Microstructural and neurochemical plasticity mechanisms interact to enhance human perceptual decision-making.

Experience and training are known to boost our skills and mold the brain's organization and function. Yet, structural plasticity and functional neurotransmission are typically studied at different scales (large-scale networks, local circuits), limiting our understanding of the adaptive interactions that support learning of complex cognitive skills in the adult brain. Here, we employ multimodal brain imaging to investigate the link between microstructural (myelination) and neurochemical (GABAergic) plasticity for decision-making. We test (in males, due to potential confounding menstrual cycle effects on GABA measurements in females) for changes in MRI-measured myelin, GABA, and functional connectivity before versus after training on a perceptual decision task that involves identifying targets in clutter. We demonstrate that training alters subcortical (pulvinar, hippocampus) myelination and its functional connectivity to visual cortex and relates to decreased visual cortex GABAergic inhibition. Modeling interactions between MRI measures of myelin, GABA, and functional connectivity indicates that pulvinar myelin plasticity interacts-through thalamocortical connectivity-with GABAergic inhibition in visual cortex to support learning. Our findings propose a dynamic interplay of adaptive microstructural and neurochemical plasticity in subcortico-cortical circuits that supports learning for optimized decision-making in the adult human brain.

Learning at your brain's rhythm: individualized entrainment boosts learning for perceptual decisions.

Training is known to improve our ability to make decisions when interacting in complex environments. However, individuals vary in their ability to learn new tasks and acquire new skills in different settings. Here, we test whether this variability in learning ability relates to individual brain oscillatory states. We use a visual flicker paradigm to entrain individuals at their own brain rhythm (i.e. peak alpha frequency) as measured by resting-state electroencephalography (EEG). We demonstrate that this individual frequency-matched brain entrainment results in faster learning in a visual identification task (i.e. detecting targets embedded in background clutter) compared to entrainment that does not match an individual's alpha frequency. Further, we show that learning is specific to the phase relationship between the entraining flicker and the visual target stimulus. EEG during entrainment showed that individualized alpha entrainment boosts alpha power, induces phase alignment in the pre-stimulus period, and results in shorter latency of early visual evoked potentials, suggesting that brain entrainment facilitates early visual processing to support improved perceptual decisions. These findings suggest that individualized brain entrainment may boost perceptual learning by altering gain control mechanisms in the visual cortex, indicating a key role for individual neural oscillatory states in learning and brain plasticity.

Ultra-High-Field Neuroimaging Reveals Fine-Scale Processing for 3D Perception.

Binocular disparity provides critical information about three-dimensional (3D) structures to support perception and action. In the past decade significant progress has been made in uncovering human brain areas engaged in the processing of binocular disparity signals. Yet, the fine-scale brain processing underlying 3D perception remains unknown. Here, we use ultra-high-field (7T) functional imaging at submillimeter resolution to examine fine-scale BOLD fMRI signals involved in 3D perception. In particular, we sought to interrogate the local circuitry involved in disparity processing by sampling fMRI responses at different positions relative to the cortical surface (i.e., across cortical depths corresponding to layers). We tested for representations related to 3D perception by presenting participants (male and female, N = 8) with stimuli that enable stable stereoscopic perception [i.e., correlated random dot stereograms (RDS)] versus those that do not (i.e., anticorrelated RDS). Using multivoxel pattern analysis (MVPA), we demonstrate cortical depth-specific representations in areas V3A and V7 as indicated by stronger pattern responses for correlated than for anticorrelated stimuli in upper rather than deeper layers. Examining informational connectivity, we find higher feedforward layer-to-layer connectivity for correlated than anticorrelated stimuli between V3A and V7. Further, we observe disparity-specific feedback from V3A to V1 and from V7 to V3A. Our findings provide evidence for the role of V3A as a key nexus for disparity processing, which is implicated in feedforward and feedback signals related to the perceptual estimation of 3D structures.SIGNIFICANCE STATEMENT Binocular vision plays a significant role in supporting our interactions with the surrounding environment. The fine-scale neural mechanisms that underlie the brain's skill in extracting 3D structures from binocular signals are poorly understood. Here, we capitalize on recent advances in ultra-high-field functional imaging to interrogate human brain circuits involved in 3D perception at submillimeter resolution. We provide evidence for the role of area V3A as a key nexus for disparity processing, which is implicated in feedforward and feedback signals related to the perceptual estimation of 3D structures from binocular signals. These fine-scale measurements help bridge the gap between animal neurophysiology and human fMRI studies investigating cross-scale circuits, from micro circuits to global brain networks for 3D perception.

