Neural substrates of human fear generalization: A 7T-fMRI investigation.

Fear generalization - the tendency to interpret ambiguous stimuli as threatening due to perceptual similarity to a learned threat - is an adaptive process. Overgeneralization, however, is maladaptive and has been implicated in a number of anxiety disorders. Neuroimaging research has indicated several regions sensitive to effects of generalization, including regions involved in fear excitation (e.g., amygdala, insula) and inhibition (e.g., ventromedial prefrontal cortex). Research has suggested several other small brain regions may play an important role in this process (e.g., hippocampal subfields, bed nucleus of the stria terminalis [BNST], habenula), but, to date, these regions have not been examined during fear generalization due to limited spatial resolution of standard human neuroimaging. To this end, we utilized the high spatial resolution of 7T fMRI to characterize the neural circuits involved in threat discrimination and generalization. Additionally, we examined potential modulating effects of trait anxiety and intolerance of uncertainty on neural activation during threat generalization. In a sample of 31 healthy undergraduate students, significant positive generalization effects (i.e., greater activation for stimuli with increasing perceptual similarity to a learned threat cue) were observed in the visual cortex, thalamus, habenula and BNST, while negative generalization effects were observed in the dentate gyrus, CA1, and CA3. Associations with individual differences were underpowered, though preliminary findings suggested greater generalization in the insula and primary somatosensory cortex may be correlated with self-reported anxiety. Overall, findings largely support previous neuroimaging work on fear generalization and provide additional insight into the contributions of several previously unexplored brain regions.

Taxonomic relations evoke more fear than thematic relations after fear conditioning: An EEG study.

When fear is generalized, knowledge based on concepts is also retrieved. Concepts have two very different relations: thematic relations based on the co-occurrence of events or scenarios, and taxonomic relations based on similarity or shared features. However, it remains unclear whether thematic and taxonomic relationships differentially affect fear generalization. To clarify the underlying cognitive mechanisms of these relations, the current study combined the classical fear conditioning procedure with electroencephalography (EEG). Forty participants were conditioned to a neutral word by pairing the presentation of the word with an unpleasant electrical pulse. A different stimulus was not paired with the electrical pulse. Next, during generalization testing, thematically related or taxonomic-related words were presented. Behavioral responses (shock expectancy and response time) and brain responses (event-related potentials [ERP] and oscillation activity) were recorded. Behavioral results showed that taxonomic relations initiated higher shock expectancy compared with thematic relations, and that conceptual relations did not affect response times. Taxonomic relations induced larger P2 components than thematic relations, and danger generalization stimuli initiated smaller P600 components than safe generalization stimuli. In addition, the magnitudes of alpha and beta oscillations were larger for danger generalization stimuli. These results suggested that taxonomic stimuli generalize broader responses compared with thematic relations after fear conditioning. Therefore, we report a possible new electrophysiological evidence for the presentation of fear generalization. These findings aid our understanding of fear generalization at the concept level and have clinical implications for the cognitive treatment of anxiety disorders.

Relationship of Reaction Time to Perception of a Stimulus and Volitionally Delayed Response.

BACKGROUND AND OBJECTIVE: Initiation of response in a simple reaction time (RT) task may precede conscious perception of the stimulus. Since volitionally delayed responses may require conscious perception of the stimulus before response initiation, it has been hypothesized that volitionally delayed responses will markedly delay RT. METHODS: We conducted two experiments with separate groups of healthy volunteers (n=16; n=13) who performed computerized simple and choice RT tasks. In the standard condition, we instructed the participants to respond to a visual stimulus by pushing a button as quickly as possible. In the second condition, we instructed the participants to respond after a slight volitional delay. The second experiment had an additional volitional delay condition in which we asked participants to delay their responses by an estimated 50% above their usual standard response. RESULTS: We found marked delays and increased variability when participants volitionally delayed their responses, averaging 322 ms for standard and 861 ms for delayed simple RTs (267% increase), and 650 ms for standard and 1018 ms for delayed choice RTs (157% increase). Effects did not differ across age, sex, or handedness. However, a minority of participants did not meaningfully delay their RT during the volitional delay conditions. CONCLUSIONS: On average, participants had marked delays when they tried to delay their responses slightly, but a subset of participants exhibited essentially no delay despite trying to delay. We suggest some potential mechanisms that future investigations might delineate.

