NSCI Final (quilt)

association cortices

- concerned with attending to complex tasks, identifying relevant features, recognizing related objects and planning appropriate responses
- cognition (most of the surface of the brain devoted to it, only a fraction of cerebral cortex processes sensory and motor info)

neocortex

- covers cerebral hemispheres
- has 6 layers/laminaes
- distinctive cell population based on different densities, sizes, shapes, inputs and outputs
- subdivisions (based on variation in thickness and cell density)
- circuitry of all regions has common features

Brodman

- 50 cytoarchitectonic areas
- regions defined purely based on anatomical observations without knowledge of their functional significance
- later work sowed their functional significance

circuity of layers of neocortex

- each layer has a primary input source and output target
- connections in vertical axis (columnar, radial) and in horizontal axis (lateral)
- cells with similar functions are arrayed in vertical groups, spanning their layer and they receive inputs segregated into columns
- interneurons horizontally link vertical groups (extensive local axons)

Differences with Primary cortices

1. input comes from other regions of cortex
2. enrichment in projections from other cortical areas
3. modulatory inputs

1. input comes from other regions of cortex

- 2 thalamic nuclei (pulvinar and medial dorsal) only project to association cortices and other thalamic nuclei project there as well
- input to thalamic nuclei from other cortical regions
- reflect sensory and motor info already processed in primary areas (get thalamic info related to peripheral sense organs)
- "pre-processing"

2. enrichment in projections from other cortical areas

- corticocortical connections
- ipsilateral \= primary and secondary sensory and motor cortices
- also arise from corresponding and non corresponding cortical areas
- also some contralateral regions in opposite hemisphere project via corpus callossum and anterior commissure (interhemispheric connections)

3. modulatory inputs

- dopaminergic, noradrenergic, serotonergic inputs from brainstem and midbrain
- contribute to learning, motivation, arousal

Parietal Association Cortex

- Attention
- Brain reported 3 patients with unilateral parietal lobe lesions and their primary problem was paying attention to objects and events on side contralateral to lesion
- contralateral neglect syndrome (inability to attend to objects or one's body in a a portion of space even if visual acuity, somatic sensation and motor ability are intact)
- fail to report, respond to or orient to stimuli presented to the side of the body/visual space opposite to the side of lesion
- motor deficits \= apraxia (on neglected side)
- damage to right parietal cortex (unequal distribution; right mediates both sides while left cortex mediates mostly right attention so can be compensated)
- not just inattentive to left visual field but also left side of objects

Monkey attention neurons

- monkey trained to attend a light by pairing it with fruit juice reward, when it attends the stimulus, the activity of the neurons in posterior parietal cortex increased but is unchanged when the monkey ignores the stimulus
- monkey then rewarded with different amount of juice for attending different stimulus (will attend more to stimulus paired with more juice and firing rate of neurons increases with amount of juice associated \= neuronal response reflects amount of attention paid to stimulus)

Balint's syndrome

- inability to perceive parts of complex visual scenes as a whole (simultagnosia)
- deficits in visually guided reaching (optic ataxia)
- difficulty in voluntary scanning of visual scenes (ocular apraxia)
- parietal cortex contains neurons that respond specifically when animal attends behaviorally meaningful stimulus and vigor of response reflects amount of attention
- enhanced response to stimuli when attended (higher speed so higher accuracy of response)

Temporal association cortex-

- Recognition
- particularly complex stimuli
- agnosia \= can't recognize, identify or name objects but acknowledge presence of stimulus (just can't report what it is), lexical aspect (mismatching of verbal and stimuli) and mnemonic (can't recall stimuli when confronted with them again)
- prosopagnosia (highly specific to faces, can recognize people using other characteristics like body shape but can't identify familiar individuals by facial ones and sometime scan't recognize a face at all) - lesions in or near fusiform gyrus
- inferior temporal cortex (usually on the right for faces and left for language related deficit)
- cells quite selective (front face vs profile)
- faces identified by comparison with mental standard/norm (respond best to caricatures and extreme features)

