Science Section 5

Dulles Only!!!

Who launched the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative

Barack Obama

When did Obama launch BRAIN

2013

What is the purpose of BRAIN

A bold research effort focused on giving scientists the tools they need to get a dynamic picture of the brain in action

Who does BRAIN involve

The National Institutes of Health (NIH)

• Experts from many other government and private research groups, working together to develop a plan for high-priority research areas to target within the field of neuroscience

When did BRAIN funding start

2014

How much money has BRAIN raised so far

$46 million

What are the outcomes from the BRAIN Initiative

Human Connectome Project

• Resulted in the publishing of a free and open atlas of the mammalian primary motor cortex

• Led to brand new microscopy technology

Human Connectome Project

Main goal is creating the world’s largest map of neural circuit structure and function, otherwise known as connectome

Publishing of a free and open atlas of the mammalian primary motor cortex

Extremely detailed map is like a census of the cells in that region, complete with genetic information and data about the function or activity of those cells

Many aspects of the nervous system have been studied from the early 20th century via what 2 main mechanisms

Perturbing the brain, meaning changing or altering something in it and then seeing what changes occur in the resulting behavior

• Recording from the brain, using electrodes to gather data about what the cells of the brain are doing

Both perturbing and recording the brain require what

The opening of a hole in the skull

What is the most straightforward way to learn about a brain region or particular cell type

To either remove it or damage (lesion) it and then see what changes in that organism’s ability to interact with the world

Lesion studies

Still done on animals

• But it’s considered unethical to lesion a region of the brain of a healthy human being in order to learn about the brain

Which French surgeon and scientist visited Patient Tan

Paul Broca

When did Paul Broca visit Patient Tan

1861

Why was the patient called Patient Tan

“tan” was the only syllable he was able to utter

Where did Broca discover a huge lesion in the brain of Patient Tan

Discovered a huge lesion to the left frontal area of the patient’s cerebral cortex

Why was there a huge lesion to the left frontal area of Patient Tan

Due to damage from a longstanding case of syphilis

Speech and language areas that reside on the left side of the brain is also called what

Broca’s Area

Electrical brain stimulation or EBS

Implanting (hole) an electrode into the brain allows scientists to add current to the brain, stimulating specific neurons, neural networks, or brain regions in a particular way

What was EBS used for in the early 19th century

To investigate the function of the cerebral cortex in animals and in the occasional human subject (that already had a hole in their skull)

When did a detailed map of the mammalian cortex start to emerge based on what happened to the animal or human in question when a particular area of their cortex was directly stimulated with an implanted electrode

In the 1950s

Deep brain stimulation

Uses implanted electrodes as a treatment for Parkinson’s disease and tremors

Electroshock therapy

Using electrodes on the scalp surface for treatment-resistant major depression

Transcranial direct current stimulation or tDCS

Uses one positive and one negative electrode to run current through the brain, increasing or decreasing activity in particular regions

Is tDCS noninvasive or invasive

Noninvasive

What are the disadvantages of tDCS

The stimulation produced by this method is very small, much smaller than that produced by an implanted electrode and smaller than TMS

What are the advantages of tDCS

Method is inexpensive and easy to use, with few side effects

What is difficult to maintain constant with EBS

Difficult to specifically target a certain subset of neurons in a living organism, as the charge from an electrode spreads

• Impossible to consistently target similar populations of neurons in a group of animals with implanted electrodes or to target the same populations of cells from person to person

What solves the problem with maintaining consistency for EBS

Optogenetics

What are optogenetics

Introduces foreign genes that express the code for ion channels that open or close in response to light, much like those found in the retina of the eye

How did researchers find channelrhodopsin-2 (ChR2)

In the early 2000s, researchers in Germany studying how green algae cells respond to light found a type of opsin or light absorbing pigment called ChR2

• Acts as an ion channel

What type of light is ChR2 sensitive to

Blue wavelengths of light

What happens when ChR2 is injected into neurons

ChR2 is expressed as an ion channel sensitive to blue wavelengths of light

• If blue light is shone onto the surface of the brain, the ChR2 channel will open

• Neighboring neurons that didn’t get the ChR2 gene had no response to the light

What ions do ChR2 channels allow through

Sodium, which depolarizes the cell

What can be attached into the brains of rodents who have had a certain subset of neurons injected with channel rhodopsin

Tiny fiber optics

• Fiber optic electrodes can target a variety of brain regions and use different wavelengths of light to activate different channel rhodopsin proteins, allowing particular ions to flow into or out of the neuron

What is the benefit of producing ChR2 using a DNA promoter that only woks in certain types of neurons

Scientists can be highly specific about which neurons they are targeting

Transcranial magnetic stimulation or TMS

Produces a magnetic field to modulate the excitability of a region of the cortex

• The magnetic field induces an electric field within the cortex, causing neurons there to either depolarize or hyperpolarize

• Scrambling the normal electrical activity of the neurons creates a temporary or reversible lesion

