>I am now the most miserable man living. If what I feel were equally distributed to the whole human family, there would not be one cheerful face on earth. Whether I shall ever be better, I cannot tell; I awfully forebode I shall not. To remain as I am is impossible. I must die or be better, it appears to me.
>I am now the most miserable man living. If what I feel were equally distributed to the whole human family, there would not be one cheerful face on earth. Whether I shall ever be better, I cannot tell; I awfully forebode I shall not. To remain as I am is impossible. I must die or be better, it appears to me.
Lincoln was unconscious following a horse kicking him in the head for 24hrs at 9 yrs old.
He was clubbed on the head during a robbery attempt in 1828.
Sympathetic Fight or flight, preganglionc: in the intermediolateral column. Postganglionic: Sympathetic chain
blood vessels in skin and gut contract, rerouting blood to muscles
hairs stand on end, piloerection making us look more fearsome, bronchi dilate for incr oxygenation, heart rate accelerates. Sympathetic activity also stimulates adrenal medulla to relesase adrenaline and noradrenaline into the bloodstream to mobilize glucagon release from pancreas.
Preganglionic is in the brainstem or sacral spinal cord, Peripheral ganglia in close to the organ they control (think ciliary ganglion or cardiac plexus)
sympathetic:
preganglionic is in spinal cord, peripheral ganglia is in the specialized sympathetic chain ganglia
<div><img src="figs/Neuroscience5e-Box-29A-2R_d6db3b0.jpg" height="300px"><figcaption>Neuroscience 5e Box 29A, Ross and Mathiesen *N Engl J Med* 1998</figcaption></div>
extrapyramidal system: is a neural network that is part of the motor system causing involuntary movements
pyramidal pathways (corticospinal and some corticobulbar tracts) may directly innervate motor neurons of the spinal cord or brainstem
extrapyramidal system centers on the modulation and regulation (indirect control)
Extrapyramidal tracts are chiefly found in the reticular formation of the pons and medulla, and target neurons in the spinal cord involved in reflexes, locomotion, complex movements, and postural control
paresis: muscle weakness
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## Hypothalamus as a coordinator of emotional behavior
* Lesion huge areas of the forebrain in cats and angry behavior occurs spontaneously, including the autonomic correlates of anger. Increased blood pressure and heart rate, dilation of pupil, hair raising. Also contained somatic motor components such as arching the back and tail. Called sham rage
* Phillip Bard / Walter Hess, early 1900s. Conducted seminal studies that determined the hypothalamus is a critical center for coordination of both the autonomic and somatic components of emotional behavior
started by removing cerebral hemispheres of cats, when anesthesia wears off they acted as if enraged. Involved all the autonomic components of the sympathetic nervous system. Called sham rage because no obvious target.
Sham rage: Angry behavior occurred spontaneously included autonomic correlates of anger. Increased blood pressure and heart rate, dilation of pupil, hair raising. Also contained somatic motor components such as arching the back and tail.
Connection from ventral hypothalamus to midbrain needs to be present to elicit sham rage.
Bard suggested that emotional behaviors are often directed towards self-preservation (point also made by Charles Darwin).
* Both a volitional (with deliberate action) and a non-volitional component. Are in separate pathways. Both pathways ultimately lead to motor neuron pools that activate muscle contraction or smooth muscle/gland secretions
* major targets of the hypothalamus is the reticular formation (tangled nerve web of over 100 cell groups including those that regulate sleep/wakefulness, cardiovascular function, respiration, urination, vomiting, swallowing). Reticular output is to somatic and visceral motor effector systems.
* Anatomists had shown that there was a subregion of the brain that formed a rim around the corpus callosum and the medial aspects of the cerebral hemispheres
* These areas found to form a circuit with other areas, including hypothalamus, amygdala, and parts of the thalamus. Together these areas make up the **limbic system**
Green is modern view of limbic system critical for processing emotion. Blue includes other areas of the traditional limbic system such as the hippocampus and mammillary bodies that are not considered critical to circuits for emotional processing.
orbitofrontal and medial prefrontal cortex together with the amygdala are especially important components of the limbic systm.
