Neuroethics exam 3

What does it mean to be responsible for one’s actions?

to accept accountability for all choices, behaviors, and their positive and negative consequences, rather than blaming others or external circumstances. linked to free will, agency and rationality.

what is brain dysfunction?

condition were the brain is does not function properly, affection various aspects of brain function like cognitive function.

the neuroscience of responsible behavior: Determinism 

belief that all events are predetermined by prior causes

the neuroscience of responsible behavior: free will

the capacity of agents to make choices unrestrained by predetermined or prior causes

compatibilism

free will is compatible with determinism, a person can be both free and determined. An action is free if not externally constrained even if it caused by an individuals own desires. 

what areas are associated with self control

Prefrontal cortex, especially ventral and medial areas

what parts of brain are associated with motivation

primarily subcortical, complex systems and involve dopamine

when is one capable of self-control?

developing skill with capabilities emerging and changing significantly from early childhood to adulthood.

how does the law treat minors in terms of responsible behavior?

typically through the juvenile justice systems, which balance accountability with a focus on rehab.

what is empathy

the more empathetic the observer, the more the observed person’s pain activates pain regions in the observer

what is the ability to discriminate right from wrong

gut level reactions to the wrongness of a certain action. More rational approach—weights benefits and dangers of each course of action.

are people’s brains less capable of activating one of these systems?

individuals higher in psychopathic tendencies show less activation of brain regions associated with gut responses to immoral actions

what is the brains role in deviance?

structural and functional abnormalities in areas responsible for decision-making, emotion regulation, and impulse control such as the prefrontal cortex and amygdala

if a brain tumor causes a change in an individual’s behavior, is that

individual responsible?

Typically no because the tumor can impair their ability to control their actions and understand the moral implications of their behavior. Changes that occur are the results of physical and psychological effects of the tumor itself and not a conscious choice or lack of character

if one’s actions were caused by brain damage and a disrupted neural network, where they acting under their own free will?

• should they be held morally responsible for their actions?

some may say no because the self that would normally make a choice has been fundamentally altered or overridden by a physical condition. Many ethical systems posit that moral responsibility requires a capacity to understand the consequences of one's actions, differentiate right from wrong, and control one's behavior [2]. If brain damage compromises these capacities, the person may be considered less, or not at all, morally responsible for their actionsLegal proceedings focus on an individual's competence and their state of mind at the time of the offense to determine appropriate legal and punitive measures.

Neurologic conditions affecting behavior

the case of a 9 old boy for maiming another child, defense claimed previous head injury as the organ of destructiveness which caused him to be more aggressive, judge threw out this info but was significant in terms of explaining socially unacceptable behaviors by characteristics of the brain

Charles Withman

killed his wife and mother, and climbed the Univeristy of texas tower and began firing his rifle at the people below, killed 14 people. Before he did this, he wrote that he could not rationally pimpoint any specific reasons for doing this. During autopsy he was found to have an astrocytoma in the diencephalon. Medical examiner concluded that it had not influenced his behavior but a legislative commission stated the tumor could have led to whitman’s inability to control his emotions and actions

John Hinckley

landmark case in the use of neuroscience in law. in his trial, defense introduced CT scan of his brain which showed atrophy, which they alleged indicated schizophrenia. verdict not guilty by reason of insanity, sentenced to institutional psychiatric care

Jared Lee Loughner

mental health experts who have examined him concluded he suffer from schizophrenia, defense claimed not competent to stand trial, pled guilty and sentenced.

neurologic conditions affecting behavior-head injuries

a recent study investigated whether there was a correlation between

head injuries and the development of violent, repetitive criminal

behavior, particularly serial killers

• analyzed documented cases of 11 serial killers with history of head injuries

• neuroimaging results showed reduced connectivity between amygdala and

frontal cortex, decreased gray matter in ~80% of these high-profile killers

lesions network localizing of criminal behavior

a systematic review of 17 known cases where criminal behavior was preceded by the onset of a brain lesion, the lesions were widely distributed through the brain, but some were all part of the same functional network

rsfMRI

functional connectivity was determined using this. lesions temporarily associated with criminality were part of a unique connected brain networ (criminality-associated network).k

theory of mind

cognitive ability to attribute mental states like thoughts to oneself and other, understanding that others can have perspectives different from ones own.

