</td>
			<td></td>
			<td>injecting the drug for anesthesia&#160;</td>
		</tr>
		<tr>
			<td>3mL syringe</td>
			<td>KOREAVACCINE CORPORATION</td>
			<td></td>
			<td>injecting the drug for anesthesia&#160;</td>
		</tr>
		<tr>
			<td>Bone rongeur</td>
			<td>Fine Science Tools</td>
			<td>16220-14</td>
			<td>remove the skull</td>
		</tr>
		<tr>
			<td>connector</td>
			<td>Gbrain</td>
			<td></td>
			<td>Connect graphene electrode to headstage</td>
		</tr>
		<tr>
			<td>drill</td>
			<td>FALCON tool</td>
			<td></td>
			<td>grind the skull</td>
		</tr>
		<tr>
			<td>drill bits</td>
			<td>Osstem implant</td>
			<td></td>
			<td>grind the skull</td>
		</tr>
		<tr>
			<td>Graefe iris forceps slightly curved serrated</td>
			<td>vubu</td>
			<td>vudu-02-73010</td>
			<td>remove the tissue from the skull or hold wiper</td>
		</tr>
		<tr>
			<td>graphene multielectrode array</td>
			<td>Gbrain</td>
			<td></td>
			<td>records signals from neuron</td>
		</tr>
		<tr>
			<td>isoflurane</td>
			<td>Hana Pharm Corporation</td>
			<td></td>
			<td>sacrifce the subject</td>
		</tr>
		<tr>
			<td>ketamine</td>
			<td>yuhan corporation</td>
			<td></td>
			<td>used for anesthesia</td>
		</tr>
		<tr>
			<td>lidocaine(2%)</td>
			<td>Daihan pharmaceutical&#160;</td>
			<td></td>
			<td>local anesthetic</td>
		</tr>
		<tr>
			<td>Matlab R2021b</td>
			<td>Mathworks</td>
			<td></td>
			<td>Data analysis Software</td>
		</tr>
		<tr>
			<td>mosquito hemostats</td>
			<td>Fine Science Tools</td>
			<td>91309-12</td>
			<td>fasten the scalp</td>
		</tr>
		<tr>
			<td>ointment</td>
			<td>Alcon</td>
			<td></td>
			<td>prevent eye from drying out&#160;</td>
		</tr>
		<tr>
			<td>povidone</td>
			<td>Green Pharmaceutical corporation</td>
			<td></td>
			<td>disinfect the incision area</td>
		</tr>
		<tr>
			<td>RHS 32ch Stim/Record headstage</td>
			<td>intan technologies</td>
			<td>M4032</td>
			<td>connect connector to interface cable and contain intan RHS stim/amplifier chip</td>
		</tr>
		<tr>
			<td>RHS 6-ft (1.8m) Stim SPI interface cable</td>
			<td>intan technologies</td>
			<td>M3206</td>
			<td>connect graphene electrode to headstage</td>
		</tr>
		<tr>
			<td>RHS Stim/Recording controller software</td>
			<td>intan technologies</td>
			<td></td>
			<td>Data Acquisition Software</td>
		</tr>
		<tr>
			<td>RHS stimulation/ Recording controller</td>
			<td>intan technologies</td>
			<td>M4200</td>
			<td></td>
		</tr>
		<tr>
			<td>saline</td>
			<td>JW Pharmaceutical</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>scalpel</td>
			<td>Hammacher</td>
			<td>HSB 805-03</td>
			<td></td>
		</tr>
		<tr>
			<td>stereotaxic instrument</td>
			<td>stoelting</td>
			<td></td>
			<td>fasten the subject</td>
		</tr>
		<tr>
			<td>sterile Hypodermic Needle</td>
			<td>KOREAVACCINE CORPORATION</td>
			<td></td>
			<td>remove the dura mater</td>
		</tr>
		<tr>
			<td>Steven Iris Tissue Forceps</td>
			<td>KASCO</td>
			<td>50-2026</td>
			<td>remove the dura mater</td>
		</tr>
		<tr>
			<td>surgical blade no.11</td>
			<td>FEATHER</td>
			<td></td>
			<td>inscise the scalp</td>
		</tr>
		<tr>
			<td>surgical sicssors</td>
			<td>Fine Science Tools</td>
			<td>14090-09</td>
			<td>inscise the scalp and remove the dura mater</td>
		</tr>
		<tr>
			<td>wooden stick</td>
			<td></td>
			<td></td>
			<td>whisker stimulation</td>
		</tr>
		<tr>
			<td>xylazine</td>
			<td>Bayer Korea</td>
			<td></td>
			<td>used for anesthesia</td>
		</tr>
	</tbody>
</table>

