Watching the brain work: imaging, EEG and the sleeping brain

Transcript

RyanA woman comes to a sleep clinic because of her husband. He's been shouting in his sleep, kicking, even punching. He woke up once with a bruised hand and no memory of anything.

SoheeAnd there's a strange detail. Normally, in dreaming sleep, the body is almost completely paralyzed. In him, that paralysis isn't happening.

RyanWelcome to EPPP Prep, the podcast. I'm Ryan.

SoheeI'm Sohee. Today is about the tools we use to watch the brain: structural and functional imaging, EEG and event-related potentials. We'll use sleep to bring EEG to life, and we'll finish with what the evidence says these tools can and can't do clinically.

RyanLet's start with the OpenStax psychology textbook's three families of tools: those using radiation, those using magnetic fields, and those using electrical activity.

SoheeRadiation first. A computerized tomography scan, or CT, takes a number of x-rays of an area. X-rays pass through tissues of different densities at different rates, and a computer builds an image. CT is often used to check for a tumor or significant brain atrophy.

RyanPositron emission tomography, PET, shows the living, active brain. The person drinks or is injected with a mildly radioactive tracer. As a brain area becomes more active, more blood flows there, and the computer builds a rough map of active and inactive areas.

SoheeBut PET has drawbacks. The textbook says it shows little detail, can't pinpoint events precisely in time, and exposes the brain to radiation. It says fMRI has replaced it as an alternative diagnostic tool, although combined CT and PET is still used, for example to image neurotransmitter receptors in schizophrenia research.

RyanThen magnetic fields. In magnetic resonance imaging, MRI, a strong magnetic field makes hydrogen atoms in the body's cells move. When the field is turned off, they give off signals as they return to position, and tissues of different densities give off different signals.

SoheeFunctional MRI, fMRI, works on the same principles, but it shows changes in brain activity over time by tracking blood flow and oxygen levels. It gives more detailed images and better timing than PET.

RyanSo structure versus function. CT and MRI show structure. PET and fMRI show activity. That's a core distinction to have cold.

SoheeThen electrical activity. Electroencephalography, EEG, places an array of electrodes on the head and records brainwaves, showing their frequency, the number of waves per second, and their amplitude, their height. It doesn't tell you much about location, but its timing is accurate within milliseconds.

RyanAnd an open-access review on event-related potentials makes the trade-off crisp. PET and fMRI have high anatomical resolution, but coarse temporal resolution, on the order of one to two seconds. Electrophysiological tools work on the order of milliseconds.

SoheeThe same review describes event-related potentials, or ERPs, as averaged EEG responses that are time-locked to the processing of a stimulus. It names well-studied components like the P300, the mismatch negativity, and the error-related negativity.

RyanPause and think. A researcher wants to know exactly when, within a fraction of a second, the brain registers an unexpected tone. And a second researcher wants to know exactly where in the brain a memory task activates. Which tool fits each?

SoheeThe first needs millisecond timing, so EEG with event-related potentials. The second needs spatial detail, so fMRI. The tempting wrong answer is fMRI for the timing question, because it's the famous one. But its temporal resolution is in seconds.

RyanNow let's see EEG at work, in sleep. When we're awake, the textbook says beta waves dominate. They have the highest frequency, 13 to 30 hertz, and the lowest amplitude.

SoheeAs we drift into stage 1 sleep, we see alpha waves, 8 to 12 hertz, like someone very relaxed but awake. Then theta waves increase, 4 to 7 hertz. People woken from stage 1 often say they weren't asleep.

RyanStage 2 is still mostly theta, but with two signatures. Sleep spindles, rapid bursts of higher-frequency waves that may matter for learning and memory. And K-complexes, very high amplitude patterns that may occur in response to things in the environment.

SoheeStage 3 is deep sleep, or slow-wave sleep, with delta waves under 3 hertz. The lowest frequency and the highest amplitude of our sleeping brain waves. Heart rate and breathing slow dramatically, and it's much harder to wake someone.

RyanAnd then REM, rapid eye movement sleep. Its brain waves look very similar to wakefulness, and it's when dreaming occurs. But the voluntary muscles are paralyzed. That combination of high brain activity and no muscle tone is why it's called paradoxical sleep.

SoheeDeprive someone of REM and then let them sleep, and they spend more time in REM. That's REM rebound, which suggests REM is homeostatically regulated.

