The effects of frontal lobe lesions on goal achievement in the water jug task.

Patients with prefrontal cortex lesions are impaired on a variety of planning and problem-solving tasks. We examined the problem-solving performance of 27 patients with focal frontal lobe damage on the Water Jug task. The Water Jug task has never been used to assess problem-solving ability in neurologically impaired patients nor in functional neuroimaging studies, despite sharing structural similarities with other tasks sensitive to prefrontal cortex function, including the Tower of Hanoi, Tower of London, and Wisconsin Card Sorting Task (WCST). Our results demonstrate that the Water Jug task invokes a unique combination of problem-solving and planning strategies, allowing a more precise identification of frontal lobe lesion patients' cognitive deficits. All participants (patients and matched controls) appear to be utilizing a hill-climbing strategy that does not require sophisticated planning; however, frontal lobe lesion patients (FLLs) struggled to make required "counterintuitive moves" not predicted by this strategy and found within both solution paths. Left and bilateral FLLs were more impaired than right FLLs. Analysis of the left hemisphere brain regions encompassed by the lesions of these patients found that poor performance was linked to left dorsolateral prefrontal cortex damage. We propose that patients with left dorsolateral prefrontal cortex lesions have difficulty making a decision requiring the conceptual comparison of nonverbal stimuli, manipulation of select representations of potential solutions, and are unable to appropriately inhibit a response in keeping with the final goal.     

Impairment of social perception associated with lesions of the prefrontal cortex

OBJECTIVE: Behavioral and social impairments have been frequently reported after damage to the prefrontal cortex in humans. This study evaluated social perception in patients with prefrontal cortex lesions and compared their performance on a social perception task with that of healthy volunteers. METHOD: Thirty-three patients with prefrontal cortex lesions and 31 healthy volunteers were tested with the Interpersonal Perception Task. In this task, subjects viewed videotaped social interactions and relied primarily on nonverbal cues to make interpersonal judgments, such as determining the degree of intimacy between two persons depicted in the videotaped scene. Patients with prefrontal cortex lesions were classified according to lesion involvement of specific regions, including the orbitofrontal cortex, dorsolateral prefrontal cortex, and anterior cingulate cortex. RESULTS: Relative to the comparison subjects, patients whose lesions involved the orbitofrontal cortex demonstrated impaired social perception. Contrary to predictions, patients with lesions in the dorsolateral prefrontal cortex also showed deficits in using social cues to make interpersonal judgments. All patients, particularly those with lesions in the dorsolateral prefrontal cortex, showed poorer insight into their deficits, relative to healthy volunteers. CONCLUSIONS: These findings of deficits in social perception after damage to the orbitofrontal cortex extend previous clinical and experimental evidence of damage-related impairment in other aspects of social cognition, such as the ability to accurately evaluate emotional facial expressions. In addition, the results suggest that the dorsolateral prefrontal cortex is recruited when inferences about social interactions are made on the basis of nonverbal information.     

A distributed cortical network for auditory sensory memory in humans

Auditory sensory memory is a critical first stage in auditory perception that permits listeners to integrate incoming acoustic information with stored representations of preceding auditory events. Here, we investigated the neural circuits of sensory memory using behavioral and electrophysiological measures of auditory processing in patients with unilateral brain damage to dorsolateral prefrontal cortex, posterior association cortex, or the hippocampus. We used a neurophysiological marker of an automatic component of sensory memory, the mismatch negativity (MMN), which can be recorded without overt attention. In comparison with control subjects, temporal-parietal patients had impaired auditory discrimination and reduced MMN amplitudes with both effects evident only following stimuli presented in the ear contralateral to the lesioned hemisphere. This suggests that auditory sensory memories are predominantly stored in auditory cortex contralateral to the ear of presentation. Dorsolateral prefrontal damage impaired performance and reduced MMNs elicited by deviant stimuli presented in either ear, implying that dorsolateral prefrontal cortices have a bilateral facilitatory effect on sensory memory storage. Hippocampal lesions did not affect either performance or electrophysiological measures. The results provide evidence of a temporal-prefrontal neocortical network critical for the transient storage of auditory stimuli.     

