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1.  Famous face identification in temporal lobe epilepsy: Support for a multimodal integration model of semantic memory 
This study aims to demonstrate that the left and right anterior temporal lobes (ATLs) perform critical but unique roles in famous face identification, with damage to either leading to differing deficit patterns reflecting decreased access to lexical or semantic concepts but not their degradation. Famous face identification was studied in 22 presurgical and 14 postsurgical temporal lobe epilepsy (TLE) patients and 20 healthy comparison subjects using free recall and multiple choice (MC) paradigms. Right TLE patients exhibited presurgical deficits in famous face recognition, and postsurgical deficits in both famous face recognition and familiarity judgments. However, they did not exhibit any problems with naming before or after surgery. In contrast, left TLE patients demonstrated both pre-and postsurgical deficits in famous face naming but no significant deficits in recognition or familiarity. Double dissociations in performance between groups were alleviated by altering task demands. Postsurgical right TLE patients provided with MC options correctly identified greater than 70% of famous faces they initially rated as unfamiliar. Left TLE patients accurately chose the name for nearly all famous faces they recognized (based on their verbal description) but initially failed to name, although they tended to rapidly lose access to this name. We believe alterations in task demands activate alternative routes to semantic and lexical networks, demonstrating that unique pathways to such stored information exist, and suggesting a different role for each ATL in identifying visually presented famous faces. The right ATL appears to play a fundamental role in accessing semantic information from a visual route, with the left ATL serving to link semantic information to the language system to produce a specific name. These findings challenge several assumptions underlying amodal models of semantic memory, and provide support for the integrated multimodal theories of semantic memory and a distributed representation of concepts.
PMCID: PMC3679345  PMID: 23040175
Famous face naming and recognition; Epilepsy surgery; Models of semantic memory
2.  Differential Contribution of Right and Left Temporo-Occipital and Anterior Temporal Lesions to Face Recognition Disorders 
In the study of prosopagnosia, several issues (such as the specific or non-specific manifestations of prosopagnosia, the unitary or non-unitary nature of this syndrome and the mechanisms underlying face recognition disorders) are still controversial. Two main sources of variance partially accounting for these controversies could be the qualitative differences between the face recognition disorders observed in patients with prevalent lesions of the right or left hemisphere and in those with lesions encroaching upon the temporo-occipital (TO) or the (right) anterior temporal cortex. Results of our review seem to confirm these suggestions. Indeed, they show that (a) the most specific forms of prosopagnosia are due to lesions of a right posterior network including the occipital face area and the fusiform face area, whereas (b) the face identification defects observed in patients with left TO lesions seem due to a semantic defect impeding access to person-specific semantic information from the visual modality. Furthermore, face recognition defects resulting from right anterior temporal lesions can usually be considered as part of a multimodal people recognition disorder. The implications of our review are, therefore, the following: (1) to consider the components of visual agnosia often observed in prosopagnosic patients with bilateral TO lesions as part of a semantic defect, resulting from left-sided lesions (and not from prosopagnosia proper); (2) to systematically investigate voice recognition disorders in patients with right anterior temporal lesions to determine whether the face recognition defect should be considered a form of “associative prosopagnosia” or a form of the “multimodal people recognition disorder.”
PMCID: PMC3108284  PMID: 21687793
prosopagnosia; multimodal people recognition disorders; unilateral lesions; visual object agnosia; familiarity feelings; configurational processing
3.  The anatomic correlate of prosopagnosia in semantic dementia 
Neurology  2008;71(20):1628-1633.
To determine the anatomic correlate of prosopagnosia in subjects with semantic dementia.
We identified all subjects who had been evaluated by an experienced behavioral neurologist, met criteria for semantic dementia, and had completed a volumetric head MRI scan. In all subjects, historical records were reviewed and subjects in which the presence (n = 15) or absence (n = 12) of prosopagnosia was specifically ascertained by the neurologist were identified. Voxel-based morphometry was used to assess patterns of gray matter atrophy in subjects with and without prosopagnosia compared to a group of age and gender-matched normal controls, and compared to each other.
Compared to controls, both groups showed prominent temporal lobe volume loss. Those with prosopagnosia showed bilateral loss but with greater involvement of the right temporal lobe, while those without prosopagnosia showed predominantly left anterior temporal lobe loss. On direct comparison, subjects with prosopagnosia showed greater loss predominantly in the right amygdala, hippocampus, fusiform gyrus, and anterior temporal pole than those without prosopagnosia. No regions were involved to a greater degree in those without prosopagnosia, compared to those with prosopagnosia.
Prosopagnosia appears to be associated with volume loss of the right temporal lobe, particularly medial temporal lobe, fusiform gyrus, and anterior temporal pole, although in semantic dementia it is occurring in the context of bilateral temporal lobe volume loss.
