Midterm Flashcards
What are the 2 main things that are studied in neurodevelopment?
- mechanisms that govern the developmental trajectories of the NS
- alternative pathways underlying pathological outcomes
What are some factors that can influence neurodevelopment?
Genes and environment (drugs, toxins, stressors)
What is neuropsychology?
it is the study of brain-behaviour relationships
>assessment of brain function based on behavioural expression
What is the main function of neurons?
They form the basis of communication within the brain through networks
What is the main function of glial cells?
they are the “supportive” cells in the NS that help the neurons function
What two things are integral to proper function of the brain (like learning and memory)
growth and change
Important changes on the brain occur when? What can interfere with this?
at critical periods
Teratogens that disrupt proper development
Neuroplasticity
Mechanisms that allow the brain to change and adapt to environmental stimuli
What does neuroplasticity allow for?
- compensatory mechanisms after an injury
- adaptation to changes
Do we have the same amount of neuroplasticity at all ages in life?
No
Younger individuals have more plasticity
Early embryonic cells become what?
Neural progenitors
Do neurons and glial cells have different progenitor cells?
No, they can stem from the same progenitor cells
What genes regulate neurogenesis and gliogenesis?
Different genes
Do neurons or glial cells usually develop first?
Neurons
Do we keep generating neurons throughout our lives?
No, we have most of our neurons at birth
If we do not generate any more neurons after birth, why does our brain get bigger?
Because we develop more glia during life
Do we need all the neurons we are born with?
No, the neurons we do not use get pruned
What are the electrical and chemical communicators in the brain
Electrical = action poteital Chemical = neurotransmitters
Why do some babies who were exposed to alcohol in utero get fetal alcohol syndrome and some do not? (2)
- It depends on the stage of development they were exposed
2. Some genes are protective and some genes put you more at risk
Embryogenesis:
Process by which an embryo develops
Inner cell mass develops into what?
embryo
What does the trophoblast contribute to?
the placenta
How many days after fertilization does implantation occur?
7 days
What layer does the nervous system develop from?
ectoderm germ layer
The neural tube is developed by what time point?
3 weeks
What part of the neural tube develops into the brain
the front part
What factors can impact the development of the NS
Genetic Factors
Environmental Factors
- toxins, drugs, diet
***often a combination
What is the progression of the central dogma? What is a last additional factor?
Genes – DNA – mRNA – Protein
Post translational modification
How are human’s brains similar to other animals?
Similar types of neurons, synapses and neurotransmitters
How many genes were mapped in the human genome project
30 000
What can post-translational modification depend on?
Another protein
What happens when a gene that codes for something like BDNF becomes mutated?
It can impair the functioning of other proteins that depend on it for post-translational modification
What is a SNP
Single nucleotide polymorphism = there is a different nucleotide at a single location
Do SNPs always cause problems?
No, they can be non-consequentical
What is “whole genome sequencing”?
It identifies the complete DNA sequence of an organism’s genome at a single point in time
How many genes were mapped in the human genome project
30 000
What can post-translational modification depend on?
Another protein
What happens when a gene that codes for something like BDNF becomes mutated?
It can impair the functioning of other proteins that depend on it for post-translational modification
What is a SNP
Single nucleotide polymorphism = there is a different nucleotide at a single location
Do SNPs always cause problems?
No, they can be non-consequentical
What is “whole genome sequencing”?
It identifies the complete DNA sequence of an organism’s genome at a single point in time
What is RNA-sequencing and what can it be used for?
Detects the presence and quantity of RNA in a genome
> Used to see how much of a protein is being made
- What is CRISPR,
2 How does it work - What was it originally created to do?
- It is a gene editing tool
- It targets gene activation or repression within a 20-nucleotide target sequence
- It was created to manipulate animal DNA to make animal models for diseases
Genotype:
genes- raw material and blueprints
Phenotype
structural and functional expression (like behaviour or physical appearance)
Critical Periods:
Specific period during development when external stimuli may help to shape neurodevelopmental processes
Complete penetrance
ALL individuals with the gene mutation will show disease symptoms
High penetrance
highly likely that individuals with the mutation will show disease symptoms
Incomplete penetrance
Some individuals fail to show symptoms even though the mutant genotype is present
Most neurodevelopmental disorders have _____ penetrance
What does this suggest?