Frontal association cortex

- Planning and decision making
- integrates information from the sensory and motor cortices and parietal and temporal association cortices
- appreciation of self in relation to the world, allowing behaviors to be planned and executed
- "personality"
- Phineas Gage (character change after incident)
- damage \= impaired restraint, disordered thought, perseveration, inability to plan appropriate action, repetitive behavior, inability to plan for future, reduced creativity and initiative
- frontal lobes are the largest so damage has profound effect
- no obvious sensory, motor or language deficits or loss of intellect (Joe A- bilateral frontal lobe resection)
- these deficits can be localized to subregions (working memory in dorsolateral prefrontal cortex and restraint and social restraint in ventromedial prefrontal)
- dorsolateral prefontral activated when suppressing behavioral response
- ventromedial prefrontal activity when receiving a reward correlates with an individual's preference for different types for reward (--\> attribution, important for adaptive decision making)

Delayed response task

- monkey must wait o make a choice to access a reward
- to perform the task, monkey must store info in working memory to plan a behavioral response
- performance on the task is impaired when lesioning the prefrontal cortex
- neurons in dorsolateral prefrontal maximally active during delay period suggesting that they encode the info the monkey is retaining to perform the task
- these neurons are also active when monkey uses stored info to guide behavior
- some prefrontal neurons are activated during learned motor sequences and are important fro executing motor sequences from memory

Language

- ability to associate arbitrary symbols with specific meanings to express thoughts and emotions in thoughts, speech or writing
- failure to develop it is incapacitating
- located in the left hemisphere (frontal and temporal association cortices)
- centers specialized for symbolic representation and communication rather than hearing and speech (seen in deaf individuals)
- representation distinct from sensory and motor control of speech production and auditory and visual perception

Grammar

obedience to a set of rues for using symbols

Syntax

ordering symbols to generate useful meaning

Prosody

providing appropriate emotion by varying intensity, rhythm and pitch

Aphasia

- ability to produce or perceive spoken language can be compromised without affecting the ability to use the language to communicate (deaf, mute...)
- damage to specific brain regions can compromise language abilities while leaving the sensory and motor control mechanisms intact
- aphasia diminish or abolish ability to understand and/or produce language as a means of communication, while sparing the ability to perceive the relevant stimuli and produce intelligible words
- fundamental deficit is ability to recognize the use of symbolic value words correctly

Broca

- suggested that language was located in the ventroposterior frontal lobe
- observed that the loss of ability to produce meaningfull language (different from ability to move mouth and produce words) was associated with damage to the left hemisphere (unitary function)

Broca's aphasia

- affect production
- motor/expressive aphasia
- not dysarthia (can't move muscles that mediate speaking)
- posterior and inferior frontal lobe (close to primary motor)
- symptoms \= halting speech, repeat, disordered syntax, grammar, structure of individual words but intact comprehension
- can still eventually convey meaning

Wernicke

- distinguished between patients who had lost the ability to understand and thoes who had lost ability to produce

Wernicke's aphasia

- affect understanding of language
- sensory/receptive aphasia
- not alexia (reading) and agraphia (writing)
- posterior and superior temporal lobe
- symptoms \= fluent speech without meaningful content, no repeat, syntax and grammar adequate, inappropriate words, comprehension not intact

conduction aphasia

- lesions to pathways between relevant frontal and temporal regions (arcuate fasicuclus in subcortical white matter linking broca and wernicke area)
- inability to produce appropriate responses to a heard communication even if communication is understood

Roger Sperry

- split brain patients (anterior commissure and corpus callossum severed)
- possible to independently assess function of the left and right cerebral hemispheres
- confirmed lateralization of language
- patient asked to use each hand to identify objects without visual cues and then describe these items
- when in right hand (left hemisphere) could name objects but not when in left hand (could produce indirect description like "round thing" instead of "ball")

left hemisphere functions

- analysis of right visual field
- stereognosis of right hand (hold objects to identify them)
- lexical and syntactic language
- wrting
- speech

Right hemisphere functions

- analysis of left visual field
- stereognosis of left hand
- emotional coloring of language
- spatial abilities
- rudimentary speech

planum temporale

- asymmetry in superior aspect of temporal lobe
- larger on left side in 2/3 humans
- near cortical language areas
- unlikely it correlates with lateralization because it is already present at birth and is not observed in all humans but lateralization is in most people

