Post Midterm #2 Flashcards
Implicit memory
Unconscious memory (implicit memory, nondeclarative memory)
Just “happens” (don’t know when you learn this
“show me”
Memories that influence behavior in an automatic, involuntary manner
Relates to automatic adjustments to perceptual, cognitive, and motor systems that occur beneath the level of conscious awareness
- procedural memories (how to ride a bike)
- perceptual memories (how to tell identical twins apart, unconsciously)
- stimulus-response memories (salivating in response to a tone)
Explicit memory
Consciously accessible memory (explicit memory, declarative memory)
Memories of events and facts that we can think and talk about.
“tell me”
What are the two types of episodic memories?
Episodic and Semantic memory
What is Episodic memory
Personal experiences associated with a time and place. Autobiographical memory that involves contextual information and is learned all at once.
What is SemaNtic memory
Encyclopedic memory of facts and general information, often acquired gradually over time. This knowledge need not be associated with the time or place in which we learned the information.
Describe Motor learning [HINT] (procedural learning) – implicit memory
Learning to make skilled, choreographed movements. Procedural learning
The basis of motor skills (bike riding, ball throwing, etc.…)
Involves different brain areas involved in movement
Motor learning involves learning how to make a sequence of coordinated movements
*Between-session learning, where improvements in motor behavior are seen following a period of memory consolidation
What parts of the brain are involved in motor learning?
The cerebellum, thalamus, basal ganglia, and motor cortex are all involved in motor learning
What is Perceptual learning – implicit memory
Learning to recognize stimuli as distinct entities.
The basis of recognition & categorization
Perceptual learning enables us to recognize and identify object or situations.
It is a pattern recognition system. (allows you to recognize when things change)
Through perceptual learning we recognize changes / variations in familiar stimuli and respond to those changes.
See picture – if something in that picture changes, this allows you to notice what changed
What parts of the brain are involved in perceptual learning?
Largely dependent on the neocortex – sensory association areas
This unconscious, implicit learning involves changes in the strength of connections between neurons in primary and association sensory cortices
What is Relational learning (stimulus-stimulus learning) – explicit memory? What parts of the brain is involved with this?
Learning relationships among individual stimuli. Stimulus-Stimulus learning
The basis of declarative memory (episodic and semantic)
Largely dependent on the hippocampus and neocortex
What is Stimulus–response learning – implicit and explicit memory? What parts of the brain are involved with this?
Learning to perform a particular behavior when a particular stimulus is present. Includes classical and instrumental conditioning.
The basis of classical (Pavlovian) and instrumental (operant) conditioning
Involves different brain areas depending on the stimulus and response
Unconditioned stimulus vs. conditioned stimulus?
Unconditioned stimulus
a stimulus that has inherent value, like food or a painful shock.
Conditioned Stimulus
a stimulus that was initially perceived as neutral (e.g., a tone) but now is perceived as predictive of an US.
Unconditioned Response vs. Conditioned Response
Unconditioned response
a behavioral response that is largely innate, hard-wired (unlearned, unconditioned).
Conditioned Response
a behavioral response that occurs in response to a CS. The behavior is often similar to the UR that was elicited by the US during training.
What is sensory memory?
Perceptual memory; lasts only a couple of seconds or less
Allows an individual to retain the experience of the sensation slightly longer than the original stimulus. Occurs in each of the senses.
Example; people often reflexively say “what?” when they hear something while distracted, but then they quickly realize they did hear what was said.
What is short-term memory?
Lasts for seconds to minutes
Small fraction of sensory information enters short-term memory.
The memory capacity of short-term memory is limited to a few items, such as the digits in a phone number or the letters in a name.
The length of short-term memory can be extended through rehearsal. For example, you might be able to keep a phone number in short-term memory by repeating it to yourself.
What is long-term memory?
Persists after getting distracted and after a nap
Select information from short-term memory is consolidated into long-term memory.
Long-term memories can be retrieved throughout a lifetime and are strengthened with every retrieval event
What is implied motion?
Movement is processed through the dorsal stream (in parietal cortex)
There is more stimulus in the dorsal stream when looking at a picture of someone doing an action (i.e.) hitting a baseball
What does visual agnosia have to do with memory?
Damage to regions of the brain involved in visual perception not only impair ability to recognize visual stimuli but also disrupt people’s memory of visual properties of familiar stimuli
What is Instrumental conditioning (aka Operant conditioning aka Reinforcement learning) ?
Learning from the consequences of your actions, from the receipt of reinforcement or punishment. The likelihood of you repeating an action depends on whether it was previously reinforced or punished.
In contrast to Classical (Pavlovian) learning, operant conditioning requires that the animal can move and make decisions that influence their environment (i.e., decisions that have consequences).
What is Reinforcing Stimulus
Appetitive stimulus. When it follows a particular behavior, it increases the likelihood the animal will repeat the behavior. Reinforcement makes the behavior more likely to occur.
What is a Punishing stimulus?
Aversive stimulus. When it follows a particular behavior, it decreases the likelihood the animal will repeat the behavior. Punishment makes the behavior less likely to occur
What type of instrumental learning happens beneath level of consciousness?
Particularly relevant in drug addiction
Take it in an environment
Brain likes it
Next time when you are in that situation you are more likely to do it again
More you take the drug – the more the brain says YES
Example of our conscious control not being in full charge
Unconscious part of the brain takes charge
What are the two main pathways between sensory and motor cortices
Direct transcortical connections
The basal ganglia
What is the pathway of direct transcortical connections between the sensory and motor cortices?
Connections from one area of the cerebral cortex to another
Involved in the creation of new complex motor sequences that involve deliberation or instruction
What is the pathway of the basal ganglia? It is between the sensory and motor cortices
Collection of nuclei in the forebrain that regulate habit learning.
It integrates sensory and motor information from throughout the brain, initially acting as a passive “observer”
When successful behaviors are repeated over and over, the basal ganglia starts to automate the stimulus-response process.
The basal ganglia creates habitual ways of responding, leaving transcortical circuits free to do something else.
When this happens, habitual movements can be effective without any conscious consideration of the details.
What is Dopamine signaling?
Drives habit learning by controlling synaptic plasticity in the basal ganglia.
It provides a “thumbs up / thumbs down” signal that determines the likelihood an animal will repeat a behavior
Where do most areas of the cerebral cortex project to?
Nearly every area of the cerebral cortex projects to the basal ganglia.
Where do inputs to the basal ganglia primarily synapse?
Inputs to the basal ganglia primarily synapse in an area called the striatum, which consists of three parts: the caudate, putamen, and nucleus accumbens.
How do dopamine neurons in the midbrain (substantia nigra and ventral tegmental area) signal reinforcement and punishment?
by releasing more or less dopamine in the striatum (caudate, putamen, nucleus accumbens).
True of False: The overall amount of dopamine in the striatum seems to reflect the animal’s motivational state and the value of moving in and engaging with the environment
TRUE
Transient fluctuations in dopamine signaling seem to drive learning by signaling how unexpectedly good or bad the current moment is
What does the striatum do?
Different areas of the striatum process information from different cortical areas.
For example, the nucleus accumbens in the ventral striatum receives input from limbic areas such as the hippocampus, amygdala, and parts of PFC
Seems to regulate people’s priorities and cravings.
What happens to learning when lesions of the basal ganglia occurs?
Disrupt reinforcement learning and habit learning, but they do not strongly affect perceptual learning or stimulus-stimulus learning.
Who is Henry Gustav Molaison (HM)?
Doctors cut out his hippocampus bilaterally to cure his epilepsy
It worked, but he lost the ability to form new explicit memories (severe anterograde amnesia).
He also suffered from a graded retrograde amnesia (events that occurred within 1 or 2 years were lost as well as some events that happened even longer ago than that).
He still had a brief working memory and a high IQ, but he could not learn new words or names or learn to navigate a new space.
What is Korsakoff’s syndrome?
Permanent anterograde amnesia caused by brain damage, usually resulting from chronic alcoholism. Korsakoff’s patients are unable to form new memories but can still remember old ones before the brain damage occurred.
What is Confabulation?
Reporting of memories of events that did not take place without intention to deceive
Seen in people with Korsakoff’s syndrome
What is memory consolidation?
