BRAIN CONTROLS EATING
Since the early twentieth century, we have known that damage to the base of the brain can influence food intake and body weight. One critical region is the ventromedial hypothalamus. Bilateral lesions of this area (i.e. two-sided, damaging both the left and right) in animals leads to hyperphagia (overeating) and obesity. By contrast, Anand and Brobeck (1951) discovered that bilateral lesions (that is, damage) of the lateral hypothalamus can lead to a reduction in feeding and body weight. Evidence of this type led, in the 1950s and 1960s, to the view that food intake is controlled by two interacting ‘centres’ – a feeding centre in the lateral hypothalamus and a satiety centre in the ventromedial hypothalamus. But problems arose with this dual centre hypothesis. Lesions of the ventromedial hypothalamus were found to act indirectly by increasing the secretion of insulin by the pancreas, which in turn reduces plasma glucose concentration, resulting in feeding. This has been demonstrated by cutti ng the vagus nerve, which disconnects the brain from the pancreas, preventing ventromedial hypothalamic lesions from causing hypoglycaemia, and therefore preventing the consequent overeating. So the ventromedial nucleus of the hypothalamus is now thought of as a region that can influence the secretion of insulin and, indirectly, affect body weight, but not as a satiety centre per se. On the other hand, the hypothesis that damage to the lateral hypothalamus produces a lasting decrease in food intake and body weight has been corroborated by injecting focal neurotoxins (agents that kill brain cells in a very specific manner, such as ibotenic acid), into rats. These damage the local cell bodies of neurons but not the nerve fibres passing nearby. Rats with lateral hypothalamus lesions also fail to respond to experimental interventions that normally cause eating by reducing the availability of glucose (Clark et al., 1991).
A matter of taste
How are taste signals (which provide one of the most significant rewards for eating) processed through different stages in our brains, to produce (among other effects) activation of the lateral hypothalamic neurons.
Some of the brain connections and pathways in the macaque monkey. The monkey is used to illustrate these pathways because neuronal activity in non-human primates is considered to be especially relevant to understanding brain function and its disorders in humans. During the first few stages of taste processing (from the rostral part [rostral towards the head or front end of an animal, as opposed to caudal (towards the tail)] of the nucleus of the solitary tract, through the thalamus, to the primary taste cortex), representations of sweet, salty, sour, bitter and protein tastes are developed (protein represents a fifth taste, also referred to as ‘umami’). The reward value or pleasantness of taste is not involved in the processing of the signal as yet, because the primary responses of these neurons are not influenced by whether the monkey is hungry or satiated. The organization of these first few stages of processing therefore allows the primate to identify tastes independently of whether or not it is hungry. In contrast, in the secondary cortical taste area (the orbitofrontal cortex), [orbitofrontal cortex above the orbits of the eyes, part of the prefrontal cortex, which is the part of the frontal lobes in front of the motor cortex and the premotor cortex] the responses of taste neurons to a food with which the monkey is fed to satiety decrease to zero (Rolls et al., 1989, 1990). In other words, there is modulation or regulation of taste responses in this tasteprocessing region of the brain. This modulation is also sensoryspecific (see, for example, figure 5.6). So if the monkey had recently eaten a large number of bananas, then there would be a decreased response of neurons in this region of the orbitofrontal cortex to the taste of banana, but a lesser decrease in response to the taste of an orange or melon. This decreased responding in the orbitofrontal cortex neurons would be associated with a reduced likelihood for the monkey to eat any more bananas (and, to a lesser degree, any more orange or melon) until the satiety had reduced.
So as satiety develops, neuronal activity in the secondary taste cortex appears to make food less acceptable and less pleasant – the monkey stops wanting to eat bananas. In addition, electrical stimulation in this area produces reward, which also decreases in value as satiety increases (Mora et al., 1979). It is possible that outputs from the orbitofrontal cortex subsequently influence behaviour via the connections of this region to the hypothalamus, where it may activate the feeding-related neurons described earlier.
