Biomedical subjects

Jay A Gottfried

Publications and source records attributed to Jay A Gottfried.

10 recordsLinked to original sources

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

Integrated neural representations of odor intensity and affective valence in human amygdala.

Arousal and valence are proposed to represent fundamental dimensions of emotion. The neural substrates for processing these aspects of stimuli are studied widely, with recent studies of chemosensory processing suggesting the amygdala processes intensity (a surrogate for arousal) rather than valence. However, these investigations have assumed that a valence effect in the amygdala is linear such that testing valence extremes is sufficient to infer responses across valence space. In this study, we tested an alternative hypothesis, namely that valence responses in the amygdala are nonlinear. Using event-related functional magnetic resonance imaging, we measured amygdala responses to high- and low-concentration variants of pleasant, neutral, and unpleasant odors. Our results demonstrate that the amygdala exhibits an intensity-by-valence interaction in olfactory processing. In other words, the effect of intensity on amygdala activity is not the same at all levels of valence. Specifically, the amygdala responds differentially to high (vs low)-intensity odor for pleasant and unpleasant smells but not for neutral smells. This implies that the amygdala codes neither intensity nor valence per se, but a combination that we suggest reflects the overall emotional value of a stimulus.

Adult↗

PubMed2005

A truffle in the mouth is worth two in the bush: odor localization in the human brain.

It is widely thought that locating the source of a smell is an ability best left to nonhuman members of the animal kingdom. In this issue of Neuron, two complementary articles highlight the neural mechanisms underlying the localization of an odor, either to the left or right side of the nose (Porter et al.) or to the inside or outside of the mouth (Small et al.). Together, these studies validate the idea that the human brain is equipped with the apparatus necessary to pinpoint the location of an odor source.

Animals↗

PubMed2004

Human orbitofrontal cortex mediates extinction learning while accessing conditioned representations of value.

In extinction, an animal learns that a previously conditioned stimulus (CS+) no longer predicts delivery of a salient reinforcer (unconditioned stimulus, UCS). Rodent studies indicate that extinction relies on amygdala-prefrontal interactions and involves formation of memories that inhibit, without actually erasing, the original conditioning trace. Whether extinction learning in humans follows similar neurobiological principles is unknown. We used functional magnetic resonance imaging to measure human brain activity evoked during olfactory aversive conditioning and extinction learning. Neural responses in orbitofrontal cortex and amygdala were preferentially enhanced during extinction, suggesting potential cross-species preservation of learning mechanisms that oppose conditioning. Moreover, by manipulating UCS aversiveness via reinforcer inflation, we showed that a CS+ retains access to representations of UCS value in distinct regions of ventral prefrontal cortex, even as extinction proceeds.

Adolescent↗

PubMed2004

Remembrance of odors past: human olfactory cortex in cross-modal recognition memory.

Episodic memory is often imbued with multisensory richness, such that the recall of an event can be endowed with the sights, sounds, and smells of its prior occurrence. While hippocampus and related medial temporal structures are implicated in episodic memory retrieval, the participation of sensory-specific cortex in representing the qualities of an episode is less well established. We combined functional magnetic resonance imaging (fMRI) with a cross-modal paradigm, where objects were presented with odors during memory encoding. We then examined the effect of odor context on neural responses at retrieval when these same objects were presented alone. Primary olfactory (piriform) cortex, as well as anterior hippocampus, was activated during the successful retrieval of old (compared to new) objects. Our findings indicate that sensory features of the original engram are preserved in unimodal olfactory cortex. We suggest that reactivation of memory traces distributed across modality-specific brain areas underpins the sensory qualities of episodic memories.

Adolescent↗

PubMed2003

Encoding predictive reward value in human amygdala and orbitofrontal cortex.

Adaptive behavior is optimized in organisms that maintain flexible representations of the value of sensory-predictive cues. To identify central representations of predictive reward value in humans, we used reinforcer devaluation while measuring neural activity with functional magnetic resonance imaging. We presented two arbitrary visual stimuli, both before and after olfactory devaluation, in a paradigm of appetitive conditioning. In amygdala and orbitofrontal cortex, responses evoked by a predictive target stimulus were decreased after devaluation, whereas responses to the nondevalued stimulus were maintained. Thus, differential activity in amygdala and orbitofrontal cortex encodes the current value of reward representations accessible to predictive cues.

Adult↗

PubMed2003

The nose smells what the eye sees: crossmodal visual facilitation of human olfactory perception.

