Separate value comparison and learning mechanisms in macaque medial and lateral orbitofrontal cortex.

Uncertainty about the function of orbitofrontal cortex (OFC) in guiding decision-making may be a result of its medial (mOFC) and lateral (lOFC) divisions having distinct functions. Here we test the hypothesis that the mOFC is more concerned with reward-guided decision making, in contrast with the lOFC's role in reward-guided learning. Macaques performed three-armed bandit tasks and the effects of selective mOFC lesions were contrasted against lOFC lesions. First, we present analyses that make it possible to measure reward-credit assignment--a crucial component of reward-value learning--independently of the decisions animals make. The mOFC lesions do not lead to impairments in reward-credit assignment that are seen after lOFC lesions. Second, we examined how the reward values of choice options were compared. We present three analyses, one of which examines reward-guided decision making independently of reward-value learning. Lesions of the mOFC, but not the lOFC, disrupted reward-guided decision making. Impairments after mOFC lesions were a function of the multiple option contexts in which decisions were made. Contrary to axiomatic assumptions of decision theory, the mOFC-lesioned animals' value comparisons were no longer independent of irrelevant alternatives.

Distinct roles of three frontal cortical areas in reward-guided behavior.

Functional magnetic resonance imaging was used to measure activity in three frontal cortical areas, the lateral orbitofrontal cortex (lOFC), medial orbitofrontal cortex (mOFC)/ventromedial frontal cortex (vmPFC), and anterior cingulate cortex (ACC), when expectations about type of reward, and not just reward presence or absence, could be learned. Two groups of human subjects learned 12 stimulus-response pairings. In one group (Consistent), correct performances of a given pairing were always reinforced with a specific reward outcome, whereas in the other group (Inconsistent), correct performances were reinforced with randomly selected rewards. The mOFC/vmPFC and lOFC were not distinguished by simple differences in relative preference for positive and negative outcomes. Instead lOFC activity reflected updating of reward-related associations specific to reward type; lOFC was active whenever informative outcomes allowed updating of reward-related associations, regardless of whether the outcomes were positive or negative, and the effects were greater when consistent stimulus-outcome and response-outcome mappings were present. A psychophysiological interaction analysis demonstrated changed coupling between lOFC and brain areas for visual object representation, such as perirhinal cortex, and reward-guided learning, such as the amygdala, ventral striatum, and habenula/mediodorsal thalamus. In contrast, mOFC/vmPFC activity reflected expected values of outcomes and occurrence of positive outcomes, regardless of consistency of outcome mappings. The third frontal cortical region, the ACC, reflected the use of reward type information to guide response selection. ACC activity reflected the probability of selecting the correct response, was greater when consistent outcome mappings were present, and was related to individual differences in propensity to select the correct response.

Re-evaluating the role of the orbitofrontal cortex in reward and reinforcement.

The orbitofrontal cortex and adjacent ventromedial prefrontal cortex carry reward representations and mediate flexible behaviour when circumstances change. Here we review how recent experiments in humans and macaques have confirmed the existence of a major difference between the functions of the ventromedial prefrontal cortex and adjacent medial orbitofrontal cortex (mOFC) on the one hand and the lateral orbitofrontal cortex (lOFC) on the other. These differences, however, may not be best accounted for in terms of specializations for reward and error/punishment processing as is commonly assumed. Instead we argue that both lesion and functional magnetic resonance imaging studies reveal that the lOFC is concerned with the assignment of credit for both reward and error outcomes to the choice of specific stimuli and with the linking of specific stimulus representations to representations of specific types of reward outcome. By contrast, we argue that the ventromedial prefrontal cortex/mOFC is concerned with evaluation, value-guided decision-making and maintenance of a choice over successive decisions. Despite the popular view that they cause perseveration of behaviour and inability to inhibit repetition of a previously made choice, we found that lesions in neither orbitofrontal subdivision caused perseveration. On the contrary, lesions in the lOFC made animals switch more rapidly between choices when they were finding it difficult to assign reward values to choices. Lesions in the mOFC caused animals to lose their normal predisposition to repeat previously successful choices, suggesting that the mOFC does not just mediate value comparison in choice but also facilitates maintenance of the same choice if it has been successful.

