Greg Detre
Wednesday, 31 May, 2000
Prof. Rolls - B&B V
Rolls
handout on hunger � central factors
Set-point or
settling point: thermostat or leaky barrel?
What other
factors influence what and how much we eat?
Hypothalamic
regulation of eating: how does the brain control eating?
food + water are rewards (in that the organism will work to obtain them)
signals (which originate internally) operate to alter (modulate) the reward value with food/water has for the hungry/thirsty organism
2 separate aspects of information processing of the sensory stimulation produced by food:
decoded as a physical stimulus
then coded in terms of reward value
the learning of which visual stimuli are (or are associated with) food/water:
takes place in specialised parts of the brain for this type of learning
functions of the:
different factors outside the brain (e.g. taste, smell, gastric distension)
the control signals (e.g. the amount of glucose in the blood)
which sensory inputs produce rewards
and which inputs acts as hunger/satiety signals to modulate the reward value of the sensory inputs
how the brain:
integrates these different signals
learns about which stimuli in the environment provide food
initiates behaviour to obtain the correct variety + amount of food
Frohlich�s syndrome (1902)
over-eating and obesity associated with damage to the base of the brain
Hetherington (1943)
lesions of VMH, even after hypophysectomy, cause overeating and obesity. Therefore, the VMH provides a neural control of how much is eaten
Le Magnen (1973)
VMH lesions p������ roduce hyperinsulinemia
York & Bray (1972)
the overeating and obesity produced by VMH lesions are abolished if the vagus is cut, preventing the hyperinsulinemia
therefore, VMH lesions affect eating indirectly, by causing an elevation of insulin, which then stimulates feeding
the VMH could certainly affect the body weight �set point� in this way, indirectly
Hess, Brugger (1943)
electrical stimulation of the LH elicits feeding
Anand & Brobeck, 1951
lesions of the LH produce aphagia and adipsia
Stellar, 1954
the LH as a �hunger� centre
Winn & Dunnett, 1984
ibotenic acid LH lesions, which spare fibres of passage, produce aphagia
therefore, the LH is involved in the control of feeding
what is its role?
Rolls, 1976
LH neurons respond to the taste of food
LH neurons respond to the sight of food
LH neurons� responses to the taste + sight of food are modulated by hunger
Sensory-specific satiety discovered in LH neurons, and then in feeding behaviour
LH as interface between sensory inputs which produce reward, and the hunger/satiety signals that modulate reward
LH outputs may produce rewards and autonomic responses to the taste + sight of food
how do inputs reach the LH?
tuning becomes more specific from the NTS through the primary taste cortex to the secondary taste cortex
satiety operates in the secondary taste cortex, but not before � representation of reward here
sensory-specific satiety effects are shown by orbitofrontal cortex neurons
the mechanism + adaptivfe significance of computation of sensory-specific satiety in the orbitofrontal cortex
satiety modulates olfactory responses in the secondary olfactory cortex (in the orbitofrontal cortex)
multimodal, e.g. olfactory + taste neuronal responses are found in the orbitofrontal cortex � representation of flavour
learning can influence the formation of olfactory-taste associations:
the computation of new multimodal representations by learning � the representation in the OFC of the reward association of the odour
from the inferior temporal cortex directly and via the amygdala to the orbitofrontal cortex
in the orbitofrontal cortex, but not in the inferior temporal cortex, neuronal repsonses to the sigh of food are modulated by hunger: reward is represented
visual-taste association learning is also reflected in the responses of OFC visual neurons, as shown by reversal
discrimination learning and particularly reversal, and also food selection, are impaired by orbitofrontal damage
discrimination learning, and also food selection, are impaired by amygdala damage
discrimination learning (especially rapid reversal) and also food selection, are impaired by orbitofrontal cortex damage
the orbitofrontal cortex contains the secondary taste and olfactory cortices
the OFC builds representations of flavour
satiety modulates the taste, olfactory + visual representation of food in the OFC
sensory-specific satiety for the taste, smell and sight of food is computed in the OFC
the OFC has a representation of the texture of food
the OFC is involved in visual-to-taste and olfactory-to-taste association learning
provide reinforcement/reward
food is still reinforcing when it can only be tasted + smelled, and is not absorbed: evidence from sham feeding with oesophageal or gastric fistulae
small volumes, e.g. 0.1ml, provide reinforcement when provided orally
