Language and Aphasia Concepts

Language Lateralization

• Speech comprehension is located in the left side of the brain
• Prosody (rhythm, emphasis, tone of speech) is processed in the right hemisphere
• Emotional state is indicated by prosody
• Regular rhythm and emphasis on words in speech indicate phrasing (statement vs. question)
• Individuals with left brain damage still comprehend emotional state and phrasing of speech
• Voice recognition is independent of word comprehension

Aphasia

• Defined as difficulty understanding, repeating, or producing meaningful speech
• Not caused by sensory/motor deficits or lack of motivation
• Individuals must be isolated but aware of the environment around them
• Middle cerebral artery damage can cause aphasia with varied symptoms depending on the location of cell death, including damage to the sensory association cortex (can't understand language) or the frontal lobe (can't speak or write)

Posterior Language Area

• Function: language comprehension
• Location: junction of temporal, occipital, and parietal lobes
• Neurons in the posterior language area activate neurons throughout the sensory association cortex
• Helps understand the meaning of words

Transcortical Sensory Aphasia

• Damage to the posterior language area
• Difficulty understanding the meaning of words
• Ability to speak, but unable to express thoughts through speech
• Can repeat words
• Capable of reading and writing without understanding

Other Language Disorders

• Conduction Aphasia: Inability to repeat words
• Damage to the arcuate fasciculus connecting Wernicke's area and Broca's area
• Language comprehension and expression are still good
• Wernicke's Aphasia: Damage to Wernicke's area and posterior language area
• Combination of transcortical sensory aphasia and pure word deafness
• Poor language comprehension
• Fluent, but meaningless speech
• Difficulty with receptive aphasia and fluent aphasia
• Cannot repeat what is said
• Spoken word recognition and word comprehension are not distinguishable in brain scans
• Pure Word Deafness: Inability to recognize auditory words
• Damage to the small part of Wernicke's area
• Can still hear, interpret non-speech sounds, and read/write, but cannot recognize words
• Pure Alexia: Inability to recognize written words
• Damage to the visual word-form area (VWFA) in the left hemisphere's visual association cortex
• Disrupts the ability to perceive written words

Reading

• Two processes for reading: sight reading and sound reading
• Sight reading (whole-word reading) is using the VWFA
• Sound reading (phonetic reading) is decoding words by sounding out letters

Dyslexia

• Reading difficulty, often hereditary
• Surface dyslexia: recognize whole words, but struggle with irregularly spelled words
• Phonological dyslexia: read familiar words but cannot read unfamiliar or non-words
• Developmental dyslexia: struggles with grammar, spelling, and ordering of sounds.

Broca's Area

• Function: speech production
• Location: left inferior temporal lobe
• Damage leads to slow, labored, non-fluent speech
• Articulation issues: difficulties with sequencing
• Agrammatism: difficulty employing grammatical devices and word order
• Anomia: difficulty recalling appropriate words (may be a symptom of any aphasia)

Emotions

• Abstract thinking and expressing emotions happen in the neocortex
• Raw, reflexive feelings processed in the limbic system
• Two streams of sensory inputs: thought and feeling
• Wheel of emotion: four opposite dimensions that create emotional blends
• Many emotions don't have clear boundaries
• Key dimensions of emotion: arousal and valence

Expression of Emotions

• Facial expressions are innate
• Displayed in babies, but less when alone
• Rapid, accurate recognition through facial expressions
• Examples of identifiable expressions: fear, anger, sadness, disgust, happiness, and surprise

Reading Emotions

• Emotional expressions are not as specific to one emotion
• Inferring emotions is not completely reliable
• There are many blends of emotions, and no clear prototypical facial expressions

Animals and Emotions

• Emotional feelings in animals coincide with behavioral and physiological responses
• Includes behavioral, autonomic, and hormonal responses
• Lack of communication and culture; anthropomorphizing (giving human characteristics) vs anthropectomy (denying animals human qualities).
• Intracranial self-stimulation in animals indicates that dopamine is linked to reinforcement learning, not necessarily pleasure.

