Delineating the functional organization of the prefrontal cortex is central to advancing models of goal-directed cognition. Considerable evidence indicates that specific forms of cognitive control are associated with distinct subregions of the left ventrolateral prefrontal cortex (VLPFC), but less is known about functional specialization within the right VLPFC. We report a functional MRI meta-analysis of two prominent theories of right VLPFC function: stopping of motor responses and reflexive orienting to abrupt perceptual onsets. Along with a broader review of right VLPFC function, extant data indicate that stopping and reflexive orienting similarly recruit the inferior frontal junction (IFJ), suggesting that IFJ supports the detection of behaviorally relevant stimuli. By contrast, other right VLPFC subregions are consistently active during motor inhibition, but not reflexive reorienting tasks, with posterior-VLPFC being active during the updating of action plans and mid-VLPFC responding to decision uncertainty. These results highlight the rich functional heterogeneity that exists within right VLPFC.
© 2011 New York Academy of Sciences.
Anatomical divisions within the ventrolateral prefrontal cortex (VLPFC). VLPFC, or inferior frontal gyrus, is bounded superiorly by the inferior frontal sulcus (green) and inferiorly by the lateral sulcus (blue). Cytoarchitectonic and connectivity patterns– as well as neuroimaging dissociations within the left hemisphere,,– suggest functional distinctions between three distinct subregions within VLPFC. The most caudal extent (
A), which we refer to as posterior-VLPFC, is bounded by the precentral sulcus (red) and the ascending ramus of the lateral sulcus (orange). This region corresponds roughly to the region referred to as pars opercularis or Brodmann area (BA). Rostral to the ascending ramus (orange) is mid-VLPFC ( B), which corresponds roughly to pars triangularis or area 45. The horizontal ramus of the lateral sulcus (yellow) separates mid-VLPFC from anterior-VLPFC ( C), which roughly corresponds to pars orbitalis or area. In addition to these three VLPFC subregions, recent evidence also suggests that there may be another distinct functional subregion– that falls at the most posterior and superior region of VLPFC, where VLPFC intersects with the middle frontal gyrus dorsally and the premotor cortex caudally. This region ( D) is referred to as the inferior frontal junction (IFJ) and is situated at the intersection of the posterior end of the inferior frontal sulcus (green) and the precentral sulcus (red).
Behavioral tasks used to study Motor Inhibition and Reflexive Reorienting. (
A) Motor inhibition is typically studied using either the Go/No-Go or Stop Signal task. In the Go/No-Go task, subjects see a stream of centrally presented stimuli and must make a button-press for every stimulus except one, the no-go stimulus (here shown as an “X”). Behavioral performance is measured by the subject's ability to withhold their response on the no-go trials. In the Stop Signal task, subjects also see a stream of centrally presented stimuli and typically must make a decision about each stimulus (e.g., is the arrow pointing right or left?). On a minority of trials a stop signal (e.g., a tone) is presented, indicating that the subject should withhold their response on that trial. Behavioral performance is assessed by computing a stop signal reaction time (SSRT), which provides an estimate of how long it takes to cancel an initiated movement. In both motor inhibition tasks, brain activity putatively associated with motor inhibition is measured by contrasting activity during the inhibition trials (no-go and stop signal) with activity during go trials. ( B) Reflexive Reorienting is typically studied using either the Posner Cueing or Oddball task. In the Posner Cueing task, a cue orients subjects to attend to one of two spatial positions. Then the subject is asked to make a judgment about a stimulus when it appears (e.g., is the letter a “L” or an “X”?). On valid trials subjects are correctly cued to the spatial position where the target will appear, but on infrequent invalid trials they are instructed to attend to the wrong position. The behavioral index of attentional engagement in this paradigm is that subjects are typically slower to respond on invalidly cued trials than during validly cued trials. Brain activity putatively associated with attentional capture is assessed by contrasting activity during invalid trials with activity during valid trials. In the Oddball task, subjects are asked to attend to a stream of stimuli. Most trials present the same “standard” stimulus, but infrequently an oddball appears and this requires subjects to press a button to note its occurrence. Behavioral performance is measured by the subject's ability to detect these oddballs and brain activity putatively associated with attentional capture is measured by contrasting activity in response to the oddballs compared to when the standards are presented.
Meta-analysis of Motor Inhibition and Reflexive Reorienting tasks. The top two rows display the Activation Likelihood Estimate (ALE) maps for motor inhibition tasks, collapsing across Go/No-Go and Stop Signal tasks, and reflexive reorienting tasks, collapsing across Posner Cueing and Oddball tasks (thresholded at
P < 0.05, cluster corrected for multiple comparisons). At the bottom is a voxel-wise map of the difference score between the two unthresholded ALE maps. This image is arbitrarily thresholded (at 0.0125) to show voxels where there are large differences in the two ALE maps; accordingly, this map provides qualitative leverage on possible differences between conditions, but does not constitute a formal statistical comparison. On the axial slices, specific VLPFC subregions are labeled: anterior insula (A), posterior-VLPFC (B), mid-VLPFC (C), inferior frontal junction (D), middle frontal gyrus (E), and pre-supplementary motor area (F).
Meta-analysis of two different types of Motor Inhibition tasks. The top row displays the ALE map for tasks that involve response override. These Stop Signal and Go/No-Go tasks encourage subjects to prepare a motor response before the stop cue appears, such that the cue triggers the need to cancel a specific prepared motor action. The second row displays the ALE map for tasks that involve response uncertainty. These are Go/No-Go tasks where the two trial types are equiprobable, such that subjects are unlikely to prepare a motor response before the trial begins. Accordingly, to the extent that they do not preparing a response, then there is no need to override a specific response. Instead these tasks create a situation of high decision uncertainty. The bottom row displays a voxel-wise map of the difference score between the two unthresholded ALE maps. This image is arbitrarily thresholded (at 0.0125) to show voxels where there are large differences in the two ALE maps; accordingly, this map provides qualitative leverage on possible differences between conditions, but does not constitute a formal statistical comparison. On the axial slices, specific VLPFC subregions are labeled: anterior insula (A), posterior-VLPFC (B), mid-VLPF (C), inferior frontal junction (D), and pre-supplementary motor area (E).
Encoding visuo-spatial information activates similar VLPFC regions as motor inhibition. Here the activations from the motor inhibition meta-analysis are re-plotted in red, and overlaid in blue is an ALE meta-analysis of three episodic memory encoding studies.,, Each of these latter studies contrasted encoding phases with difficult-to-verbalize visuo-spatial stimuli (e.g., textures) to ones with verbal stimuli. While several other studies reported similar patterns both at encoding,, and during retrieval,– many of these studies did not report peak coordinates. This sample was too small to justify a formal meta-analytic treatment; nevertheless, the apparent overlap suggests that similar right VLPFC regions are engaged during motor inhibition and during non-verbal episodic encoding tasks. This overlap would appear difficult to explain in terms of either motor inhibition or reflexive reorienting.
Common and differential ventrolateral prefrontal activity during inhibition of hand and eye movements.
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Research Support, N.I.H., Extramural
Motor Neurons / physiology*
Neural Inhibition / physiology*
Orientation / physiology*
Prefrontal Cortex / anatomy & histology
Prefrontal Cortex / diagnostic imaging
Prefrontal Cortex / physiology*
Spatial Behavior / physiology*