Incomplete
Suggests that it is not only the mutation but other factors like the environment that cause a disease
Bidirectionality of environment and gene
Environmental “stimuli” can affect neuronal activity during development
Neuronal activity can influence the expression of many genes
How is the gene-environment interaction studied in humans
Twin studies
Usually twins reared apart
What is medical genetics?
The study of inherited factors and mechanisms that influence medical/behavioural outcomes
Heredity:
Circumstance where phenotypic trait is passed form parents to children through genetic inheritance
What is it called when there is an abnormal chromosome number?
Aneuploidy
Karyotype:
Technique that checks the number and appearance of chromosomes
What are 3 types of monogenic genetic disorders?
- Sex-Linked = inheritance related to the sex of the individual (X-linked mutations)
- Autosomal Dominant = one allele possessed gene mutation, another is normal but the phenotype is still observed
- Autosomal recessive = both alleles in gene pair are mutated and produce the phenotype
What make multifactorial (polygenic) conditions more complicated/
It does not follow the same rules of inheritance and there are variable phenotypes
What are 3 factors of mitochondrial disorders?
- “Non-traditional” inheritance (more rare)
- Only a few disorders
- Characterized by alterations in the mitochondrial DNA
Expressivity:
variability in clinical severity
Penetrance:
Frequency of expression of genotype that results in specific phenotype
What are 3 DNA technology/linkage analysis for disorders
- Condition seen in other family members
- Gene mapping to ID possible variants/mutations
- Localize gene to chromosome
Linkage analysis:
Searching for genetic code that could allow genetic testing for inheritable conditions
Genetic factors operate in the context of what?
Environmental conditions
Detrimental environmental exposure when during brain development result in a potential of a greater impact on brain structure and function?
Earlier stages
> Critical periods
Fetal brain is most vulnerable to chemical and infectious agents in the _____ ______ ______
Maternal blood stream
What can make some people more prone to the detrimental effects of teratogens?
People who possess a genetic susceptibility
Teratogen:
Agent or factor external to the fetus that can cause structural or functional malformations during prenatal development
Ex. Alcohol
Why can infection during pregnancy be bad?
They trigger an immune response and the immune factors might alter the neurodevelopment
What is an example of an activity that can promote neurogenesis
Exercise
If mom has a mental health disorder is it more or less likely for the child to have a mental health disorder?
Higher
What are 5 environmental factors that can impact neurodevelopment
- Intrauterine infections
- Neurotoxins
- Heavy metal exposure
- Stress/diet
- Maternal mental health
How does Zika harm the fetus and what can be the result?
The virus diverts resources away from mechanisms needed to produce neurons and there will be a heightened immune response
» Microcephaly
What exactly can Zika do to neurons
It can either directly kill developing neurons or it can just limit their growth
What are the primary (3) effects of prenatal HSV infection
- lesions appear within 2 weeks of exposure
- genital inflammation
- Fever, headache, nausea
What are the secondary effects of prenatal HSV infection (4)
- Psychological effects including depression (for mom)
- Possible weakening of the BBB
- Inflammatory mechanisms can result in a pre-term birth
- Activates inflammatory mechanisms
What bacterial infection can be passed from the mother to the child that affects the genitals and eyes?
Chlamydia Trachomatis
What 4 issues can happen to pregnant women (and their babies) with clamydia?
- Reproductive issues
- Blindness for child
- Preterm birth
- Infertility or miscarriage
When there is increased inflammation during pregnancy, what is happening in the fetal brain (4)?
