Where bottom-up meets top-down: neuronal interactions during perception and imagery

Functional magnetic resonance imaging (fMRI) studies have identified category-selective regions in ventral occipito-temporal cortex that respond preferentially to faces and other objects. The extent to which these patterns of activation are modulated by bottom-up or top-down mechanisms is currently unknown. We combined fMRI and dynamic causal modelling to investigate neuronal interactions between occipito-temporal, parietal and frontal regions, during visual perception and visual imagery of faces, houses and chairs. Our results indicate that, during visual perception, category-selective patterns of activation in extrastriate cortex are mediated by content-sensitive forward connections from early visual areas. In contrast, during visual imagery, category-selective activation is mediated by content-sensitive backward connections from prefrontal cortex. Additionally, we report content-unrelated connectivity between parietal cortex and the category-selective regions, during both perception and imagery. Thus, our investigation revealed that neuronal interactions between occipito-temporal, parietal and frontal regions are task- and stimulus-dependent. Sensory representations of faces and objects are mediated by bottom-up mechanisms arising in early visual areas and top-down mechanisms arising in prefrontal cortex, during perception and imagery respectively. Additionally non-selective, top-down processes, originating in superior parietal areas, contribute to the generation of mental images, regardless of their content, and their maintenance in the 'mind's eye'.     

Experience-dependent modulation of category-related cortical activity

Naming pictures of objects from different categories (e.g. animals or tools) evokes maximal responses in different brain regions. However, these 'category-specific' regions typically respond to other object categories as well. Here we used stimulus familiarity to further investigate category representation. Naming pictures of animals and tools elicited category-related activity in a number of previously identified regions. This activity was reduced for familiar relative to novel stimuli. Reduced activation occurred in all object responsive areas in the ventral occipito-temporal cortex, regardless of which category initially produced the maximal response. This suggests that object representations in the ventral occipito-temporal cortex are not limited to a discrete area, but rather are widespread and overlapping. In other regions (e.g. the lateral temporal and left premotor cortices), experience-dependent reductions were category specific. Together, these findings suggest that category-related activations reflect the retrieval of information about category-specific features and attributes.     

Additive effects of emotional content and spatial selective attention on electrocortical facilitation

Affectively arousing visual stimuli have been suggested to automatically attract attentional resources in order to optimize sensory processing. The present study crosses the factors of spatial selective attention and affective content, and examines the relationship between instructed (spatial) and automatic attention to affective stimuli. In addition to response times and error rate, electroencephalographic data from 129 electrodes were recorded during a covert spatial attention task. This task required silent counting of random-dot targets embedded in a 10 Hz flicker of colored pictures presented to both hemifields. Steady-state visual evoked potentials (ssVEPs) were obtained to determine amplitude and phase of electrocortical responses to pictures. An increase of ssVEP amplitude was observed as an additive function of spatial attention and emotional content. Statistical parametric mapping of this effect indicated occipito-temporal and parietal cortex activation contralateral to the attended visual hemifield in ssVEP amplitude modulation. This difference was most pronounced during selection of the left visual hemifield, at right temporal electrodes. In line with this finding, phase information revealed accelerated processing of aversive arousing, compared to affectively neutral pictures. The data suggest that affective stimulus properties modulate the spatiotemporal process along the ventral stream, encompassing amplitude amplification and timing changes of posterior and temporal cortex.     

Modulation of ventral prefrontal cortex functional connections reflects the interplay of cognitive processes and stimulus characteristics