Most psychologists believe that learning consists of at least two stages: short-term memory and long-term memory
Simplest model of the memory process
The hippocampus is not the location of either short or long-term memories, but it is critical for the consolidation of short-term memories into explicit long-term memories
What is Anterograde amnesia?
inability to learn new information
or retain new information ‘after’ brain injury. Memory for events that
occurred before the injury remain largely intact
What is retrograde amnesia
inability to remember events that
occurred ‘before‘ the brain injury.
What is amnesia
A deficit in memory caused by brain damage or brain diseases (it can also be temporarily caused by different drugs).
Complete amnesia in either direction is rare
What is Anterograde amnesia
Refers to the inability to form new explicit memories ‘after’ brain injury. Memory for events before the injury remain largely intact.
what is retrograde amnesia
Refers to the inability to remember events that occurred ‘before‘ the brain injury.
Commonly seen in neurodegenerative diseases that are associated with brain-wide neurodegeneration and that also affect one’s ability to think, learn, and make decisions.
What is relational learning?
Damage to the hippocampus or to regions of the brain that supply its inputs and receive its outputs causes anterograde amnesia, but nondeclarative learning ability remains intact.
What are spared learning abilities
When amnesic patients are trained and tested, we find that they are capable of three of the four major types of learning: perceptual learning, motor learning, and stimulus–response learning.
However, amnesic patients do not explicitly remember anything about what they have learned.
What is lateralization? Which part of the brain is responsible for language?
Verbal behavior is lateralized in the brain.
Most language disturbances occur after damage to left side of brain, regardless if people are left-handed or right-handed
The left hemisphere is dominant for speech in 90 percent of the population
Right-hemisphere speech dominance is seen in 4 percent of right-handed people and 27 percent of left-handed people
At around what age can people recognize the voices of particular individuals?
Even newborn infants can recognize the voices of their parents.
Can people with left hemisphere damage recognize voices even if they might not be able to understand words?
YES. People with left hemisphere damage might not be able to understand words but they could still recognize voices.
Phonagnosia
A disorder where people have great difficulty recognizing voices.
It results from localized brain damage to the right superior temporal cortex
What is aphasia
Refers to a disturbance in understanding, repeating, or producing meaningful speech.
The difficulty must not be caused by simple sensory or motor deficits or by lack of motivation.
You can see, hear, move but you can’t speak
Damage to sensory association cortex causes deficits in understanding language. The aphasia may be described as a: (multiple answers)
posterior aphasia
sensory aphasia
receptive aphasia
Wernicke’s aphasia
fluent aphasia
Damage to the frontal lobe causes deficits in speaking. The aphasia may be described as a: (multiple answers)
anterior aphasia
motor aphasia
expressive aphasia
Broca’s aphasia
non-fluent aphasia
What happens if one gets a stroke in the “Language comprehension ‘posterior language area’”?
you cannot understand language/don’t use it intelligently
They can read but they can’t understand what they are reading
They can point at something that they want but they cannot TELL you what it is.
What is the Posterior Language Area
Located at the junction of the temporal, occipital, and parietal lobes, around the posterior end of the lateral fissure.
It is critical for language comprehension (regardless of whether the words are heard, seen, or spoken).
Damage to the posterior language area causes…
Transcortical Sensory Aphasia
what is Transcortical Sensory Aphasia
Speak fluently but words have no meaning to you
Failure to comprehend the meaning of words and an inability to express thoughts with meaningful speech.
Word perception and speaking might be fine (without any comprehension of what is heard or spoken).
For example:
Word repetition (e.g., repeat after me…)
Reading (without understanding)
Writing (without understanding)
What is conduction aphasia
Characterized by an inability to repeat the exact words you hear. Other than that, you are fine, that is you have meaningful, fluid speech and good speech comprehension.
When asked to repeat the word ‘house’, the person may say “home”.
When asked to repeat a nonsense word like ‘blaynge’, the person will be unable to do it. They will just say I didn’t hear you.
connection between Wernicke’s area and Broca’s area
arcuate fasciculus
Where and what is the Wernicke’s area
Involved in analysis of speech sounds and in recognition of spoken words.
Region of auditory association cortex on left temporal lobe of humans.
What is Pure word deafness
result of damage to a small part of Wernicke’s area
Pure word deafness is a disorder of auditory word recognition, an inability to comprehend or repeat spoken words.
“I can hear you, but I don’t recognize the words you are saying. I even have trouble repeating what you say.”
What is the Wernicke’s Aphasia
the result of damage to both Wernicke’s area and the Posterior language area, which means you have features of transcortical sensory aphasia and pure word deafness.
poor language comprehension
These people can have fluent speech production, but what they say is meaningless and typically filled with function words, such as a, the, in, about (as opposed to content words that convey meaning, such as nouns, verbs, and adjectives).
Transcortical sensory aphasia
Patients with transcortical sensory aphasia have trouble with language comprehension, but they can repeat what other people say to them; they can recognize spoken words.
Wernicke’s aphasia
Patients with Wernicke’s aphasia have trouble with language comprehension and are generally not capable of repeating what other people say to them.
What would a brain scan of Transcortical sensory aphasia and Wernicke’s aphasia look like?
Both of these aphasias are associated with damage in and around Wernicke’s area, including Posterior Language Area.
These brain areas aren’t really separable, or rather the functions of language comprehension and spoken word recognition are interweaved in and around Wernicke’s area.
You wouldn’t be able to differentiate between Wernicke’s aphasia and transcortical sensory aphasia just by looking at a brain scan
What does damage to the visual word form area (VWFA) do?
Disrupts the ability to perceive written words
People with this damage (Pure Alexia or Pure Word Blindness) cannot read, as they cannot recognize written words. However, they can write just fine. They just can’t read what they write.
What does damage to Broca’s area in the (left) inferior frontal lobe do?
makes it difficult for patients to express themselves verbally
Hard time talking and writing: they recognize it and become frustrated
Comprehension is fine and their hands and mouths work but they can’t communicate (hear their mouth saying something different than what they want to say)
What are three of the semi-distinct issues in Broca’s Aphasia
Articulation problems, Agrammatism and anomia
What are articulation problems?
Movement of tongue, lips, jaw, and other speech organs to make speech sounds. Articulation problems might make it hard for someone to hear the words you are saying. Or it could cause a sequencing problem: lipstick saying likstip.
What is agrammatism
Difficulty comprehending or using grammatical devices, such as verb endings (-ed) and word order (e.g., man bit dog).
People with agrammatism typically do not derive meaning from the sequence of words or the grammar of sentences. Thus, they almost exclusively use content words (nouns, adjectives, verbs, etc.) without any function words (the, on, about, etc.)
What is anomia
Difficulty in finding (remembering) the appropriate word to describe object, action, or attribute; one of symptoms of Broca’s aphasia
What is Anomic Aphasia
People with anomic aphasia have a hard time thinking of the word they want to say. They can understand what other people say just fine. If their speech is fluent, they will often describe things in roundabout ways (circumlocution)
what is Circumlocution
Strategy by which people with anomia find alternative ways to say something when they are unable to think of most appropriate word
Byron is a Wernicke’s aphasia patient. According to his wife, what can and can’t he do?
He understands over half of what he hears, and he can understand what he reads in a book or newspaper.
Byron cannot spell or repeat words.
He can read numbers, do math problems, make change, and analyze a financial statement better than I can.
So, from 0% comprehension and “word salad” to 60% comprehension and some functional language is not bad in 5 years.
What is the likelihood of having a stroke related to?
Related to age – probability doubles each decade after 45 years of age and reaches 1–2 percent per year by age 75
What is Atherosclerosis
Process in which linings of arteries develop a layer of plaque, deposits of cholesterol, fats, calcium, and cellular waste products.
Risk factors include high blood pressure, cigarette smoking, diabetes, and high blood levels of cholesterol.
Precursor to heart attacks (myocardial infarction) and strokes
What is a hemorrhagic stroke
rupture of cerebral blood vessel
what is an ischemic stroke?
occlusion of a blood vessel
87% of strokes are ischemic
What is a thrombus
Blood clot that forms within a blood vessel, which may block it and reduce blood flow to the affected area.
what is an embolus
Piece of matter (such as a blood clot, fat, or bacterial debris) that dislodges from its site of origin and occludes an artery. In the brain, an embolus can lead to a stroke
What is an example of an approach to minimize amount of brain damage caused by strokes?