Wada test

- short acting anesthetic injected into patient's left carotid artery to transiently anesthetize the left hemisphere
- patient will become transiently aphasic if hemisphere dominant for language
- very accurate but involves some risks
- less invasive tests include PET, fMRI, transcranial magnetic stimulation and tachistoscopic stimulus presentations (in normal patients, response if delayed)

Mapping language

- penfield
- variable localization of language from patient to patient
- language areas approximate the textbook version but many individuals show interference of language function with stimulation well outside broca and wernicke areas
- bilingual patients show variability in cortical site of storage for the name of a single object in 2 languages
- fMRI studies have shown distinct regions of temporal cortex activated by language tasks involving specific categories (explains why focal damage to temporal lobe can sometimes lead to deficits for specific categories of objects)

aprosodia

- deficiencies in prosody
- damage to right hemisphere

sign language

- Cortical organization of language is not just about specializations for hearing & speaking
- Language regions are broadly specialized for processing symbols of social communication
- Sign language also have grammar, syntax & emotional tone
- Studies of congenitally deaf patients with lesions to either the left or right hemisphere showed that damage to the left-hemisphere lead to deficits in sign production & understanding
- Damage to the right hemisphere lead to deficits in the emotional tone of signing

emotions

- behavioural displays, subjective feelings and physiological states
- most psychoatric problems involve disordered emotion
- expressed through movements in facial muscles
- limbic system coordinates emotional responses

emotional arousal

- changes in visceral motor system
- altered heart rate
- altered cutaneous blood flow (blushing, turning pale)
- piloerection (hair standing up)
- sweating
- gastrointestinal motility

Walter Cannon

- sympathetic division (govern smooth muscle, cardiac muscle and glands) of visceral motor system prepares an animal to utilize metabolic and other resources in challenging situations
- parasympathetic and enteric division promote build up of metabolic reserves

autonomic responses and emotion

- correlate with specific emotions
- can be induced by stimulating facial expressions of emotions
- voluntary facial expressions may also signal circuits that produce emotional states
- sensory input from muscles and internal organs are one source of emotion
- physiological responses can also be produced by complex stimuli processed by the forebrain (like social interactions)

The Duchenne Smile

- used electrical stimulation to examine the contribution of facial muscles to emotional expression
- obicularis oculi muscles are only contracted in true emotional smiles
- the neural correlates of forced and voluntary smiles are distinct

voluntary facial paresis

- lesion to descending fibres from motor cortex (and brainstem)
- can't fully contract muscles to make a smile when asked to (pyramidal smile) but can smile spontaneously (Duchenne Smile)

emotional facial paresis

- lesion to descending non-motor cortical areas (from medial forebrain and hypothalamus)
- can contract facial muscles when told to smile but can't smile spontaneously

Integration of emotional behavior

- hypothalamus is critical for coordinating visceral and somatic motor components of emotional behavior
- lesion to large amounts of the cerebral hemispheres in cats resulted in angry behaviors (and increased blood pressure and heart rate, dilation of the pupils, piloerection --\> sham rage because it has no clear target)
- sham rage not observed when caudal hypothalamus was damaged
- expression of emotional behavior does not require cortical processes (but subjective experience of emotion might depend on them)
- behaviors are directed toward self preservation
- electrical stimulation of discrete areas of the hypothalamus in awake cats could also lead to rage response and other ares produced a defensive posture
--\> basic circuits for organized behaviors accompanied by emotion are in diencephalon and brainstem structures connected to it

Reticular formation and emotion

- target of hypothalamus
- output to somatic and visceral motor effector systems
- controls sleep and wakefulness, cardiovascular functions, respiration, urination, vomiting, swallowing
- also receives input from forebrain that contribute to expression of emotional behavior

The limbic system

- limbic lobe around the corpus callossum on the medial aspect of the cerebral hemisphere (identified by Broca)
- Papez showed that the cingulate cortex and hypothalamus are connected to the anterior nucleus of the thalamus (via projections from the mamillary bodies)
- thalamus then projects to the cingulate gyrus, which projects to the hippocampus, which projects back to the hypothalamus (via fornix)
--\> Papez circuit (cortical control of emotions)
- other regions added: orbital and medial prefrontal cortex, ventral portions of basal ganglia, mediodorsal nucleus of thalamus, amygdala