= Alzheimer’s Disease Patient Registry;
= Alzheimer’s Disease Research Center;
= Boston Naming Test;
= Clinical Dementia Rating score sum of boxes;
= discrete cosine transformation;
= Dementia Rating Scale;
= frontotemporal lobar degeneration with ubiquitin-only-immunoreactive changes;
= full-width at half-maximum;
= gray matter;
= Mini-Mental State Examination;
= Montreal Neurological Institute;
= spoiled gradient echo;
= Short Test of Mental Status;
= voxel-based morphometry;
= white matter.
PMCID: PMC2676968  PMID: 19001253
4.  Cognitive and Anatomical Underpinnings of the Conceptual Knowledge for Common Objects and Familiar People: A Repetitive Transcranial Magnetic Stimulation Study 
PLoS ONE  2013;8(5):e64596.
Several studies have addressed the issue of how knowledge of common objects is organized in the brain, whereas the cognitive and anatomical underpinnings of familiar people knowledge have been less explored. Here we applied repetitive transcranial magnetic stimulation (rTMS) over the left and right temporal poles before asking healthy individuals to perform a speeded word-to-picture matching task using familiar people and common objects as stimuli. We manipulated two widely used semantic variables, namely the semantic distance and the familiarity of stimuli, to assess whether the semantic organization of familiar people knowledge is similar to that of common objects. For both objects and faces we reliably found semantic distance and familiarity effects, with less accurate and slower responses for stimulus pairs that were more closely related and less familiar. However, the effects of semantic variables differed across categories, with semantic distance effects larger for objects and familiarity effects larger for faces, suggesting that objects and faces might share a partially comparable organization of their semantic representations. The application of rTMS to the left temporal pole modulated, for both categories, semantic distance, but not familiarity effects, revealing that accessing object and face concepts might rely on overlapping processes within left anterior temporal regions. Crucially, rTMS of the left temporal pole affected only the recognition of pairs of stimuli that could be discriminated at specific levels of categorization (e.g., two kitchen tools or two famous persons), with no effect for discriminations at either superordinate or individual levels. Conversely, rTMS of the right temporal pole induced an overall slowing of reaction times that positively correlated with the visual similarity of the stimuli, suggesting a more perceptual rather than semantic role of the right anterior temporal regions. Results are discussed in the light of current models of face and object semantic representations in the brain.
PMCID: PMC3660352  PMID: 23704999
5.  Neuroanatomical correlates of visual car expertise 
Neuroimage  2012;62-334(1):147-153.
Expertise in non-visual domains such as musical performance is associated with differences in gray matter volume of particular regions of the human brain. Whether this is also the case for expertise in visual object recognition is unknown. Here we tested whether individual variability in the ability to recognize car models, from novice performance to high level of expertise, is associated with specific structural changes in gray matter volume. We found that inter-individual variability in expertise with cars was significantly and selectively correlated with gray matter volume in prefrontal cortex. Inter-individual differences in the recognition of airplanes, that none of the participants had expertise with, were correlated with structural variability of regions bordering the visual cortex. These results highlight the role of prefrontal regions outside the visual cortex in accessing and processing visual knowledge about objects from the domain of expertise and suggest that expertise in visual object recognition may entail structural changes in regions associated with semantic knowledge.
► We examined neuroanatomical correlates of expertise in car recognition. ► The neural structure of prefrontal regions predicted expertise in car recognition. ► No structural correlates within ventral occipital cortex were found for car expertise.
PMCID: PMC3387385  PMID: 22587898
Visual expertise; VBM; PFC
6.  The Early Time Course of Compensatory Face Processing in Congenital Prosopagnosia 
PLoS ONE  2010;5(7):e11482.
Prosopagnosia is a selective deficit in facial identification which can be either acquired, (e.g., after brain damage), or present from birth (congenital). The face recognition deficit in prosopagnosia is characterized by worse accuracy, longer reaction times, more dispersed gaze behavior and a strong reliance on featural processing.
Methods/Principal Findings
We introduce a conceptual model of an apperceptive/associative type of congenital prosopagnosia where a deficit in holistic processing is compensated by a serial inspection of isolated, informative features. Based on the model proposed we investigated performance differences in different face and shoe identification tasks between a group of 16 participants with congenital prosopagnosia and a group of 36 age-matched controls. Given enough training and unlimited stimulus presentation prosopagnosics achieved normal face identification accuracy evincing longer reaction times. The latter increase was paralleled by an equally-sized increase in stimulus presentation times needed achieve an accuracy of 80%. When the inspection time of stimuli was limited (50ms to 750ms), prosopagnosics only showed worse accuracy but no difference in reaction time. Tested for the ability to generalize from frontal to rotated views, prosopagnosics performed worse than controls across all rotation angles but the magnitude of the deficit didn't change with increasing rotation. All group differences in accuracy, reaction or presentation times were selective to face stimuli and didn't extend to shoes.
Our study provides a characterization of congenital prosopagnosia in terms of early processing differences. More specifically, compensatory processing in congenital prosopagnosia requires an inspection of faces that is sufficiently long to allow for sequential focusing on informative features. This characterization of dysfunctional processing in prosopagnosia further emphasizes fast and holistic information encoding as two defining characteristics of normal face processing.