Administer drugs that dissolve blood clots in an attempt to reestablish circulation to an ischemic brain region
This approach has met with some success. For example, administration of a clot-dissolving drug called tPA (tissue plasminogen activator) after the onset of a stroke has clear benefits, but only if it is given within 3-4 hours.
What is an approach to minimize amount of brain damage caused by strokes with a device?
Devices can be deployed through the vascular system to the site of an occlusion. The devices use various strategies to secure and/or remove occlusions. The devices can include coils (a), aspiration devices (b), or be incorporated into stents (c).
After Stroke Treatments
Drugs that reduce swelling and inflammation
Physical, speech, and/or occupational therapy
Exercise and sensory stimulation (constraint-induced movement therapy)
What is a tumor
mass of cells whose growth is uncontrolled and that serves no useful function
What is a non-malignant tumor
Noncancerous, “benign” tumor.
Has distinct border and cannot metastasize
what is a malignant tumor
Cancerous (literally, “harm-producing”) tumor.
Lacks distinct border and may metastasize
what is a metastasis?
Process by which cells break off of a tumor, travel through the vascular system, and grow elsewhere in the body
What is the difference between a malignant and non-malignant tumor
Malignant
If the tumor is cancerous it grows by infiltrating the surrounding tissue, and there will be no clear-cut border between tumor and normal tissue
Non-Malignant
If there is a border (encapsulate), the tumor is non-malignant; the surgeon can cut it out, and it will not regrow
What happens when surgeons remove malignant tumore and miss some cancer cells?
These cells will produce new tumors
Any tumor growing in the brain, malignant or benign, can produce neurological symptoms and threaten the patient’s life. Tumors damage brain tissue by two means
compression and infiltration.
What can a compression tumor do?
Can directly destroy brain tissue, or it can do so indirectly by blocking flow of cerebrospinal fluid and causing hydrocephalus
What is an example of a malignant tumor
Glioma
What is a Glioma
The tumor initiating cells originate from the neural stem cells that make glia.
They rapidly proliferate and are more resistant to chemotherapy and radiation than most tumor cells.
The survival rate from malignant gliomas is very low
What is an example of a non-malignant tumor
Meningioma
What is a Meningiomatumor
Encapsulated tumor
It is composed of cells that constitute the meninges – the dura mater or arachnoid membrane – often right between the two cerebral hemispheres.
Tumor of the cells of the meninges
May be encapsulated but it is still very damaging.
It can (i.e.) displaced the right side of the brain. The right ventricle is almost completely occluded.
What are disorders caused by infectious diseases?
Encephalitis
Meningitis
Polio
Rabies
Herpes simplex virus
What is Encephalitis
Inflammation of the brain caused by infection (bacterial or viral), toxic chemicals, or allergic reaction
The first symptoms are headache, fever, and nausea
What is meningitis
Inflammation of meninges caused by viruses or bacteria
The first symptoms are headache and stiff neck
What is Polio (acute anterior poliomyelitis)
Viral disease that destroys motor neurons of the brain and spinal cord
Paralyzed if it gets to the brain
What is Rabies
Fatal viral disease that causes brain damage; usually transmitted through the bite of an infected animal
What is herpes simplex virus
Virus that normally causes cold sores near the lips or genitals. In rare cases, it instead enters the brain causing encephalitis and brain damage
Rarely but possible to get to the brain
What is a closed head injury
Caused by a blow to the head with a blunt object
The brain comes into violent contact with the inside of the skull (coup)
The brain then recoils in the opposite direction and smashes against the skull again (contrecoup)
What is an open head injury
Penetrating brain injuries (also called open head injuries) obviously cause damage to the portion of the brain that is damaged by the object or the bone
In addition, damage to blood vessels can deprive parts of the brain of their normal blood supply
Accumulation of blood within the brain can cause further damage by exerting pressure within the brain
what is a traumatic brain injury
A serious health problem
Almost a third of deaths caused by injury involve TBI.
In survivors, scarring often forms within the brain, around the sites of injury, which increases risk of developing seizures.
Many people receive brain injuries but are not diagnosed.
Even mild cases of TBI (mTBI) greatly increase a person’s risk of developing brain problems down the road.
For example, the likelihood of Alzheimer’s disease is much higher in a person who has received blows to the head earlier in life
What is seizure disorder
Preferred term for epilepsy
Sometimes, if neurons that make up motor system are involved, a seizure can cause a convulsion, which is wild, uncontrollable activity of the muscles But not all seizures cause convulsions; in fact, most do not
what are convulsions
Violent sequence of uncontrollable muscular movements caused by seizure
What are causes of seizures
The most common cause is scarring, which may relate to an injury, a stroke, the irritating effect of a growing tumor, or a developmental abnormality in the brain
Other causes are high fevers (especially in young children) and withdrawal from GABA agonists, such as alcohol and barbiturates.
Many cases are idiopathic (of unknown causes).
Neural network instability and increased risk of seizures can come about for genetic reasons, involving gene mutations that affect what?
The amount or function of different ion channels in the brain
The reciprocal wiring of excitatory and inhibitory neurons
The rules that govern synaptic plasticity
What is a Partial (focal) seizure
Seizure that begins at a focus and remains localized, not generalizing to rest of brain
What is a simple partial seizure
Seizure that does not produce loss of consciousness.
What is a complex partial seizure?
Seizure that produces a loss of consciousness.
What is a generalized seizure
Seizure that involves most of the brain (nonlocalized seizure).
Includes tonic-clonic seizures, atonic seizures, and absence seizures
True or false: Every time a seizure occurs, they get worse than the time before
TRUE
What is an aura
Sensation that precedes a seizure. Its exact nature depends on the location of the seizure focus
What is a tonic-clonic seizure
A generalized, grand mal seizure that typically starts with an aura that is followed by a tonic phase and then a clonic phase. This type of seizure involves convulsions.
Usually aware when it is happening – tingling in hand, blackout vision…
What is a tonic phase
First phase of tonic-clonic seizure, in which all of patient’s skeletal muscles are contracted
What is a clonic phase
Second phase of a tonic-clonic seizure, in which patient shows rhythmic jerking movements
Fetal alcohol syndrome
Babies born to alcoholic women are typically smaller than average and develop more slowly.
A particularly serious condition associated with alcohol consumption during the 3rd and 4th week of pregnancy is fetal alcohol syndrome, which is associated with certain facial anomalies and severe intellectual disabilities
What causes Inherited Metabolic Disorders ?
Several inherited “errors of metabolism” can cause brain damage or impair brain development
what are “errors of metabolism”?
Genetic abnormalities in which recipe for a particular protein is in error.
Typically, the cause is that an enzyme is not synthesized on account of mutations in both copies of the gene. (both = mom and dad)
If the enzyme is a critical one, results can be very serious
what is Phenylketonuria (PKU)
Hereditary disorder caused by the absence of enzyme that converts the amino acid phenylalanine to tyrosine
Accumulation of phenylalanine causes brain damage unless a special diet is implemented soon after birth
what is Tay-Sachs disease?
Heritable, fatal, metabolic storage disorder
Lack of enzymes in lysosomes causes accumulation of waste produces and swelling of cells of brain
what is Down Syndrome caused by?
Caused not by inheritance of a faulty gene but by possession of extra twenty-first chromosome.
What does congenital mean
not necessarily mean hereditary;
Congenital refers to a disorder that one is born with.
What is down syndrome characterized by?
It is characterized by moderate to severe intellectual disability and often physical abnormalities
After age 30, the brain of a person with Down syndrome begins to degenerate in a manner similar to Alzheimer’s disease
what is Multiple sclerosis (MS)
Autoimmune demyelinating disease that usually occurs in people’s late twenties or thirties.
At scattered locations within the central nervous system, myelin sheaths are attacked by the person’s own immune system, leaving behind hard patches of debris called sclerotic plaques
What occurs with symptoms of MS?
Go through cycles where they flare up and then decrease after varying periods of time
In most cases, this pattern (remitting-relapsing MS) is followed by progressive MS later in course of disease.
Progressive MS is characterized by a slow, continuous increase in symptoms.