Activity of the anterior cingulate cortex and ventral hippocampus underlie increases in contextual fear generalization.

Memories for context become less specific with time resulting in animals generalizing fear from training contexts to novel contexts. Though much attention has been given to the neural structures that underlie the long-term consolidation of a context fear memory, very little is known about the mechanisms responsible for the increase in fear generalization that occurs as the memory ages. Here, we examine the neural pattern of activation underlying the expression of a generalized context fear memory in male C57BL/6J mice. Animals were context fear conditioned and tested for fear in either the training context or a novel context at recent and remote time points. Animals were sacrificed and fluorescent in situ hybridization was performed to assay neural activation. Our results demonstrate activity of the prelimbic, infralimbic, and anterior cingulate (ACC) cortices as well as the ventral hippocampus (vHPC) underlie expression of a generalized fear memory. To verify the involvement of the ACC and vHPC in the expression of a generalized fear memory, animals were context fear conditioned and infused with 4% lidocaine into the ACC, dHPC, or vHPC prior to retrieval to temporarily inactivate these structures. The results demonstrate that activity of the ACC and vHPC is required for the expression of a generalized fear memory, as inactivation of these regions returned the memory to a contextually precise form. Current theories of time-dependent generalization of contextual memories do not predict involvement of the vHPC. Our data suggest a novel role of this region in generalized memory, which should be incorporated into current theories of time-dependent memory generalization. We also show that the dorsal hippocampus plays a prolonged role in contextually precise memories. Our findings suggest a possible interaction between the ACC and vHPC controls the expression of fear generalization.

Linking perceptual learning with identical stimuli to imagery perceptual learning.

Perceptual learning is usually thought to be exclusively driven by the stimuli presented during training (and the underlying synaptic learning rules). In some way, we are slaves of our visual experiences. However, learning can occur even when no stimuli are presented at all. For example, Gabor contrast detection improves when only a blank screen is presented and observers are asked to imagine Gabor patches. Likewise, performance improves when observers are asked to imagine the nonexisting central line of a bisection stimulus to be offset either to the right or left. Hence, performance can improve without stimulus presentation. As shown in the auditory domain, performance can also improve when the very same stimulus is presented in all learning trials and observers were asked to discriminate differences which do not exist (observers were not told about the set up). Classic models of perceptual learning cannot handle these situations since they need proper stimulus presentation, i.e., variance in the stimuli, such as a left versus right offset in the bisection stimulus. Here, we show that perceptual learning with identical stimuli occurs in the visual domain, too. Second, we linked the two paradigms by telling observers that only the very same bisection stimulus was presented in all trials and asked them to imagine the central line to be offset either to the left or right. As in imagery learning, performance improved.

Fear generalization in humans: impact of feature learning on conditioning and extinction.

Little is known about the role of discrete stimulus features in the regulation of fear. This study examined the effects of feature learning on the acquisition and extinction of fear conditioning. Human participants were fear conditioned to a yellow triangle (CS+) using an electrical shock. We manipulated feature learning through differential conditioning. The nonconditioned control stimulus (CS-) was a red triangle in one group (Color-Relevant), but a yellow circle in the other group (Shape-Relevant). Next, two generalization stimuli were tested that shared the shape- or color-feature with the CS+ (a blue triangle and a yellow square). Online shock-expectancy ratings and skin conductance responding showed that the CS- determined the pattern of fear generalization: the same-color stimulus elicited more fear in Group Color-Relevant, versus the same-shape stimulus in group Shape-Relevant. Furthermore, extinguishing these two generalization stimuli had no detectable effect on fear of the CS+. These results show that fear generalization is influenced by feature learning through differential conditioning, and that exposures to different features of a stimulus are not sufficient to extinguish fear of that stimulus as a whole.

Individual differences in stimulus identification, rule induction, and generalization of learning.

