Lesley K. Fellows

Food and drug cues activate similar brain regions: a meta-analysis of functional MRI studies.

In healthy individuals, food cues can trigger hunger and feeding behavior. Likewise, smoking cues can trigger craving and relapse in smokers. Brain imaging studies report that structures involved in appetitive behaviors and reward, notably the insula, striatum, amygdala and orbital frontal cortex, tend to be activated by both visual food and smoking cues. Here, by carrying out a meta-analysis of human neuro-imaging studies, we investigate the neural network activated by: 1) food versus neutral cues (14 studies, 142 foci) 2) smoking versus neutral cues (15 studies, 176 foci) 3) smoking versus neutral cues when correlated with craving scores (7 studies, 108 foci). PubMed was used to identify cue-reactivity imaging studies that compared brain response to visual food or smoking cues to neutral cues. Fourteen articles were identified for the food meta-analysis and fifteen articles were identified for the smoking meta-analysis. Six articles were identified for the smoking cue correlated with craving analysis. Meta-analyses were carried out using activation likelihood estimation. Food cues were associated with increased blood oxygen level dependent (BOLD) response in the left amygdala, bilateral insula, bilateral orbital frontal cortex, and striatum. Smoking cues were associated with increased BOLD signal in the same areas, with the exception of the insula. However, the smoking meta-analysis of brain maps correlating cue-reactivity with subjective craving did identify the insula, suggesting that insula activation is only found when craving levels are high. The brain areas identified here are involved in learning, memory and motivation, and their cue-induced activity is an index of the incentive salience of the cues. Using meta-analytic techniques to combine a series of studies, we found that food and smoking cues activate comparable brain networks. There is significant overlap in brain regions responding to conditioned cues associated with natural and drug rewards.

Physiological Stimulation Increases Nonoxidative Glucose Metabolism in the Brain of the Freely Moving Rat

Abstract: The effects of mild stress on nonoxidative glucose metabolism were studied in the brain of the freely moving rat. Extracellular lactate levels in the hippocampus and striatum were monitored at 2.5‐min intervals with microdialysis coupled with an enzyme‐based flow injection analysis system. Ten minutes of restraint stress led to a 235% increase in extracellular lactate levels in the striatum. A 5‐min tail pinch caused an increase of 193% in the striatum and 170% in the hippocampus. Local application of tetrodotoxin in the striatum blocked the rise in lactate following tail pinch and inhibited the subsequent clearance of lactate from the extracellular fluid. Local application of the noncompetitive N‐methyl‐d‐aspartate receptor antagonist MK‐801 had no effect on the tail pinch‐stimulated increase in lactate in the striatum. These results show that mild physiological stimulation can lead to a rapid increase in nonoxidative glucose metabolism in the brain.

The Cognitive Neuroscience of Human Decision Making: A Review and Conceptual Framework:

Decision making, the process of choosing between options, is a fundamental human behavior that has been studied intensively by disciplines ranging from cognitive psychology to economics. Despite the importance of this behavior, the neural substrates of decision making are only beginning to be understood. Impaired decision making is recognized in neuropsychiatric conditions such as dementia and drug addiction, and the inconsistencies and biases of healthy decision makers have been intensively studied. However, the tools of cognitive neuroscience have only recently been applied to understanding the brain basis of this complex behavior. This article reviews the literature on the cognitive neuroscience of human decision making, focusing on the roles of the frontal lobes, and provides a conceptual framework for organizing this disparate body of work.

Extracellular Brain Glucose Levels Reflect Local Neuronal Activity: A Microdialysis Study in Awake, Freely Moving Rats

Abstract: The relationship between brain extracellular glucose levels and neuronal activity was evaluated using microdialysis in awake, freely moving rats. The sodium channel blocker tetrodotoxin and the depolarizing agent veratridine were administered through the dialysis probe to provoke local changes in neuronal activity. The extracellular glucose content was significantly increased in the presence of tetrodotoxin and decreased sharply following veratridine application. The systemic injection of a general anaesthetic, chloral hydrate, led to a large and prolonged increase in extracellular glucose levels. The brain extracellular glucose concentration was estimated by comparing dialysate glucose efflux over a range of inlet glucose concentrations. A mean value of 0.47 mM was obtained in five animals. The results are discussed in terms of the coupling between brain glucose supply and metabolism. The changes observed in extracellular glucose levels under various conditions suggest that supply and utilization may be less tightly linked in the awake rat than has previously been postulated.

Dissociable elements of human foresight: a role for the ventromedial frontal lobes in framing the future, but not in discounting future rewards.

Impaired future thinking may be a core aspect of impulsive decision making. Recent efforts to understand the brain processes that underlie impulsivity have suggested a role for the frontal lobes. However, future thinking is unlikely to be a unitary process, and the frontal lobes are not a homogeneous entity. The present study contrasted the effects of dorsolateral and ventromedial frontal lobe damage on two distinct aspects of future thinking in humans. Temporal discounting, the subjective devaluation of reward as a function of delay, is not affected by frontal lobe injury. In contrast, a normal future time perspective (a measure of the length of an individuals self-defined future) depends on the ventromedial, but not dorsolateral, frontal lobes. Furthermore, investigation of the relationship of these two measures with classical symptoms of frontal lobe damage indicates that future time perspective correlates with apathy, not impulsivity. Apathy may deserve more attention in understanding both impaired future thinking and the impaired decision making that may result.