brain mapping using a graphene electrode array

Cortical maps represent the spatial organization of location-dependent neural responses to sensorimotor stimuli in the cerebral cortex, enabling the prediction of physiologically relevant behaviors. Various methods, such as penetrating electrodes, electroencephalography, positron emission tomography, magnetoencephalography, and functional magnetic resonance imaging, have been used to obtain cortical maps. However, these methods are limited by poor spatiotemporal resolution, low signal-to-noise ratio (SNR), high costs, and non-biocompatibility or cause physical damage to the brain. This study proposes a graphene array-based somatosensory mapping method as a feature of electrocorticography that offers superior biocompatibility, high spatiotemporal resolution, desirable SNR, and minimized tissue damage, overcoming the drawbacks of previous methods. This study demonstrated the feasibility of a graphene electrode array for somatosensory mapping in rats. The presented protocol can be applied not only to the somatosensory cortex but also to other cortices such as the auditory, visual, and motor cortex, providing advanced technology for clinical implementation.

This protocol describes how a graphene multichannel array is mounted on the surface of the brain. The somatosensory map was constructed by acquiring neural responses to physical stimuli and calculating the amplitude of the response. Figure 1 shows the schematic of this experiment.
Figure 2A presents the structural characteristics of a graphene electrode array. There are thru-holes of the substrate between the electrodes. These holes h...

Watch this Scientific Journal Video about Brain Mapping Using a Graphene Electrode Array at JoVE.com

Brain Mapping Using a Graphene Electrode Array

We present a graphene array-based brain mapping procedure to reduce the invasiveness and improve spatiotemporal resolution. Graphene array-based surface electrodes exhibit long-term biocompatibility, mechanical flexibility, and suitability for brain mapping in a convoluted brain. This protocol allows for constructing multiple forms of sensory maps simultaneously and sequentially.

Cortical maps represent the spatial organization of location-dependent neural responses to sensorimotor stimuli in the cerebral cortex, enabling the ...