Neurochemical and functional interactions for improved perceptual decisions through training.

Learning and experience are known to improve our ability to make perceptual decisions. Yet, our understanding of the brain mechanisms that support improved perceptual decisions through training remains limited. Here, we test the neurochemical and functional interactions that support learning for perceptual decisions in the context of an orientation identification task. Using magnetic resonance spectroscopy (MRS), we measure neurotransmitters (i.e., glutamate, GABA) that are known to be involved in visual processing and learning in sensory [early visual cortex (EV)] and decision-related [dorsolateral prefrontal cortex (DLPFC)] brain regions. Using resting-state functional magnetic resonance imaging (rs-fMRI), we test for functional interactions between these regions that relate to decision processes. We demonstrate that training improves perceptual judgments (i.e., orientation identification), as indicated by faster rates of evidence accumulation after training. These learning-dependent changes in decision processes relate to lower EV glutamate levels and EV-DLPFC connectivity, suggesting that glutamatergic excitation and functional interactions between visual and dorsolateral prefrontal cortex facilitate perceptual decisions. Further, anodal transcranial direct current stimulation (tDCS) in EV impairs learning, suggesting a direct link between visual cortex excitation and perceptual decisions. Our findings advance our understanding of the role of learning in perceptual decision making, suggesting that glutamatergic excitation for efficient sensory processing and functional interactions between sensory and decision-related regions support improved perceptual decisions.NEW & NOTEWORTHY Combining multimodal brain imaging [magnetic resonance spectroscopy (MRS), functional connectivity] with interventions [transcranial direct current stimulation (tDCS)], we demonstrate that glutamatergic excitation and functional interactions between sensory (visual) and decision-related (dorsolateral prefrontal cortex) areas support our ability to optimize perceptual decisions through training.

Functional Interactions between Sensory and Memory Networks for Adaptive Behavior.

The brain's capacity to adapt to sensory inputs is key for processing sensory information efficiently and interacting in new environments. Following repeated exposure to the same sensory input, brain activity in sensory areas is known to decrease as inputs become familiar, a process known as adaptation. Yet, the brain-wide mechanisms that mediate adaptive processing remain largely unknown. Here, we combine multimodal brain imaging (functional magnetic resonance imaging [fMRI], magnetic resonance spectroscopy) with behavioral measures of orientation-specific adaptation (i.e., tilt aftereffect) to investigate the functional and neurochemical mechanisms that support adaptive processing. Our results reveal two functional brain networks: 1) a sensory-adaptation network including occipital and dorsolateral prefrontal cortex regions that show decreased fMRI responses for repeated stimuli and 2) a perceptual-memory network including regions in the parietal memory network (PMN) and dorsomedial prefrontal cortex that relate to perceptual bias (i.e., tilt aftereffect). We demonstrate that adaptation relates to increased occipito-parietal connectivity, while decreased connectivity between sensory-adaptation and perceptual-memory networks relates to GABAergic inhibition in the PMN. Thus, our findings provide evidence that suppressive interactions between sensory-adaptation (i.e., occipito-parietal) and perceptual-memory (i.e., PMN) networks support adaptive processing and behavior, proposing a key role of memory systems in efficient sensory processing.

A New Remote Guided Method for Supervised Web-Based Cognitive Testing to Ensure High-Quality Data: Development and Usability Study.

BACKGROUND: The global COVID-19 pandemic has triggered a fundamental reexamination of how human psychological research can be conducted safely and robustly in a new era of digital working and physical distancing. Online web-based testing has risen to the forefront as a promising solution for the rapid mass collection of cognitive data without requiring human contact. However, a long-standing debate exists over the data quality and validity of web-based studies. This study examines the opportunities and challenges afforded by the societal shift toward web-based testing and highlights an urgent need to establish a standard data quality assurance framework for online studies. OBJECTIVE: This study aims to develop and validate a new supervised online testing methodology, remote guided testing (RGT). METHODS: A total of 85 healthy young adults were tested on 10 cognitive tasks assessing executive functioning (flexibility, memory, and inhibition) and learning. Tasks were administered either face-to-face in the laboratory (n=41) or online using remote guided testing (n=44) and delivered using identical web-based platforms (Cambridge Neuropsychological Test Automated Battery, Inquisit, and i-ABC). Data quality was assessed using detailed trial-level measures (missed trials, outlying and excluded responses, and response times) and overall task performance measures. RESULTS: The results indicated that, across all data quality and performance measures, RGT data was statistically-equivalent to in-person data collected in the lab (P>.40 for all comparisons). Moreover, RGT participants out-performed the lab group on measured verbal intelligence (P<.001), which could reflect test environment differences, including possible effects of mask-wearing on communication. CONCLUSIONS: These data suggest that the RGT methodology could help ameliorate concerns regarding online data quality-particularly for studies involving high-risk or rare cohorts-and offer an alternative for collecting high-quality human cognitive data without requiring in-person physical attendance.

