Repetition Suppression Research Articles

Ketamine improves short-term plasticity in depression by enhancing sensitivity to prediction errors

Major depressive disorder negatively impacts the sensitivity and adaptability of the brain's predictive coding framework. The current electroencephalography study into the antidepressant properties of ketamine investigated the downstream effects of ketamine on predictive coding and short-term plasticity in thirty patients with depression using the auditory roving mismatch negativity (rMMN). The rMMN paradigm was run 3–4 h after a single 0.44 mg/kg intravenous dose of ketamine or active placebo (remifentanil infused to a target plasma concentration of 1.7 ng/mL) in order to measure the neural effects of ketamine in the period when an improvement in depressive symptoms emerges. Depression symptomatology was measured using the Montgomery-Asberg Depression Rating Scale (MADRS); 70% of patients demonstrated at least a 50% reduction their MADRS global score. Ketamine significantly increased the MMN and P3a event related potentials, directly contrasting literature demonstrating ketamine's acute attenuation of the MMN. This effect was only reliable when all repetitions of the post-deviant tone were used. Dynamic causal modelling showed greater modulation of forward connectivity in response to a deviant tone between right primary auditory cortex and right inferior temporal cortex, which significantly correlated with antidepressant response to ketamine at 24 h. This is consistent with the hypothesis that ketamine increases sensitivity to unexpected sensory input and restores deficits in sensitivity to prediction error that are hypothesised to underlie depression. However, the lack of repetition suppression evident in the MMN evoked data compared to studies of healthy adults suggests that, at least within the short term, ketamine does not improve deficits in adaptive internal model calibration.

Measures of repetition suppression in the fusiform face area are inflated by co-occurring effects of statistically learned visual associations

Repeated presentation of a stimulus leads to reductions in measures of neural responses. This phenomenon, termed repetition suppression (RS), has recently been conceptualized using models based on predictive coding, which describe RS as due to expectations that are weighted toward recently-seen stimuli. To evaluate these models, researchers have manipulated the likelihood of stimulus repetition within experiments. They have reported findings that are inconsistent across hemodynamic and electrophysiological measures, and difficult to interpret as clear support or refutation of predictive coding models. We instead investigated a different type of expectation effect that is apparent in stimulus repetition experiments: the difference in one's ability to predict the identity of repeated, compared to unrepeated, stimuli. In previous experiments that presented pairs of repeated or alternating images, once participants had seen the first stimulus image in a pair, they could form specific expectations about the repeated stimulus image but not the alternating image, which was often randomly chosen from a large stimulus set. To assess the contribution of stimulus predictability effects to previously observed RS, we measured BOLD signals while presenting pairs of repeated and alternating faces. This was done in contexts whereby stimuli in alternating trials were either i.) predictable through statistically learned associations between pairs of stimuli or ii.) chosen randomly and therefore unpredictable. We found that RS in the right fusiform face area (FFA) was much larger in trials with unpredictable compared to predictable alternating faces. This was primarily due to unpredictable alternating stimuli evoking larger BOLD signals than predictable alternating stimuli. We show that imbalances in stimulus predictability across repeated and alternating trials can greatly inflate measures of RS, and potentially even mimic RS effects. Our findings indicate that stimulus-specific expectations as described by predictive coding models may account for a sizeable portion of observed RS effects.

The effect of NMDA-R antagonist, MK-801, on neuronal mismatch along the rat auditory thalamocortical pathway

Efficient sensory processing requires that the brain maximize its response to unexpected stimuli, while suppressing responsivity to expected events. Mismatch negativity (MMN) is an auditory event-related potential that occurs when a regular pattern is interrupted by an event that violates the expected properties of the pattern. According to the predictive coding framework there are two mechanisms underlying the MMN: repetition suppression and prediction error. MMN has been found to be reduced in individuals with schizophrenia, an effect believed to be underpinned by glutamate N-methyl-d-aspartate receptor (NMDA-R) dysfunction. In the current study, we aimed to test how the NMDA-R antagonist, MK-801 in the anaesthetized rat, affected repetition suppression and prediction error processes along the auditory thalamocortical pathway. We found that low-dose systemic administration of MK-801 differentially affect thalamocortical responses, namely, increasing thalamic repetition suppression and cortical prediction error. Results demonstrate an enhancement of neuronal mismatch, also confirmed by large scale-responses. Furthermore, MK-801 produces faster and stronger dynamics of adaptation along the thalamocortical hierarchy. Clearly more research is required to understand how NMDA-R antagonism and dosage affects processes contributing to MMN. Nonetheless, because a low dose of an NMDA-R antagonist increased neuronal mismatch, the outcome has implications for schizophrenia treatment.

