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Three Inferior Prefrontal Regions Of The Brain
Posted: Thursday, November 21, 2002
Source: American Physiological Society

Three Inferior Prefrontal Regions Of The Brain Found Receptive To Somatosensory Stimuli

November 19, 2002) - Bethesda, MD -- We know quite a bit about the orbitofrontal cortex (OFC). It is part of the frontal lobe that lies superior to the orbit of the eyes. This area of the brain plays an important role in emotional behavior, receives direct inputs from the dorsomedial thalamus, temporal cortex, ventral tegmental area, olfactory system, and the amygdala (illustration). Its outputs go to several brain regions, including the cingulate cortex, hippocampal formation, temporal cortex, lateral hypothalamus, and amygdala. Finally, it communicates with other regions of the frontal cortex. Thus its inputs provide it with information about what is happening in the environment and what plans are being made by the rest of the frontal lobes. Its outputs permit it to affect a variety of behaviors and physiological responses, including emotional responses organized by the amygdala.

However, there is still much that we do not know about this important part of the brain. Research has shown that three inferior prefrontal regions of the monkey's brain (OFC, ventral area of the principal sulcus, and the anterior frontal operculum) all receive somatosensory stimuli (indirect sensations to the body as opposed to specific stimuli such as light). Now a groundbreaking research effort has incorporated two studies, combining positron emission tomography with neutral tactile (touch) stimulation to determine if these same regions in the human brain respond accordingly.

The authors of "Somatosensory Processing in the Human Inferior Prefrontal Cortex" are Matthew C. Hagen and Jose´ V. Pardo, both from the Veterans Affairs Medical Center and the University of Minnesota Medical School, Minneapolis, MN; and David H. Zald and Tricia A. Thornton, both from Vanderbilt University, Nashville, TN. Their findings are published in the Journal of Neurophysiology, a publication of the American Physiological Society (APS).

S T U D Y 1


Thirty-three individuals (18 males, 15 females, 30 were right-handed, two left-handed, one ambidextrous, and the mean age was 38 + 15 participated. An additional ten right-handed subjects (four males, six females; mean age 35) participated in a small experiment outside of the scanner to assess the subjective evaluation of the stimulus used in this study. The stimulation entailed subjects lying with eyes closed while tactile stimulation was administered by manually applying a repetitive (approximately 2–3 Hz) tap at one of four stimulation sites (right index finger, right great toe, left index finger, left great toe). Subjects were instructed to count the number of pauses in the tactile stimulation; 0–3 pauses were administered prior to injection of the isotope or following scan acquisition. No pause in tactile stimulation was provided during the period of scan. Each subject participated in stimulation of one or more sites. Under the control condition, subjects lay resting with their eyes closed (ECR) with no somatosensory stimulation. The ten subjects selected for subjective evaluation were given the same stimulation and instructions as were delivered during the scanning sessions. All subjects were first stimulated on the toe, since the likelihood of rating the stimulus negatively appeared greatest at this site. Following the session of toe stimulation, subjects were asked to rate the pleasantness/unpleasantness of the stimulus using a Likert scale. PET imaging and analysis regional cerebral blood flow (rCBF) were estimated from normalized tissue activity (with measured attenuation correction).


Two sectors of the ventral frontal lobe accounted for most of these foci, a large area that encompassed the posterior-most portions of the inferior frontal gyrus (IFG) (pars orbitalis and triangularis) and the underlying frontal operculum. In contrast, the left hemisphere equivalent only reached statistical significance in one comparison. A second strong area of activation localized to the OFC. In all cases the activation included the right anterior orbital gyrus and the neighboring lateral orbital gyrus. Additional activations arose in other sectors of the right and left OFC, but without as much consistency. The data did not provide consistent evidence for the involvement of an area equivalent to the ventral principal sulcus in monkeys. In the subjective evaluation of the stimulus, 9 of the 10 subjects rated the tactile stimulation of the toe as neutral. One subject found it mildly unpleasant. Eight of the nine subjects rating the stimulus as neutral for the toe also found it similarly neutral for the finger. One subject found the finger stimulation mildly unpleasant, although they rated the toe stimulation as neutral. The individual that found it mildly unpleasant on the toe rated the stimulation of the finger as neutral.