In the field of stimulus generalization, an old yet unresolved discussion pertains to what extent stimulus misidentifications contribute to the pattern of conditioned responding. In this article, we perform cluster analysis on six datasets (four published datasets and two unpublished datasets, included N = 950) to examine the relationship between interindividual differences in (a) stimulus identification, (b) patterns of generalized responding, and (c) verbalized generalization rules. The datasets were obtained from online predictive learning tasks where participants learned associations between colored cues and the presence or absence of a hypothetical outcome. In these datasets, stimulus identification and expectancy ratings were assessed in separate phases to a range of colors varying between blue-green. Using cluster analyses on performance during stimulus identification, we identified different subgroups of participants (good vs. bad identifiers). In all six datasets, we found a close relationship between the pattern of stimulus identification and the shape of the expectancy gradient across the test dimension between the identified subgroups. Furthermore, participants classified as good identifiers were more likely to report a similarity generalization rule than a relational or linear rule, suggesting that individual differences in stimulus identification are related to individual differences in generalization rules. These findings suggest that greater consideration should be given to interindividual variability in stimulus identification, inductive rules, and their relationship in explaining patterns of generalized responses. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Brain modularity in arthropods: individual neurons that support "what" but not "where" memories.

Experiments with insects and crabs have demonstrated their remarkable capacity to learn and memorize complex visual features (Giurfa et al., 2001; Pedreira and Maldonado, 2003; Chittka and Niven, 2009). Such abilities are thought to require modular brain processing similar to that occurring in vertebrates (Menzel and Giurfa, 2001). Yet, physiological evidence for this type of functioning in the small brains of arthropods is still scarce (Liu et al., 1999, 2006; Menzel and Giurfa, 2001). In the crab Chasmagnathus granulatus, the learning rate as well as the long-term memory of a visual stimulus has been found to be reflected in the performance of identified lobula giant neurons (LGs) (Tomsic et al., 2003). The memory can only be evoked in the training context, indicating that animals store two components of the learned experience, one related to the visual stimulus and one related to the visual context (Tomsic et al., 1998; Hermitte et al., 1999). By performing intracellular recordings in the intact animal, we show that the ability of crabs to generalize the learned stimulus into new space positions and to distinguish it from a similar but unlearned stimulus, two of the main attributes of stimulus memory, is reflected by the performance of the LGs. Conversely, we found that LGs do not support the visual context memory component. Our results provide physiological evidence that the memory traces regarding "what" and "where" are stored separately in the arthropod brain.

Detection of an inhibitory cortical gradient underlying peak shift in learning: a neural basis for a false memory.

Experience often does not produce veridical memory. Understanding false attribution of events constitutes an important problem in memory research. "Peak shift" is a well-characterized, controllable phenomenon in which human and animal subjects that receive reinforcement associated with one sensory stimulus later respond maximally to another stimulus in post-training stimulus generalization tests. Peak shift ordinarily develops in discrimination learning (reinforced CS+, unreinforced CS-) and has long been attributed to the interaction of an excitatory gradient centered on the CS+ and an inhibitory gradient centered on the CS-; the shift is away from the CS-. In contrast, we have obtained peak shifts during single tone frequency training, using stimulation of the cholinergic nucleus basalis (NB) to implant behavioral memory into the rat. As we also recorded cortical activity, we took the opportunity to investigate the possible existence of a neural frequency gradient that could account for behavioral peak shift. Behavioral frequency generalization gradients (FGGs, interruption of ongoing respiration) were determined twice before training while evoked potentials were recorded from the primary auditory cortex (A1), to obtain a baseline gradient of "habituatory" neural decrement. A post-training behavioral FGG obtained 24h after three daily sessions of a single tone paired with NB stimulation (200 trials/day) revealed a peak shift. The peak of the FGG was at a frequency lower than the CS while the cortical inhibitory gradient was at a frequency higher than the CS frequency. Further analysis indicated that the frequency location and magnitude of the gradient could account for the behavioral peak shift. These results provide a neural basis for a systematic case of memory misattribution and may provide an animal model for the study of the neural bases of a type of "false memory".

Toward an account of clinical anxiety predicated on basic, neurally mapped mechanisms of Pavlovian fear-learning: the case for conditioned overgeneralization.