Kluver-Bucy syndrome

- removal of the medial temporal lobe led to visual agnosia (not blind but couldn't recognize objects), unusual oral behaviors, hyperactivity, hypersexuality, tame, fearless
- could be induced by removal of the amygdala alone

Amygdala and emotions

- mediates neural processes that attribute emotional significance to experience
- conditioned fear response in rats used to understand its role

conditioned fear response

- initially neutral stimulus repeatedly paired with aversive one
- learn to attach new meaning to neutral stimulus (when paired with electric shock for example) and will respond with behaviors and physiological changes elicited by aversive stimulus
- in rats, high blood pressure and length of freezing are measured when they react to tone that used to be neutral
- Pathway for fear learning\= auditory pahways (or other sensory pathway) -\> medial geniculate nucleus of thalamus -\> basal-lateral amygdala
- Pathway for expression of fear response \= central nucleus of amygdala-\> reticular formation

associative learning in amygdala

- site of learning about fearful stimuli
- amygdala participates in learning about neutral stimuli (tone or light ie sensory stimuli) and stimuli with primary reinforcement value (positive like food or negative like electric shock)
- if sensory input (taste, touch, pain..) depolarizes an amygdala neuron at the same time as input from a sensory stimulus, synaptic connections are strengthened between previously neutral inputs and the amygdala neuron
- output signals to centers controlling somatic and visceral motor expression of emotion and behavioral control of reward seeking or punishment avoidance
- Long term potentiation occurs and supports this hebbian-plasticity
- acquisition of conditioned fear is blocked by infusing NMDA receptor antagonists in the amygdala prior to training (also prevents LTP at glutamatergic synapses)

fear and the human amygdala

- case study of SM (Urbach-Wiethe disease) demonstrates role of amygdala in fear because when there is highly selective damage to amygdala, the person fails to recognize the emotion of fear when asked to rate faces and fails to report fear in normally fear-provoking situations

neocortex and amygdala

- the amygdala is a key node in a network linking cortical and subcortical brain regions involved in emotional processing
- interactions between the amygdala, the neocortex and subcortical circuits likely accounts for the feelings associated with emotional states
- feelings likely arise from a more general cognitive capacity for self-awareness
- feelings could be thought of as the product of an emotional working memory that sustains neural activity related to processing emotional experience, likely occurring in the prefrontal cortex (orbital and medial aspects of frontal lobe associate info from every sensory modality so integrate variety of inputs pertinent to moment to moment experiences)
- amygdala projects to the prefrontal cortex through the thalamus
- these connections to the prefrontal cortex and the ventral basal ganglia are likely to influence selection and initiation of behaviors aimed at obtaining rewards or avoiding punishments

lateralization of emotion

- right hemisphere is specialized for the expression and comprehension of emotion in speech (prosody)
- damage to right posterior frontal and anterior parietal lobes lead to aprosodia
- patients speak in a monotone voice without emotional expression
- left hemisphere more important in processing positive emotions and right hemisphere in processing negative emotions
- increased incidence of depression in left anterior hemisphere lesions
- more rapid processing of emotional information by left hemisphere in healthy controls

affective disorders - depression

- 10-25% in women
- 5-12% in men
- symptoms: feelings of worthlessness and guilt, despair, sleep disturbances, metabolic changes, inability to experience pleasure, poor concentration
- genetic contributes but environment also plays a role
- reflects neurobiological alterations (aberrant activity in regions including amygdala)

Emotional reinforcement and addiction

- aberrant recruitment of emotional neural circuits that guide goal-directed behavior
- in physiological conditions, limbic emotional processing signals the presence or prospect of reward or punishment and promotes motor programs to seek reward or avoid punishment
- most drugs have effects on limbic circuits, many via dopamine

the limbic loop

- the amygdala, hippocampus, orbitofrontal cortex, anterior cingulate and temporal cortex convey information about emotional reinforcement to the nucleus acumbens (ventral striatum)
- medium spiny neurons in the nucleus acumbens integrate these glutamatergic inputs with modulatory dopaminerguc inputs from the ventral tegmental area to direct motivated behavior
- then projects to inhibit ventral pallidum, substantia nigra, pars reticulata, which usually inhibit the mediodorsal nucleus of thalamus
- this activates the rewarding effects of natural stimuli (food, sex...)