Cultural differences in visual perceptual learning.

Cultural differences in visual perceptual learning (VPL) could be attributed to differences in the way that people from individualistic and collectivistic cultures preferentially attend to local objects (analytic) or global contexts (holistic). Indeed, individuals from different cultural backgrounds can adopt distinct processing styles and learn to differentially construct meaning from the environment. Therefore, the present work investigates if cross-cultural differences in VPL can vary as a function of holistic processing. A shape discrimination task was used to investigate whether the individualistic versus collectivistic backgrounds of individuals affected the detection of global shapes embedded in cluttered backgrounds. Seventy-seven participants-including Asian (collectivistic background) and European (individualistic background) students-were trained to discriminate between radial and concentric patterns. Singelis's self-construal scale was also used to assess whether differences in learning could be attributed to independent or interdependent self-construal. Results showed that collectivists had faster learning rates and better accuracy performance than individualists following training-thereby reflecting their tendency to attend holistically when learning to extract global forms. Further, we observed a negative association between independent self-construal-which has previously been linked to analytic processing-with performance. This study provides insight into how socio-cultural backgrounds affect VPL.

GABA and glutamate deficits from frontotemporal lobar degeneration are associated with disinhibition.

Behavioural disinhibition is a common feature of the syndromes associated with frontotemporal lobar degeneration (FTLD). It is associated with high morbidity and lacks proven symptomatic treatments. A potential therapeutic strategy is to correct the neurotransmitter deficits associated with FTLD, thereby improving behaviour. Reductions in the neurotransmitters glutamate and GABA correlate with impulsive behaviour in several neuropsychiatric diseases and there is post-mortem evidence of their deficit in FTLD. Here, we tested the hypothesis that prefrontal glutamate and GABA levels are reduced by FTLD in vivo, and that their deficit is associated with impaired response inhibition. Thirty-three participants with a syndrome associated with FTLD (15 patients with behavioural variant frontotemporal dementia and 18 with progressive supranuclear palsy, including both Richardson's syndrome and progressive supranuclear palsy-frontal subtypes) and 20 healthy control subjects were included. Participants undertook ultra-high field (7 T) magnetic resonance spectroscopy and a stop-signal task of response inhibition. We measured glutamate and GABA levels using semi-LASER magnetic resonance spectroscopy in the right inferior frontal gyrus, because of its strong association with response inhibition, and in the primary visual cortex, as a control region. The stop-signal reaction time was calculated using an ex-Gaussian Bayesian model. Participants with frontotemporal dementia and progressive supranuclear palsy had impaired response inhibition, with longer stop-signal reaction times compared with controls. GABA concentration was reduced in patients versus controls in the right inferior frontal gyrus, but not the occipital lobe. There was no group-wise difference in partial volume corrected glutamate concentration between patients and controls. Both GABA and glutamate concentrations in the inferior frontal gyrus correlated inversely with stop-signal reaction time, indicating greater impulsivity in proportion to the loss of each neurotransmitter. We conclude that the glutamatergic and GABAergic deficits in the frontal lobe are potential targets for symptomatic drug treatment of frontotemporal dementia and progressive supranuclear palsy.

Neural representations for object perception: structure, category, and adaptive coding.

Object perception is one of the most remarkable capacities of the primate brain. Owing to the large and indeterminate dimensionality of object space, the neural basis of object perception has been difficult to study and remains controversial. Recent work has provided a more precise picture of how 2D and 3D object structure is encoded in intermediate and higher-level visual cortices. Yet, other studies suggest that higher-level visual cortex represents categorical identity rather than structure. Furthermore, object responses are surprisingly adaptive to changes in environmental statistics, implying that learning through evolution, development, and also shorter-term experience during adulthood may optimize the object code. Future progress in reconciling these findings will depend on more effective sampling of the object domain and direct comparison of these competing hypotheses.