value based decision making

process of making choice by aligning them with your core beliefs, priorities and desired outcomes

Aberrant gray matter in murderers

compared gray matter differences in incarcerated adult males, who had committed homicide to other non-homicide offender

what regions are impacted by aberrant gray matter

reduced gray matter in brain areas critical for behavioral control and social cognition. ventromedial/orbitofrontal cortex, anterior temporal cortex, insula, etc, may indicate impairment across a range of emotion and cognitive systems

prefrontal cortex

critical for executive functions = impulse control, decision-making structural and functional abnormalities may be associated with criminal behavior

Amygdala

plays key roke in processing emotions, especially fear and aggression dysfucntion can be linked to aggressive behavior

anterior cingulate cortex

involved in executive functions, linked to reoffending rates

the neuroscience of criminal behavior

each case needs to be evaluated in light of the wide array of factors besides neurologic injury that influence behavior, including genetics, childhood adveristy, etc

insanity defense

lack of culpability based on mental illness, this is not a psychological term. The criminal law will generally only impose its retributive or deterrent

sanctions upon those who are morally blameworthy – those who know they

are doing wrong but nonetheless persist in wrongdoing.

Doctrine of mens rea (guilty mind)

the act does not make a person guilty unless the mind is also guilty. Culpable mental states: purposeful, knowing, recklessness, negligence

not guilty by the reason of mental illness

rarely used (less than 1% of cases) individuals usually committed to a secure mental health treatment facility

diminished responsibility/diminished capacity

mitigating factor, the US supreme court has been clear in decisions that jury instructions in death penalty cases that do not ask about mitigating factors regarding the defendants mental health violate the defendants 8 amendment rights

what types of neuroimaging might be used in criminal cases?

structural MRI and fMRI, PET and EEG

when would neuroimaging be used in criminal cases, and for what purpose?

cases primarily to support arguments for sentencing mitigation, demonstrating brain abnormalities that may have contributed to the crime sometimes to help determine fitness to stand trial

what is mitigation

act of reducing severity of sentencing

Farah 5.1 overview of the impact of neuroscience

Two main ideas of criminal law: the determination of guilt so proving that an individual acted with intention and the imposition of punishment, aiming at meting out justice, deterring future misconduct and expressing societies condemnation

5.2 for the law, neuroscience changes nothing and everything

two theories of punishment: Consequentialism—> punishment justified by future benefits, future crimes prevented by deterrent effects of law and incarceration. Retributivism—> people who engage in criminall behavior deserve to be punished

neuroimaging using in criminal cases

support argument that defendant is incompetent to stand trial. proffered by defense at the guilt-determination phase, in effort to negate mens rea element of a crime

what are the two standards for the use of scientific evidence in cases

fyre admits that only scientific testimony regarding theories and methodologies that have gained general acceptance. Daubert invest the trial judge with the responsibility to assess whether the proffered expert testimony is both reliable and scientifically valid

A more inclusive legal system

pecifically, advancements in neuroscience and imaging could be

used to support individuals with difficult to prove injury claims

○ PTSD

○ Concussions

○ Emotional damage

● However, given the current technology, this is not yet quite

possible

involuntary medication

Jared Loughner has schizophrenia and was not fit to stand trial, the question was whether or not he should be forcefully medicated to stand trial. he ultimately was forced to be medicated because he was a danger to himself and others, in doing so restoring his compentency

sell vs united states

Sell v. United States

•sets limits in which a court can order medication for a defendant

•reserved for cases in which the government has an important

interest in adjudicating the crime

•criticism: forced medication has become routine; the decision laid

out very general rules for when defendants can be medicated.

Judges default to medicating defendants.

17

Narrative identity

the perspective that a persons sense of self is constructed through the stories they tell about their life (past, present, and future) provides coherence and meaning

psychological continuity

the perspective that identity is maintained over time through interconnected psychological states, such as memories, beliefs, intentions, and desires

deep brain stimulation (DBS)

a form of how neurotechnology challenges to authenticity, has therapeutic effects, has also been associated with unintended personality shifts, including altered creativity

pharmacological enhancement

some argue that drugs for ADHD or depression can reveal a

person’s authentic potential

• conversely, one may dislike the personality changes caused by

medication

• are the drug-induced changes inherently authentic?