Impulsive choice in hippocampal but not orbitofrontal cortex-lesioned rats on a nonspatial decision-making maze task.

Orbitofrontal cortical (OFC) and hippocampal (HPC) lesions in primates and rodents have been associated with impulsive behaviour. We showed previously that OFC- or HPC-lesioned rats chose the immediate low-reward (LR) option in preference to the delayed high-reward (HR) option, where LR and HR were associated with different spatial responses in a uniform grey T-maze. We now report that on a novel nonspatial T-maze task in which the HR and LR options are associated with patterned goal arms (black-and-white stripes vs. gray), OFC-lesioned rats did not show impulsive behaviour, choosing the delayed HR option, and were indistinguishable from controls. In contrast, HPC-lesioned rats exhibited impulsive choice in the nonspatial decision-making task, although they chose the HR option on the majority of trials when there was a 10-s delay associated with both goal arms. The previously reported impairment in OFC-lesioned rats on the spatial version of the intertemporal choice task is unlikely to reflect a general problem with spatial learning, because OFC lesions were without effect on acquisition of the standard reference memory water-maze task and spatial working memory performance (nonmatching-to-place) on the T-maze. The differential effect of OFC lesions on the two versions of the intertemporal choice task may be explained instead in terms of the putative role of OFC in using associative information to represent expected outcomes and generate predictions. The impulsivity in HPC-lesioned rats may reflect impaired temporal information processing, and emphasizes a role for the hippocampus beyond the spatial domain.

Anatomical connectivity of the subgenual cingulate region targeted with deep brain stimulation for treatment-resistant depression.

Chronic deep brain stimulation (DBS) of subgenual cingulate white matter results in dramatic remission of symptoms in some previously treatment-resistant depression patients. The effects of stimulation may be mediated locally or via corticocortical or corticosubcortical connections. We use tractography to define the likely connectivity of cingulate regions stimulated in DBS-responsive patients using diffusion imaging data acquired in healthy control subjects. We defined 2 distinct regions within anterior cingulate cortex based on anatomical connectivity: a pregenual region strongly connected to medial prefrontal and anterior midcingulate cortex and a subgenual region with strongest connections to nucleus accumbens, amygdala, hypothalamus, and orbitofrontal cortex. The location of electrode contact points from 9 patients successfully treated with DBS lies within this subgenual region. The anatomical connectivity of the subgenual cingulate region targeted with DBS for depression supports the hypothesis that treatment efficacy is mediated via effects on a distributed network of frontal, limbic, and visceromotor brain regions. At present, targeting of DBS for depression is based on landmarks visible in conventional magnetic resonance imaging. Preoperatively acquired diffusion imaging for connectivity-based cortical mapping could improve neurosurgical targeting. We hypothesize that the subgenual region with greatest connectivity across the distributed network described here may prove most effective.

Cognitive neuroscience: resolving conflict in and over the medial frontal cortex.

The medial surface of the brain's frontal lobe has been implicated both in the voluntary initiation of action and in monitoring actions in situations where several conflicting responses are possible. Recent work casts light on how these functions are parcelled out in the medial frontal cortex.

Contrasting roles for cingulate and orbitofrontal cortex in decisions and social behaviour.

There is general acknowledgement that both the anterior cingulate and orbitofrontal cortex are implicated in reinforcement-guided decision making, and emotion and social behaviour. Despite the interest that these areas generate in both the cognitive neuroscience laboratory and the psychiatric clinic, ideas about the distinctive contributions made by each have only recently begun to emerge. This reflects an increasing understanding of the component processes that underlie reinforcement-guided decision making, such as the representation of reinforcement expectations, the exploration, updating and representation of action values, and the appreciation that choices are guided not just by the prospect of reward but also by the costs that action entails. Evidence is emerging to suggest that the anterior cingulate and orbitofrontal cortex make distinct contributions to each of these aspects of decision making.

