Biomedical subjects

David H Zald

Publications and source records attributed to David H Zald.

15 recordsLinked to original sources

PubMed2006

A meta-analysis of cognitive change with haloperidol in clinical trials of atypical antipsychotics: dose effects and comparison to practice effects.

Prospective, double-blind, randomized trials comparing atypical antipsychotic drugs (APDs) to typical APDs, such as haloperidol, indicate that atypical APDs provide a modest benefit to cognitive function in schizophrenia. However, the validity of this inference has been contested by suggestions that the cognitive improvements observed with atypical APDs reflect practice effects associated with repeated testing on the same neuropsychological instruments, or an avoidance of a deleterious effect of haloperidol on cognitive function that might be dose related. These alternate hypotheses were assessed by meta-analyses that 1) examined the relationship between cognitive change and dose of haloperidol within the control arms of prospective atypical vs. typical APD clinical trials; and 2) compared the magnitude of change observed within the haloperidol arms of these studies to estimated practice effects for several commonly used neuropsychological measures. The results indicate that overall cognitive performance improves while on haloperidol. Studies that used a low dose of haloperidol (<10 mg) did not yield larger effect sizes for overall cognitive function or specific neuropsychological measures than studies that used a high dose (>10 mg), although doses greater than 24 mg appear to have deleterious effects. For two of the six neuropsychological tests examined (digit symbol substitution and verbal fluency) the magnitude of change observed was significantly less than practice effects. The results indicate that although haloperidol may cause deleterious effects at very high doses, or in specific cognitive domains, these effects are not likely to explain the broader range of cognitive improvements observed with atypical APDs.

Antipsychotic Agents↗

PubMed2006

The rodent orbitofrontal cortex gets time and direction.

The orbitofrontal cortex (OFC) helps direct decision making through its flexible coding of reward and economic value. In this issue of Neuron, papers by Roesch et al. and Feierstein et al. demonstrate the importance of temporal and spatial features to processing in the rodent OFC.

Animals↗

PubMed2006

Individual differences in oral thermosensation.

Although oral thermosensation is critical to the perception of food and drinks, little information is available on the organization of individual differences in these abilities. We examined the relationship between measures of cooling and warming on the tongue and lip and the association of these measures to taste sensitivity in a sample of 76 healthy subjects. Thermal abilities were assessed with a computer-controlled, 1.5 cm2 peltier plate that was placed on the anterior dorsal surface of the tongue or the lower lip. Thermal testing consisted of both cooling and warming threshold detection, and intensity ratings of warm and cool suprathreshold temperatures. Intensity ratings of different temperatures were highly correlated, especially for temperatures in the same class. Similarly, warming and cooling thresholds were highly correlated. In contrast, thermal detection abilities were largely dissociable from suprathreshold intensity ratings, especially in the cooling direction. Suprathreshold ratings of cooling on the tongue were also modestly associated with ratings of the taste intensity of 6-n-propylthiouracil (PROP). However, a similar association was observed for the lower lip, indicating that the effect does not reflect an isolated characteristic of lingual physiology. Unexpectedly, two subjects with no history of oral trauma demonstrated abnormally deficient (4 S.D. below the mean) cool threshold detection abilities for the tongue, suggesting that there may exist subjects in the population who have profoundly poor lingual temperature processing.

Adult↗

PubMed2006

An emotion-induced attentional blink elicited by aversively conditioned stimuli.

The current study examines whether aversively conditioned stimuli can modulate attention to such a degree that they impair the perception of subsequently presented nonemotional targets. In the initial phase of this study, participants viewed 3 categories of photographs, 1 of which was paired with an aversive noise. Following conditioning, participants searched for a target embedded within a series of 17 rapidly presented images on each trial. Critically, a conditioned or unconditioned item from the initial phase appeared 200 ms or 800 ms before the target. At 200-ms lags but not 800-ms lags, the conditioned images impaired target detection relative to the other distractors. Thus, temporary visual deficits can be induced by otherwise neutral distractors whose aversive associations have only recently been learned.

Acoustic Stimulation↗

PubMed2005

On the scent of human olfactory orbitofrontal cortex: meta-analysis and comparison to non-human primates.

It is widely accepted that the orbitofrontal cortex (OFC) represents the main neocortical target of primary olfactory cortex. In non-human primates, the olfactory neocortex is situated along the basal surface of the caudal frontal lobes, encompassing agranular and dysgranular OFC medially and agranular insula laterally, where this latter structure wraps onto the posterior orbital surface. Direct afferent inputs arrive from most primary olfactory areas, including piriform cortex, amygdala, and entorhinal cortex, in the absence of an obligatory thalamic relay. While such findings are almost exclusively derived from animal data, recent cytoarchitectonic studies indicate a close anatomical correspondence between non-human primate and human OFC. Given this cross-species conservation of structure, it has generally been presumed that the olfactory projection area in human OFC occupies the same posterior portions of OFC as seen in non-human primates. This review questions this assumption by providing a critical survey of the localization of primate and human olfactory neocortex. Based on a meta-analysis of human functional neuroimaging studies, the region of human OFC showing the greatest olfactory responsivity appears substantially rostral and in a different cytoarchitectural area than the orbital olfactory regions as defined in the monkey. While this anatomical discrepancy may principally arise from methodological differences across species, these results have implications for the interpretation of prior human lesion and neuroimaging studies and suggest constraints upon functional extrapolations from animal data.

