Using Extinction-Renewal to Circumvent the Memory Strength Boundary Condition in Fear Memory Reconsolidation

Reconsolidation is a process by which memories are destabilized, updated, and then restabilized. Strong memories are resistant to undergoing reconsolidation. Here, we addressed whether an overtrained fear memory could be made susceptible to reconsolidation by first extinguishing, and then renewing, the memory. Rats were trained with ten tone-footshock pairings, followed by eight days of tone extinction in the training context. The next day, rats were placed into a second context and memory for the tone was renewed/reactivated with a single tone presentation. Immediately following reactivation, rats received an injection of midazolam or vehicle. Rats were then tested for freezing to the tone in a third context. Midazolam had no effect in rats that did not undergo tone extinction, but significantly attenuated freezing to the tone in extinguished rats. Thus, rats that received tone extinction underwent tone memory reconsolidation following its renewal. In a second experiment, we administered the reactivation session and midazolam injections prior to extinction. Midazolam had no effect and rats extinguished at a rate similar to controls. These data suggest that strong emotional memories are capable of updating following weakening of memory expression through extinction.

Rhythm Violation Enhances Auditory-Evoked Responses to the Extent of Overriding Sensory Adaptation in Passive Listening

Sensory systems utilize temporal structure in the environment to build expectations about the timing of forthcoming events. We investigated the effects of rhythm-based temporal expectation on auditory responses measured with EEG recorded from the frontocentral sites implicated in auditory processing. By manipulating temporal expectation and the interonset interval (IOI) of tones, we examined how neural responses adapted to auditory rhythm and reacted to stimuli that violated the rhythm. Participants passively listened to the tones while watching a silent nature video. In Experiment 1 ( n = 22), in the long-IOI block, tones were frequently presented (80%) with 1.7-sec IOI and infrequently presented (20%) with 1.2-sec IOI, generating unexpectedly early tones that violated temporal expectation. Conversely, in the short-IOI block, tones were frequently presented with 1.2-sec IOI and infrequently presented with 1.7-sec IOI, generating late tones. We analyzed the tone-evoked N1–P2 amplitude of ERPs and intertrial phase clustering in the theta–alpha band. The results provided evidence of strong delay-dependent adaptation effects (short-term, sensitive to IOI), weak cumulative adaptation effects (long-term, driven by tone repetition over time), and robust temporal-expectation violation effects over and above the adaptation effects. Experiment 2 ( n = 22) repeated Experiment 1 with shorter IOIs of 1.2 and 0.7 sec. Overall, we found evidence of strong delay-dependent adaptation effects, weak cumulative adaptation effects (which may most efficiently accumulate at the tone presentation rate of ∼1 Hz), and robust temporal-expectation violation effects that substantially boost auditory responses to the extent of overriding the delay-dependent adaptation effects likely through mechanisms involved in exogenous attention.

Audio-visual synchrony and spatial attention enhance processing of dynamic visual stimulation independently and in parallel: a frequency-tagging study

ABSTRACTThe neural processing of a visual stimulus can be facilitated by attending to its position or by a co-occurring auditory tone. Using frequency-tagging we investigated whether facilitation by spatial attention and audio-visual synchrony rely on similar neural processes. Participants attended to one of two flickering Gabor patches (14.17 and 17 Hz) located in opposite lower visual fields. Gabor patches further “pulsed” (i.e. showed smooth spatial frequency variations) at distinct rates (3.14 and 3.63 Hz). Frequency-modulating an auditory stimulus at the pulse-rate of one of the visual stimuli established audio-visual synchrony. Flicker and pulsed stimulation elicited stimulus-locked rhythmic electrophysiological brain responses that allowed tracking the neural processing of simultaneously presented stimuli. These steady-state responses (SSRs) were quantified in the spectral domain to examine visual stimulus processing under conditions of synchronous vs. asynchronous tone presentation and when respective stimulus positions were attended vs. unattended. Strikingly, unique patterns of effects on pulse- and flicker driven SSRs indicated that spatial attention and audiovisual synchrony facilitated early visual processing in parallel and via different cortical processes. We found attention effects to resemble the classical top-down gain effect facilitating both, flicker and pulse-driven SSRs. Audio-visual synchrony, in turn, only amplified synchrony-producing stimulus aspects (i.e. pulse-driven SSRs) possibly highlighting the role of temporally co-occurring sights and sounds in bottom-up multisensory integration.