Sexual Behavior Circuitry

• Glutamate and GABA neurons on the medial amygdala (light activates specific cell types)
• GABA stimulation: low frequency = normal sexual response; medium frequency = high sexual response; high frequency = high aggressive behavior
• Glutamate stimulation: grooming and complete social disengagement

Theories of Emotion

• Common sense: stimulus -> feeling -> behavior/physiological response
• Emotion precedes physiological responses.
• James-Lange theory: stimulus -> behavioral/physiological responses -> emotional response from PNS feedback.
• Internal organs do not react quickly enough to cause an emotional response
• Cutting sensory nerves between internal organs and the CNS does not eliminate the feeling of emotion
• Artificially stimulating the nervous system does not produce specific emotions

Limbic System

• Cingulate cortex: interconnects limbic areas
• Hippocampus: explicit memory formation
• Amygdala: recognition of fear
• Both amygdala and hippocampus have their own nuclei
• Central nucleus of amygdala stimulation: fear, anxiety, agitation
• Consistent stimulation: stress-induced illness
• Lesion: no more innate or learned response to fear; only fear through suffocation
• Damage to visual cortices: still activity in amygdala when viewing faces and can mimic facial reactions

Beyond the Amygdala

• Somatosensory cortex, insular cortex, premotor cortex, and cingulate cortex are activated when seeing emotional faces.
• Right hemisphere: emotion recognition
• Damage in these areas: hard to identify emotional facial expressions in others
• Eye movements and fixation in emotion recognition

Phineas Gage

• Rod injury to skull
• Before injury = kind; after injury = childlike, irresponsible, outbursts, unable to plan

Strokes

• Ischemic stroke: blocked cerebral blood vessel
• Treatment: drugs that dissolve blood clots (like tPA) and devices (coils, aspiration devices, stents)
• Hemorrhagic stroke: ruptured blood vessel
• Treatment: anti-inflammatory drugs, physiotherapy, speech therapy, occupational therapy, etc

Tumors

• Cause: uncontrolled cell growth -> rogue cell division
• Metastasis: cells break off the tumors, transported by blood vessels, and grow elsewhere in the body
• Malignant: cancerous; not encapsulated; grows by infiltrating tissue
• Glioma: specific rapidly proliferating, neural stem cell-originating tumors resistant to treatments
• Non-malignant: not cancerous; encapsulated

Infectious Diseases (Brain)

• Encephalitis: inflammation of the brain (caused by infection)
• Meningitis: inflammation of the meninges (caused by viruses or bacteria)
• Polio: viral disease destroys motor neurons of the brain and spinal cord
• Rabies: viral disease caused by brain damage and death
• Herpes simplex virus: viral disease that usually creates cold sores; rare cases enter the brain cause encephalitis and brain damage

Traumatic Brain Injuries

• Closed-head injury: blow to head with blunt object
• Coup: brain violently hits inside of skull
• Contrecoup: brain recoils and hits opposite side of skull
• Open-head injury: penetrating brain injuries, exacerbated by damaged blood vessels

Seizure Disorder

• Causes: scarring related to injury, stroke, tumor, abnormal brain development, high fever
• Many are idiopathic
• Gene mutations affect ion channels, excitatory/inhibitory neurons and synaptic plasticity
• Treatments: anticonvulsant drugs, sometimes requiring brain surgery

Grand Mal Seizures

• Aura: sensation preceding seizure, located on seizure's focus
• Tonic phase: skeletal muscles contract
• Clonic phase: rhythmic jerking movements

Developmental Disorders

• Exposure to toxins, drugs, viruses, heavy metals during pregnancy
• Fetal alcohol syndrome causes facial abnormalities and intellectual disabilities
• Inherited metabolic disorders: errors of metabolism -> genetic abnormalities.
• Phenylketonuria (PKU): hereditary disorder from enzyme absence.
• Tay-Sachs disease: hereditary, fatal disorder

Down Syndrome

• Cause: extra twenty-first chromosome
• Congenital, moderate to severe intellectual disability, and physical abnormalities
• Brain degeneration after age 30

Multiple Sclerosis

• Sporadic (not obviously caused by inherited gene mutation or infectious agent)
• Symptoms include cycles of flare-ups and remission (remitting-relapsing MS followed by progressive MS)
• Consequences include demyelination of axons, action potentials don't propagate well
• Myelin sheaths attacked by own immune system affecting neurological disorders
• Autoimmune disease
• Starts in late 20s
• Sclerotic plaques: hard patches of debris

Prion Disease

• Cause: accumulation of misfolded prion protein
• Widespread degeneration (brain looks like a sponge)
• Contagious; spreads within body and across animals. Prion = only infectious agent that is a protein.