The past two decades have brought dramatic progress in the neuroscience of anxiety due, in no small part, to animal findings specifying the neurobiology of Pavlovian fear-conditioning. Fortuitously, this neurally mapped process of fear learning is widely expressed in humans, and has been centrally implicated in the etiology of clinical anxiety. Fear-conditioning experiments in anxiety patients thus represent a unique opportunity to bring recent advances in animal neuroscience to bear on working, brain-based models of clinical anxiety. The current presentation details the neural basis and clinical relevance of fear conditioning, and highlights generalization of conditioned fear to stimuli resembling the conditioned danger cue as one of the more robust conditioning markers of clinical anxiety. Studies testing such generalization across a variety of anxiety disorders (panic, generalized anxiety disorder, and social anxiety disorder) with systematic methods developed in animals will next be presented. Finally, neural accounts of overgeneralization deriving from animal and human data will be described with emphasis given to implications for the neurobiology and treatment of clinical anxiety.

Looking like a criminal: stereotypical black facial features promote face source memory error.

The present studies tested whether African American face type (stereotypical or nonstereotypical) facilitated stereotype-consistent categorization, and whether that categorization influenced memory accuracy and errors. Previous studies have shown that stereotypically Black features are associated with crime and violence (e.g., Blair, Judd, & Chapleau Psychological Science 15:674-679, 2004; Blair, Judd, & Fallman Journal of Personality and Social Psychology 87:763-778, 2004; Blair, Judd, Sadler, & Jenkins Journal of Personality and Social Psychology 83:5-252002); here, we extended this finding to investigate whether there is a bias toward remembering and recategorizing stereotypical faces as criminals. Using category labels, consistent (or inconsistent) with race-based expectations, we tested whether face recognition and recategorization were driven by the similarity between a target's facial features and a stereotyped category (i.e., stereotypical Black faces associated with crime/violence). The results revealed that stereotypical faces were associated more often with a stereotype-consistent label (Study 1), were remembered and correctly recategorized as criminals (Studies 2-4), and were miscategorized as criminals when memory failed. These effects occurred regardless of race or gender. Together, these findings suggest that face types have strong category associations that can promote stereotype-motivated recognition errors. Implications for eyewitness accuracy are discussed.

Learning-induced biases in the ongoing dynamics of sensory representations predict stimulus generalization.

Sensory stimuli have long been thought to be represented in the brain as activity patterns of specific neuronal assemblies. However, we still know relatively little about the long-term dynamics of sensory representations. Using chronic in vivo calcium imaging in the mouse auditory cortex, we find that sensory representations undergo continuous recombination, even under behaviorally stable conditions. Auditory cued fear conditioning introduces a bias into these ongoing dynamics, resulting in a long-lasting increase in the number of stimuli activating the same subset of neurons. This plasticity is specific for stimuli sharing representational similarity to the conditioned sound prior to conditioning and predicts behaviorally observed stimulus generalization. Our findings demonstrate that learning-induced plasticity leading to a representational linkage between the conditioned stimulus and non-conditioned stimuli weaves into ongoing dynamics of the brain rather than acting on an otherwise static substrate.

Global inhibition and stimulus competition in the owl optic tectum.

Stimulus selection for gaze and spatial attention involves competition among stimuli across sensory modalities and across all of space. We demonstrate that such cross-modal, global competition takes place in the intermediate and deep layers of the optic tectum, a structure known to be involved in gaze control and attention. A variety of either visual or auditory stimuli located anywhere outside of a neuron's receptive field (RF) were shown to suppress or completely eliminate responses to a visual stimulus located inside the RF in nitrous oxide sedated owls. The essential mechanism underlying this stimulus competition is global, divisive inhibition. Unlike the effect of the classical inhibitory surround, which decreases with distance from the RF center and shapes neuronal responses to individual stimuli, global inhibition acts across the entirety of space and modulates responses primarily in the context of multiple stimuli. Whereas the source of this global inhibition is as yet unknown, our data indicate that different networks mediate the classical surround and global inhibition. We hypothesize that this global, cross-modal inhibition, which acts automatically in a bottom-up manner even in sedated animals, is critical to the creation of a map of stimulus salience in the optic tectum.