Learning Predictive Statistics: Strategies and Brain Mechanisms.

When immersed in a new environment, we are challenged to decipher initially incomprehensible streams of sensory information. However, quite rapidly, the brain finds structure and meaning in these incoming signals, helping us to predict and prepare ourselves for future actions. This skill relies on extracting the statistics of event streams in the environment that contain regularities of variable complexity from simple repetitive patterns to complex probabilistic combinations. Here, we test the brain mechanisms that mediate our ability to adapt to the environment's statistics and predict upcoming events. By combining behavioral training and multisession fMRI in human participants (male and female), we track the corticostriatal mechanisms that mediate learning of temporal sequences as they change in structure complexity. We show that learning of predictive structures relates to individual decision strategy; that is, selecting the most probable outcome in a given context (maximizing) versus matching the exact sequence statistics. These strategies engage distinct human brain regions: maximizing engages dorsolateral prefrontal, cingulate, sensory-motor regions, and basal ganglia (dorsal caudate, putamen), whereas matching engages occipitotemporal regions (including the hippocampus) and basal ganglia (ventral caudate). Our findings provide evidence for distinct corticostriatal mechanisms that facilitate our ability to extract behaviorally relevant statistics to make predictions.SIGNIFICANCE STATEMENT Making predictions about future events relies on interpreting streams of information that may initially appear incomprehensible. Past work has studied how humans identify repetitive patterns and associative pairings. However, the natural environment contains regularities that vary in complexity from simple repetition to complex probabilistic combinations. Here, we combine behavior and multisession fMRI to track the brain mechanisms that mediate our ability to adapt to changes in the environment's statistics. We provide evidence for an alternate route for learning complex temporal statistics: extracting the most probable outcome in a given context is implemented by interactions between executive and motor corticostriatal mechanisms compared with visual corticostriatal circuits (including hippocampal cortex) that support learning of the exact temporal statistics.

Contour Integration over Time: Psychophysical and fMRI Evidence.

The brain integrates discrete but collinear stimuli to perceive global contours. Previous contour integration (CI) studies mainly focus on integration over space, and CI is attributed to either V1 long-range connections or contour processing in high-visual areas that top-down modulate V1 responses. Here, we show that CI also occurs over time in a design that minimizes the roles of V1 long-range interactions. We use tilted contours embedded in random orientation noise and moving horizontally behind a fixed vertical slit. Individual contour elements traveling up/down within the slit would be encoded over time by parallel, rather than aligned, V1 neurons. However, we find robust contour detection even when the slit permits only one viewable contour element. Similar to CI over space, CI over time also obeys the rule of collinearity. fMRI evidence shows that while CI over space engages visual areas as early as V1, CI over time mainly engages higher dorsal and ventral visual areas involved in shape processing, as well as posterior parietal regions involved in visual memory that can represent the orientation of temporally integrated contours. These results suggest at least partially dissociable mechanisms for implementing the Gestalt rule of continuity in CI over space and time.

The Effect of Task Instruction on Haptic Texture Processing: The Neural Underpinning of Roughness and Spatial Density Perception.

Perceived roughness is associated with a variety of physical factors and multiple peripheral afferent types. The current study investigated whether this complexity of the mapping between physical and perceptual space is reflected at the cortical level. In an integrative psychophysical and imaging approach, we used dot pattern stimuli for which previous studies reported a simple linear relationship of interdot spacing and perceived spatial density and a more complex function of perceived roughness. Thus, by using both a roughness and a spatial estimation task, the physical and perceived stimulus characteristics could be dissociated, with the spatial density task controlling for the processing of low-level sensory aspects. Multivoxel pattern analysis was used to investigate which brain regions hold information indicative of the level of the perceived texture characteristics. While information about differences in perceived roughness was primarily available in higher-order cortices, that is, the operculo-insular cortex and a ventral visual cortex region, information about perceived spatial density could already be derived from early somatosensory and visual regions. This result indicates that cortical processing reflects the different complexities of the evaluated haptic texture dimensions. Furthermore, this study is to our knowledge the first to show a contribution of the visual cortex to tactile roughness perception.

Learning predictive statistics from temporal sequences: Dynamics and strategies.