What are two drugs that have been approved to ‘treat’ MS (there is no cure)?
interferon β - a protein that modulates immune system activity
glatiramer acetate – peptides that mimic myelin (decoy approach)
Why are people who spend their childhood in places far from equator more likely to come down with MS than are those who live close to equator?
It is likely that some disease contracted during childhood spent in region in which virus is prevalent causes person’s immune system to attack his or her own myelin
What is degeneration
Degeneration is typically the result of apoptosis
What is apoptosis
Apoptosis is typically triggered by collections (aggregates) of misfolded proteins that disrupt normal cellular function.
What is Transmissible spongiform encephalopathy
Contagious brain disease (includes mad cow and Creutzfeldt-Jacob disease) whose degenerative process gives the brain a sponge-like appearance
Accumulation of misfolded prion protein is responsible for transmissible spongiform encephalopathies
What is Prion
Misfolded proteins with the ability to transmit their misfolded shape onto normal variants of the same protein.
Accordingly, prion protein diseases spread from cell and cell and animal to animal by means of contact with misfolded prion protein
What is Huntington’s disease caused by?
One dominant mutation in the Huntingtin gene. Over time, aggregates of huntingting protein form in the basal ganglia, causing neurodegeneration. It affects 1 in 10,000 people
When do symptoms that lead to death occur?
Symptoms usually begin between 30 and 50 years of age and death follows 15-20 years later.
What is Huntington’s disease characterized by?
It is characterized by an increasingly severe lack of coordination, uncontrollable jerky limb movements, and eventually dementia followed by death.
Movements in Huntington’s disease look like fragments of purposeful movements but occur involuntarily.
Where is Huntington’s protein is expressed?
Huntingtin protein is heavily expressed in the input nuclei of the basal ganglia (the striatum - caudate nucleus and putamen).
What causes degeneration of neurons in these regions?
Mutated Huntington’s protein tends to aggregate (clump) and overtime
What is Antisense theory
Antisense DNA (or RNA) can be administered intrathecally (in the spinal cord). Researchers are hopeful that this approach (or viral-mediated gene delivery and gene editing technologies) will one day become a practical and effective approach to altering gene expression in the brains of living people
What is Parkinson’s disease
Another degenerative “movement” disorder.
What is Parkinson’s disease associated with?
It is associated with degeneration of dopamine neurons in the midbrain, specifically in the substantia nigra.
How many people are affected by Parkinson’s disease? When do symptoms occur?
It affects 1% of the population. Symptoms usually appear after the age of 60.
What is Parkinson’s disease characterized by?
It is characterized by shaking, muscular rigidity, slowness of movement, difficulty walking, and eventually dementia. Without treatment, people have increasing difficulty initiating purposeful movement.
What are the causes of Parkinson’s disease?
unknown (partly genetic, partly environmental), however the death of midbrain dopamine neurons seems to relate to aggregation of the protein alpha-synuclein.
The protein alpha-synuclein, which is heavily expressed in dopamine neurons, tends to aggregate (clump together) at some rate.
Overtime these protein aggregates cause dopamine neurons to undergo apoptosis.
What does reduced dopamine signaling in the basal ganglia do?
Disrupts movement
Is there a cure for Parkinson’s disease?
There is presently no cure, but there are many ways to somewhat successfully treat the motor problems.
What is Alphasynuclein
Protein heavily express in midbrain dopamine neurons.
Its function is not entirely clear.
Abnormal accumulations are associated with dopamine neuron degeneration in Parkinson’s disease.
What do mutations in alphasynuclein gene do?
Mutations in the alphasynuclein gene can promote alpha-synuclein aggregation and cause Parkinson’s disease. These mutations can be dominant, in that only one bad gene (from one parent) can cause the problem.
What is are Lewy body’s
Aggregate of misfolded alpha-synuclein protein; found in the cytoplasm of midbrain dopamine neurons in people with Parkinson’s disease
What is Ubiquitin
Protein that is put on faulty/old/ misfolded proteins, which targets them for degradation.
Ubiquitinated proteins get brought to proteasomes, which breaks them into their constituent amino acids for recycling.
What is a Parkin protein
Protein that plays a critical role ubiquitination.
Mutated parkin is a cause of familial Parkinson’s disease.
If parkin is defective, misfolded proteins accumulate, aggregate, and eventually kill the cell.
What is Proteasome
Organelle responsible for destroying ubiquitinated proteins within a cell.
Dopaminergic neurons are especially sensitive to loss of parkin function and alpha-synuclein aggregation.
What is Toxic gain of function
Genetic disorder caused by a dominant gene mutation that produces a protein with toxic effects
e.g., mutations in the alpha-synuclein gene and huntingtin gene can produce proteins that create problems, causing Parkinson’s and Huntingtin’s disease, respectively.
What is Loss of function disorder
Genetic disorder caused by a recessive gene mutation that fails to produce a protein that is necessary to avoid problems
e.g., loss of or mutations in the parkin gene can cause misfolded alpha-synuclein protein to not be degraded
What are the main symptoms of PD
are the result of reduced dopamine signaling.
What are potential Treatment for PARKINSON’S
L-dopa treatments diminish the motor symptoms of PD.
Brain lesions and deep brain stimulation (DBS) devices are also common treatments for PD.
What are the main targets for lesions and DBS?
Parts of the basal ganglia that become overactive in PD, the globus pallidus and subthalamic nucleus, respectively
Damaging the globus pallidus or disrupting subthalamic nucleus activity seems to relieve symptoms of Parkinson’s disease by removing one of the brakes on motor behavior.
What is dementia
Progressive impairments to memory, thinking, and behavior that affect the ability to perform everyday activities as a result of a neurological disorder
Common causes are neurodegenerative disease, MS, multiple strokes, and repeated brain trauma (chronic traumatic encephalopathy).
What is Alzheimer’s disease? Describe it a little bit.
Neurodegenerative disorder that causes progressive memory loss, motor deficits, and eventual death.
Occurs in approximately 10 percent of the population above the age of 65 and almost 50 percent of people older than 85 years
It is associated with aggregates of misfolded β-amyloid protein and severe degeneration within and around the hippocampus and neocortex.
What is β-amyloid precursor protein (APP) ?
Protein that is the precursor for β-amyloid protein.
The gene for this protein is located on chromosome 21, which is the one duplicated (triplicated) in down syndrome.
What is secretase?
Class of enzymes that cut the β-amyloid precursor protein into smaller fragments, including βamyloid
What is Presenilin
Protein that forms part of the secretases that cut APP.
Mutations in presenilin can cause it to preferentially generate the abnormal long form β-amyloid, which causes early onset Alzheimer’s disease.
What is Apolipoprotein E (ApoE)
Glycoprotein that transports cholesterol in the blood and plays a role in cellular repair
Presence of the E4 allele of the apoE gene increases risk of late-onset Alzheimer’s disease
What is β-amyloid (Aβ)
Protein found in excessive amounts in brains of patients with Alzheimer’s disease
What is the Amyloid plaque
Extracellular aggregation of β-amyloid protein surrounded by glial cells and degenerating neurons
What is a Tau protein
Microtubule protein that becomes hyper-phosphorylated in Alzheimer’s disease, disrupting intracellular transport.
What is Neurofibrillary tangle
Intracellular accumulation of twisted Tau protein in dying neurons
Other than age, what is the strongest risk factor for Alzheimer’s disease?
traumatic brain injury
What does the Impact of Lifestyle have on chances of getting Alzheimer’s disease?
Alzheimer’s disease is less prevalent in well-educated people, especially those that keep their minds and body highly active
Other risk factors include obesity, hypertension, high cholesterol levels, and diabetes.
What are the most promising trials for cures for Alzheimer’s
Forms of Immunotherapy
Why do many use an immunotherapy approach when dealing with Alzheimer’s disease?
To get antibodies to recognize and destroy Aβ protein (or Tau protein, or both), either by sensitizing the patient’s own immune systems to these proteins or by directly injecting antibodies that are made elsewhere
What is Amyotrophic lateral sclerosis (ALS)
Degenerative disorder that attacks spinal cord and cranial nerve motor neurons
Also known as Lou Gehrig’s Disease or motor neuron disease
Incidence of this disease is approximately 3 in 100,000.
The disease typically starts after the age of 50.
