Hierarchical stimulus processing in rodent primary and lateral visual cortex as assessed through neuronal selectivity and repetition suppression.

Similar to primates, visual cortex in rodents appears to be organized in two distinct hierarchical streams. However, there is still little known about how visual information is processed along those streams in rodents. In this study, we examined how repetition suppression and position and clutter tolerance of the neuronal representations evolve along the putative ventral visual stream in rats. To address this question, we recorded multiunit spiking activity in primary visual cortex (V1) and the more downstream visual laterointermediate (LI) area of head-restrained Long-Evans rats. We employed a paradigm reminiscent of the continuous carry-over design used in human neuroimaging. In both areas, stimulus repetition attenuated the early phase of the neuronal response to the repeated stimulus, with this response suppression being greater in area LI. Furthermore, stimulus preferences were more similar across positions (position tolerance) in area LI than in V1, even though the absolute responses in both areas were very sensitive to changes in position. In contrast, the neuronal representations in both areas were equally good at tolerating the presence of limited visual clutter, as modeled by the presentation of a single flank stimulus. When probing tolerance of the neuronal representations with stimulus-specific adaptation, we detected no position tolerance in either examined brain area, whereas, on the contrary, we revealed clutter tolerance in both areas. Overall, our data demonstrate similarities and discrepancies in processing of visual information along the ventral visual stream of rodents and primates. Moreover, our results stress caution in using neuronal adaptation to probe tolerance of the neuronal representations. NEW & NOTEWORTHY Rodents are emerging as a popular animal model that complement primates for studying higher level visual functions. Similar to findings in primates, we demonstrate a greater repetition suppression and position tolerance of the neuronal representations in the downstream laterointermediate area of Long-Evans rats compared with primary visual cortex. However, we report no difference in the degree of clutter tolerance between the areas. These findings provide additional evidence for hierarchical processing of visual stimuli in rodents.

Divisive Normalization Predicts Adaptation-Induced Response Changes in Macaque Inferior Temporal Cortex.

UNLABELLED: Stimulus repetition alters neural responses to the repeated stimulus. This so-called adaptation phenomenon has been commonly observed at multiple spatial and temporal scales and in different brain areas, and has been hypothesized to affect the neural representation of the sensory input. Yet, the neural mechanisms underlying adaptation still remain unclear, especially in higher-order cortical areas. Here we employ a divisive normalization model of neural responses to predict adaptation-induced changes in responses of single neurons in the macaque inferior temporal (IT) cortex. According to this model, the response of a neuron is determined by an interplay between its direct excitatory and divisive normalizing inputs, with each input being subject to adaptation. To test the model, we recorded the responses of single IT cortex neurons to complex visual stimuli while separately adapting the two putative types of input to those neurons. We compared the changes in responses of these neurons following such adaptation with predictions derived from the divisive normalization model. As predicted by the model, we show that adaptation in the IT cortex can, depending on the relative strength of each putative type of input to a neuron, suppress or enhance the neural response to a complex stimulus. More generally, our data suggest that adaptation serves to selectively enhance processing of the stimuli that differ from recently experienced ones, even when these occur within a configuration of multiple stimuli. SIGNIFICANCE STATEMENT: Stimulus repetition alters neural responses to the repeated stimulus. This so-called adaptation phenomenon has been robustly demonstrated in brains of different species and is considered to be a form of short-term plasticity inherent to the processing of sensory stimuli. Nevertheless, the functional role and underlying mechanisms of adaptation remain unclear. Here we demonstrate that divisive normalization, a canonical neural computation operating throughout the brain, predicts the adaptation-induced changes in response of single neurons to complex stimulus configurations in the macaque inferotemporal cortex. Our findings embed adaptation effects of inferotemporal neurons into the context of a broader neural network perspective that includes divisive normalization. Additionally, our findings have implications for understanding of the function of adaptation in higher-order sensory cortices.

Neurons in macaque inferior temporal cortex show no surprise response to deviants in visual oddball sequences.

