Hippocampal lesions and stimulus generalization in rats

Wild, J. Martin; Blampied, Neville M.

doi:10.1016/0031-9384(72)90005-4

Cited by 27 publications

(14 citation statements)

References 33 publications

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“…Among them are results suggesting a critical role for the hippocampus, with lesions of either hippocampus (17,18) or cortical inputs to the hippocampus (i.e., postrhinal and perirhinal cortex) (19) increasing generalization of fear from CS+ to resembling safety cues (i.e., CS−) in animals. These findings suggest that hippocampal activations are necessary for successful discrimination of CS+ from GSs, potentially attributable to the pattern separation function of the hippocampus (20), through which brain representations of resembling, yet distinct, sensory experiences are discriminated.…”

Section: Discussionmentioning

confidence: 99%

Generalized Anxiety Disorder Is Associated With Overgeneralization of Classically Conditioned Fear

Lissek

Kaczkurkin

Rabin

et al. 2014

Biological Psychiatry

393

360

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Background Meta-analytic results of fear-conditioning studies in the anxiety disorders implicate generalization of conditioned fear to stimuli resembling the conditioned danger cue as one of the more robust conditioning markers of anxiety pathology. Due to the absence of conditioning studies assessing generalization in generalized anxiety disorder (GAD), results of this meta-analysis do not reveal whether such generalization abnormalities also apply to GAD. The current study fills this gap by behaviorally and psychophysiologically assessing levels of conditioned fear-generalization across adults with and without GAD. Methods Twenty-two patients with a DSM-IV-TR diagnosis of GAD and 26 healthy comparisons were recruited and tested. The employed generalization paradigm consists of quasi-randomly presented rings of gradually increasing size, with extreme sizes serving as conditioned danger cues (CS+) and conditioned safety-cues (CS−). The rings of intermediary size serve as generalization stimuli, creating a continuum-of-similarity between CS+ and CS− across which to assess response slopes, referred to as generalization gradients. Primary outcome variables included slopes for fear-potentiated startle (EMG) and self-reported risk ratings. Results Behavioral and psychophysiological findings demonstrate overgeneralization of conditioned fear among patients with GAD. Specifically, generalization gradients were abnormally shallow among GAD patients, reflecting less degradation of the conditioned fear response as the presented stimulus differentiated from the CS+. Conclusions Overgeneralization of conditioned fear, to safe encounters resembling feared situations, may contribute importantly to the psychopathology of GAD by proliferating anxiety cues in the individual’s environment that are then capable of evoking and maintaining anxiety and worry associated with GAD.

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Section: Discussionmentioning

confidence: 99%

Generalized Anxiety Disorder Is Associated With Overgeneralization of Classically Conditioned Fear

Lissek

Kaczkurkin

Rabin

et al. 2014

Biological Psychiatry

393

360

View full text Add to dashboard Cite

show abstract

“…Owing to the cross-species relevance of this conditioning process, hypotheses for human generalization were informed by neurobiological findings in animals. Among them are findings suggesting a critical role for the hippocampus, with increased generalization of conditioned responses to stimuli resembling the CS+ in lower mammals with lesions of the hippocampus 22, 23 . Of note, generalization constitutes a failure to discriminate CS+ from CS− and, as such, previously reported deficits evoked by hippocampal lesions can also be interpreted as impairments in discriminative conditioning.…”

Section: The Neurobiology Of Generalizationmentioning

confidence: 99%

Toward an Account of Clinical Anxiety Predicated on Basic, Neurally Mapped Mechanisms of Pavlovian Fear-Learning: The Case for Conditioned Overgeneralization

2012

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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 over-generalization deriving from animal and human data will be described with emphasis given to implications for the neurobiology and treatment of clinical anxiety.

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“…In all these cases, with the exception of Wild and Blampied (1972), the lesioned animals showed good gradients, both of excitation and inhibition. Thus, tones which were similar to the S + elicited responding, while those similar to the S -elicited considerably less responding.…”

Section: Operants 333mentioning

confidence: 88%

“…Schmaltz et al (1973) have reported that rats with hippocampal lesions are deficient in go-no-go, and that this deficiency involves over-responding to the S -and, during the later stages of the study, the S + as well. * * Similarly, Wild and Blampied (1972) and Woodruff, Means, and Isaacson (1973) report that hippocampal rats are impaired both on retention and acquisition of go-no-go. On the other hand, Schwartzbaum, Thompson, and Kellicutt (1964) showed that hippocampal rats could retain a preoperatively acquired go-no-go discrimination, the only abnormality in * We have already discussed the fact that when the cue is at a remove from the lever normal animals perform less well than do hippocampals (p. 268).…”

Section: Go-no-go and Non-spatial Alternationmentioning

confidence: 90%

“…In five of the studies (Schwartzbaum et al 1964, Wild and Blampied 1972, Gaffan 1973Freeman and Kramarcy 1974) go-no-go training was followed by tests of the generalization gradients established to the discriminative * This deficit might relate to the difference seen in intact animals between feature-positive and feature-negative tasks. When the S + is a discrete stimulus learning is faster than when this stimulus is the S -.…”

mentioning

confidence: 99%

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