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1.  A common neural substrate for perceiving and knowing about color 
Neuropsychologia  2007;45(12):2802-2810.
Functional neuroimaging research has demonstrated that retrieving information about object-associated colors activates the left fusiform gyrus in posterior temporal cortex. Although regions near the fusiform have previously been implicated in color perception, it remains unclear whether color knowledge retrieval actually activates the color perception system. Evidence to this effect would be particularly strong if color perception cortex was activated by color knowledge retrieval triggered strictly with linguistic stimuli. To address this question, subjects performed two tasks while undergoing fMRI. First, subjects performed a property verification task using only words to assess conceptual knowledge. On each trial, subjects verified whether a named color or motor property was true of a named object (e.g., TAXI-yellow, HAIR-combed). Next, subjects performed a color perception task. A region of the left fusiform gyrus that was highly responsive during color perception also showed greater activity for retrieving color than motor property knowledge. These data provide the first evidence for a direct overlap in the neural bases of color perception and stored information about object-associated color, and they significantly add to accumulating evidence that conceptual knowledge is grounded in the brain’s modality-specific systems.
doi:10.1016/j.neuropsychologia.2007.05.002
PMCID: PMC3596878  PMID: 17575989
conceptual knowledge; fusiform gyrus; fMRI; color perception; property verification
2.  Tracking Problem Solving by Multivariate Pattern Analysis and Hidden Markov Model Algorithms 
Neuropsychologia  2011;50(4):487-498.
Multivariate pattern analysis can be combined with hidden Markov model algorithms to track the second-by-second thinking as people solve complex problems. Two applications of this methodology are illustrated with a data set taken from children as they interacted with an intelligent tutoring system for algebra. The first “mind reading” application involves using fMRI activity to track what students are doing as they solve a sequence of algebra problems. The methodology achieves considerable accuracy at determining both what problem-solving step the students are taking and whether they are performing that step correctly. The second “model discovery” application involves using statistical model evaluation to determine how many substates are involved in performing a step of algebraic problem solving. This research indicates that different steps involve different numbers of substates and these substates are associated with different fluency in algebra problem solving.
doi:10.1016/j.neuropsychologia.2011.07.025
PMCID: PMC3236279  PMID: 21820455
Problem solving; Multi-voxel pattern analysis; Hidden Markov Models; Intelligent Tutoring Systems; Model discovery
3.  Direction-Selective Patterns of Activity in Human Visual Cortex Suggest Common Neural Substrates for Different Types of Motion 
Neuropsychologia  2011;50(4):514-521.
A sense of motion can be elicited by the movement of both luminance- and texture-defined patterns, what is commonly referred to as first- and second-order, respectively. Although there are differences in the perception of these two classes of motion stimuli, including differences in temporal and spatial sensitivity, it is debated whether common or separate direction-selective mechanisms are responsible for processing these two types of motion. Here, we measured direction-selective responses to luminance- and texture-defined motion in the human visual cortex by using functional MRI (fMRI) in conjunction with multivariate pattern analysis (MVPA). We found evidence of direction selectivity for both types of motion in all early visual areas (V1, V2, V3, V3A, V4, and MT+), implying that none of these early visual areas is specialized for processing a specific type of motion. More importantly, linear classifiers trained with cortical activity patterns to one type of motion (e.g., first-order motion) could reliably classify the direction of motion defined by the other type (e.g., second-order motion). Our results suggest that the direction-selective mechanisms that respond to these two types of motion share similar spatial distributions in the early visual cortex, consistent with the possibility that common mechanisms are responsible for processing both types of motion.
doi:10.1016/j.neuropsychologia.2011.09.016
PMCID: PMC3272144  PMID: 21945806
second-order motion; direction selectivity; fMRI; decoding; multivoxel pattern analysis
4.  Decoding the internal focus of attention 
Neuropsychologia  2011;50(4):470-478.
The significance of the recent introduction to cognitive neuroscience of multivariate pattern analysis (MVPA) is that, unlike univariate approaches which are limited to identifying magnitudes of activity in localized parts of the brain, it affords the detection and characterization of patterns of activity distributed within and across multiple brain regions. This technique supports stronger inferences because it captures neural representations that have markedly higher selectivity than do univariate activation peaks. Recently, we used MVPA to assess the neural consequences of dissociating the internal focus of attention from short-term memory (STM), finding that the information represented in delay-period activity corresponds only to the former (Lewis-Peacock, Drysdale, Oberauer, & Postle, in press). Here we report several additional analyses of these data in which we directly compared the results generated by MVPA vs. those generated by univariate analyses. The sensitivity of MVPA to subtle variations in patterns of distributed brain activity revealed a novel insight: Although overall activity remains elevated in category-selective brain regions corresponding to unattended STM items, the multivariate patterns of activity within these regions reflect the representation of a different category, i.e., the one that is currently being attended to. In addition, MVPA was able to dissociate attended from unattended STM items in brain regions whose univariate activity did not appear to be sensitive to the task. These findings highlight the fallacy of the assumption of homogeneity of representation within putative category-selective regions. They affirm the view that neural representations in STM are highly distributed and overlapping, and they demonstrate the necessity of multivariate analysis for dissociating such representations.
