Auditory associative learning and its neural correlates in the auditory midbrain

Interpreting the meaning of environmental stimuli to generate optimal behavioral responses is essential for survival. Simply sensing a sound, without accessing prior knowledge in the brain, will not benefit behavior. How sensation and memory interact to form behavior is one of the fundamental questions in the field of neuroscience. In this thesis, I have addressed this question from two perspectives: I investigated the behavioral outcome of this interaction using discrimination, and the circuit underlying this interaction using electrophysiological recordings in the behaving mouse. Behaviorally, we found that the physical difference between to-be-discriminated sounds, had a constraining effect on discrimination. This effect occurred even though physical differences were significantly larger than reported discrimination limens, thus reflecting a high overlap between the memory traces of the relevant stimuli. The results suggest a strong role of pre-wired tonotopic organization and the involvement of peripheral stations with wider tuning (Ehret and Merzenich, 1985; Taberner and Liberman, 2005). To further understand the influence of sensation on behavior, we tested the interaction between sound features with generalization. Using sounds that differed in two dimensions, we found that bi-dimensional generalization can be either biased towards a single dimension or an integration of both. Whether it was one or the other depended on the two dimensions used. As the first convergence station in the auditory system (Casseday et al., 2002), the role of the inferior colliculus in encoding behavioral relevant information is not well understood. Recording from freely behaving mouse, we found task engagement modulated neural activity in the IC in a stimulus-specific manner. Our lab found previously that relevant sound exposure induced enhancement in neural activity and shifts in tonal representation in the IC (Cruces-Solís et al., 2018). As a continuation, we found that movement-sound association is essential for this plasticity. Furthermore, recording in freely behaving mice also found that this association modulated the ongoing LFP in the IC, suggesting a new role of IC in filtering movement-related acoustic stimuli. To conclude, our results support the view that the IC is not simply an auditory structure that relays auditory information into the cortex, but plays important role in interpreting the meaning of the sound. The new role of IC in encoding movement-related information suggests that the filtering function of the auditory system starts already in subcortical stages of the auditory pathway

Mapping dynamic interactions among cognitive biases in depression

Depression is theorized to be caused in part by biased cognitive processing of emotional information. Yet, prior research has adopted a reductionist approach that does not characterize how biases in cognitive processes such as attention and memory work together to confer risk for this complex multifactorial disorder. Grounded in affective and cognitive science, we highlight four mechanisms to understand how attention biases, working memory difficulties, and long-term memory biases interact and contribute to depression. We review evidence for each mechanism and highlight time- and context-dependent dynamics. We outline methodological considerations and recommendations for research in this area. We conclude with directions to advance the understanding of depression risk, cognitive training interventions, and transdiagnostic properties of cognitive biases and their interactions

Examining the impact of cue similarity and fear learning on perceptual tuning

Past research on the effects of associative aversive learning on discrimination acuity has shown mixed results, including increases, decreases, and no changes in discrimination ability. An animal study found that the type of learning experience determined the direction and extent of learning-induced changes. The current preregistered web-based study aimed to translate these findings to humans. Experiment 1 (N = 245) compared changes in stimulus discrimination between simple learning (only one oriented grating cue), coarse differential conditioning (physically distinct cues), and fine differential conditioning (physically similar cues) as well as to their three respective control groups. The discrimination task consisted of a two-alternative-forced-choice task with oriented grating stimuli. During learning, a specific orientation was paired with unpleasant pictures. Our analysis using generative modeling demonstrated weak to moderate evidence that aversive learning did not alter discrimination acuity in any of the groups. In a follow-up experiment (N = 121), we replicated these findings despite successful learning trajectories in all three groups and a more detailed assessment of discrimination acuity. Contrary to prior assumptions, our findings indicate that aversive learning does not enhance perceptual discrimination, and the presence of additional safety cues does not appear to moderate this effect.</p

Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation

Novelty facilitates formation of memories. The detection of novelty and storage of contextual memories are both mediated by the hippocampus, yet the mechanisms that link these two functions remain to be defined. Dentate granule cells (GCs) of the dorsal hippocampus fire upon novelty exposure forming engrams of contextual memory. However, their key excitatory inputs from the entorhinal cortex are not responsive to novelty and are insufficient to make dorsal GCs fire reliably. Here we uncover a powerful glutamatergic pathway to dorsal GCs from ventral hippocampal mossy cells (MCs) that relays novelty, and is necessary and sufficient for driving dorsal GCs activation. Furthermore, manipulation of ventral MCs activity bidirectionally regulates novelty-induced contextual memory acquisition. Our results show that ventral MCs activity controls memory formation through an intra-hippocampal interaction mechanism gated by novelty

