What the orbitofrontal cortex does not do Thomas A Stalnaker,
Response inhibition is one of the first and perhaps still most influential ideas put forth as the function of prefrontal…But is response inhibition a core function of OFC?
In short, the growing number of reports showing that OFC is not necessary for reversal learning violates a key prediction of the response inhibition hypothesis, which proposes that the OFC should always be necessary for inhibiting responses. As we shall see, there are also numerous studies showing effects of OFC damage on tasks that do not seem to require response inhibition at all. Together, these works provide strong evidence that response inhibition is not a core function of the OFC.
Flexible representation of stimulus-outcome associations
Another highly influential idea suggests that OFC operates as an especially flexible associative look-up table…However, as reviewed above, the OFC is often not necessary for reversal learning. Just as this evidence contradicts the response inhibition hypothesis, it also contradicts predictions of the flexible encoding idea…These observations raise the question of precisely which aspect of associative information is being encoded in OFC52, and which task features define when OFC-dependent information is required for flexible behavior.
Emotions or somatic markers
A third influential proposal, which begins to address the question regarding the content of associative representations in OFC, is that the OFC has a central role in signaling emotions. This idea harkens back to the idea that we experience emotions as a result of peripheral feedback about bodily states. In this implementation, the OFC guides behavior via its modulation of these bodily states or somatic markers…This proposal has had an enormous effect, particularly in reawakening interest in the OFC, yet, although the basic result has been replicated many times in humans and animals, there is relatively little evidence that the deficit reflects a fundamental inability to trigger emotions. Patients with OFC damage do not exhibit flat affect or lack of emotion, nor are they unable to engage emotions in decision-making. They simply do so in a way that is unlike normal subjects…
A more recent proposal suggests that the OFC is critical for signaling value. Although firmly grounded in the historical understanding of OFC’s role in associative encoding and emotion, this idea is most strongly associated with the emergence of economic theory as a framework for neuroscience research. Here the OFC has been proposed to serve as a final accountant of value, converting information about available outcomes—their probability, magnitude, time to receipt, current desirability, costs, etc.—into a common neural currency on which to base choices, particularly between different goods.
Subsequent studies have replicated this result and shown further that these neural responses obey key principles for economic value including transitivity and menu invariance, and similar results have been reported in humans using functional magnetic resonance imaging (fMRI). For example, BOLD responses in medial orbital areas are correlated with a subject’s ‘willingness to pay’ for items during a decision-making task. In addition, BOLD correlates of value in nearby medial OFC that are specifically invariant to the identity of the expected outcomes have been reported.
Of course, these are correlative measures. Although no single approach is without drawbacks, this issue is particularly problematic for fMRI, as the analysis inherently aggregates single units and may therefore average out their unique functions, such as coding of information about identity. In unit recording work, such specific correlates are plentiful, and in at least one instance, the strength of such value-neutral outcome representations was closely related to choice behavior. Although one might argue that the aggregate signal is likely to be the function of the area overall, it seems equally likely that individual units or small ensembles could send their unique product downstream. BOLD signal is also sensitive to input and even subthreshold events. Thus, it may reflect as much what is happening upstream of an area as it does the unique output product of that region, as is the case for prediction error signals reported in ventral striatum commonly thought to reflect dopaminergic input. Similarly, although the demonstration that individual single units fire in a way that reflects pure value is more definitive, there are issues with using this as a theoretical foundation without additional causal evidence.
Value is heavily confounded with arousal and salience, and there is some evidence that OFC neurons signal salience (or risk or decision confidence, which are concepts associated with salience). Disentangling value and related constructs has been problematic in studies of other brain regions.
Although solving all these issues here may not be realistic, they illustrate the limitations of making arguments solely on the basis of neural correlates. What one wants of course is convergent, causal evidence that the OFC is required for the function reflected in the correlates. With the economic value hypothesis, the supporting causal data come from studies of preference reporting that OFC-damaged subjects exhibit choices that violate transitivity, which requires that choices reflecting economic value should reveal a consistent rank ordering across a group of items. Simply put, if you prefer A to B and B to C, then you should also prefer A to C.
Also problematic to this account, value signals, broadly defined, are generally ubiquitous in the brain, and there is growing evidence that even the very specific economic value correlate is not unique to OFC. For example, similar signals have been found in parietal cortex, anterior cingulate and other prefrontal regions. Recordings from across several prefrontal areas in monkeys choosing between cues predictive of rewards differing in probability, payoff or effort required found that the anterior cingulate cortex had the simplest pure value correlates, as neurons there were more likely than those in OFC or lateral prefrontal cortex to code value monotonically across all three value dimensions…OFC manipulations cannot be said to generally disrupt value-guided behavior.