doi:10.1016/j.neuropsychologia.2011.11.006
PMCID: PMC3288445  PMID: 22108440
memory; short-term memory; attention; fMRI; GLM; MVPA
5.  Neural responses to visual scenes reveals inconsistencies between fMRI adaptation and multivoxel pattern analysis 
Neuropsychologia  2011;50(4):530-543.
Human observers can recognize real-world visual scenes with great efficiency. Cortical regions such as the parahippocampal place area (PPA) and retrosplenial complex (RSC) have been implicated in scene recognition, but the specific representations supported by these regions are largely unknown. We used functional magnetic resonance imaging adaptation (fMRIa) and multi-voxel pattern analysis (MVPA) to explore this issue, focusing on whether the PPA and RSC represent scenes in terms of general categories, or as specific scenic exemplars. Subjects were scanned while viewing images drawn from 10 outdoor scene categories in two scan runs and images of 10 familiar landmarks from their home college campus in two scan runs. Analyses of multi-voxel patterns revealed that the PPA and RSC encoded both category and landmark information, with a slight advantage for landmark coding in RSC. fMRIa, on the other hand, revealed a very different picture: both PPA and RSC adapted when landmark information was repeated, but category adaptation was only observed in a small subregion of the left PPA. These inconsistencies between the MVPA and fMRIa data suggests that these two techniques interrogate different aspects of the neuronal code. We propose three hypotheses about the mechanisms that might underlie adaptation and multi-voxel signals.
doi:10.1016/j.neuropsychologia.2011.09.042
PMCID: PMC3288674  PMID: 22001314
Visual scene recognition; fMRI adaptation; multivoxel pattern analysis; parahippocampal cortex; retrosplenial cortex; spatial navigation
6.  Lexical and syntactic representations in the brain: An fMRI investigation with multi-voxel pattern analyses 
Neuropsychologia  2011;50(4):499-513.
Work in theoretical linguistics and psycholinguistics suggests that human linguistic knowledge forms a continuum between individual lexical items and abstract syntactic representations, with most linguistic representations falling between the two extremes and taking the form of lexical items stored together with the syntactic/semantic contexts in which they frequently occur. Neuroimaging evidence further suggests that no brain region is selectively sensitive to only lexical information or only syntactic information. Instead, all the key brain regions that support high-level linguistic processing have been implicated in both lexical and syntactic processing, suggesting that our linguistic knowledge is plausibly represented in a distributed fashion in these brain regions. Given this distributed nature of linguistic representations, multi-voxel pattern analyses (MVPAs) can help uncover important functional properties of the language system. In the current study we use MVPAs to ask two questions: 1) Do language brain regions differ in how robustly they represent lexical vs. syntactic information?; and 2) Do any of the language bran regions distinguish between “pure” lexical information (lists of words) and “pure” abstract syntactic information (jabberwocky sentences) in the pattern of activity? We show that lexical information is represented more robustly than syntactic information across many language regions (with no language region showing the opposite pattern), as evidenced by a better discrimination between conditions that differ along the lexical dimension (sentences vs. jabberwocky, and word lists vs. nonword lists) than between conditions that differ along the syntactic dimension (sentences vs. word lists, and jabberwocky vs. nonword lists). This result suggests that lexical information may play a more critical role than syntax in the representation of linguistic meaning. We also show that several language regions reliably discriminate between “pure” lexical information and “pure” abstract syntactic information in their patterns of neural activity.
doi:10.1016/j.neuropsychologia.2011.09.014
PMCID: PMC3292791  PMID: 21945850
7.  Multi-voxel patterns of visual category representation during episodic encoding are predictive of subsequent memory 
Neuropsychologia  2011;50(4):458-469.