Is TMS noninvasive or invasive

Noninvasive

What is TMS mainly used for

Confirming findings from lesion studies and imaging studies

How is TMS used to treat diseases

It’s approved by the FDA to treat depression, using repeated TMS applied to particular brain regions over the course of several days or weeks

What is an advantage of TMS over electroshock therapy or tDCS

It can stimulate a small, specific area of the brain without much spread

What is a disadvantage of TMS compared to implanted electrodes

It can only target regions of the brain that are close to the surface

Intracellular or single-unit recording

Recording from the brain using an implanted electrode in a particular neuron

• Quite challenging because neurons are very small and because it requires the drilling of a hole

Extracellular recording

An electrode measures the membrane potentials from a population of cells from just outside those cells

• More popular in any areas of neuroscience research

• Still uses a hole in the brain

What is another name for extracellular recording

Can be called multi-unit recordings or local field potentials, depending on exactly what aspect of the electrical output is measured and how

What can extracellular recording be done on

Animals under local anesthesia

• Extracellular recordings can be gathered from these animals as they perform natural behavior or learned tasks, like mazes, to give us a wealth of data about how neurons drive behavior

What was one hugely popular method of early neuroimaging in the 19th century

Phrenology, in which an experienced practitioner would feel the bumps on a subject’s skull to explain their neurological traits

Who developed phrenology

German neuroanatomist Franz Joseph Gall

• Theorized abilities and personalities were localized in particular regions of the brain, and that these could be read by feeling the bumps and contours of the skull

What was phrenology used as around the world

A way to justify the “inferiority” of certain races, classes, or sexes of human beings

• Used in America prior to the Civil War to argue that the enslavement of people who were African or black was ethical

• Used by the Nazi Germany in WWII to argue that Jews, homosexuals or other queer individuals, and the Romani people should be killed or removed from society

Theory of localization

An idea that particular areas of the brain have particular unique jobs to do

• Brought up by phrenology

What was the first noninvasive method of truly recording information from actual neurons without drilling holes into the skull

Electroencephalogram or EEG

Who invented the EEG

German psychiatrist Hans Berger

When did Hans Berger invent the EEG for use on humans

In the 1920s

At first, how did the EEG work

Inserted metal wires directly into the subject’s scalp

Over time, how did the EEG change its methods

Used small discs called electrodes that are held together by a fabric cap and attached to the surface of the scalp with a little sticky jelly-like material and can be easily pulled right off once the experiment is over

Using the EEG, what was Berger the first to describe

The different types of electrical waves that are present in the typical functioning brain and showed differences in individuals who might have had conditions such as epilepsy

What other use is of the EEG

Used in studying sleep, as the human brain produces very different types of electrical waves during each phase of sleep

What is a dipole

An area of negative charge next to an area of positive charge

What causes a dipole in the brain

Most large neurons in a given section of cerebral cortex tend to be in alignment with each other, creaing a dipole in the field of dendrites when all those neurons are active in the same way at the same time, as may commonly occur during a task

By the 1960s, what new method was used for the EEG

Instead of looking at the overall brain waves over time, scientists could look at the electrical potential directly resulting from a particular stimulus or event shown to a subject - called event-related potential or ERP

What types of stimuli tend to provoke reliable and particular peaks in the EEG output in relevant regions of the brain

Visual and auditory stimuli

What happens when a subject is presented a human face

Produces a negative peak of electrical activity in the visual processing areas of the cerebral cortex about 170 milliseconds after presentation

• This peak is called the N170

How does the N170 change

Changes in size or amplitude based on the type of face shown

• Larger N170s typically observed for faces (compared to objects that just look similar to faces) and emotional faces (compared to neutral or expressionless faces)

We also see differences in the N170 peak in people with which neurological conditions

Individuals with schizophrenia

What are some of the shortcomings of the EEG

It has very poor spatial resolution, meaning it’s not terribly useful for pinpointing where in the brain certain activity is coming from

• It’s only useful for detecting or imaging activity from the outermost areas of the brain, as the electrodes can only detect activity close to the brain surface through the thick skull and scalp

What is cognitive neuroscience

Neuroscience focused on the cognitive or active thinking processes of living human beings

What is the breakthrough that helped cognitive neuroscience the most

Magnetic resonance imaging or MRI

Magnetic resonance imaging or MRI

Medical imaging technique that uses a strong magnetic field to produce detailed images of the inside of the body or other organism

• Uses an MRI scanner, and the magnetic field is set up surrounding them

What is the MRI often used for

Diagnosing injuries

• Detecting abnormalities

• Monitor the progression of diseases

• Frequently used in research studies to better understand the human body and various medical conditions

What is the process of an MRI scan

Patient is placed inside a strong magnetic field, which causes some of the hydrogen atoms in the body to align

• These atoms are normally randomly oriented within the water molecules of the tissue being examined

• This alignment is then disrupted by the introduction of a separate radio frequency (RF) pulse of energy that only lasts a moment