OFC is not typically necessary for value-guided choices106. For example, OFC damage produces no deficits in Pavlovian or instrumental learning when subjects are required to discriminate between cues or actions predicting different-sized rewards. Similarly, both blocking and unblocking, when they can be accounted for by value, do not require the OFC. On the other hand, OFC is necessary for superficially similar behaviors when they require knowledge of specific outcome features to recognize errors or to infer a value.
These observations lead to a weaker or more nuanced form of the value hypothesis, in which the OFC is necessary only when the value driving behavior or learning is derived from mental simulation or model-based processing. Thus, the OFC is not necessary for Pavlovian conditioning, which can be driven by prior experience, but it is necessary for modifying that response if the predicted outcome is devalued by pairing it with illness38. The feature of this design that may require OFC is not response inhibition, as sometimes assumed given that lesioned rats extinguish responses normally during the probe test (in which food is omitted), but rather the need to link two independently acquired pieces of associative information, the cue-outcome association and the outcome-illness association. Notably, similar results have been obtained in monkeys after OFC lesions (even fiber sparing)12, 24, 110, and OFC BOLD signal and single-unit responses to predictive cues change selectively after outcome devaluation32, 107, 111, 112 or preference changes75. These deficits are observed even if lesions are made after initial learning and devaluation or if OFC is transiently inactivated only during the critical probe test113, 114.
…If economic value were conceptualized as only reflecting such computed-on-the-fly or inferred values, then the strong and weak versions of this hypothesis would converge. Although this assertion seems reasonable, the experimental procedures employed to examine neural correlates of economic value have not explicitly controlled for the associative basis of the underlying behavior in the way that formal learning theory requires.
Why is the OFC sometimes important for learning? One powerful proposal is that the OFC signals prediction errors…Overall, these data fail to support direct error signaling as a viable explanation for OFC-dependent learning deficits. However, OFC may still participate in learning through its influence on error signals elsewhere. Consistent with this idea, when OFC and midbrain data were juxtaposed, anticipatory activity in the OFC was inversely related to dopaminergic error signaling downstream…
A Cognitive Map?
Perhaps the most recent proposal, which may resolve some of the above issues, suggests that the OFC may support the formation of a so-called cognitive map that defines the current task space. Such an associative structure is at the heart of ideas about the implementation of behavioral control. It is necessary for what has been termed goal-directed behavior by learning theorists and model-based behavior by computational neuroscientists. Behavior guided by inference or mental simulation of consequences not directly experienced previously, such as changes in learned behaviors after reinforcer devaluation, would be iconic examples of this. A cognitive map would also be required to generate specific predictions about impending events, such as their identity or features, and for using contextual or temporal structure in the environment to allow old rules to be disregarded so that new ones can be rapidly acquired, as is sometimes the case after reversal. It might also help maintain information about what specific events had just transpired, so that in particularly complex tasks, one could appropriately assign credit when errors are detected.
Of course, constructing and using this associative structure would not depend on any single brain area, but would reflect the operation of a circuit, perhaps spanning much of the brain. This then raises the obvious question of OFC’s precise contribution in this circuit. The OFC may represent the underlying structure (for example, the cognitive map) once it has been acquired143, perhaps with an emphasis on structures related to biologically relevant outcomes. The OFC receives input from hippocampal areas144, which may be important for organizing complex associative representations, and the OFC interacts with broad areas of dorsal and ventral striatum145, 146. These connections may allow the OFC to acquire and maintain associative representations and to utilize them to influence how simpler associative information is accessed to guide behavior and learning. This would be consistent with the OFC’s involvement during both the learning and utilization phases of tasks that require cognitive maps of the task’s space119. Alternatively, the OFC might only represent the individual parts that comprise the task space, such as the states used to define the space and various events. This would still make the OFC critical to the circuit’s operation, but would no longer make this area essential for explicitly signaling value or directly driving learning or response inhibition, all of which appear to characterize some, but not all, of the deficits caused by OFC damage.
The idea of state creation would explain the OFC’s involvement in value-guided behaviors and would also be broadly consistent with its role in well-constrained learning tasks. This view also aligns with unit-recording and fMRI studies that emphasize the complex nature of representations in lateral OFC, where units and BOLD responses are driven not only by reward value, but also by reward identity, cues that precede rewards and even structure in the trial sequence. Such rich representations would allow the derivation of values in new situations, would facilitate the appropriate assignment of credit, and so on.
Although the verdict is less clear on more recent proposals, such as signaling economic or derived value, credit assignment, and cognitive mapping, we think that there is already some data that at least forces modification of key predictions of many of these accounts.