What are symptoms of ALS
Spasticity (Increased tension of muscles, causing stiff and awkward movements)
Exaggerated stretch reflexes, progressive weakness and muscular atrophy, and paralysis
What is the average life span following a diagnosis of ALS?
2-4 years, but some people live much longer than that
For example, Stephan Hawking lived with the disease for over 50 years
What are Inherited gene mutations
Gene mutations that lower reproductive success tend to get eliminated from the gene pool fairly quickly.
Very harmful gene variants are typically eliminated within a few generations, so they tend to be extremely rare and recent in origin.
What is gene fixation
Over evolutionary time, natural selection favors higher-fitness genes.
Common gene variants
Not increasing or decreasing in prevalence
Means they must not have conferred an overall advantage or disadvantage on reproductive success in ancestral environments
i.e., they must have been neutral on average in all past environments
What are Neutral gene variants
Produce variations in human nature that are not associated with better or worse reproductive success (like different personality traits).
What are Common but harmful gene variants
Our environment, culture, and life span have changed so dramatically in the last few hundred years, it is likely that some common gene variants that were completely neutral across all ancestral environments are now harmful.
What are gene-environment interactions: The environmental risk factors associated with disorders that were not present in ancestral environments
- Late onset disorders, due to rapid increase in human life spans
- Obesity and diabetes, due to the abundance and low price of unnaturally tasty food
- Asthma, due to new types and unnaturally high levels of antigens and pollutants
- Addictions to highly purified synthetic drugs, such as heroin and meth
- Depression and anxiety – although the cause is unclear, prevalence rates have changed rapidly in recent history and vary enormously between cultures.
What are Susceptibility genes
Some of the gene mutations associated with mental illness were neutral or advantageous in ancestral environments
What happens across evolutionary time to gene variants that are not neutral?
They are either selected out (and should be extremely rare)
or
have gone to fixation (and everyone should have them).
What is the prevalence of Schizophrenia
Prevalence: about ~1% of the population, and this has been fairly consistent across cultures and recent history
Theory for the prevalence of these schizophrenia susceptibility genes
certain combinations of them may be advantageous for reproductive success.
According to the theory for the prevalence of schizophrenia genes, gene-wise, what is schizophrenia associated with?
Generally not associated with one bad gene, one bad protein, or one dysregulated brain region. Rather, hundreds of relatively common gene variants each individually confer a very small statistical increase in the risk of developing schizophrenia.
According to the theory for the prevalence of schizophrenia genes what would be relevant to the siblings of schizophrenics?
The siblings of schizophrenics who don’t have the disease should have increased reproductive success on average, because they would be more likely to have the good combination of these schizophrenia genes in comparison to the general population.
However, siblings of schizophrenics seem to have the same reproductive success as the general population.
Aren’t mental disorders discrete, unitary diseases?
It doesn’t seem like it.
There is too much:
- Heterogeneity within diagnostic categories
- Comorbidity across categories
- Continuity with normality
- For mental disorders to qualify as discrete, unitary diseases
What is Mutation-Selection Balance
Mental disorder susceptibility genes are continually being selected out through evolution, but new mutations keep arising.
All of us have gene mutations associated with a slight reduction in “fitness” that arose within the last 100 generations or so of our family tree.
Most bad genes are a family legacy, old mutations that have yet to go extinct, rather than new mutations specific to the individual.
These mutations will get eliminated over time, but new ones keep coming.
What is Inherited gene mutation
The human genome has evolved to buffer many insults
environmental variation – can have a dramatic or healthy upbringing and the brain can adapt to any environment
genetic variation – brain can compensate for 5-10 bad gene variations
molecular noise – randomness of genes: slight probability that 2 genes together is NO GOOD
This robustness allows genetic variation to accumulate in the population if the individual mutations are not too severe.
Much depends on chance in brain development like what?
So much unavoidable randomness at a molecular level impacting brain development that even
Some people argue that body symmetry is indicative of the robustness of the underlying genetic instructions, which have to contend with environmental variation and molecular noise. What is meant by that?
The two sides of the body develop independently from the same set of genomic instructions. If the instructions are clear then the body should be symmetrical. If the instructions are a bit confusing or open to interpretation, however, then the person may be more asymmetric
These gene variants are thought to be indicative of neurodevelopmental robustness (due to clear genetic instructions)
What is schizophrenia characterized by?
social withdrawal, disorganized thinking, abnormal speech, and an inability to understand reality.
Affects approximately 1% of world’s population.
Symptoms typically come on gradually in schizophrenia
Begin in young adulthood, and in many cases never resolve (although 20% of people eventually do quite well).
30-50% of people with schizophrenia do not believe they have an illness or comply with their recommended treatment.
What is the difference in Development of Schizophrenia in males and females?
Both at late adolescence/early adulthood because:
Earlier in development there is a change in living situations and brain development (early 20s)
Myelination occurs (frontal lobe is the last place to do so)
***Action potential goes as fast as ever before and optimizes itself: synapses eliminated and brain needs to adapt
Males around 12-20
Females around 20-30 and again 44-49 (menopause)
Menopause for females
Women go through BIG hormonal changes and the brain needs to adapt
“FREES” bad mutations.
The symptoms of schizophrenia are often grouped into 3 categories
Negative
Cognitive
Positive
What are negative symptoms of schizophrenia?
Negative: the absence of behaviors
Social withdrawal, reduced emotional expression, poverty of speech, and reduced motivation
What are cognitive symptoms of schizophrenia
Disorganized and irrational thinking, deficits in learning and memory, poor abstract thinking, and poor problem solving
What are positive symptoms of schizophrenia?
Positive: the presence of delusions
Typically delusions of persecution, grandeur, or control - beliefs that contradict reality
Hallucinations (perception of stimuli that are not actually present)
Superstisions
What order do the symptoms appear in?
Negative symptoms typically emerge first, followed by cognitive symptoms and, years later, by positive symptoms.
What increases your risk of developing schizophrenia?
Both of you parents have it (or an identical twin has it) is ~50%
One of your parents has it is ~13%
Your sibling has it is ~8%
Around 5% of cases are attributed to rare gene copy number variations (duplicated or missing genes), which are frequently comorbid with autism and intellectual disabilities
What are Environmental factors pf schizophrenia
Mother’s nutrition during pregnancy
Mother’s stress during pregnancy
Certain infections (particularly during pregnancy)
Birth month
Being raised in a city
Childhood trauma
Social isolation
Perinatal hypoxia / brain damage
What is the seasonality effect
The number of schizophrenic births in late winter and early spring is especially high if the temperature was lower than normal during previous autumn
This condition keeps people indoors and favors transmission of viral illnesses
Is schizophrenia more prevelant in people who live in the middle of large cities or to those who live in rural areas?
Schizophrenia is also about three times more prevalent in people who live in the middle of large cities as compared to those who live in rural areas
This result suggests transmission of infectious illnesses is facilitated by increased population density
Prenatal environments of monochorionic twins (i.e., they share one placenta) are more similar than those of dichorionic twins. Which pair of twins have a higher rate for schizophrenia?
Some evidence suggests that the concordance rate for schizophrenia is higher for monochorionic twins than for dichorionic twins, which suggests that the prenatal environment is an important factor
When are Symptoms of schizophrenia prevelant
are not normally seen in childhood, but behavioural and anatomical evidence indicates that abnormal prenatal development is associated with schizophrenia
What are behavioural vs. Anatomical symptoms of schizophrenia
Behavioural
Children who go on to develop schizophrenia display less sociability and deficient psychomotor functioning as kids.
Anatomical
Minor physical abnormalities are often seen in children who go on to develop schizophrenia, such as partial webbing of the two middle toes and a high-steepled palate
What are Treatment of Schizophrenia
There is no cure for schizophrenia.
The main treatment is medication, often in combination with psychological and social supports.
What are typical drugs that help with schizophrenia
Many drugs have been developed that relieve the positive symptoms of schizophrenia.
They typically block dopamine D2 receptors and are called antipsychotics or neuroleptics.
In contrast, dopamine receptor agonists, like crystal meth and cocaine, tend to temporarily elicit certain aspects of the positive symptoms of schizophrenia in people who do not have the disorder.
