aggressive behaviour

Joe Herbert and Manuela Martinez

Introduction

Inappropriate aggression and violence is a pervasive feature of contemporary society. In humans, it affects all ages; violent behaviour in children (e.g.

conduct disorder) is relatively common. Understanding, prevention and treat-ment of these conditions is frequently incomplete and unsatisfactory. At a research level, there is often little integration between sociological, psychologi-cal and neurobiologipsychologi-cal approaches, even though the three address the same topic. An additional problem with aggression is that it is a compendium of different behaviours.

The great advances in our knowledge of brain function have helped our understanding of the neural mechanisms underlying behaviour. This chapter focuses on what we know of these as they apply to aggression. It draws evidence both from studies on experimental animals, and investigations of normal humans or those with a variety of illnesses. Experimental and clinical studies give very different information, but must be integrated if rational therapy for unwanted or excessive aggression is to be developed.

First, we define aggression and its relation to other social behaviours. Next, we discuss the structure of the brain as it relates to aggression, with particular emphasis on the limbic system. This anatomical view of the brain is comple-mented by its neurochemical architecture, and we discuss this in relation to aggressive behaviour. We draw our evidence both from experimental studies, which give information about the role of different neural systems, but often under the constraints of laboratory conditions, and from clinical studies that allow direct observation of aggression on humans, but often lack the precise neurobiological information available from animals. The wide variety of methods and approaches used both in animals and humans is nowhere more evident than on studies on aggression. This increases the difficulties of integra-ting results across disciplines.

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Aggression: its relation to other behaviours

Behaviour is complex, and is initiated by complex sets of stimuli and circum-stances. Different categories of behaviour may occur during comparatively short spans of time. All this has led to experimental efforts to simplify behav-iour. Thus, sexual behaviour is commonly studied by providing circumstances in which it, rather than – say – eating, occurs at high intensity. Furthermore, the essential stimuli that elicit such behaviour can be reduced to the minimum;

for example, by the pairing of a potent male with a sexually receptive female in an otherwise empty cage. Parallel studies have been made on other categories of behaviour; eating can be studied by placing food-deprived animals in cages containing either food, or the means (e.g. an operant response) of obtaining food. The rationale for this approach is that such behaviours have definable characteristics, and equally distinct biological or motivational boundaries.

Manipulations of the brain can be made to see what effect this has on these distinct behaviours, with the reasonable assumption this will yield information relevant to the neural mechanisms responsible for the behaviour.

The problem with similar approaches to aggression is that some of these assumptions do not apply to this behaviour. Aggression, unlike some other behaviours, has no biological function or purpose in isolation (Attili & Hinde, 1986). Aggressive interactions occur mostly as part of some other pattern of behaviour; for example, as a strategy to achieve sexual goals, or access to preferred foods, or – more generally – as part of the process whereby individ-uals define their position in the social groups to which they belong, and hence ensure access to restricted resources without the need for constant conflict; a form of social control. So, the attempts to elicit ‘aggression’ under experimental conditions must be viewed in this light; the underlying reasons why animals fight may be related to different motivational systems, depending on the circumstances under which this occurs. This will be reflected in the neural mechanisms brought into play; different mechanisms may underlie aggressive behaviour when the circumstances and contexts of the aggression change. We have to make a careful distinction between neural mechanisms that underlie the display of aggression (that is, as an identifiable motor pattern) and those that influence whether or not it will be used as a strategy (offence), or determine how one animal responds to aggression from another (defence).

The classification of aggression continues to be unsatisfactory, partly for these reasons. It has been defined as a behaviour characterized by the intent to inflict noxious stimulation on another individual, but this underestimates its subtlety and omits some important features. It is well-known that aggression is

not a unitary concept. Several classifications of aggression have been proposed, some elaborate, others more simple. On the basis of functional criteria, aggres-sion has been classified as (a) competition for resources and (b) defence (Archer, 1988). Within this classification different subtypes can be differentiated depend-ing on the stimuli that elicit them and the pattern of behaviour displayed (Brain, 1981; Moyer, 1968). Distinctions have been made between the different types of aggression, largely on the basis of context or stimuli eliciting this behaviour: (a) intermale (or interfemale) (territorial, social conflict etc), (b) maternal, (c) self-defence and (d) infanticide. Predation (interspecific aggression), sometimes included in discussions of aggressive behaviour, more properly belongs to a different category of behaviour (feeding). This chapter is limited to intraspecific aggression (i.e. that occurs between members of the same species), and this has been divided more simply into ‘offence’ and ‘defence’ on the basis of the structure of the behaviour (Adams, 1979; Blanchard & Blanchard, 1988).