The cortical map is a set of local patches representing response properties to sensory motor stimuli in the cerebral cortex. It can discover the spatial formation of neural networks which can offer a prediction for perception and cognition. Hence, cortical maps are used to study neural responses from external stimuli and the processing of sensory motor information To create cortical maps are invasive and non-invasive methods.Using intracortical electrodes is one of the most common invasive methods used for mapping the cerebral cortex. As it can damage the brain for high resolution, it prevents further measurements from being made. Alternative brain mapping tools such as EEG, PET, MEG, fMRI, are non-invasive methods that allow for whole brain mapping and repeated sampling.However, several disadvantages are low spatial temporal resolution, temporal lag, errors due to unspecified modulatory inputs and prohibitive costs. Optical techniques such as calcium imaging and optogenetic fMRI provide large scale brain mapping but are not clinically beneficial due to indicator toxicity and low spatial temporal resolution. The Graphene electrode array exhibits long-term biocompatibility and mechanical flexibility which provides stable recordings of the convoluted brain.Recently, our group has developed a graphene electrode array that provides high resolution recordings for neural signals on the cortical surface. This protocol uses a graphene electrode array to record the SEPs from an SD rat's forepaw, forelimb, hind paw, hind limb, trunk, and whisker to create a cortical map. Administer an intraperitoneal injection of ketamine and xylazine cocktail using a dosage of 90 milligram per kilogram for ketamine and 10 milligram per kilogram for xylazine.To maintain a desired depth of anesthesia throughout the surgery, inject a 45 milligram per kilogram ketamine, and five milligram per kilogram xylazine cocktail if the rat shows signs of awakening. Pinch the toe to confirm the depth of anesthesia. If the rat trembles, wait for additional minutes until it shows no response.Shave the fur on the rat's head from the space between the eyes to the back of the ears using a trimmer. Then apply an ophthalmic ointment onto the eyes. Using ear bars and stereotaxic adaptors, fix the rat's head onto the stereotaxic apparatus.Make sure that the rat's head is fixed properly. Sterilize a shaved area with povidone-soaked cotton swap. Scrub the shaved area with alcohol.Repeat the sterilization process three times. Then inject 0.1 milliliters of 2%lidocaine into the scalp to induce local anesthesia. Creates a two to three-centimeter midline incision and laterally pull apart the scalp To expose the skull.Clamp the scalp to expose the skull with mosquito forceps. Start by removing the periosteum by scratching the surface of the skull with forceps. In a straight line towards the lambda, locate the sternum magna by tearing the muscle behind the occipital bone on the posterior edge.Use a microscope to get a close view of the cisterna magna. Incise the cisterna magna gently. After tearing the cisterna magna, cerebral spinal fluids flow out.Drain the cerebral spinal fluid with the coiled sterile gauze to sink down the brain. Mark where the graphene electrode will be placed based on the predefined stereotaxic coordinates according to the position of the bregma. The somatosensory cortex is located three millimeters in the anterior posterior axis and six millimeters in the right lateral direction from the bregma of the right hemisphere skull.Drill the area marked according to the stereotaxic coordinate. Remove the skull with the bone rongeur. Stick a cotton swab into a 26 garish needle.Bend the needle to 90 degrees. To remove the dura mater, create a hole using a bent needle. Lift the dura mater upward, insert forceps into that hole and proceed to cut the dura mater with scissors or tear it with forceps.Attach the sterile gauze wet with saline on the somatosensory cortex to prevent the cortex from drying out. Detach the graphene multielectrode array without causing any damage by applying saline solution. Remove the outer covering of the reference and ground wires from the connector.To set up the graphene multi electrode array for mapping, connect the head stage with the connector. Connect the graphene electrode array with the connector. Plug the interface cable into the recording controller.Connect the graphene multielectrode array and connector complex to an interface cable. Then secure the graphene multielectrode array complex onto the stereotaxic arm. Place the graphene electrode array onto the somatosensory cortex based on the predefined stereotaxic coordinates.Place the reference wire in the tissue behind the occipital bone. Then connect the ground wire to the grounded optical table. Open the recording software and set the sampling rate at 30 kilohertz and click the OK button.Set the 60 hertz notch filter to remove the noise from power. Bend the whisker with a fine stick. Record neural signals through the data acquisition system for the desired time.These signals are neural signals obtained through stimuli for whiskers. Other body parts also stimulate the same way to record SEPs. Open the MATLAB code named read_Intan_RHS2000 file.Click the Run button. Choose the recording file and click that file and then wait for the file to be read. Enter the command plot to create a 2D line plot.Select the representative peak signals that were in response to the stimulus, and calculate the amplitudes of the SEPs by measuring the maximum and minimum values. Obtain the topographic map by coloring the grade with the different shade of color according to the SEP's amplitude. The graphene electrode array is on the left.There are through holes of the substrate between all electrodes. These holes help the electrodes maintain strong contact with the cortex. On the right, the image shows the electrode array on the cortex.On the left, the ratio of each location-dependent neural response caused by stimulations to different parts of the rat's body is displayed in the shape of a rat. Each body part is represented with a different color. This configures a somatosensory cortex map.On the right, the following figure shows a stimuli specific responses gained through the multichannel graphene electrodes that were placed on the surface of the cortex. Each colored box represents the responses that different body parts had on the 30 channels. The figure above represents the LFPs detected on the surface of the somatosensory cortex by using graphene electrode arrays.The color bar shows that a larger amplitude is represented by a darker shade of color and each color represents a different body part. The figure flex the amplitude based on the shades in the color bar. This homunculus of of the rodent was created using the results that were just explained.The larger the amplitude a certain body parts had, the larger it would be illustrated on the homonculus. The figure below represents a separate data of LFPs collected from each body part. It represents the varying amplitudes of LFPs detected based on the color bar.There are several precautions for this procedure. When removing the cerebral spinal fluid, the experimenter should be careful not to touch the brainstem or a spinal cord. This step takes practice.The rodents whisker is developed enough to sense a deflection direction, stimulus intensity and location of the whisker that was stimulated. That is why the whiskers should be stimulated in a constant direction and intensity for this protocol. Other body parts should also be stimulated consistently.The limitation of this protocol is that signals evoked in deep brain structures can't be recorded as a graphene electrode array is mounted on the cortical surface. Thus, the experimenter can't identify how the columnar network is hierarchically organized concerning the neural responses. Nonetheless, this protocol can be further applied if the experimenter changes the multiple areas where the electrode arrays are placed.For instance, if the experimenter places the electrode on the auditory or visual cortex to extract auditory and visual information, they can acquire the auditory or visual maps. Also, this protocol can be extended to the chronic implantation of the graphene multielectrode array.