- Activated microglia
- activated astrocytes
- maturation arrest or death of oligodendrocytes
- Axonal loss or death of neurons
What are the potential phenotypic consequences of increased inflammation in the developing brain (4)
- preterm birth
- motor deficits
- cognitive and behavioural impairment
- psychiatric illness
Stress can lead to the release of what?
Cytokines
What are the effects of cytokines on the fetus?
Not clear, but it could impact neuronal development
Stress reduces what factors in the brain that are important for survival??
BDNF
Stress can also increase levels of proteins that are ____ to neurodevelopment
toxic
What important function does BDNF do?
It is important for the growth and survival of neurons
Neurotoxin:
A chemical/substance that is toxic to neurons (impacts brain development)
What are 2 neurotoxins and what do they do?
Tetrodotoxin - inhibits sodium channels (kills all activity dependent mechanisms)
Botulinum Toxin - inhibits ACh at the neuromuscular junction and results in paralysis
Why is activity at the neuromuscular junction during development important?
It helps to fine tune muscle activity and proper neuronal development
How do pesticides affect neurons?
they damage neurons
What is an example of a pesticide that has been linked to Parkinson’s
Paraquat
What are 4 elements in a proper diet that are very important in facilitating neuronal development?
- Folate
- Choline
- Omega 3 fatty acids
- Water
What can happen to the baby if the mom has folic acid deficiencies
Spina Bifida
What heavy metal is known to be toxic to neurons and what does it do (3)?
Mercury:
- Delay neuronal development
- Sensory impairment
- reactive with selenium
What is the consequence when mercury reacts with selenium?
It will disable selenium form being able to protect neurons from oxidative damage
A mother can transfer unbalanced _______ ______ to the fetus
Neurotransmitter processing
Children born of mentally ill mothers can more likely to develop which 2 mental illnesses?
Depression and schizophrenia
What timeline of the mother smoking can cause harm to the fetus?
Only with prolonged smoking
If she stops smoking early in pregnancy it does not seem to have as great of an effect
What is a potential impact on the baby of the mother smoking
Head size
What is the effect of PAHS, an air pollutant, on neurodevelopment
It has a potential neurotoxic effect that could impact neurodevelopmental trajectory
What is BPA found in and what are the potiential effects of it?
Plastics
> Can have neurodevelopmental issues and impact feeding behaviours
Paternal exposure:
Anything the father of the baby is exposed to before his partner’s pregnancy can cause possible epigenetic effects
What can be the impact of paternal alcoholism on the baby
May exhibit hyperactivity and decreased cognitive performance
What are the potential epigenetic mechanisms of stress that can impact a child?
Exposure to stress –> Modulation of BDNF signalling –> Changes in synaptic plasticity–>:
1. Vulnerability to anxiety
or
2. Vulnerability to alcohol consumption
What are some of the multiple factors on how the environment can affect the brain (5)
- Loss of protein homeostasis
- DNA damage
- Lysosomal dysfunction
- Epigenetic changes
- Immune dysregulation
What behavioural signatures that are tested to determine if there is a neurological disorder (4)
- Learning and memory (attention and executive function)
- visual-motor integration
- social behaviour
- motor skills
What is ultrasound used for?
To detect structural aspects during embryonic and fetal development
Prenatal testing is done especially for what?
High risk pregnancies
What is considered a high risk pregnancy?
mother over 35 years
What is Integrated Prenatal Screening (IPS)
testing the maternal blood to look for biomarkers from the fetus
What is the nuchal translucency test?
It measures the fluid-filled space between the back of the feral neck and the uterine lining
What measurement on the nuchal translucency is considered abnormal
More then 3.5mm
What do the nuchal translucency correlate with? (4)
- Miscarriage
- Still birth
- Down syndrome
- heart defects and rare genetic disorders
Karyotype:
chart of chromosomes
What does karyotyping allow for?
allows for the identification of genetic disorders caused by chromosome alterations/abnormalities
Aneuploidy:
an abnormal number of chromosomes
What is an amniocentesis test?