Age-related changes in repetition suppression of neural activity during emotional future simulation

Despite advances in understanding the consequences of age-related episodic memory decline for future simulation, much remains unknown regarding changes in the neural underpinnings of future thinking with age. We used a repetition suppression paradigm to explore age-related changes in the neural correlates of emotional future simulation. Younger and older adults simulated positive, negative, and neutral future events either 2 or 5 times. Reductions in neural activity for events simulated 5 versus 2 times (i.e., repetition suppression) identify brain regions responsive to the specific emotion of simulated events. Critically, older adults showed greater repetition suppression than younger adults in the temporal pole for negative simulations, and the cuneus for positive simulations. These findings suggest that older adults distance themselves from negative future possibilities by thinking about them in a more semantic way, consistent with the view that older adults down-regulate negative affect and up-regulate positive affect. More broadly this study increases our understanding of the impact of aging on the neural underpinnings of episodic future simulation.

Diverse Temporal Dynamics of Repetition Suppression Revealed by Intracranial Recordings in the Human Ventral Temporal Cortex.

Repeated stimulus presentations commonly produce decreased neural responses-a phenomenon known as repetition suppression (RS) or adaptation-in ventral temporal cortex (VTC) of humans and nonhuman primates. However, the temporal features of RS in human VTC are not well understood. To fill this gap in knowledge, we utilized the precise spatial localization and high temporal resolution of electrocorticography (ECoG) from nine human subjects implanted with intracranial electrodes in the VTC. The subjects viewed nonrepeated and repeated images of faces with long-lagged intervals and many intervening stimuli between repeats. We report three main findings: 1) robust RS occurs in VTC for activity in high-frequency broadband (HFB), but not lower-frequency bands; 2) RS of the HFB signal is associated with lower peak magnitude (PM), lower total responses, and earlier peak responses; and 3) RS effects occur early within initial stages of stimulus processing and persist for the entire stimulus duration. We discuss these findings in the context of early and late components of visual perception, as well as theoretical models of repetition suppression.

Neural repetition suppression effects in the human hippocampus

Neurons in the temporal lobe cortex exhibit reduced responses when a stimulus or a stimulus feature is repeated. This phenomenon, termed “repetition suppression”, is the basis for many functional imaging studies that have used Blood Oxygenation Level Dependent (BOLD) activity differences between novel and repeated items as an index of neural selectivity in hippocampal subfields. However, it is not clear how hippocampal neural activity changes across repeated exposure to a stimulus. Here, we used direct intracranial electroencephalography (iEEG) recordings of hippocampal activity to examine whether neural activity in the human hippocampus is modulated across successive repetitions of an item. Time-frequency analyses revealed that high-frequency activity, which is thought to include gamma oscillations and possible correlates of multi-unit activity, declined monotonically across successive presentations of an item. In contrast, low-frequency oscillations in the alpha and beta bands monotonically increased across successive presentations of an object. These results provide support for the assumption that, at least under some circumstances, repetition suppression (as measured by declines in high-frequency activity) can be observed in the hippocampus, and these effects are accompanied by increases in low-frequency oscillations as well.

Deviance detection in physiologically identified cell types in the rat auditory cortex

Auditory deviance detection is a function of the auditory system that allows reduction of the processing demand for repetitive stimuli while stressing unpredictable ones, which are potentially more informative. Deviance detection has been extensively studied in humans using the oddball paradigm, which evokes an event-related potential known as mismatch negativity (MMN). The same stimulation paradigms are used in animal studies that aim to elucidate the neuronal mechanisms underlying deviance detection. In order to understand the circuitry responsible for deviance detection in the auditory cortex (AC), it is necessary to determine the properties of excitatory and inhibitory neurons separately. Measuring the spike widths of neurons recorded extracellularly from the anaesthetized rat AC, we classified them as fast spiking or regular spiking units. These two neuron types are generally considered as putative inhibitory or excitatory, respectively. In response to an oddball paradigm, we found that both types of units showed similar amounts of deviance detection overall. When considering each AC field separately, we found that only in A1 fast spiking neurons showed higher deviance detection levels than regular spiking neurons, while in the rest of the fields there was no such distinction. Interpreting these responses in the context of the predictive coding framework, we found that the responses of both types of units reflect mainly prediction error signaling (i.e., genuine deviance detection) rather than repetition suppression.