taste + smell guide intake � the preference/aversion function has the normal shape during sham feeding
provide only little satiety:
overfeeding with sham feeding
however, sensory-specific satiety is a contributory factor to satiety; and conditioned satiety can occur
not necessary for hunger/feeding:
hunger pangs are not closely associated with gastric contractions
gastrectomised humans feel hunger
eating still occurs after vagotomy which severs gastric afferents to the brain
necessary for normal satiety:
gastric preloads inhibit subsequent feeding
gastric emptying leads to a resumption of feeding
not sufficient for reinforcement:
intragastric food delivery is not reinforcing (i.e. are not worked for)
necessary for normal satiety:
duodenal sham feeding with a duodenal fistula: overfeeding occurs
duodenal feedback via an enterogastric loop is necssary for gastric distension to occur
food infusions to the duodenum produce some satiety via chemosensors: glucose via a vagal pathway, and fats by an endocrine pathway, as shown by the effects of vagotomy
cholecystokinin and bombesin, hormones releasted when food reaches the gut, themselves contribute to satiety as shown by infusions
|
|
Reinforcement |
Satiety |
|
Oropharyngeal factors |
1 |
0 |
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Gastric and intestinal factors |
0 |
1 |
Therefore, there must be an interaction (in the brain) between gastric + oropharyngeal factors, with satiety signals mediated by gastric + intestinal factors modulating the reward value of oropharyngela factors (taste + smell)
homeostasis � Gk homos (same) and stasis (stoppage) � Cannon, 1929
= process by which an organism maintains fairly constant internal (bodily) environment
e.g. body temperature, blood sugar level, salt concentration in the blood etc.
a state of imbalance arises
something must happen to correct the imabalance and restore equiibrium
appropriate behaviour restores the internal balance
sates/reduces the homeostatic drive
Green (1980) � internal environment requires regular supply of raw materials from the external world
(in)voluntary/(dis)continuous
hunger as the bit that happens during internal imbalance to signal the homeostatic drive
hunger = neither necessary or sufficient for eating
we eat when we�re not hungry and we don�t always eat when we are hungry
Blundell & Hill (1995) and other experiments � strong link between intensity of experienced hunger sensations and the amount of food eaten
appetite control system = hunger, eating and physiological mechanisms are coupled together (imperfectly)
circumstances of uncoupling, e.g. hunger strikes or eating disorders (obesity or anorexia nervosa)
believed that the hunger drive is caused by stomach contractions (hunger pangs)
Washburn swallowed an empty balloon tied to the end of a thin tube � pumped it up, then connected the tube to a water-filled U-tube so that Washburn�s contractions would cause an increase in the level of water at the other end of the U-tube
reported a pang of hunger every time a large stomach contraction was recorded
Carlson (1992) confirmed � patient with tube implanted through his stomach wall, just above his navel
when there was food in his stomach, small rhythmic contractions (peristalsis) mixed the food and moved it along the digestive tract
when it was empty the contractions were large and associated with the patients� reports of hunger
Pinel, 1993 � however, patients who have had their stomachs removed
e.g. oesophagus connected directly � duodenum (small intestine � the upper portion of the intestine through which most of the glucose and amino acids are absorbed into the bloodstream)
still report feeling hungry and sated
still maintain normal body weights by eating more frequent, smaller meals
similarly: cutting neural connections to the brain (i.e. the vagus nerve) from the gastrointestinal tract (stomach + intestines)
has little effect on food intake in humans or animals
suggests that Cannon exaggerated the importance of stomach contractions in causing hunger
but the gastrointestinal tract still plays a part in hunger + satiety
if the vagus nerve is cut, signals from the gut can still get to the brain via the circulatory system
also, stomach loading (the presence of food in the stomach) is important in regulation of feeding
if the stomach exit to the duodenum is blocked off, rats still eat normal-sized meals, i.e. information about the stretching of the stomach wall � brain (via the vagus nerve)
the physiological signals to start and stop eating need not be the same (Carlson, 1992)
delay between the correctional mechanism (eating) and the change in the state of the body (several hours to completely digest)
\ the signals for hunger + satiety (the state of no longer being hungry) must be different
the information from the GIT � brain via the circulatory system:
concerns the components of the food that has been absorbed
the depletion of which nutrients acts as a signal to start eating?