Takes up amniotic fluid that contains fetal cells that can be tested
What tests can be done after an amniocentesis (5)
- karyotyping
- molecular testing
- PCR
- FISH
- PAPP-A
What levels of PAPP-A is associated with down syndrome?
low levels
Why don’t mons like having an amniocentesis
Because it can result in the loss of the fetus
What is Chronic Villus Sampling (CVS)
The collection and examination of fragments of placental tissue (chorionic villi)
What are the 5 aspects of multi-method approaches to diagnosis neurodevelopmental disorders
- imaging
- molecular testing
- genetic testing
- psychological testing
- assessment of mental retardation
Why is it hard to do clinical assessments during development?
Because a child changes so quickly and there is no “normal” trajectory
What behavioural assessments CAN you do with a newborn to assess normal development? (6)
- lack of alertness
- poor quality of sleep
- abnormal cry
- feeding problems or constant drooling
- spastic movement
- abnormal head size
What are structural imaging techniques
Ultrasound
CT scan
MRi
What are functional imaging techniqies
fMRI
PET
What are standards of normality?
Early developmental assessments that involve age and stage specific testing and “normative reference”
What is fragile X syndrome?
Abnormal FMR protein makes astrocytes not properly support the neuron so it has delayed development
Cognitive psychology
Study of the effects of brain function on psychological processes
Cognitive neuroscience
Molecular and biochemical processes underlying cognitive function
Why is there a focus on the development of the adolescent brain over the adult brain?
Because the adolescent brain is still developing a lot
What part of the brain do we keep lots of plasticity even as adults? Why?
Hippocampus
For memory formation
The bursts and plateaus of neurodevelopment are correlated with what?
Social and academic changes
Some conditions do not become apparent until late adolescence or young adulthood, what makes them apparent?
There are increases multi-tasking demands and higher work load
What are the 3 areas of speech assessment
Articulation = pronounce words
Expressive Language = express thoughts coherently
Receptive Language = ability to understand language and follow directions
What makes diagnosis in adolescence easier than in infancy
They are able to communicate with language
There are more concrete developmental milestones for defined characteristics of neurological testing
What is new on the DSM 5?
There are treatment strategies suggested
Learning disorder:
Neurological condition affecting the brain’s ability to receive, process, retain, and respond to information
What are some of the areas affected by learning disorders? (6)
Reading Writing Listening Speaking Reasoning Math
Are people with learning disabilities unintelligent?
No, they generally have average or above average intelligence
Learning disorders are now thought of as on a _____
spectrum
Why is it that many people fall under the category of “multiple impairments” for learning disorders?
Because often if there is an abnormality with part of the brain there will be more than one problem
Psychosocial manifestations fo a LD (6)
- Attention
- Concentration
- Inference
- Emotional labelling
- Interactional dysfunction
- Social and communicative competence
The cause if LD is unknown, but there have been correlations
- Prenatal exposure to drugs, toxins or heavy metals
- Birth complications
- Genetic (run in families)
Concordance:
Both twins have disability
Discordance:
One twin has the disability
Dysregulation of ______ in the brain is thought to be linked to LD, either hyper or hypo
pruning
Linkage analysis has found correlations between which two chromosomes and dyslexia
15 and 6
Although statistically boys have more LD than girls, why might those stats be wrong?
Difference in how the problem manifests itself in boys and girls:
- Boys act out
- Girls get chatty or quiet
what can be the reason that two disorders often occur together? (comorbid)
There is overlap in risk factors and/or genetic susceptibilities
there is an increased risk for juvenile delinquency and substance abuse for what disorder
Learning disorder
Do people grow out of learning disorders?