brain-mapping-using-a-graphene-electrode-array

Research

JoVE Journal

Neuroscience

Multi-electrode Array Recordings of Neuronal Avalanches in Organotypic Cultures

The cortex is spontaneously active, even in the absence of any particular input or motor output. During development, this activity is important for the migration and differentiation of cortex cell types and the formation of neuronal connections1. In the mature animal, ongoing activity reflects the past and the present state of an animal into which sensory stimuli are seamlessly integrated to compute future actions. Thus, a clear understanding of the organization of ongoing i.e. spontaneous activity is a prerequisite to understand cortex function. 
Numerous recording techniques revealed that ongoing activity in cortex is comprised of many neurons whose individual activities transiently sum to larger events that can be detected in the local field potential (LFP) with extracellular microelectrodes, or in the electroencephalogram (EEG), the magnetoencephalogram (MEG), and the BOLD signal from functional magnetic resonance imaging (fMRI). The LFP is currently the method of choice when studying neuronal population activity with high temporal and spatial resolution at the mesoscopic scale (several thousands of neurons). At the extracellular microelectrode, locally synchronized activities of spatially neighbored neurons result in rapid deflections in the LFP up to several hundreds of microvolts. When using an array of microelectrodes, the organizations of such deflections can be conveniently monitored in space and time. 
Neuronal avalanches describe the scale-invariant spatiotemporal organization of ongoing neuronal activity in the brain2,3. They are specific to the superficial layers of cortex as established in vitro4,5, in vivo in the anesthetized rat 6, and in the awake monkey7. Importantly, both theoretical and empirical studies2,8-10 suggest that neuronal avalanches indicate an exquisitely balanced critical state dynamics of cortex that optimizes information transfer and information processing.
In order to study the mechanisms of neuronal avalanche development, maintenance, and regulation, in vitro preparations are highly beneficial, as they allow for stable recordings of avalanche activity under precisely controlled conditions. The current protocol describes how to study neuronal avalanches in vitro by taking advantage of superficial layer development in organotypic cortex cultures, i.e. slice cultures, grown on planar, integrated microelectrode arrays (MEA; see also 11-14).

A robust way to study neuronal avalanches, i.e. scale-invariant spatio-temporal activity bursts, indicative of critical state dynamics in cortex. Avalanches emerge spontaneously in developing superficial layers of cultured cortex which allows for long-term measurements of the activity with planar integrated multi-electrode arrays (MEA) under precisely controlled conditions.

The cortex is spontaneously active, even in the absence of any particular input or motor output.  During development, this activity is important for the ...

Mapping Cortical Dynamics Using Simultaneous MEG/EEG and Anatomically-constrained Minimum-norm Estimates: an Auditory Attention Example