TMS in the parietal cortex: updating representations for attention and action.

Transcranial magnetic stimulation (TMS) is one of the most recent techniques to have been used in investigations of the parietal cortex but already a number of studies have employed it as a tool in investigations of attentional and sensorimotor processes in the human parietal cortices. The high temporal resolution of TMS has proved to be a particular strength of the technique and the experiments have led to hypotheses about when circumscribed regions of parietal cortex are critical for specific attentional and sensorimotor processes. A consistent theme that runs through many reports is that of a critical contribution of parietal areas when attention or movements are re-directed and representations for attention or action must be updated.

Visual neglect after right posterior cerebral artery infarction.

OBJECTIVES: To investigate the characteristics and neuroanatomical correlates of visual neglect after right-sided posterior cerebral artery (PCA) infarction. METHODS: 15 patients with acute PCA strokes were screened for the presence of neglect on a comprehensive battery of cognitive tests. Extra tests of visual perception were also carried out on six patients. To establish which areas were critically associated with neglect, the lesions of patients with and without neglect were compared. RESULTS: Neglect of varying severity was documented in 8 patients. In addition, higher-order visual perception was impaired in 5 of the 6 patients. Neglect was critically associated with damage to an area of white matter in the occipital lobe corresponding to a white matter tract connecting the parahippocampal gyrus with the angular gyrus of the parietal lobe. Lesions of the thalamus or splenium of the corpus callosum did not appear necessary or sufficient to cause neglect, but may mediate its severity in these patients. CONCLUSIONS: PCA stroke can result in visual neglect. Interruption of the white matter fibres connecting the parahippocampal gyrus to the angular gyrus may be important in determining whether a patient will manifest neglect.

Weighing up the benefits of work: behavioral and neural analyses of effort-related decision making.

How we decide whether a course of action is worth undertaking is largely unknown. Recently, neuroscientists have been turning to ecological approaches to address this issue, examining how animals evaluate the costs and benefits of different options. We present here evidence from rodents and monkeys that demonstrate the degree to which they take into account work and energetic requirements when deciding what responses to make. These calculations appear to be critically mediated by the anterior cingulate cortex (ACC) and mesolimbic dopamine (DA) pathways, with damage to either causing a bias towards options that are easily obtained but yield relatively smaller reward rather than alternatives that require more work but result in greater reward. The evaluation of such decisions appears to be carried out in systems independent of those involved in delay-discounting. We suggest that top-down signals from ACC to nucleus accumbens (NAc) and/or midbrain DA cells may be vital for overcoming effort-related response costs.

Action sets and decisions in the medial frontal cortex.

Activations in human dorsomedial frontal and cingulate cortices are often present in neuroimaging studies of decision making and action selection. Interpretations have emphasized executive control, movement sequencing, error detection and conflict monitoring. Recently, however, experimental approaches, using lesions, inactivation, and cell recording, have suggested that these are just components of the areas' functions. Here we review these results and integrate them with those from neuroimaging. A medial superior frontal gyrus (SFG) region centred on the pre-supplementary motor area (pre-SMA) is involved in the selection of action sets whereas the anterior cingulate cortex (ACC) has a fundamental role in relating actions to their consequences, both positive reinforcement outcomes and errors, and in guiding decisions about which actions are worth making.

The mesocortical dopamine projection to anterior cingulate cortex plays no role in guiding effort-related decisions.