Many studies measured neural responses in oddball paradigms, showing a different response to the same stimulus when presented with a low (deviant) compared with a high probability (standard) in a sequence. Such a differential response is manifested in event-related potential studies as the mismatch negativity (MMN) and has been observed in several sensory modalities, including vision. Other studies showed that stimulus repetition suppresses the neural response. It has been suggested that this adaptation effect underlies the smaller responses to the standard compared with the deviant stimulus in oddball sequences. However, the MMN may also reflect the violation of a prediction based on the sequence of standards, i.e., a surprise response. We examined the presence of a surprise response to deviants in visual oddball sequences in macaque (Macaca mulatta) inferior temporal (IT) cortex, a higher-order cortical area. In agreement with visual MMN studies, single-unit IT responses were greater for the deviant than for the standard stimuli. However, single IT neurons showed no greater response to the deviant stimulus in the oddball sequence than to the same stimulus presented with the same probability in a sequence that consisted of many stimuli. LFPs also showed no evidence of a surprise response. These data suggest that stimulus-specific adaptation, without a surprise-related boost of activity to the deviant, underlies the responses in visual oddball sequences even in higher visual cortex. Furthermore, we show that for IT neurons such adaptive mechanisms take into account a relatively short stimulus history, with weaker effects at longer time scales.

Repetition probability does not affect fMRI repetition suppression for objects.

Previously several functional magnetic resonance imaging (fMRI) studies point toward the role of perceptual expectations in determining adaptation or repetition suppression (RS) in humans. These studies showed that the probability of repetitions of faces within a block influences the magnitude of adaptation in face-related areas of the human brain (Summerfield et al., 2008). However, a current macaque single-cell/local field potential (LFP) recording study using objects as stimuli found no evidence for the modulation of the neural response by the repetition probability in the inferior temporal cortex (Kaliukhovich and Vogels, 2010). Here we examined whether stimulus repetition probability affects fMRI repetition suppression for nonface object stimuli in the human brain. Subjects were exposed to either two identical [repetition trials (RTs)] or two different [alternation trials (ATs)] object stimuli. Both types of trials were presented blocks consisting of either 75% [repetition blocks (RBs)] or 25% [alternation blocks (ABs)] of RTs. We found strong RS, i.e., a lower signal for RTs compared to ATs, in the object sensitive lateral occipital cortex as well as in the face-sensitive occipital and fusiform face areas. More importantly, however, there was no significant difference in the magnitude of RS between RBs and ABs in each of the areas. This is in agreement with the previous monkey single-unit/LFP findings and suggests that RS in the case of nonface visual objects is not modulated by the repetition probability in humans. Our results imply that perceptual expectation effects vary for different visual stimulus categories.

Effect of adaptation on object representation accuracy in macaque inferior temporal cortex.

Stimulus repetition produces a decrease of the response in many cortical areas and different modalities. This adaptation is highly prominent in macaque inferior temporal (IT) neurons. Here we ask how these repetition-induced changes in IT responses affect the accuracy by which IT neurons encode objects. This question bears on the functional consequences of adaptation, which are still unclear. We recorded the responses of single IT neurons to sequences of familiar shapes, each shown for 300 msec with an ISI of the same duration. The difference in shape between the two successively presented stimuli,that is, adapter and test, varied parametrically. The discriminability of the test stimuli was reduced for repeated compared with nonrepeated stimuli. In some conditions for which adapter and test shapes differed, the cross-adaptation resulted in an enhanced discriminability. These single cell results were confirmed in a second experiment in which we recorded multiunit spiking activity using a laminar microelectrode in macaque IT. Two familiar stimuli were presented successively for 500 msec each and separated with an ISI of the same duration. Trials consisted either of a repetition of the same stimulus or of their alternation. Small neuronal populations showed decreased classification accuracy for repeated compared with nonrepeated test stimuli, but classification was enhanced for the test compared with adapter stimuli when the test stimulus differed from recently seen stimuli. These findings suggest that short-term, stimulus-specific adaptation in IT supports efficient coding of stimuli that differ from recently seen ones while impairing the coding of repeated stimuli.

Stimulus repetition affects both strength and synchrony of macaque inferior temporal cortical activity.

