José V. Pardo

Human cortical gustatory areas : A review of functional neuroimaging data

In an effort to define human cortical gustatory areas we reviewed functional neuroimaging data for which coordinates standardized in Talairach proportional space were available. We observed a wide distribution of peaks within the insula and parietal and frontal opercula, suggesting multiple gustatory regions within this cortical area. Multiple peaks also emerged in the orbitofrontal cortex. However, only two peaks, both in the right hemisphere, were observed in the caudolateral orbitofrontal cortex, the region likely homologous to the secondary taste area described in monkeys. Overall significantly more peaks originated from the right hemisphere suggesting asymmetrical cortical representation of taste favoring the right hemisphere.

Functional neuroimaging of the olfactory system in humans

Positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have begun to provide unique information regarding the neural underpinnings of olfactory functioning in humans. We review the relative strengths and weaknesses of PET and fMRI techniques for studying olfaction. We then review PET and fMRI studies relating to the olfactory functions of the pyriform cortex, orbitofrontal cortex, amygdala and the entorhinal/hippocampal region. A pixelwise correlational analysis of PET data is also presented in order to clarify the relationship between blood flow in the medial temporal lobes and psychoperceptual variables.

The functional neuroanatomy of voluntary swallowing

Swallowing is a complex physiological process involving voluntary and reflexive motor activity, sensorimotor integration, salivation, and visceral regulation. Despite the numerous processes required for normal deglutition, traditional models of the central control of swallowing only emphasize the involvement of the brainstem and the inferior precentral gyrus (IPCG). However a number of neurological disorders involving other brain regions also cause dysphagia. To determine the brain regions participating in voluntary swallowing, we assayed regional cerebral blood flow (rCBF) with positron emission tomography (PET) while healthy human subjects swallowed, performed lateral tongue movements, or rested with their eyes closed. Voluntary swallowing produced strong rCBF increases within the IPCG bilaterally, the right anterior insula/claustrum, and the left cerebellum. The maxima in these regions differed from those induced by lateral tongue movements. Swallowing also produced rCBF increases in the putamen, thalamus, and several additional cortical areas, but these foci were not as clearly distinguishable from activity arising during tongue movements. These findings indicate that swallowing involves the recruitment of a large‐scale distributed neural network that includes the anterior insula and cerebellum. The distributed nature of this network helps to explain why so many neurological conditions produce dysphagia.

Tactile motion activates the human middle temporal/V5 (MT/V5) complex.

The human middle temporal/V5 complex (hMT/V5) plays a central role in the perception of visual motion. This region is considered a unimodal visual area with little direct involvement of other sensory modalities. The current study uses H215O PET to test whether tactile motion influences the activity of hMT/V5. Regional cerebral blood flow (rCBF) within hMT/V5 was estimated in eight subjects in separate tactile motion and visual motion conditions, each contrasted with a resting, control. The tactile motion condition involved a brush stroked proximal‐to‐distal along the volar forearm and palm, while the subject attended to the stimulus with closed eyes. The visual motion condition consisted of low contrast, grey‐scale rings radiating at 15°/s from a central point, upon which the subject was instructed to fixate. The location of hMT/V5 was defined for each subject separately as the local maximum of rCBF change during the visual motion condition (vs. control). The average change in rCBF within spherical regions of interest at each peak revealed significant bilateral activation of hMT/V5 in the tactile motion condition contrasted with a second, independent set of control scans. Additionally, a single subject received a sufficient number of scans to perform a pixel‐wise, within‐subject analysis. His functional images were coregistered to his anatomical MRI. In this subject, tactile motion produced a significant increase in rCBF that directly overlapped a region activated by visual motion at the posterior continuance of the inferior temporal sulcus, consistent with the known location of hMT/V5. These results suggest involvement of the hMT/V5 complex in tactile motion processing.

Sex-related differences in amygdala functional connectivity during resting conditions

Recent neuroimaging studies have established a sex-related hemispheric lateralization of amygdala involvement in memory for emotionally arousing material. Here, we examine the possibility that sex-related differences in amygdala involvement in memory for emotional material develop from differential patterns of amygdala functional connectivity evident in the resting brain. Seed voxel partial least square analyses of regional cerebral blood flow data revealed significant sex-related differences in amygdala functional connectivity during resting conditions. The right amygdala was associated with greater functional connectivity in men than in women. In contrast, the left amygdala was associated with greater functional connectivity in women than in men. Furthermore, the regions displaying stronger functional connectivity with the right amygdala in males (sensorimotor cortex, striatum, pulvinar) differed from those displaying stronger functional connectivity with the left amygdala in females (subgenual cortex, hypothalamus). These differences in functional connectivity at rest may link to sex-related differences in medical and psychiatric disorders.

