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Learning & Memory (Cold Spring Harbor,... Sep 2015The entorhinal cortex (EC)-hippocampal (HPC) network plays an essential role for episodic memory, which preserves spatial and temporal information about the occurrence... (Review)
Review
The entorhinal cortex (EC)-hippocampal (HPC) network plays an essential role for episodic memory, which preserves spatial and temporal information about the occurrence of past events. Although there has been significant progress toward understanding the neural circuits underlying the spatial dimension of episodic memory, the relevant circuits subserving the temporal dimension are just beginning to be understood. In this review, we examine the evidence concerning the role of the EC in associating events separated by time--or temporal associative learning--with emphasis on the function of persistent activity in the medial entorhinal cortex layer III (MECIII) and their direct inputs into the CA1 region of HPC. We also discuss the unique role of Island cells in the medial entorhinal cortex layer II (MECII), which is a newly discovered direct feedforward inhibitory circuit to CA1. Finally, we relate the function of these entorhinal cortical circuits to recent findings concerning hippocampal time cells, which may collectively activate in sequence to bridge temporal gaps between discontiguous events in an episode.
Topics: Animals; Association Learning; Entorhinal Cortex; Hippocampus; Humans; Neural Pathways; Time Perception
PubMed: 26286654
DOI: 10.1101/lm.038687.115 -
The Journal of Neuroscience : the... Aug 2018Behavioral evidence suggests that beliefs about causal structure constrain associative learning, determining which stimuli can enter into association, as well as the... (Comparative Study)
Comparative Study
Behavioral evidence suggests that beliefs about causal structure constrain associative learning, determining which stimuli can enter into association, as well as the functional form of that association. Bayesian learning theory provides one mechanism by which structural beliefs can be acquired from experience, but the neural basis of this mechanism is poorly understood. We studied this question with a combination of behavioral, computational, and neuroimaging techniques. Male and female human subjects learned to predict an outcome based on cue and context stimuli while being scanned using fMRI. Using a model-based analysis of the fMRI data, we show that structure learning signals are encoded in posterior parietal cortex, lateral prefrontal cortex, and the frontal pole. These structure learning signals are distinct from associative learning signals. Moreover, representational similarity analysis and information mapping revealed that the multivariate patterns of activity in posterior parietal cortex and anterior insula encode the full posterior distribution over causal structures. Variability in the encoding of the posterior across subjects predicted variability in their subsequent behavioral performance. These results provide evidence for a neural architecture in which structure learning guides the formation of associations. Animals are able to infer the hidden structure behind causal relations between stimuli in the environment, allowing them to generalize this knowledge to stimuli they have never experienced before. A recently published computational model based on this idea provided a parsimonious account of a wide range of phenomena reported in the animal learning literature, suggesting a dedicated neural mechanism for learning this hidden structure. Here, we validate this model by measuring brain activity during a task that involves both structure learning and associative learning. We show that a distinct network of regions supports structure learning and that the neural signal corresponding to beliefs about structure predicts future behavioral performance.
Topics: Anticipation, Psychological; Association Learning; Bayes Theorem; Brain Mapping; Causality; Cues; Female; Frontal Lobe; Humans; Magnetic Resonance Imaging; Male; Models, Neurological; Models, Psychological; Parietal Lobe; Prefrontal Cortex
PubMed: 29959234
DOI: 10.1523/JNEUROSCI.3336-17.2018 -
Psychonomic Bulletin & Review Aug 2016An extensive program of research in the past 2 decades has focused on the role of modal sensory, motor, and affective brain systems in storing and retrieving concept... (Review)
Review
An extensive program of research in the past 2 decades has focused on the role of modal sensory, motor, and affective brain systems in storing and retrieving concept knowledge. This focus has led in some circles to an underestimation of the need for more abstract, supramodal conceptual representations in semantic cognition. Evidence for supramodal processing comes from neuroimaging work documenting a large, well-defined cortical network that responds to meaningful stimuli regardless of modal content. The nodes in this network correspond to high-level "convergence zones" that receive broadly crossmodal input and presumably process crossmodal conjunctions. It is proposed that highly conjunctive representations are needed for several critical functions, including capturing conceptual similarity structure, enabling thematic associative relationships independent of conceptual similarity, and providing efficient "chunking" of concept representations for a range of higher order tasks that require concepts to be configured as situations. These hypothesized functions account for a wide range of neuroimaging results showing modulation of the supramodal convergence zone network by associative strength, lexicality, familiarity, imageability, frequency, and semantic compositionality. The evidence supports a hierarchical model of knowledge representation in which modal systems provide a mechanism for concept acquisition and serve to ground individual concepts in external reality, whereas broadly conjunctive, supramodal representations play an equally important role in concept association and situation knowledge.