No, adolescent LD generally will persist into adulthood
What are the co-morbidities of LD? (4)
- Depression
- Aggressive behaviour
- Social incompetence
- Emotional problems
What is the neurological underpinning to a learning disorder
The improper development of the cortex
Cognitive impairment is almost always associates with what
a learning disability
What gene has been linked with learning disability
SHANK3
What percentage of people have some form or dyslexia?
~1 in 5
People with dyslexia can read, it just takes what?
More time and more cognitive resources
Dyslexia is not a visual disorder but rather a _____ disorder
Language
What type of spelling is common in people with dyslexia
Phonetic spelling
The lateral (Sylvian) fissure is important for ______ processing
Language
What are the functions of the lateral fissure
Receiving both auditory and visual information
Wernicke’s area
Evolutionarily, why are learning disabilities associated with reading not speaking
Because our brains are automatically designed to make speech sounds, not to read
What can you do to mitigate the symptoms of a LD
Reading
> A skill that can be strengthened through practice
What is a key feature of all the fetal alcohol spectrum disorders?
Brain damage
Which FASD is the most severe?
Fetal alcohol syndrome
What is the prevalence of FASD
24-48/1000
Why is alcohol so dangerous to a fetus?
Because it crosses the placental barrier
What are the 3 principles of teratology?
- Results in abnormal development
- Time of exposure (most risk in 1st trimester)
- Dose and duration of exposure (unknown)
FAS is known as a _______ condition
Teratogenic
What are the major criteria for FAS diagnosis (3)`
- Prenatal and/or post natal growth deficiencies
- 3 cardinal facial features
- CNS abnormalities
What are the 3 cardinal facial features of FAS
Small eyes
Smooth philtrum (cupid’s bow)
Thin upper lip
Is FASD heritable?
No
What 2 types of drinking increase the risk that a baby will have FASD
binge drinking
drinking during the first trimester
What are 3 distinct brain characteristics of FASD
Microcephaly
Thin corpus callosum
Abnormal cerebellum
What is the critical period for most damaging effect of alcohol on the structure/function of the brain?
3-12 weeks gestation
People with FASD have a predisposition to what?
Addictive behaviour
What are 3 cognitive disabilities of FASD
- Learning disorders and general mental retardation
- Attention deficits
- Reasoning and problem solving issues
Behavioural symptoms of FASD (6)
- Attention deficit
- hyperactivity
- Memory loss
- Conduct issues
- Cognitive deficits
- Learning disabilities
What receptor does alcohol (ethanol) stimulate
GABA
GABA-A receptor:
Ionotropic
Gates Cl channel
GABA-B receptor:
Metabotropic
Gates K+ channels
Which of the GABA receptors does ethanol bind to?
GABA-A
What happens when ethanol binds to the GABA-A receptor
It increases the time that the Na channel is open, so more sodium comes in and an action potential is more likely
4 cormorbidities of FASD
- Anxiety and mood disorders (depression)
- ADHD
- Addiction
- Suicide
Is there a cure for FASD
There is no cure, the damage is permanent
>Focus on prevention
What are the treatments/interventions for FASD
- Optimize environmental environment
- Limit alcohol consumption
- Give parents strategies to deal with kid
- Social support
What is a limit to animal research on FASD
Animals metabolize alcohol differently than humans
What is resveratrol
An antioxidant that is found in red wine
Is having a single drink during pregnancy ok?
It can have just as much of an effect as binge drinking, so don’t risk it
What is an issue with retrospective studies on FASD
Moms likely do not want to admit how much they drank while pregnant because they know it is bad
What are the different binding sites on the GABA A receptor (5)
GABA Alcohol Benzodiazepine Barbiturates Steroids
Most of the etiology of ADHD is speculative and extrapolated based on what?
based on treatments that work
What were the 3 early criterion for attention
- Central feature of awareness, what we choose to focus on
- Effortful
- Motivated by a goal `
Executive function requires what 3 things?
- Sustained mental effort
- self regulation
- planning and execution
What are the 2 symptoms of ADHD?
- Faulty attention
2. Hyperactivity and impulsivity
Which symptom of ADHD is more prevalent in females?