Brain activity in ventromedial prefrontal cortex correlates with individual differences in negative affect

Individuals differ in the extent to which they experience negative mood states over time. To explore the relationship between individual differences in negative affect (NA) and brain activity, we asked healthy subjects participating in positron-emission tomography scans to rate the extent to which they had experienced NA terms during the month before scanning. In two independent samples of subjects, resting regional cerebral blood flow within the ventromedial prefrontal cortex (VMPFC) correlated with ratings of NA. The finding converges with recent evidence implicating the VMPFC in emotional and autonomic processing. Moreover, it demonstrates that variability in basal VMPFC activity across subjects is related to individual differences in subjective emotional experience.

Neuronal Substrates for Choice Under Ambiguity, Risk, Gains, and Losses

Economic forces shape the behavior of individuals and institutions. Forces affecting individual behavior are attitudes about payoffs (gains and losses) and beliefs about outcomes (risk and ambiguity). Under risk, the likelihoods of alternative outcomes are fully known. Under ambiguity, these likelihoods are unknown. In our experiment, payoffs and outcomes were manipulated independently during a classical choice task as brain activity was measured with positron emission tomography (PET). Here, we show that attitudes about payoffs and beliefs about the likelihood of outcomes exhibit interaction effects both behaviorally and neurally. Participants are risk averse in gains and risk-seeking in losses; they are ambiguity-seeking in neither gains nor losses. Two neural substrates for choice surfaced in the interaction between attitudes and beliefs: a dorsomedial neocortical system and a ventromedial system. This finding reveals that the brain does not honor a prevalent assumption of economics--the independence of the evaluations of payoffs and outcomes. The demonstration of a relationship between brain activity and observed economic choice attests to the feasibility of a neuroeconomic decision science.

Where the brain grows old: decline in anterior cingulate and medial prefrontal function with normal aging.

Even healthy adults worry about declines in mental efficiency with aging. Subjective changes in mental flexibility, self-regulation, processing speed, and memory are often cited. We show here that focal decreases in brain activity occur with normal aging as measured with fluorodeoxyglucose and positron emission tomography. The largest declines localize to a medial network including the anterior cingulate/medial prefrontal cortex, dorsomedial thalamus, and sugenual cingulate/basal forebrain. Declining metabolism in this network correlates with declining cognitive function. The medial prefrontal metabolic changes with aging are similar in magnitude to the hypometabolism found in Mild Cognitive Impairment or Alzheimers disease. These results converge with data from healthy elderly indicating dysfunction in the anterior attention system. The interaction of attention in the anterior cingulate cortex with memory in the medial temporal lobe may explain the global impairment that defines dementia. Despite the implications for an aging population, the neurophysiologic mechanisms of these metabolic decreases remain unknown.

The Neural Correlates of Aversive Auditory Stimulation

Previous neuroimaging studies indicate that the human amygdala activates during exposure to aversive visual, olfactory and gustatory stimuli. To examine amygdala responses to aversive auditory stimuli, we exposed healthy human subjects to unpleasant sounds while regional cerebral blood flow (rCBF) was assayed with O-15 PET. Eight subjects, all of whom described themselves as reactive to aversive sounds, participated in the study. Relative to white noise, the aversive sounds produced significant rCBF increases in the lateral amygdala/claustrum region. Significant activations also localized to the dorsal brainstem, medial temporal pole, basal forebrain (nucleus accumbens), insula, right auditory association cortices, putamen, thalamus and cerebellum. These data indicate that the amygdala responds to aversive auditory stimuli in a manner similar to its response to unpleasant stimuli in other sensory modalities. The data further highlight a widely distributed network of cortical and subcortical areas activated during exposure to aversive sounds.

A computer-controlled olfactometer for fMRI and electrophysiological studies of olfaction

A design for an inexpensive and reliable olfactometer is presented. The design has several advantages for fMRI and electrophysiology investigators. These advantages include relatively rapid odorant rise times, computer control, multiple odor administration, and no ferrous materials near the subjects. In addition, the device is contamination resistant, and, because the air is neither warmed nor humidified, it is unlikely to become an incubator for bacteria. The olfactometer is constructed of off-the-shelf chromatography parts that require little modification.