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Philosophy, Psychology and Informatics Group

04/03/09 r.kyle@ed.ac.uk

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The biological basis of cognitive controlfrom the immune, endocrine, or central nervous system?

BEYOND NEUROTRANSMISSION JOURNAL CLUB - 05/02/09

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Aims

To introduce an example of cognition outside the brain.

To discuss the biological mechanisms involved

To show how these mechanisms might be used as the basis for a model of mind that is not purely in the head.

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Cognitive control : definitions

“We define cognitive control as the ability to flexibly adapt behavior to current demands, by promoting task-relevant information and behaviors over temporally-extended periods

and in the face of interference or competition. This ability is central to most higher cognitive functions, and contributes to the unique character of human behavior.”

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Cognitive control : definitions

Executive functions - Broadbent (1950), automatic + controlled processes - Baddeley’s central executive - Who is the executive? Is sense of self important?

“We define cognitive control as the ability to flexibly adapt behavior to current demands, by promoting task-relevant information and behaviors over temporally-extended periods

and in the face of interference or competition. This ability is central to most higher cognitive functions, and contributes to the unique character of human behavior.”

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Cognitive control : definitions

Executive functions - Broadbent (1950), automatic + controlled processes - Baddeley’s central executive - Who is the executive? Is sense of self important?

Decision making

“We define cognitive control as the ability to flexibly adapt behavior to current demands, by promoting task-relevant information and behaviors over temporally-extended periods

and in the face of interference or competition. This ability is central to most higher cognitive functions, and contributes to the unique character of human behavior.”

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The prefrontal cortex

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The prefrontal cortexNeuropsychology

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The prefrontal cortexNeuropsychology

Evidence from fMRI, TMS

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The prefrontal cortexNeuropsychology

Evidence from fMRI, TMS

Miller & Cohen - “the function of the PFC is cognitive control”

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The prefrontal cortexNeuropsychology

Evidence from fMRI, TMS

Miller & Cohen - “the function of the PFC is cognitive control”

“At the biological level, our work focuses on the functions of prefrontal cortex and anterior cingulate, and their regulation by brainstem neuromodulatory systems, such as

those using the neurotransmitters dopamine and norepinephrine....”

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The prefrontal cortexNeuropsychology

Evidence from fMRI, TMS

Miller & Cohen - “the function of the PFC is cognitive control”

More recently : Dopamine, neuromodulation

“At the biological level, our work focuses on the functions of prefrontal cortex and anterior cingulate, and their regulation by brainstem neuromodulatory systems, such as

those using the neurotransmitters dopamine and norepinephrine....”

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Parasitic manipulation - An example of control?

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Parasitic manipulation - An example of control?

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How might parasites control their hosts?

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How might parasites control their hosts?

Neurotransmitters

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How might parasites control their hosts?

Neurotransmitters

Neuromodulation

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How might parasites control their hosts?

Neurotransmitters

Neuromodulation

Gene expression

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How might parasites control their hosts?

Neurotransmitters

Neuromodulation

Gene expression

Neuroendocrine changes

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How might parasites control their hosts?

Neurotransmitters

Neuromodulation

Gene expression

Neuroendocrine changes

Immune perturbation

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How might parasites control their hosts?

Neurotransmitters

Neuromodulation

Gene expression

Neuroendocrine changes

Immune perturbation

Which are mechanisms, and which are measurables?

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Is the parasite truly in control?

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Is the parasite truly in control?

Is the parasite conscious and in control?

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Is the parasite truly in control?

Is the parasite conscious and in control?

Has the parasite usurped the host’s conscious control?

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Is the parasite truly in control?

Is the parasite conscious and in control?

Has the parasite usurped the host’s conscious control?

Or is the parasite merely triggering existing behavioural programs without any real sense of control?

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The quality of control?

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The quality of control?

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Examples

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Examples

Parasitic wasp

Polymorphous paradoxus

Trematode

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Examples

Parasitic wasp

Polymorphous paradoxus

Trematode

“In at least two of three of these examples, it appears that the host, not the parasite produces the neuromodulators that alter host behaviour.”

“Parasites may induce the host’s immune system to produce the appropriate neuromodulators.”

Adamo (2002)

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Examples

Parasitic wasp

Polymorphous paradoxus

Trematode

“In at least two of three of these examples, it appears that the host, not the parasite produces the neuromodulators that alter host behaviour.”

“Parasites may induce the host’s immune system to produce the appropriate neuromodulators.”

Adamo (2002)

IS THE PARASITE CONTROLLING THE HOST USING THE IMMUNE SYSTEM?

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Where is the locus of control?

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Where is the locus of control?

The brain

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Where is the locus of control?

The brain

The immune system

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Where is the locus of control?

The brain

The immune system

Both

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Where is the locus of control?

The brain

The immune system

Both

Neither

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How should we model/explain control?

What components are needed in a model of decision making?

What components are in existing models?

Is it reasonable to view control as a purely neural process occurring in the brain?

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Who is controlling the ant?

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Who is controlling the ant?

If the immune system functionally defines self....

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Who is controlling the ant?

If the immune system functionally defines self....

...immune perturbation leads to loss of self-control....

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Who is controlling the ant?