Behavioral effects of sequential and one-stage ablations of orbital prefrontal cortex in the monkey

The purpose of this investigation was to determine whether sequential (i.e., serial) ablation of the monkey's orbital prefrontal cortex would lead to a reduction in the severity of the behavioral impairment usually associated with one-stage bilateral removal of this tissue. The lateral orbital cortex was ablated in four operations spaced 3 weeks apart or in a one-stage procedure. The monkeys were examined on a visual go-no go differentiation task, spatial delayed-alternation, and object reversal learning. The results reveal no differences between the effects of sequential and one-stage ablations. These findings differ from previous experiments that demonstrated a degree of functional recovery after the sequential removal of a sector of the dorsolateral prefrontal cortex. Since lesion studies with infant monkeys have also demonstrated that functional recovery occurs after early ablation of dorsolateral cortex but not after early removal of orbital frontal cortex, recovery of behavioral functions after infant and sequential lesions may involve similar neural mechanisms.     

Electrophysiologic evidence of increased distractibility after dorsolateral prefrontal lesions

Patients with left prefrontal lesions and control subjects showed enhanced event-related potentials (ERPs) to attended tone sequences presented in a dichotic attention task. ERP enhancements were comparable at short and long interstimulus intervals (ISIs), and did not depend upon whether attended stimuli were preceded by other attended stimuli or by distracting stimuli in the opposite ear. In contrast, patients with right prefrontal lesions showed absent ERP attention effects to contralateral (left ear) tones at all ISIs, and reduced attention effects to ipsilateral tones at long ISIs and when these were preceded by distracting sounds. The results are consistent with an asymmetric organization of dorsolateral prefrontal cortex, and indicate that increased distractibility may contribute to the attention disorders that follow prefrontal lesions.     

Frontal lobe involvement in spatial span: converging studies of normal and impaired function

Although monkey lesion studies involving the prefrontal cortex commonly report working memory deficits, and neuroimaging studies consistently show prefrontal involvement in such tasks, patients with damage to this region commonly fail to show any working memory impairment. Such a discrepancy may be due to insensitive testing measures for patients, as well as small, yet critical differences between working memory tasks in imaging and patient studies. The current study utilised a more sensitive measure of spatial working memory spans, based either on structured or unstructured spatial arrays. A PET study in normal subjects confirmed that both variants did indeed activate prefrontal cortex. The same tasks were given to frontal lobe patients and closely matched controls. Patients with large frontal lesions were significantly impaired on this task, with those patients with damage to the right dorsolateral prefrontal cortex appearing particularly impaired. This result demonstrates that prefrontal cortex is necessary for normal working memory, even in simple tasks, such as spatial span. It is suggested, however, that the patient deficit reflects strategic or goal-based dysfunction, rather than storage limitations.     

Disorders of executive consciousness

Executive function is a higher order cognitive capacity that involves memory, perception and performance of complex tasks. Disorders of the executive functions are sign of lesions in the prefrontal cortex, involving the prefrontal-striatal-thalamic networks and the parietal association areas. According to signs and localization, five basic prefrontal syndromes are recognised. 1. Damage in posterior dorsolateral prefrontal cortex and subcortical nuclei causes the dorsolateral syndrome with impaired decision making, working memory and planning. 2. The ventromedial-orbitofrontal syndrome: if lesion spares the basal forebrain, memory can be preserved, but poor social decision making develops. 3. The dorsomedial syndrome consists of attention disorder, akinesia, mutism and apathy. 4. The bilateral ventrolateral prefrontal regions serve perception of self and environment. 5. The ventral lateral (verbalizer) area of the dominant hemisphere coordinates language. Executive impairments can be found in cerebrovascular, Parkinson's and other diseases of basal ganglia, and in frontotemporal lobar degeneration. The dorsolateral syndrome can be examined by the use of Wisconsin card sorting test, self ordered pointing task and the delayed response task. Prefrontal-basal function can be assessed by Gambling-, Faux Pas-, and Emotion identification tasks. Conclusions: 1. A dysexecutive syndrome does not fulfil the criteria of dementia. 2. A "frontal syndrome" is an indefinite eponym. Focal lesions in prefrontal systems lead to localization-specific symptoms, which can be defined by psychometric tests. 3. In neurological diseases associated with multifocal damage of the brain neuropsychologic tests may help to determine strategic lesions, which are responsible for the actual syndromes.     