Topics: Association; Brain; Cognition; Concept Formation; Humans; Knowledge; Neuroimaging; Recognition, Psychology; Semantics
PubMed: 27294428
DOI: 10.3758/s13423-015-0909-1 -
Psychopharmacology Jan 2019It has been recognized that drug addiction engages aberrant process of learning and memory, and substantial studies have focused on developing effective treatment to... (Review)
Review
It has been recognized that drug addiction engages aberrant process of learning and memory, and substantial studies have focused on developing effective treatment to erase the enduring drug memories to reduce the propensity to relapse. Extinction, a behavioral intervention exposing the individuals to the drug-associated cues repeatedly, can weaken the craving and relapse induced by drug-associated cues, but its clinic efficacy is limited. A clear understanding of the neuronal circuitry and molecular mechanism underlying extinction of drug memory will facilitate the successful use of extinction therapy in clinic. As a key component of mesolimbic system, medial prefrontal cortex (mPFC) has received particular attention largely in that PFC stands at the core of neural circuits for memory extinction and manipulating mPFC influences extinction of drug memories and subsequent relapse. Here, we review the recent advances in both animal models of drug abuse and human addicted patients toward the understanding of the mechanistic link between mPFC and drug memory, with particular emphasis on how mPFC contributes to the extinction of drug memory at levels ranging from neuronal architecture, synaptic plasticity to molecular signaling and epigenetic regulation, and discuss the clinic relevance of manipulating the extinction process of drug memory to prevent craving and relapse through enhancing mPFC function.
Topics: Animals; Association Learning; Cues; Disease Models, Animal; Extinction, Psychological; Humans; Male; Memory; Nerve Net; Neuronal Plasticity; Neurons; Prefrontal Cortex; Recurrence; Substance-Related Disorders
PubMed: 30392133
DOI: 10.1007/s00213-018-5069-3 -
Behavioural Brain Research Jan 2016The neurophysiology of human associative memory has been studied with electroencephalographic techniques since the 1930s. This research has revealed that different types... (Review)
Review
The neurophysiology of human associative memory has been studied with electroencephalographic techniques since the 1930s. This research has revealed that different types of electrophysiological processes in the human brain can be modified by conditioning: sensory evoked potentials, sensory induced gamma-band activity, periods of frequency-specific waves (alpha and beta waves, the sensorimotor rhythm and the mu-rhythm) and slow cortical potentials. Conditioning of these processes has been studied in experiments that either use operant conditioning or repeated contingent pairings of conditioned and unconditioned stimuli (classical conditioning). In operant conditioning, the appearance of a specific brain process is paired with an external stimulus (neurofeedback) and the feedback enables subjects to obtain varying degrees of control of the CNS-process. Such acquired self-regulation of brain activity has found practical uses for instance in the amelioration of epileptic seizures, Autism Spectrum Disorders (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). It has also provided communicative means of assistance for tetraplegic patients through the use of brain computer interfaces. Both extra and intracortically recorded signals have been coupled with contingent external feedback. It is the aim for this review to summarize essential results on all types of electromagnetic brain processes that have been modified by classical or operant conditioning. The results are organized according to type of conditioned EEG-process, type of conditioning, and sensory modalities of the conditioning stimuli.
Topics: Association Learning; Brain Waves; Cerebral Cortex; Conditioning, Psychological; Evoked Potentials; Humans
PubMed: 26367470
DOI: 10.1016/j.bbr.2015.09.011 -
Neuron Oct 2020The representation of odor in olfactory cortex (piriform) is distributive and unstructured and can only be afforded behavioral significance upon learning. We performed...
