Extrastriate Research Articles

A neural code supporting prospective probabilistic reasoning for instrumental information demand in humans

When making adaptive decisions, we actively demand information, but relatively little is known about the mechanisms of active information gathering. An open question is how the brain prospectively estimates the information gains that are expected to accrue from various sources by integrating simpler quantities of prior certainty and the reliability (diagnosticity) of a source. We examine this question using fMRI in a task in which people placed bids to obtain information in conditions that varied independently in the rewards, decision uncertainty, and information diagnosticity. We show that, consistent with value of information theory, the participants’ bids are sensitive to prior certainty (the certainty about the correct choice before gathering information) and expected posterior certainty (the certainty expected after gathering information). Expected posterior certainty is decoded from multivoxel activation patterns in the posterior parietal and extrastriate cortices. This representation is independent of instrumental rewards and spatially overlaps with distinct representations of prior certainty and expected information gains. The findings suggest that the posterior parietal and extrastriate cortices are candidates for mediating the prospection of posterior probabilities as a key step to anticipating information gains during active gathering of instrumental information.

Neural Dynamics Underlying False Alarms in Extrastriate Cortex.

The unfolding of neural population activity can be approximated as a dynamical system. Stability in the latent dynamics that characterize neural population activity has been linked with consistency in animal behavior, such as motor control or value-based decision-making. However, whether similar dynamics characterize perceptual activity and decision-making in the visual cortex is not well understood. To test this, we recorded V4 populations in monkeys engaged in a non-match-to-sample visual change-detection task that required sustained engagement. We measured how the stability in the latent dynamics in V4 might affect monkeys' perceptual behavior. Specifically, we reasoned that unstable sensory neural activity around dynamic attractor boundaries may make animals susceptible to taking incorrect actions when withholding action would have been correct ("false alarms"). We made three key discoveries: 1) greater stability was associated with longer trial sequences; 2) false alarm rate decreased (and reaction times slowed) when neural dynamics were more stable; and, 3) low stability predicted false alarms on a single-trial level, and this relationship depended on the elapsed time during the trial, consistent with the latent neural state approaching an attractor boundary. Our results suggest the same outward false alarm behavior can be attributed to two different potential strategies that can be disambiguated by examining neural stability: 1) premeditated false alarms that might lead to greater stability in population dynamics and faster reaction time and 2) false alarms due to unstable sensory activity consistent with misperception.

Bilateral connections from the amygdala to extrastriate visual cortex in the marmoset monkey.

It is known that the primate amygdala forms projections to many areas of the ipsilateral cortex, but the extent to which it forms connections with the contralateral visual cortex remains less understood. Based on retrograde tracer injections in marmoset monkeys, we report that the amygdala forms widespread projections to the ipsilateral extrastriate cortex, including V1 and areas in both the dorsal (MT, V4T, V3a, 19M, and PG/PFG) and the ventral (VLP and TEO) streams. In addition, contralateral projections were found to target each of the extrastriate areas, but not V1. In both hemispheres, the tracer-labeled neurons were exclusively located in the basolateral nuclear complex. The number of labeled neurons in the contralateral amygdala was small relative to the ipsilateral connection (1.2% to 5.8%). The percentage of contralateral connections increased progressively with hierarchical level. An injection in the corpus callosum demonstrated that at least some of the amygdalo-cortical connections cross through this fiber tract, in addition to the previously documented path through the anterior commissure. Our results expand knowledge of the amygdalofugal projections to the extrastriate cortex, while also revealing pathways through which visual stimuli conveying affective content can directly influence early stages of neural processing in the contralateral visual field.

Prefrontal working memory signal primarily controls phase-coded information within extrastriate cortex.

In order to understand how prefrontal cortex provides the benefits of working memory (WM) for visual processing we examined the influence of WM on the representation of visual signals in V4 neurons in two macaque monkeys. We found that WM induces strong β oscillations in V4 and that the timing of action potentials relative to this oscillation reflects sensory information- i.e., a phase coding of visual information. Pharmacologically inactivating the Frontal Eye Field part of prefrontal cortex, we confirmed the necessity of prefrontal signals for the WM-driven boost in phase coding of visual information. Indeed, changes in the average firing rate of V4 neurons could be accounted for by WM-induced oscillatory changes. We present a network model to describe how WM signals can recruit sensory areas primarily by inducing oscillations within these areas and discuss the implications of these findings for a sensory recruitment theory of WM through coherence.