What is the Dopamine Hypothesis
Excessive dopamine D2 receptor activity, particularly in the nucleus accumbens (striatum), underlies the positive symptoms of schizophrenia
Dopamine D2 receptor antagonists typically reduce the positive symptoms of schizophrenia but not the negative symptoms.
What is hypofrontality
In general, the negative symptoms of schizophrenia may be caused by hypofrontality
Decreased activity of the frontal lobes, particularly the dorsolateral prefrontal cortex, which may relate to hypoactivity of local dopamine D1 receptors.
What is associated with the positive symptoms of schizophrenia
Excess dopamine signaling in the striatum has been associated with the positive symptoms of schizophrenia, reduced dopamine signaling in the prefrontal cortex has been associated with the negative symptoms.
Is it possible that schizophrenics have too little dopamine in the prefrontal cortex and too much elsewhere?
YES.
What are Atypical antipsychotic medications
Recently developed medications which aim to reduce both the positive symptoms and negative symptoms of schizophrenia. They typically influence the activity of several neurotransmitter receptors (beyond blocking the dopamine D2 receptor).
What is Clozapine
First of the atypical antipsychotic medications.
It blocks both dopamine D2 and serotonin 2A receptors.
What is Aripiprazole
An atypical antipsychotic
Acts as partial agonist at the dopamine D2 and D3 receptors.
What is a Partial dopamine D2 receptor agonist.
A partial agonist is a drug with very high affinity for a receptor, but it activates it less than the normal ligand does.
A partial agonist can act as an agonist in regions of low concentration of normal ligand and as antagonist in regions of high concentrations
Thought to reduce dopamine receptor activity in the striatum (nucleus accumbens) but boost it in the prefrontal cortex.
Do patients with Schizophrenia know they have a disorder?
NO
Autism – Autistic Disorder
General information
Autistic spectrum disorder describes a wide range of developmental disorders that are characterized by troubles with social interaction and communication, and by restricted and repetitive behavior.
The incidence of autism is around 1% of population
In many cases there are clear cognitive impairments, intellectual disability, or reduced imaginative ability, but this is not always the case
Parents usually notice signs during the first two or three years of their child’s life.
first symptoms to emerge of autism
Social impairments are often the first symptoms to emerge.
Some infants with autistic disorder do not seem to care whether they are held. Some arch their backs when picked up, as if they do not want to be held
Causes for autism
Combination of genetic and environmental factors that affect early brain development
Estimates of the heritability of autism are around 70%, but as high as 90% for autism spectrum disorder.
Many cases have been linked to spontaneous rare gene mutations that have severe effects. These include chromosomal abnormalities involving deletions, duplications or inversions of genetic material.
Other cases are associated with rare multigene interactions involving common gene variants.
Some cases have been linked to maternal viral infections during pregnancy
Mild forms of autistic spectrum disorder
Often do not include a delay in language development or the presence of important cognitive deficits
Often called Asperger’s syndrome – mostly just involve deficient or absent social interactions and repetitive and stereotyped behaviors along with obsessional interest in narrow subjects
More common in males or females?
Disorder is four times more common in males than in females
If only cases of autism with intellectual disability are considered, the ratio falls to 2:1 (males:females)
If only cases of high-functioning autism are considered (those with average or above-average intelligence and reasonably good communicative ability), the ratio rises to approximately 7:1 (males:females)
Abnormalities in the development of the brains of autistic children
Kids who develop autism tend to have a slightly small brain at birth, but it grows abnormally fast and by 2–3 years of age is often about 10% larger than a normal brain
Following this early spurt, growth of the autistic brain slows down, and by adolescence it is only about 1–2 percent larger than normal.
Hypotheses for the cellular and molecular bases of early brain overgrowth include what?
Altered neuronal migration during early gestation
Abnormal formation of synapses and dendritic spines
Overconnectivity in key brain regions
Unbalanced excitatory / inhibitory neural networks
fMRI studies
Have revealed marked abnormalities in brain activity.
For example, there is little or no activity in fusiform face area of autistic adults looking at pictures of human faces
Treatment for autism
The main goals when treating children with autism are to lessen the impact of the associated deficits and family distress, and to increase quality of life and functional independence.
Intensive, sustained special education programs and behavior therapy early in life can help children acquire self-care, communication, and life skills, and often improve functioning and decrease symptom severity and maladaptive behaviors.
Medications generally do not address the core symptoms, but often help reduce the irritability, inattention, and repetitive behaviors.
What are medications used for people with autism
All kinds of medications may be tried, including:
anticonvulsants (↑ GABA receptor activity)
antidepressants (↑ serotonin receptor activity)
antipsychotics (↓ dopamine receptor activity)
stimulants (↑ dopamine receptor activity)
Refering to Depression and Bipolar, what does Affect mean?
As a noun, affect refers to feelings or emotions
Just as the primary symptom of schizophrenia is disordered thoughts, affective disorders (mood disorders) are characterized by disordered feelings
Mood (affective) disorder
Serious mood disorder
There are two principal types of mood disorders: bipolar disorder and major depressive disorder
What are affective disorders
Are prevalent and dangerous
A diagnosis of depression has a prevalence of approximately 7% in women and 3% in men.
Severely depressed people usually feel unworthy, hopeless, and have strong feelings of guilt
People with mood disorders have a very risk of self-harm and suicide
MAJOR Affective Disorders
Bipolar disorder and Major Depressive Disorder
What are environmental factors for mood disorders?
traumatic/abusive childhood experiences.
WHat is Bipolar disorder
Serious mood disorder characterized by cyclical periods of mania and depression.
It affects ~1% of the population.
~80% of the risk is attributed to genetics
What is Mania
Episodes of mania are characterized by sense of euphoria that does not seem to be justified by circumstances
People with mania usually exhibit nonstop speech and motor activity
Diagnosis of mania is partly a matter of degree; one would not call exuberance and a zest for life pathological
What are treatments for Mania in Bipolar Disorder
Lithiutm
Chemical element
Lithium salts (and anticonvulsants) are commonly prescribed for bipolar disorder
Most effective for treating the manic phase of bipolar disorder
Once mania is eliminated, depression usually does not follow
Therapeutic effect of lithium is very rapid.
The mechanism of action is unknown
Major depressive disorder (MDD)
Serious mood disorder that consists of unremitting depression or periods of depression (that do not alternate with periods of mania).
~40% of the risk is attributed to genetics.
What are Biological treatments of MDD?
Drugs that increase serotonin and/or norepinephrine signaling by inhibiting their enzymatic breakdown (e.g., monoamine oxidase inhibitors, MAOi) or by blocking their reuptake (e.g., tricyclics and serotonin specific reuptake inhibitors, SSRIs)
Ketamine (NMDA glutamate receptor blocker)
Electroconvulsive therapy (ECT)
Deep brain stimulation
Transcranial magnetic stimulation
Vagus nerve stimulation
Bright-light therapy (phototherapy)
Sleep deprivation
Tricyclic antidepressant
Serotonin specific reuptake inhibitor (SSRI)
Serotonin and norepinephrine reuptake inhibitor (SNRI)
What is a Tricyclic antidepressant
Inhibits reuptake of serotonin and norepinephrine but also affects other neurotransmitters; Named for the molecular structure
Serotonin specific reuptake inhibitor (SSRI)
A class of drugs that specifically inhibit the reuptake of serotonin without affecting the reuptake of other neurotransmitters. The most common one is Prozac (fluoxetine). Similar drugs are Celexa, Paxil, Zoloft, etc…
Serotonin and norepinephrine reuptake inhibitor (SNRI)
Antidepressant drug that specifically inhibits reuptake of norepinephrine and serotonin without affecting reuptake of other neurotransmitters.
What is the idea of the Monoamine hypothesis
Based largely on the success tricyclic and SSRI treatments, the monoamine hypothesis of depression was developed.
The idea is that depression is caused by insufficient monoamine receptor activity (the monoamines are serotonin, norepinephrine, and dopamine)
Because symptoms of depression are generally not relieved by potent dopamine receptor agonists such as amphetamine or cocaine, most investigators have focused their research efforts on the other two monoamines: norepinephrine and serotonin.
Tryptophan is the molecular precursor to serotonin what does the monoamine hypothesis do?
Giving people a low-tryptophan diet and then a tryptophan-free amino acid “cocktail” lowers brain tryptophan levels and consequently decreases their synthesis of serotonin (5-HT).