Inattention
What 2 things are required for a diagnosis of ADHD?
- Inattention and/or hyperactivity and impulsivity
2. Skill impairment
People with the inattentive subtype of ADHA have difficulty attending to ______ and _____ tasks
repetitive and effortful
What is the performance vs skill paradigm in ADHD
People with ADHD have all of the necessary skills, they cannot access the skill at that time
Inattention in ADHD
Inability to inhibit need to perform a more interesting task
Impulsivity in ADHD
Do not think before they act and have issues weighing the consequences of their actions
Over-arousal in ADHD
Lack of inhibition, restless, and emotionally reactive
Difficulty with gratification in ADHD
They required frequent, immediate, and predictable rewards. They are not good at waiting for long term goals
Emotions and locus of control in ADHD
Have rapid ups and downs and blame behaviour on others
Where are the delays in brain maturation in people with ADHD
- Basal ganglia
- PFC
- Cerebellum
What role does the abnormal PFC play in ADHD (5)
Difficulty with:
- attention
- spatial working memory
- short term memory
- planning and organization
- language skills
What role does the abnormal cerebellum play in ADHD
response inhibition and motor coordination
Brain structure abnormalities in ADHD (4)
- Smaller right PFC
- Delayed maturation of PFC
- Smaller cerebellum
- Abnormal structure and function of basal ganglia
What role does the basal ganglia play in ADHD
improper self-regulation of emotions
What 3 NT are possibly affected in ADHD
Dopamine
Norepinephrine
Serotonin
What is the role of dopamine in ADHD
Reward/motivation and pleasure seeking behaviours
What role does norepinephrine play in ADHD
Emotional and behavioural regulation
Dopamine can be converted into what?
Norepinephrine
What converts dopamine into norepinephrine
Dopamine-bata-hydroxylase
An imbalance in dopamine can lead to an imbalance of what?
Norepinephrine
Norepinephrine is related to fight or flight, how could this be impacted in ADHD
Thought that it might play a role in the hyperactivity
It has been shown that what reward pathway is impaired in ADHD
Mesolimbic Dopamine system
what brain structures are involved in the mesolimbic dopamine system?
Ventral tegmental area
Nucleus accumbens
PFC
How could stimulants help ADHD
It will allow for more dopamine in the mesolimbic dopamine system and potentially decrease hyperactivity
4 genes that have been linked to impulsive behaviour
DAT1 (dopamine transporter)
DRD2 (dopamine receptor)
MAO-A (monoamine oxidase-A)
5HTT (serotonin transporter)
High levels of manganese in the hair of ADHD ppl has been correlated with:
soy-based infant formulas
What is the hypothesis of manganese and ADHD
It can accumulate in the brain and has been correlated with the loss of dopamine in the mesolimbic dopamine system
What are 4 other prenatal environmental risk factors for ADHD
alcohol
cocaine
lead
smoking
If the mom or child has any of these 4 disorders it could be a risk factor for ADHD
- Hyperthyroidism
- Encephalitis
- radiation from cancer
- TBI
3 co-morbid factors with ADHD
- Speech and language problems
- Poor academic performance
- Learning disability
Do symptoms of ADHD carry into adulthood?
Most do carry into adulthood but some diminish
What is the multi-pronged approach to ADHD treatment
- medical
- behavioural
- environmental (limit drug use)
Stimulant drugs for ADHD affect which 2 NT
dopamine and norepinephrine
2 chemical compound names for stimulant drugs
Methylphenidate
Dextroamphetamine
What are 3 common names for methylphenidate
Ritalin
Cincerta
Metadate
What is the common name for dextroamphetamine
Adderall
Which of the stimulant drugs is more effective and why?
Adderall
Allows for more dopamine by blocking reuptake
What is the non-stimulant alternative for an ADHD drug? What NT does it target?
Atomoxetine
Norepinephrine
Why would you choose a non-stimulant ADHD drug?