Both mesolimbic dopamine (DA) and the anterior cingulate cortex (ACC) have been implicated in enabling animals to expend effort to obtain greater reward. To investigate the role of the DA pathway to ACC in working for reward, the authors tested rats on a cost-benefit T-maze paradigm in which they could either climb a barrier to obtain large reward in 1 arm (high reward [HR]) or select the low-effort alternative containing less reward (low reward [LR]). Surprisingly, ACC DA depletions had no effect on choice performance. Manipulations of barrier and reward sizes demonstrated that lesioned rats were as sensitive to the costs and benefits of the alternatives as controls. These results imply that the DA projection to ACC is not involved in guiding effort-related decisions.

Differential involvement of serotonin and dopamine systems in cost-benefit decisions about delay or effort.

RATIONALE: Although tasks assessing the role of dopamine in effort-reward decisions are similar to those concerned with the role of serotonin in impulsive choice in that both require analysis of the costs and benefits of possible actions, they have never been directly compared. OBJECTIVES: This study investigated the involvement of serotonin and dopamine in two cost-benefit paradigms, one in which the cost was delay and the other in which it was physical effort. METHODS: Sixteen rats were trained on a T-maze task in which they chose between high and low reward arms. In one version, the high reward arm was obstructed by a barrier, in the other, delivery of the high reward was delayed by 15 s. Serotonin and dopamine function were manipulated using systemic pCPA and haloperidol injections, respectively. RESULTS: Haloperidol-treated rats were less inclined either to exert more effort or to countenance a delay for a higher reward. pCPA had no effect on the performance of the rats on the effortful task, but significantly increased the rats' preference for an immediate but smaller reward. All animals (drug treated and controls) chose the high reward arm on the majority of trials when the delay or effort costs were matched in both high and low reward arms. CONCLUSION: A dissociation was found between the neurotransmitter systems involved in different types of cost-benefit decision making. While dopaminergic systems were required for decisions about both effort and delay, serotonergic systems were only needed for the latter.

Components of attentional set-switching.

A series of distinct event-related potentials (ERPs) have been recorded from the scalp of human subjects as they switch from one task to another. It is possible that task switching may depend on different mechanisms depending on whether the switch requires a change in attentional set, in other words the redirecting of attention to different aspects of a sensory stimulus, or whether it requires a change in intentional set, in others words a change in the way that responses are selected. To address this issue, the current study recorded ERPs while subjects switched between attentional sets and the results were compared with those of a previous investigation in which subjects switched between intentional sets. Subjects selected stimuli according to two conflicting attentional sets, each emphasizing one visual stimulus dimension (colour, shape). Pairs of stimuli, only one of which was to be attended, were presented for between eight and seventeen trials then either a switch or a stay cue was shown. The switch cue instructed subjects to switch from the current attentional set to the other set, while the stay cue instructed subjects to maintain the current set. Comparing ERPs time-locked to the switch and stay cues revealed neural correlates of the initiation of a task switch. Comparing the ERPs time locked to the first stimuli after either stay or switch cues identified neural correlates of the implementation of a task switch. A similar modulation over parietal electrodes was seen when subjects were switching between either attentional or intentional sets. While an intentional set switch began with a medial frontal modulation, attentional set switching began with a lateral frontal modulation. Implementing a new attentional set was associated with modulation of relatively early visual potentials, while implementing a new intentional set was associated with modulation of later response-related potentials. The results confirm that task switching consists of a number of constituent processes which may be taxed to different degrees depending on whether a task-switch paradigm requires subjects to change the way in which they select stimuli or responses.

The effect of cingulate lesions on social behaviour and emotion.

Functional and structural neuroimaging of the human cingulate cortex has identified this region with emotion and social cognition and suggested that cingulate pathology may be associated with emotional and social behavioural disturbances. The importance of the cingulate cortex for emotion and social behaviour, however, has not been clear from lesion studies. Bilateral lesions in the cingulate cortex were made in three macaques and their social interactions were compared with those of controls. Subsequently, cingulate lesions were made in the three controls and their behaviour was compared before and after surgery. Cingulate lesions were associated with decreases in social interactions, time spent in proximity with other individuals, and vocalisations but an increase in manipulation of an inanimate object. The results are consistent with a cingulate role in social behaviour and emotion.