VTA dopamine neurons and reward

- dopamine neuron activity is altered by experience-dependent plasticity in associative learning
- before learning, the presentation of a reward evokes burst firing of dopamine neurons
- after learning, the dopamine neurons instead burst during a stimulus that predicts the reward
- if the predicted reward is omitted, activity of dopamine neurons is suppressed
- suggests that dopamine neurons are signaling reward relative to prediction
- these signals lead to activation of instrumental behavior aimed at obtaining the reward

Drug effects on VTA dopamine projections to nucleus acumbens

- plasticity in limbic circuits gets hijacked by drugs
- most drugs potentiate dopamine signaling in the nucleus acumbens or by increasing the activity of nucelus acumbens neurons by increasing glutamatergic inputs
- in addicted sate, cellular and molecular adaptations in this circuit lead to lasting alterations in glutamatergic and dopaminergic (from VTA) inputs to the nucleus acumbens
- ultimately, addiction dampens the response of limbic circuits to natural rewards and intensifies the response to addictive drugs

Drugs of abuse

- Opiates affect GABA interneurons affecting VTA and nucleus acumbens directly
- Alcohol affect synapse of VTA interneurons and VTA projection neuron
- Nicotine affects synapse between glutamate inputs and VTA and nucleus acumbens
- Cocaine and amphetamines affect the dopamine reuptake in synapse between VTA and nucleus acumbens
- Cannabinoids affect nucleus acumbens

Sex

- chromosomal (XY,XX, defined at fertilization)
- gonadal (ovaries or testes)
- gametic (ova or sperm)
- hormonal (androgen for males and estrogen for females)
- morphological (body form, size, external genitalia)
- behavioral (typical sex behaviors)

gender

- additional category pf sex classification specific to humans
- gender identity is the psychological self perception of being either males or female
- gender role is the collection of behaviors considered normal to each sex in each culture
- sexual preference/orientation is the process of developing sexual attraction for other individuals

sexual dimorphism

- differences between the sexes (in size, shape pf body, physiology, behavior..)
- rises from nurture-nature interplay (not hard wired)
- relates to reproductive function

seuxal differentiation

- developmental process by which individuals develop the characteristics associated with being male or female

sexual determination

- primary step in sexual differentiation
- at fertilization, the chromosomal complement of the sperm (X or Y) determines the sex
- the SRY gene is the determinant of developing male gonadal tissue
- its presence (on the Y) initiates a cascade of gene expression and hormonal signaling that results in masculinization, starting with the development of testes
- with no SRY, ovaries develop

chromosomal sex -\> gonadal -\> hormonal -\> morphological -\> behavioral

hormonal influences on dimorphism

- different gonadal tissue (testes or ovaries) will secrete different concentration of steroid hormones (testosterone and estrogen) to influence dimorphism
- they both secrete estrogen and androgen but with deifferent developmental time courses
- in males there is an early surge of testosterone and mullerian inhibiting substance (MIS) that masculinizes genitalia
- all are lipophilic so are transported via carrie proteins in blood
- fetuses exposed to ovary's and placenta's estrogen bu alpha fetoprotein binds to it to protect from early brain exposure but doesn't affect testosterone so brain is exposed to early dose of masculinizing steroids

Klinefelter's syndrome

- congenital condition in which an individual has XXY chromosomes
- male genitalia but sterile
- some secondary female characteristics
- slightly increased height

Turner syndrome

- lack X chromosome (XO)
- female appearance but limited ovarian development
- do not attain puberty without external hormone treatment
- not exposed to steroid hormones except for treatment

congenital adrenal hyperplasia

- genetic deficiency resulting in excess androgen production by the adrenal glands
- causes masculinization of genitalia in females
- can lead to erroneous sex assignment at birth