Animals↗

PubMed2005

A meta-analysis of neuropsychological change to clozapine, olanzapine, quetiapine, and risperidone in schizophrenia.

Cognitive impairment is a core feature of schizophrenia and a major impediment to social and vocational rehabilitation. A number of studies have claimed cognitive benefits from treatment with various atypical antipsychotic drugs (APDs). The currently available evidence supporting cognitive improvement with atypical APDs was evaluated in two meta-analyses. Studies that (1) prospectively examined cognitive change to the atypical APDs clozapine, olanzapine, quetiapine, and risperidone, (2) included a commonly used neuropsychological test, and (3) provided data from which relevant effect sizes could be calculated, were included. Forty-one studies met these criteria. Neuropsychological test data from each study were combined into a Global Cognitive Index and nine cognitive domain scores. Two meta-analyses were carried out. The first included 14 controlled, random assignment trials that assigned subjects to an atypical APD and a typical APD control arm. The second analysis included all prospective investigations of atypical treatment and the within-group change score divided by its standard deviation served as an estimate of effect size (ES). The first analysis revealed that atypicals are superior to typicals at improving overall cognitive function (ES=0.24). Specific improvements were observed in the learning and processing speed domains. The second analysis extended the improvements to a broader range of cognitive domains (ES range=0.17-0.46) and identified significant differences between treatments in attention and verbal fluency. Moderator variables such as study blind and random assignment influence results of cognitive change to atypical APDs. Atypical antipsychotics produce a mild remediation of cognitive deficits in schizophrenia, and specific atypicals have differential effects within certain cognitive domains.

Antipsychotic Agents↗

PubMed2005

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↗

PubMed2005

Attentional rubbernecking: cognitive control and personality in emotion-induced blindness.

Emotional stimuli often attract attention, but at what cost to the processing of other stimuli? Given the potential costs, to what degree can people override emotion-based attentional biases? In Experiment 1, participants searched for a single target within a rapid serial visual presentation of pictures; an irrelevant, emotionally negative or neutral picture preceded the target by either two or eight items. At the shorter lag, negative pictures spontaneously induced greater deficits in target processing than neutral pictures did. Thus, attentional biases to emotional information induced a temporary inability to process stimuli that people actively sought. Experiment 2 revealed that participants could reduce this effect through attentional strategy, but that the extent of this reduction was related to their level of the personality trait harm avoidance. Participants lower in harm avoidance were able to reduce emotion-induced blindness under conditions designed to facilitate the ignoring of the emotional stimuli. Those higher in harm avoidance were unable to do so.

Adult↗

PubMed2004

Dopamine transmission in the human striatum during monetary reward tasks.

Previous studies have demonstrated the ability of the [11C]raclopride positron emission tomography (PET) technique to measure behaviorally induced changes in endogenous dopamine transmission in humans. However, these studies have lacked well matched sensorimotor control conditions, making it difficult to know what sensory, cognitive, or motor features contributed to changes in dopaminergic activity. Here we report on [11C]raclopride PET studies in which healthy humans performed card selection tasks for monetary rewards. During separate scans, subjects completed a variable ratio (VR) reward schedule with a 25% reward rate in which they did not know the outcome of their responses in advance, a fixed ratio (FR) 25% reward schedule in which outcomes were fully predictable, and a sensorimotor control (SC) condition involving similar sensory and motor demands but no rewards. Relative to the SC condition, the FR schedule produced only modest increases in dopamine transmission and no decreases relative to the SC condition. In contrast, the VR schedule produced significant increases in dopamine transmission in the left medial caudate nucleus while simultaneously producing significant decreases in other areas of the caudate and putamen. These data indicate: (1) the feasibility of measuring alterations in dopamine transmission even after controlling for sensorimotor features and (2) the complex and regionally specific influence of VR schedules on dopamine transmission. The implications of these results are discussed in relation to conflicting models of dopaminergic functioning arising from studies using electrophysiological and microdialysis techniques in animals.

Adult↗

PubMed2003

The human amygdala and the emotional evaluation of sensory stimuli.

A wealth of animal data implicates the amygdala in aspects of emotional processing. In recent years, functional neuroimaging and neuropsychological studies have begun to refine our understanding of the functions of the amygdala in humans. This literature offers insights into the types of stimuli that engage the amygdala and the functional consequences that result from this engagement. Specific conclusions and hypotheses include: (1) the amygdala activates during exposure to aversive stimuli from multiple sensory modalities; (2) the amygdala responds to positively valenced stimuli, but these responses are less consistent than those induced by aversive stimuli; (3) amygdala responses are modulated by the arousal level, hedonic strength or current motivational value of stimuli; (4) amygdala responses are subject to rapid habituation; (5) the temporal characteristics of amygdala responses vary across stimulus categories and subject populations; (6) emotionally valenced stimuli need not reach conscious awareness to engage amygdala processing; (7) conscious hedonic appraisals do not require amygdala activation; (8) activation of the amygdala is associated with modulation of motor readiness, autonomic functions, and cognitive processes including attention and memory; (9) amygdala activations do not conform to traditional models of the lateralization of emotion; and (10) the extent and laterality of amygdala activations are related to factors including psychiatric status, gender and personality. The strengths and weakness of these hypotheses and conclusions are discussed with reference to the animal literature.

Amygdala↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

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↗