Because it does not contain amphetamine so it is less damaging to the developing brain and it is not addictive
Aggressive behaviour
characterized by verbal or physical attack that could be a “protective” response or may destructive toward the self and others
Impaired cognitive function in aggression
May leas to incorrect perception of danger or offence
Impaired escape or avoidance in aggression
Behaviours likely causes by high levels of anxiety and impaired stress response
Impulsivity and aggression
Can be a precursor to aggressive behaviours
Can be frustration at inability to express one’s self
Delayed neurodevelopment in aggression
aggression may be an altered mechanism for communicating emotions *especially in delays with cognitive and communication areas
Significant life trauma or maltreatment and aggression
May lead to aggressive behaviours
Low threshold for anger
associated with impairment in emotional regulation
6 potential causes of aggressive behaviour
- Impaired cog function
- Impaired escape or avoidance
- Impulsivity
- Delayed neurodevelopment
5 Trauma or maltreatment - Low anger threshold
2 categories of aggressive behaviours
Proactive and reactive
Proactive aggression
Seeking out to do harm to a specific person
Reactive aggression
A response to perceived harm, slight or violation
Aggressive behaviour is characteristic of what neurological conditions (7)
depression bioplar disorder TBI PTSD Alzheimer's Dementia Down syndrome ADHD
How is aggressive behaviour treated?
Treating the specific individual characteristics by identifying the underlying the “primary symptoms”
5 symptoms of aggressive behaviour
Impulsivity Emotional instability Anxious Cognitive disorganization Predatory aggressive behaviour
2 major types of aggressive disorders
Oppositional defiant disorder (ODD) Conduct disorder (CD)
What is the current focus in research on aggression
Studying adolescents and identifying precursors through longitudinal studies
What are the risk factors that can be identified at an early age for aggressive behaviour
Difficult infant/temperamental
Negative parenting behaviour
»both together
Where is an ____ and ____ difference in the prevalence rates
age and gender
What are 2 potential prenatal risk factors to aggressive behaviour
Smoking and other drug use during pregnancy
Brain inhibition is linked to 4 executive functions
- working memory
- self regulation
- internalization
- reconstruction
What area of the brain processes much of the executive functions in aggressive behaviour
Prefrontal cortex fronto-striatal region (part of the basal ganglia)
4 brain regions implicated in aggression
Ventro-medial PFC
Orbitofrontal cortex
Nucleus accubmens
Amygdaya
Ventromedia PFC in aggression
Delay of gratification
Orbitofrontal cortex in aggression. Is it larger or smaller?
restrain impulsive aggression
> larger
Nucleus accubmens in aggression
Reward and reinforcement
Amygdala in aggression. Is it larger or smaller?
Emotional memories used for decision making
>Smaller
Which NT plays the biggest role in aggression
serotonin
>central role in impulsivity
Serotinin interacts with what 4 NT in aggression
Norepinephrine (irritability)
Dopamine (reward)
Glutamate (excitation)
GABA (inhibition)
Is it the amount of serotonin that is important in aggression?
No, it is its balance with other NT
Mice lacking which serotonin receptor exhibited increased impulsivity and aggression
5-HT1B
4 neurodevelopmental predispositions to aggressive behaviour
- Genetic influence
- Prenatal exposure to high levels of testosterone (males)
- Childhood trauma or stress
- intrauterine exposure to smoke
What is the hypothesis of MAO and aggression. Why?
Inhibition of brain MAO during fetal brain development is a risk factor for aggression. Leads to excess dopamine in the synapse and the brain gets used to the excess excitation and seeks it out
vasopressin in aggression
it is involved in the stress response and seems to be more of it in aggressive males
Long term exposure to cortisol _______ serotonin in the limbic system. What does this impact?