Cortical fMRI Activation to Sequences of Tones Alternating in Frequency: Relationship to Perceived Rate and Streaming

Human listeners were functionally imaged while reporting their perception of sequences of alternating-frequency tone bursts separated by 0, 1/8, 1, or 20 semitones. Our goal was to determine whether functional magnetic resonance imaging (fMRI) activation of auditory cortex changes with frequency separation in a manner predictable from the perceived rate of the stimulus. At the null and small separations, the tones were generally heard as a single stream with a perceived rate equal to the physical tone presentation rate. fMRI activation in auditory cortex was appreciably phasic, showing prominent peaks at the sequence onset and offset. At larger-frequency separations, the higher- and lower-frequency tones perceptually separated into two streams, each with a rate equal to half the overall tone presentation rate. Under those conditions, fMRI activation in auditory cortex was more sustained throughout the sequence duration and was larger in magnitude and extent. Phasic to sustained changes in fMRI activation with changes in frequency separation and perceived rate are comparable to, and consistent with, those produced by changes in the physical rate of a sequence and are far greater than the effects produced by changing other physical stimulus variables, such as sound level or bandwidth. We suggest that the neural activity underlying the changes in fMRI activation with frequency separation contribute to the coding of the co-occurring changes in perceived rate and perceptual organization of the sound sequences into auditory streams.

The extinction of conditioned fear: structural and molecular basis and therapeutic use

OBJECTIVE: Through association, a large variety of stimuli acquire the property of signaling pleasant or aversive events. Pictures of a wedding or of a plane disaster may serve as cues to recall these events and/or others of a similar nature or emotional tone. Presentation of the cues unassociated with the events, particularly if repeated, reduces the tendency to retrieve the original learning based on that association. This attenuation of the expression of a learned response was discovered by Pavlov 100 years ago, who called it extinction. In this article we review some of the most recent findings about the behavioral and biochemical properties of extinction. RESULTS AND DISCUSSION: It has been shown that extinction is a new learning based on a new link formed by the cues and the absence of the original event(s) which originated the first association. Extinction does not consist of the erasure of the original memory, but of an inhibition of its retrieval: the original response reappears readily if the former association is reiterated, or if enough time is allowed to pass (spontaneous recovery). Extinction requires neural activity, signaling pathways, gene expression and protein synthesis in the ventromedial prefrontal cortex and/or basolateral amygdala, hippocampus, entorhinal cortex and eventually other areas. The site or sites of extinction vary with the task. CONCLUSIONS: Extinction was advocated by Freud in the 1920's for the treatment of phobias, and is used in cognitive therapy to treat diseases that rely on conditioned fear (phobias, panic, and particularly posttraumatic stress disorder). The treatment of learned fear disorders with medications is still unsatisfactory although some have been shown useful when used as adjuncts to behavioral therapy.

Cross-modal Interactions in Time and Space: Auditory Influence on Visual Attention in Hemispatial Neglect

Recent studies indicate that auditory tone presentation and auditory alerting can temporarily ameliorate visuospatial attention deficits in patients with unilateral neglect [Frassinetti, F., Pavani, F., & Ladavas, E. Acoustical vision of neglected stimuli: Interaction among spatially converging audiovisual inputs in neglect patients. Journal of Cognitive Neuroscience, 14, 62–69, 2002; Robertson, I. H., Mattingley, J. B., Rorden, C., & Driver, J. Phasic alerting of neglect patients overcomes their spatial deficit in visual awareness. Nature, 395, 169–172, 1998]. The current study investigated proposed mechanisms of cross-modal interaction to determine conditions in which auditory stimulation affects spatial and nonspatially lateralized attention deficits in a patient with hemispatial neglect. In Experiment 1, a target was presented among related distracters (conjunction search) while a tone was presented either bilaterally or in a congruent or incongruent spatial location with respect to the visual target. Whereas the results suggest a benefit of both general alerting and cross-modal spatial integration on visual search efficiency, the most significant improvement occurred when the target and tone were both presented in contralesional space. In Experiment 2, the effect of auditory alerting on selective attention was examined in a rapid serial visual search procedure with visual targets embedded in a stream of distracters presented at central fixation. When two targets were presented without an alerting tone, the patient missed the second target for up to 1000 msec after the first target appeared (a finding known as the “attentional blink” [AB] and, on average, about 400–500 msec in normals). An alerting tone presented at a fixed temporal location significantly reduced the AB in a tone-duration-dependent manner. Experiment 3 examined the effect of cross-modal space on selective attention in an AB paradigm in which T2 occurred randomly to the left or right of T1 with a spatially congruent or incongruent tone. Discrimination of T2 in contralesional space significantly improved when the tone was presented in the same location, and was impaired when the tone was presented on the ipsilesional side. The findings are discussed as they relate to cross-modal interactions and their influence on spatial and nonspatially lateralized attention deficits in neglect.