Human Face-Selective Cortex Does Not Distinguish between Members of a Racial Outgroup.

People often fail to individuate members of social outgroups, a phenomenon known as the outgroup homogeneity effect. Here, we used functional magnetic resonance imaging (fMRI) repetition suppression to investigate the neural representation underlying this effect. In a preregistered study, White human perceivers (N = 29) responded to pairs of faces depicting White or Black targets. In each pair, the second face depicted either the same target as the first face, a different target from the same race, or a scrambled face outline. We localized face-selective neural regions via an independent task, and demonstrated that neural activity in the fusiform face area (FFA) distinguished different faces only when targets belonged to the perceivers’ racial ingroup (White). By contrast, face-selective cortex did not discriminate between other-race individuals. Moreover, across two studies (total N = 67) perceivers were slower to discriminate between different outgroup members and remembered them to a lesser extent. Together, these results suggest that the outgroup homogeneity effect arises when early-to-mid-level visual processing results in an erroneous overlap of representations of outgroup members.

Expectations about word stress modulate neural activity in speech-sensitive cortical areas

A recent dual-stream model of language processing proposed that the postero-dorsal stream performs predictive sequential processing of linguistic information via hierarchically organized internal models. However, it remains unexplored whether the prosodic segmentation of linguistic information involves predictive processes. Here, we addressed this question by investigating the processing of word stress, a major component of speech segmentation, using probabilistic repetition suppression (RS) modulation as a marker of predictive processing. In an event-related acoustic fMRI RS paradigm, we presented pairs of pseudowords having the same (Rep) or different (Alt) stress patterns, in blocks with varying Rep and Alt trial probabilities. We found that the BOLD signal was significantly lower for Rep than for Alt trials, indicating RS in the posterior and middle superior temporal gyrus (STG) bilaterally, and in the anterior STG in the left hemisphere. Importantly, the magnitude of RS was modulated by repetition probability in the posterior and middle STG. These results reveal the predictive processing of word stress in the STG areas and raise the possibility that words stress processing is related to the dorsal “where” auditory stream.

Auditory and tactile frequency representations are co-embedded in modality-defined cortical sensory systems

Sensory information is represented and elaborated in hierarchical cortical systems that are thought to be dedicated to individual sensory modalities. This traditional view of sensory cortex organization has been challenged by recent evidence of multimodal responses in primary and association sensory areas. Although it is indisputable that sensory areas respond to multiple modalities, it remains unclear whether these multimodal responses reflect selective information processing for particular stimulus features. Here, we used fMRI adaptation to identify brain regions that are sensitive to the temporal frequency information contained in auditory, tactile, and audiotactile stimulus sequences. A number of brain regions distributed over the parietal and temporal lobes exhibited frequency-selective temporal response modulation for both auditory and tactile stimulus events, as indexed by repetition suppression effects. A smaller set of regions responded to crossmodal adaptation sequences in a frequency-dependent manner. Despite an extensive overlap of multimodal frequency-selective responses across the parietal and temporal lobes, representational similarity analysis revealed a cortical “regional landscape” that clearly reflected distinct somatosensory and auditory processing systems that converged on modality-invariant areas. These structured relationships between brain regions were also evident in spontaneous signal fluctuation patterns measured at rest. Our results reveal that multimodal processing in human cortex can be feature-specific and that multimodal frequency representations are embedded in the intrinsically hierarchical organization of cortical sensory systems.

Layer-Specific Contributions to Imagined and Executed Hand Movements in Human Primary Motor Cortex.