The representation of odor in olfactory cortex (piriform) is distributive and unstructured and can only be afforded behavioral significance upon learning. We performed 2-photon imaging to examine the representation of odors in piriform and in two downstream areas, the orbitofrontal cortex (OFC) and the medial prefrontal cortex (mPFC), as mice learned olfactory associations. In piriform, we observed that odor responses were largely unchanged during learning. In OFC, 30% of the neurons acquired robust responses to conditioned stimuli (CS+) after learning, and these responses were gated by internal state and task context. Moreover, direct projections from piriform to OFC can be entrained to elicit learned olfactory behavior. CS+ responses in OFC diminished with continued training, whereas persistent representations of both CS+ and CS- odors emerged in mPFC. Optogenetic silencing indicates that these two brain structures function sequentially to consolidate the learning of appetitive associations.
Topics: Animals; Appetitive Behavior; Association Learning; Conditioning, Classical; Intravital Microscopy; Mice; Microscopy, Fluorescence, Multiphoton; Neurons; Odorants; Olfactory Pathways; Optogenetics; Piriform Cortex; Prefrontal Cortex
PubMed: 32827456
DOI: 10.1016/j.neuron.2020.07.033 -
BioRxiv : the Preprint Server For... Jun 2024Human cortical development follows a sensorimotor-to-association sequence during childhood and adolescence . The brain's capacity to enact this sequence over decades...
Human cortical development follows a sensorimotor-to-association sequence during childhood and adolescence . The brain's capacity to enact this sequence over decades indicates that it relies on intrinsic mechanisms to regulate inter-regional differences in the timing of cortical maturation, yet regulators of human developmental chronology are not well understood. Given evidence from animal models that thalamic axons modulate windows of cortical plasticity , here we evaluate the overarching hypothesis that structural connections between the thalamus and cortex help to coordinate cortical maturational heterochronicity during youth. We first introduce, cortically annotate, and anatomically validate a new atlas of human thalamocortical connections using diffusion tractography. By applying this atlas to three independent youth datasets (ages 8-23 years; total = 2,676), we reproducibly demonstrate that thalamocortical connections develop along a maturational gradient that aligns with the cortex's sensorimotor-association axis. Associative cortical regions with thalamic connections that take longest to mature exhibit protracted expression of neurochemical, structural, and functional markers indicative of higher circuit plasticity as well as heightened environmental sensitivity. This work highlights a central role for the thalamus in the orchestration of hierarchically organized and environmentally sensitive windows of cortical developmental malleability.
PubMed: 38915591
DOI: 10.1101/2024.06.13.598749 -
NeuroImage Apr 2020Creative thinking relies on the ability to make remote associations and fruitfully combine unrelated concepts. Hence, original associations and bi-associations (i.e.,...
Creative thinking relies on the ability to make remote associations and fruitfully combine unrelated concepts. Hence, original associations and bi-associations (i.e., associations to one and two concepts, respectively) are considered elementary cognitive processes of creative cognition. In this work, we investigated the cognitive and brain mechanisms underlying these association processes with tasks that asked for original associations to either one or two adjective stimuli. Study 1 showed that the generation of more original associations and bi-associations was related to several indicators of creativity, corroborating the validity of these association performances as basic processes underlying creative cognition. Study 2 assessed brain activity during performance of these association tasks by means of fMRI. The generation of original versus common associations was related to higher activation in bilateral lingual gyri suggesting that cued search for remote representatives of given properties are supported by visually-mediated search strategies. Parametric analyses further showed that the generation of more original associations involved activation of the left inferior frontal cortex and the left ventromedial prefrontal cortex, which are consistently implicated in constrained retrieval and evaluation processes, and relevant for making distant semantic connections. Finally, the generation of original bi-associations involved higher activation in bilateral hippocampus and inferior parietal lobe, indicating that conceptual combination recruits episodic simulation processes. Together, these findings suggest that the generation of verbally cued, original associations relies not only on verbal semantic memory but involves mental imagery and episodic simulation, offering new insights in the nuanced interplay of memory systems in creative thought.