Successful encoding of episodic memories is thought to depend on contributions from prefrontal and temporal lobe structures. Neural processes that contribute to successful encoding have been extensively explored through univariate analyses of neuroimaging data that compare mean activity levels elicited during the encoding of events that are subsequently remembered vs. those subsequently forgotten. Here, we applied pattern classification to fMRI data to assess the degree to which distributed patterns of activity within prefrontal and temporal lobe structures elicited during the encoding of word-image pairs were diagnostic of the visual category (Face or Scene) of the encoded image. We then assessed whether representation of category information was predictive of subsequent memory. Classification analyses indicated that temporal lobe structures contained information robustly diagnostic of visual category. Information in prefrontal cortex was less diagnostic of visual category, but was nonetheless associated with highly reliable classifier-based evidence for category representation. Critically, trials associated with greater classifier-based estimates of category representation in temporal and prefrontal regions were associated with a higher probability of subsequent remembering. Finally, consideration of trial-by-trial variance in classifier-based measures of category representation revealed positive correlations between prefrontal and temporal lobe representations, with the strength of these correlations varying as a function of the category of image being encoded. Together, these results indicate that multi-voxel representations of encoded information can provide unique insights into how visual experiences are transformed into episodic memories.
doi:10.1016/j.neuropsychologia.2011.09.002
PMCID: PMC3357999  PMID: 21925190
Episodic memory; Encoding; fMRI; Pattern classification; Category selectivity; Prefrontal cortex
8.  Computational advances towards linking BOLD and behavior 
Neuropsychologia  2011;50(4):435-446.
Traditionally, fMRI studies have focused on analyzing the mean response amplitude within a cortical area. However, the mean response is blind to many important patterns of cortical modulation, which severely limits the formulation and evaluation of linking hypotheses between neural activity, BOLD responses, and behavior. More recently, multivariate pattern classification analysis (MVPA) has been applied to fMRI data to evaluate the information content of spatially distributed activation patterns. This approach has been remarkably successful at detecting the presence of specific information in targeted brain regions, and provides an extremely flexible means of extracting that information without a precise generative model for the underlying neural activity. However, this flexibility comes at a cost: since MVPA relies on pooling information across voxels that are selective for many different stimulus attributes, it is difficult to infer how specific sub-sets of tuned neurons are modulated by an experimental manipulation. In contrast, recently developed encoding models can produce more precise estimates of feature-selective tuning functions, and can support the creation of explicit linking hypotheses between neural activity and behavior. Although these encoding models depend on strong – and often untested – assumptions about the response properties of underlying neural generators, they also provide a unique opportunity to evaluate population-level computational theories of perception and cognition that have previously been difficult to assess using either single-unit recording or conventional neuroimaging techniques.
doi:10.1016/j.neuropsychologia.2011.07.013
PMCID: PMC3384549  PMID: 21840553
9.  Tracking Cognitive Fluctuations with Multivoxel Pattern Time Course (MVPTC) Analysis 
Neuropsychologia  2011;50(4):479-486.
The posterior parietal cortex, including the medial superior parietal lobule (mSPL), becomes transiently more active during acts of cognitive control in a wide range of domains, including shifts of spatial and nonspatial visual attention, shifts between working memory representations, and shifts between categorization rules. Furthermore, spatial patterns of activity within mSPL, identified using multivoxel pattern analysis (MVPA), reliably distinguish between different acts of control. Here we describe a novel multivoxel pattern-based analysis that uses fluctuations in cognitive state over time to reveal inter-regional functional connectivity. First, we used MVPA to model patterns of activity in mSPL associated with shifting or maintaining spatial attention. We then computed a multivoxel pattern time course (MVPTC) that reflects, moment-by-moment, the degree to which the pattern of activity in mSPL more closely matches an attention-shift pattern or a sustained-attention pattern. We then entered the MVPTC as a regressor in a univariate (i.e., voxelwise) general linear model (GLM) to identify voxels whose BOLD activity covaried with the MVPTC. This analysis revealed several regions, including the striatum of the basal ganglia and bilateral middle frontal gyrus, whose activity was significantly correlated with the MVPTC in mSPL. For comparison, we also conducted a conventional functional connectivity analysis, entering the mean BOLD time course in mSPL as a regressor in a univariate GLM. The latter analysis revealed correlations in extensive regions of the frontal lobes but not in any subcortical area. The MVPTC analysis provides greater sensitivity (e.g., revealing the striatal-mSPL connectivity) and greater specificity (i.e., revealing more-focal clusters) than a conventional functional connectivity analysis. We discuss the broad applicability of MVPTC analysis to a variety of neuroimaging contexts.
doi:10.1016/j.neuropsychologia.2011.07.007
PMCID: PMC3425447  PMID: 21787796
10.  White Matter Integrity and Reaction Time Intraindividual Variability in Healthy Aging and Early-Stage Alzheimer Disease 
Neuropsychologia  2011;50(3):357-366.
