Two Distinct Scene-Processing Networks Connecting Vision and Memory

The human entorhinal-hippocampal circuitry is characterized by an information-specific functional organization where two routes, that are preferentially connected to the parahippocampal cortex or the perirhinal and retrosplenial cortices, divide the entorhinal cortex as well as hippocampal subiculum and CA1 subregions.

The perception and imagery of landmarks activate similar content‐dependent brain areas, including occipital and temporo‐medial brain regions. However, how these areas interact during visual perception and imagery of scenes, especially when recollecting their spatial location, remains unknown. Here, we combined functional magnetic resonance imaging (fMRI), resting‐state functional connectivity (rs‐fc), and effective connectivity to assess spontaneous fluctuations and task‐induced modulation of signals among regions entailing scene‐processing, the primary visual area and the hippocampus (HC), responsible for the retrieval of stored information. First, we functionally defined the scene‐selective regions, that is, the occipital place area (OPA), the retrosplenial complex (RSC) and the parahippocampal place area (PPA), by using the face/scene localizer, observing that two portions of the PPA—anterior and posterior PPA—were consistently activated in all subjects. Second, the rs‐fc analysis (n = 77) revealed a connectivity pathway similar to the one described in macaques, showing separate connectivity routes linking the anterior PPA with RSC and HC, and the posterior PPA with OPA. Third, we used dynamic causal modelling to evaluate whether the dynamic couplings among these regions differ between perception and imagery of familiar landmarks during a fMRI task (n = 16). We found a positive effect of HC on RSC during the retrieval of imagined places and an effect of occipital regions on both RSC and pPPA during the perception of scenes. Overall, we propose that under similar functional architecture at rest, different neural interactions take place between regions in the occipito‐temporal higher‐level visual cortex and the HC, subserving scene perception and imagery.

Neural responses to visual scenes reveals inconsistencies between fMRI adaptation and multivoxel pattern analysis

The parahippocampal place area (PPA) is one of several brain regions that respond more strongly to scenes than to non-scene items such as objects and faces. The mechanism underlying this scene-preferential response remains unclear. One possibility is that the PPA is tuned to low-level stimulus features that are found more often in scenes than in less-preferred stimuli. Supporting this view, Nasr et al. (2014) recently observed that some of the stimuli that are known to strongly activate the PPA contain a large number of rectilinear edges. They further demonstrated that PPA response is modulated by rectilinearity for a range of non-scene images. Motivated by these results, we tested whether rectilinearity suffices to explain PPA selectivity for scenes. In the first experiment, we replicated the previous finding of modulation by rectilinearity in the PPA for arrays of 2-d shapes. However, two further experiments failed to find a rectilinearity effect for faces or scenes: high-rectilinearity faces and scenes did not activate the PPA any more strongly than low-rectilinearity faces and scenes. Moreover, the categorical advantage for scenes vs. faces was maintained in the PPA and two other scene-selective regions—the retrosplenial complex (RSC) and occipital place area (OPA)—when rectilinearity was matched between stimulus sets. We conclude that selectivity for scenes in the PPA cannot be explained by a preference for low-level rectilinear edges.

The occipital place area represents the local elements of scenes

Neural representation of scene boundaries

Perceived egocentric distance sensitivity and invariance across scene-selective cortex

Asymmetrical specialization of cognitive processes across the cerebral hemispheres is a hallmark of healthy brain development and an important evolutionary trait underlying higher cognition in humans. While previous research, including studies of priming, divided visual field presentation, and split-brain patients, demonstrates a general pattern of right/left asymmetry of form-specific versus form-abstract visual processing, little is known about brain organization underlying this dissociation. Here, using repetition priming of complex visual scenes and high-resolution functional magnetic resonance imaging (MRI), we demonstrate asymmetrical form specificity of visual processing between the right and left hemispheres within a region known to be critical for processing of visual spatial scenes (parahippocampal place area [PPA]). Next, we use resting-state functional connectivity MRI analyses to demonstrate that this functional asymmetry is associated with differential intrinsic activity correlations of the right versus left PPA with regions critically involved in perceptual versus conceptual processing, respectively. Our results demonstrate that the PPA comprises lateralized subregions across the cerebral hemispheres that are engaged in functionally dissociable yet complementary components of visual scene analysis. Furthermore, this functional asymmetry is associated with differential intrinsic functional connectivity of the PPA with distinct brain areas known to mediate dissociable cognitive processes.

