Perirhinal Cortex is Involved in the Resolution of Learned Approach-Avoidance Conflict Associated with Discrete Objects.
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ABSTRACT:
SUBMITTER: Chu S
PROVIDER: S-EPMC8023846 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Neural models of approach-avoidance (AA) conflict behavior and its dysfunction have focused traditionally on the hippocampus, with the assumption that this medial temporal lobe (MTL) structure plays a ubiquitous role in arbitrating AA conflict. We challenge this perspective by using three different AA behavioral tasks in conjunction with optogenetics, to demonstrate that a neighboring region in male rats, perirhinal cortex, is also critically involved but only when conflicting motivational values are associated with objects and not contextual information. The ventral hippocampus, in contrast, was found not to be essential for object-associated AA conflict, suggesting its preferential involvement in context-associated conflict. We propose that stimulus type can impact MTL involvement during AA conflict and that a more nuanced understanding of MTL contributions to impaired AA behavior (e.g., anxiety) is required. These findings serve to expand upon the established functions of the perirhinal cortex while concurrently presenting innovative behavioral paradigms that permit the assessment of different facets of AA conflict behavior.
| S-EPMC10292842 | biostudies-literature
Project description:Our brain disambiguates the objects in our cluttered visual world seemingly effortlessly, enabling us to understand their significance and to act appropriately. The role of anteromedial temporal structures in this process, particularly the perirhinal cortex, is highly controversial. In some accounts, the perirhinal cortex is necessary for differentiating between perceptually and semantically confusable objects. Other models claim that the perirhinal cortex neither disambiguates perceptually confusable objects nor plays a unique role in semantic processing. One major hurdle to resolving this central debate is the fact that brain damage in human patients typically encompasses large portions of the anteromedial temporal lobe, such that the identification of individual substructures and precise neuroanatomical locus of the functional impairments has been difficult. We tested these competing accounts in patients with Alzheimer's disease with varying degrees of atrophy in anteromedial structures, including the perirhinal cortex. To assess the functional contribution of each anteromedial temporal region separately, we used a detailed region of interest approach. From each participant, we obtained magnetic resonance imaging scans and behavioural data from a picture naming task that contrasted naming performance with living and non-living things as a way of manipulating perceptual and semantic confusability; living things are more similar to one another than non-living things, which have more distinctive features. We manually traced neuroanatomical regions of interest on native-space cortical surface reconstructions to obtain mean thickness estimates for the lateral and medial perirhinal cortex and entorhinal cortex. Mean cortical thickness in each region of interest, and hippocampal volume, were submitted to regression analyses predicting naming performance. Importantly, atrophy of the medial perirhinal cortex, but not lateral perirhinal cortex, entorhinal cortex or hippocampus, significantly predicted naming performance on living relative to non-living things. These findings indicate that one specific anteromedial temporal lobe region-the medial perirhinal cortex-is necessary for the disambiguation of perceptually and semantically confusable objects. Taken together, these results support a hierarchical account of object processing, whereby the perirhinal cortex at the apex of the ventral object processing system is required to bind properties of not just perceptually, but also semantically confusable objects together, enabling their disambiguation from other similar objects and thus comprehension. Significantly, this model combining a hierarchical object processing architecture with a semantic feature statistic account explains why category-specific semantic impairments for living things are associated with anteromedial temporal lobe damage, and pinpoints the root of this syndrome to perirhinal cortex damage.
| S-EPMC3525054 | biostudies-literature
Project description:Damage to rat perirhinal cortex (PR) profoundly impairs fear conditioning to 22kHz ultrasonic vocalizations (USVs), but has no effect on fear conditioning to continuous tones. The most obvious difference between these two sounds is that continuous tones have no internal temporal structure, whereas USVs consist of strings of discrete calls separated by temporal discontinuities. PR was hypothesized to support the fusion or integration of discontinuous auditory segments into unitary representations or "auditory objects". This transform was suggested to be necessary for normal fear conditioning to occur. These ideas naturally assume that the effect of PR damage on auditory fear conditioning is not peculiar to 22kHz USVs. The present study directly tested these ideas by using a different set of continuous and discontinuous auditory cues. Control and PR-damaged rats were fear conditioned to a 53kHz USV, a 53kHz continuous tone, or a 53kHz discontinuous tone. The continuous and discontinuous tones matched the 53kHz USV in terms of duration, loudness, and principle frequency. The on/off pattern of the discontinuous tone matched the pattern of the individual calls of the 53kHz USV. The on/off pattern of the 50kHz USV was very different from the patterns in the 22kHz USVs that have been comparably examined. Rats with PR damage were profoundly impaired in fear conditioning to both discontinuous cues, but they were unimpaired in conditioning to the continuous cue. The implications of this temporal discontinuity effect are explored in terms of contemporary ideas about PR function.