Asymmetrical number-space mapping in the avian brain.

When trained to peck a selected position in a sagittally-oriented series of identical food containers, and then required to generalize to an identical series rotated by 90°, chicks identify as correct only the target position from the left end, while choosing the right one at chance. Here we show that when accustomed to systematic changes in inter-elements distances during training or faced with similar spatial changes at test, chicks identify as correct both the target positions from left and right ends. However, ordinal position is spontaneously encoded even when inter-element distances are kept fixed during training (in spite of the fact that distances between elements suffice for target identification without any numerical computation). We explain these findings in terms of intra-hemispheric coupling of bilateral numerical (ordinal) representation and unilateral (right hemispheric) spatial representation of the number line, producing differential allocation of attention in the left and right visual hemifields.

A single footshock causes long-lasting hypoactivity in unknown environments that is dependent on the development of contextual fear conditioning.

Exposure to a single session of footshocks induces long-lasting inhibition of activity in unknown environments that markedly differ from the shock context. Interestingly, these effects are not necessarily associated to an enhanced anxiety and interpretation of this hypoactivity remains unclear. In the present experiment we further studied this phenomenon in male Sprague-Dawley rats. In a first experiment, a session of three shocks resulted in hypoactivity during exposure, 6-12days later, to three different unknown environments. This altered behaviour was not accompanied by a greater hypothalamic-pituitary-adrenal (HPA) activation, although greater HPA activation paralleling higher levels of freezing was observed in the shock context. In a second experiment we used a single shock and two procedures, one with pre-exposure to the context before the shock and another with immediate shock that did not induce contextual fear conditioning. Hypoactivity and a certain level of generalization of fear (freezing) to the unknown environments only appeared in the group that developed fear conditioning, but no evidence for enhanced anxiety in the elevated plus-maze was found in any group. The results suggest that if animals are able to associate an aversive experience with a distinct unknown environment, they would display more cautious behaviour in any unknown environment and such strategy persists despite repeated experience with different environments. This long-lasting cautious behaviour was not associated to greater HPA response to the unknown environment that was however observed in the shock context. The present findings raised some concerns about interpretation of long-lasting behavioural changes caused by brief stressors.

The influence of reward magnitude on stimulus memory and stimulus generalization in categorization decisions.

Reward magnitude is a central concept in most theories of preferential decision making and learning. However, it is unknown whether variable rewards also influence cognitive processes when learning how to make accurate decisions (e.g., sorting healthy and unhealthy food differing in appeal). To test this, we conducted 3 studies. Participants learned to classify objects with 3 feature dimensions into two categories before solving a transfer task with novel objects. During learning, we rewarded all correct decisions, but specific category exemplars yielded a 10 times higher reward (high vs. low). Counterintuitively, categorization performance did not increase for high-reward stimuli, compared with an equal-reward baseline condition. Instead, performance decreased reliably for low-reward stimuli. To analyze the influence of reward magnitude on category generalization, we implemented an exemplar-categorization model and a cue-weighting model using a Bayesian modeling approach. We tested whether reward magnitude affects (a) the availability of exemplars in memory, (b) their psychological similarity to the stimulus, or (c) attention to stimulus features. In all studies, the evidence favored the hypothesis that reward magnitude affects the similarity gradients of high-reward exemplars compared with the equal-reward baseline. The results from additional reward-judgment tasks (Studies 2 and 3) strongly suggest that the cognitive processes of reward-value generalization parallel those of category generalization. Overall, the studies provide insights highlighting the need for integrating reward- and category-learning theories. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

The effect of tDCS on recognition depends on stimulus generalization: Neuro-stimulation can predictably enhance or reduce the face inversion effect.