FNIRS Changes in the Middle Temporal and Occipital Cortices After a Cochlear Implant.

The relationship between the middle temporal (MTG) and occipital cortices in post-lingually deaf (PLD) individuals is unclear. This study aimed to investigate changes in the MTG and occipital cortices excitability and their effects on the occipital cortex in individuals with PLD after receiving a cochlear implant (CI). Twenty-six individuals with severe-to-profound binaural sensorineural PLD were assessed clinically. Nine individuals had received a unilateral cochlear implant over 6 months, while 17 had not. Brodmann area 19 (BA19, extra-striate occipital cortex) and MTG (auditory-related area of cortex) were selected as regions of interest. The excitability of the ROI was observed and compared in the surgery and no-surgery groups by functional near-infrared spectroscopy (fNIRS) in the resting state, and correlations between connectivity of the MTG and occipital cortex, and as well as the duration of time that had elapsed following CI surgery, were investigated. fNIRS revealed enhanced global cortical connectivity in the BA19 and MTG on the operative side (p < 0.05) and the connectivity between BA19 and the MTG also increased (p < 0.05). The connectivity between the MTG and BA19 was positively correlated with the duration of cochlear implantation, as was the case for BA18. There was evidence for remodeling of the cerebral cortex: increased excitability was observed in the MTG and BA19, and their connectivity was enhanced, indicating a synergistic effect. Moreover, the MTG may further stimulate the visual cortex by strengthening their connectivity after CI. 3 Laryngoscope, 2024.

Naturalistic movies and encoding analysis define areal borders in marmoset third-tier visual cortex

Accurate definition of the borders of cortical visual areas is essential for the study of neuronal processes leading to perception. However, data used for definition of areal boundaries have suffered from issues related to resolution, uniform coverage, or suitability for objective analysis, leading to ambiguity. Here, we present a novel approach that combines widefield optical imaging, presentation of naturalistic movies, and encoding model analysis, to objectively define borders in the primate extrastriate cortex. We applied this method to test conflicting hypotheses about the third-tier visual cortex, where areal boundaries have remained controversial. We demonstrate pronounced tuning preferences in the third-tier areas, and an organizational structure in which the dorsomedial area (DM) contains representations of both the upper and lower contralateral quadrants, and is located immediate anterior to V2. High-density electrophysiological recordings with a Neuropixels probe confirm these findings. Our encoding-model approach offers a powerful, objective way to disambiguate areal boundaries.

Neural correlates of phonetic categorization under auditory (phoneme) and visual (grapheme) modalities.

We tested whether the neural mechanisms of phonetic categorization are specific to speech sounds or generalize to graphemes (i.e., visual letters) of the same phonetic label. Given that linguistic experience shapes categorical processing, and letter-speech sound matching plays a crucial role during early reading acquisition, we hypothesized sound phoneme and visual grapheme tokens representing the same linguistic identity might recruit common neural substrates, despite originating from different sensory modalities. Behavioral and neuroelectric brain responses (ERPs) were acquired as participants categorized stimuli from sound (phoneme) and homologous letter (grapheme) continua each spanning a /da/ - /ga/ gradient. Behaviorally, listeners were faster and showed stronger categorization of phoneme compared to graphemes. At the neural level, multidimensional scaling of the EEG revealed responses self-organized in a categorial fashion such that tokens clustered within their respective modality beginning ∼150-250 ms after stimulus onset. Source-resolved ERPs further revealed modality-specific and overlapping brain regions supporting phonetic categorization. Left inferior frontal gyrus and auditory cortex showed stronger responses for sound category members compared to phonetically ambiguous tokens, whereas early visual cortices paralleled this categorical organization for graphemes. Auditory and visual categorization also recruited common visual association areas in extrastriate cortex but in opposite hemispheres (auditory = left; visual=right). Our findings reveal both auditory and visual sensory cortex supports categorical organization for phonetic labels within their respective modalities. However, a partial overlap in phoneme and grapheme processing among occipital brain areas implies the presence of an isomorphic, domain-general mapping for phonetic categories in dorsal visual system.

Working memory expedites the processing of visual signals within the extrastriate cortex

Working memory is the ability to maintain information in the absence of sensory input. In this study, we investigated how working memory benefits processing in visual areas. Using a measure of phase consistency to detect the arrival time of visual signals to the middle temporal (MT) area, we assessed the impact of working memory on the speed of sensory processing. We recorded from MT neurons in two monkeys during a spatial working memory task with visual probes. When the memorized location closely matches the receptive field center of the recording site, visual input arrives sooner, but if the memorized location does not match the receptive field center then the arrival of visual information is delayed. Thus, working memory expedites the arrival of visual input in MT. These results reveal that even in the absence of firing rate changes, working memory can still benefit the processing of information within sensory areas.