Human behavior is guided by our expectations about the future. Often, we make predictions by monitoring how event sequences unfold, even though such sequences may appear incomprehensible. Event structures in the natural environment typically vary in complexity, from simple repetition to complex probabilistic combinations. How do we learn these structures? Here we investigate the dynamics of structure learning by tracking human responses to temporal sequences that change in structure unbeknownst to the participants. Participants were asked to predict the upcoming item following a probabilistic sequence of symbols. Using a Markov process, we created a family of sequences, from simple frequency statistics (e.g., some symbols are more probable than others) to context-based statistics (e.g., symbol probability is contingent on preceding symbols). We demonstrate the dynamics with which individuals adapt to changes in the environment's statistics-that is, they extract the behaviorally relevant structures to make predictions about upcoming events. Further, we show that this structure learning relates to individual decision strategy; faster learning of complex structures relates to selection of the most probable outcome in a given context (maximizing) rather than matching of the exact sequence statistics. Our findings provide evidence for alternate routes to learning of behaviorally relevant statistics that facilitate our ability to predict future events in variable environments.

Learning Temporal Statistics for Sensory Predictions in Aging.

Predicting future events based on previous knowledge about the environment is critical for successful everyday interactions. Here, we ask which brain regions support our ability to predict the future based on implicit knowledge about the past in young and older age. Combining behavioral and fMRI measurements, we test whether training on structured temporal sequences improves the ability to predict upcoming sensory events; we then compare brain regions involved in learning predictive structures between young and older adults. Our behavioral results demonstrate that exposure to temporal sequences without feedback facilitates the ability of young and older adults to predict the orientation of an upcoming stimulus. Our fMRI results provide evidence for the involvement of corticostriatal regions in learning predictive structures in both young and older learners. In particular, we showed learning-dependent fMRI responses for structured sequences in frontoparietal regions and the striatum (putamen) for young adults. However, for older adults, learning-dependent activations were observed mainly in subcortical (putamen, thalamus) regions but were weaker in frontoparietal regions. Significant correlations of learning-dependent behavioral and fMRI changes in these regions suggest a strong link between brain activations and behavioral improvement rather than general overactivation. Thus, our findings suggest that predicting future events based on knowledge of temporal statistics engages brain regions involved in implicit learning in both young and older adults.

Decoding the future from past experience: learning shapes predictions in early visual cortex.

Learning the structure of the environment is critical for interpreting the current scene and predicting upcoming events. However, the brain mechanisms that support our ability to translate knowledge about scene statistics to sensory predictions remain largely unknown. Here we provide evidence that learning of temporal regularities shapes representations in early visual cortex that relate to our ability to predict sensory events. We tested the participants' ability to predict the orientation of a test stimulus after exposure to sequences of leftward- or rightward-oriented gratings. Using fMRI decoding, we identified brain patterns related to the observers' visual predictions rather than stimulus-driven activity. Decoding of predicted orientations following structured sequences was enhanced after training, while decoding of cued orientations following exposure to random sequences did not change. These predictive representations appear to be driven by the same large-scale neural populations that encode actual stimulus orientation and to be specific to the learned sequence structure. Thus our findings provide evidence that learning temporal structures supports our ability to predict future events by reactivating selective sensory representations as early as in primary visual cortex.

Learning to predict is spared in mild cognitive impairment due to Alzheimer's disease.

Learning the statistics of the environment is critical for predicting upcoming events. However, little is known about how we translate previous knowledge about scene regularities to sensory predictions. Here, we ask whether patients with mild cognitive impairment due to Alzheimer's disease (MCI-AD) that are known to have spared implicit but impaired explicit recognition memory are able to learn temporal regularities and predict upcoming events. We tested the ability of MCI-AD patients and age-matched controls to predict the orientation of a test stimulus following exposure to sequences of leftwards or rightwards oriented gratings. Our results demonstrate that exposure to temporal sequences without feedback facilitates the ability to predict an upcoming stimulus in both MCI-AD patients and controls. Further, we show that executive cognitive control may account for individual variability in predictive learning. That is, we observed significant positive correlations of performance in attentional and working memory tasks with post-training performance in the prediction task. Taken together, these results suggest a mediating role of circuits involved in cognitive control (i.e. frontal circuits) that may support the ability for predictive learning in MCI-AD.

Adaptive shape coding for perceptual decisions in the human brain.