| S-EPMC2700730 | biostudies-literature
Project description:The recollection of environmental cues associated with threat or reward allows animals to select the most appropriate behavioral responses. Neurons in the prelimbic (PL) cortex respond to both threat- and reward-associated cues. However, it remains unknown whether PL regulates threat-avoidance vs. reward-approaching responses when an animals' decision depends on previously associated memories. Using a conflict model in which male Long-Evans rats retrieve memories of shock- and food-paired cues, we observed two distinct phenotypes during conflict: (1) rats that continued to press a lever for food (Pressers) and (2) rats that exhibited a complete suppression in food seeking (Non-pressers). Single-unit recordings revealed that increased risk-taking behavior in Pressers is associated with persistent food-cue responses in PL, and reduced spontaneous activity in PL glutamatergic (PLGLUT) neurons during conflict. Activating PLGLUT neurons in Pressers attenuated food-seeking responses in a neutral context, whereas inhibiting PLGLUT neurons in Non-pressers reduced defensive responses and increased food approaching during conflict. Our results establish a causal role for PLGLUT neurons in mediating individual variability in memory-based risky decision-making by regulating threat-avoidance vs. reward-approach behaviors.
| S-EPMC8853658 | biostudies-literature
Project description:The perirhinal cortex (PRC) is known to play an important role in object recognition. Little is known, however, regarding the activity of PRC neurons during the presentation of stimuli that are commonly used for recognition memory tasks in rodents, that is, three-dimensional objects. Rats in the present study were exposed to three-dimensional objects while they traversed a circular track for food reward. Under some behavioral conditions, the track contained novel objects, familiar objects, or no objects. Approximately 38% of PRC neurons demonstrated "object fields" (a selective increase in firing at the location of one or more objects). Although the rats spent more time exploring the objects when they were novel compared to familiar, indicating successful recognition memory, the proportion of object fields and the firing rates of PRC neurons were not affected by the rats' previous experience with the objects. Together, these data indicate that the activity of PRC cells is powerfully affected by the presence of objects while animals navigate through an environment; but under these conditions, the firing patterns are not altered by the relative novelty of objects during successful object recognition.
| S-EPMC3447635 | biostudies-other
Project description:Animal models of human anxiety often invoke a conflict between approach and avoidance. In these, a key behavioral assay comprises passive avoidance of potential threat and inhibition, both thought to be controlled by ventral hippocampus. Efforts to translate these approaches to clinical contexts are hampered by the fact that it is not known whether humans manifest analogous approach-avoidance dispositions and, if so, whether they share a homologous neurobiological substrate. Here, we developed a paradigm to investigate the role of human hippocampus in arbitrating an approach-avoidance conflict under varying levels of potential threat. Across four experiments, subjects showed analogous behavior by adapting both passive avoidance behavior and behavioral inhibition to threat level. Using functional magnetic resonance imaging (fMRI), we observe that threat level engages the anterior hippocampus, the human homolog of rodent ventral hippocampus. Testing patients with selective hippocampal lesions, we demonstrate a causal role for the hippocampus with patients showing reduced passive avoidance behavior and inhibition across all threat levels. Our data provide the first human assay for approach-avoidance conflict akin to that of animal anxiety models. The findings bridge rodent and human research on passive avoidance and behavioral inhibition and furnish a framework for addressing the neuronal underpinnings of human anxiety disorders, where our data indicate a major role for the hippocampus.
| S-EPMC3969259 | biostudies-literature
Project description:Approach-Avoidance conflict (AAC) arises from decisions with embedded positive and negative outcomes, such that approaching leads to reward and punishment and avoiding to neither. Despite its importance, the field lacks a mechanistic understanding of which regions are driving avoidance behavior during conflict. In the current task, we utilized transcranial magnetic stimulation (TMS) and drift-diffusion modeling to investigate the role of one of the most prominent regions relevant to AAC-the dorsolateral prefrontal cortex (dlPFC). The first experiment uses in-task disruption to examine the right dlPFC's (r-dlPFC) causal role in avoidance behavior. The second uses single TMS pulses to probe the excitability of the r-dlPFC, and downstream cortical activations, during avoidance behavior. Disrupting r-dlPFC during conflict decision-making reduced reward sensitivity. Further, r-dlPFC was engaged with a network of regions within the lateral and medial prefrontal, cingulate, and temporal cortices that associate with behavior during conflict. Together, these studies use TMS to demonstrate a role for the dlPFC in reward sensitivity during conflict and elucidate the r-dlPFC's network of cortical regions associated with avoidance behavior. By identifying r-dlPFC's mechanistic role in AAC behavior, contextualized within its conflict-specific downstream neural connectivity, we advance dlPFC as a potential neural target for psychiatric therapeutics.