Suppresses
Major impact of emotional stability and impulsivity
There is an ________ relationship between serotonin and aggressive behaviour
Inverse
Activating the 5TH1A receptor _______ aggression
decreases
Vasopressin (which has been linked to aggressive behaviour) is dependent on what hormone?
Testosterone
There is high levels of vasopressin and testosterone in what brain area. What does this do?
Lateral septum
Plays a key role in emotional process and stress response
What are the treatment strategies for aggression
CBT
Medication
What is the medical interventions for aggression focused on
Targeting the underlying symptoms, like impulsivity
What drugs can be used to treat aggression
Stimulants
Antipsychotics
Mood stabilizers
What is Tourette’s Syndrome?
Neurological condition characterized by repetitive, involuntary movements and vocalizations called tics
When is onset for Tourette’s
Early childhood or adolescence (2-15 y/o)
Do motor or vocal tics typically appear first
Motor
Sometimes the motor tics go un-noticed until when?
Until the vocal tics set in
Categorization of Tourette’s tics
Simple and complex
Simple tics
Involves a few muscles or simple sounds
Complex tics
Involves multiple groups of muscles
>Orchestrated in bouts of muscle contractions or is manifested as single words or complete sentences
Examples of simple motor tics
- eye blinking
- jerking of the neck
- shrugging of shoulders
- face grimacing
- coughing
Examples of complex motor tics
- grooming behaviours
- facial gestures
- jumping, stomping of feet
- smelling objects
Examples of simple vocal tics
- Clearing of throat
- Sniffing
- Grunting
- Barking
Examples of complex vocal tics
Repetition of words or phrases out of context
- Coprolalia
- Palilalia
- Echolalia
Coporalia
Use of obscenities (rare)
Parilalia
Repetition of one’s own sounds or words
Echolalia
Repetition of recently heard words, sounds, or phrases
Do complex tics always develop
No, some people just have simple tics
What is a misconception of Tourettes that can make diagnosis hard
Misconception that Tourette’s is often associated with coporalia, so it can lead to people not going for diagnosis
What are the core features of TS (3)
Multiple motor tics
One or more vocal tics
Motor and vocal tics may appear separately or simultaneously
Diagnostics criteria of TS
- Tics must be seen many times a day for a year
- Tics must be present for 3 months straight
- Tics impair aspects of social and emotional well being
Are people aware of the tics before they happen in TS
Most have a premonition they will happen but some do not
TS movements are described as “_______” but _______
Purposeful but unwanted
What is more concrete proof that TS tics are involuntary
They can happen during sleep
MRI of TS patients show what
A generally normal brain
What brain abnormality has been seen in TS. It is more prevalent in who?
Corpus callosum
Males
There is hypoperfusion in what brain areas in TS
Basal ganglia
Orbitofrontal cortex
Temporal lobe
There is decrease activity in what 2 brain regions in TS
Cortex and striatum
Is the cause of TS known
No
People with parents with TS are ____ more likely to get it too
3 times
What are the candidate genes implicated in TS
Dopamine receptors (DRD1, 2, 4, 5) Dopamine transporters
Environmental risk factors of TS (5)
- Infection in childhood
- Low birth weight
- First trimester sickness
- Smoking during pregnancy
- Labour more that 24 hours (possible hypoxia)
PANDAS and TS
Hypothesis that the immunological response to anti-streptococcal antibodies target neuron in the basal ganglia
What cortical pathway has been associated with TS
Cortirostriatal-Thalamocortical pathway
What size of caudate nucleus is associated with tics
smaller
What pharmacological treatment involvng dopamine has shown some success in treating TS. What drug is used
Blocking dopamine receptors has been shown to reduce tics
> Haloperidol
What are SSRIs used for in treating TS
Treating comorbid impulsivity, obsession and compulsions, anxiety
What are 2 alternative methods of treating TS
- Fish oil supplements
- Deep brain stimulation of basal ganglia
Behavioural therapy can be combined with what pharmacological therapy to treat TS
- Antipsychotics
Risperidone - Stimulants