• After these radio waves change the alignment of the atoms, they slowly begin to relax back into their original alignment with the magnetic field

As the atoms return to their normal alignment in an MRI scan, what do they emit

A faint radio signal, which can be measured

How is the radio signal emitted by the hydrogen atom recorded on an MRI scanner

The frequency information from each location in the imaged tissue can be converted into a map of signal strength or intensity levels, which is often represented as shades of black, white, and grey

• Used to create detailed images of the inside of the body or whatever tissue is being imaged in the MRI scanner

What does the magnet do in the MRI scanner

Produces the static magnetic field

What does the gradient coils do

Allow for the scanner to assess where in the scanner a particular signal is coming from

What does the radio frequency coils do

Produce the RF pulse

An MRI can tell the difference between what

Grey matter, white matter, bone, cerebral spinal fluid, and many other types and densities of tissues

• Also can tell the difference between oxygenated blood cells and deoxygenated blood cells

What is the use of tracking oxygenated blood cells on a MRI

It shows which part of the brain is active during a certain time point

• Higher neural activity demands more nutrients and oxygen, and in order to meet this increase demand, oxygenated blood flow increases to these active regions of the brain

Functional MRI (fMRI)

Sometimes called blood oxygen level dependent (BOLD) imaging

• Allows us to create activation maps of which parts of the brain may be involved in a particular task by tracking the flow of oxygenated blood cells

When was fMRI developed

In the 1990s

Fusiform face area or FFA

In the late 1990s, scientists were able to use fMRI to find compelling evidence that there is a small area of the brain that is specifically involved in processing faces

Where is the FFA found

Found on the lower surface of the temporal lobe

What is the size of the FFA

About the size of a grape

What are the drawbacks of MRI

All forms of MRI produce a fuzzy image if the subject isn’t able to hold still within the scanner

• MRI scanners are incredibly expensive and usually located in hospitals or research labs only

• These scanners rely on a strong magnetic field, so individuals who rely on implanted electronic devices or have other metal in their bodies are unable to undergo an MRI

fMRI compared to EEG

fMRI has a better spatial resolution thatn EEG, but as each pixel of an fMRI image is 1mm³, it’s still not detailed enough to tell us what specific populations of neurons are doing at a particular time

• fMRI has a lower temporal resolution than EEG because it only tracks the movement of blood every few seconds because that’s how long it takes for the blood flow to change in response to a change in neural activity

• fMRI isn’t directly recording the activity of neurons but rather using a proxy measure to assess overall brain activity in a region, which isn’t nearly as specific as EEG or direct neural recording

Brain-machine interface or BMI

Sometimes called brain-computer interface

• A system that allows a person to control a device or machine using only their thoughts

• Consists of a device that records neural activity from a particular brain region, and a computer system that translates that activity into commands that can be used to control external devices

• Only experimental purposes currently

When did research on BMI’s began in the United States

In the 1970s

Who funds BMI research

The military and nonprofits

What are some of the benefits of BMIs

Can help people with disabilities as well as enhance human-computer interactions

• Members of the military might be able to operate a drone hands-free on the battlefield

• People with paralysis or other movement disorders might be able to pilot a wheelchair or prosthetic or potentially regain control of their limbs via stimulation of their muscles

Neuroprosthetic technology created by BRAIN Initiative funded researchers at the University of California, San Francisco

Records from the brain’s speech centers and translates that brain activity into speech

One paralyzed subject was able to communicate at a rate of up to how many words per minute

18 wpm

One paralyzed subject was able to communicate with how much accuracy

93%

What is the long training process for new BMI users

Subjects can learn to produce signals the machine will recognize, and the computer is trained to translate the signals to operate a device using machine learning

What are the 2 ways in which BMI users get their brain recorded

Implanted or wearable devices

• Implanted devices are often surgically attached directly to brain tissue and thus are only appropriate for individuals with severe disorders or damage to their nervous system

• Wearable BMI devices are often based on tDCS technology or similar external electrodes - pose fewer risks and side effects, but their ability to record brain activity is very limited

How does BMI raise questions about security, bioethics, and equity

If you can use your mind to control a device, how can we work to ensure that the device isn’t hackable?

• Will some people in the future be able to give themselves an unfair advantage at school or work with these devices?

• Will this sort of technology be available to everyone or only those individuals with the money to afford the expensive devices

Why is computational neuroscience important for the next generation of BMI devices

It helps us understand how the brain works and even being able to model or predict the behavior of the brain or individual neurons

What is another name for computational neuroscience

Also called theoretical neuroscience

What is computational neuroscience or theoretical neuroscience

Any type of neuroscience that employs mathematical models, computer simulations, or theoretical analysis to understand the development, structure, function, and cognitive abilities of the nervous system

When was computational neuroscience first coined

In the 1980s

Who do most computational neuroscientists collaborate with

Experimentalists, those who work with actual neurons, brains, or living organisms

• Helps them analyze data or develop and test new models of nervous system functions