Neural correlates of human wayfinding in stroke patients

Wayfinding is a complex cognitive function involving different types of information, such as knowledge about landmarks and direction information. This variety of processes suggest that multiple neural mechanisms are involved, e.g., the hippocampal system, the posterior parietal and temporal cortical areas. Although patient studies and imaging studies have given important insights in the exact neural circuitry underlying wayfinding, many controversies remain. Therefore, the current study sets out to further examine the neuroanatomical correlates of wayfinding in a sample of 31 stroke patients with unilateral lesions, tested with a series of different wayfinding tasks, including landmark recognition, landmark ordering, route reversal and route drawing. For all patients, the exact location of their lesion was determined using CT or MRI scans. Based on existing literature, a number of relevant brain areas were demarcated, after which the extent of damage to these areas was determined for each patient separately. Performance on the landmark recognition task was impaired by damage to the right hippocampal formation, whereas a weak correlation was found between damage to the dorsolateral prefrontal cortex and processing the order of the landmarks. Several brain areas were found to be involved in retracing a route from the end to the beginning, including the right hippocampal formation, the right posterior parietal cortex, the right dorsolateral prefrontal cortex and the right temporal lobe. Finally, damage to the right temporal lobe impaired the ability to draw the route.     

Amygdalar interaction with the mediodorsal nucleus of the thalamus and the ventromedial prefrontal cortex in stimulus-reward associative learning in the monkey

Cynomolgus monkeys (Macaca fascicularis) were assessed for their ability to associate visual stimuli with food reward. They learned a series of new 2-choice visual discriminations between colored patterns displayed on a monitor screen. The feedback for correct choice was the delivery of food. In order to promote associative learning between the visual stimuli and the incentive value of the food reward, reward delivery was not accompanied by any distinctive visual feedback on the display screen. The rate of learning new problems was assessed before and after surgery in a total of 16 monkeys. Three groups of 3 monkeys received bilaterally symmetrical ablations in either the amygdala, the mediodorsal nucleus of the thalamus, or the ventromedial prefrontal cortex. All these groups showed a severe postoperative learning impairment. Seven other animals were given a unilateral ablation in 1 of those 3 structures and a second unilateral ablation, in each case contralateral to and different from the first, in order to produce 2 groups in which a putative amygdalo-thalamo-prefrontal pathway had been disconnected by crossed unilateral lesions. One disconnection group had lesions in the amygdala and ventromedial prefrontal cortex; the other had lesions in the amygdala and the mediodorsal nucleus of the thalamus. The disconnection groups showed a significant impairment, but the effect of the disconnection surgeries was significantly milder than the effect of any of the 3 bilaterally symmetrical lesions. Therefore, symmetrical bilateral lesions in either the amygdala, the mediodorsal nucleus, or the ventromedial prefrontal cortex produce similar impairments in the present task, implying that these structures are functionally related to each other; but the relatively mild effect of disconnecting these structures from each other argues against the hypothesis that they are serial stages in a single, tightly linked functional pathway.     

Visual recognition impairment follows ventromedial but not dorsolateral prefrontal lesions in monkeys

Visual recognition in monkeys appears to involve the participation of two limbothalamic pathways, one including the amygdala and the magnocellular portion of the medial dorsal nucleus (MDmc) and the other, the hippocampus and the anterior nuclei of the thalamus (Ant N). Both MDmc and Ant N project, in turn, to the prefrontal cortex, mainly to its ventral and medial portions. To test whether the prefrontal projection targets of the two limbothalamic pathways also participate in memory functions, performance on a variety of learning and memory tasks was assessed in monkeys with lesions of the ventromedial prefrontal cortex (Group VM). Normal monkeys and monkeys with lesions of dorsolateral prefrontal cortex (Group DL) served as controls. Group VM was severely impaired on a test of object recognition, whereas Group DL did not differ appreciably from normal animals. Conversely, the animals in Group VM were able to learn a spatial delayed response task, whereas 2 of the 3 animals in Group DL could not. Neither group was impaired in the acquisition of visual discrimination habits, even though the successive trials on a given discrimination were separated by 24-h intervals. The patterns of deficit suggest that ventromedial prefrontal cortex constitutes another station in the limbothalamic system underlying cognitive memory processes, whereas the dorsolateral prefrontal cortex lies outside this system. The results support the view that the classical delayed-response deficit observed after dorsolateral prefrontal lesions represents a perceptuo-mnemonic impairment in spatial functions selectively rather than a memory loss of a more general nature.     