Since the early twentieth century, we have known that damage to the base of the brain can influence food intake and body weight. One critical region is the ventromedial hypothalamus. Bilateral lesions of this area (i.e. two-sided, damaging both the left and right) in animals leads to hyperphagia (overeating) and obesity. By contrast, Anand and Brobeck (1951) discovered that bilateral lesions (that is, damage) of the lateral hypothalamus can lead to a reduction in feeding and body weight. Evidence of this type led, in the 1950s and 1960s, to the view that food intake is controlled by two interacting ‘centres’ – a feeding centre in the lateral hypothalamus and a satiety centre in the ventromedial hypothalamus. But problems arose with this dual centre hypothesis. Lesions of the ventromedial hypothalamus were found to act indirectly by increasing the secretion of insulin by the pancreas, which in turn reduces plasma glucose concentration, resulting in feeding. This has been demonstrated by cutti ng the vagus nerve, which disconnects the brain from the pancreas, preventing ventromedial hypothalamic lesions from causing hypoglycaemia, and therefore preventing the consequent overeating. So the ventromedial nucleus of the hypothalamus is now thought of as a region that can influence the secretion of insulin and, indirectly, affect body weight, but not as a satiety centre per se. On the other hand, the hypothesis that damage to the lateral hypothalamus produces a lasting decrease in food intake and body weight has been corroborated by injecting focal neurotoxins (agents that kill brain cells in a very specific manner, such as ibotenic acid), into rats. These damage the local cell bodies of neurons but not the nerve fibres passing nearby. Rats with lateral hypothalamus lesions also fail to respond to experimental interventions that normally cause eating by reducing the availability of glucose (Clark et al., 1991).
A matter of taste
How are taste signals (which provide one of the most significant rewards for eating) processed through different stages in our brains, to produce (among other effects) activation of the lateral hypothalamic neurons.
Some of the brain connections and pathways in the macaque monkey. The monkey is used to illustrate these pathways because neuronal activity in non-human primates is considered to be especially relevant to understanding brain function and its disorders in humans. During the first few stages of taste processing (from the rostral part [rostral towards the head or front end of an animal, as opposed to caudal (towards the tail)] of the nucleus of the solitary tract, through the thalamus, to the primary taste cortex), representations of sweet, salty, sour, bitter and protein tastes are developed (protein represents a fifth taste, also referred to as ‘umami’). The reward value or pleasantness of taste is not involved in the processing of the signal as yet, because the primary responses of these neurons are not influenced by whether the monkey is hungry or satiated. The organization of these first few stages of processing therefore allows the primate to identify tastes independently of whether or not it is hungry. In contrast, in the secondary cortical taste area (the orbitofrontal cortex), [orbitofrontal cortex above the orbits of the eyes, part of the prefrontal cortex, which is the part of the frontal lobes in front of the motor cortex and the premotor cortex] the responses of taste neurons to a food with which the monkey is fed to satiety decrease to zero (Rolls et al., 1989, 1990). In other words, there is modulation or regulation of taste responses in this tasteprocessing region of the brain. This modulation is also sensoryspecific (see, for example, figure 5.6). So if the monkey had recently eaten a large number of bananas, then there would be a decreased response of neurons in this region of the orbitofrontal cortex to the taste of banana, but a lesser decrease in response to the taste of an orange or melon. This decreased responding in the orbitofrontal cortex neurons would be associated with a reduced likelihood for the monkey to eat any more bananas (and, to a lesser degree, any more orange or melon) until the satiety had reduced.
So as satiety develops, neuronal activity in the secondary taste cortex appears to make food less acceptable and less pleasant – the monkey stops wanting to eat bananas. In addition, electrical stimulation in this area produces reward, which also decreases in value as satiety increases (Mora et al., 1979). It is possible that outputs from the orbitofrontal cortex subsequently influence behaviour via the connections of this region to the hypothalamus, where it may activate the feeding-related neurons described earlier.
No comments:
Post a Comment