The human ability to imagine motor actions without executing them (i.e., motor imagery) is crucial to a number of cognitive functions, including motor planning and learning, and has been shown to improve response times and accuracy of subsequent motor actions [1, 2]. Although these behavioral findings suggest the possibility that imagined movements directly influence primary motor cortex (M1), how this might occur remains unknown [3]. Here, we use a non-blood-oxygen-level-dependent (BOLD) method for collecting fMRI data, called vascular space occupancy (VASO) [4, 5], to measure neural activations across cortical laminae in M1 while participants either tapped their thumb and forefinger together or simply imagined doing so. We report that, whereas executed movements (i.e., finger tapping) evoked neural responses in both the superficial layers of M1 that receive cortical input and the deep layers of M1 that send output to the spinal cord to support movement, imagined movements evoked responses in superficial cortical layers only. Furthermore, we found that finger tapping preceded by both imagined and executed movements showed a reduced response in the superficial layers (repetition suppression) coupled with a heightened response in the deep layers (repetition enhancement). Taken together, our results provide evidence for a mechanism whereby imagined movements can directly affect motor performance and might explain how neural repetition effects lead to improvements in behavior (e.g., repetition priming).

Changes in human brain dynamics during behavioral priming and repetition suppression.

Behavioral responses to a perceptual stimulus are typically faster with repeated exposure to the stimulus (behavioral priming). This implicit learning mechanism is critical for survival but impaired in a variety of neurological disorders, including Alzheimer's disease. Many studies of the neural bases for behavioral priming have encountered an interesting paradox: in spite of faster behavioral responses, repeated stimuli usually elicit weaker neural responses (repetition suppression). Several neurophysiological models have been proposed to resolve this paradox, but noninvasive techniques for human studies have had insufficient spatial-temporal precision for testing their predictions. Here, we used the unparalleled precision of electrocorticography (ECoG) to analyze the timing and magnitude of task-related changes in neural activation and propagation while patients named novel vs repeated visual objects. Stimulus repetition was associated with faster verbal responses and decreased neural activation (repetition suppression) in ventral occipito-temporal cortex (VOTC) and left prefrontal cortex (LPFC). Interestingly, we also observed increased neural activation (repetition enhancement) in LPFC and other recording sites. Moreover, with analysis of high gamma propagation we observed increased top-down propagation from LPFC into VOTC, preceding repetition suppression. The latter results indicate that repetition suppression and behavioral priming are associated with strengthening of top-down network influences on perceptual processing, consistent with predictive coding models of repetition suppression, and they support a central role for changes in large-scale cortical dynamics in achieving more efficient and rapid behavioral responses.

Reconsidering longstanding assumptions about the role of medial prefrontal cortex (MPFC) in social evaluation

The psychological nature of the association between MPFC modulation and social evaluation remains poorly understood. Despite confounds, small samples, and mixed results in existing research, MPFC activation is often interpreted as a reflection of socioemotional association and/or perceived similarity between the self and an evaluation target. The present research addressed issues from the existing literature by examining whether MPFC is modulated by (a) socioemotional associations unconfounded by previous knowledge (memory effects (Study 1, N = 48), repetition suppression (Study 2, N = 43), multi-voxel pattern analysis (Study 1 & 2)) and (b) perceived similarity to self (Study 2). MPFC was modulated by self-reference and trait-relevance, but there was not significant empirical support for the interpretation that MPFC modulation reflects socioemotional association or perceived similarity. These findings highlight the weak basis for prevailing assumptions about the psychological significance of MPFC in social evaluation and the need for studies which test multiple mechanisms.

Representation of viewed and recalled film clips in patterns of brain activity in a person with developmental amnesia

As clear memories transport us back into the past, the brain also revives prior patterns of neural activity, a phenomenon known as neural reactivation. While growing evidence indicates a link between neural reactivation and typical variations in memory performance in healthy individuals, it is unclear how and to what extent reactivation is disrupted by a memory disorder. The current study characterizes neural reactivation in a case of amnesia using Multivoxel Pattern Analysis (MVPA). We tested NC, an individual with developmental amnesia linked to a diencephalic stroke, and 19 young adult controls on a functional magnetic resonance imaging (fMRI) task during which participants viewed and recalled short videos multiple times. An encoding classifier trained and tested to identify videos based on brain activity patterns elicited at perception revealed superior classification in NC. The enhanced consistency in stimulus representation we observed in NC at encoding was accompanied by an absence of multivariate repetition suppression, which occurred over repeated viewing in the controls. Another recall classifier trained and tested to identify videos during mental replay indicated normal levels of classification in NC, despite his poor memory for stimulus content. However, a cross-condition classifier trained on perception trials and tested on mental replay trials—a strict test of reactivation—revealed significantly poorer classification in NC. Thus, while NC's brain activity was consistent and stimulus-specific during mental replay, this specificity did not reflect the reactivation of patterns elicited at perception to the same extent as controls. Fittingly, we identified brain regions for which activity supported stimulus representation during mental replay to a greater extent in NC than in controls. This activity was not modeled on perception, suggesting that compensatory patterns of representation based on generic knowledge can support consistent mental constructs when memory is faulty. Our results reveal several ways in which amnesia impacts distributed patterns of stimulus representation during encoding and retrieval.