Interaction of the Amygdala with the Frontal Lobe in Reward Memory

Five cynomolgus monkeys (Macaca fascicularis) were assessed for their ability to associate visual stimuli with food reward. They learned a series of new two-choice visual discriminations between coloured patterns displayed on a touch-sensitive monitor screen; the feedback for correct choice was delivery of food. Normal learning in this task is known to be dependent on the amygdala. The monkeys received brain lesions which were designed to disconnect the amygdala from interaction with other brain structures thought to be involved in this memory task. All the monkeys received an amygdalectomy in one hemisphere and lesions in the other hemisphere of some of the projection targets of the amygdala, namely the ventral striatum, the mediodorsal thalamus and the ventromedial prefrontal cortex. The rate of learning new problems was assessed before and after each operation. Disconnection of the amygdala from the ventral striatum was without effect on learning rate. An earlier study had shown that disconnection of the amygdala from either the mediodorsal thalamus or the ventromedial prefrontal cortex produced only a mild impairment, significantly less severe than that produced by bilateral lesions of any of these three structures. The present results show, however, that disconnection of the amygdala from both the mediodorsal thalamus and the ventromedial prefrontal cortex in the same animal, by crossed unilateral lesions of the amygdala in one hemisphere and of both the mediodorsal thalamus and the ventromedial prefrontal cortex in the other hemisphere, produces an impairment as severe as that which follows bilateral lesions of any of these three structures. These results show that, in stimulus – reward associative memory, the role of the amygdala is entirely dependent on its interaction with the frontal lobe, either by direct projections or by indirect subcortical pathways including the mediodorsal nucleus of the thalamus; and that there are at least two partially independent pathways by which the amygdala can influence the frontal lobe.     

Schizophrenia patients demonstrate a distinctive pattern of decision-making impairment on the Iowa Gambling Task

Although dorsolateral prefrontal cortex (DLPFC) abnormalities in schizophrenia are well established, several lines of evidence suggest the orbitofrontal cortex (OFC) may also be dysfunctional in this disorder. We examined the performance of schizophrenia patients and nonpatient controls on the Iowa Gambling Task [Cognition 50 (1994) 7], a decision-making task sensitive to OFC damage that involves a series of selections from four decks of cards that vary in their reward/punishment profiles. Patients also completed neuropsychological tests assessing DLPFC functions and clinical symptom assessments. The schizophrenic patients demonstrated a pattern of impaired performance that differed both from healthy controls and from the "non-conservative" pattern typically found in patients with OFC lesions. The patients selected from the two card decks that had low frequency and high magnitude punishments significantly more often than the decks with high frequency and low magnitude punishments. Performance on the task was not strongly related to tests sensitive to DLPFC dysfunction but was correlated with negative symptoms. Results suggest that individuals with schizophrenia display a pattern of compromised decision-making that is somewhat distinct from that found in OFC lesion patients and that may be linked to certain clinical symptoms.     

Inefficiency in self-organized attentional switching in the normal aging population is associated with decreased activity in the ventrolateral prefrontal cortex

Studies of the aging brain have demonstrated that areas of the frontal cortex, along with their associated top-down executive control processes, are particularly prone to the neurodegenerative effects of age. Here, we investigate the effects of aging on brain and behavior using a novel task, which allows us to examine separate components of an individual's chosen strategy during routine problem solving. Our findings reveal that, contrary to previous suggestions of a specific decrease in cognitive flexibility, older participants show no increased level of perseveration to either the recently rewarded object or the recently relevant object category. In line with this lack of perseveration, lateral and medial regions of the orbito-frontal cortex, which are associated with inhibitory control and reward processing, appear to be functionally intact. Instead, a general loss of efficient problem-solving strategy is apparent with a concomitant decrease in neural activity in the ventrolateral prefrontal cortex and the posterior parietal cortex. The dorsolateral prefrontal cortex is also affected during problem solving, but age-related decline within this region appears to occur at a later stage.     