Aging and early-stage Alzheimer disease (AD) have been shown to be associated with increased RT intraindividual variability (IIV, as reflected by the coefficient of variation) and an exaggeration of the slow tail of the RT distribution in attentional control tasks, based on ex-Gaussian analyses. The current study examined associations between white matter volume, IIV, and ex-Gaussian RT distribution parameters in cognitively normal aging and early-stage AD. Three RT attention tasks (Stroop, Simon, and a consonant-vowel odd-even switching task) in conjunction with MRI-based measures of cerebral and regional white matter volume were obtained in 133 cognitively normal and 33 early-stage AD individuals. Larger volumes were associated with less IIV and less slowing in the tail of the RT distribution, and larger cerebral and inferior parietal white matter volumes were associated with faster modal reaction time. Collectively, these results support a role of white matter integrity in IIV and distributional skewing, and are consistent with the hypothesis that IIV and RT distributional skewing are sensitive to breakdowns in executive control processes in normal and pathological aging.
doi:10.1016/j.neuropsychologia.2011.11.024
PMCID: PMC3302689  PMID: 22172547
mu; sigma; tau; coefficient of variation; default network; attentional control
11.  Underlying Cause(s) of Letter Perseveration Errors 
Neuropsychologia  2011;50(2):305-318.
Perseverations, the inappropriate intrusion of elements from a previous response into a current response, are commonly observed in individuals with acquired deficits. This study specifically investigates the contribution of failure-to activate and failure-to-inhibit deficit(s) in the generation of letter perseveration errors in acquired dysgraphia. We provide evidence from the performance 12 dysgraphic individuals indicating that a failure to activate graphemes for a target word gives rise to letter perseveration errors. In addition, we also provide evidence that, in some individuals, a failure-to-inhibit deficit may also contribute to the production of perseveration errors.
doi:10.1016/j.neuropsychologia.2011.12.001
PMCID: PMC3259193  PMID: 22178232
letter perseveration errors; dysgraphia; spelling; inhibition
12.  Ventromedial prefrontal cortex damage does not impair the development and use of common ground in social interaction: Implications for cognitive theory of mind 
Neuropsychologia  2011;50(1):145-152.
During conversation, interactants draw on their shared communicative context and history (“common ground”) to help decide what to say next, tailoring utterances based on their knowledge of what the listener knows. The use of common ground draws on an understanding of the thoughts and feelings of others to create and update a model of what is known by the other person, employing cognitive processes such as theory of mind. We tested the hypothesis that the ventromedial prefrontal cortex (vmPFC), a neural region involved in processing and interpreting social and emotional information, would be critical for the development and use of common ground. We studied seven patients with bilateral vmPFC damage and seven age-, sex-, and education-matched healthy comparison participants, each interacting with a familiar partner. Across 24 trials, participants verbally directed their partners how to arrange a set of 12 abstract tangram cards. Our hypothesis was not supported: the vmPFC and healthy comparison groups showed similar development and use of common ground, evident in reduction in time and words used to describe the cards, similar increases in the use of definite references (e.g., the horse), and comparable use of verbal play (playful language) in their interactions. These results argue against the idea that the vmPFC is critical for the development and use of common ground in social interaction. We propose that a cognitive and neuroanatomical bifurcation in theory of mind processes may explain this outcome. The vmPFC may be important for affective theory of mind (the ability to understand another’s feelings); however, the development and use of common ground in social interaction may place higher demands on the ability to understand another’s knowledge, or cognitive theory of mind, which may not require the vmPFC.
doi:10.1016/j.neuropsychologia.2011.11.012
PMCID: PMC3261371  PMID: 22120006
ventromedial prefrontal cortex; common ground; discourse; collaborative referencing
13.  Chromaticity of color perception and object color knowledge 
Neuropsychologia  2011;50(2):327-333.
Sensorimotor theories of semantic memory require overlap between conceptual and perceptual representations. One source of evidence for such overlap comes from neuroimaging reports of co-activation during memory retrieval and perception; for example, regions involved in color perception (i.e., regions that respond more to colored than grayscale stimuli) are activated by retrieval of object color. One unanswered question from these studies is whether distinctions that are observed during perception are likewise observed during memory retrieval. That is, are regions defined by a chromaticity effect in perception similarly modulated by the chromaticity of remembered objects (e.g., lemons more than coal)? Subjects performed color perception and color retrieval tasks while undergoing fMRI. We observed increased activation during both perception and memory retrieval of chromatic compared to achromatic stimuli in overlapping areas of the left lingual gyrus, but not in dorsal or anterior regions activated during color perception. These results support sensorimotor theories but suggest important distinctions within the conceptual system.
doi:10.1016/j.neuropsychologia.2011.12.003
PMCID: PMC3261614  PMID: 22192637
fMRI; semantic memory; perception; color
14.  A “concrete view” of aging: Event related potentials reveal age-related changes in basic integrative processes in language 
Neuropsychologia  2011;50(1):26-35.