Huntington's Disease

• Cause: mutation in Huntington gene -> misfolding of Huntington protein, degeneration of basal ganglia
• Symptoms/consequences: lack of coordination, jerky movements, and dementia -> death
• Treatment: Antisense therapy (promising)
• Injected DNA compliments mRNA into spinal cord
• DNA + mRNA -> no translation -> no protein

Parkinson's Disease

• Cause: degeneration of dopamine neurons in the midbrain (substantia nigra) -> misfolding and clumping of alpha-synuclein protein
• Symptoms/consequences: reduced dopamine signaling (muscle rigidity, slowed movements, shaking), cognitive, emotional, and sleep disturbances

Alzheimer's Disease

• Cause: clumping of misfolded beta-amyloid protein and severe degeneration in and around hippocampus, and neocortex
• Symptoms/consequences: progressive memory loss, motor deficits, death
• Treatments: Immunotherapy (injection antibodies are tagged to be destroyed)

ALS-FTD

• Cause: mostly unknown
• Starts at age 50
• Symptoms/consequences: ALS attacks motor neurons in spinal cord and cranial nerves, spasticity (increased muscle tension), progressive weakness, muscular atrophy, paralysis -> death

Reproductive Success

• Not all individuals reproduce.
• Reproductive success is impacted by physical and mental health.
• Theory of Evolution and Natural Selection -> gene variants that increase risk of severe health issues will eventually get eliminated

Bad Genes

• Natural selection eliminates bad genes over time

Good Genes

• Beneficial alleles increase until everyone has them. Promotes survival and reproduction.

Genetic Basis of Disease

• Variety of alleles
• Most diseases and disorders have a genetic basis but some alleles increase the risk of disease, but others are protective
• Strong evolutionary pressure on gene variants
• Gene-environment interaction: strong genetic component but prevalence varies across the world.

Gene-Environment Interactions

• In stable environments, only beneficial and neutral alleles are maintained.
• Prevalence of diseases vary across different cultures.

Mental Illness

• Doesn't always show gene-environment interactions
• Schizophrenia and autism = heritable, large genetic basis, but prevalence rates are not consistent (don't vary)

Schizophrenia

• Hundreds of common gene variants that individually contribute a small increase in schizophrenia susceptibility
• Combination of gene variants = likely mental illness
• If one twin has schizophrenia, 50% chance the other will get it regardless if raised together or apart

Diagnostic Categories

• Mental illnesses vary; people present differently, making grouping difficult.
• Diagnostic categories often result from historical conventions and are arbitrary.

Mental Disorder Susceptibility Genes

• Gene variants increase risk of schizophrenia, autism, bipolar disorder, depression and OCD, ADHD
• Gene variants tell vulnerability to developing a mental illness in general, but not for specific conditions.

Neurodevelopment Robustness

• Both sides of the body develop independently.
• Clear genetic instructions are crucial and robust to withstand environmental variations.

To Maintain a Healthy Brain

• General health is essential for brain health (active lifestyle, well-balanced diet, etc)
• Limiting external factors like alcohol, tobacco and drug use is a must
• Identification of gene variants and neural circuits are key to develop appropriate treatments for mental illnesses and related issues like gene editing and targeting intracellular signaling cascades

Schizophrenia: Consequences

• Social withdrawal
• Disorganized thinking
• Abnormal speech
• Inability to understand reality

Heritability in Schizophrenia (and other disorders)

• Measures of how much of a trait/phenotype is caused by genetics
• 50% chance of identical twins, 13% for having one parent with condition, 8% for having a sibling with the condition
• Highly penetrant gene mutations = rare gene copy number variations

Environmental Factors in Schizophrenia

• Mother's nutrition and stress during pregnancy are implicated
• Infections
• Birth month (seasonality effect)
• Childhood trauma
• Social isolation
• Brain damage
• Prenatal environment

Schizophrenia Evidence of Abnormal Brain Development

• Behavioral + anatomical evidence of abnormal prenatal development
• Less social, and difficulty with motor skills in children
• Possible physical abnormalities (e.g., slightly webbed feet, highly-steepled palate)

Schizophrenia: Treatment

• Medication + psychological/social support
• Antipsychotics/neuroleptics block dopamine D2 receptors
• Drugs to relieve positive symptoms

Dopamine Hypothesis

• Excessive dopamine D2 activity in nucleus accumbens (striatum) = positive symptoms
• Dopamine D2 antagonists reduce positive symptoms but not negative symptoms
• Negative symptoms are largely responsible for long-term disability
• Result of abnormal activity in prefrontal cortex
• Hypo-frontalty: decrease in activity of frontal lobes

Atypical Antipsychotic Drugs

• Second generation antipsychotics reduce positive and negative symptoms
• Influence multiple neurotransmitter receptors
• Examples: clozapine, aripiprazole