Beyond Reversal: A Critical Role for Human Orbitofrontal Cortex in Flexible Learning from Probabilistic Feedback

Damage to the orbitofrontal cortex (OFC) has been linked to impaired reinforcement processing and maladaptive behavior in changing environments across species. Flexible stimulus–outcome learning, canonically captured by reversal learning tasks, has been shown to rely critically on OFC in rats, monkeys, and humans. However, the precise role of OFC in this learning remains unclear. Furthermore, whether other frontal regions also contribute has not been definitively established, particularly in humans. In the present study, a reversal learning task with probabilistic feedback was administered to 39 patients with focal lesions affecting various sectors of the frontal lobes and to 51 healthy, demographically matched control subjects. Standard groupwise comparisons were supplemented with voxel-based lesion-symptom mapping to identify regions within the frontal lobes critical for task performance. Learning in this dynamic stimulus-reinforcement environment was considered both in terms of overall performance and at the trial-by-trial level. In this challenging, probabilistic context, OFC damage disrupted both initial and reversal learning. Trial-by-trial performance patterns suggest that OFC plays a critical role in interpreting feedback from a particular trial within the broader context of the outcome history across trials rather than in simply suppressing preexisting stimulus–outcome associations. The findings show that OFC, and not other prefrontal regions, plays a necessary role in flexible stimulus–reinforcement learning in humans.

Ventromedial frontal lobe damage disrupts value maximization in humans

Recent work in neuroeconomics has shown that regions in orbitofrontal and medial prefrontal cortex encode the subjective value of different options during choice. However, these electrophysiological and neuroimaging studies cannot demonstrate whether such signals are necessary for value-maximizing choices. Here we used a paradigm developed in experimental economics to empirically measure and quantify violations of utility theory in humans with damage to the ventromedial frontal lobe (VMF). We show that people with such damage are more likely to make choices that violate the generalized axiom of revealed preference, which is the one necessary and sufficient condition for choices to be consistent with value maximization. These results demonstrate that the VMF plays a critical role in value-maximizing choice.

Ventromedial frontal lobe plays a critical role in facial emotion recognition

The ventromedial prefrontal cortex has been implicated in a variety of emotion processes. However, findings regarding the role of this region specifically in emotion recognition have been mixed. We used a sensitive facial emotion recognition task to compare the emotion recognition performance of 7 subjects with lesions confined to ventromedial prefrontal regions, 8 subjects with lesions elsewhere in prefrontal cortex, and 16 healthy control subjects. We found that emotion recognition was impaired following ventromedial, but not dorsal or lateral, prefrontal damage. This impairment appeared to be quite general, with lower overall ratings or more confusion between all six emotions examined. We also explored the relationship between emotion recognition performance and the ability of the same patients to experience transient happiness and sadness during a laboratory mood induction. We found some support for a relationship between sadness recognition and experience. Taken together, our results indicate that the ventromedial frontal lobe plays a crucial role in facial emotion recognition, and suggest that this deficit may be related to the subjective experience of emotion.

A Longitudinal View of Apathy and Its Impact After Stroke

Background and Purpose— Stroke survivors are often described as apathetic. Because apathy may be a barrier to participation in promising therapies, more needs to be learned about apathy symptoms after stroke. The specific objective was to estimate the extent to which apathy changes with time over the first year after stroke and the impact of apathy on recovery. Methods— The Apathy Assessed cohort was formed from stroke survivors participating in a longitudinal study of health-related quality of life after stroke. A family caregiver completed an apathy questionnaire by telephone at 1, 3, 6, and 12 months after stroke (n=408). Group-based trajectory modeling and ordinal regression were used to identify distinctive groups of individuals with similar trajectories of apathy over the first year after stroke and predictors of apathy trajectory. Results— Both 3- and 5-group trajectory models fit the data. We used the 5-group model because of the potential to further explore the apathy construct. The largest group (50%) had low apathy and 33% had minor apathy that remained stable throughout the first year after stroke. A small proportion (3%) of the study sample had high apathy that remained high. Two other groups of almost equal size (7%) showed worsening and improving apathy. Poor cognitive status, low functional status, and high comorbidity predicted higher apathy. High apathy had a significant negative effect on physical function, participation, health perception, and physical health over the first 12 months after stroke. Conclusion— Some degree of apathy was prevalent and persistent after stroke and was predicted by older age, poor cognitive status, and low functional status after stroke. Even a minor level of apathy had an important and statistically significant impact on stroke outcomes.

Double Dissociation of Stimulus-Value and Action-Value Learning in Humans with Orbitofrontal or Anterior Cingulate Cortex Damage

Adaptive decision making involves selecting the most valuable option, typically by taking an action. Such choices require value comparisons, but there is debate about whether these comparisons occur at the level of stimuli (goods-based) value, action-based value, or both. One view is that value processes occur in series, with stimulus value informing action value. However, lesion work in nonhuman primates suggests that these two kinds of choice are dissociable. Here, we examined action-value and stimulus-value learning in humans with focal frontal lobe damage. Orbitofrontal damage disrupted the ability to sustain the correct choice of stimulus, but not of action, after positive feedback, while damage centered on dorsal anterior cingulate cortex led to the opposite deficit. These findings argue that there are distinct, domain-specific mechanisms by which outcome value is applied to guide subsequent decisions, depending on whether the choice is between stimuli or between actions.