| S-EPMC9077265 | biostudies-literature
Project description:Animal approach-avoidance conflict paradigms have been used extensively to characterize effects of anxiolytic agents and probe neural circuitry related to anxiety. However, there are few behavioral approaches to measure conflict in human populations, limiting the translation of findings from animal conflict tasks to human clinical research. We developed a novel approach-avoidance conflict (AAC) paradigm involving situations in which the same decision is associated with "reward" (points) and "punishment" (negative affective stimuli). The AAC task was completed by 95 young adults (56 female) with varying levels of self-reported trait anxiety. As expected, conflict-related approach behavior correlated with self-reported motivation to approach reward and avoid punishment and greater reward level increased approach behavior. Additionally, females exhibited less approach behavior than males. Anxiety Sensitivity Index (Physical subscale) scores related negatively to approach behavior for males, while Behavioral Activation Scale (BAS, Fun Seeking subscale) scores related positively to approach behavior for females. Results support the utility of the AAC task as a behavioral test that has strong reverse translational features. Findings indicate that approach drives and anxiety sensitivity may be important in determining conflict behavior for females and males respectively. The approach-avoidance conflict task offers a novel, translational measure to probe neural systems underlying conflict behavior, motivational processes, and anxiety disorders.
| S-EPMC3381365 | biostudies-other
Project description:Animal approach-avoidance conflict paradigms have been used extensively to operationalize anxiety, quantify the effects of anxiolytic agents, and probe the neural basis of fear and anxiety. Results from human neuroimaging studies support that a frontal-striatal-amygdala neural circuitry is important for approach-avoidance learning. However, the neural basis of decision-making is much less clear in this context. Thus, we combined a recently developed human approach-avoidance paradigm with functional magnetic resonance imaging (fMRI) to identify neural substrates underlying approach-avoidance conflict decision-making. Fifteen healthy adults completed the approach-avoidance conflict (AAC) paradigm during fMRI. Analyses of variance were used to compare conflict to nonconflict (avoid-threat and approach-reward) conditions and to compare level of reward points offered during the decision phase. Trial-by-trial amplitude modulation analyses were used to delineate brain areas underlying decision-making in the context of approach/avoidance behavior. Conflict trials as compared to the nonconflict trials elicited greater activation within bilateral anterior cingulate cortex, anterior insula, and caudate, as well as right dorsolateral prefrontal cortex (PFC). Right caudate and lateral PFC activation was modulated by level of reward offered. Individuals who showed greater caudate activation exhibited less approach behavior. On a trial-by-trial basis, greater right lateral PFC activation related to less approach behavior. Taken together, results suggest that the degree of activation within prefrontal-striatal-insula circuitry determines the degree of approach versus avoidance decision-making. Moreover, the degree of caudate and lateral PFC activation related to individual differences in approach-avoidance decision-making. Therefore, the approach-avoidance conflict paradigm is ideally suited to probe anxiety-related processing differences during approach-avoidance decision-making.
| S-EPMC4300249 | biostudies-literature
Project description:The ability of animals to maximize benefits and minimize costs during approach-avoidance conflicts is an important evolutionary tool, but little is known about the emergence of specific strategies for conflict resolution. Accordingly, we developed a simple approach-avoidance conflict task in rats that pits the motivation to press a lever for sucrose against the motivation to step onto a distant platform to avoid a footshock delivered at the end of a 30 s tone (sucrose is available only during the tone). Rats received conflict training for 16 days to give them a chance to optimize their strategy by learning to properly time the expression of both behaviors across the tone. Rats unexpectedly separated into three distinct subgroups: those pressing early in the tone and avoiding later (Timers, 49%); those avoiding throughout the tone (Avoidance-preferring, 32%); and those pressing throughout the tone (Approach-preferring, 19%). The immediate early gene cFos revealed that Timers showed increased activity in the ventral striatum and midline thalamus relative to the other two subgroups, Avoidance-preferring rats showed increased activity in the amygdala, and Approach-preferring rats showed decreased activity in the prefrontal cortex. This pattern is consistent with low fear and high behavioral flexibility in Timers, suggesting the potential of this task to reveal the neural mechanisms of conflict resolution.
| S-EPMC7947632 | biostudies-literature