Emerging ideas of brain function emphasize the context-dependency of regional contributions to cognitive operations, where the function of a particular region is constrained by its pattern of functional connectivity. We used functional magnetic resonance imaging to examine how modality of input (auditory or visual) affects prefrontal cortex (PFC) functional connectivity for simple working memory tasks. The hypothesis was that PFC would show contextually dependent changes in functional connectivity in relation to the modality of input despite similar cognitive demands. Participants were presented with auditory or visual bandpass-filtered noise stimuli, and performed 2 simple short-term memory tasks. Brain activation patterns independently mapped onto modality and task demands. Analysis of right ventral PFC functional connectivity, however, suggested these activity patterns interact. One functional connectivity pattern showed task differences independent of stimulus modality and involved ventromedial and dorsolateral prefrontal and occipitoparietal cortices. A second pattern showed task differences that varied with modality, engaging superior temporal and occipital association regions. Importantly, these association regions showed nonzero functional connectivity in all conditions, rather than showing a zero connectivity in one modality and nonzero in the other. These results underscore the interactive nature of brain processing, where modality-specific and process-specific networks interact for normal cognitive operations.     

Category-selective background connectivity in ventral visual cortex

Ventral visual cortex contains specialized regions for particular object categories, but little is known about how these regions interact during object recognition. Here we examine how the face-selective fusiform gyrus (FG) and the scene-selective parahippocampal cortex (PHC) interact with each other and with the rest of the brain during different visual tasks. To assess these interactions, we developed a novel approach for identifying patterns of connectivity associated with specific task sets, independent of stimulus-evoked responses. We tested whether this "background connectivity" between the FG and PHC was modulated when subjects engaged in face and scene processing tasks. In contrast to what would be predicted from biased competition or intrinsic activity accounts, we found that the strength of FG-PHC background connectivity depended on which category was task relevant: connectivity increased when subjects attended to scenes (irrespective of whether a competing face was present) and decreased when subjects attended to faces (irrespective of competing scenes). We further discovered that posterior occipital cortex was correlated selectively with the FG during face tasks and the PHC during scene tasks. These results suggest that category specificity exists not only in which regions respond most strongly but also in how these and other regions interact.     

Domain-general and domain-sensitive prefrontal mechanisms for recollecting events and detecting novelty

Recollecting the past and discriminating novel from familiar memoranda depend on poorly understood prefrontal cortical (PFC) mechanisms hypothesized to vary according to memory task (e.g. recollection versus novelty detection) and domain of targeted memories (e.g. perceptual versus conceptual). Using event-related fMRI, we demonstrate that recollecting conceptual or perceptual details surrounding object encounters similarly recruits left frontopolar and posterior PFC compared with detecting novel stimuli, suggesting that a domain-general control network is engaged during contextual remembering. In contrast, left anterior ventrolateral PFC coactivated with a left middle temporal region associated with semantic representation, and right ventrolateral PFC with bilateral occipito-temporal cortices associated with representing object form, depending on whether recollections were conceptual or perceptual. These PFC/posterior cortical dissociations suggest that during recollection, lateralized ventrolateral PFC mechanisms bias posterior conceptual or perceptual feature representations as a function of memory relevance, potentially improving the gain of bottom-up memory signals. Supporting this domain-sensitive biasing hypothesis, novelty detection also recruited right ventrolateral PFC and bilateral occipito-temporal cortices compared with conceptual recollection, suggesting that searching for novel objects heavily relies upon perceptual feature processing. Collectively, these data isolate task- from domain-sensitive PFC control processes strategically recruited in the service of episodic memory.     

Multisensory visual-auditory object recognition in humans: a high-density electrical mapping study

Multisensory object-recognition processes were investigated by examining the combined influence of visual and auditory inputs upon object identification--in this case, pictures and vocalizations of animals. Behaviorally, subjects were significantly faster and more accurate at identifying targets when the picture and vocalization were matched (i.e. from the same animal), than when the target was represented in only one sensory modality. This behavioral enhancement was accompanied by a modulation of the evoked potential in the latency range and general topographic region of the visual evoked N1 component, which is associated with early feature processing in the ventral visual stream. High-density topographic mapping and dipole modeling of this multisensory effect were consistent with generators in lateral occipito-temporal cortices, suggesting that auditory inputs were modulating processing in regions of the lateral occipital cortices. Both the timing and scalp topography of this modulation suggests that there are multisensory effects during what is considered to be a relatively early stage of visual object-recognition processes, and that this modulation occurs in regions of the visual system that have traditionally been held to be unisensory processing areas. Multisensory inputs also modulated the visual 'selection-negativity', an attention dependent component of the evoked potential this is usually evoked when subjects selectively attend to a particular feature of a visual stimulus.     

