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Biomedical subjects

José V Pardo

Publications and source records attributed to José V Pardo.

15 recordsLinked to original sources

Neurocognitive dysfunction in antidepressant-free, non-elderly patients with unipolar depression: alerting and covert orienting of visuospatial attention.

BACKGROUND: Cognition is impaired across various domains in young and middle-age adults with unipolar depression. Performance appears in general worse in effortful tasks requiring executive function and attention. Probing specific cognitive operations in depressed patients, such as alerting and covert orienting of visuospatial attention, can better define and characterize the pathophysiology. METHODS: Nine antidepressant-free, clinically depressed patients and fourteen age-matched healthy subjects performed a Posner task with components of phasic alerting and covert orienting of visuospatial attention. Reaction times were analyzed by repeated-measures ANOVA with DIAGNOSIS as the between-group measure. Visual field (FIELD), stimulus onset asynchrony (SOA), and orienting CUE condition were within-subject, repeated measures. RESULTS: ANOVA showed intact attentional orienting in both groups. There were no FIELD differences across groups nor main effects of DIAGNOSIS. Interactions of DIAGNOSIS with SOA and DIAGNOSIS with CUE condition identified a phasic alerting deficit in the depressed patients. There were no significant effects of time-on-task, suggesting adequate vigilance or sustained attention in both groups. Plotting depressed versus control subjects' reaction time for each task condition (Brinley plot) showed linearity with a slope of 1.6 (i.e., patients were 1.6-fold slower) and a correlation coefficient of 0.98 (accounting for 96% of the overall variance). LIMITATIONS: This study contains a small sample with potential for Type II error. The study addressed depression at the syndrome level. Depressed patients selected on particular symptom dimensions (e.g., anxiety, psychomotor retardation, etc.) could reveal abnormalities in hemisphere asymmetries that were not observed here. CONCLUSIONS: These data highlight that global slowing is a major cognitive deficit in depression and arises across levels of difficulty. Putative specific deficits in depression need adjustment for the large effects of global slowing which can mimic selective impairments in more effortful task conditions.

Adolescent↗

About the mechanisms of auditory verbal hallucinations: a positron emission tomographic study.

OBJECTIVE: Auditory verbal hallucinations (AVHs) likely result from disorders, as yet unspecified, of the neural mechanisms of language. Here we examine the functional neuroanatomy of single-word reading in patients with and without a history of AVH. METHOD: Eighteen medicated schizophrenia patients (8 with AVH and 10 without AVH) and 12 healthy control subjects were scanned with PET (15)O-water technique under 2 conditions: reading aloud English nouns and passively looking at English nouns without reading them. RESULTS: The contrast between the 2 conditions shows higher activation in Wernicke's area during the reading condition in the patient group and a reversed laterality index for the supplementary motor area in the AVH group. CONCLUSIONS: These findings provide indications about the possible mechanisms of AVH. We suggest that the abnormal laterality of the supplementary motor area activity accounts for the failure to attribute speech generated by one's own brain to one's self and that the activation of Wernicke's area accounts for the perceptual nature (hearing) of the patient's experience.

Adult↗

Double dissociation of exteroceptive and interoceptive feedback systems in the orbital and ventromedial prefrontal cortex of humans.

The primate ventral prefrontal cortex contains two densely interconnected subregions: a lateral/orbital cortex processing primarily sensory/exteroceptive information, and a ventromedial cortex processing primarily visceroappetitive/interoceptive information. These regions have major afferents from and efferents to other associative cortices. The organization of these structures leads to an hypothesized role in feedback processing. We use neuroimaging to test this model, defined so far mostly through anatomical studies. Healthy volunteers were trained operantly on a transitive inference task (A>B, B>C ==> A>C) requiring flexible manipulation of feedback to solve. Two groups of subjects learned an arbitrary face hierarchy, one adjacent face pair at a time; each group received either visual/exteroceptive ("XXXX") or visceroappetitive/interoceptive (fruit juice) feedback for correct responses to adjacent face pairs. After task acquisition, the subjects were tested on novel stimulus pairs (i.e., nonadjacent, TEST) derived from the acquired hierarchy. The TEST condition required transitive inference. No feedback was provided during TEST. Brain activity during TEST in the group trained with visual/exteroceptive feedback increased in the orbital prefrontal cortex and decreased in the ventromedial prefrontal cortex. In contrast, brain activity during TEST in the group trained with visceroappetitive/interoceptive feedback decreased in the orbital prefrontal cortex and increased in the ventromedial prefrontal cortex. These results provide functional evidence, consistent with previous anatomical studies, for two major feedback systems in human ventral prefrontal cortex: a lateral system specialized for exteroceptive information and a medial system specialized for interoceptive information. Although highly interconnected, there is a double dissociation of function between these networks in healthy humans.