This tryptophan/serotonin depletion procedure can elicit a depressive episode in people susceptible to depression.
Do the SSRIs and SNRIs increase the levels of 5-HT and norepinephrine in the brain fast or slow? Do they relieve the symptoms right away or long term?
Although SSRIs and SNRIs increase the levels of 5-HT and norepinephrine in the brain very rapidly, the drugs do not relieve symptoms of depression until they have been taken for several weeks
Role of the frontal cortex
There are few (if any) correlations. However, the argument has been made that one area of the anterior cingulate cortex (the subgenual region known as area 25) becomes less active after successful treatments.
What are some promising approaches to know more about mental illnesses?
Deep Brain stimulation
Other promising approaches involve transcranial magnetic stimulation (TMS) directed to areas of the PFC or vagal nerve stimulation (VNS).
What is Electroconvulsive therapy (ECT)
Used therapeutically to alleviate severe depression and bipolar disorder.
Seizures are electrically induced by applying brief electrical shocks to the head
In contrast to the delayed therapeutic effects seen with monoamine related treatments, the effects of other treatments (including ECT, lithium, DBS, VNS, and sleep deprivation) are more rapid. The seizures induced by ECT often reduce symptoms within days.
Role of Sleep
One of the most prominent symptoms of depression is disordered sleep.
People with depression often have shallow, fragmented sleep.
They tend to awaken frequently, especially toward morning.
In general, they spend more time in stage 1 sleep and less time in deep, slow-wave sleep (stages 3 and 4).
They also enter REM sleep soon after falling asleep, much earlier in the night in comparison to other people.
Total Sleep Deprivation
One of most effective antidepressant treatments is total sleep deprivation.
Total sleep deprivation has immediate antidepressant effects in some people
Typically, depression is lifted by staying up overnight, but it returns after a normal night’s sleep
This suggests that a chemical builds up during waking hours that has some antidepressant effect, and it gets cleared away during sleep.
REM sleep deprivation also works, although more slowly, over the course of several weeks (similar to SSRIs).
What is stress? Why is in not-healthy?
Stress refers to the physiological reaction caused by the perception of aversive or threatening situations.
These physiological responses prepare people for fight or flight situations and include autonomic and endocrine responses that help to mobilize the body’s energy resources and support vigorous activity.
Stress-related autonomic and endocrine responses can cause adverse effects on health over time
Physiology of the stress response
- Stress activates the sympathetic branch of autonomic nervous system, causing the adrenal gland to release epinephrine and norepinephrine into the blood.
- Stress also activates the HPA axis (Hypothalamus-Pituitary-Adrenal gland), which increases glucocorticoid signaling in the blood.
a) Stress initially triggers the hypothalamus to release CRH/CRF (corticotropin-releasing hormone/factor).
b) CRH causes the pituitary to secrete ACTH (adrenocorticotropic hormone).
c) ACTH causes the adrenal gland to release glucocorticoids, primarily cortisol.
what is the result of stress in a physical way?
Overall, these autonomic and hormone responses work together to increase heart rate, blood pressure, and blood flow to muscles
What are Glucocorticoids
A group of hormones (including cortisol) that help make glucose and fat available for immediate use, increase blood flow, suppress secretion of sex hormones, and stimulate behavioral responsiveness.
Many of the actions of glucocorticoids are not well understood.
What expresses glucocorticoid receptors?
Almost every cell in the body expresses glucocorticoid receptors, which suggests that every organ is affected by these hormones.
The short-term effects of glucocorticoids are essential for survival. What happens in the long-term effects of this same thing?
While the short-term effects of glucocorticoids are essential for survival, persistent glucocorticoid signaling can increase blood pressure, damage muscle tissue, inhibit body growth, suppress the immune system, and cause infertility and steroid diabetes.
Effects of stress on immune functions ?
Stress can slow the healing of (flesh) wounds and predispose people to infections.
In one study, people were found to have experienced more undesirable, stressful events 3-5 days before developing an upper respiratory infection.
Effects of stress on the brain
Monkeys near bottom of their social hierarchy are often stressed, and they more often die from stress-related issues.
Post-mortem examinations reveal signs of chronic stress, such as gastric ulcers, enlarged adrenal glands, and damaged hippocampi.
Episodes of emotional maltreatment during childhood has been associated with a small reduction in volume of dorsomedial prefrontal cortex
Post Traumatic Stress Disorder (PTSD)
PTSD is a mental disorder that can develop after a person is exposed to a traumatic event, such as sexual assault, warfare, traffic collisions, or other threats on a person’s life.
It is no longer classified as an anxiety disorder since it entails multiple emotions (e.g., guilt, shame, anger) outside the fear/anxiety spectrum.
Symptoms of PTSD
disturbing thoughts, feelings, or dreams related to the events
mental or physical distress to trauma-related cues and efforts to avoid them
Increased fight-or-flight response.
The symptoms can interfere with social activities, cause feelings of hopelessness and increase risk for suicide.
What increases your likelihood of getting PTSD
Most people who experience trauma do not develop PTSD, but the likelihood of developing it increases with the number of traumatic events.
About 30% of the variance in PTSD relates to genetics.
The main treatments for PTSD
cognitive behavioural therapy, group therapy, and medication.
Selective serotonin reuptake inhibitors (SSRIs) are the first-line medications and benefit about half of people.
PTSD has been associated with abnormalities where?
in the HPA axis which coordinates hormonal responses to stress
Increased amygdala activity may contribute to the emotional reactions of people with PTSD.
Do people often have more than one type of anxiety disorder?
YES
Anxiety disorder
A variety of psychological disorders characterized by unrealistic and unfounded fear and anxiety.
Includes muscle tension, over activity of the autonomic nervous system, expectation of an impending disaster, and continuous vigilance for danger.
Generalized anxiety disorder
Disorder characterized by excessive anxiety and worry serious enough to disrupt daily life
Social anxiety disorder
Characterized by excessive fear of being exposed to the scrutiny of other people, leading to avoidance of social situations in which they may be called on to perform
Panic disorder
Characterized by episodic periods of severe and unremitting terror.
Includes symptoms such as shortness of breath, irregularities in heartbeat, and other autonomic symptoms, accompanied by intense fear
Anticipatory anxiety
Fear of having a panic attack promotes anticipatory anxiety that sometimes leads to the development of agoraphobia
Agoraphobia
Fear of being away from home or other protected places
General information about anxiety disorders.
In any given year, about 12% of people are affected by an anxiety disorder, but it is twice as common in females than males.
Symptoms generally start before the age of 25.
12% of people develop a specific phobia at some point in their life.
About 10% develop social anxiety disorder at some point in their life
The cause of anxiety disorders is a combination of genetic and environmental factors.
Environmental risk factors include a history of child abuse and poverty.
Anxiety disorders often occur with other mental disorders, particularly major depressive disorder, personality disorder, and substance use disorder.
Older people who have dementia often have problems with anxiety.
Brain activity of Anxiety Disorders
studies suggest that the amygdala and prefrontal cortex are involved
Adolescents with generalized anxiety disorder showed increased activation of the amygdala and decreased activation of the ventrolateral prefrontal cortex while looking at angry faces
College students with a high level of anxiety showed increased activation of the amygdala, which positively correlates with students’ anxiety measures
Treatment for anxiety
Treatment options include lifestyle changes, behavioural therapy, and medications.
Lifestyle changes may include exercise, regularizing sleep patterns, and reducing caffeine intake and smoking.
Cognitive behavioral therapy (CBT) is often effective and is a first line treatment.
When medication is called for
- Benzodiazepines are sometimes used, particularly in emergency settings because of their rapid onset
- Selective serotonin reuptake inhibitors (SSRIs) are frequently used as a first line treatment for anxiety disorders
Obsessive-Compulsive Disorder (OCD)
OCD (less than 2% of population) is characterized by
repeatedly having certain thoughts (“obsessions”) and
a need to repeatedly check things or repeatedly perform certain routines (“rituals“ or “compulsions”) to an extent that it causes distress & impairs general functioning.