Normal aging is accompanied by changes in both structural and functional cerebral organization. Although verbal knowledge seems to be relatively stable across the lifespan, there are age-related changes in the rapid use of that knowledge during on-line language processing. In particular, aging has been linked to reduce effectiveness in preparing for upcoming words and building an integrated sentence-level representation. The current study assessed whether such age-related changes extend even to much simpler language units, such as modification relations between a centrally presented adjective and a lateralized noun. Adjectives were used to elicit concrete and abstract meanings of the same, polysemous lexical items (e.g., “green book” vs. “interesting book”). Consistent with findings that lexical information is preserved with age, older adults, like younger adults, exhibited concreteness effects at the adjectives, with more negative responses to concrete adjectives over posterior (300–500 ms; N400) and frontal (300–900 ms) channels. However, at the noun, younger adults exhibited concreteness-based predictability effects linked to left hemisphere processing and imagery effects linked to right hemisphere processing, contingent on whether the adjectives and nouns formed a cohesive conceptual unit. In contrast, older adults showed neither effect, suggesting that they were less able to rapidly link the adjective–noun meaning to form an integrated conceptual representation. Age-related changes in language processing may thus be more pervasive than previously realized.
doi:10.1016/j.neuropsychologia.2011.10.018
PMCID: PMC3405910  PMID: 22044648
Aging; Language processing; Laterality; Concreteness effects; Event-related potentials; N400; Frontal imagery effects
15.  It does not look odd to me: Perceptual impairments and eye movements in amnesic patients with medial temporal lobe damage 
Neuropsychologia  2013;51(1):168-180.
Studies of people with memory impairments have shown that a specific set of brain structures in the medial temporal lobe (MTL) is vital for memory function. However, whether these structures have a role outside of memory remains contentious. Recent studies of amnesic patients with damage to two structures within the MTL, the hippocampus and the perirhinal cortex, indicated that these patients also performed poorly on perceptual tasks. More specifically, they performed worse than controls when discriminating between objects, faces and scenes with overlapping features. In order to investigate whether these perceptual deficits are reflected in their viewing strategies, we tested a group of amnesic patients with MTL damage that included the hippocampus and perirhinal cortex on a series of oddity discrimination tasks in which they had to select an odd item from a visual array. Participants' eye movements were monitored throughout the experiment. Results revealed that patients were impaired on tasks that required them to discriminate between items that shared many features, and tasks that required processing items from different viewpoints. An analysis of their eye movements revealed that they exhibited a similar viewing pattern as controls: they fixated more on the target item on trials answered correctly, but not on trials answered incorrectly. In addition, their impaired performance was not explained by an abnormal viewing-strategy that assessed their use of working memory. These results suggest that the perceptual deficits in the MTL patients are not a consequence of abnormal viewing patterns of the objects and scenes, but instead, could involve an inability to bind information gathered from several fixations into a cohesive percept. These data also support the view that MTL structures are important not only for long-term memory, but are also involved in perceptual tasks.
Highlights
► MTL patients performed worse than controls on perceptual discrimination tasks. ► Eye movement patterns of MTL patients were not different than those of controls. ► Deficits in MTL patients are not a consequence of impaired working memory. ► MTL structures are important not only for declarative memory, but also for perception.
doi:10.1016/j.neuropsychologia.2012.11.003
PMCID: PMC3557385  PMID: 23154380
Medial temporal lobe; Amnesia; Perception; Memory; Eye movements; Perirhinal cortex
16.  Time, action and psychosis: Using subjective time to investigate the effects of ketamine on sense of agency 
Neuropsychologia  2013;51(2):377-384.
Sense of agency refers to the experience of initiating and controlling actions in order to influence events in the outside world. A disturbed sense of agency is found in certain psychiatric and neurological disorders, most notably schizophrenia. Sense of agency is associated with a subjective compression of time: actions and their outcomes are perceived as bound together in time. This is known as ‘intentional binding’ and, in healthy adults, depends partly on advance prediction of action outcomes. Notably, this predictive contribution is disrupted in patients with schizophrenia. In the present study we aimed to characterise the psychotomimetic effect of ketamine, a drug model for psychosis, on the predictive contribution to intentional binding. It was shown that ketamine produced a disruption that closely resembled previous data from patients in the early, prodromal, stage of schizophrenic illness. These results are discussed in terms of established models of delusion formation in schizophrenia. The link between time and agency, more generally, is also considered.
Highlights
► Voluntary actions and outcomes are bound together in subjective time. ► This binding depends partly on advance prediction, something that is disrupted in schizophrenia. ► Administering ketamine, a drug model of psychosis, to healthy adults disrupted prediction. ► This effect closely resembled previous data from prodromal patients. ► Results are discussed in terms of (a) models of delusion formation and (b) the relationship between time and agency.
doi:10.1016/j.neuropsychologia.2012.07.005
PMCID: PMC3562439  PMID: 22813429
Sense of agency; Time; Ketamine; Consciousness; Schizophrenia; Prodrome; Prodromal; Volition; Action
17.  Reading about the Actions of Others: Biological Motion Imagery and Action Congruency Influence Brain Activity 
Neuropsychologia  2010;48(6):1607-1615.