Positron emission tomography study of letter and object processing: empirical findings and methodological considerations.

The study of functional-anatomical correlations of higher-order cognitive processing has benefited from recent advances in brain imaging techniques such as positron emission tomography (PET) measurements of regional cerebral blood flow (CBF). Comparisons of CBF changes by paired image subtraction provide the opportunity to isolate cerebral areas participating in the realization of the processes that differentiate two tasks. However, the subtraction method is based on assumptions that are not entirely compatible with cerebral cognitive processing, and the derived pattern of activation specifically associated with the processes that differentiate two tasks is relative to the activation associated with the subtracted task and may therefore vary as a function of the processes actually performed in this subtracted task. To examine the implications of this procedure, a PET study with the 15O water bolus technique was carried out on normal adults. Subjects performed three tasks that made nonoverlapping cognitive processing demands: a semantic categorization of visual objects, a spatial discrimination of visually presented letters, and a phonological decision on visually presented single letters. Each task produced distinct patterns of activation consistent with evidence from neurological patients, specifically in the left occipital cortex in the semantic categorization of objects, in the parietal cortex of both hemispheres in the letter-spatial task, and in the left frontal and superior temporal cortex in the letter-sound task. However, the comparisons between the two letter tasks did not result in the expected CBF changes even though these two tasks make distinct processing requirements and are dissociable by brain injury. In addition, the phonological task resulted in activation of areas of the frontal cortex that earlier PET studies had identified as participating in semantic operations, whereas letters have no semantic property. These results suggest that the interpretation of patterns of activation is confronted with difficulties due to the automatic, and uncontrolled, processing of verbal stimuli that raises the threshold for significant CBF changes between two conditions that use the same stimuli but different task demands.     

The effect of prior visual information on recognition of speech and sounds

To identify and categorize complex stimuli such as familiar objects or speech, the human brain integrates information that is abstracted at multiple levels from its sensory inputs. Using cross-modal priming for spoken words and sounds, this functional magnetic resonance imaging study identified 3 distinct classes of visuoauditory incongruency effects: visuoauditory incongruency effects were selective for 1) spoken words in the left superior temporal sulcus (STS), 2) environmental sounds in the left angular gyrus (AG), and 3) both words and sounds in the lateral and medial prefrontal cortices (IFS/mPFC). From a cognitive perspective, these incongruency effects suggest that prior visual information influences the neural processes underlying speech and sound recognition at multiple levels, with the STS being involved in phonological, AG in semantic, and mPFC/IFS in higher conceptual processing. In terms of neural mechanisms, effective connectivity analyses (dynamic causal modeling) suggest that these incongruency effects may emerge via greater bottom-up effects from early auditory regions to intermediate multisensory integration areas (i.e., STS and AG). This is consistent with a predictive coding perspective on hierarchical Bayesian inference in the cortex where the domain of the prediction error (phonological vs. semantic) determines its regional expression (middle temporal gyrus/STS vs. AG/intraparietal sulcus).     

Segregation of areas related to visual working memory in the prefrontal cortex revealed by rTMS

The functional organization of working memory (WM) in the human prefrontal cortex remains unclear. Storage and processing functions might be segregated in ventral and dorsal areas of the prefrontal cortex, respectively. If so, storage functions might be spared, irrespective of informational domain, following damage or dysfunction in dorsolateral areas. Alternatively, WM and prefrontal function in general might be segregated according to informational domains (e.g. spatial versus object-based information). In the present study we used repetitive transcranial magnetic stimulation (rTMS) to directly test these competing hypotheses. We applied rTMS to transiently and selectively disrupt the function of the dorsomedial, dorsolateral or ventral prefrontal cortex in normal human volunteers performing either a spatial or a face-recognition delayed-response task. Performance in the spatial task was impaired by rTMS of the dorsomedial prefrontal cortex. Performance in the face-recognition (non-spatial) task was impaired by rTMS of the ventral prefrontal cortex. Transient disruption of the dorsolateral prefrontal cortex affected performance in both tasks. These findings provide evidence of domain-specific segregation of WM functions in widely separated areas of prefrontal cortex.     