Magneto- and electroencephalography (MEG/EEG) are neuroimaging techniques that provide a high temporal resolution particularly suitable to investigate the cortical networks involved in dynamical perceptual and cognitive tasks, such as attending to different sounds in a cocktail party. Many past studies have employed data recorded at the sensor level only, i.e., the magnetic fields or the electric potentials recorded outside and on the scalp, and have usually focused on activity that is time-locked to the stimulus presentation. This type of event-related field / potential analysis is particularly useful when there are only a small number of distinct dipolar patterns that can be isolated and identified in space and time. Alternatively, by utilizing anatomical information, these distinct field patterns can be localized as current sources on the cortex. However, for a more sustained response that may not be time-locked to a specific stimulus (e.g., in preparation for listening to one of the two simultaneously presented spoken digits based on the cued auditory feature) or may be distributed across multiple spatial locations unknown a priori, the recruitment of a distributed cortical network may not be adequately captured by using a limited number of focal sources.
Here, we describe a procedure that employs individual anatomical MRI data to establish a relationship between the sensor information and the dipole activation on the cortex through the use of minimum-norm estimates (MNE). This inverse imaging approach provides us a tool for distributed source analysis. For illustrative purposes, we will describe all procedures using FreeSurfer and MNE software, both freely available. We will summarize the MRI sequences and analysis steps required to produce a forward model that enables us to relate the expected field pattern caused by the dipoles distributed on the cortex onto the M/EEG sensors. Next, we will step through the necessary processes that facilitate us in denoising the sensor data from environmental and physiological contaminants. We will then outline the procedure for combining and mapping MEG/EEG sensor data onto the cortical space, thereby producing a family of time-series of cortical dipole activation on the brain surface (or "brain movies") related to each experimental condition. Finally, we will highlight a few statistical techniques that enable us to make scientific inference across a subject population (i.e., perform group-level analysis) based on a common cortical coordinate space.

We use magneto- and electroencephalography (MEG/EEG), combined with anatomical information captured by magnetic resonance imaging (MRI), to map the dynamics of the cortical network associated with auditory attention.

Magneto- and electroencephalography (MEG/EEG) are neuroimaging techniques that provide a high temporal resolution particularly suitable to investigate the ...

A Computer-assisted Multi-electrode Patch-clamp System

The patch-clamp technique is today the most well-established method for recording electrical activity from individual neurons or their subcellular compartments. Nevertheless, achieving stable recordings, even from individual cells, remains a time-consuming procedure of considerable complexity. Automation of many steps in conjunction with efficient information display can greatly assist experimentalists in performing a larger number of recordings with greater reliability and in less time. In order to achieve large-scale recordings we concluded the most efficient approach is not to fully automatize the process but to simplify the experimental steps and reduce the chances of human error while efficiently incorporating the experimenter's experience and visual feedback. With these goals in mind we developed a computer-assisted system which centralizes all the controls necessary for a multi-electrode patch-clamp experiment in a single interface, a commercially available wireless gamepad, while displaying experiment related information and guidance cues on the computer screen. Here we describe the different components of the system which allowed us to reduce the time required for achieving the recording configuration and substantially increase the chances of successfully recording large numbers of neurons simultaneously.

Multi-electrode patch-clamp recordings constitute a complex task. Here we show how, by automating of many of the experimental steps, it is possible to accelerate the process leading to qualitative improvement in performance and number of recordings.

The patch-clamp technique is today the most  well-established method for recording electrical activity from individual  neurons or their subcellular ...

Functional Imaging of Auditory Cortex in Adult Cats using High-field fMRI

Current knowledge of sensory processing in the mammalian auditory system is mainly derived from electrophysiological studies in a variety of animal models, including monkeys, ferrets, bats, rodents, and cats. In order to draw suitable parallels between human and animal models of auditory function, it is important to establish a bridge between human functional imaging studies and animal electrophysiological studies. Functional magnetic resonance imaging (fMRI) is an established, minimally invasive method of measuring broad patterns of hemodynamic activity across different regions of the cerebral cortex. This technique is widely used to probe sensory function in the human brain, is a useful tool in linking studies of auditory processing in both humans and animals and has been successfully used to investigate auditory function in monkeys and rodents. The following protocol describes an experimental procedure for investigating auditory function in anesthetized adult cats by measuring stimulus-evoked hemodynamic changes in auditory cortex using fMRI. This method facilitates comparison of the hemodynamic responses across different models of auditory function thus leading to a better understanding of species-independent features of the mammalian auditory cortex.

Functional studies of the auditory system in mammals have traditionally been conducted using spatially-focused techniques such as electrophysiological recordings. The following protocol describes a method of visualizing large-scale patterns of evoked hemodynamic activity in the cat auditory cortex using functional magnetic resonance imaging.

Current knowledge of sensory processing in the mammalian auditory system is mainly derived from electrophysiological studies in a variety of animal ...