Human physical aggression has also been separated into ‘emotional’ or ‘reac-tive’ (angry outbursts in response to provocation, or aggression carried out with the main intention to harm someone) and ‘instrumental’ or ‘proactive’

(goal-oriented, aggression carried out with some other objective that is more important than their victim’s injury) (Berkowitz, 1993). In general, both the form of the aggressive act and the context in which it occurs has to be taken into account if a coherent relation to brain function is to be made. Finally, aggression varies over time and place in the real world; this means that there is a constant process of social adaptation to aggression or its consequences – animals and people learn whether or not aggression pays off, and the contexts in which to use it or how best to respond to it. These processes also involve neural mechanisms that lie at the heart of understanding why some individuals use aggression either effectively or inappropriately. It is clear that adequate and theoretically satisfying definitions of aggression are still lacking; the reasons for this are the multiple roles of aggression and a parallel plethora of causative factors (see above). Furthermore, there is often little communication between those studying aggression experimentally, and those concerned with this be-haviour in social or clinical contexts in humans.

Most species, including human beings, live in social groups whose structure affects access by individuals to items in short supply (e.g. food, mates, shelter).

Direct aggressive confrontation may be used to determine which individual has priority, but it is more usual that animals come to know, through a process of social learning, who is likely to win such an encounter. This determines their strategy, and also gives the group its dominance structure. Animals (or people) low in the hierarchy may not challenge those higher in the scale, presumably

because of the perceived cost in terms of potential injury. This mechanism of social control, based on previous aggressive interactions, functions to reduce aggression; but it does have potent effects on individuals. If it is to be effective, social control by hierarchy requires extremely sophisticated neural processing;

indeed, there are those who claim that the primary function of the primate brain is to facilitate social interaction (see Herbert, 1987). To understand the role of the brain in aggression requires consideration not only of the means whereby aggression is expressed, but also how individuals respond to aggres-sive actions by others, and regulate aggression in accordance with social needs.

An important aspect is that physical aggression is displayed mainly by males both in human and other species. This is responsible for the fact that most research both in experimental and clinical studies has been conducted in males.

However, it is not true to say that females lack aggressive behaviour. For example, maternal aggression (that is, defence of the young) is commonplace, and, in humans, verbal aggression is part of the behaviour of both sexes.

The brain and aggression

It is axiomatic that the brain plays a central role in aggression, both by recognizing aggression-provoking stimuli, and formulating aggressive re-sponses. Neurons consist of three major elements: dendrites, that collect input information; axons that transmit integrated information using electrical con-duction, and synapses that release chemical signals as the result of this action potential. Neurons themselves are gathered together into recognizable struc-tures (‘nuclei’) and it has long been known that these have functional signifi-cance. Nuclei project to other nuclei, and a collection of interconnected regions of the brain forms a neural ‘system’.

Thus we can look at the brain as a neuroanatomical structure in which different parts play different roles in aggression. However, we can also look at the brain as formed by neurochemical systems, some of which are more involved in aggression than others. Clinical approaches reflect this: attempts to treat abnormal aggression by localized lesions (e.g. of the amygdala) reflect the first view; the development of drugs that act on aggression relate to the second.

Our objective is to draw a picture in which the neuroanatomy and neurochem-istry of the brain will be specifically related to the different aspects of aggres-sion.

Although we are not specifically concerned here with the development of the brain, it is important to note that the clues to later aggression may lie in the brain’s developmental history. Whether or not there are genetic

predisposi-Fig. 4.1. Flow chart showing the process by which social stimuli give rise to aggressive responses.