Autism

• Wide range of disorders, wide range of causes (genetic and environmental factors affecting early brain development)
• Symptoms and consequences:
  • Category 1: Trouble with social interaction and communication
  • Category 2: Restricted interests, repetitive behaviors

Autism: Trouble with Social Interactions and Communication

• Ppl with autism = abnormal behaviour, no language
• A third don't develop speech to meet daily needs
• Repeat what is said to them; refer to themselves in 2nd or 3rd person

Autism Heritability and Brain Development

• 70-90% heritability with rare chromosomal abnormalities and multigene interactions linked to common variants
• But, often differences in brain development at birth
• Hypotheses of quick brain growth during early gestation
• Altered neuronal migration, abnormal formation of synapses/dendritic spines
• Overconnectivity in many brain regions
• Unbalanced excitatory-inhibitory neural networks; less active activity in fusiform gyrus when looking at face in fMRI

Autism: Treatments

• Lessen impact of deficits and family distress (increase quality of life)
• Intensive special education programs
• Behavior Therapy in early life
• Medication: Anticonvulsants (increase GABA receptor activity), antidepressants (increase serotonin receptor activity) and Antipsychotics (decrease dopamine receptor activity); Stimulants (increase dopamine receptor activity)

ADHD

• Symptoms and consequences:
  • Problems paying attention
  • Difficulty controlling behavior
  • Hyperactivity
  • Act without reflecting
  • Easily bored and distracted
• More than 5% of children are diagnosed with ADHD.
• Symptoms appear before age 12
• Comorbidity with learning disabilities, depression, anxiety, low self-esteem, aggression, conduct disorder
• Mostly genetic, but some factors like drug/alcohol/smoking during pregnancy or low birth weight

ADHD: Treatments

• Counselling
• Medication (stimulants increase dopamine levels, block dopamine reuptake transporter).
• Antidepressants

Mood Disorders

• Affect (feelings, emotions)
• Affective disorder = disordered feelings
• Serious mood disorders: bipolar disorder, major depressive disorder

Bipolar Disorder

• Cyclical periods of mania and depression
• Major depressive disorder: unremitting depression, periods of depression do not alternate with periods of mania

Bipolar Disorder: Symptoms/Consequences

• Mania: state of unjustified euphoria, nonstop speech and motor activity, and risky behaviors.
• Mania followed by depression
• Treatments:
  • Lithium (chemical element, rapid effect; unknown mechanism)
  • Anticonvulsants (drugs) block VG sodium channels
  • Antipsychotics/antidepressants

Major Depressive Disorder

• Treatments: drugs increase serotonin/norepinephrine signaling; inhibiting enzymatic breakdown or blocking reuptake
• Electro-convulsive Therapy (ECT) is most effective
• Treatments also include: Ketamine, Transcranial magnetic stimulation (TMS), deep brain stimulation, Vagal nerve stimulation, Bright light therapy and sleep deprivation

Tricyclic Antidepressants and Other Antidepressants

• Tricyclic antidepressants: inhibit the reuptake of serotonin and norepinephrine
• Serotonin-specific reuptake inhibitors (SSRIs) specifically inhibit serotonin reuptake
• Serotonin and norepinephrine reuptake inhibitors (SNRIs) inhibit the reuptake of both norepinephrine and serotonin

Monoamine Hypothesis of Depression

• Depression may relate to insufficient monoamine receptor activity (monoamine = serotonin, norepinephrine, dopamine)
• Success of tricyclic and SSRI treatments focuses on norepinephrine and serotonin
• Low tryptophan diet + tryptophan-free cocktail decrease serotonin synthesis (can cause depressive episodes)
• SSRIs and SNRIs increase serotonin and norepinephrine levels

Role of Frontal Cortex

• Subgenual ACC less active when depression is gone
• Deep brain stimulation targeting it is unsuccessful
• Electroconvulsive therapy (ECT): highly effective, treats severe depression and bipolar disorder.

Sleep and Depression

• Disordered sleep is common in depression
• Reduced time in deep sleep stages (stage 3 and 4); quick entry into REM sleep (earlier in the night)
• Sleep deprivation may be an effective treatment for depression.