Face space representations of movement

The challenging computational problem of perceiving dynamic faces “in the wild” goes unresolved because most research focuses on easier questions about static photograph perception. This literature conceptualizes face representation as a dissimilarity-based “face space”, with axes that describe the dimensions of static images. Some versions express positions in face space relative to a central tendency (norm). Are facial movements represented like this? We tested for representations that accord with an a priori hypothesized motion-based face space by experimentally manipulating faces’ motion-based dissimilarity. Because we caricatured movements, we could test for representations of dissimilarity from a motion-based norm. Behaviorally, participants perceived these caricatured expressions as convincing and recognizable. Moreover, as expected, caricature enhanced perceived dissimilarity between facial expressions. Functional magnetic resonance imaging showed that occipitotemporal brain responses, including face-selective and motion-sensitive areas, reflect this face space. This evidence converged across methods including analysis of univariate mean responses (which additionally exhibited norm-based responses), repetition suppression and representational similarity analysis. This accumulated evidence for “representational geometry” shows how perception and visual brain responses to facial dynamics reflect representations of movement-based dissimilarity spaces, including explicit computation of distance from a norm movement.

Effects of Repetition Suppression on Sound Induced Flash Illusion With Aging.

The sound-induced flash illusion (SiFI) is a classical auditory-dominated multisensory integration phenomenon in which the observer misperceives the number of visual flashes due to the simultaneous presentation of a different number of auditory beeps. Although the SiFI has been documented to correlate with perceptual sensitivity, to date there is no consensus as to how it corresponds to sensitivity with aging. The present study was based on the SiFI paradigm (Shams et al., 2000), adding repeated auditory stimuli prior to the appearance of audiovisual stimuli to investigate the effects of repetition suppression (RS) on the SiFI with aging. The repeated auditory stimuli consisted of one or two of the same auditory stimuli presented twice in succession, which were then followed by the audiovisual stimuli. By comparing the illusions in old and young adults, we aimed to explore the influence of aging on the RS of auditory stimuli on the SiFI. The results showed that both age groups showed SiFI effects, however, the RS performance of the two age groups had different effects on the fusion and fission illusions. The illusion effect in old adults was weaker than in young adults. Specifically, RS only affected fission illusions in the old adults but both fission and fusion illusions in young adults. Thus, the present study indicated that the decreased perceptual sensitivity based on auditory RS could weaken the SiFI effect in multisensory integration and that old adults are more susceptible to RS, showing that old adults perceived the SiFI effect weakly under auditory RS.

Warmth is more influential than competence: an fMRI repetition suppression study.

Previous neuroimaging studies have revealed neural representation of traits in the medial prefrontal cortex (mPFC), but related studies mainly investigated the neural representation of warmth or competence trait respectively. To identify the potential differences of trait codes of warmth and competence in the mPFC, we applied functional magnetic resonance imaging (fMRI) repetition suppression which is a rapid reduction of neuronal responses upon repeated presentation of the same implied trait. Participants read two successive trait-implying behavioral descriptions. In each trial, the critical target sentence implied either a warmth-related or competence-related trait was preceded by a prime sentence that implied trait from the other dimension of the 'Big Two' with a same or opposite valence, or no trait. The results revealed robust repetition suppression from prime to target in the mPFC only when the prime was a warmth-related trait, regardless of valence. Critically, the suppression effect was much stronger after being primed with a similar and opposite warmth trait compared with a trait-irrelevant prime. This suppression pattern was found nowhere else in the brain. The result seems to indicate that humans do not completely interpret and represent warmth and competence traits as independent dimensions and the warmth trait is more influential than Competence trait. The finding extends the understanding of the 'Big Two' theory of impression formation from the aspect of neural activity.