There are three major components: the complex formed by social stimuli (from con-specifics);

the reception and processing of this information by the brain, and the formulation of the aggressive response (also by the brain). Each component has several subcomponents, as shown, which together make up the processing step.

tions for aggression, these will be modifed by experience or the environment – particularly during early life. The integrated results of these formative influen-ces have their counterpart in changes in the structure or neurochemical architecture of the brain, whether or not this is apparent at present. One objective of research is to identify critical genetic and environmental factors that influence aggressive behaviour, and to understand more about the way they alter the brain function in relation to this behaviour.

Neuroanatomical basis of aggressive behaviour

The brain is the organ where behaviour – including aggression – is produced.

Although the brain works as a whole, it is constructed so that different parts are involved in specific tasks. For aggression, this implies that different parts of the brain are involved from sensory reception of the aggression-provoking stimu-lus to the appropriate (or inappropriate) motor display. Neural mechanisms are required to recognize in others social stimuli that elicit aggression, or aggres-sive acts on their part; to determine the context in which these occur, to formulate the motor, endocrine and autonomic responses that characterize the typical aggressive act and to learn from the results of the aggressive encounters (see Fig. 4.1). Intraspecific aggressive responses depend upon the reception and processing of complex social stimuli. These stimuli are carried by the visual, auditory, tactile and olfactory sensory systems. Thus, it should be noted that it is unwise to draw too precise a boundary round a neural system involved in aggression; clearly, many parts of the brain contribute to this complex behav-iour. In all these processes past experiences, state of the individual and the social context influence the way the individual perceives the stimuli and responds to them.

Methods

There are many methods for studying the brain, and most have been used in the study of aggression. A few of the more common techniques are as follows.

Classical studies in experimental animals have been carried out by using lesions or electrical stimulation as the main methods of altering the functioning of specific areas of the brain and to observe the changes produced in aggressive behaviour. In humans, similar information has mainly been obtained from clinical cases in which lesions in specific brain areas (e.g. damage) or electrical stimulation (e.g. epilepsy) are related to changes in aggressive behaviour. A refinement of these techniques involves chemical activation of the brain either generally (i.e. using systemic drugs altering neurochemical systems) or locally (i.e. using injection of neuroactive substances into specific areas of the brain).

More recently, new techniques have allowed us to study the role of specific areas of the brain without the need to alter them. In animals, mapping the brain activity related to aggressive behaviour is possible by the use of the immediate-early gene (IEG) technique (Kollack-Walker & Newman, 1995; Martinez et al., 1998). This technique is based on the fact that the activation of neurons results in the rapid expression of a number of genes, such as c-fos, that act as transcriptional (DNA) regulators. Whilst the identity of the downstream genes are, in most cases, still obscure, this technique can be used to show which brain areas are active during aggression. For other genes with known functions, such as peptides, the product of the gene (either the mRNA or the protein) can be identified by immunohistochemical processes and quantified by image analysis.

In humans, brain-imaging techniques allow us to get information about both the structure and the functioning of specific areas of the brain in people with disorders in aggressive behaviour. The main techniques that give information about the structure are computerized tomography (CT) and magnetic reson-ance imaging (MRI), while those informing on function are positron emission tomography (PET) and regional cerebral blood flow (RCBF).

The modular limbic system and aggression

If we are to map neural systems onto specific patterns of behaviour – like aggression – then we must discuss how we classify neural systems. The limbic system (see Fig. 4.2) has been particularly associated with aggressive behaviour.

This system, like many others (e.g. the motor system), is recognized as being composed of anatomically discrete structures, such as the amygdala, hypo-thalamus, septum, ventral striatum, hippocampus, orbital frontal and cingulate cortex and certain parts of the brain stem (Nieuwenhuys, 1996). This definition relies on two anatomical features; the structures in question can be delineated

Fig. 4.2. The limbic system in the human brain. The regions referred to in the text are indicated.

from other, nearby ones (e.g. the amygdala can be separated from the stri-atum); and there are particularly profuse neural connections between compo-nents of the system in question. For example, it is well-known that the amygdala has strong projections to the hypothalamus, many of them routed via the septum. The essential corollary is that there is a function, or set of functions, that can be ascribed to a system. In the case of the motor system, this is the generation and control of movement. For the limbic system, there is considerable controversy, but the function we will assume is that this system is concerned with organizing appropriate responses to defined biological needs (e.g. food, water, reproduction, self-defence), a process that includes both homeostasis and adaptation. Aggression, by its nature and function, is an important part of this process. If this is so, then our task will be to try to map the different components of aggression onto the various structures of the limbic system and also to see whether other systems may contribute to this behaviour. We need, therefore, to try to define the special role of the limbic system in aggression, recognizing that this system operates in concert with all the other parts of the brain and that the limbic system has functions other than the regulation of aggression.