fats (lipids)
carbohydrates (incl glucose)
vitamins/mineral salts
proteins/amino acids
fats + carbohydrates are burnt up in cellular reactions, providing the energy to fuel metabolic processes
metabolism = all the chemical processes occurring in the body�s cells essential for the body�s normal functioning
metabolic rate = the amount of energy the body uses
when we engage in vigorous physical activity, the muscles are fuelled by fats and carbohydrates
fat reserves are called adipocytes, which clump together as adipose tissue (fat)
carbohydrates are stored as energy as glycogen (a complex carbohydrate)
1940s/1950s glucostat:
primary stimulus for hunger is a decrease in the level of blood glucose below a certain set point
(with corresponding increase primary stimulus for satiety being an increase above this set-point)
glucose = the body�s (especially the brain�s) primary fuel
the glucostat = a neuron (probably in the hypothalamus) that detects the level of blood glucose
i.e. although it hadn�t been identified, it was assumed that there is a mechanism that responds to changes in the level of blood glucose
Mayer (1955) � influential because proposed that feeding regulates:
the glucose utilisation (the rate at which it is used)
rather than absolute blood glucose level
usually, utilisation and absolute blood glucose levels are very closely correlated
but Mayer could also account for hyperphagia
(over-eating)
e.g. diabetes mellitus � overeat despite high glucose levels, because
their pancreas cannot produce the insulin necessary for the glucose to enter
cells and be utilised
glucose utilisation = monitored by glucoreceptors that compare glucose
entering + leaving the brain, �/span> stimulates/inhibits feeding
experiments appeared to locate the glucoreceptors (Mayer & Marshall, 1958)
injected mice with gold thioglucose
the glucose binds to the glucoreceptors
which would be destroyed by the gold (a neurotoxin)
then the mice began to eat loads
examination showed damage to tissue in the VMH
ventromedial hypothalamus (VMH) = satiety
centre
however: although a fall in blood glucose may be the most important physiological signal for hunger, it is not the only one
if eating were controlled exclusively by blood glucose, we would expect them to overeat and get fat (Carlson, 1992)
1950s + 1960s:
focuses on the end product of glucose metabolism � the storage of fats (lipids) in adipocytes
body fat is normally maintained at a relatively constant level
Kennedy (1953): everyone has a set-point for body fat, and deviations from this lead to compensatory adjustments in food intake
Nisbett (1972): fluctuations in the amount of stored fats largely determines variations in body weight � everyone has a body weight set-point
(hence the failure of short-term diets to produce long-term weight loss)
animal experiments � lesions in they hypothalamus:
damage to the lateral hypothalamus �/span> rats will stop eating (even when food is readily available) to the point of starvation (aphagia)
was thought to indicate that the LH normally functions to stimulate eating
Keesey & Powley (1975):
deprived rats of food then lesioned their LHs
they then started eating more food (not less)
in normal rats: the lesion lowers the body weight set point
if you lesion rats who are already below this set point: they increase feeding in order to reach the new (higher) set point
i.e. damage doesn�t affect feeding directly, but only by altering the body weight set point
Pinel (1993): the glucostatic + lipostatic theories are complementary, rather than mutually exclusive because:
glucostatic theory
was meant to account for the initiation + termination of eating, i.e. relatively short-term processes
lipostatic theory
was meant to explain long-term feeding habits and the regulation of body weight
both are based on the assumption that homeostasis implies the existence of set-point mechanisms
current biopsychological theories: body weight tends to drift around a natural settling point
(the level at which the various factors influencing it are balanced)
early theorists seduced by the analogy of the thermostat
better analogy for settling
point theory: the leaky barrel model
the water level in a leaky barrel is regulated around a natural settling point rather than a predetermined set point
(i.e. a balance between the rate of water leaking out and the amount coming in???)