Face and scene perception rely on distinct neural networks centered on the Fusiform Face Area (FFA) and Parahippocampal Place Area (PPA). However, how these regions interact with broader brain networks remains unclear. Using resting-state fMRI and MEG data, we mapped the spatial and frequency-specific functional connectivity of the FFA and PPA. We found that the FFA showed predominant fMRI connectivity with lateral occipitotemporal, inferior temporal, and temporoparietal regions, while the PPA connected more strongly with ventral medial visual, posterior cingulate, and entorhinal-perirhinal areas. MEG analyses further revealed this network segregation was reflected in beta and gamma bands. Importantly, connectome-based predictive modeling showed that the strength of these intrinsic fMRI connectivity patterns predicted individual reaction times on corresponding face and scene perception tasks. Our findings demonstrate that the FFA and PPA anchor distinct intrinsic networks with unique spatio-temporal profiles that provide a functional architecture supporting their specialized roles in face and scene perception.

Spatial knowledge about an environment can be cued from memory by perception of a visual scene during active navigation or by imagination of the relationships between nonvisible landmarks, such as when providing directions. It is not known whether these different ways of accessing spatial knowledge elicit the same representations in the brain. To address this issue, we scanned participants with fMRI, while they performed a judgment of relative direction (JRD) task that required them to retrieve real-world spatial relationships in response to either pictorial or verbal cues. Multivoxel pattern analyses revealed several brain regions that exhibited representations that were independent of the cues to access spatial memory. Specifically, entorhinal cortex in the medial temporal lobe and the retrosplenial complex (RSC) in the medial parietal lobe coded for the heading assumed on a particular trial, whereas the parahippocampal place area (PPA) contained information about the starting location of the JRD. These results demonstrate the existence of spatial representations in RSC, ERC, and PPA that are common to visually guided navigation and spatial imagery.

Repetition suppression (RS) is a rapid decrease of stimulus-related neuronal responses upon repeated presentation of a stimulus. Previous studies have demonstrated that negative emotional salience of stimuli enhances RS. It is, however, unclear how motivational salience of stimuli, such as reward-predicting value, influences RS for complex visual stimuli, and which brain regions might show differences in RS for reward-predicting and neutral stimuli. Here we investigated the influence of motivational salience on RS of complex scenes using event-related functional magnetic resonance imaging. Thirty young healthy volunteers performed a monetary incentive delay task with complex scenes (indoor vs. outdoor) serving as neutral or reward-predicting cue pictures. Each cue picture was presented three times. In line with previous findings, reward anticipation was associated with activations in the ventral striatum, midbrain, and orbitofrontal cortex (OFC). Stimulus repetition was associated with pronounced RS in ventral visual stream areas like the parahippocampal place area (PPA). An interaction of reward anticipation and RS was specifically observed in the anterior hippocampus, where a response decrease across repetitions was observed for the reward-predicting scenes only. Functional connectivity analysis further revealed specific activity-dependent connectivity increases of the hippocampus and the PPA and OFC. Our results suggest that hippocampal RS is sensitive to reward-predicting properties of stimuli and might therefore reflect a rapid, adaptive neural response mechanism for motivationally salient information.

Background and PurposeTemporomandibular disorders (TMD), especially pain-related TMD, are closely related to social and psychological factors. We aimed to measure changes in spontaneous brain activity and its related functional connectivity (FC), as well as FC characteristics within the mood-regulating circuits (MRC) in TMD patients by resting-state functional magnetic resonance imaging (RS-fMRI), and to analyze the relationship between these parameters and emotional symptoms.Materials and MethodsTwenty-one adult TMD patients and thirty demographically matched healthy controls (HCs) underwent clinical scale evaluation and RS-fMRI scanning. After processing RS-fMRI data, the values of the amplitude of low-frequency fluctuation (ALFF) between the two groups were compared. Regions with abnormal ALFF values were selected as areas of interest (ROIs) to compare the differences of whole-brain seed-based FC between groups. The FCs between regions within MRC were also analyzed and compared. In addition, the relationships between RS-fMRI characteristics and pain and mood were explored by correlation and mediation analyses.ResultsCompared with HCs, TMD patients showed increased ALFF in the right parahippocampal gyrus (PHG), the right supplementary motor area, and the bilateral precentral gyrus, with decreased ALFF in the right cerebelum_crus2. Patients showed enhanced right PHG-related FC in the vermis and posterior cingulate cortex, orbitofrontal cortex (OFC)-related FC in the striatal-frontal regions, while decreased dorsolateral prefrontal cortex-related FC in the amygdala. In TMD patients, ALFF values in the right PHG and FC values between the right PHG and the vermis were positively correlated with depressive symptoms. Abnormal FCs in the left striatal-orbitofrontal pathway were correlated with pain and depressive symptoms. More importantly, mediation analysis revealed that chronic pain mediates the relationship between FC of right PHG with vermis and depressive symptoms, and abnormal FC in the left striatal-orbitofrontal pathway can mediate the association between pain and depressive symptoms.ConclusionTMD patients have dysregulated spontaneous activity and FC in the default mode network, sensorimotor network and pain-related regions, as well as dysfunction of the fronto-striatal-limbic circuits. The development of negative emotions in TMD may be related to the dysfunction of components within the reward system (especially hippocampus complex, OFC, striatum) due to chronic pain.

