Stimulus-evoked neural activity is attenuated upon stimulus repetition ('repetition suppression'), a phenomenon attributed to largely automatic processes in sensory neurons. By manipulating the likelihood of stimulus repetition, we show that repetition suppression in the human brain is reduced when stimulus repetitions are improbable (and thus, unexpected). These data suggest that repetition suppression reflects a relative reduction in top-down perceptual 'prediction error' when processing an expected compared to an unexpected stimulus.Stimulus-specific repetition suppression (RS) -the relative attenuation in neural signal evoked by the repeated occurrence of a stimulus -is among the best-known neural phenomena [1][2][3][4] , and has been widely employed in functional magnetic resonance imaging (fMRI) studies to define functional properties of brain regions 5,6 and explore neural substrates of behavioral priming effects 2,4 . However, the neurocomputational basis for RS remains controversial 1 . Two influential theories view RS as a relatively automatic consequence of the bottom-up flow of perceptual information through sensory cortex: either neurons tuned to the repeated stimulus fatigue 1 , or subsequent presentations of a stimulus are encoded more sparsely (and efficiently), leading to a sharpening in the population of neurons recruited 4,7 . By contrast, a recent model of perceptual inference casts RS as a consequence of top-down perceptual expectations 2,8 : here, RS reflects a reduction in perceptual 'prediction error' (the neural signal evoked by a mismatch between expected and observed percepts) that occurs when sensory evidence conforms to a more probable (previously seen) compared to a less probable (novel) percept. Unlike other theories, the prediction error model holds that RS will vary with contextual factors that affect subjects' perceptual expectations, and suggests that RS will be reduced under conditions where stimulus repetitions are unexpected.We created such a situation by presenting subjects (n = 16), who had provided informed written consent, on each trial with either the same face twice, or two different faces, in two experimental contexts -one where repetitions occurred more frequently than alternations, and one where the reverse was the case. Importantly, all face exemplars were trial-unique, such that the NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript probability of a repetition per se, and not the frequency of repetition of a specific face, varied between blocks ( Fig. 1a and Supplementary Methods online). Incidental to this manipulation, subjects were required to make a speeded response to occasional inverted faces ('targets') 9 . Limiting our analysis to non-target trials, we measured how face-sensitive visual cortex responded to face repetitions ('rep trials') and face alternations ('alt trials') that were either expected (in 'REP BLOCKS') or unexpected (in 'ALT BLOCKS'), comparing these estimates in 2 × 2 factorial mixed block/event-related desi...

Visual cortex is traditionally viewed as a hierarchy of neural feature detectors, with neural population responses being driven by bottom-up stimulus features. Conversely, "predictive coding" models propose that each stage of the visual hierarchy harbors two computationally distinct classes of processing unit: representational units that encode the conditional probability of a stimulus and provide predictions to the next lower level; and error units that encode the mismatch between predictions and bottom-up evidence, and forward prediction error to the next higher level. Predictive coding therefore suggests that neural population responses in categoryselective visual regions, like the fusiform face area (FFA), reflect a summation of activity related to prediction ("face expectation") and prediction error ("face surprise"), rather than a homogenous feature detection response. We tested the rival hypotheses of the feature detection and predictive coding models by collecting functional magnetic resonance imaging data from the FFA while independently varying both stimulus features (faces vs houses) and subjects' perceptual expectations regarding those features (low vs medium vs high face expectation). The effects of stimulus and expectation factors interacted, whereby FFA activity elicited by face and house stimuli was indistinguishable under high face expectation and maximally differentiated under low face expectation. Using computational modeling, we show that these data can be explained by predictive coding but not by feature detection models, even when the latter are augmented with attentional mechanisms. Thus, population responses in the ventral visual stream appear to be determined by feature expectation and surprise rather than by stimulus features per se.

Visual search is aided by previous knowledge regarding distinguishing features and probable locations of a sought-after target. However, how the human brain represents and integrates concurrent feature-based and spatial expectancies to guide visual search is currently not well understood. Specifically, it is not clear whether spatial and feature-based search information is initially represented in anatomically segregated regions, nor at which level of processing expectancies regarding target features and locations may be integrated. To address these questions, we independently and parametrically varied the degree of spatial and feature-based (color) cue information concerning the identity of an upcoming visual search target while recording blood oxygenation level-dependent (BOLD) responses in human subjects. Search performance improved with the amount of spatial and feature-based cue information, and cue-related BOLD responses showed that, during preparation for visual search, spatial and feature cue information were represented additively in shared frontal, parietal, and cingulate regions. These data show that representations of spatial and feature-based search information are integrated in source regions of top-down biasing and oculomotor planning before search onset. The purpose of this anticipatory integration could lie with the generation of a "top-down salience map," a search template of primed target locations and features. Our results show that this role may be served by the intraparietal sulcus, which additively integrated a spatially specific activation gain in relation to spatial cue information with a spatially global activation gain in relation to feature cue information.

Physical activity (PA) and cardiorespiratory fitness (CRF) are associated with better cognitive function in late life, but the neural correlates for these relationships are unclear. To study these correlates, we examined the association of both PA and CRF with measures of white matter (WM) integrity in 88 healthy low-fit adults (age 60–78). Using accelerometry, we objectively measured sedentary behavior, light PA, and moderate to vigorous PA (MV-PA) over a week. We showed that greater MV-PA was related to lower volume of WM lesions. The association between PA and WM microstructural integrity (measured with diffusion tensor imaging) was region-specific: light PA was related to temporal WM, while sedentary behavior was associated with lower integrity in the parahippocampal WM. Our findings highlight that engaging in PA of various intensity in parallel with avoiding sedentariness are important in maintaining WM health in older age, supporting public health recommendations that emphasize the importance of active lifestyle.

Evidence suggests that a history of head trauma is associated with memory deficits later in life. The majority of previous research has focused on moderate-to-severe traumatic brain injury (TBI), but recent evidence suggests that even a mild TBI (mTBI) can interact with the aging process and produce reductions in memory performance. This study examined the association of mTBI with memory and the brain by comparing young and middle-aged adults who have had mTBI in their recent (several years ago) and remote (several decades ago) past, respectively, with control subjects on a face-scene relational memory paradigm while they underwent functional magnetic resonance imaging (fMRI). Hippocampal volumes were also examined from high-resolution structural images. Results indicated middle-aged adults with a head injury in their remote past had impaired memory compared to gender, age, and education matched control participants, consistent with previous results in the study of memory, aging, and TBI. The present findings extended previous results by demonstrating that these individuals also had smaller bilateral hippocampi, and had reduced neural activity during memory performance in cortical regions important for memory retrieval. These results indicate that a history of mTBI may be one of the many factors that negatively influence cognitive and brain health in aging.