RyanBack to our man at the sleep clinic. The textbook calls this REM sleep behavior disorder. It occurs when the muscle paralysis of REM sleep doesn't occur, so people act out, kicking, punching, yelling, especially during disturbing dreams, and they have no memory of it.

SoheeAnd here's the comorbidity that makes this a Domain 1 favorite. The disorder is associated with neurodegenerative diseases such as Parkinson's disease. The link is robust enough that some view it as a potential aid in diagnosing those diseases.

RyanThe textbook says clonazepam is most often used to treat it, sometimes with melatonin, and the sleep environment is often modified to make it safer.

SoheeCompare two other parasomnias by stage. Sleepwalking most often occurs during slow-wave sleep. Night terrors occur during non-REM sleep, and people generally have no memory of them.

RyanAnd narcolepsy looks like REM breaking into waking life. Sleep episodes are often accompanied by cataplexy, a loss of muscle tone similar to REM paralysis, and some people have vivid dream-like hallucinations. It's associated with reduced levels of a signaling molecule called hypocretin.

SoheePause and think. During which stage do delta waves dominate, and which parasomnia most often occurs then?

RyanStage 3, slow-wave sleep, and sleepwalking. The tempting wrong answer is REM, because people link any sleep behavior to dreaming. But in REM the body is normally paralyzed. Acting out dreams in REM is the disorder, not the norm.

SoheeNow the evidence question. How useful are these tools in mental health care? A 2018 open-access review of 40 years of structural imaging is a good guide.

RyanIt says structural imaging was introduced into routine practice more than 40 years ago, hoping it would support diagnosis and treatment. Today it's widely used to exclude organic brain disease, like tumors and vascular or inflammatory processes.

SoheeWhere it clearly adds diagnostic value is Alzheimer disease. The review says hippocampal volume on structural MRI is an established parameter to support the diagnosis and its at-risk states.

RyanFor schizophrenia, depression and bipolar disorder, the review says the search for diagnostic biomarkers is harder, because these disorders lack an established neuropathological basis.

SoheeIn schizophrenia, for instance, imaging has identified a pattern of differences, in the hippocampus, amygdala, thalamus and lateral ventricles among others. But no single regional or global measure has been unequivocally associated with psychosis.

RyanAnd it notes that a large study found no excess of brain pathology explaining psychotic symptoms, which the UK's National Institute for Health and Care Excellence, or NICE, took as a lack of evidence for including brain imaging in the diagnostic process for schizophrenia. The authors themselves think that conclusion is premature.

SoheeFun history point from the same review. Brain imaging entered the field of mental disorders more broadly in 1976, when ventricular enlargement was described in patients with schizophrenia.

RyanAnd EEG? The event-related potential review calls it inexpensive and noninvasive, a valuable first-line method to exclude epilepsy, drug intoxication or sleep disorders in psychiatric patients.

SoheeOne more evidence example the exam could use. The U.S. Food and Drug Administration, the FDA, has classified an EEG-based assessment aid for attention-deficit/hyperactivity disorder, ADHD, called NEBA. It uses the ratio of theta to beta waves at one electrode site, in patients 6 to 17, combined with a clinician's evaluation.

RyanAnd the FDA summary is emphatic. It should be used only as confirmatory support for a completed clinical evaluation, or to support a decision to pursue more testing. It's not to be used as a stand-alone tool to evaluate or diagnose ADHD.

SoheeSo the big-picture lesson: in psychiatry, imaging and EEG mainly rule out other causes or support a clinical evaluation. They don't replace it.

RyanRecap. CT and MRI show structure. PET and fMRI show activity, through blood flow, with PET using a radioactive tracer. fMRI beats PET on detail and timing. EEG and event-related potentials give millisecond timing but little location.

SoheeAwake: beta. Stage 1: alpha then theta. Stage 2: spindles and K-complexes. Stage 3: delta, slow-wave sleep, where sleepwalking happens. REM: waking-like waves, dreams and paralysis. REM sleep behavior disorder is the loss of that paralysis and is linked to Parkinson's disease.

RyanAnd clinically, structural imaging mainly excludes organic disease, with real diagnostic support in Alzheimer disease. EEG helps rule out epilepsy, intoxication and sleep disorders, and the ADHD EEG aid is only an aid.

SoheeSpeaking of sleep, the same chapter says slow-wave sleep after learning a new task can improve performance on it. So getting real sleep tonight is part of studying, not a break from it.

RyanRest well. Thanks for listening to EPPP Prep.

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