In its search for neural codes, the field of visual neuroscience has uncovered neural representations that reflect the structure of stimuli of variable complexity from simple features to object categories. However, accumulating evidence suggests an adaptive neural code that is dynamically shaped by experience to support flexible and efficient perceptual decisions. Here, we review work showing that experience plays a critical role in molding midlevel visual representations for perceptual decisions. Combining behavioral and brain imaging measurements, we demonstrate that learning optimizes feature binding for object recognition in cluttered scenes, and tunes the neural representations of informative image parts to support efficient categorical judgements. Our findings indicate that similar learning mechanisms may mediate long-term optimization through development, tune the visual system to fundamental principles of feature binding, and optimize feature templates for perceptual decisions.

Mechanisms for extracting a signal from noise as revealed through the specificity and generality of task training.

Visual judgments critically depend on (1) the detection of meaningful items from cluttered backgrounds and (2) the discrimination of an item from highly similar alternatives. Learning and experience are known to facilitate these processes, but the specificity with which these processes operate is poorly understood. Here we use psychophysical measures of human participants to test learning in two types of commonly used tasks that target segmentation (signal-in-noise, or "coarse" tasks) versus the discrimination of highly similar items (feature difference, or "fine" tasks). First, we consider the processing of binocular disparity signals, examining performance on signal-in-noise and feature difference tasks after a period of training on one of these tasks. Second, we consider the generality of learning between different visual features, testing performance on both task types for displays defined by disparity, motion, or orientation. We show that training on a feature difference task also improves performance on signal-in-noise tasks, but only for the same visual feature. By contrast, training on a signal-in-noise task has limited benefits for fine judgments of the same feature but supports learning that generalizes to signal-in-noise tasks for other features. These findings indicate that commonly used signal-in-noise tasks require at least three distinct components: feature representations, signal-specific selection, and a generalized process that enhances segmentation. As such, there is clear potential to harness areas of commonality (both within and between cues) to improve impaired perceptual functions.

A dorsal visual route necessary for global form perception: evidence from neuropsychological fMRI.

Hierarchical models of visual processing assume that global pattern recognition is contingent on the progressive integration of local elements across larger spatial regions, operating from early through intermediate to higher-level cortical regions. Here, we present results from neuropsychological fMRI that refute such models. We report two patients, one with lesions to intermediate ventral regions and the other with damage around the intraparietal sulcus (IPS). The patient with ventral damage showed normal behavioral and BOLD responses to global Glass patterns. The patient with IPS damage was impaired in discriminating global patterns and showed a lack of significant responses to these patterns in intermediate visual regions spared by the lesion. However, this patient did show BOLD activity to translational patterns, where local element relations are important. These results suggest that activation of intermediate ventral regions is not necessary to code global patterns; instead global patterns are coded in a heterarchical fashion. High-level regions of dorsal cortex are necessary to generate global pattern coding in intermediate ventral regions; in contrast, local integration processes are not sufficient.

Spatial-temporal modelling of fMRI data through spatially regularized mixture of hidden process models.

Previous work investigated a range of spatio-temporal constraints for fMRI data analysis to provide robust detection of neural activation. We present a mixture-based method for the spatio-temporal modelling of fMRI data. This approach assumes that fMRI time series are generated by a probabilistic superposition of a small set of spatio-temporal prototypes (mixture components). Each prototype comprises a temporal model that explains fMRI signals on a single voxel and the model's "region of influence" through a spatial prior over the voxel space. As the key ingredient of our temporal model, the Hidden Process Model (HPM) framework proposed in Hutchinson et al. (2009) is adopted to infer the overlapping cognitive processes triggered by stimuli. Unlike the original HPM framework, we use a parametric model of Haemodynamic Response Function (HRF) so that biological constraints are naturally incorporated in the HRF estimation. The spatial priors are defined in terms of a parameterised distribution. Thus, the total number of parameters in the model does not depend on the number of voxels. The resulting model provides a conceptually principled and computationally efficient approach to identify spatio-temporal patterns of neural activation from fMRI data, in contrast to most conventional approaches in the literature focusing on the detection of spatial patterns. We first verify the proposed model in a controlled experimental setting using synthetic data. The model is further validated on real fMRI data obtained from a rapid event-related visual recognition experiment (Mayhew et al., 2012). Our model enables us to evaluate in a principled manner the variability of neural activations within individual regions of interest (ROIs). The results strongly suggest that, compared with occipitotemporal regions, the frontal ones are less homogeneous, requiring two HPM prototypes per region. Despite the rapid event-related experimental design, the model is capable of disentangling the perceptual judgement and motor response processes that are both activated in the frontal ROIs. Spatio-temporal heterogeneity in the frontal regions seems to be associated with diverse dynamic localizations of the two hidden processes in different subregions of frontal ROIs.