Responses to visual motion of neurons in the extrastriate visual cortex of macaque monkeys with experimental amblyopia.

Amblyopia is a developmental disorder that results from abnormal visual experience in early life. Amblyopia typically reduces visual performance in one eye. We studied the representation of visual motion information in area MT and nearby extrastriate visual areas in two monkeys made amblyopic by creating an artificial strabismus in early life, and in a single age-matched control monkey. Tested monocularly, cortical responses to moving dot patterns, gratings, and plaids were qualitatively normal in awake, fixating amblyopic monkeys, with primarily subtle differences between the eyes. However, the number of binocularly driven neurons was substantially lower than normal; of the neurons driven predominantly by one eye, the great majority responded only to stimuli presented to the fellow eye. The small population driven by the amblyopic eye showed reduced coherence sensitivity and a preference for faster speeds in much the same way as behavioral deficits. We conclude that, while we do find important differences between neurons driven by the two eyes, amblyopia does not lead to a large scale reorganization of visual receptive fields in the dorsal stream when tested through the amblyopic eye, but rather creates a substantial shift in eye preference toward the fellow eye.

Layer-specific enhancement of visual-evoked activity in the audiovisual cortex following a mild degree of hearing loss in adult rats

Following adult-onset hearing impairment, crossmodal plasticity can occur within various sensory cortices, often characterized by increased neural responses to visual stimulation in not only the auditory cortex, but also in the visual and audiovisual cortices. In the present study, we used an established model of loud noise exposure in rats to examine, for the first time, whether the crossmodal plasticity in the audiovisual cortex that occurs following a relatively mild degree of hearing loss emerges solely from altered intracortical processing or if thalamocortical changes also contribute to the crossmodal effects. Using a combination of an established pharmacological ‘cortical silencing’ protocol and current source density analysis of the laminar activity recorded across the layers of the audiovisual cortex (i.e., the lateral extrastriate visual cortex, V2L), we observed layer-specific changes post-silencing in the strength of the residual visual, but not auditory, input in the noise exposed rats with mild hearing loss compared to rats with normal hearing. Furthermore, based on a comparison of the laminar profiles pre- versus post-silencing in both groups, we can conclude that noise exposure caused a re-allocation of the strength of visual inputs across the layers of the V2L cortex, including enhanced visual-evoked activity in the granular layer; findings consistent with thalamocortical plasticity. Finally, we confirmed that audiovisual integration within the V2L cortex depends on intact processing within intracortical circuits, and that this form of multisensory processing is vulnerable to disruption by noise-induced hearing loss. Ultimately, the present study furthers our understanding of the contribution of intracortical and thalamocortical processing to crossmodal plasticity as well as to audiovisual integration under both normal and mildly-impaired hearing conditions.

Attention spotlight in V1-based cortico-cortical interactions in human visual hierarchy

Attention is often viewed as a mental spotlight, which can be scaled like a zoom lens at specific spatial locations and features a center-surround gradient. Here, we demonstrate a neural signature of attention spotlight in signal transmission along the visual hierarchy. fMRI background connectivity analysis was performed between retinotopic V1 and downstream areas to characterize the spatial distribution of inter-areal interaction under two attentional states. We found that, compared to diffused attention, focal attention sharpened the spatial gradient in the strength of the background connectivity. Dynamic causal modeling analysis further revealed the effect of attention in both the feedback and feedforward connectivity between V1 and extrastriate cortex. In a context which induced a strong effect of crowding, the effect of attention in the background connectivity profile diminished. Our findings reveal a context-dependent attention prioritization in information transmission via modulating the recurrent processing across the early stages in human visual cortex.

Differential cortical and subcortical visual processing with eyes shut.