Fig. 4.3. Information flow through the amygdala. Major sources of input are shown on the left;

these terminate in regions of the amygdala (BL: basolateral; CM: cortico-medial; CE: central nuclei). Outputs are shown on the right. The functions of these areas in the context of aggressive behaviour are discussed in the text.

The amygdala

Stimuli involved in aggression are analysed by neocortical areas. There must be a pathway that allows this information to gain access to those neural structures that compose aggressive responses. The evidence strongly suggests that the amygdala is an essential component of this pathway. The amygdala receives extensive sensory input from the neocortex (see Fig. 4.3). The cortical associ-ation area for visual, auditory, tactile and gustatory informassoci-ation all project to the amygdala through the temporal neocortex. The amygdala also receives direct input from the olfactory bulbs and projections from polysensory conver-gence areas in frontal and temporal neocortex.

The amygdaloid complex is involved in processes determining the way in which the individual’s brain perceives and interprets a given stimulus or situation. Its central function is to associate a sensory stimulus with an emo-tional response. Thus, the amygdala plays an important role in aggressive behaviour (reviewed by Albert et al., 1993; Blanchard & Blanchard, 1988;

Eichelman, 1983; Kling & Brothers, 1992; Miller, 1994; Ursin, 1981; Weiger &

Bear, 1988). Damage to the amygdala produces a range of difficulties with the

identification of complex natural stimuli, such as losing the capacity to respond to important external cues and it has long been known to induce ‘tameness’

(that is, loss of an expected aggressive or fearful response to a given situation).

Conversely, electrical stimulation of the amygdala can induce aggressive reac-tions. These are not random, but are mainly directed towards objects that might be expected to elicit them under more normal conditions (e.g. another con-specific – member of the same species – rather than an inanimate object).

Similarly, localized seizures in the temporal lobe and sometimes specifically in the amygdala are associated in human beings with aggressive outbursts. These violent episodes occur before as well as during episodes of abnormal electrical activity. Patients with temporal lobe tumours exhibit assaultive rages (see references above).

One conclusion is that the amygdala is part of the system that classifies a set of stimuli on the basis of cortical processing, and passes this emotionally classified information to other parts of the limbic system (e.g. the hypo-thalamus) that compose the behavioural, endocrine and autonomic responses characteristic of aggression (see Fig. 4.4). However, a large body of experimen-tal work shows that the amygdala is also concerned with the generation of fear, including conditioned fear (that is, learning that previously neutral events may signal aversive events) (Kagan & Schulkin, 1995; Maren & Fanselow, 1996). If an animal loses the capacity to experience fear, then one correlate will be loss of aggression – since many aggressive episodes are born from fear or anticipated fearful events. Similar findings are reported for humans; the amygdala is activated by fearful stimuli in humans (LaBar et al., 1998) and bilateral amyg-daloid lesions impair the recognition of fear in others (Adolphs et al., 1995). So whilst there is little doubt that the amygdala is critical for the expression of aggression, its exact role remains enigmatic. However, this has not prevented attempts to control aggression in humans by amygdalectomy (Narabayashi et al., 1963). Furthermore, it is important to remember that the amygdala is also concerned with classifying other categories of response, such as sexual and ingestive behaviours (McGregor & Herbert, 1992) which excludes it being concerned solely with aggression (or fear). Thus, we need to understand how the amygdala provides an essential ‘label’ on complex social stimuli, how this information is coded, and how it is passed to the executive parts of the limbic system. This includes the septum and the hypothalamus.

The septum

The septum (see Fig. 4.2), the bed nucleus of stria terminalis and the nucleus accumbens have been considered as a ‘defence inhibitory system’ (reviewed by

Fig. 4.4. Inputs and outputs of the hypothalamus. The major source of inputs is shown on the left;

the three categories of output on the right. Specific patterns of the latter constitute aggressive responses. ACTH: adrenocorticotrophic hormone.