Hippocampal and brain stem activation during word retrieval after repeated and semantic encoding

Repeated word presentation during learning and the use of a semantic encoding task both increase the accuracy of subsequent word retrieval. Previous neuroimaging studies have shown that successful word retrieval depends on the recruitment of the hippocampus, whereas the effort of retrieval is linked to activation of prefrontal cortex modules. We studied the effects of repetition (4x versus 1x presentation) and encoding task (semantic versus perceptual) on hippocampal and prefrontal cortex activation during word-stem cued recall using positron emission tomography. Repeated and semantic encoding resulted in increased recall accuracy, with word repetition showing a greater effect when using a semantic encoding task. The more successful retrieval of words presented repeatedly compared with words presented once was associated with activation of the left anterior hippocampus. The more successful retrieval of words encoded using a semantic compared with a perceptual task was associated with activation of the right posterior and, less significantly, the left anterior hippocampus. The greater benefit of repeated learning when using the semantic task was linked to activation of the right brainstem, in the region of the ventral tegmentum. Our results suggest that word repetition and semantic encoding increase recall accuracy during subsequent word retrieval via distinct hippocampal mechanisms and that ventral tegmentum activation is relevant for word retrieval after semantic encoding. These findings confirm the importance of hippocampal recruitment during word retrieval and provide novel evidence for a role of brainstem neurons in word retrieval after semantic encoding.     

Neural interactions at the core of phonological and semantic priming of written words

Word processing is often probed with experiments where a target word is primed by preceding semantically or phonologically related words. Behaviorally, priming results in faster reaction times, interpreted as increased efficiency of cognitive processing. At the neural level, priming reduces the level of neural activation, but the actual neural mechanisms that could account for the increased efficiency have remained unclear. We examined whether enhanced information transfer among functionally relevant brain areas could provide such a mechanism. Neural activity was tracked with magnetoencephalography while subjects read lists of semantically or phonologically related words. Increased priming resulted in reduced cortical activation. In contrast, coherence between brain regions was simultaneously enhanced. Furthermore, while the reduced level of activation was detected in the same area and time window (superior temporal cortex [STC] at 250-650 ms) for both phonological and semantic priming, the spatiospectral connectivity patterns appeared distinct for the 2 processes. Causal interactions further indicated a driving role for the left STC in phonological processing. Our results highlight coherence as a neural mechanism of priming and dissociate semantic and phonological processing via their distinct connectivity profiles.     

Human neural systems for conceptual knowledge of proper object use: a functional magnetic resonance imaging study

Ideational apraxia is characterized by impaired knowledge of action concepts and proper object usage. The present functional magnetic resonance imaging study aimed at investigating the neural system underlying conceptual knowledge for proper object use in healthy subjects, when the effects of visuospatial properties and perceptual modality were taken into account. Subjects performed semantic decision tasks requiring retrieval of knowledge about either object functional purposes (functional task) or visuospatial object properties (visuospatial task) and perceptual control tasks. The semantic tasks were performed with pairs of either written object names or object drawings. Activation for the functional task in common for words and pictures, compared with the visuospatial and control tasks, was found in left parietal-temporal-occipital (PTO) junction, inferior frontal, anterior dorsal premotor, and presupplementary motor areas. Ventral inferior frontal cortex activation correlated negatively with reaction time in the functional condition. No specific activation characterized the visuospatial task compared with the functional task. The conceptual tasks, compared with the control tasks, demonstrated overlapping activation in left PTO junction, prefrontal, dorsal premotor, cuneus, and inferior temporal areas. These results outline the neural processes underlying conceptual knowledge for proper object use. The left ventral inferior frontal gyrus might facilitate behavioral decisions regarding functional/pragmatical object properties.     