* mammilary bodies are part of the posterior hypothalamus and is important for interconnecting the cingulate cortex with the hypothalamus through the anterior nucleus of the thalamus
* hippocampus projects back to the hypothalamus via the fornix
* [Kluver-Bucy syndrome– a disease due to damage of temporal lobe and limbic system https://www.youtube.com/watch?v=7RDFRASiq4M](https://www.youtube.com/watch?v=7RDFRASiq4M)
* Cut out only 1 amygdala (remember there is one on each side of brain) at the same time as transecting the optic chiasm, corpus callosum and anterior commissure
* Optic chiasm cut blocks contralateral retinal axons thus now each eye’s information goes to same-side visual cortex
* Creates an animal with a single amygdala that had access only to visual inputs from the eye on the same side of the head
* Fearsome stimuli in visual hemifield mapping to side of brain with lesioned amygdala showed no fear responses. Fearsome stimuli in visual hemifield mapping to side of brain with intact amygdala then animal shows normal fear behaviors. Therefore the amygdala is required for fear behaviors
Patient S.M. can’t recognize the emotion of fear in photographs. She also exhibits little fear herself (e.g. to dangerous animals, scary houses, films, etc)
<figure><figcaption class="big">Amygdala damage in patient S.M</figcaption><img src="figs/Neuroscience5e-Box-29D-1R_9161c18.jpg" height="200px"><figcaption>Neuroscience 5e Box 29d</figcaption></figure>
patient SM has rare autosomal recessive condition called Urbach-Wiethe disease. Disorder of bilateral calcification an atrophy of anterior-medial temporal lobes. Both amygdalas are extensively damaged. Little to no injury of the hippocampus.
She has no motor or sensory or intelligence or memory or language impairment. However she can’t recognize the emotion of fear in photographs. Furthermore, she exhibits little fear herself (to dangerous animals, scary houses, films, etc).
* Among 603 operations for control of untreatable aggressiveness...
* ...there were 481 cases with bilateral amygdalotomies and 122 cases with mostly secondary posteromedian hypothalamotomies that have been performed
* Initially excellent or moderate improvement was achieved in 76%. After a follow-up of more than three years this figure only slightly decreased to 70%. The group of patients who did not positively respond (30%) needs further study to discover the reasons for failure
* Pair a normally neutral stimulus with an inherently aversive one. Over time the animal will show behaviors to the neutral stimulus similar to that when given the aversive one. The animal learns to attach new meaning to a stimulus through classical conditioning
A white rat presented to an infant does not innately elicit fear, but pairing the rat with an aversive noise, produces crying and attempts to crawl away, even when the rat was presented without the noise.
Classic experiments from Watson and Rayner demonstrating fear conditioning in an infant
As early as the 1920s, fear conditioning was demonstrated in infants. A white rat presented to an infant does not innately elicit fear, but pairing the rat with an aversive noise, produces crying and attempts to crawl away, even when the rat was presented without the noise.
<figure><figcaption class="big">Conditioned fear response in rats after associating foot shocks with sound</figcaption><img src="figs/50_520a5cf_copy_904c366.jpg" height="400px"><figcaption>Principals of Neural Science, Kandel, Schwarz, Jessel Fig. 50.07</figcaption></figure>
<figure><figcaption class="big">Amygdala can associate diverse sensory inputs</figcaption><img src="figs/Neuroscience5e-Fig-29.05-0_63e692d.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 29.5</figcaption></figure>
CG– central gray or PAG (periaqueductal gray). Primary control center for descending pain modulation. Enkephalin releasing neurons that project to raphe nuclei (and 5-HT in turn excites inhibitory interneurons in the spinal cord dorsal horn). Role in analgesia and defensive behavior. Responsible for the ‘freezing’ behavior of conditioned fear, the arresting of somatomotor activity.
LH– lateral hypothalamus. Contains orexinergic neurons. Projects widely throughout nervous system. Promotes feeding behavior, arousal, reduces pain perception, regulates body temperature, digestive functions and blood pressure. Glutamate, endocannabinoids (anandamide), and orexin neuropeptides are main neurotransmitters in orexin neurons. Robust projections to posterior hypothalamus, tuberomammillary nucleus (histamine projection nucleus in posterior hypothalamus. Sole source of histamine pathways in human), arcuate nucleus (neuroendocrine neurons in mediobasal hypothalamus, prolactin, GHRH, ghrelin, neuropeptide-Y), paraventricular hypothalamic nucleus.
PVN– paraventricular nucleus of hypothalamus. Contains groups of neurons activated by stressful or other physiological changes. Release oxytocin or vasopressin into circulation through terminals in the pituitary.
