Frontal lobe and behaviour disorders

Correspondent to its cytoarchitectonic structure, the frontal lobe is traditionally divided into two parts, which are important in two major areas. The posterior part controls motor movement and is subdivided into a premotor and a motor area, which control movement preparation and actual execution of movement respectively. The anterior part of the frontal lobe, the prefrontal cortex, is especially important in higher mental function, as in anticipation and planning, initiative, judgement, and in affect control, will power, and the determination of personality (Bechara et al., 1999; Raine et al., 2000). The prefrontal cortex can be further subdivided into the dorso-lateral cortex and the orbito-frontal cortex. This subdivision of the prefrontal cortex is still simple and it should be noted that the orbito-frontal cortex itself is a heterogeneous area connected with a wide range of other prefrontal, limbic, premotor, sensory areas and subcortical nuclei (Cavada et al., 2000). For the purpose of this article it is important to know that there is evidence that damage of the dorso-lateral part of the prefrontal cortex is more associated with impairment of executive functions and functions of working memory, whereas damage of the orbito-frontal cortex leads to impairment of the choice of behaviour, the establishment of emotional valences, and the evaluation and balancing of the past and future consequences of a given behaviour (Bechara et al., 2000; Rolls, 2000; Sarazin et al., 1998). Studies in common marmosets suggest a dissociation between the lateral and the orbital-medial division of the prefrontal cortex according to which the first selects and controls actions on the basis of higher-order rules while the latter controls different behaviour on the basis of lower-order rules (see Roberts and Wallis, 2000).

The significance of the orbito-frontal cortex for social and interpersonal behaviour recently came into focus when Anderson et al. (1999) reported two patients, one with an accident at 15 months, the other with a frontal tumour resection at 16 months, both showing severe impairment of social and moral behaviour.

Traditionally, behavioural dyscontrol has been attributed to temporo-limbic structures. Evidence for the involvement of the amygdala in aggression comes from human and animal stimulation studies, from activating and inhibiting effects of anti-epileptic drugs on aggression, and recently also from direct correlations of amygdala volumes with aggression in patients with mesial epilepsies (Azouvi et al., 1999; Bearn and Gibson, 1998; Trimble and Van Elst, 1999; Van Elst et al., 2000). However, aggression associated with the amygdala seems more defensive than offensive in nature (Kalynchuk et al., 1999). Disinhibition phenomena, or a loss of impulse control as it is observed with frontal lesions, may be an additional prerequisite for showing impulsive aggressive behaviour. The orbito-frontal cortex as the border zone between the frontal lobe and the limbic system is thus critical for the linkage of the frontal and limbic aspects of behavioural dyscontrol disorders. Another important area in this respect is the anterior-cingulate gyrus, which is also strongly connected to the amygdala, and whose damage has also been associated with deviant social behaviour and affect states (for overview see Devinsky et al., 1995).

The finding of antisocial and aggressive behaviour with frontal lobe damage is not in itself new. A prominent and often cited example is the historic case of Phineas Gage, who after an accident with a severe frontal brain injury changed from a well-mannered man into an irresponsible and convention-neglecting person (Damasio et al., 1994; Harlow, 1868). New in the study of Anderson et al. (1999) is the finding that whether patients not only display severe behavioural disorders but also fail to see the moral of the behaviour depends on the age at the lesion onset (Dolan, 1999). Consequently, the orbito-frontal cortex seems not only important for behaviour control but also for the acquisition of social and interpersonal rules. It is important to note that irresponsible, aggressive and sociopathic behaviours can occur independent of intellectual abilities, which are often well preserved in frontal lesions. Other areas in which the orbital and medial prefrontal cortex are believed to play a central role are addictive behaviour, attention-deficit hyperactivity disorder, negative emotion and major depression (Drevets and Raichle, 1996; London et al., 2000; Northoff et al., 2000; Rubia et al., 2000). Davidson et al. (2000) propose a key role of the prefrontal cortex in the regulation of emotion in violent subjects and those predisposed to violence.

A theoretical basis of the role of the prefrontal cortex in the interplay of cognition and emotion has been provided with Damasio's 'somatic marker' hypothesis (Damasio, 1996). This proposes that responses to external stimuli do not rely on either conditioning processes or cognition alone, but on somatic 'marker signals' or autonomic response sets, which determine the conscious/unconscious connection between stimulus conditions, feelings and behaviour.

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