Repetition of a visual stimulus reduces the firing rate of macaque inferior temporal (IT) neurons. The neural mechanisms underlying this adaptation or repetition suppression are still unclear. In particular, we do not know how the IT circuit is affected by stimulus repetition. To address this, we measured local field potentials (LFPs) and multiunit spiking activity (MUA) simultaneously at 16 sites with a laminar electrode in IT while repeating visual images. Stimulus exposures and interstimulus intervals were each 500 ms. The rhesus monkeys were performing a passive fixation task during the recordings. Induced LFP power decreased with repetition for spectral frequencies above 60 Hz but increased with repetition for lower frequencies, the latter because of a delayed decrease in power when repeating a stimulus. LFP-LFP and MUA-LFP coherences decreased with repetition for frequencies above 60 Hz. This repetition suppression of the MUA-LFP coherence was not due to differences in firing rate since it was present when spike counts were equated for the adapter and repeated stimuli. For frequencies between 15 and 40 Hz, the effect of repetition on synchronization depended on the electrode depth: For the putative superficial layers synchronization was enhanced with repetition, while the LFPs of the putative deep layers decreased their synchrony across layers. The between-site, trial-to-trial covariations in MUA ("noise correlations") decreased with repetition, but this might have reflected repetition suppression of the firing rate. This work demonstrates that short-term stimulus repetition affects the synchronized activity, in addition to response strength, in IT cortex.

Stimulus repetition probability does not affect repetition suppression in macaque inferior temporal cortex.

Recent human functional magnetic resonance imaging studies (Summerfield C, Trittschuh EH, Monti JM, Mesulam MM, Egner T. 2008. Neural repetition suppression reflects fulfilled perceptual expectations. Nat Neurosci. 11:1004-1006.) showed that adaptation or repetition suppression is affected by contextual factors related to perceptual expectations, suggesting that adaptation results from a fulfillment of perceptual expectation or a reduction in prediction error. This view contrasts with the bottom-up fatigue or sharpening mechanisms of adaptation proposed in single-cell studies. We examined whether stimulus repetition probability affects adaptation of spiking activity and local field potentials (LFPs) in macaque inferior temporal (IT) cortex, using a protocol similar to that of Summerfield et al. Monkeys were exposed to 2 randomly interleaved trials, each consisting of either 2 identical (rep trial) or 2 different stimuli (alt trial). Trials were presented in repetition (rep) blocks consisting of 75% of rep trials and 25% of alt trials or in alternation (alt) blocks having opposite repetition probabilities. For both spiking and LFP activities, the stimulus-selective adaptation did not differ significantly between rep and alt blocks. The number of preceding rep or alt trials and the trial position within a block did not affect adaptation. This absence of any effect of stimulus repetition probability on adaptation suggests that adaptation in IT is not caused by contextual factors related to perceptual expectation.

Context Modulates Attention to Faces in Dynamic Social Scenes in Children and Adults with Autism Spectrum Disorder.

Individuals with autism spectrum disorder (ASD) have been found to view social scenes differently compared to typically developing (TD) peers, but results can vary depending on context and age. We used eye-tracking in children and adults (age 6-63) to assess allocation of visual attention in a dynamic social orientation paradigm previously used only in younger children. The ASD group (n = 94) looked less at the actor's face compared to TD (n = 38) when they were engaged in activity (mean percentage of looking time, ASD = 30.7% vs TD = 34.9%; Cohen's d = 0.56; p value < 0.03) or looking at a moving toy (24.5% vs 33.2%; d = 0.65; p value < 0.001). Findings indicate that there are qualitative differences in allocation of visual attention to social stimuli across ages in ASD.ClinicalTrials.gov identifier: NCT02668991.

The Association Between Home Stay and Symptom Severity in Major Depressive Disorder: Preliminary Findings From a Multicenter Observational Study Using Geolocation Data From Smartphones.