Three systems of insular functional connectivity identified with cluster analysis

Despite much research on the function of the insular cortex, few studies have investigated functional subdivisions of the insula in humans. The present study used resting-state functional connectivity magnetic resonance imaging (MRI) to parcellate the human insular lobe based on clustering of functional connectivity patterns. Connectivity maps were computed for each voxel in the insula based on resting-state functional MRI (fMRI) data and segregated using cluster analysis. We identified 3 insular subregions with distinct patterns of connectivity: a posterior region, functionally connected with primary and secondary somatomotor cortices; a dorsal anterior to middle region, connected with dorsal anterior cingulate cortex, along with other regions of a previously described control network; and a ventral anterior region, primarily connected with pregenual anterior cingulate cortex. Applying these regions to a separate task data set, we found that dorsal and ventral anterior insula responded selectively to disgusting images, while posterior insula did not. These results demonstrate that clustering of connectivity patterns can be used to subdivide cerebral cortex into anatomically and functionally meaningful subregions; the insular regions identified here should be useful in future investigations on the function of the insula.     

A genetic model for understanding higher order visual processing: functional interactions of the ventral visual stream in Williams syndrome

Williams syndrome (WS) is a rare neurodevelopmental disorder caused by a 1.6 Mb microdeletion on chromosome 7q11.23 and characterized by hypersocial personality and prominent visuospatial construction impairments. Previous WS studies have identified functional and structural abnormalities in the hippocampal formation, prefrontal regions crucial for amygdala regulation and social cognition, and the dorsal visual stream, notably the intraparietal sulcus (IPS). Although aberrant ventral stream activation has not been found in WS, object-related visual information that is processed in the ventral stream is a critical source of input into these abnormal regions. The present study, therefore, examined neural interactions of ventral stream areas in WS. Using a passive face- and house-viewing paradigm, activation and functional connectivity of stimulus-selective regions in fusiform and parahippocampal gyri, respectively, were investigated. During house viewing, significant activation differences were observed between participants with WS and a matched control group in IPS. Abnormal functional connectivity was found between parahippocampal gyrus and parietal cortex and between fusiform gyrus and a network of brain regions including amygdala and portions of prefrontal cortex. These results indicate that abnormal upstream visual object processing may contribute to the complex cognitive/behavioral phenotype in WS and provide a systems-level characterization of genetically mediated abnormalities of neural interactions.     

Mechanisms of top-down facilitation in perception of visual objects studied by FMRI

Prior knowledge regarding the possible identity of an object facilitates its recognition from a degraded visual input, though the underlying mechanisms are unclear. Previous work implicated ventral visual cortex but did not disambiguate whether activity-changes in these regions are causal to or merely reflect an effect of facilitated recognition. We used functional magnetic resonance imaging to study top-down influences on processing of gradually revealed objects, by preceding each object with a name that was congruent or incongruent with the object. Congruently primed objects were recognized earlier than incongruently primed, and this was paralleled by shifts in activation profiles for ventral visual, parietal, and prefrontal cortices. Prior to recognition, defined on a trial-by-trial basis, activity in ventral visual cortex rose gradually but equivalently for congruently and incongruently primed objects. In contrast, prerecognition activity was greater with congruent priming in lateral parietal, retrosplenial, and lateral prefrontal cortices, whereas functional coupling between parietal and ventral visual (and also left lateral prefrontal and parietal) cortices was enhanced in the same context. Thus, when controlling for recognition point and stimulus information, activity in ventral visual cortex mirrors recognition success, independent of condition. Facilitation by top-down cues involves lateral parietal cortex interacting with ventral visual areas, potentially explaining why parietal lesions can lead to deficits in recognizing degraded objects even in the context of top-down knowledge.     