Closing our eyes largely shuts down our ability to see. That said, our eyelids still pass some light, allowing our visual system to coarsely process information about visual scenes, such as changes in luminance. However, the specific impact of eye closure on processing within the early visual system remains largely unknown. To understand how visual processing is modulated when eyes are shut, we used functional magnetic resonance imaging (fMRI) to measure responses to a flickering visual stimulus at high (100%) and low (10%) temporal contrasts, while participants viewed the stimuli with their eyes open or closed. Interestingly, we discovered that eye closure produced a qualitatively distinct pattern of effects across the visual thalamus and visual cortex. We found that with eyes open, low temporal contrast stimuli produced smaller responses across the lateral geniculate nucleus (LGN), primary (V1) and extrastriate visual cortex (V2). However, with eyes closed, we discovered that the LGN and V1 maintained similar blood oxygenation level-dependent (BOLD) responses as the eyes open condition, despite the suppressed visual input through the eyelid. In contrast, V2 and V3 had strongly attenuated BOLD response when eyes were closed, regardless of temporal contrast. Our findings reveal a qualitatively distinct pattern of visual processing when the eyes are closed-one that is not simply an overall attenuation but rather reflects distinct responses across visual thalamocortical networks, wherein the earliest stages of processing preserve information about stimuli but are then gated off downstream in visual cortex.NEW & NOTEWORTHY When we close our eyes coarse luminance information is still accessible by the visual system. Using functional magnetic resonance imaging, we examined whether eyelid closure plays a unique role in visual processing. We discovered that while the LGN and V1 show equivalent responses when the eyes are open or closed, extrastriate cortex exhibited attenuated responses with eye closure. This suggests that when the eyes are closed, downstream visual processing is blind to this information.

Measurement of Cerebral Glucose Metabolism in the Visual Cortex Predicts the Prognosis of Hemianopia

Background and Objective Homonymous hemianopia caused by cerebrovascular disease may improve over time. This study investigated whether functional neuroimaging can predict the prognosis of hemianopia due to cerebral infarction. Methods We studied 19 patients (10 men and 9 women) with homonymous hemianopia and compared them with 34 healthy subjects (20 men and 14 women). Cerebral glucose metabolism was measured by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), 1 to 6 months after the onset. Bilateral regions of interest (ROIs) were selected from the posterior and, anterior striate cortices, extrastriate cortex, and thalamus. Furthermore, semi-quantitative data on cerebral glucose metabolism were obtained for ROIs and compared with the data obtained for homologous regions in the contralateral hemisphere by calculating the ipsilateral/contralateral (I/C) ratio. Results The I/C ratio for the cerebral glucose metabolism in the posterior striate cortex was high (>0.750) in 8 patients, and the central visual field of these patients improved or showed macular sparing. The I/C ratio for cerebral glucose metabolism in the anterior striate cortex was high (>0.830) in 7 patients, and the peripheral visual field of these patients improved. However, no improvement was observed in 9 patients with a low I/C ratio for cerebral glucose metabolism in both the posterior and anterior striate cortices. Conclusion Measurement of cerebral glucose metabolism in the striate cortex is useful for estimating visual field prognosis. Furthermore, FDG-PET is useful in predicting the prognosis of hemianopia.

The extrastriate symmetry response is robust to alcohol intoxication.

Visual symmetry activates a network of regions in the extrastriate cortex and generates an event-related potential (ERP) called the sustained posterior negativity (SPN). Previous work has found that the SPN is robust to experimental manipulations of task, spatial attention, and memory load. In the current study, we investigated whether the SPN is also robust to alcohol-induced changes in mental state. A pilot experiment (N = 13) found that alcohol unexpectedly increased SPN amplitude. We followed this unexpected result with two new experiments on separate groups, using an alcohol challenge paradigm. One group completed an Oddball discrimination task (N = 26). Another group completed a Regularity discrimination task (N = 26). In both groups, participants consumed a medium dose of alcohol (0.65 g/kg body weight) and a placebo drink, in separate sessions. Alcohol reduced SPN amplitude in the Oddball task (contrary to the pilot results) but had no effect on SPN amplitude in the Regularity task. In contrast, the N1 wave was consistently dampened by alcohol in all experiments. Exploratory analysis indicated that the inconsistent effect of alcohol on SPN amplitude may be partly explained by individual differences in alcohol use. Alcohol reduced the SPN in light drinkers and increased it in heavier drinkers. Despite remaining questions, the results highlight the automaticity of symmetry processing. Symmetry still produces a large SPN response, even when participants are intoxicated, and even when symmetry is not task relevant.

Functional connectivity-hemodynamic (un)coupling changes in chronic mild brain injury are associated with mental health and neurocognitive indices: a resting state fMRI study.