Review of: Watrous AJ, Tandon N, Conner CR, Pieters T, Ekstrom AD. Frequency-specific network connectivity increases underlie accurate spatiotemporal memory retrieval. Nat Neurosci 2013 doi:10.1038/nn.3315. Humans depend on a memory system to rapidly and veraciously store the massive stream of incoming information documenting their experiences, and faithfully represent and recall that information for future use. Devastating dysfunction in the system is observed in schizophrenia and Alzheimer’s disease. While the medial temporal lobe (MTL), prefrontal cortex (PFC), and parietal lobe have been implicated in an episodic memory retrieval network, the processes underlying successful retrieval remain undetermined, particularly regarding simultaneous recall of different classes of information represented by shared neuronal ensembles. Leading hypotheses propose that retrieval may be defined by changes in connectivity and activity of one region in the network, connections throughout the network, or phase-synchronized activity at specific frequencies. In a recent study, Watrous et al. tested these theories with simultaneous electrocortigraphical (ECoG) recordings from these regions during episodic memory retrieval. Six patients with medically intractable epilepsy underwent invasive monitoring, and the derived data were used for this study. Electrodes were localized to subregions of the MTL, PFC, and parietal cortex. Patients performed a spatiotemporal memory-dependent task with a virtual taxi game, in which they drove passengers to five irregularly spaced stores in a specific sequential order. Once patients reached criteria levels of accuracy or training time, retrieval of spatial and temporal information was tested separately. Phase synchronization was utilized as a measure of functional connectivity to test the different hypotheses. Pairwise phase consistency (PPC) index, which is based on phase angle difference between signals from different electrodes, was used to quantify the phase synchronization across electrode pairs. Two subregions, termed nodes within the network, were considered functionally connected when the PPC between them differed significantly depending on the condition (correct vs. incorrect responses, spatial vs. temporal memory retrieval). The node degree, a node’s total number of connections, also marked the magnitude of connectivity. Nodes with the highest node degree were defined as hubs. With the greatest connectivity, a hub is thought to play a central role in mediating interactions across the network for retrieval. The percent connectivity was also calculated as the number of connections a node has in a given condition out of the total possible connections. The authors found that functional connectivity, derived by measuring phase-synchronized low-frequency oscillations, was augmented both globally and in the parahippocampal gyrus (PHG) with successful retrieval of spatiotemporal memory. PPC of delta-theta frequency (1-10 Hz) range was greater for correct responses than incorrect. While percent connectivity increased throughout the network with successful retrieval, a disproportionately greater increase in the PHG node was also observed. PHG was designated a hub in the retrieval network. According to these findings, both network-wide and regional, but not frequency-specific, increases in functional connectivity occur for retrieval of spatiotemporal information. Comparing spatial versus temporal memory retrieval uncovered spectral, temporal, and regional segregation of functional connectivity within the retrieval network. For retrieval of spatial information, PPC and percent connectivity were increased between PHG, superior frontal gyrus (SFG), and middle frontal gyrus (MFG), and precuneus areas, at 1-4 Hz, and early in memory retrieval. Temporal memory retrieval was characterized by greater PPC and percent connectivity between PHG, SFG, MFG, and the inferior parietal lobule, at 7-10 Hz, and later in memory retrieval. The PHG was a hub in both conditions, making the same number of overall connections with other nodes, and with differential clustering of connectivity (Figure 1).Figure 1: Frequency-specific synchronization occurs among several components of the human memory system during context retrieval. (G-J) Correct spatial and temporal retrieval networks (within the context of the virtual taxi game task) in the 1–4-Hz and 7–10-Hz bands.This work has notable implications for neuroscience and neurosurgery. The role of mesial temporal lobe structures (particularly the hippocampus) in memory recall remains controversial, particularly after memory consolidation. The hippocampus’s role in memory encoding is well established. Theories of consolidation typically argue that retrieval of consolidated information is independent of the hippocampus, while the Multiple Trace Theory (MTT) proposes that memory recall is hippocampus-dependent. The identification of the PHG, which is intimately connected with the hippocampus, as a hub, lends indirect support for MTT. Since the PHG includes connections from entorhinal, parahippocampal, and perirhinal cortices, but not the hippocampus proper, the evidence does not directly indicate specific action of the hippocampus but rather the MTL in general. Additionally, processes supporting functional connectivity and recall of distinct types of information were elucidated by the authors. This discovery could lead to clinical interventions targeting specific types of cognitive processes including memory retrieval. As neurosurgery continues to expand toward treating cognitive disorders, a network-level understanding of mechanisms and components of memory systems will prove invaluable.