prefrontal cortex

a neural substrate of authenticity. ventromedial prefrontal cortex plays a role in social cognition, decision-making, integration of emotional and cognitive processes. 

what is the medial prefrontal cortex as a neural substrate of authenticity

. critical for introspection, identity, and self-referential thought. authentic actions activate the mPFC improving self awareness and decision making

what is the lateral prefrontal cortex as a neural substrate of authenticity?

involved in executive function during authentic engagement

what is the default mode network for substrates of authenticity?

posterior cingulate cortex, key hub of the default mode network, autobiographical memory

what is the insula as a neural substrate of authenticity?

role in interception (body internal state). emotional awareness from integrating sensory info with emotional states. 

what is the right anterior insula for

involved in building a coherent sense of ones physical and emotional self

what are the rewards circuits associated with it

ventral striatum where authentic interactions activate reward pathways, resulting in dopamine release and increasing motivation

what is involved in emotional regulation

the amydgala for fear and threat stimuli. high authenticity is associated with lower amygdala activation

• inauthentic situations associated with increased amygdala

activation and cortisol activity

what are mirror neurons

neurons that are active when one engages in a task and when

watching someone else engage in the task

• the brain uses these neurons to mirror the movements that it sees

• also likely involved in empathy

what is acquisition

synonymous with learning, the initial encoding of information

what is consolidation

processes involved in stabilizing memory over time

what is forgetting

mechanisms whereby memories can be erased or hidden from retrieval

what is retrieval

the recollection or recall or existing memories

what is neuroplasticity

the ability of neurons and neural circuits to change in response to experience and the environment, may be post or pre synaptic

Who is donald hebb

he proposed that when a presynaptic neuron repeatedly activates a postsynaptic neyron, the synaptic connection between them becomes stronger and more stable.“neurons that fire together wire together”

what are cell assemblies and what are their function?

they are formed when neurons are repeatedly coactivated (hebb synapses). the excitation of a small part of the assembly causes the entire group to fire and could act together to store memory traces

What is long term potentiation (LTP) in the hippocampus?

LTP is the main form of synaptic plasticity. for example schaffer collateral are the axons of pyramidal neurons in CA3 that connect to CA1 neurons exhibiting the classic Hebbian form of LTP

What causes LTP

pairing presynaptic and postsynaptic activity. A single stimuluts to a Schaffer collateral synaptic input evokes EPSPs in the post synaptic CA1 neuron. WHEN CA1 neuron potential is briefly depolarixed in conjunction with the Schaffer collateral stim, then there is a persistent increase in the EPSPs

the presynaptic neuron release large amount of glutamate, the strong post synaptic depolarization removes mg block from NMDArs allowing Calcium to enter postsynaptic neuron. the calcium influx activates enzymes like CAMKII that causes more AMPA receptors to be moved to postsyn membrane, since there are more, postsyn neurons are more sensitive to glutamate release. making the synapse stronger and more efficient for transmitting signals.

what is the principal cellular events of memory formation

Acquisition → (engram cell, cellular memory traces) → consolidation (internal or external stimulus in engram matrix) → engram could lead to retrieval and forgetting

how can passive forgetting happen

can occur from a loss of retrieval cues or the decay of neural traces

What is active forgetting and how may that happen

involves the prefrontal cortex suppressing hippocampal activity, this is an effortful process to forget unwanted memories and reduces the strength of the memories neural trace

What is fear learning

our brains are programmed to learn and fear is innately programmed. This is because you have to learn about potential new dangers and important to learn the predictors of danger

what is fear learning in associated learning

A dog was really aggressive and it bit you really bad when you tried to pet it. You then would be fearful of dogs in general because if this dog bit you others might too. you associate dogs with danger and getting bit

3.1 memory blunting ethical analysis

This one was about the concerns of the use of memory-dampener. They placed emphasis on that remembering the emotionally charged memories fitly and truly.. We may have an obligation to remember certain events (personal or societal). May endanger our sense of moral responsibility of our actions if we selectively edit our memories also potentially our sense of self may contribute to the pursuit of happiness that is not entirely human

Chemical desensitization

Drugs like propranolol could be taken before potentially going to do a very traumatic job. For example a firefighter at a catastrophic fire, but is this ethical?

shared concerns about the use of memory dampeners and neuroenhancers

Respect for the given, balancing out potential for coercion vs. broad restriction on use. how to develop appropriate policies that account for the unprescribed use