To examine hemodynamic and functional connectivity alterations and their association with neurocognitive and mental health indices in patients with chronic mild traumatic brain injury (mTBI). Resting-state functional MRI (rs-fMRI) and neuropsychological assessment of 37 patients with chronic mTBI were performed. Intrinsic connectivity contrast (ICC) and time-shift analysis (TSA) of the rs-fMRI data allowed the assessment of regional hemodynamic and functional connectivity disturbances and their coupling (or uncoupling). Thirty-nine healthy age- and gender-matched participants were also examined. Patients with chronic mTBI displayed hypoconnectivity in bilateral hippocampi and parahippocampal gyri and increased connectivity in parietal areas (right angular gyrus and left superior parietal lobule (SPL)). Slower perfusion (hemodynamic lag) in the left anterior hippocampus was associated with higher self-reported symptoms of depression (r = - 0.53, p = .0006) and anxiety (r = - 0.484, p = .002), while faster perfusion (hemodynamic lead) in the left SPL was associated with lower semantic fluency (r = - 0.474, p = .002). Finally, functional coupling (high connectivity and hemodynamic lead) in the right anterior cingulate cortex (ACC)) was associated with lower performance on attention and visuomotor coordination (r = - 0.50, p = .001), while dysfunctional coupling (low connectivity and hemodynamic lag) in the left ventral posterior cingulate cortex (PCC) and right SPL was associated with lower scores on immediate passage memory (r = - 0.52, p = .001; r = - 0.53, p = .0006, respectively). Uncoupling in the right extrastriate visual cortex and posterior middle temporal gyrus was negatively associated with cognitive flexibility (r = - 0.50, p = .001). Hemodynamic and functional connectivity differences, indicating neurovascular (un)coupling, may be linked to mental health and neurocognitive indices in patients with chronic mTBI.

The structure-function relationship between multifocal pupil perimetry and retinal nerve fibre layer in glaucoma.

Multifocal pupillographic objective perimetry (mfPOP) is a novel method for assessing functional change in diseases like glaucoma. Previous research has suggested that, in contrast to the pretectally-mediated melanopsin response of intrinsically photosensitive retinal ganglion cells, mfPOP responses to transient onset stimuli involve the extrastriate cortex, and thus the main visual pathway. We therefore investigate the correlation between peripapillary retinal nerve fibre layer (pRNFL) thickness and glaucomatous visual field changes detected using mfPOP. Parallel analyses are undertaken using white on white standard automated perimetry (SAP) for comparison. Twenty-five glaucoma patients and 24 normal subjects were tested using SAP, 3 mfPOP variants, and optical coherence tomography (OCT). Arcuate clusters of the SAP and mfPOP deviations were weighted according to their contribution to published arcuate divisions of the retinal nerve fibre layer. Structure-function correlation coefficients (r) were computed between pRNFL clock-hour sector thickness measurements, and the local visual field sensitivities from both SAP and mfPOP. The strongest correlation was observed in the superior-superotemporal disc sector in patients with worst eye SAP MD < -12dB: r = 0.93 for the mfPOP LumBal test (p < 0.001). Correlations across all disc-sectors were strongest in these same patients in both SAP and mfPOP: SAP r = 0.54, mfPOP LumBal r = 0.55 (p < 0.001). In patients with SAP MD ≥ -6dB in both eyes, SAP correlations across all sectors were higher than mfPOP; mfPOP correlations however, were higher than SAP in more advanced disease, and in normal subjects. For both methods the largest correlations with pRNFL thickness corresponded to the inferior nasal field of more severely damaged eyes. Head-to-head comparison of mfPOP and SAP showed similar structure-function relationships. This agrees with our recent reports that mfPOP primarily stimulates the cortical drive to the pupils.

Parallel Streams of Direct Corticogeniculate Feedback from Mid-level Extrastriate Cortex in the Macaque Monkey.