Prior neuroimaging research has implicated regions within and near the posterior superior temporal sulcus (pSTS) in the visual processing of biological motion and of the intentions implied by specific movements. However, it is unknown whether this region is engaged during the processing of human motion at a conceptual level, such as during story comprehension. Here, we obtained functional magnetic resonance images from subjects reading brief stories that described a human character’s background and then concluded with an action or decision made by the character. Half of the stories contained incidental descriptions of biological motion (such as the character’s walking or grasping) while the remaining half did not. As a second factor, the final action of the story was either congruent or incongruent with the character’s background and implied goals and intentions. Stories that contained biological motion strongly activated the pSTS bilaterally, along with ventral temporal areas, premotor cortex, left motor cortex, and the precuneus. Active regions of pSTS in individual subjects closely overlapped with regions identified with a separate biological motion localizer (point-light display) task. Reading incongruent versus congruent stories activated dorsal anterior cingulate cortex and bilateral anterior insula. These results support the hypothesis that reading can engage higher visual cortex in a content-specific manner, and suggest that the presence of biological motion should be controlled as a potential confound in fMRI studies using story comprehension tasks.
doi:10.1016/j.neuropsychologia.2010.01.028
PMCID: PMC3515847  PMID: 20138900
biological motion; intention; reading; story comprehension; superior temporal sulcus
18.  Face Processing without Awareness in the Right Fusiform Gyrus 
Neuropsychologia  2007;45(13):3087-3091.
We investigated brain activity evoked by faces which were not consciously perceived by subjects. Subdural electrophysiological recordings and functional neuroimaging studies have each demonstrated face-specific processing in the fusiform gyrus (FFG) of humans. Using pattern masks, a stimulus can be presented but not consciously perceived, and thus can be used to assay obligatory or automatic processes. Here, using event-related functional magnetic resonance imaging and pattern masking, we observed that masked faces but not masked objects activated the right FFG. Other regions activated by consciously perceived unmasked faces were not activated when faces were masked. These data provide strong evidence for an automatic face processing region in the right FFG.
doi:10.1016/j.neuropsychologia.2007.05.020
PMCID: PMC3514457  PMID: 17643452
19.  Age-related changes in the attentional control of visual cortex: A selective problem in the left visual hemifield 
Neuropsychologia  2011;49(7):1670-1678.
To what extent does our visual-spatial attention change with age? In this regard, it has been previously reported that relative to young controls, seniors show delays in attention-related sensory facilitation. Given this finding, our study was designed to examine two key questions regarding age-related changes in the effect of spatial attention on sensory-evoked responses in visual cortex –– are there visual field differences in the age-related impairments in sensory processing, and do these impairments co-occur with changes in the executive control signals associated with visual spatial orienting? Therefore, our study examined both attentional control and attentional facilitation in seniors (aged 66 to 74 years) and young adults (aged 18 to 25 years) using a canonical spatial orienting task. Participants responded to attended and unattended peripheral targets while we recorded event-related potentials (ERPs) to both targets and attention-directing spatial cues. We found that not only were sensory-evoked responses delayed in seniors specifically for unattended events in the left visual field as measured via latency shifts in the lateral occipital P1 elicited by visual targets, but seniors also showed amplitude reductions in the anterior directing attentional negativity (ADAN) component elicited by cues directing attention to the left visual field. At the same time, seniors also had significantly higher error rates for targets presented in the left vs. right visual field. Taken together, our data thus converge on the conclusion that age-related changes in visual spatial attention involve both sensory-level and executive attentional control processes, and that these effects appear to be strongly associated with the left visual field.
doi:10.1016/j.neuropsychologia.2011.02.040
PMCID: PMC3514549  PMID: 21356222 CAMSID: cams2320
Aging; Visual-spatial attention; Attentional control; Event-related potentials
20.  Degree of Bilingualism Predicts Age of Diagnosis of Alzheimer’s Disease in Low-Education but not in Highly-Educated Hispanics 
Neuropsychologia  2011;49(14):3826-3830.
The current study investigated the relationship between bilingual language proficiency and onset of probable Alzheimer’s disease (AD) in 44 Spanish-English bilinguals at the UCSD Alzheimer’s Disease Research Center. Degree of bilingualism along a continuum was measured using Boston Naming Test (BNT) scores in each language. Higher degrees of bilingualism were associated with increasingly later age-of-diagnosis (and age of onset of symptoms), but this effect was driven by participants with low education level (a significant interaction between years of education and bilingualism) most of whom (73%) were also Spanish-dominant. Additionally, only objective measures (i.e., BNT scores), not self-reported degree of bilingualism, predicted age-of-diagnosis even though objective and self-reported measures were significantly correlated. These findings establish a specific connection between knowledge of two languages and delay of AD onset, and demonstrate that bilingual effects can be obscured by interactions between education and bilingualism, and by failure to obtain objective measures of bilingualism. More generally, these data support analogies between the effects of bilingualism and “cognitive reserve” and suggest an upper limit on the extent to which reserve can function to delay dementia.
doi:10.1016/j.neuropsychologia.2011.09.041
PMCID: PMC3223277  PMID: 22001315
21.  Cortical regions recruited for complex active-learning strategies and action planning exhibit rapid reactivation during memory retrieval 
Neuropsychologia  2011;49(14):3956-3966.