Stroop performance in bipolar disorder: further evidence for abnormalities in the ventral prefrontal cortex

OBJECTIVES: Bipolar patients are impaired in Stroop task performance, a measure of selective attention. Structural and functional abnormalities in task-associated regions, in particular the prefrontal cortex (PFC), have been reported in this population. We aimed to examine the relationship between functional abnormalities, impaired task performance and the severity of depressive symptoms in bipolar patients. METHODS: Remitted bipolar patients (n = 10; all medicated), either euthymic or with subsyndromal depression, and age-matched control subjects (n = 11) viewed 10 alternating blocks of incongruent Stroop and control stimuli, naming the colour of the ink. Neural response was measured using functional magnetic resonance imaging. We computed between-group differences in neural response and within-group correlations with mood and anxiety. RESULTS: There were no significant between-group differences in task performance. During the Stroop condition, controls demonstrated greater activation of visual and dorsolateral and ventrolateral prefrontal cortical areas; bipolar patients demonstrated relative deactivation within orbital and medial prefrontal cortices. Depression scores showed a trend towards a negative correlation with the magnitude of orbitofrontal cortex deactivation in bipolar patients, whereas state anxiety correlated positively with activation of dorsolateral PFC and precuneus in controls. CONCLUSIONS: Our findings confirm previous reports of decreased ventral prefrontal activity during Stroop task performance in bipolar patients, and suggest a possible negative correlation between this and depression severity in bipolar patients. These findings further highlight the ventromedial PFC as a potential candidate for illness related dysfunction in bipolar disorder.     

Deficits in social knowledge following damage to ventromedial prefrontal cortex

Patients with damage to the frontal lobes frequently exhibit impaired social behavior, but it is not clear which specific processes are disrupted. The authors investigated the ability to interpret nonverbal emotional expression in patients with lesions involving ventromedial (N=20) or dorsolateral prefrontal cortex (N=9) and in healthy volunteers (N=23). As hypothesized, only patients with ventromedial prefrontal lesions showed impaired task performance relative to normal comparison subjects. These results suggest that deficits in social knowledge, namely difficulty interpreting nonverbal emotional expression, contribute to the aberrant social behavior observed following ventromedial prefrontal cortex lesions.     

Cortical hemodynamic mechanisms of reversal learning using high-resolution functional near-infrared spectroscopy: A pilot study

ObjectivesReversal learning is widely used to analyze cognitive flexibility and characterize behavioral abnormalities associated with impulsivity and disinhibition. Recent studies using fMRI have focused on regions involved in reversal learning with negative and positive reinforcers. Although the frontal cortex has been consistently implicated in reversal learning, few studies have focused on whether reward and punishment may have different effects on lateral frontal structures in these tasks.MethodsDuring this pilot study on eight healthy subjects, we used functional near infra-red spectroscopy (fNIRS) to characterize brain activity dynamics and differentiate the involvement of frontal structures in learning driven by reward and punishment.ResultsWe observed functional hemispheric asymmetries between punishment and reward processing by fNIRS following reversal of a learned rule. Moreover, the left dorsolateral prefrontal cortex (l-DLPFC) and inferior frontal gyrus (IFG) were activated under the reward condition only, whereas the orbito-frontal cortex (OFC) was significantly activated under the punishment condition, with a tendency towards activation for the right cortical hemisphere (r-DLPFC and r-IFG). Our results are compatible with the suggestion that the DLPFC is involved in the detection of contingency change. We propose a new representation for reward and punishment, with left lateralization for the reward process.ConclusionsThe results of this pilot study provide insights into the indirect neural mechanisms of reversal learning and behavioral flexibility and confirm the use of fNIRS imaging in reversal-learning tasks as a translational strategy, particularly in subjects who cannot undergo fMRI recordings.     

The role of prefrontal cortex in object-in-place learning in monkeys

Previous ablation studies in monkeys suggest that prefrontal cortex is involved in a wide range of learning and memory tasks. However, monkeys with crossed unilateral lesions of frontal and temporal cortex are unimpaired at concurrent object-reward association learning but are impaired at conditional learning and the implementation of memory-based performance rules. We trained seven monkeys preoperatively on an associative learning task that required them to associate objects embedded in unique complex scenes with reward. Three monkeys then had crossed unilateral lesions of frontal and inferior temporal cortex and the remaining monkeys had bilateral prefrontal cortex ablation. Both groups were severely impaired postoperatively. These results show that both bilateral prefrontal cortex ablation and frontal-temporal disconnection impair associative learning for objects embedded in scenes. The results provide evidence that the function of frontal-temporal interactions in memory is not limited to conditional learning tasks and memory-dependent performance rules. We propose that rapid object-in-place learning requires the interaction of frontal cortex with inferotemporal cortex because visual object and contextual information which is captured over multiple saccades must be processed as a unique complex event that is extended in time. The present results suggest a role for frontal-temporal interaction in the integration of visual information over time.     

