Greg Detre
Thursday, 08 June, 2000
Prof. Rolls � B&B
Reading � Brain stimulation reward + thirst - misc
Discovery by
James Olds (1954)
What is the
nature of the reward?
Neural basis
of brain stimulation reward
Pharmacology
of brain stimulation reward
What are the
normal functions of the ventral striatum/nucleus accumbens?
Neuronal
responses in the ventral striatum
Brain &
Emotion � ch 5 pp 148-167
a reward is something that an animal will work to obtain
humans, monkeys and rats will perform arbitrary operant responses to obtain electrical stimulatoin of some brain regions (e.g. lateral hypothalamus)
at some sites, BSR is like food reward for a hungry animal:
hunger increases BSR in the lateral hypothalamus, and in the orbitofrontal cortex (OFC)
the reward can be lkike a specific natural reward:
rats choose BSR at one site when hungry, and at another when thirsty (Gallistel & Beagley, 1971)
neurons activated by BSR in the hypothalamus and orbitofrontal cortex are also activated by the taste, sight or smell of food, if hungry
BSR occurs because it taps into natural reward systems in the brain
BSR provides evidence that neurons activated in the hypothalamus and orbitofrontal cortex by food when hungry mediate reward
At other sites, (e.g. septum), BSR is not modulated by hunger, thirst etc.
equivalent to pleasure, mood elevation etc.
Sem-Jacobsen: at some sites (e.g. amygdala) in humans, the subjective state induced by BSR is pleasure, happiness, relaxation, relief from tension
Conclusion
BSR at some sites produces mood states like those involved in emotion
lateral hypothalamus, medial forebrain bundle and the orbitofrontal cortex � equivalent to food, water reward etc.
activates taste, visual + olfactory reward systems in these regions, as shown by sites for BSR, and by activation of these neurons by BSR
limbic: amygdala, ventral striatum:
tap into a system involved in learning stimulus-response associations, e.g. visual-taste associations, as shown by sites where BSR occurs, and by activation of neurons involved in this type of learning in these systems
brain stem + ventral striatum:
dopamine system implicated in reward
brainstem central gray:
opiate reward system
block synthesis of catecholamines with alpha-methyl-para-tyrosine:
decrease of BSR
block catecholamine receptors with chlorpromzines:
decrease of BSR
monoamine oxidase inhibitors + amphetamine:
increase BSR
BSR sites along the medial forebrain bundle/dorsal noradrenergic bundle
However
the above pharmacological treatments affect dopamine as well as noradrenaline
disulfiram, which inhibits noradrenaline synthesis:
decreases BSR
all the above pharmacological treatments produce a large decrease in arousal/locomotor activity � therefore, non-specific side effects
BSR still occurs after destruction of the dorsal noradrenergic bundle with d-OHDA
Conclusion
noradrenaline is not involved in reward
above evidence on catecholamines
spioperidol or pimozide, which block dopamine receptors:
decrease BSR, but not locomotor activity
pharmacologically + behaviourally specific
amphetamine (which increases the rleease of dopamine and noradrenaline) is self-administered i.v.
amphetamine self-injection is blocked by pimozide (rate increases) (Yokel & Wise, 1975)
apomorphine (which activates D2 receptors) is self-administered i.v.
which brain regions mediate the dopamine reward?
self-administration of amphetamine to orbitofrontal cortex (Phillips, Mora & Rolls, 1981)
cocaine self-administration i.v. is blocked by 6-OHDA lesions of the nucleus accumbens, a site of termination of the meso-limbic dopamine pathway (Roberts et al., 1980)
amphetamine self-administration i.v. is blocked by 6-OHDA lesions of the nucleus accumbens, a site of termination of the meso-limbic dopamine pathway (Lyness et al., 1980)
self-administration of amphetamine to the nucleus accumbens: effect abolished by 6-OHDA lesions of the meso-limbic dopamine npathway.
does dopamine release normally mediate reward?
impaired effects of conditioned incentives
|
|
�% of 1013 neurons |
|
Visual, recognition-related |
|
|
novel |
3.5 |
|
familiar |
1.1 |
|
Visual, association with reinforcement |
|
|
aversive |
1.4 |
|
food |
4.3 |
|
food and S+ |
1.8 |
|
food, context dependent |
1.3 |
|
opposite to food/aversive |
1.1 |
|
differential to S+ or S- only |
4.0 |
|
Visual |
|
|
general interest |
5.0 |
|
non-specific |
7.0 |
|
face |
1.7 |
|
Movement-related, conditional |
4.5 |
|
Somatosensory |
6.8 |
|
Cue-related |
15.9 |
|
Responses to all-arousing stimuli |
0.8 |
|
Task-related (non-discriminating) |
1.5 |
|
During feeding |
4.7 |
|
Peripheral visual + auditory stimuli |
13.4 |
|
Unresponsive |
54.7 |
Animals (including humans) learn to stimulate electrically certain areas of the brain. At some sites, the stimulation may be equivalent to a natural reward such as food for a hungry animal, in that hunger increases working for brain-stimulation reward at these (but not at other) sites. It has been found in the monkey that one population of neurons activated by the brain-stimulation reward at these sites is in the region of the lateral hypothalamus and substantia innominata. Some of these neurons are also activated by the sight and/or taste of food if the monkey is hungry, that is when the food is rewarding. The latency of the responses of sensory neurons to the sight of food is 150-200ms. This is longer than the responses of sensory neurons to visual stimuli in the inferotemporal cortex and dorsolateral amygdala, but shorter than the latency of the animal�s behavioural responses to the sight of food, as shown by electrographic recording of the muscles that implement the motor responses. Thus, it is possible that these hypothalamic neurons mediates some of the reactions of the hungry animal to food reward, such as the initiation of feeding and/or autonomic and endocrine responses. In a comparable way, brain-stimulation reward of the primate orbitofrontal cortex occurs because it is activating systems normally concerned with decoding and representing taste, olfactory and tactile rewards. In this way, reward-related processes can be identified and studied by analysing the operations (from sensory input through central control processes to motor output) which are involved in the responses of animals to rewarding stimuli. Self-stimulation of some sites may occur because neurons whose activity is associated with food reward are activated by stimulation at these sites. At other sites, brain-stimulation reward may be produced because the stimulation mimics other types of natural reward such as, in the nucleus accumbens, the effects of secondary reinforcers. At other sites, as shown by verbal reports in humans, the electrical stimulation is rewarding because it is producing mood states such as a feeling of happiness normally produced by emotional stimuli.