This article reports results from three experiments that investigate how a particular neuro-stimulation procedure is able, in certain circumstances, to selectively increase the face inversion effect by enhancing recognition for upright faces, and argues that these effects can be understood in terms of the McLaren-Kaye-Mackintosh (MKM) theory of stimulus representation. We demonstrate how a specific transcranial direct current stimulation (tDCS) methodology can improve performance in circumstances where error-based salience modulation is making face recognition harder. The 3 experiments used an old/new recognition task involving sets of normal versus Thatcherized faces. The main characteristic of Thatcherized faces is that the eyes and the mouth are upside down, thus emphasizing features that tend to be common to other Thatcherized faces and so leading to stronger generalization making recognition worse. Experiment 1 combined a behavioral and event-related potential study looking at the N170 peak component, which helped us to calibrate the set of face stimuli needed for subsequent experiments. In Experiment 2, we used our tDCS procedure (between-subjects and double-blind) in an attempt to reduce the negative effects induced by error-based modulation of salience on recognition of upright Thatcherized faces. Results largely confirmed our predictions. In addition, they showed a significant improvement on recognition performance for upright normal faces. Experiment 3 provides the first direct evidence in a single study that the same tDCS procedure is able to both enhance performance when normal faces are presented with Thatcherized faces, and to reduce performance when normal faces are presented with other normal faces (i.e., male vs. female faces). We interpret our results by analyzing how salience modulation influences generalization between similar categories of stimuli. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Pigeons exhibit flexibility but not rule formation in dimensional learning, stimulus generalization, and task switching.

A prominent model of categorization (Ashby, Alfonso-Reese, Turken, & Waldron, 1998) posits that 2 separate mechanisms-one declarative, one associative-can be recruited in category learning. These 2 systems can effectively be distinguished by 2 task structures: rule-based (RB) tasks are unidimensional and encourage analytic processing, whereas information-integration (II) tasks are bidimensional and encourage nonanalytic associative learning. Humans and nonhuman primates have been reported to learn RB tasks more quickly than II tasks; however, pigeons and rats have shown no learning speed differences are thus believed to lack the declarative system. In the present trio of experiments, we further explored pigeons' dimensional category learning. We replicated the finding that pigeons learn RB and II tasks at equal speeds. Further, we found that stimulus generalization performance was equivalent on both tasks. We also explored the effect of switching from one task to another. Task switches between phases of training as well as within individual training sessions posed little difficulty for pigeons; they quickly and flexibly switched their categorization responses with no cost in choice speed or accuracy. Together, our data indicate that, although pigeons may lack the capacity to form explicit dimensional rules, their associative learning system is both powerful and flexible. Further exploration of this associative system would help us better appreciate possible contributions of the declarative system. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Understanding evaluation of faces on social dimensions.

People reliably and automatically make personality inferences from facial appearance despite little evidence for their accuracy. Although such inferences are highly inter-correlated, research has traditionally focused on studying specific traits such as trustworthiness. We advocate an alternative, data-driven approach to identify and model the structure of face evaluation. Initial findings indicate that specific trait inferences can be represented within a 2D space defined by valence/trustworthiness and power/dominance evaluation of faces. Inferences along these dimensions are based on similarity to expressions signaling approach or avoidance behavior and features signaling physical strength, respectively, indicating that trait inferences from faces originate in functionally adaptive mechanisms. We conclude with a discussion of the potential role of the amygdala in face evaluation.

Inactivation of the basolateral amygdala impairs the retrieval of recent and remote taste-potentiated odor aversion memory.

Memory reorganization as a time-dependent process can be investigated using various learning tasks such as the taste-potentiated odor aversion (TPOA). In this paradigm rats acquire a strong aversion to an olfactory cue presented simultaneously with a gustatory cue. Together these cues are paired with a delayed visceral illness. The basolateral amygdaloid nucleus (BLA) plays a key role in TPOA acquisition but its involvement in retrieval remains unclear. We investigated the involvement of the BLA in either recent or remote retrieval of TPOA. In each case, the number of licks observed in response to the presentation of either the odor or the taste was used to assess retrieval. Before the retrieval test, rats received a bilateral infusion of lidocaine to inactivate the BLA. We observed that both recent and remote TPOA retrieval tests induced by the odor presentation were disrupted in the lidocaine-injected rats. By contrast, the BLA inactivation had no effect upon the aversion towards the taste cue regardless of the time of retrieval. The present study provides evidence that BLA functioning is necessary for retrieval of aversive odor memory, even with a long post-acquisition delay.