Neuroscience: a more dynamic view of the social brain.

Information relevant for social interactions is thought to be processed in specific neural circuits. Recent studies shed new light on how that social information is encoded and processed by different brain areas.

Social network size affects neural circuits in macaques.

It has been suggested that variation in brain structure correlates with the sizes of individuals' social networks. Whether variation in social network size causes variation in brain structure, however, is unknown. To address this question, we neuroimaged 23 monkeys that had been living in social groups set to different sizes. Subject comparison revealed that living in larger groups caused increases in gray matter in mid-superior temporal sulcus and rostral prefrontal cortex and increased coupling of activity in frontal and temporal cortex. Social network size, therefore, contributes to changes both in brain structure and function. The changes have potential implications for an animal's success in a social context; gray matter differences in similar areas were also correlated with each animal's dominance within its social network.

The contribution of distinct subregions of the ventromedial frontal cortex to emotion, social behavior, and decision making.

Damage to the ventromedial frontal cortex (VMFC) in humans is associated with deficits in decision making. Decision making, however, often happens while people are interacting with others, where it is important to take the social consequences of a course of action into account. It is well known that VMFC lesions also lead to marked alterations in patients' emotions and ability to interact socially; however, it has not been clear which parts of the VMFC are critical for these changes. Recently, there has been considerable interest in the role of the VMFC in choice behavior during interpersonal exchanges. Here, we highlight recent research that suggests that two areas within or adjacent to the VMFC, the orbitofrontal cortex (OFC) and the anterior cingulate cortex (ACC), may play distinct but complementary roles in mediating normal patterns of emotion and social behavior. Converging lines of evidence from human, macaque, and rat studies now suggest that the OFC may be more specialized for simple emotional responses, such as fear and aggression, through its role in representing primary reinforcement or punishment. By contrast, the ACC may play a distinct role in more complex aspects of emotion, such as social interaction, by virtue of its connections with the discrete parts of the temporal lobe and subcortical structures that control autonomic responses.

Probabilistic diffusion tractography with multiple fibre orientations: What can we gain?

We present a direct extension of probabilistic diffusion tractography to the case of multiple fibre orientations. Using automatic relevance determination, we are able to perform online selection of the number of fibre orientations supported by the data at each voxel, simplifying the problem of tracking in a multi-orientation field. We then apply the identical probabilistic algorithm to tractography in the multi- and single-fibre cases in a number of example systems which have previously been tracked successfully or unsuccessfully with single-fibre tractography. We show that multi-fibre tractography offers significant advantages in sensitivity when tracking non-dominant fibre populations, but does not dramatically change tractography results for the dominant pathways.

Connection patterns distinguish 3 regions of human parietal cortex.

Three regions of the macaque inferior parietal lobule and adjacent lateral intraparietal sulcus (IPS) are distinguished by the relative strengths of their connections with the superior colliculus, parahippocampal gyrus, and ventral premotor cortex. It was hypothesized that connectivity information could therefore be used to identify similar areas in the human parietal cortex using diffusion-weighted imaging and probabilistic tractography. Unusually, the subcortical routes of the 3 projections have been reported in the macaque, so it was possible to compare not only the terminations of connections but also their course. The medial IPS had the highest probability of connection with the superior colliculus. The projection pathway resembled that connecting parietal cortex and superior colliculus in the macaque. The posterior angular gyrus and the adjacent superior occipital gyrus had a high probability of connection with the parahippocampal gyrus. The projection pathway resembled the macaque inferior longitudinal fascicle, which connects these areas. The ventral premotor cortex had a high probability of connection with the supramarginal gyrus and anterior IPS. The connection was mediated by the third branch of the superior longitudinal fascicle, which interconnects similar regions in the macaque. Human parietal areas have anatomical connections resembling those of functionally related macaque parietal areas.