BACKGROUND: Most smartphones and wearables are currently equipped with location sensing (using GPS and mobile network information), which enables continuous location tracking of their users. Several studies have reported that various mobility metrics, as well as home stay, that is, the amount of time an individual spends at home in a day, are associated with symptom severity in people with major depressive disorder (MDD). Owing to the use of small and homogeneous cohorts of participants, it is uncertain whether the findings reported in those studies generalize to a broader population of individuals with MDD symptoms. OBJECTIVE: The objective of this study is to examine the relationship between the overall severity of depressive symptoms, as assessed by the 8-item Patient Health Questionnaire, and median daily home stay over the 2 weeks preceding the completion of a questionnaire in individuals with MDD. METHODS: We used questionnaire and geolocation data of 164 participants with MDD collected in the observational Remote Assessment of Disease and Relapse-Major Depressive Disorder study. The participants were recruited from three study sites: King's College London in the United Kingdom (109/164, 66.5%); Vrije Universiteit Medisch Centrum in Amsterdam, the Netherlands (17/164, 10.4%); and Centro de Investigación Biomédica en Red in Barcelona, Spain (38/164, 23.2%). We used a linear regression model and a resampling technique (n=100 draws) to investigate the relationship between home stay and the overall severity of MDD symptoms. Participant age at enrollment, gender, occupational status, and geolocation data quality metrics were included in the model as additional explanatory variables. The 95% 2-sided CIs were used to evaluate the significance of model variables. RESULTS: Participant age and severity of MDD symptoms were found to be significantly related to home stay, with older (95% CI 0.161-0.325) and more severely affected individuals (95% CI 0.015-0.184) spending more time at home. The association between home stay and symptoms severity appeared to be stronger on weekdays (95% CI 0.023-0.178, median 0.098; home stay: 25th-75th percentiles 17.8-22.8, median 20.9 hours a day) than on weekends (95% CI -0.079 to 0.149, median 0.052; home stay: 25th-75th percentiles 19.7-23.5, median 22.3 hours a day). Furthermore, we found a significant modulation of home stay by occupational status, with employment reducing home stay (employed participants: 25th-75th percentiles 16.1-22.1, median 19.7 hours a day; unemployed participants: 25th-75th percentiles 20.4-23.5, median 22.6 hours a day). CONCLUSIONS: Our findings suggest that home stay is associated with symptom severity in MDD and demonstrate the importance of accounting for confounding factors in future studies. In addition, they illustrate that passive sensing of individuals with depression is feasible and could provide clinically relevant information to monitor the course of illness in patients with MDD.

Visual Preference for Biological Motion in Children and Adults with Autism Spectrum Disorder: An Eye-Tracking Study.

Participants with autism spectrum disorder (ASD) (n = 121, mean [SD] age: 14.6 [8.0] years) and typically developing (TD) controls (n = 40, 16.4 [13.3] years) were presented with a series of videos representing biological motion on one side of a computer monitor screen and non-biological motion on the other, while their eye movements were recorded. As predicted, participants with ASD spent less overall time looking at presented stimuli than TD participants (P < 10-3) and showed less preference for biological motion (P < 10-5). Participants with ASD also had greater average latencies than TD participants of the first fixation on both biological (P < 0.01) and non-biological motion (P < 0.02). Findings suggest that individuals with ASD differ from TD individuals on multiple properties of eye movements and biological motion preference.

Learning Scan Paths of Eye Movement in Autism Spectrum Disorder.

Eye tracking studies have demonstrated deficits in attention in individuals with Autism Spectrum Disorder (ASD) for a range of different social attention-based tasks. Here we examined social attention skills in a large sample of ASD participants (n = 120), using eye tracking data from a social information processing task, and compared them with a typically developing (TD) group (n = 35). Assuming eye movement parameters are random variables generated by an underlying stochastic process, we modeled the fixation sequences of participants in ASD and TD groups with a Hidden Markov Model. The Regions of Interests (ROIs), modeled as hidden states, corresponded to the true ROIs with a prediction accuracy of >90% for each group. The transition between ROIs revealed bias towards a specific area in the scene in ASD group, which deviated from the TD group. Objective time-dynamic measures of gaze patterns can potentially serve as useful endpoints in ASD diagnosis. Clinical Trial Registration: NCT02299700.

Social attention to activities in children and adults with autism spectrum disorder: effects of context and age.