If the immune system functionally defines self....

...immune perturbation leads to loss of self-control....

...and in the process the immune system redefines the self in terms of the needs of the parasite

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The immune brain

Examples show pathological cases, but immune, brain, and endocrine systems are in constant interaction in healthy individuals.

Are similar processes occurring in physiological conditions?

Cognitive control via neural computation

Cognitive control via assertion of the self?

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Intermission

Outline cases where the immune system and brain are functionally interacting

Offer an account of how these interactions might support an immune-centric view of cognition.

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The immune brain : examplesAder and Cohen (1975) - The immune system can be classically conditioned by CNS stimuli

A single pairing between a CNS and an immune stimuli

can result in the CNS stimuli alone triggering an immune response

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The immune brain : examples

Cytokines produced during an immune response can modulate synaptic plasticity

cytokines can effect release of hormones, modulators and transmitters in the brain

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The immune brain : examples

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The immune brain : examples

animals and people with a proactive coping style also display higher HPA activity - Hawks and Doves

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The immune brain : examples

animals and people with a proactive coping style also display higher HPA activity - Hawks and Doves

‘hyperdopaminergic’ rats show increased HPA activity, whilst ‘hypodopaminergic’ rats show increased susceptibility to autoimmune disease. Kavelaars et al (1997)

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The immune brain : examples

animals and people with a proactive coping style also display higher HPA activity - Hawks and Doves

‘hyperdopaminergic’ rats show increased HPA activity, whilst ‘hypodopaminergic’ rats show increased susceptibility to autoimmune disease. Kavelaars et al (1997)

behavioural patterns of wild-type rats can be used to predict susceptibility to autoimmune disease. Kavelaars et al (1999)

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The immune brain : examples

animals and people with a proactive coping style also display higher HPA activity - Hawks and Doves

‘hyperdopaminergic’ rats show increased HPA activity, whilst ‘hypodopaminergic’ rats show increased susceptibility to autoimmune disease. Kavelaars et al (1997)

behavioural patterns of wild-type rats can be used to predict susceptibility to autoimmune disease. Kavelaars et al (1999)

Do personality and immunity emerge from a shared root?

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The immune brain : A sketch

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The immune brain : A sketch50-90% (?!?) of cells in the brain are glial cells

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The immune brain : A sketch50-90% (?!?) of cells in the brain are glial cells

Our models of the nervous system typically assume that neurons alone are capable of causing actions, representing mental states, and learning, while glial cells act in a supporting role.

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The immune brain : A sketch50-90% (?!?) of cells in the brain are glial cells

Our models of the nervous system typically assume that neurons alone are capable of causing actions, representing mental states, and learning, while glial cells act in a supporting role.

Microglia (15% of the brain) are the brain’s macrophages and are capable of producing and responding to cytokines

Glial cells metabolise glutamate and many other transmitters required for neurons to function

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The immune brain : A sketch

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The immune brain : A sketch

Neuron : Glia relationship = Mother : Child?

By controlling neural metabolism glial cells set constraints for self(ish) behaviour

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The immune brain : A sketch

Neuron : Glia relationship = Mother : Child?

By controlling neural metabolism glial cells set constraints for self(ish) behaviour

Neurons are rarely able to act in a way that compromises the integrity of the self.

in this sense the co-ordinated activity of the brain and body can be seen as the result of an assertion of self.

if the immune system defines the immune self, does the immune brain define the cognitive self?

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Parasites take control of the self

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Parasites take control of the self

In the case of the parasites

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Parasites take control of the self

In the case of the parasites

parasites aim to take over the host’s self

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Parasites take control of the self

In the case of the parasites

parasites aim to take over the host’s self

evolution have shown the most direct way to do this - by secreting immunomodulators which perturb the biological sense of self

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Parasites take control of the self

In the case of the parasites

parasites aim to take over the host’s self

evolution have shown the most direct way to do this - by secreting immunomodulators which perturb the biological sense of self

in taking control of the self, the host organism begins to secret cytokines, then hormones, then neuromodulators which effectively change the constraints for what constitutes self(ish) behaviour

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The immune brain model

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The immune brain model

offers a different perspective on brain function from the computationalist account

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The immune brain model

offers a different perspective on brain function from the computationalist account

provides an account of behaviour which is inherently integrated with the body

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The immune brain model

offers a different perspective on brain function from the computationalist account

provides an account of behaviour which is inherently integrated with the body

The metaphor of self assertion and identity is psychologically interesting and potentially more useful in clinical or therapeutic settings.

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The immune brain model

offers a different perspective on brain function from the computationalist account

provides an account of behaviour which is inherently integrated with the body

The metaphor of self assertion and identity is psychologically interesting and potentially more useful in clinical or therapeutic settings.

opens up the possibility of relating a scientific understanding of the brain and of identity to philosophical debate + vice versa.

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Summary

processes such as cognitive control can have their genesis outside the CNS

It is possible to develop a scientific account of the mind which is not restricted to the central nervous system

interactions and cooperation between the immune system and brain offer an avenue for understanding the body:brain relationship

the concept of self as it has been used in immunology has great potential as a metaphor for understanding the biological basis of the cognitive self

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questions....

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