The findings with brain-stimulation reward are helpful, because they provide additional evidence about whether a particular part of the brain is involved in reward processes. Consistent with this point, in general brain-stimulation reward does not occur early in sensory processing (e.g. in visual cortical areas up to and including the inferior temporal visual cortex), where on independent grounds it is believed that in primates the reward value of stimuli is not represented. Nor does brian-stimulation reward occur ingeneral in motor structures such as the globus pallidus, nor in motor cortical areas. Thus the evidence from brain-stimulation reward complements other evidence that it is at special stages of the pathways which lead from sensory input to motor output that reward is represented, and that this is part of brain design.
Brain-stimulation reward also historically helped to draw attention to important points such as the fact that reward per se does not produce satiety; and� that the time between the operant response and the delivery of the reward (or a stimulus associated with the reward) has important implications for what happnes when the reward is no longer available.
There was a great deal of research on electrical brian-stimulation reward in the years after its discovery (reported by J. Olds and Milner in 1954) until 1980. After that, research on brain-stimulation reward tailed off. Why was this? I think that one reason was that by the middle 1970s it was becoming possible to study reward mechanisms in the brain directly, by recording from single neurons in order to provide a fundamental understanding of how natural rewards are being processed by the brain. This led to the analysis of the neural mechanisms involved in the sensory processing, and eventually the decoding of the reward value, in taste, olfactory, visual and touch systems of primates. In the case of visual processing, this involved investigating the learning mechanisms that enable visual stimuli and primary reinforcers such as taste. By analysing such sensory information processing, an explanation of why electrical sitmulation of some parts of the brain could produce reward became evident. At the same time, the investigations of brain-stimulation reward were very helpful, because they provided additional evidence that neurons putatively involved in reward because of the nature of their responses (e.g. hypothalamic, orbitofrontal cortex, or amygdala neurons responding to the sight, smell or taset of ofood) were actually involved in food reward, because electrical sitmulation which activated these neurons could produce reward. In a comparable way, electrical brian-stimulation reward was also of significance because it pointed the way towards brian regions suhc as the ventral tegmental area dopamine neurons, which, via their projections to the nucleus accumbens, can influence brain processing normally involved in connecting stimuli in the environment decoded as being rewarding by the amygdala and orbitofrontal cortex, to behavioural output. The implication of this brian system in reward led eventually to the discoveries that this neural system, and its projections to the orc, are involved in the rewarding and indeed addictive properties of drugs of abuse such as amphetamine and cocaine.
A second reason why research on electrical brain-stimulation reward decreased after about 1980 is that it then became possible to study the pharmacological substrates of reward not only by investigating how pharmacological agents affect electrical brain-stimulation reward, which required very careful controls to show that the drugs did not affect rewarded behaviour just because of motor or arousal side effects, but also by investigating directly to the brain. The results of these investigations, taken together with the increasing understanding of brain mechanisms involve reward processing and learning, led directly to rapid advances in understanding the processing the neural systems that provides the neural basis of the self-administration of drugs.
Brain-stimulation reward, though less investigated today, does nevertheless provide a way to present repeatedly for hour on end a reward which does not satiate. Indeed, the persistence of responding to obtain brain-stimulation reward was one of the startling facts that led to the clear exposition of how reward and satiety signals are very distinct in their sensory origin, and how motivational signals such as hunger and thirst actually modulate the reward value of sensory input produced, for example, by the taste of food. Studies with brain-stimulation reward emphasised the fact that (apart from sensory-specific satiety), the delivery of reward per se does not produce satiety.
reinforcers������������������������������������������������� 164, 180
a stimulus that is naturally reinforcing, e.g. food, water
a stimulus that becomes reinforcing through association with a primary reinforcer
an automatic, reflex, involuntary, biologically built-in response
a stimulus that triggers an unconditioned response
is it important that Rolls� definitions of reward, representation etc. are all functional?
operant response?
tegmental
reward vs reinforcement
phenomenology of reward
i.v. = intravenously???
cue-related
inferotemporal vs inferior temporal