BACKGROUND: Diminished visual monitoring of faces and activities of others is an early feature of autism spectrum disorder (ASD). It is uncertain whether deficits in activity monitoring, identified using a homogeneous set of stimuli, persist throughout the lifespan in ASD, and thus, whether they could serve as a biological indicator ("biomarker") of ASD. We investigated differences in visual attention during activity monitoring in children and adult participants with autism compared to a control group of participants without autism. METHODS: Eye movements of participants with autism (n = 122; mean age [SD] = 14.5 [8.0] years) and typically developing (TD) controls (n = 40, age = 16.4 [13.3] years) were recorded while they viewed a series of videos depicting two female actors conversing while interacting with their hands over a shared task. Actors either continuously focused their gaze on each other's face (mutual gaze) or on the shared activity area (shared focus). Mean percentage looking time was computed for the activity area, actors' heads, and their bodies. RESULTS: Compared to TD participants, participants with ASD looked longer at the activity area (mean % looking time: 58.5% vs. 53.8%, p < 0.005) but less at the heads (15.2% vs. 23.7%, p < 0.0001). Additionally, within-group differences in looking time were observed between the mutual gaze and shared focus conditions in both participants without ASD (activity: Δ = - 6.4%, p < 0.004; heads: Δ = + 3.5%, p < 0.02) and participants with ASD (bodies: Δ = + 1.6%, p < 0.002). LIMITATIONS: The TD participants were not as well characterized as the participants with ASD. Inclusion criteria regarding the cognitive ability [intelligence quotient (IQ) > 60] limited the ability to include individuals with substantial intellectual disability. CONCLUSIONS: Differences in attention to faces could constitute a feature discriminative between individuals with and without ASD across the lifespan, whereas between-group differences in looking at activities may shift with development. These findings may have applications in the search for underlying biological indicators specific to ASD. Trial registration ClinicalTrials.gov identifier NCT02668991.

Unsupervised Temporal Contiguity Experience Does Not Break the Invariance of Orientation Selectivity Across Spatial Frequency.

The images projected onto the retina can vary widely for a single object. Despite these transformations primates can quickly and reliably recognize objects. At the neural level, transformation tolerance in monkey inferotemporal cortex is affected by the temporal contiguity statistics of the visual input. Here we investigated whether temporal contiguity learning also influences the basic feature detectors in lower levels of the visual hierarchy, in particular the independent coding of orientation and spatial frequency (SF) in primary visual cortex. Eight male Long Evans rats were repeatedly exposed to a temporal transition between two gratings that changed in SF and had either the same (control SF) or a different (swap SF) orientation. Electrophysiological evidence showed that the responses of single neurons during this exposure were sensitive to the change in orientation. Nevertheless, the tolerance of orientation selectivity for changes in SF was unaffected by the temporal contiguity manipulation, as observed in 239 single neurons isolated pre-exposure and 234 post-exposure. Temporal contiguity learning did not affect orientation selectivity in V1. The basic filter mechanisms that characterize V1 processing seem unaffected by temporal contiguity manipulations.

Decoding of repeated objects from local field potentials in macaque inferior temporal cortex.

Stimulus repetition produces a decrease of the response and affects neuronal synchronization of macaque inferior temporal (IT) neurons. Previously we showed that such stimulus-specific adaptation results in a decreased accuracy by which IT neurons encode repeated compared to non-repeated objects. Not only spiking activity, but also local field potentials (LFPs) are affected by repetition. Here we ask how the repetition-induced changes in IT LFPs affect object decoding accuracy. To answer this, we recorded local field potentials using a laminar microelectrode in macaque IT. We presented two familiar stimuli each for 500 ms successively with an inter-stimulus interval of 500 ms. Trials consisted either of a repetition of the same stimulus or of their alternation. Machine learning-based classifier was employed to decode stimulus identity from the LFP power in different frequency bands of each penetration. We found that the object classification accuracy depended strongly on spectral frequency, with frequencies below 30 Hz (alpha and beta) producing greater accuracies than gamma bands. However, the effect of repetition on classification accuracy was stronger at the gamma frequencies, showing a decrease in classification accuracy for repeated stimuli and a tendency for an improved object encoding when the stimulus was preceded by a different stimulus. The present results demonstrate that due to adapting input, stimulus encoding in IT (1) can be more accurate for stimuli that differ from recently preceding ones while being impaired for stimuli that are repeated, and (2) these effects are more pronounced at high spectral frequencies of the LFP.