Topics: Adolescent; Adult; Association; Brain Mapping; Cerebral Cortex; Creativity; Cues; Female; Hippocampus; Humans; Imagination; Language; Magnetic Resonance Imaging; Male; Memory, Episodic; Young Adult
PubMed: 32001370
DOI: 10.1016/j.neuroimage.2020.116586 -
NeuroImage Jun 2020Inappropriate behaviors may result from acquiring maladaptive associations between irrelevant information in the environment and important events, such as reward or...
Inappropriate behaviors may result from acquiring maladaptive associations between irrelevant information in the environment and important events, such as reward or punishment. Pre-exposure effects are believed to prevent the expression of irrelevant associations. For example, learned irrelevance delays the expression of associations between conditioned (CS) and unconditioned (US) stimuli following their uncorrelated presentation. The neuronal substrates of pre-exposure effects in humans are largely unknown because these effects rapidly attenuate when using traditional pre-exposure paradigms. The latter are therefore incompatible with neuroimaging approaches that require many trial repetitions. Moreover, large methodological differences between animal and human research on pre-exposure effects challenge the presumption of shared neurocognitive substrates, and question the prevalent use of pre-exposure effects in animals to model symptoms of human mental disorders. To overcome these limitations, we combined a novel learned irrelevance task with model-based fMRI. We report the results of a model that describes learned irrelevance as a dynamic process, which evolves across trials and integrates the weighting between two state-action values pertaining to 'CS-no US' associations (acquired during pre-exposure) and 'CS-US' associations (acquired during subsequent conditioning). This relative weighting correlated i) positively with the learned irrelevance effect observed in the behavioral task, ii) positively with activity in the entorhinal cortex, and iii) negatively with activity in the nucleus accumbens (NAcc). Furthermore, the model updates the relative weighting of the two state-action values via two separate prediction error (PE) signals that allow the dynamic accumulation of evidence for the CS to predict the 'US' or a 'no US' outcome. One PE signal, designed to increase the relative weight of 'CS-US' associations following 'US' outcomes, correlated with activity in the NAcc, while another PE signal, designed to increase the relative weight of 'CS-no US' associations following 'no US' outcomes, correlated with activity in the basolateral amygdala. By extending previous animal observations to humans, the present study provides a novel approach to foster translational research on pre-exposure effects.
Topics: Adult; Association Learning; Brain; Conditioning, Classical; Decision Making; Female; Humans; Inhibition, Psychological; Magnetic Resonance Imaging; Male
PubMed: 32156624
DOI: 10.1016/j.neuroimage.2020.116719 -
Biological Psychology Dec 2016Anxiety is characterized by the anticipation of aversive future events. The importance of prestimulus anticipatory factors, such as goals and expectations, is... (Review)
Review
Anxiety is characterized by the anticipation of aversive future events. The importance of prestimulus anticipatory factors, such as goals and expectations, is well-established in both visual perception and attention. Nevertheless, the prioritized perception of threatening stimuli in anxiety has been attributed to the automatic processing of these stimuli and the role of prestimulus factors has been neglected. The present review will focus on the role of top-down processes that occur before stimulus onset in the perceptual and attentional prioritization of threatening stimuli in anxiety. We will review both the cognitive and neuroscience literature, showing how top-down factors, and interactions between top-down and bottom-up factors may contribute to biased perception of threatening stimuli in normal function and anxiety. The shift in focus from stimulus-driven to endogenous factors and interactions between top-down and bottom-up factors in the prioritization of threat-related stimuli represents an important conceptual advance. In addition, it may yield important clues into the development and maintenance of anxiety, as well as inform novel treatments for anxiety.
Topics: Amygdala; Anxiety; Arousal; Association Learning; Attentional Bias; Brain; Brain Mapping; Cues; Emotions; Fear; Feedback, Physiological; Humans; Individuality; Nerve Net; Pattern Recognition, Visual; Recognition, Psychology; Visual Cortex
PubMed: 27546616
DOI: 10.1016/j.biopsycho.2016.08.006