setting point theory is more compatible with research findings:
point to factors other than internal energy deficits as causes of eating (Pinel, 1993):
learning determines: what, when, how much and how to digest the food we eat
feeding system = flexible system that opertaes within certain general guidelines but is �fine-tuned� by experience
we are drawn to eat by food�s incentive properties, i.e. the anticipated pleasure-producing effects of food (palatability)
both internal and external factors influence eating in the same way, by changing the incentive value of available foods
signals from the taste receptors produce an immediate decline in the incentive value of similar tasting food
signals associated with increased energy supply from a meal produce a general decrease in the incentive properties of all foods
Rolls & Rolls (1982): discovered LH neurons that respond to the incentive properties of food, rather than food itself
when monkeys were repeatedly allowed to eat one palatable food, the response of LH neurons to it declined, though not to other palatable foods
neurons that responded to the sight of food �/span> respond to a neutral stimulus that reliably predicted the presentation of food
classically conditioned responses � cephalic phase responses
Pavlov (1927): the sight/smell of milk produced abundant salivation in puppies raised on a milk diet, but not in those raised on a solid diet
conditioned salivation to a metronome or a light bulb
or feeling hungry at certain times of the day when we usually eat, even if there is no energy deficit
could we learn to find things palatable in the first place?
innate preferences for tastes associated in nature with vital neutrients
e.g. sweetness detectors helped ancestors identify safe foods (even when not hungry, sweet tastes are pleasant, and sweet things tend to increase appetite (Carlson, 1992) )
but can also learn relationship between taste and post-ingestion consequences of eating certain food
taste aversion studies (Garcia et al., 1966):
rats learn to avoid novel tastes that are followed by illness
rats can learn to prefer tastes that are followed by infusion of nutrients + flavours that they smell on the breath of other rats
both rats and humans require a varied diet
humans usually prefer a plate of mixed foods than a huge plate of only one food
soon become tired of the same food =
sensory-specific satiety
cultural evolution e.g.
Mexicans � calcium by adding lime to tortillas
Europe + N America: prefer diets deterimental to our health
food manufacturers sell highly palatable + energy dense food with less nutritional value, �/span> overeating, fat deposits + body weight
Blundell & Hill (1995): this does not generates a compensatory biological drive to undereat
may explain � obesity
evolved a strong defence against undernutrition, weak defence against the effects of overnutrition
Pinel (1993): the number of different foods consumed in the West is so large that our bodies are unable to learn which foods are beneficial and which not
satiety = feeling �full up� or satisfied
meal size is influenced by several factors
Blundell & Hill (1995)
satiety is not an instantaneous event, but occurs over a period of time
there are different phases of satiety, associated with different mechanisms
together, they comprise the satiety
cascade
(which maintains inhibition over hunger and eating during the early + late phases of satiety)
sensory effects
generated by the smell, taste, temperature and texture of food
inhibit eating in the very short term
cognitive effects
beliefs we hold about the properties of food
may inhibit hunger in the short term
post-ingestive effects
including gastric distension, rate of gastric emptying, release of hormones (e.g. CCK) and stimulation of GIT receptors
post-absorptive effects
mechanisms arising from the action of glucose, fats, amino acids (+ other metabolites) after absorption across the intestine into the bloodstream
post-ingestive and post�absoptive effects are the most important re suppression + subsequent control of hunger
food of varying nutritional composition will have different effects on the mediating processes
research into possible differences in satiating efficiency + capacity to reduce hunger between: protein, fat and carbohydrate
found so far:
carbohydrates are efficient appetite suppressants
the fat content of food influences its texture + palatability, but has a disproportionately weak effect on satiety
although the stomach may not be very important in causing hunger, it is important in satiety
the gastric branch of the vagus nerve carries emergency signals from the stretch receptors in the stomach wall � prevents us from overeating and damaging the stomach