Complete androgen insensitivity syndrome

- in genetic males in which functional androgen receptors are absent
- mutation on X chromosome
- female external genitalia leads to sex assignment and rearing as girls
- internal genital not fully developed

Organizational hypothesis

- hormones early in development differentiate the nervous system in a male or female direction
- constrained to early development
- ireeversible
- perinatal critical periods of maximal susceptibility

Activational hypothesis

- hormones act on these differentiated circuits later in life to drive behavior in a sex typical manner
- in adulthood
- activational effects are temporary

gonadal sex steroid hormones

- made from cholesterol, converted to progesterone (common precursor)
- progesterone converted to testosterone
- testosterone can be converted to its active form (5 alpha dihydrotestosterone by 5 alpha reductase)
- or can be converted to the active form of estrogen (17 beta estradiol via aromatase)
- most hormonal effects in the brain are mediated via this last one
- many of the effects of testosterone in the male brain are due to estrogens during mid-gestation
- testosterone can also act directly (females without aromatase are masculinized because no testosterone is converted to estrogen so there are increased effects on testosterone sensitive cells)
- when active forms of testosterone and estrogen bind their receptors, the receptors translocate to the nucleus where they bind DNA to influence gene expression

effects of sex steroids on neurons

- direct effects both pre (alter neurotransmitter synthesis, release and reuptake) and post (alter membrane permability) synaptically as well as indirect effects via regulation of gene expression in the nucleus
- estradiol sensitive neurons are widely distributed throughout the brain with many located in the pre-optic area, hypothalamus and amygdala

Spinal nucleus of the bulbocavernosus (SNB)

- innervates muscles of genitalia (2 striated muscles of male perineum at base of penis for penile erection and urination)
- in males, the androgen receptors become occupied by circulating testosterone, but in females the receptors remain unoccupied (not enough testosterone)
- when testosterone binds, it activates the receptors and in males they promote the survival of the muscle and cause it to secrete trophic factors, picked up by the motor neurons
- in females, the lack of receptor activation causes the muscle to die, and no trophic factors are produced
- in males, the trophic factors picked up by motor neurons promote their survival while they die in females
- in humans : onus's nucleus (dorsal medial group not dimorphic but ventral lateral is; females have fewer neurons in it)

Anteroventral paraventricular nucleus (AVPV) of hypothalamus

- larger in females than males
- preventing masculinization via inactivating estrogen receptor signaling in the male brain results in female size AVPV (testosterone induces cell death)
- AVPV projections regulate ovulation in females

nucleus of preoptic area (SDN-POA) of hypothalamus

- larger in male than female rats
- lack of testosterone lead to cell death
- giving genotypically female rats testosterone results in male size SDN POA
- SDN POA is linked to dimorphic sexual behaviors of mate selection and preparatory behaviors
- lesions in males alter mounting and copulation
- lesions in females alter mate selection and copulatory responses

dimorphisms in pregnancy and lactation

- in pregnancy the brain is altered temporarily (ex. appetite regulation)
- leptin signaling in the arcuate and ventromedial hypothalamus (VMH) that normally signals satiety is suppressed (leading to weight gain)
- neurons in the VMH express pSTAT after binding leptin
- pSTAT expression is reduced in VMH of pregnant females (facilitate greater food intake to accommodate gestation needs)
- paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus regulate lactation (same size in male and female but sensitivity to gonadal steroids and ability to alter synaptic organization and function in response to changes in hormones and reproductive state are different)
- before birth, neurons and dendrites in the SON are separated by astrocytic processes
- during lactation, the astrocytic processes withdraw to allow electrical synapses to form
- SON neurons fire synchronously during lactation (but independently otherwise)
- SON neuronal firing, induced by pressure on the mammary gland correlates with a surge in oxytocin and milk ejection
- lactation related changes are controlled by gonadal steroid levels but also sensory feedback (vaginal distension during birth, suckling of pups...)
- increase in cortical representation of venture and receptive field decreased so more sensitivity and resolution