Associative Concept Learning in Animals

Nonhuman animals show evidence for three types of concept learning: perceptual or similarity-based in which objects/stimuli are categorized based on physical similarity; relational in which one object/stimulus is categorized relative to another (e.g., same/different); and associative in which arbitrary stimuli become interchangeable with one another by virtue of a common association with another stimulus, outcome, or response. In this article, we focus on various methods for establishing associative concepts in nonhuman animals and evaluate data documenting the development of associative classes of stimuli. We also examine the nature of the common within-class representation of samples that have been associated with the same reinforced comparison response (i.e., many-to-one matching) by describing manipulations for distinguishing possible representations. Associative concepts provide one foundation for human language such that spoken and written words and the objects they represent become members of a class of interchangeable stimuli. The mechanisms of associative concept learning and the behavioral flexibility it allows, however, are also evident in the adaptive behaviors of animals lacking language

Remote Effects of Hippocampal Sclerosis on Effective Connectivity during Working Memory Encoding: A Case of Connectional Diaschisis?

Accumulating evidence suggests a role for the medial temporal lobe (MTL) in working memory (WM). However, little is known concerning its functional interactions with other cortical regions in the distributed neural network subserving WM. To reveal these, we availed of subjects with MTL damage and characterized changes in effective connectivity while subjects engaged in WM task. Specifically, we compared dynamic causal models, extracted from magnetoencephalographic recordings during verbal WM encoding, in temporal lobe epilepsy patients (with left hippocampal sclerosis) and controls. Bayesian model comparison indicated that the best model (across subjects) evidenced bilateral, forward, and backward connections, coupling inferior temporal cortex (ITC), inferior frontal cortex (IFC), and MTL. MTL damage weakened backward connections from left MTL to left ITC, a decrease accompanied by strengthening of (bidirectional) connections between IFC and MTL in the contralesional hemisphere. These findings provide novel evidence concerning functional interactions between nodes of this fundamental cognitive network and sheds light on how these interactions are modified as a result of focal damage to MTL. The findings highlight that a reduced (top-down) influence of the MTL on ipsilateral language regions is accompanied by enhanced reciprocal coupling in the undamaged hemisphere providing a first demonstration of “connectional diaschisis.

Remote Effects of Hippocampal Sclerosis on Effective Connectivity during Working Memory Encoding: A Case of Connectional Diaschisis?

Accumulating evidence suggests a role for the medial temporal lobe (MTL) in working memory (WM). However, little is known concerning its functional interactions with other cortical regions in the distributed neural network subserving WM. To reveal these, we availed of subjects with MTL damage and characterized changes in effective connectivity while subjects engaged in WM task. Specifically, we compared dynamic causal models, extracted from magnetoencephalographic recordings during verbal WM encoding, in temporal lobe epilepsy patients (with left hippocampal sclerosis) and controls. Bayesian model comparison indicated that the best model (across subjects) evidenced bilateral, forward, and backward connections, coupling inferior temporal cortex (ITC), inferior frontal cortex (IFC), and MTL. MTL damage weakened backward connections from left MTL to left ITC, a decrease accompanied by strengthening of (bidirectional) connections between IFC and MTL in the contralesional hemisphere. These findings provide novel evidence concerning functional interactions between nodes of this fundamental cognitive network and sheds light on how these interactions are modified as a result of focal damage to MTL. The findings highlight that a reduced (top-down) influence of the MTL on ipsilateral language regions is accompanied by enhanced reciprocal coupling in the undamaged hemisphere providing a first demonstration of “connectional diaschisis.

Valence, Arousal, and Gender Effect on Olfactory Cortical Network Connectivity: a study using Dynamic Causal Modeling for EEG

The cortical network including the piriform (PC), orbitofrontal (OFC), and entorhinal (EC) cortices allows the complex processing of behavioral, cognitive, and context-related odor information and represents an access gate to the subcortical limbic regions. Among the several factors that influence odor processing, their hedonic content and gender differences play a relevant role. Here, we investigated how these factors influence EEG effective connectivity among the mentioned brain regions during emotional olfactory stimuli. To this aim, we acquired EEG data from twenty-one healthy volunteers, during a passive odor task of odorants with different valence. We used Dynamic Causal Modeling (DCM) for EEG and Parametric Empirical Bayes (PEB) to investigate the modulatory effects of odors’ valence on the connectivity strengths of the PC-EC-OFC network. Moreover, we controlled for the influence of arousal and gender on such modulatory effects. Our results highlighted the relevant role of the forward and backward PC-EC connections in odor’s brain processing. On the one hand, the EC-to-PC connection was inhibited by both pleasant and unpleasant odors, but not by the neutral one. On the other hand, the PC-to-EC forward connection was found to be modulated (posterior probability (Pp)&gt;0.95) by the arousal level associated with an unpleasant odor. Finally, the whole network dynamics showed several significant gender-related differences (Pp&gt;0.95) suggesting a better ability in odor discrimination for the female gender