signals from receptors that detect the presence of nutrients are transmitted to the brain by means of a chemical released into the blood by cells in the stomach wall (Carlson, 1992)
after food reaches the stomach, the protein is broken down into its constituent amino acids
as digestion proceeds, food gradually passes into the duodenum (small intestine), which controls the rate of stomach emptying by secreting a peptide hormone (short chains of amino acids) called cholecystokinin (CCK)
CCK is secreted in response to the presence of fats, detected by receptors in the walls of the duodenum
many studies have found that injecting CCK into hungry rats causes them to eat smaller meals
Wolkowitz et al (1990): gave people injections of a drug that blocks CCK receptors in the peripheral nervous system (but not in the brain)
they reported feeling more hungry and less full after a meal than the controls
tumours in the hypothalamus �/span> hyperphagia (excessive overeating) and obesity
stereotaxic surgery (1930s): could experiment with damage to particular areas of the hypothalamus to see the effect on eating behaviour of animals
Hetherington & Ranson (1942): large, bilateral lesions in the ventral medial nucleus (VMN) of the hypothalamus (lower, central) �/span> hyperphagia
VMH: assumed that its normal function is to inhibit feeding when the animal is �full�
= the satiety centre (found in rats, cats, dogs, chickens and monkeys (Teitelbaum, 1967) )
in fact it may be that it is the tendency to become obese that causes them to overeat
the lesions �/span>
� the body�s tendency to produce fat (lipogenesis)
and � the tendency to release fats into the bloodstream (lipolysis)
so calories eaten are converted to fat very fast, and the animal has to keep eating to ensure that it has enough calories in the blood stream
VMH syndrome behavioural complications:
most animals will eat even bad-tasting food
hyperphagic rats will become underweight if quinine is added to their food � taste becomes very important (Teitelbaum, 1955)
VMH syndrome is also anatomically complex:
damage to VMN
but also to axons which connect the paraventricular nucleus (PVN) (situated in the medial hypothalamus) with parts of the brainstem
microinjections of CCK into the PVN inhibit food intake
microinjections of a supposed hunger peptide, substance Y �/span> stimulates eating (Pinel, 1993)
2 neurotransmitters in the medial hypothalamus play an important role in eating behaviour:
noradrenaline stimulates carbohydrate intake
serotonin inhibits it
lateral hypothalamus (LH) accelerates eating
bilateral lesions to the LH � aphagia (refusal to eat, to the point of starvation) (Anand & Brobeck, 1951; Teitelbaum & Stellar, 1954)
even VMH lesioned rats �/span> aphagic if LH lesioned
LH = feeding centre
not well understood � diffuse effects
LH syndrome includes both aphagia and also adipsia (cessation of drinking)
both are part of a more general lack of responsiveness to sensory input
LH itself = large + ill-defined, many nuclei, several major nerve tracts through it
electrical stimulation of LH �/span> eating, but also drinking, gnawing, temperature changes + sexual activity
electrical stimulation to other areas (of they hypothalamus, amygdala, hippocampus, thalamus and frontal cortex) also �/span> eating
Pinel (1993) � LH �hunger centre� = misnomer
surely the (phenomenological) hunger pangs are different to the homeostatic drive itself
what�s the system of digestion like?
if the stomach exit to the duodenum is blocked off, then how does the food ever get digested?
what form does the information from the GIT to brain take � vagus nerve???
is it neurally-encoded information about the state of the GIT, or is it that the brain can tell from what is absorbed in the blood as it circulates around the brain?
does our blood sugar level rise immediately upon eating? � otherwise, this causes problems for the glucostatic theory
no, it�s a post-absorptive effect (i.e. the last of the 4 processes in satiety)
also, there is a grey area between hunger and satiety � not a fine line/stimulus level
can there be a neural mechanism that calculates glucose utilisation?
do the rats with damage to the lateral hypothalamus actually starve to death?
no, it seems they only have a much lowered body weight set point
why is it called the lipostatic theory?
because it�s based around fat (lipids) and maintaining a body weight (fatness) set point
why do sensory effects come before cognitive effects?
stomach loading vs gastric distension
duodenum chemosensors
can you get sensory-specific satiety for a particular food, e.g. spaghetti bolognaise, or only for one of the main food taste types
VMN vs VMH
what�s the NTS?