Stress, Anxiety, OCD, Addiction

• General physiological reaction to threatening situations, mobilizes body for action
• Triggers autonomic and endocrine systems; adaptive in short term, but long term = illness. Can lead to anxiety.
• Persistent feeling of worry; uneasy without and obvious trigger; more intense than stress
• Physiology of stress:
  • Sympathetic NS: adrenal releases epinephrine and norepinephrine into blood
  • HPA axis: Hypothalamus (CRH/CRF) -> Pituitary (ACTH) -> Adrenal (cortisol) -> increase heart rate, blood pressure, blood flow
• Glucocorticoids: essential to survival, maintain homeostasis, make glucose and fat available, prepare the body for immediate action, but persistent signaling weakens the immune system

PTSD

• Traumatic events: abuse, death, warfare....
• Symptoms: vivid, intrusive memories, dreams, avoidance of stimuli associated with the trauma, hyperarousal(vigilance), negative mood, hopelessness
• Treatments: CBT, group therapy, SSRIs
• More common in women with abnormalities in HPA access, smaller hippocampus and prefrontal cortex (PFC)

Anxiety Disorders

• Variety of psychological disorders characterized by unrealistic fear and anxiety
• Symptoms: expectation of impending disaster, overactive autonomic nervous system, continuous vigilance
• Generalized anxiety disorder: excessive anxiety and worry
• Social anxiety disorder: fear of being judged
• Panic disorder: episodic periods of severe terror
• Anticipatory anxiety: fear of panic attack
• Agoraphobia: avoiding places and situations

Anxiety Disorders (Treatment, Causes and Other Details)

• Causes are genetic and environmental factors
• Treatments include lifestyle changes, CBT, SSRIs, and benzodiazepines
• Often comorbid with major depressive disorder, personality disorders, or substance use disorders
• Specific neural circuit disorders are absent

Obsessive-Compulsive Disorder (OCD)

• Genetic and environmental factors involved
• Symptoms include repeated thoughts (obsessions) and ritualistic behaviors (compulsions)
• Examples: cleaning, hoarding, symmetry, forbidden thoughts
• Treatments for OCD include therapy (exposure and response prevention; a form of CBT) and antidepressants (SSRIs)
• Possible deep brain stimulation, but still being researched

Substance Use Disorder

• Genetic predisposition
• Addictive drugs positively reinforce behavior; speed of reinforcement by the brain
• Reinforcers cause dopamine increase in the striatum.
• More addictive = more rapid dopamine release
• Partially maintained by negative reinforcement, drug cravings outlast withdrawal symptoms

Substance Use Disorder (Tolerance, Withdrawal, Physical Dependence, and Comorbidity)

• Tolerance: drug effect gets smaller with repeated exposure (compensatory mechanisms).
• Withdrawal: opposite symptoms to those produced by the drug when removed from body; compensatory mechanisms
• Physical dependence: physical symptoms of tolerance and withdrawal. Tolerance and withdrawal can occur without addition.
• Comorbidity: most schizophrenics smoke cigarettes and have abnormalities in PFC and interaction between striatum and dopamine neurons associated with deficits involving PFC

Substance Use Disorder (Treatments)

• Block the receptor approach (ex. Nalterexone, Naloxone) which can be prescribed to alcoholics and opiate addicts;
• Maintenance approach (ex. Methadone, Buprenorphine, Varenicline) which can be used as a substitute for heroin. Methadone is a strong opiate, Buprenorphine is a partial opioid receptor agonist, and Varenicline is a partial agonist at acetylcholine receptors used for nicotine addiction
• Brain stimulation approach: using deep brain stimulation or transcranial magnetic stimulation (TMS) to regulate cerebral cortex activity

Similarities Between Mental Disorders

• More common in women: anxiety disorders, major depression, OCD, PTSD, anorexia, bullimia
• More common in men: ADHD, autism, intellectual disability, Tourettes
• Influenced by genes and environment: autism, schizophrenia, seizures, OCD, ADHD, developmental disorder, traumatic brain injury, PTSD

Autism Diagnoses: Males vs. Females

• Diagnosed men have fewer harmful gene variants than diagnosed females
• Rare gene copy number variations (CNVs): section of genome is duplicated or missing.

Sex Chromosomes:

• Mammals (most insects): females have 2 of the same chromosome (XX), this is called the homogametic sex.
• In contrast, male mammals (heterogametic sex) have 2 different chromosomes (XY)
• XX promotes robustness in developmental pathways in humans.

Mental Illness Differences: Females

• Social/cultural stressors
• Hormone fluctuation during puberty, childbirth, and menopause
• Anxiety and depression fluctuate during hormonal changes
• Hormone signaling affects neural networks, adapting to the changes

Autism: Symptoms

• Wide range of disorders, wide range of causes
• Genetic and environmental factors