Adult↗

Frontal lobe activation during object alternation acquisition.

Object alternation (OA) tasks are increasingly used as probes of ventral prefrontal functioning in humans. In the most common variant of the OA task, subjects must deduce the task rule through trial-and-error learning. To examine the neural correlates of OA acquisition, the authors measured regional cerebral blood flow with positron emission tomography while subjects acquired an OA task, performed a sensorimotor control condition, or performed already learned and practiced OA. As expected, activations emerged in the ventral prefrontal cortex. However, activation of the presupplemental motor area was more closely associated with successful task performance. The authors suggest that areas beyond the ventral prefrontal cortex are critically involved in OA acquisition.

Adult↗

Functional neuroanatomy of the human near/far response to blur cues: eye-lens accommodation/vergence to point targets varying in depth.

The purpose of this study was to identify the networks involved in the regulation of visual accommodation/vergence by contrasting the cortical functions subservient to eye-lens accommodation with those evoked by foveal fixation. Neural activity was assessed in normal volunteers by changes in rCBF measured with PET. Thirteen right-handed subjects participated in three monocular tasks: (i) resting with eyes closed; (ii) sustained foveal fixation upon a LED at 1.2 m (0.83 D); and (iii) accommodating alternately on a near (24 cm, 4.16 D) vs. a far (3.0 m, 0.33 D) LED alternately illuminated in sequential 2 s epochs. The contrast between the conditions of near/far accommodation and of constant foveal fixation revealed activation in cerebellar hemispheres and vermis; middle and inferior temporal cortex (BA 20, 21, 37); striate cortex and associative visual areas (BA 17/18). Comparison of the condition of constant fixation with the condition of resting with closed eyes indicated activation of cerebellar hemispheres and vermis; visual cortices (BA 17/18); a right hemisphere dominant network encompassing prefrontal (BA 6, 9, 47), superior parietal (BA 7), and superior temporal (BA 40) cortices; and bilateral thalamus. The contrast between the conditions of near/far accommodation with closed-eye rest reflected an incremental summation of the activations found in the previous comparisons (i.e. activations associated with constant fixation). Neural circuits activated selectively during the near/far response to blur cues over those during constant visual fixation, occupy posterior structures that include occipital visual regions, cerebellar hemispheres and vermis, and temporal cortex.

Accommodation, Ocular↗

The impact of the certainty context on the process of choice.

In this study we examine how the introduction of a reference lottery with nonrandom outcomes alters the way in which choices among pairs of lotteries are made, even if it does not alter the choices. We use different domains (some of the lotteries produce gains, other losses) and different contexts (one member of the pair, the reference lottery, may be either risky or certain). In our experiment, the change from gain to loss domain affects choices: subjects are risk averse in the gain domain, but not in the loss domain. On the contrary, the context effect of the certain lottery does not affect choices. However, the introduction of the certainty reference lottery affects two behavioral variables, response time and brain activation, in a dramatic way. This result suggests that the certainty lottery promotes a different process through which preferences are revealed, even if the differences among lotteries may not be large enough to induce different choices.

Journal Article↗

PET studies of somatosensory processing of light touch.

The studies discussed in this report investigate the neural mechanisms involved in processing a light tactile stimulus as measured by positron emission tomography (PET). This light tactile stimulus (a 2-Hz tap with a von Frey hair) produced a significant increase in regional cerebral blood flow (rCBF) in contralateral primary somatosensory cortex (SI) and bilateral secondary somatosensory cortex (SII), with a larger response in the side contralateral to the stimulus. Light tactile stimulation also produced activity in multiple discrete areas in the human inferior parietal lobule (IPL), which we believe to comprise a region homologous to the monkey area 7b or feline tertiary somatosensory cortex (SIII). Directing attention to the tactile stimulus increased blood flow to SIII and activated a right-lateralized cortical network, regardless of the side of body stimulated. Directed attention to the stimulus decreased blood flow to visual cortex, but minimally modulated SI rCBF.

Adult↗

Human hippocampal activation during transitive inference.