Double dissociation between hippocampal and prefrontal lesions on an operant delayed matching task and a water maze reference memory task

The hippocampus and prefrontal cortex have both been implicated in various aspects of the acquisition, retention and performance of delayed matching to position (DMTP) tasks in the rat, although their precise respective contributions remain unclear. In the present study, rats were trained preoperatively on DMTP before receiving excitotoxic bilateral lesions of either the entire hippocampus or the medial prefrontal cortex. Rats with lesions of the prefrontal cortex exhibited a significant delay-dependent impairment on retention of the DMTP task, whereas hippocampal lesions were without effect. Rats were also exposed to a switch in the contingencies to a 'non-matching' rule, as an analogue of switching between decision rules in the human Wisconsin Card Sorting Test, in which human patients with prefrontal damage are impaired. Both lesion groups acquired the new contingency at control levels, providing no evidence towards a role for either of these areas in this type of rule-switching. The same rats were also assessed in a spatial reference memory task in the water maze, which revealed an impairment in escape latencies and path length that was specific to the hippocampal lesions. The results corroborate previous evidence that the hippocampus is not necessary for at least some aspects of working memory performance in the DMTP task, whereas the delay-dependent deficit in the prefrontal lesion group support this task as a potentially powerful tool for assessing the cognitive changes associated with frontal damage and repair.     

Rhinal and dorsolateral prefrontal cortex lesions produce selective impairments in object and spatial learning and memory in canines

To examine the effects of rhinal and dorsolateral prefrontal cortex lesions on object and spatial recognition memory in canines, we used a protocol in which both an object (delayed nonmatching to sample, or DNMS) and a spatial (delayed nonmatching to position or DNMP) recognition task were administered daily. The tasks used similar procedures such that only the type of stimulus information to be remembered differed. Rhinal cortex (RC) lesions produced a selective deficit on the DNMS task, both in retention of the task rules at short delays and in object recognition memory. By contrast, performance on the DNMP task remained intact at both short and long delay intervals in RC animals. Subjects who received dorsolateral prefrontal cortex (dlPFC) lesions were impaired on a spatial task at a short, 5-second delay, suggesting disrupted retention of the general task rules; however, this impairment was transient, and long-term spatial memory performance was unaffected in dlPFC subjects. The present results provide support for the involvement of the RC in object, but not visuospatial, processing and recognition memory, whereas the dlPFC appears to mediate retention of a nonmatching rule. These findings support theories of functional specialization within the medial temporal lobe and frontal cortex and suggest that rhinal and dorsolateral prefrontal cortices in canines are functionally similar to analogous regions in other mammals.     

Delayed response tasks and prefrontal lesions in man—Evidence for self generated patterns of behaviour with poor environmental modulation

The functions of the frontal lobes in humans are still under debate, mainly because none of the neuropsychological tests used for their assessment is sufficiently specific for frontal dysfunction. In animals, the delayed reaction paradigm is considered to be a specific marker of the function of dorsolateral region of the prefrontal cortex. It seemed of interest, therefore, to attempt to apply this paradigm to patients with recent and limited cortical lesion of vascular origin. The performance of patients with dorsolateral prefrontal lesion (n = 10) was compared to that of patients with post-central lesion (n = 10) and control subjects (n = 24), in four experiments: a Delayed Response task in which the correct answer was previously indicated by an explicit cue (externally guided task); Delayed Alternation and Non-Alternation tasks coupled with a Delayed Reversal task in which the patient had to discover the rule by himself in the absence of explicit cues (internally driven tasks).

Patients with prefrontal lesion showed a specific deficit in the Delayed Response task, the emergence of a stereotyped behaviour in the Delayed Alternation task and an inability to deduce and to transfer rules (non-alternation and reversal), mainly because of difficulty in abandoning previous behaviours. Our study demonstrates that the prefrontal cortex plays a role in behavioural adaptation to challenging new situations by inhibiting not only ongoing elaborated programmes but also the emergence of previously established automatic programmes. The respective role of the prefrontal cortex and the basal ganglia in these two levels of behavioural organization is discussed.