Memory retrieval can involve activity in the same sensory cortical regions involved in perception of the original event, and this neural “reactivation” has been suggested as an important mechanism of memory retrieval. However, it is still unclear if fragments of experience other than sensory information are retained and later reactivated during retrieval. For example, learning in non-laboratory settings generally involves active exploration of memoranda, thus requiring the generation of action plans for behavior and the use of strategies deployed to improve subsequent memory performance. Is information pertaining to action planning and strategic processing retained and reactivated during retrieval? To address this question, we compared ERP correlates of memory retrieval for objects that had been studied in an active manner involving action planning and strategic processing to those for objects that had been studied passively. Memory performance was superior for actively studied objects, and unique ERP retrieval correlates for these objects were identified when subjects remembered the specific spatial locations at which objects were studied. Early-onset frontal shifts in ERP correlates of retrieval were noted for these objects, which parallel the recruitment of frontal cortex during learning object locations previously identified using fMRI with the same paradigm. Notably, ERPs during recall for items studied with a specific viewing strategy localized to the same supplementary motor cortex region previously identified with fMRI when this strategy was implemented during study, suggesting rapid reactivation of regions directly involved in strategic action planning. Collectively, these results implicate neural populations involved in learning in important retrieval functions, even for those populations involved in strategic control and action planning. Notably, these episodic features are not generally reported during recollective experiences, suggesting that reactivation is a more general property of memory retrieval that extends beyond those fragments of perceptual information that might be needed to re-live the past.
doi:10.1016/j.neuropsychologia.2011.10.012
PMCID: PMC3223278  PMID: 22023912
active learning; passive learning; volitional control; ERP; memory retrieval; content specificity
22.  Structural Correlates of Prospective Memory 
Neuropsychologia  2011;49(14):3795-3800.
Prospective memory (PM) includes the encoding and maintenance of an intention, and the retrieval and execution of this intention at the proper moment in the future. The present study expands upon previous behavioral, electrophysiological, and functional work by examining the association between grey matter volume and PM. Estimates of grey matter volume in theoretically relevant regions of interest (prefrontal, parietal, and medial temporal) were obtained in conjunction with performance on two PM tasks in a sample of 39 cognitively normal and very mildly demented older adults. The first PM task, termed focal in the literature, is supported by spontaneous retrieval of the PM intention whereas the second, termed non-focal, relies on strategic monitoring processes for successful intention retrieval. A positive relationship was observed between medial temporal volume and accuracy on the focal PM task. An examination of medial temporal lobe subregions revealed that this relationship was strongest for the hippocampus, which is considered to support spontaneous memory retrieval. There were no significant structure-behavior associations for the non-focal PM task. These novel results confirm a relationship between behavior and underlying brain structure proposed by the multiprocess theory of PM, and extend findings on cognitive correlates of medial temporal lobe integrity.
doi:10.1016/j.neuropsychologia.2011.09.035
PMCID: PMC3244302  PMID: 21982698
prefrontal cortex; hippocampus; structural MRI; aging; episodic memory
23.  FREEZING OF GAIT IS ASSOCIATED WITH A MISMATCH BETWEEN MOTOR IMAGERY AND MOTOR EXECUTION IN NARROW DOORWAYS, NOT WITH FAILURE TO JUDGE DOORWAY PASSABILITY 
Neuropsychologia  2011;49(14):3981-3988.
Background
Many patients with Parkinson’s disease (PD) develop freezing of gait (FoG), which may manifest as a hesitation or “getting stuck” when they attempt to pass through a doorway. In two experiments, we asked whether FoG is associated with (1) a deficit in internal representation of one’s body size with respect to a doorway and (2) a mismatch between imagined and actual walking times when passing through a doorway.
Method
24 subjects with PD (11 with and 13 without FoG) and 10 control subjects of similar age completed two experiments. In the Passability experiment, subjects judged the passability of doorways with different apertures scaled to their body widths. We compared passability estimates across groups. In the Imagery experiment, subjects timed themselves while: (1) imagining walking through doorways of different apertures and from different distances, and (2) actually walking in the same conditions they had just imagined. We compared imagined and actual walking durations across groups and conditions.