Human olfactory perception is notoriously unreliable, but shows substantial benefits from visual cues, suggesting important crossmodal integration between these primary sensory modalities. We used event-related fMRI to determine the underlying neural mechanisms of olfactory-visual integration in the human brain. Subjects participated in an olfactory detection task, whereby odors and pictures were delivered separately or together. By manipulating the degree of semantic correspondence between odor-picture pairs, we show a perceptual olfactory facilitation for semantically congruent (versus incongruent) trials. This behavioral advantage was associated with enhanced neural activity in anterior hippocampus and rostromedial orbitofrontal cortex. We suggest these findings can be interpreted as indicating that human hippocampus mediates reactivation of crossmodal semantic associations, even in the absence of explicit memory processing.

Adult↗

PubMed2003

Acquired mirror writing and reading: evidence for reflected graphemic representations.

Mirror writing occurs when individual letters and whole word strings are produced in reverse direction. By analogy, mirror reading refers to the preference to read mirror reversed over normally written words. These phenomena appear rarely after brain damage and offer insight into the nervous system's organization of visual-spatial and visual-motor representations. We present the case of a 51-year-old patient with persistent mirror writing and reading following traumatic brain injury. She preferred to write in the mirror direction with either hand. She drew asymmetric pictures with the same directional bias as normal right-handed subjects, and she did not exhibit left-right confusion regarding other pictures. By contrast, on picture-word matching and lexical decision tasks, she was faster and more accurate with mirrored than normally written words. This pattern of performance suggests that her behavior was not accounted for by reflected motor programs, or by the mirroring of visual-spatial representations in general. Rather, we suggest that her behavior was produced by privileged access to mirrored graphemes. Furthermore, because she seemed better able to read irregular words in mirrored than in normal formats, we suggest that mirrored representations may exist at the whole word level and not simply at the letter level.

Brain Injuries↗

PubMed2002

Functional heterogeneity in human olfactory cortex: an event-related functional magnetic resonance imaging study.

Studies of patients with focal brain injury indicate that smell perception involves caudal orbitofrontal and medial temporal cortices, but a more precise functional organization has not been characterized. In addition, although it is believed that odors are potent triggers of emotion, support for an anatomical association is scant. We sought to define the neural substrates of human olfactory information processing and determine how these are modulated by affective properties of odors. We used event-related functional magnetic resonance imaging (fMRI) in an olfactory version of a classical conditioning paradigm, whereby neutral faces were paired with pleasant, neutral, or unpleasant odors, under 50% reinforcement. By comparing paired (odor/face) and unpaired (face only) conditions, odor-evoked neural activations could be isolated specifically. In primary olfactory (piriform) cortex, spatially and temporally dissociable responses were identified along a rostrocaudal axis. A nonhabituating response in posterior piriform cortex was tuned to all odors, whereas activity in anterior piriform cortex reflected sensitivity to odor affect. Bilateral amygdala activation was elicited by all odors, regardless of valence. In posterior orbitofrontal cortex, neural responses evoked by pleasant and unpleasant odors were segregated within medial and lateral segments, respectively. The results indicate functional heterogeneity in areas critical to human olfaction. They also show that brain regions mediating emotional processing are differentially activated by odor valence, providing evidence for a close anatomical coupling between olfactory and emotional processes.

Adolescent↗

PubMed2002

Appetitive and aversive olfactory learning in humans studied using event-related functional magnetic resonance imaging.

We combined event-related functional magnetic resonance imaging (fMRI) with olfactory classical conditioning to differentiate the neural responses evoked during appetitive and aversive olfactory learning. Three neutral faces [the conditioned stimuli (CS+)] were repetitively paired with pleasant, neutral, or unpleasant odors [the unconditioned stimuli (UCS)] in a partial reinforcement schedule. A fourth face was never paired to odor [the nonconditioned stimulus (CS-)]. Learning-related neural activity, comparing unpaired (face only) CS+ stimuli with CS-, showed valence-independent activations in rostral and caudal orbitofrontal cortex (OFC). Medial OFC responded to the appetitive (app) CS+, whereas lateral OFC responded to the aversive (av) CS+. Within nucleus accumbens, neural responses showed divergent activation profiles that increased with time in response to the appCS+ but decreased in response to the avCS+. In posterior amygdala, responses were elicited by the appCS+, which habituated over time. In temporal piriform cortex, neural responses were evoked by the avCS+, which progressively increased with time. These results highlight regional and temporal dissociations during olfactory learning and imply that emotionally salient odors can engender cross-modal associative learning. Moreover, the findings suggest that the role of human primary (piriform) and secondary olfactory cortices transcends their function as mere intermediaries of chemosensory information processing.

Adult↗