* Properties consistent with role as specific coincidence detector
* Not generalized across whole neuronal ensembles, but localized
* Associativity utilized for associative learning or classical/Pavlovian conditioning (great early 20c russian physiologist, Pavlov's dogs (dinner bell association with food presentation and salivation))
## The amygdala as a key node in the brain network for emotional processing
<figure><img src="figs/Neuroscience5e-Box-29B-3R_copy_cb4899d.jpg" height="400px"><figcaption>Neuroscience 5e Box 29B</figcaption></figure>
Note:
orbito and medial prefrontal cortex
: prefrontal cortical regions in the frontal lobe associate information from every sensory modality
- amygdala projects to mediodorsal nucleus of thalamus-- this in turn projects to the prefrontal association areas
- innervates nueons in ventral basal ganglia that receive major corticostriatal projections
Amgydala and connections to prefrontal cortex and basal ganglia regulates selction and initiation of behaviors need to obtain rewards (and avoid punishments)
Feelings may be a kind of emotional working memory. Containing both immediate conscious experience of implicit emotions and explicit processing of semantic thought, orbito and medial sectors likely areas for these assocaition be maintained in conscious awareness
* Monoamine oxidase inhibitors that increase monoamine concentration at synaptic terminals– e.g. Iproniazid
* Monoamine transporter inhibitors– e.g. Imiprmine and fluoxetine (Prozac). Fluoxetine selectively inhibits serotonin reuptake as a selective serotonin reuptake inhibitor
Act at the level at the interface of the alpha and gamma subunits. Different neurons express different gamma subunits. Six different genes for the alpha subunit. Benzodiazepines only can interact with the a1,a2, and a5 subunits, have a conserved histidine.
* Emotional processing in the limbic system signals the presence or prospect for reward and punishment, and activates programs to procure rewards and avoid punishment
all act by changing the neuromodulatory influence of dopamine for processing reinforement signals in nucleus accumbens, leading to the strenghthening of circuits underlying addictive behavior in limbic systems
Much like the direct pathway. Inputs from different parts of cortex, including amygdala.
to MSNs in ventral striatum the nucleus accumbens. These gabaergic projections then inhibit inhibitory projections in the in the ventral globus pallidus called the ventral pallidum. So there is a disinhibitory effect, much as we discussed before for other basal ganglia loops.
<div style="width:500px"><figcaption class="big">Synaptic locations of action for psychoactive drugs of abuse</figcaption><img src="figs/Neuroscience5e-Fig-29.11-1R_copy_9e75248.jpg" width="500px"><figcaption>Neuroscience 5e Fig. 29.11</figcaption></div>
<div style="float:left;width:400px;margin:0 20px"><figcaption class="big">Functional changes at VTA projections in addicted individuals</figcaption><img src="figs/Neuroscience5e-Fig-29.11-2R_copy_d09517f.jpg" width="400px"><figcaption>Neuroscience 5e Fig. 29.11</figcaption></div>
Exposure to drugs of abuse causes long-lasting enhancement of excitatory input to VTA dopamine neurons, increasing AMPA/NMDA receptor ratio at these synapses.
Specifically, studies in primates and rodents have shown that many VTA dopamine neurons encode reward prediction errors. This error signal is hypothesized to direct synaptic plasticity in target neurons in the nucleus accumbens and prefrontal cortex for reinforcement-based learning. If VTA dopamine neurons signal a reward, the action or behavior that immediately preceded the reward is reinforced through dopamine modulation of downstream circuits (see Figure 10–44). Drugs of abuse bypass natural signals that activate these dopamine neurons, thus dissociating the reward system from its natural stimuli. Specifically, by increasing dopamine concentration at dopamine neurons’ presynaptic terminals, drug consumption mimics dopamine neuron activation; this reinforces the preceding actions, include drug consumption itself. Thus, addictive drugs hijack the brain’s reward system and exploit mechanisms that otherwise regulate learning and motivational
What is or is not a "drug"? Is it well defined by authoritative entities?
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**aside: this gov organization has a strange focus on a list of certain substances and not many other notable substances or behaviors giving rise to substantial human addictions and health dependencies.**
- Acts as a rheostat of reward. Tells other brain centers how rewarding an activity is. The more rewarding an activity is deemed, the more likely the organism is to remember it well and repeat it
- Neurons from ventral tegmental area (VTA) to nucleus accumbens (major neurotransmitter is dopamine)
- Critical pathway for drug addiction
2. Amygdala:
- Helps assess whether an experience is pleasurable or aversive and whether it should be repeated or avoided to forge connections between an experience and other cues
3. Hippocampus:
- Recording the memories of an experience
4. Frontal cortical regions:
- Coordinates and processes all this information and determines ultimate behavior of the individual