Neural Activity Propagation in an Unfolded Hippocampal Preparation with a Penetrating Micro-electrode Array

This protocol describes a method for preparing a new in vitro flat hippocampus preparation combined with a micro-machined array to map neural activity in the hippocampus. The transverse hippocampal slice preparation is the most common tissue preparation to study hippocampus electrophysiology. A longitudinal hippocampal slice was also developed in order to investigate longitudinal connections in the hippocampus. The intact mouse hippocampus can also be maintained in vitro because its thickness allows adequate oxygen diffusion. However, these three preparations do not provide direct access to neural propagation since some of the tissue is either missing or folded. The unfolded intact hippocampus provides both transverse and longitudinal connections in a flat configuration for direct access to the tissue to analyze the full extent of signal propagation in the hippocampus in vitro. In order to effectively monitor the neural activity from the cell layer, a custom made penetrating micro-electrode array (PMEA) was fabricated and applied to the unfolded hippocampus. The PMEA with 64 electrodes of 200 &#181;m in height could record neural activity deep inside the mouse hippocampus. The unique combination of an unfolded hippocampal preparation and the PMEA provides a new in-vitro tool to study the speed and direction of propagation of neural activity in the two-dimensional CA1-CA3 regions of the hippocampus with a high signal to noise ratio.

We have developed an in vitro unfolded hippocampus which preserves CA1-CA3 array of neurons. Combined with the penetrating micro-electrode array, neural activity can be monitored in both the longitudinal and transverse orientations. This method provides advantages over hippocampal slice preparations as the propagation in the entire hippocampus can be recorded simultaneously.

This protocol describes a method for preparing a new in vitro flat hippocampus preparation combined with a micro-machined array to map neural activity in ...

Direct-current Stimulation and Multi-electrode Array Recording of Seizure-like Activity in Mice Brain Slice Preparation

Cathodal transcranial direct-current stimulation (tDCS) induces suppressive effects on drug-resistant seizures. To perform effective actions, the stimulation parameters (e.g., orientation, field strength, and stimulation duration) need to be examined in mice brain slice preparations. Testing and arranging the orientation of the electrode relative to the position of the mice brain slice are feasible. The present method preserves the thalamocingulate pathway to evaluate the effect of DCS on anterior cingulate cortex seizure-like activities. The results of the multichannel array recordings indicated that cathodal DCS significantly decreased the amplitude of the stimulation-evoked responses and duration of 4-aminopyridine and bicuculline-induced seizure-like activity. This study also found that cathodal DCS applications at 15 min caused long-term depression in the thalamocingulate pathway. The present study investigates the effects of DCS on thalamocingulate synaptic plasticity and acute seizure-like activities. The current procedure can test the optimal stimulation parameters including orientation, field strength, and stimulation duration in an in vitro mouse model. Also, the method can evaluate the effects of DCS on cortical seizure-like activities at both the cellular and network levels.

Studies have shown that cathodal transcranial direct-current stimulation can produce suppressive effects on drug-resistant seizures. In this study, an in vitro experimental setup was devised in which the direct-current stimulation and multielectrode array recording of seizure-like activity were evaluated in mice brain slice preparation. The direct-current stimulation parameters were evaluated.

Cathodal transcranial direct-current stimulation (tDCS) induces suppressive effects on drug-resistant seizures. To perform effective actions, the ...

Adaptation of Microelectrode Array Technology for the Study of Anesthesia-induced Neurotoxicity in the Intact Piglet Brain

Every year, millions of children undergo anesthesia for a multitude of procedures. However, studies in both animals and humans have called into question the safety of anesthesia in children, implicating anesthetics as potentially toxic to the brain in development. To date, no studies have successfully elucidated the mechanism(s) by which anesthesia may be neurotoxic. Animal studies allow investigation of such mechanisms, and neonatal piglets represent an excellent model to study these effects due to their striking developmental similarities to the human brain.
This protocol adapts the use of enzyme-based microelectrode array (MEA) technology as a novel way to study the mechanism(s) of anesthesia-induced neurotoxicity (AIN). MEAs enable real-time monitoring of in vivo neurotransmitter activity and offer exceptional temporal and spatial resolution. It is hypothesized that anesthetic neurotoxicity is caused in part by glutamate dysregulation and MEAs offer a method to measure glutamate. The novel implementation of MEA technology in a piglet model presents a unique opportunity for the study of AIN.