Blanchard & Blanchard, 1988). Damage to these structures produces a transient or longer-lasting ‘release’ of defensive aggression but also many other behav-ioural effects such as hyper-reactivity and increased responsiveness to a variety of situations which include alteration in ingestion and sexual behaviour. In humans, stimulation of the septum reduces violent behaviour, and the individ-ual becomes happy and euphoric. On the contrary, tumours in this area are associated with a heightened defensiveness (reviewed by Albert et al., 1993;

Ursin, 1981). Altogether, these results indicate that the septum is important in aggression, though its role may not be limited to this behaviour.

The hypothalamus

The hypothalamus is involved in the generation of responses related to the survival of the individual and the species that include motor, endocrine and autonomic reactions (see Fig. 4.4) (Herbert, 1993). It receives internal sensory information directly through chemo- and osmoreceptors, and processed infor-mation from the external environment through inputs from the amygdala and other structures. The classical experiments of Bard (1928) showed that section of all brain structures anterior to the hypothalamus resulted in cats showing

‘sham rage’ with high sympathetic arousal and extreme anger elicited by previously unimportant stimuli. However, when the hypothalamus was also sectioned the animals did not exhibit ‘sham rage’.

There is some evidence that different nuclei of the hypothalamus may be concerned with separate forms of aggression such as offence and defence (as well as predation) (reviewed by Blanchard & Blanchard, 1988; Kruk, 1991;

Ursin, 1981). Lesions or stimulation in several areas of the hypothalamus have altered aggressive interactions and it is difficult to ascribe specific functions to individual hypothalamic nuclei. For example, Hess (1954) showed that stimu-lating the lateral hypothalamus in cats caused aggressive behaviour. This stimulation also led to either predatory attack in the presence of a prey or an offence attack when a conspecific male was present. Lesions in the medial hypothalamus (ventromedial nucleus) induced both defence and offence, and resulted in animals that were highly reactive to aggression-provoking stimuli.

Defensive aggression seems to be also represented in the anterior hy-pothalamus, as stimulation of this area resulted in this behaviour only in cornered rats. The preoptic area is also involved with the initiation, modula-tion, integration and organization of defensive aggression. However, it should be noted that these areas are also implicated in other behaviours. For example, the preoptic area has well-established roles in sexual and maternal behaviour in experimental animals, and the ventromedial hypothalamus is known to be concerned with feeding. Bearing in mind the relation between aggression and other categories of adaptive behaviour, it is clear that there is still uncertainty about the exact role of the hypothalamus in aggression, and whether this can be truly separated from its other adaptive and homeostatic functions.

There are well-documented cases describing humans with tumours in the medial or anterior hypothalamus who became highly aggressive (reviewed by Albert et al., 1993; Eichelman, 1983; van de Poll & van Goozen, 1992). They respond with aggression to stimuli they would have previously considered only annoying (reactive aggression). Damage to the anterior part of the hypo-thalamus also leads to a dramatic change of character and very aggressive and irritable episodes. ‘Sedative’ surgical interventions, involving lesions of the posterior hypothalamus have been used in the surgical treatment of aggressive patients. They were said to show remarkable success in patients with intrac-table violent behaviour (Sano et al., 1970). So it seems that the experimental and clinical evidence are in reasonable agreement about the fundamental role of the hypothalamus in aggressive behaviour.

The midbrain

The hypothalamus controls aggressive display in part through its projections to the brainstem. For example, if the connection between the hypothalamus and the midbrain is interrupted, the stimulation of the hypothalamus does not

induce aggression (Ellison & Flynn, 1968). The periaqueductal grey matter (PAG) is a crucial structure for the motor pattern of defensive aggression, although is not involved in offence (see Fig. 4.2). Lesions in this structure in rats attenuate or even abolish defence reactions, whether they be provoked either by a natural threat or by electrical stimulation of the hypothalamus. On the contrary, a lesion in the medial hypothalamus does not in any way prevent such a reaction being triggered by stimulation of the PAG (Mos et al., 1983).

