(Possibly) Dissociable Prefrontal Effects of Target and Target Class Probability

How do we detect important items in our environment? This crucial capacity has received less attention than one might think, and a number of extremely basic issues remain to be explored. For example, it has long been known that target probability has profound effects on the recruitment of the prefrontal cortex (such that lower-probability targets are associated with greater recruitment of both dorsolateral and ventrolateral prefrontal cortex), it has been unclear whether this pattern arises due to the general probability of the class of "targets" or whether it's more stimulus-specific.

An elegant new Neuroimage paper by Hon, Ong, Tan & Yang addresses this question across two experiments. As it turns out, they observe a suggestive difference between the dorsal and ventral subregions of lateral frontal cortex, such that the former area appears to be sensitive to the probability of individual targets whereas the latter area abstracts across individual targets and responds more clearly only to the probability of target items in general.

In their first experiment, Hon et al presented 17 subjects with a series of letters, one after the other; subjects were asked to press a button in response to only two letters in particular (e.g., A and B) but to ignore all others. In some blocks of trials, these target letters appeared with 25% frequency; in another set of blocks, these targets appeared with 50% frequency. Block order was counterbalanced, and a simple "manipulation check" confirmed that, as expected, there was no differential hemodynamic activation between the two target letters within either block.

What Hon et al did observe was an increased hemodynamic response in both dorsolateral and ventrolateral prefrontal cortex during the blocks where target letters occurred less frequently. While it's possible that this reflects a change in the hemodynamic responses to distractors rather than targets, and while no low-level baseline was used to check this possibility, both the authors and prior research suggest that the changes observed here are more specific to neural recruitment to targets.

(Note: it's also possible the increased target frequency effectively led to an increased sustained recruitment of PFC, which would thus appear to reduce transient responses to targets when more frequent by increasing the hemodynamic response during distractors as well. Once again, a low-level baseline would have been useful here).

Hon et al's second experiment, however, is where things get much more interesting. As in the first experiment, 19 subjects were asked to press a button in response to one of two target letters embedded within a sequential stream of other letters. Unlike the first experiment, the probability of a target (i.e., either letter) appearing was constant across all blocks of trials; these blocks differed only in whether one of the two target stimuli was more probable, given that a target would occur.

In this case, dorsal lateral prefrontal cortex showed a stronger response to the less frequent target letter. By contrast, ventrolateral prefrontal cortex showed no such effect. Unfortunately, the critical test of this regional difference was not reported (see Niewenhuis's recent paper for more on this). The authors made this mistake a second time, too: while individual differences in dorsolateral and ventrolateral prefrontal cortex (dlPFC and vlPFC respectively) recruitment were more significantly correlated in the first experiment, they were not significantly correlated in the second, and yet the authors didn't run the crucial test for a difference between these correlations.

In the end we have a paper that is suggestive of a difference between ventrolateral and dorsolateral prefrontal cortex with respect to the abstract class to which a particular stimulus/response event belongs (to which ventrolateral prefrontal cortex is most sensitive) or to the probability of an individual target stimulus (to which the dorsolateral prefrontal cortex is most sensitive). Even if the crucial tests for regional differences had been presented, there would still be some unaddressed alternative possibilities for what's going on here.

One possibility is that ventrolateral prefrontal cortex is sensitive to the frequency of a particular response; since the response was always the same for either of the two targets, manipulations of their frequency would fail to affect VLPFC activation. Note this alternative runs contrary to recent theorizing that VLPFC may be more intimately related to stimulus- rather than response-related processing (in contrast to DLPFC, which is thought to be more related to response processing or stimulus-response mappings).

Similarly, it is possible that VLPFC more coarsely distinguishes the identity of these stimuli than DLPFC, in which case it would be less capable of showing a difference owing to their differing frequency. Once again, this possibility is perhaps unlikely given that VLPFC is the seat of Broca's area, and thus is historically more intimately related to linguistic processing than DLPFC; if anything, the letter stimuli used here would be expected to be more finely coded in VL than DLPFC. (Notably, the responses of VL and DLPFC were numerically stronger on the right hemisphere; this would seem to suggest greater specialization for the right hemisphere in this kind of target detection task - consistent with much prior work on the role of a right-hemispheric vigilance system - given that left hemisphere regions are normally more responsive to stimuli like letters and words.)

In fact, there are reasons to doubt that Hon et al observed a signfiicant difference between VL and DLPFC in this experiment at all. Clearly, it is difficult to interpret a null effect; but it's even harder to interpret data when the appropriate statistical test wasn't even run in the first place. The current study appears also to contradict previous work (by Casey et al) that showed VL, but not DL prefrontal cortex was positively correlated with target frequency, although that previous work is also difficult to interpret (and was really focusing on a distinct subregion of VLPFC - Brodmann area 47 vs. 44/45 in Hon's work.)

In conclusion, Hon et al present suggestive though far from definitive evidence for a possible dissociation between dorsal and ventral lateral prefrontal cortex in the responsiveness to the frequency of individual target stimuli and/or specific stimulus-response mappings (for which DLPFC is most responsive) or to the frequency of the abstract class to which particular stimuli respond, independent of their individual features (for which VLPFC is more selectively responsive). There are alternative possibilities that seem to contradict recent theorizing, and indeed the results can be seen to contradict much earlier work; at the same time, many of the critical tests weren't run, so it's impossible to say whether these contradictions are real.

My $0.02? I'd speculate that they're right about VLPFC - particularly right VLPFC - but I don't think there's yet any study with definitive proof of this idea. Currently there are stronger computational and theoretical reasons to believe Hon et al's results about VLPFC - particularly with respect to concepts like policy and context/state abstraction - than there is empirical data. More on the computational/theoretical underpinnings in the next few posts...