This study explores the novel use of enzyme-based microelectrode array (MEA) technology to monitor in vivo neurotransmitter activity in piglets. The hypothesis was that glutamate dysregulation contributes to the mechanism of anesthetic neurotoxicity. Here, we present a protocol to adapt MEA technology to study the mechanism of anesthesia-induced neurotoxicity.

Every year, millions of children undergo anesthesia for a multitude of procedures. However, studies in both animals and humans have called into question ...

Chronic Implantation of Whole-cortical Electrocorticographic Array in the Common Marmoset

Electrocorticography (ECoG) allows the monitoring of electrical field potentials from the cerebral cortex with high spatiotemporal resolution. Recent development of thin, flexible ECoG electrodes has enabled conduction of stable recordings of large-scale cortical activity. We have developed a whole-cortical ECoG array for the common marmoset. The array continuously covers almost the entire lateral surface of cortical hemisphere, from the occipital pole to the temporal and frontal poles, and it captures whole-cortical neural activity in one shot. This protocol describes a chronic implantation procedure of the array in the epidural space of the marmoset brain. Marmosets have two advantages regarding ECoG recordings, one being the homologous organization of anatomical structures in humans and macaques, including frontal, parietal, and temporal complexes. The other advantage is that the marmoset brain is lissencephalic and contains a large number of complexes, which are more difficult to access in macaques with ECoG, that are exposed to the brain surface.These features allow direct access to most cortical areas beneath the surface of the brain. This system provides an opportunity to investigate global cortical information processing with high resolutions at a sub-millisecond order in time and millimeter order in space.

We have developed a whole-cortical electrocorticographic array for the common marmoset that continuously covers almost the entire lateral surface of cortex, from the occipital pole to the temporal and frontal poles. This protocol describes a chronic implantation procedure of the array in the epidural space of the marmoset brain.

Electrocorticography (ECoG) allows the monitoring of electrical field potentials from the cerebral cortex with high spatiotemporal resolution. Recent ...

Translational Brain Mapping at the University of Rochester Medical Center: Preserving the Mind Through Personalized Brain Mapping

The Translational Brain Mapping Program at the University of Rochester is an interdisciplinary effort that integrates cognitive science, neurophysiology, neuroanesthesia, and neurosurgery. Patients who have tumors or epileptogenic tissue in eloquent brain areas are studied preoperatively with functional and structural MRI, and intraoperatively with direct electrical stimulation mapping. Post-operative neural and cognitive outcome measures fuel basic science studies about the factors that mediate good versus poor outcome after surgery, and how brain mapping can be further optimized to ensure the best outcome for future patients. In this article, we describe the interdisciplinary workflow that allows our team to meet the synergistic goals of optimizing patient outcome and advancing scientific understanding of the human brain.

This article provides an overview of a multi-modal brain mapping program designed to identify regions of the brain that support critical cognitive functions in individual neurosurgery patients.

The Translational Brain Mapping Program at the University of Rochester is an interdisciplinary effort that integrates cognitive science, neurophysiology, ...

Real-Time fMRI Brain Mapping in Animals

Dynamic fMRI responses vary largely according to the physiological conditions of animals either under anesthesia or in awake states. We developed a real-time fMRI platform to guide experimenters to monitor fMRI responses instantaneously during acquisition, which can be used to modify the physiology of animals to achieve desired hemodynamic responses in animal brains. The real-time fMRI set-up is based on a 14.1T preclinical MRI system, enabling the real-time mapping of dynamic fMRI responses in the primary forepaw somatosensory cortex (FP-S1) of anesthetized rats. Instead of a retrospective analysis to investigate confounding sources leading to the variability of fMRI signals, the real-time fMRI platform provides a more effective scheme to identify dynamic fMRI responses using customized macro-functions and a common neuroimage analysis software in the MRI system. Also, it provides immediate troubleshooting feasibility and a real-time biofeedback stimulation paradigm for brain functional studies in animals.

Animal brain functional mapping can benefit from the real-time functional magnetic resonance imaging (fMRI) experimental set-up. Using the latest software implemented in the animal MRI system, we established a real-time monitoring platform for small animal fMRI.

Dynamic fMRI responses vary largely according to the physiological conditions of animals either under anesthesia or in awake states. We developed a ...