cellular and molecular basis of dimorphism

- sexually dimorphic effects (like differences in number of neurons) can result from gonadal steroids regulating cell survival and cell death
- gonadal steroids can also influence trophic signaling to regulate neuronal size and outgrowth of axons and dendrites (ex. estradiol can increase neurite growth)
- estradiol increases synapse number in adults (may contribute to differences in learning and memory across the estrous cycle)
- administering high dose progesterone and estrogen increases growth of dendritic spines in hippocampal pyramidal neruons
- testosterone increases growth and branching in embryonic spinal cord neurons
- in the hippocampus, estrogen receptors are present in the synapses and cell bodies
- estrogen can alter hippocampal neuronal excitbility
- at very high doses, estrogen can increase excitatory post-synaptic potentials and increase the long term potantiation induced by high frequency stimulation

sex determination for body, brain and mate selection in drosophila

- gene cascades controlling phenotypic sex do not explain the neural circuit differentiation of male and female typical courtship behavior
- the fruitless gene explains the discrepancy between genotypic sex and sex-specific behavior
- fruitless exerts control over organization of neural circuitry of male-specific behavior in drosophila and is expressed in a subset of neurons in the male brain and due to alternative splicing, the functional fruitless is only expressed in the male brain (not in female)
- it may regulate the details of neural circuit structure independent of sex hormones
- deletion of male-specific transcript of it suppresses male-typical courtship in flies
- deletion only in the olfactory bulb in males leads to lack of habituation to males
- expression in female brain leads to male-specific courtship and suppresses female-specific behavior

biology of human sexual preferences

- more complex
- twin studies indicate slightly higher probability of homosexuality in monozygotic than dizygotic twins suggesting genetic contribution
- male sibling birth order correlates with homosexuality such that increasing chance of homosexuality with every male child born
- some suggestion of hormone dependent differences in brain activity but more research needed

neural differences in humans

- evidence has been limited by small sample size that often are not replicated
- suggestion of difference in amygdala structure and function
- amygdala activation to a previously viewed image depicting a strong emotion lateralizes differently in men and women
- reported sex differences are averages
- there is more inter-individual variability within sex than between sex for most cognitive abilities
- reliable sex differences exist but the differences in ability are slight

learning

process by which new info is acquired by the nervous system and can be observed by behavioral change

memory

encoding, storage and retrieval of learned info

declarative memory

- storage and retrieval of material that is available to consciousness and can be expressed by language
- ex. remembering the words to a song
- in the brain: hippocampus and distributed cortices

non declarative memory

- procedural
- skills and associations that are largely acquired and retrieved unconsciously
- full detail not available to consciousness
- ex. knowing how to sing a song
- in the brain: distinct system from declarative memory, involves the basal ganglia and prefrontal cortex (complex motor learning) , amygdala, sensory association cortices and the cerebellum (NOT the medial temporal lobe/hippocampus)
- sensory-motor conditioning (ex. learning to blink following a tone that predicts an air puff to the eye) requires the cerebellum
- impaired motor skill learning (mirror drawing, reproducing sequence of finger movements) is observed in Huntington's patients (atrophy of caudate and putamen), Parkinson's patients (disrupted basal ganglia function due to dopaminergic neuron loss) and patients with prefrontal lesion

immediate memory

- ability to hold ongoing experiences in mind for fractions of a second to seconds
- very large capacity and semi-independent across sensory modalities
- then goes to short term and long term memory or forgetting

working/ short term memory

- ability to hold and manipulate information in mind for seconds to minutes while it is being used to achieve a goal
- ex. searching for a lost object
- commonly tested by ability to repeat random string of digits (span 7 +/- 2)
- limited in duration and capacity
- ongoing retention requires continual rehearsal
- closely related to attention (attention for internal representations)

long term memory (LTM)

- retaining information more permanently (days - lifetime)
- particularly significant information in immediate memory or STM enters LTM by conscious or unconscious rehearsal or practice
- the physical embodiment of memory or engram is thought to be stored at the level of changes in strength of synaptic connections or rewiring such connections between neurons

memory consolidation

- encoding of immediate and STM into LTM

Priming

- one way of assessing continual transfer of information to LTM (list of words shown, then only stems shown and people tend to use the words from the list to complete the stems)
- change in the processing of a stimulus due to a previous encounter with the same or related stimulus
- demonstrates that even apparently insignificant previously presented information can continue to influence behavior
- can be unreliable (subjects report with certainty having previously heard a word that is simply associated with words on the previously exposed list)
- perceptual (influence is unconscious) depends on sensory association cortex