Results
In the Passability experiment, the estimated just-passable doorway was wider, relative to body width, in PD subjects than in control subjects, but there was no difference between PD subjects with and without FoG. In the Imagery experiment, subjects in all groups walked more slowly through narrow doorways than though wide doorways, and subjects with FoG walked much more slowly through the narrowest doorways. PD subjects with FoG showed a large discrepancy between actual and imagined time to pass through narrow doorways, unlike PD subjects without FoG and control subjects.
Conclusions
The equivalent passability judgments in PD subjects with and without FoG indicate that FoG is not specifically associated with a deficit in ability to internally represent space with reference to body size. However, the large difference in duration between actual and imagined walking through narrow doorways in subjects with FoG suggests that PD subjects with FoG did not know how much they would slow down to pass through narrow doorways. The observed discrepancy between imagined and actual walking times may point to a specific problem that contributes to the occurrence of FoG. These results also suggest that caution should be used when interpreting brain imaging results from locomotor imagery studies with PD subjects who have FoG.
doi:10.1016/j.neuropsychologia.2011.10.014
PMCID: PMC3260879  PMID: 22027173
Parkinson’s disease; freezing of gait; motor imagery; body schema; internal representation; affordance
24.  EEG Correlates of Categorical and Graded Face Perception 
Neuropsychologia  2011;49(14):3847-3853.
Face perception is a critical social ability and identifying its neural correlates is important from both basic and applied perspectives. In EEG recordings, faces elicit a distinct electrophysiological signature, the N170, which has a larger amplitude and shorter latency in response to faces compared to other objects. However, determining the face specificity of any neural marker for face perception hinges on finding an appropriate control stimulus. We used a novel stimulus set consisting of 300 images that spanned a continuum between random patches of natural scenes and genuine faces, in order to explore the selectivity of face-sensitive ERP responses with a model-based parametric stimulus set. Critically, our database contained “false alarm” images that were misclassified as faces a computational face-detection system and varied in their image-level similarity to real faces. High-density (128-channel) event-related potentials (ERPs) were recorded while 23 adult subjects viewed all 300 images in random order, and determined whether each image was a face or non-face. The goal of our analyses was to determine the extent to which a gradient of sensitivity to face-like structure was evident in the ERP signal. Traditional waveform analyses revealed that the N170 component over occipitotemporal electrodes was larger in amplitude for faces compared to all non-faces, even those that were high in image similarity to faces, suggesting strict selectivity for veridical face stimuli. By contrast, single-trial classification of the entire waveform measured at the same sensors revealed that misclassifications of non-face patterns as faces increased with image-level similarity to faces. These results suggest that individual components may exhibit steep selectivity, but integration of multiple waveform features may afford graded information regarding stimulus appearance.
doi:10.1016/j.neuropsychologia.2011.09.046
PMCID: PMC3290448  PMID: 22001852
25.  Reading without the left ventral occipito-temporal cortex 
Neuropsychologia  2012;50-360(14):3621-3635.
The left ventral occipito-temporal cortex (LvOT) is thought to be essential for the rapid parallel letter processing that is required for skilled reading. Here we investigate whether rapid written word identification in skilled readers can be supported by neural pathways that do not involve LvOT. Hypotheses were derived from a stroke patient who acquired dyslexia following extensive LvOT damage. The patient followed a reading trajectory typical of that associated with pure alexia, re-gaining the ability to read aloud many words with declining performance as the length of words increased. Using functional MRI and dynamic causal modelling (DCM), we found that, when short (three to five letter) familiar words were read successfully, visual inputs to the patient’s occipital cortex were connected to left motor and premotor regions via activity in a central part of the left superior temporal sulcus (STS). The patient analysis therefore implied a left hemisphere “reading-without-LvOT” pathway that involved STS. We then investigated whether the same reading-without-LvOT pathway could be identified in 29 skilled readers and whether there was inter-subject variability in the degree to which skilled reading engaged LvOT. We found that functional connectivity in the reading-without-LvOT pathway was strongest in individuals who had the weakest functional connectivity in the LvOT pathway. This observation validates the findings of our patient’s case study. Our findings highlight the contribution of a left hemisphere reading pathway that is activated during the rapid identification of short familiar written words, particularly when LvOT is not involved. Preservation and use of this pathway may explain how patients are still able to read short words accurately when LvOT has been damaged.
Highlights
► Word reading can succeed after damage to the left occipito-temporal cortex. ► This is enabled by an alternative pathway via the left superior temporal sulcus. ► Connectivity analysis demonstrated the existence of this pathway in normal readers. ► We hypothesise that this pathway integrates semantics with phonology. ► Our work stresses the importance of mapping alternative degenerate reading pathways.
doi:10.1016/j.neuropsychologia.2012.09.030
PMCID: PMC3524457  PMID: 23017598
Effective connectivity; Alexia; Recovery; Degeneracy; Word reading pathways; Functional MRI

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