What are the four groups of symptoms for OCD
1 - Symmetry
2 - Cleaning
the “cleaning” cluster is associated with germs, bodily fluids, and contamination
3 - Hoarding
4 - Forbidden thoughts
The “forbidden thoughts” cluster is associated with intrusive and distressing thoughts of a violent, religious, or sexual nature
Why do people with OCD do these “rituals”
The compulsions are often performed to seek relief from obsession-related anxiety, driven by a fear that something bad will happen if the ritualistic behaviour is not done properly or a belief that life cannot proceed as normal while the imbalance remains.
Do people with OCD realize they have OCD?
Most adults with OCD realize that their behaviors do not make sense, they understand that their notions do not correspond with reality; however, they feel that they must act as though their notions are correct, and they are typically unable to control their obsessions or compulsions for more than a short period of time
General information of OCD
Incidence of OCD is less than 2 percent.
Lifetime prevalence rates are slightly higher in women than men, but diagnosis typically occurs later in women (after age 18) than men (during adolescence).
Symptoms usually start before age 25 in both sexes.
The cause of OCD is a combination of genetic and environmental factors.
Genetic factors account for ~50% of the variability.
Environmental risk factors include a history of child abuse or other adverse events.
Some cases have been documented following infections.
Treatment for OCD
Treatment always involves counseling, often a version of cognitive behavioral therapy (CBT) known as exposure and response prevention, which involves increasing exposure to what causes the problems while not allowing the repetitive behavior to occur.
Treatment sometimes includes antidepressants such as selective serotonin reuptake inhibitors (SSRIs)
Without treatment, the condition often lasts decades.
Treatment for severe cases can include a brain lesion, specifically a cingulotomy, which is the cutting of a fiber bundle between PFC and anterior cingulate
can you get OCD from a brain injury?
Sometimes OCD symptoms appear after brain damage, particularly to the basal ganglia, cingulate gyrus, or prefrontal cortex
General info on Substance Abuse disorders. Main ‘players’
The big players are alcohol, opiates, cocaine and meth, nicotine, barbiturates and benzos.
Problems with alcohol abuse:
automobile accidents
fetal alcohol syndrome
cirrhosis of the liver
Korsakoff’s syndrome
increased rate of heart disease
increased rate of intracerebral hemorrhage
pancreatitis, diabetes, etc., etc.
Reinforcement learning is driven by the consequences of behaviour. Addictive drugs positively reinforcer behaviour. When is reinforcement most effective? What do reinforcers do?
Reinforcement is most effective when the consequences of an action are immediate (versus delayed).
The speed by which the brain perceives reinforcement is thought to explain the relative addictive potential of different drugs, such as heroin versus morphine
All reinforcers, natural or otherwise, elicit dopamine release in the striatum, particularly in the nucleus accumbens, and the most addictive drugs rapidly increase dopamine signaling
Hereditary and distribution for alcohol consumption?
Epidemiological studies estimate that genetic factors account for 40–60% of the risk factors for alcoholism.
Alcohol consumption is not distributed equally across the population; in the United States, 10 percent of the people drink 50 percent of the alcohol
Are people with a gene variant only at risk for an addiction on a specific type of drug?
Some gene variants predispose people to becoming addicted to a specific drug. Other gene variants increase the risk of developing addiction in general.
What are Negative Reinforcements
When a behaviour is reinforced by the removal (or reduction) of an aversive stimulus.
People have argued that addiction is partially maintained by negative reinforcement, since after tolerance develops people sometimes continue to take drugs simply to prevent or reduce withdrawal symptoms.
However, drug cravings and addictive behaviours far outlast any withdrawal symptoms. To some extent, getting through withdrawal is the easy part.
What is Tolerance
When a drug effect gets smaller with repeated administration, increasingly larger doses are needed to achieve the desired effect.
Caused by compensatory mechanisms that oppose the effect of the drug. Not all addictive drugs produce tolerance and withdrawal
What is Withdrawal
Appearance of symptoms opposite to those produced by drug when the drug is suddenly no longer taken
Caused by presence of compensatory mechanisms (that relate to drug tolerance)
Prefrontal Cortex of people suffering from alcohol addiction
Some people with a history of drug use show deficits on tasks that involved the PFC, similar to people that have damage in this brain region.
When addicts (who are not currently high) perform lab tests that normally activate the prefrontal cortex, they show less activity in this brain region and perform more poorly on these tests than other people do.
In one study, the overall amount of cocaine taken by addicts in their lifetime correlated with reductions in PFC activity.
What is the comorbidity of people abusing drugs and mental illnesses?
Studies have shown a high level of comorbidity of schizophrenia, ADHD, and substance abuse
70-90% of schizophrenics smoke cigarettes and almost half are addicted to drugs other than nicotine.
One study from 2004 estimated that 7% of the population had some form of mental illness, yet a third of all cigarettes were smoked by this group
Abnormalities in the prefrontal cortex and its interactions with the striatum and dopamine neurons may be a common factor in these disorders
Different therapy approaches for drug abuse
The binding site blocker approach
Maintenance approach
Partial agonist approach
Brain Stimulation approach
What are drug examples of the binding site blocker therapy approach
Naltrexone and Naloxone (Narcan)
Naltrexone
A somewhat long-acting, slow onset, high affinity opioid receptor antagonist that is prescribed to alcoholics and opiate addicts for daily use
It reduces the high produced by opiates (because it outcompetes opiates for the receptor binding site).
It also seems to reduce cravings for food, alcohol, and other drugs in some people
Naloxone (Narcan)
Extremely rapid (and short lived) opioid receptor antagonist that reverses the effects of an opiate overdose.
During an opiate overdose, people can lose consciousness and stop breathing.
A naloxone injection can immediately reverse these effects and even elicit withdrawal symptoms (but naloxone is short-lived and cleared in 20-80 minutes).
What is a drug examples of the Maintenance approach
Methadone maintenance
What are drug examples of the Partial agonist approach
Buprenorphine and Varenicline
What is a drug examples of the Brain Stimulation approach
DBS and TMS
Methadone maintenance
Potent opiate, similar to morphine or heroin but with a slower onset and offset.
Methadone maintenance programs administer the drug to their patients in liquid form, which they must drink in the presence of supervising personnel
Similar maintenance treatments are used with nicotine addiction (nicotine patches, gum, vaping, etc.)
Buprenorphine
Buprenorphine is a high affinity partial opioid receptor agonist. It strongly binds to opioid receptors but produces only a weak effect while blocking the effect of other opiates.
It is a relatively new treatment for opiate addiction.
To reduce the potential for abuse, it is commonly mixed with a little naloxone (a short-lived opiate receptor antagonist).
Varenicline
Approved to treat nicotine addiction
It is a partial agonist at nicotinic (acetylcholine) receptors, just as buprenorphine is a partial agonist at opioid receptors
DBS and TMS
Researchers have tried deep brain stimulation (DBS) in many areas of the brain, including the basal ganglia and PFC.
Transcranial magnetic stimulation (TMS) of the PFC is also currently being tested
General Information for Attention-deficit/hyperactivity disorder (ADHD)
ADHD is a mental disorder characterized by problems paying attention, difficulty controlling (inhibiting) behavior in an age-appropriate manner, and hyperactivity.
More than 5% of children in North America are now being treated for ADHD.
The symptoms generally appear before the age of 12, are present for more than six months and cause problems in school, home, or elsewhere.
ADHD is usually first identified in the classroom, where children are expected to sit quietly and pay attention to a teacher or work steadily on project
Are children with ADHD easy to identify
No because many children with ADHD have a good attention span for tasks they find interesting, and some hyperactivity, inattention, and impulsivity are within the range of normative behaviors.
What is ADHD associated with
ADHD is often associated with learning disabilities, depression, anxiety, low self-esteem, aggression, and conduct disorder
Causes and Prevelance rates of ADHD
Prevalence rates
vary widely across different communities, ranging from 1 to 10% of children.
Boys are diagnosed three times more often than girls.
The causes of ADHD include environmental and genetic factors.
Estimated heritability of ADHD ranges from 75 to 90%.
Certain cases are related to previous infection of or trauma to the brain.
Drug and alcohol use and infections during pregnancy are associated with increased risk for the child, as is low birth weight.
Management of ADHD
Typically involves counseling and medications, often stimulants that raise dopamine levels by blocking or reversing the dopamine reuptake transporter (e.g., Ritalin and Adderall).
Antidepressants may also be helpful.