The cortico-hippocampal network is an emerging neural framework with striking evidence that it supports cognition in humans, especially memory; this network includes the anterior temporal (AT) system, the posterior medial (PM) system, the anterior hippocampus (aHIPPO), and the posterior hippocampus (pHIPPO). This study aimed to detect aberrant patterns of functional connectivity within and between large-scale cortico-hippocampal networks in first-episode schizophrenia patients compared with a healthy control group via resting-state functional magnetic resonance imaging (rs-fMRI) and to explore the correlations of these aberrant patterns with cognition. A total of 86 first-episode, drug-naïve schizophrenia patients and 102 healthy controls (HC) were recruited to undergo rs-fMRI examinations and clinical evaluations. We conducted large-scale edge-based network analysis to characterize the functional architecture of the cortico-hippocampus network and investigate between-group differences in within/between-network functional connectivity. Additionally, we explored the associations of functional connectivity (FC) abnormalities with clinical characteristics, including scores on the Positive and Negative Syndrome Scale (PANSS) and cognitive scores. Compared with the HC group, schizophrenia patients exhibited widespread alterations to within-network FC of the cortico-hippocampal network, with decreases in FC involving the precuneus (PREC), amygdala (AMYG), parahippocampal cortex (PHC), orbitofrontal cortex (OFC), perirhinal cortex (PRC), retrosplenial cortex (RSC), posterior cingulate cortex (PCC), angular gyrus (ANG), aHIPPO, and pHIPPO. Schizophrenia patients also showed abnormalities in large-scale between-network FC of the cortico-hippocampal network, in the form of significantly decreased FC between the AT and the PM, the AT and the aHIPPO, the PM and the aHIPPO, and the aHIPPO and the pHIPPO. A number of these signatures of aberrant FC were correlated with PANSS score (positive, negative, and total score) and with scores on cognitive test battery items, including attention/vigilance (AV), working memory (WM), verbal learning and memory (Verb_Lrng), visual learning and memory (Vis_Lrng), reasoning and problem-solving (RPS), and social cognition (SC). Schizophrenia patients show distinct patterns of functional integration and separation both within and between large-scale cortico-hippocampal networks, reflecting a network imbalance of the hippocampal long axis with the AT and PM systems, which regulate cognitive domains (mainly Vis_Lrng, Verb_Lrng, WM, and RPS), and particularly involving alterations to FC of the AT system and the aHIPPO. These findings provide new insights into the neurofunctional markers of schizophrenia.

Keeping oriented in the environment is a multifaceted ability that requires knowledge of at least three pieces of information: one’s own location (“place”) and orientation (“heading”) within the environment, and which location in the environment one is looking at (“view”). We used functional magnetic resonance imaging (fMRI) in humans to examine the neural signatures of these information. Participants were scanned while viewing snapshots which varied for place, view and heading within a virtual room. We observed adaptation effects, proportional to the physical distances between consecutive places and views, in scene-responsive (retrosplenial complex and parahippocampal gyrus), fronto-parietal and lateral occipital regions. Multivoxel pattern classification of signals in scene-responsive regions and in the hippocampus allowed supra-chance decoding of place, view and heading, and revealed the existence of map-like representations, where places and views closer in physical space entailed activity patterns more similar in neural representational space. The pattern of hippocampal activity reflected both view- and place-based distances, the pattern of parahippocampal activity preferentially discriminated between views, and the pattern of retrosplenial activity combined place and view information, while the fronto-parietal cortex only showed transient effects of changes in place, view, and heading. Our findings provide evidence for the presence of map-like spatial representations which reflect metric distances in terms of both one’s own and landmark locations.