Association and information storage

- memory capacity can be greatly enhanced beyond by forming associations between otherwise arbitrary items (giving meaningful context to otherwise arbitrary info)
- professional mnemonists use association strategies to greatly expand their memory capacity (ex. reciting pi by associating numbers with musical notes and singing the number string)
- memory capacity depends upon the meaning of the information to the individual (ex. an experienced chess player can remember the position of more pieces on the board than a novice because it relates to knowledge of chess; if randomly arranges board, they are disadvantaged)

Motivation and information storage

- motivation exerts an important influence on memory
- subjects correctly recognize more pictures of food related items that they previously viewed when hungry than when sated
- no effects on non-food images

conditioned learning

- through repeated presentations, a novel stimulus comes to be associated with a motivationally significant outcome and the stimulus comes to produce the same behavior as the outcome
- classical/pavlovian or operant
- generally require multiple trials to acquire

Classical conditioning

- innate reflex is modified by associating its normal triggering stimulus with an unrelated stimulus
- because of this, the unrelated stimulus eventually triggers the response
- Pavlov's dog
- unconditioned response initially present and animal has no control over it

Operant conditioning

- altered probability of a behavioral response by associating th response with a reward or a punishment
- Thorndike's cats and Skinner box
- animal has to press a lever to get food or avoid shock
- the behavior is not innate; the animal learns to do it and then has control over it

Extinction of association

- after the animal has acquired the learned association (lever press \= food) and performs the response (lever pressing), if the outcome (food) is no longer presented, the animal will gradually stop performing the behavior as the association undergoes extinction
- distinct from forgetting

forgetting

- over time, forget what is encoded in LTM
- mechanism could be either inability to access stored memories or loss of original memory trace
- unused or unrehearsed memories deteriorate over time
- the ability to forget unimportant information may be critical for normal life (make room for new memories, abnormally comprehensive memory may make it difficult to extract the most relevant info)
- excessive \= amnesia

anterograde amnesia

- inability to form new memories after some kind of neurological insult

retrograde amnesia

- difficulty retrieving previously formed memories

HM

- evidence of importance of medial temporal lobe (hippocampus) in forming new declarative memories
- experienced profound deficits in anterograde declarative memory but was still able to learn skills (undeclarative)

Morris water maze

- used to assess a rodent analog of declarative memory and the task requires the hippocampus
- rats put in a pool and have to find a platform by using spatial cues
- when there is a lesion in hippocampus, the rat will swim around and around (normal for the first trial) even after multiple trials because it hasn't learned the spatial cues to find the platform and starts anew each time
- in humans: activation in hippocampus and hippocampal cortex predicts memory performance on a list memory task
- in london taxi drivers, the volume of the posterior hippocampus positively correlates with the time spent driving a taxi

Hippocampus

- critical for formation of declarative memories
- however memories are stored elsewhere (ex. HM could remember facts and events from his life prior to surgery)
- the cerebral cortex is the likely site of long term storage

Lashley's mass action principle

- while trying to find the "engram", Lashley made cortical lesions in different locations and concluded that the site of lesion didn't matter, only the extent of the lesion did
- any degradation in learning and memory depends on the amount of cortex destroyed and the more complex the learning task, the more disruptive the lesion
- these findings imply that memories are stored in a distributed cortical network that is resilient to some damage

Distributed cortical storage hypothesis

- hippocampus receives projections from numerous cortical areas and projects back to these same areas
- memory may be formed in hippocampus but then consolidated in the cortical area specialized for processing the kind of information being stored
- supported by human neuroimaging studies
- patterns of brain activation compared when a subject views pictures and is asked to imagine the objects and shows that similar regions were activated
- retrieving memories involves the association cortices (particularly frontal cortex)
- damage to frontal association cortices is associated with failure to accurately recall details of memories and with confabulation
- temporal gradient likely influences the dependence of memory on hippocampus