Distinct patterns of functional and effective connectivity between perirhinal cortex and other cortical regions in recognition memory and perceptual discrimination

Traditionally, the medial temporal lobe (MTL) is thought to be dedicated to declarative memory. Recent evidence challenges this view, suggesting that perirhinal cortex (PrC), which interfaces the MTL with the ventral visual pathway, supports highly integrated object representations in recognition memory and perceptual discrimination. Even with comparable representational demands, perceptual and memory tasks differ in numerous task demands and the subjective experience they evoke. Here, we tested whether such differences are reflected in distinct patterns of connectivity between PrC and other cortical regions, including differential involvement of prefrontal control processes. We examined functional magnetic resonance imaging data for closely matched perceptual and recognition memory tasks for faces that engaged right PrC equivalently. Multivariate seed analyses revealed distinct patterns of interactions: Right ventrolateral prefrontal and posterior cingulate cortices exhibited stronger functional connectivity with PrC in recognition memory; fusiform regions were part of the pattern that displayed stronger functional connectivity with PrC in perceptual discrimination. Structural equation modeling revealed distinct patterns of effective connectivity that allowed us to constrain interpretation of these findings. Overall, they demonstrate that, even when MTL structures show similar involvement in recognition memory and perceptual discrimination, differential neural mechanisms are reflected in the interplay between the MTL and other cortical regions.     

"What" precedes "which": developmental neural tuning in face- and place-related cortex

Although category-specific activation for faces in the ventral visual pathway appears adult-like in adolescence, recognition abilities for individual faces are still immature. We investigated how the ability to represent "individual" faces and houses develops at the neural level. Category-selective regions of interest (ROIs) for faces in the fusiform gyrus (FG) and for places in the parahippocampal place area (PPA) were identified individually in children, adolescents, and adults. Then, using an functional magnetic resonance imaging adaptation paradigm, we measured category selectivity and individual-level adaptation for faces and houses in each ROI. Only adults exhibited both category selectivity and individual-level adaptation bilaterally for faces in the FG and for houses in the PPA. Adolescents showed category selectivity bilaterally for faces in the FG and houses in the PPA. Despite this profile of category selectivity, adolescents only exhibited individual-level adaptation for houses bilaterally in the PPA and for faces in the "left" FG. Children only showed category-selective responses for houses in the PPA, and they failed to exhibit category-selective responses for faces in the FG and individual-level adaptation effects anywhere in the brain. These results indicate that category-level neural tuning develops prior to individual-level neural tuning and that face-related cortex is disproportionately slower in this developmental transition than is place-related cortex.     

Learning-related neuronal responses in prefrontal cortex studied with functional neuroimaging

We assessed time-dependent neuronal activity accompanying learning using functional magnetic resonance imaging (fMRI). An artificial grammar learning paradigm enabled us to dissociate activations associated with individual item learning from those involved in learning the underlying grammar system. We show that a localized region of right prefrontal cortex (PFC) is preferentially sensitive to individual item learning during the early stages of the experiment, while the left PFC region is sensitive to grammar learning which occurred across the entire course of the experiment. In addition to dissociating these two types of learning, we were able to characterize the effect of rule acquisition on neuronal responses associated with explicit learning of individual items. This effect was expressed as modulation of the time-dependent right PFC activations such that the early increase in activation associated with item learning was attenuated as the experiment progressed. In a further analysis we used structural equation modelling to explore time-dependent changes in inter-regional connectivity as a function of both item and grammar rule learning. Although there were no significant effects of item learning on the measured path strengths, rule learning was associated with a decrease in right fronto-parietal connectivity and an increase in connectivity between left and right PFC. Further fronto-parietal path strengths were observed to change, with an increase in left fronto-parietal and a decrease in right fronto-parietal connectivity path strength from right PFC to left parietal cortex. We interpret our findings in terms of a left frontal system mediating the semantic analysis of study items and directly influencing a right fronto-parietal system associated with episodic memory retrieval.