The medial temporal lobe contains multiple structures whose mnemonic operations need further delineation. One model posits the function of the hippocampus as a relational binder, collaborating with overlying cortices that perform encoding and retrieval operations. For instance, lesions of the hippocampus leave intact the learning of paired-associates while impairing the ability to synthesize information across pairs. We test this relational model with two PET studies of normal humans during a transitive inference task using faces that either have or lack relationships across the stimulus pairs. Both studies converge to support a relational processing model of hippocampal function.

Adult↗

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.

Adolescent↗

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.

Acoustic Stimulation↗

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 degrees /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.

Adult↗

Neural correlates of tasting concentrated quinine and sugar solutions.

Behavioral, ethological, and electrophysiological evidence suggests that the highly unpleasant, bitter taste of a concentrated quinine hydrochloride (QHCL) should activate the human amygdala. In the present study, healthy subjects tasted 0.02 M QHCL or water while regional cerebral blood flow (rCBF) was assayed with H(2)(15)O PET. Subjects were also studied while tasting a pleasant sucrose solution and resting with eyes closed (ECR). Tasting QHCL significantly increased rCBF within the left amygdala relative to control conditions of tasting water and ECR. Sucrose and water caused small to moderate rCBF increases in the amygdala relative to ECR, but sucrose did not significantly increase activity within either amygdalae relative to water. In the frontal lobe, QHCL and sucrose both activated the right posterior orbitofrontal cortex (OFC) relative to water, but portions of the anterior OFC and inferior frontal pole showed valence specific responses to QHCL. These data indicate that the left amygdala responds robustly to QHCL and more moderately to nonaversive sapid stimuli, both pleasant and unpleasant gustatory stimuli activate the right posterior OFC, and the left inferior frontal pole/anterior OFC demonstrates valence-specific responses to aversive gustatory stimuli.

Adolescent↗

Somatosensory processing in the human inferior prefrontal cortex.

Three inferior prefrontal regions in the monkey receive afferents from somatosensory cortices: the orbitofrontal cortex (OFC), the ventral area of the principal sulcus, and the anterior frontal operculum. To determine whether these areas show responses to tactile stimuli in humans, we examined data from an ongoing series of PET studies of somatosensory processing. Unlike previous work showing ventral frontal activity to hedonic (pleasant/unpleasant) sensory stimulation, the tactile stimuli used in these studies had a neutral hedonic valence. Our data provide evidence for at least two discrete ventral frontal brain regions responsive to somatosensory stimulation: 1) the posterior inferior frontal gyrus (IFG) and adjacent anterior frontal operculum, and 2) the OFC. The former region (posterior IFG/anterior frontal operculum) may have a more specific role in attending to tactile stimuli.

Adult↗

Prefrontal contributions to delayed spatial and object alternation: a positron emission tomography study.

Delayed alternation tasks are frequently used as probes of frontal lobe functioning. To clarify the neural substrates of delayed alternation performance in humans, the authors measured regional cerebral blood flow with H2(15)O positron emission tomography in healthy subjects as they performed delayed spatial and object alternation. Consistent with the monkey lesion literature, increased dorsolateral prefrontal activity emerged during delayed spatial alternation but not delayed object alternation, whereas orbitofrontal activations emerged in both alternation tasks. The possible cognitive processes contributing to the orbitofrontal and dorsolateral prefrontal involvement in delayed alternation are discussed. Additional activations localized to several nonfrontal regions suggest caution in interpreting alternation deficits in patients as strictly reflecting frontal lobe impairment.

Adult↗

Functional neuroimaging of gastric distention.

This study aimed to measure brain activation during gastric distention as a way to investigate short-term satiety. We estimated regional cerebral blood flow with positron emission tomography (15O-water) during gastric balloon inflation and deflation in 18 healthy young women. The contrast between inflated minus deflated conditions showed activation in the following four key regions that were identified a priori: dorsal brain stem; left inferior frontal gyrus; bilateral insula; and right subgenual, anterior cingulate cortex. Extant neuroimaging literature provides context for these areas as follows: the brain stem represents vagal projection zones for visceral afferent processing; the inferior frontal gyrus serves as a convergence zone for processing food-related stimuli; and both the insula and subgenual anterior cingulate cortex respond to emotional stimulation. The identification of neural correlates of gastric distention is a key step in the discovery of new treatments for obesity. New therapies could intervene by modifying the perception of gastric distention, an important contributor to meal termination and short-term satiety. This first study of brain activation during nonpainful, proximal gastric distention provides the groundwork for future research to discover novel treatments for obesity.

Brain↗