First-order thalamic nuclei receive feedforward signals from peripheral receptors and relay these signals to primary sensory cortex. Primary sensory cortex, in turn, provides reciprocal feedback to first-order thalamus. Because the vast majority of sensory thalamocortical inputs target primary sensory cortex, their complementary corticothalamic neurons are assumed to be similarly restricted to primary sensory cortex. We upend this assumption by characterizing morphologically diverse neurons in multiple mid-level visual cortical areas of the primate (Macaca mulatta) brain that provide direct feedback to the primary visual thalamus, the dorsal lateral geniculate nucleus (LGN). Although the majority of geniculocortical neurons project to primary visual cortex (V1), a minority, located mainly in the koniocellular LGN layers, provide direct input to extrastriate visual cortex. These "V1-bypassing" projections may be implicated in blindsight. We hypothesized that geniculocortical inputs directly targeting extrastriate cortex should be complemented by reciprocal corticogeniculate circuits. Using virus-mediated circuit tracing, we discovered corticogeniculate neurons throughout three mid-level extrastriate areas: MT, MST, and V4. Quantitative morphological analyses revealed nonuniform distributions of unique cell types across areas. Many extrastriate corticogeniculate neurons had spiny stellate morphology, suggesting possible targeting of koniocellular LGN layers. Importantly though, multiple morphological types were observed across areas. Such morphological diversity could suggest parallel streams of V1-bypassing corticogeniculate feedback at multiple stages of the visual processing hierarchy. Furthermore, the presence of corticogeniculate neurons across visual cortex necessitates a reevaluation of the LGN as a hub for visual information rather than a simple relay.

Процессы когнитивного контроля в тесте Струпа и их отражение в связанных с событиями потенциалах (обзор)

The review summarizes the data of Russian and foreign studies on the psychophysiological parameters of the Stroop task execution. In addition, the article considers the main modifications of the task and similar paradigms as well as the key hypotheses explaining the causes of the interference effect and the increase in reaction time to stimuli containing conflicting information. Further, the paper presents data on eventrelated potential (ERP) waves, which are supposed to reflect cognitive control processes, such as conflict detection, overcoming of interference and conflict resolution. The frontocentral N2 wave characterizes the processes of conflict detection and overcoming of interference, and its main neural generator is the anterior cingulate cortex. The N450 wave is primarily generated in the anterior cingulate cortex and prefrontal cortex and is thought to reflect interference suppression. The centroparietal P300 wave and the late positive complex, which appears to be generated in the middle or inferior frontal gyrus and in the extrastriate cortex, are associated with the conflict resolution process. The readiness potential is, supposedly, generated in the motor cortex and reflects the process of selecting and preparing a motor response. Moreover, the review presents the main directions of studies that use the Stroop test paradigm and its modifications. Despite a significant number of existing psychophysical and neurophysiological papers, the question of the brain mechanisms of cognitive control in tasks that cause cognitive conflict remains open, and the neuropsychological role of the ERP waves recorded in such tasks is still not fully explored. Studies into the influence of different types of competing information and the degree of conflict on the psychophysiological indicators in the Stroop task are of considerable interest.

Intersubject representational similarity analysis uncovers the impact of state anxiety on brain activation patterns in the human extrastriate cortex.

The current study used functional magnetic resonance imaging (fMRI) and showed that state anxiety modulated extrastriate cortex activity in response to emotionally-charged visual images. State anxiety and neuroimaging data from 53 individuals were subjected to an intersubject representational similarity analysis (ISRSA), wherein the geometries between neural and behavioral data were compared. This analysis identified the extrastriate cortex (fusiform gyrus and area MT) to be the sole regions whose activity patterns covaried with state anxiety. Importantly, we show that this brain-behavior association is revealed when treating state anxiety data as a multidimensional response pattern, rather than a single composite score. This suggests that ISRSA using multivariate distances may be more sensitive in identifying the shared geometries between self-report questionnaires and brain imaging data. Overall, our findings demonstrate that a transient state of anxiety may influence how visual information - especially those relevant to the valence dimension - is processed in the extrastriate cortex.

Neural processing of prototypicality and simplicity of product design in forming design preferences.

The current study investigates the neural correlates when processing prototypicality and simplicity-affecting the preference of product design. Despite its significance, not much is known about how our brain processes these visual qualities of design when forming design preferences. We posit that, although fluency is the perceptual judgment accounting for the positive effects of both prototypicality and simplicity on design preference, the neural substrates for the fluency judgment associated with prototypicality would differ from those associated with simplicity. To investigate these issues, we conducted an fMRI study of preference decisions for actual product designs with different levels of prototypicality and simplicity. The results show a significant functional gradient between the preference processing of simplicity and prototypicality-i.e., involvement of the early ventral stream of visual information processing for simplicity evaluation but recruitment of the late ventral stream and parietal-frontal brain regions for prototypicality evaluation. The interaction between the simplicity and prototypicality evaluations was found in the extrastriate cortex in the right hemisphere. The segregated brain involvements suggest that the fluency judgment for prototypicality and simplicity contribute to preference choice in different levels of cognitive hierarchy in the perceptual mechanism of the design preference.