What are some concerns for memory dampener

The tough love → memory blunting will prevent us from effectively processing trauma. memory is important for creation of identity. do we prioritize feelings of pleasure over genuine experiences

what is the neural prosthesis for hippocampal memory function

It consists of a multi electrode array that records ensemble spike trains from input area (CA3) region, VLSI chip then uses a MIMO nonlinear model and put spike trains to predict output, and electrical stimulator delivers predicted output to downstream hippocampal area (CA1)

what is dementia

the umbrella term for the loss of memory and other thinking abilities severe enough to interfere with daily life.

Alzheimers

progressive, neurodegenerative disorder

• gradually destroys a person’s memory, ability to learn, reasoning,

making judgements, communicate, carry out daily activities

• as the disease progresses, individuals may also experience changes in

personality and behavior:

• anxiety

• suspiciousness

• agitation

• delusions

• hallucinations

are there any reversible causes of dementia

yes, depression, B12 deficiency, hypothyroidism, and alcohol or medication related

Etiology

gradual and progressive neurodegeneration caused by neuronal death, typically begins in entorhinal cortex

what are some risk factors for AD?

Risk factors

• age

• modifiable risk factors:

• cardiovascular disease

• obesity

• diabetes

• traumatic head injury

• depression

• smoking

• family history of dementia

• presence of APOE e4 allele

what is the pathophysiology of AD

senile plaques and neurofibrillary tangles (tau)

Amyloid cascade hypothesis

deposition of the amyloid-beta peptide in the brain is a central event in disease pathology

cholinergic hypothesis

reduced levels of acetylcholine in the brain, resulting from neuronal loss in the Nucleus Basalis of Meynert, play significant role in AD

What is the genetic basis?

Down Syndrome

• inherited as an autosomal dominant disorder:

• mutations in one of three genes: AAP gene on chromosome 21, Presenilin 1

(PSEN1) on chromosome 14, Presenilin 2 (PSEN2) on chromosome 1

• rare mutations, associated with early-onset AD

• APOE e4 allele

What is the histopathology of neuritic plaques in AD

AB deposision, found around meningeal and cerebral vessels in cortical gray matter

what is the histopathology of neurofibrillary tangles

aggregation of AB leads to hyperphosphorylation of tau: tau becomes misfolded and aggregates within neurons first appear in hippocampus

what is Braak and Braak staging

categorizes progression of neurofibrillary tangles, which have a stronger connection with AD severity. amyloid better defines AD than other forms of dementia

how do we diagnose AD

no single definitive test

• cognitive assessment: MMSE commonly used

• review medical history to rule out other conditions or medications

• MRI – may show features compatible with AD (atrophy of entorhinal

cortex, medical temporal cortex, or hippocampus)

• Functional imaging – amyloid PET, tau PET, fMRI

what are CSF biomarkers used for

Aβ42, p-tau, t-tau

• decreased CSF Aβ42 and increased tau isoforms

• ratios of CSF biomarkers - Aβ42/40, have provided a more accurate and sensitive index of

the underlying amyloid-related pathology in patients

what are amyloid PET biomarkers 

detection of amyloid aggregates

• however, normal elderly individuals can have amyloid aggregates

• best use is to differentiate between neurodegenerative disorders

how is AD treated/managed

cholinesterase inhibitors

• galantamine, benzgalantamine, rivastigmine, & donepezil

• help reduce or control some cognitive and behavioral symptoms

how are disease modifying medications used to treat AD

Aducanumab

• approved via FDA’s accelerated approval program in 2020

• reduces abnormal amyloid plaques in the brain

• however – did not meet the primary phase III trial endpoint of clinical

improvement

immunotherapy drugs

• lecanemab and donanemab

• approved via FDA’s accelerated approval program

• target amyloid-beta protein to help reduce amyloid plaques

• primary phase III trial showed ~25% slowing of disease progression over 18

months

what are used to manage the symptoms of moderate to severe AD

NMDA antagonist

• memantine

• regulates glutamate

• can be used in combination with cholinesterase inhibitors

• donepezil, rivastigmine, and combination of memantine and donepezil are also

used

what are other causes of dementia

artifical sweeteners, anesthesia, COVID-19, Anticholigernic drugs