This indicates the direction of the neural pathways connecting the two struc-tures. Stimulation of the PAG can elicit highly characteristic defence reactions (including attack or flight) (Bandler et al., 1991). However, it should be noted that the PAG has been implicated in other behavioural functions in addition to aggression or fearful responses (Nieuwenhuys, 1996).

The ventral tegmental area (VTA) is involved in the motor patterns of offence (see Fig. 4.2). Experimental lesions here reduced offence but did not alter defence (or predation) (Adams, 1986). This finding suggests that offence has a discrete substrate in the midbrain and that this is different from that of the defence system. However, it is important to note that VTA lesions interfere with many other behaviours, particularly those that require an active reponse, so it is unlikely that the VTA is specifically concerned with aggression. The VTA is also a major source of forebrain dopaminergic neurons, and the role of the monoamines in aggression is discussed further below.

The frontal neocortex

We have seen that aggression forms an important part of social regulation and social interaction. Cortical regions are essential for social learning, anticipation of the consequences of behaviour and response selection. However, decortica-tion does not affect the ability to express aggression. Completely decorticated rats retain the vast majority of motor patterns of aggression. The frontal neocortex is intimately connected with both the amygdala and the hypo-thalamus and is therefore in a position to influence these other brain centres which control aggression. More specifically, the prefrontal cortex has an inhibitory influence on the expression of aggressive behaviour (see Fig. 4.2).

The orbitofrontal cortex receives information from both external sensory source and from the lower centres which control aggression, and it projects back onto these lower centres (Fuster, 1989). Therefore, this part of the cortex qualifies anatomically as a potential higher level in the control of aggression and this is supported by both experimental and clinical evidence. Stimulation of the deeper orbital layers of the prefrontal cortex inhibits attacks elicited from the hypothalamus in the rat. As a corollary, bilateral lesions of the orbitofrontal

cortex resulted in an enhancement of offensive aggression (de Bruin, 1990; de Bruin et al., 1983). In humans, aggression can occur as a feature of frontal lobe damage (reviewed by Giancola, 1995; Miller, 1994). Humans with lesions in the orbitofrontal cortex reacted with impulsivity, without planning or taking into account the consequences of their behaviour. These patients were irritable and had short tempers, responding to minor provocation. They experienced brief outbursts of anger during which they might take impulsive action and, after committing an aggressive act, they were usually indifferent to the conse-quences (Luria, 1980). Thus, this region is implicated in the process that decides the time, place and strategy of response appropriate to the anger induced by the environment. Techniques determining the activity of the frontal lobes (e.g.

glucose uptake by PET) show this is reduced in the frontal lobes (but also other areas, including the amygdala) of violent murderers (Raine et al., 1994, 1997) Recently, the orbitofrontal cortex and dorsolateral cortex have been suggested to be involved in the expression of different categories of aggressive behaviour in humans (Giancola, 1995). It seems likely that the frontal cortex plays a major part in the social regulation of aggression, and the way that aggressive interac-tions are used to determine social relainterac-tionships.

Neurochemical modulation of aggressive behaviour

The brain is a chemical machine, and the recognition that neural systems can be defined by the chemical transmitters they use offers a different perspective from the neuroanatomical one. Neurons release a range of chemicals (neuro-transmitters) into synapses; these stimulate or suppress the activity of the next set of neurons in the chain, and so on. The release of transmitters is the result of electrical impulses travelling down axons, and the effect of released transmit-ters is dependent on their binding to specific receptors on the membranes of the next neuron. An important point is that a given neurotransmitter can have many effects, depending on the nature of the receptor with which it comes into contact. This is particularly relevant to the limbic system, which contains a profusion of such neurochemicals and receptors. We will focus on the major chemical groups implicated in neurotransmission: amino acids, monoamines, peptides and steroid hormones; all have been found to be involved in aggres-sion. Chemical neuroanatomy shows us that chemically identifiable systems are organized in the brain as structures that cut across the conventional, modular (anatomical) definitions – the ‘systems’ referred to above. If we are to understand how the brain controls aggression, then we have to understand the relation between modular and chemical views of the brain. The vast majority of pharmacological treatments to control pathologically aggressive behaviours