Similar Expectation Effects for Immediate and Delayed Stimulus Repetitions.

A prior cue or stimulus allows prediction of the future occurrence of an event and therefore reduces the associated neural activity in several cortical areas. This phenomenon is labeled expectation suppression (ES) and has recently been shown to be independent of the generally observed effects of stimulus repetitions (repetition suppression, RS: reduced neuronal response after the repetition of a given stimulus). While it has been shown that attentional cueing is strongly affected by the length of the cue-target delay, we have no information on the temporal dynamics of expectation effects, as in most prior studies of ES the delay between the predictive cue and the target (i.e., the inter-stimulus interval, ISI) was in the range of a few hundred milliseconds. Hence, we presented participants with pairs of faces where the first face could be used to build expectations regarding the second one, in the sense that one gender indicated repetition of the same face while the other gender predicted the occurrence of novel faces. In addition, we presented the stimulus pairs with two different ISIs (0.5 s for Immediate and 1.75 or 3.75 s for Delayed ISIs). We found significant RS as well as a reduced response for correctly predicted when compared to surprising trials in the fusiform face area. Importantly, the effects of repetition and expectation were both independent of the length of the ISI period. This implies that Immediate and Delayed cue-target stimulus arrangements lead to similar expectation effects in the face sensitive-visual cortex.

Long-latency event-related responses to vowels: N1-P2 decomposition by two-step principal component analysis

The N1-P2 complex of the auditory event-related potential (ERP) has been used to examine neural activity associated with speech sound perception. Since it is thought to reflect multiple generator processes, its functional significance is difficult to infer. In the present study, a temporospatial principal component analysis (PCA) was used to decompose the N1-P2 response into latent factors underlying covariance patterns in ERP data recorded during passive listening to pairs of successive vowels. In each trial, one of six sounds drawn from an /i/−/e/ vowel continuum was followed either by an identical sound, a different token of the same vowel category, or a token from the other category. Responses were examined as to how they were modulated by within- and across-category vowel differences and by adaptation (repetition suppression) effects. Five PCA factors were identified as corresponding to three well-known N1 subcomponents and two P2 subcomponents. Results added evidence that the N1 peak reflects both generators that are sensitive to spectral information and generators that are not. For later latency ranges, different patterns of sensitivity to vowel quality were found, including category-related effects. Particularly, a subcomponent identified as the Tb wave showed release from adaptation in response to an /i/ followed by an /e/ sound. A P2 subcomponent varied linearly with spectral shape along the vowel continuum, while the other was stronger the closer the vowel was to the category boundary, suggesting separate processing of continuous and category-related information. Thus, the PCA-based decomposition of the N1-P2 complex was functionally meaningful, revealing distinct underlying processes at work during speech sound perception.

Temporal tuning of repetition suppression across the visual cortex.

The visual system adapts to its recent history. A phenomenon related to this is repetition suppression (RS), a reduction in neural responses to repeated compared with nonrepeated visual input. An intriguing hypothesis is that the timescale over which RS occurs across the visual hierarchy is tuned to the temporal statistics of visual input features, which change rapidly in low-level areas but are more stable in higher level areas. Here, we tested this hypothesis by studying the influence of the temporal lag between successive visual stimuli on RS throughout the visual system using functional (f)MRI. Twelve human volunteers engaged in four fMRI sessions in which we characterized the blood oxygen level-dependent response to pairs of repeated and nonrepeated natural images with interstimulus intervals (ISI) ranging from 50 to 1,000 ms to quantify the temporal tuning of RS along the posterior-anterior axis of the visual system. As expected, RS was maximal for short ISIs and decayed with increasing ISI. Crucially, however, and against our hypothesis, RS decayed at a similar rate in early and late visual areas. This finding challenges the prevailing view that the timescale of RS increases along the posterior-anterior axis of the visual system and suggests that RS is not tuned to temporal input regularities.NEW & NOTEWORTHY Visual areas show reduced neural responses to repeated compared with nonrepeated visual input, a phenomenon termed repetition suppression (RS). Here we show that RS decays at a similar rate in low- and high-level visual areas, suggesting that the short-term decay of RS across the visual hierarchy is not tuned to temporal input regularities. This may limit the specificity with which the mechanisms underlying RS could optimize the processing of input features across the visual hierarchy.