S T U D Y 2

Study 1 indicated that rCBF increases in areas of the ventral frontal lobe during somatosensory stimulation. However, it remains unclear what cognitive or perceptual processes are associated with these increases. These activations could, for instance, reflect a passive sensory representation, a general attentional process (unrelated to a specific sensory modality), or a more modality-specific sensory process. To partially clarify these issues, the researchers employed an intermodal attention task. In both conditions subjects viewed a fixation point and received somatosensory stimulation. In one condition subjects were instructed to attend to the somatosensory dimension while in the other condition they attended to the visual dimension. Because the actual sensory stimulation was identical across conditions, differences in activation between conditions likely reflect modality-specific processing. In contrast, passive sensory representations or more general attentional factors should largely cancel out in this experiment.


Thirteen healthy, right-handed individuals (8 males, 5 females) participated in Study 2. Subjects fixated continuously on a 1 x 1 cm crosshair against a black background that was displayed on a 38-cm computer monitor placed 43 cm in front of their eyes. Concomitantly, tactile stimulation was administered by manually applying a repetitive von Frey hair (3–5 Hz) at one of two stimulation sites (right index finger and right great toe). During each stimulation event, the subject performed under one of two attentional conditions: count the number of pauses in the tactile stimulation and to passively fixate on the central fixation point; and count the number of times the luminance of the central fixation point dimmed and to ignore the somatosensory stimulus. No pause in tactile stimulation or change in the luminance of the fixation point occurred under either condition during scan acquisition. Thus the difference lay in the sensory modality to which the subject attended. Each subject performed one attend somatosensory/passive fixation and one attend visual/ignore somatosensory condition at each of the two stimulation sites.


The regions of interest (ROI) located in the right IFG pars triangularis/operculum showed a significant increase in rCBF with attention to the somatosensory stimulus when compared with attending to the visual stimulus. The ROI in the OFC showed a slight, though nonsignificant increase in rCBF with attention to the visual stimulus. In the pixel-wise analysis, the contrast of attending to somatosensory stimulation/passive fixation versus attend vision/ignore somatosensory produced a significant activation of the right IFG pars triangularis


The data from the two studies provide evidence for at least two discrete ventral frontal brain regions that respond to somatosensory stimulation: posterior IFG/frontal operculum and anterior OFC. Contrasts between somatosensory stimulation and resting with eyes closed produced consistent activations in these regions regardless of the site and side of stimulation. Although there are some differences in the specific locations of peak significance, the overall pattern of activity shows strong convergence across stimulation conditions.

In the first study, the largest ventral frontal area of activation was found in the posterior IFG and underlying anterior frontal opercular region. The involvement of this area in somatosensory processing is consistent with the existing, although limited, data on the neural connections in monkeys. Although the nature of the processing in this region cannot be fully determined from this study, this area of the posterior IFG appears to have a role in selective attention to touch. In the second study, subjects showed significantly greater activation under the "attend somatosensory" condition than under the "attend visual" condition. Since stimulation was identical between conditions, the modulation in activity cannot simply reflect a passive representation of touch.

In summary, the present studies clearly demonstrate the presence of inferior frontal brain regions responsive to somatosensory stimulation. The areas identified show reasonable correspondence to areas previously observed to possess somatosensory input in monkeys and thus appear to indicate a conservation of these pathways in humans. Future studies will hopefully clarify the specific task conditions that engage these areas.


Source: Journal of Neurophysiology.

The American Physiological Society (APS) was founded in 1887 to foster basic and applied science, much of it relating to human health. The Bethesda, MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals every year.

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