PMCID: PMC2908115  PMID: 20657764
7.  Episodic memory: insights from semantic dementia. 
Semantic dementia, also known as the temporal lobe variant of fronto-temporal dementia, results in a progressive yet relatively pure loss of semantic knowledge about words, objects and people, and is associated with asymmetric, focal atrophy of the antero-lateral temporal lobes. Semantic dementia provides a unique opportunity to study the organization of long-term memory particularly since initial observations suggested sparing of episodic memory. Recent studies reveal, however, a more complex but theoretically revealing pattern. On tests of autobiographical memory, patients with semantic dementia show a 'reverse step function' with sparing of recall of events from the most recent 2 to 5 years but impairment on more distant life periods. Anterograde recognition memory for visual materials is extremely well preserved, except in the most deteriorated cases, although performance is heavily reliant upon perceptual information about the studied stimuli, particularly for items that are no longer known by the subjects. On tests of verbal anterograde memory such as word learning, performance is typically poor even for words which are 'known' to the patients. A source discrimination experiment, designed to evaluate familiarity and recollection-based anterograde memory processes, found that patients with semantic dementia showed good item detection, although recollection of source was sometimes impaired. Semantic knowledge about studied items and measures of item detection and source discrimination were largely independent. The implications of these findings for models of long-term memory are discussed. The results support the concept that episodic memory, or at least the recall of temporally specific autobiographical experiences, draws upon a number of separable memory processes, some of which can function independently of semantic knowledge.
PMCID: PMC1088525  PMID: 11571033
8.  A cortical pathway to olfactory naming: evidence from primary progressive aphasia 
Brain  2013;136(4):1245-1259.
It is notoriously difficult to name odours. Without the benefit of non-olfactory information, even common household smells elude our ability to name them. The neuroscientific basis for this olfactory language ‘deficit’ is poorly understood, and even basic models to explain how odour inputs gain access to transmodal representations required for naming have not been put forward. This study used patients with primary progressive aphasia, a clinical dementia syndrome characterized by primary deficits in language, to investigate the interactions between olfactory inputs and lexical access by assessing behavioural performance of olfactory knowledge and its relationship to brain atrophy. We specifically hypothesized that the temporal pole would play a key role in linking odour object representations to transmodal networks, given its anatomical proximity to olfactory and visual object processing areas. Behaviourally, patients with primary progressive aphasia with non-semantic subtypes were severely impaired on an odour naming task, in comparison with an age-matched control group. However, with the availability of picture cues or word cues, odour matching performance approached control levels, demonstrating an inability to retrieve but not to recognize the name and nature of the odorant. The magnitude of cortical thinning in the temporal pole was found to correlate with reductions in odour familiarity and odour matching to visual cues, whereas the inferior frontal gyrus correlated with both odour naming and matching. Volumetric changes in the mediodorsal thalamus correlated with the proportion of categorical mismatch errors, indicating a possible role of this region in error-signal monitoring to optimize recognition of associations linked to the odour. A complementary analysis of patients with the semantic subtype of primary progressive aphasia, which is associated with marked temporopolar atrophy, revealed much more pronounced impairments of odour naming and matching. In identifying the critical role of the temporal pole and inferior frontal gyrus in transmodal linking and verbalization of olfactory objects, our findings provide a new neurobiological foundation for understanding why even common odours are hard to name.
PMCID: PMC3613711  PMID: 23471695
olfaction; odour object knowledge; recognition; naming; language; semantics; temporal pole; inferior frontal gyrus; primary progressive aphasia; human brain; MRI
9.  Visual Discrimination Predicts Naming and Semantic Association Accuracy in Alzheimer’s Disease 
Language impairment is a common symptom of Alzheimer’s disease (AD) and is thought to be related to semantic processing. The present study examines the contribution of another process, namely visual perception, on measures of confrontation naming and semantic association abilities in persons with probable AD.
Twenty individuals with probable mild-moderate Alzheimer’s disease and twenty age-matched controls completed a battery of neuropsychological measures assessing visual perception, naming, and semantic association ability. Visual discrimination tasks that varied in the degree to which they likely accessed stored structural representations were used to gauge whether structural processing deficits could account for deficits in naming and in semantic association in AD.
Visual discrimination abilities of nameable objects in AD strongly predicted performance on both picture naming and semantic association ability but lacked the same predictive value for controls. Although impaired, performance on visual discrimination tests of abstract shapes and novel faces showed no significant relationship with picture naming and semantic association. These results provide additional evidence to support that structural processing deficits exist in AD and may contribute to object recognition and naming deficits.
Our findings suggest that there is a common deficit in discrimination of pictures using nameable objects, picture naming and semantic association of pictures in AD. Disturbances in structural processing of pictured items may be associated with lexical-semantic impairment in AD due to degraded internal storage of structural knowledge.
PMCID: PMC3058303  PMID: 21042208
Alzheimer’s disease; Anomia; Semantic Memory; Visual Perception; Agnosia; Confrontation Naming
10.  Lexical retrieval and semantic knowledge in patients with left inferior temporal lobe lesions 
Aphasiology  2008;22(3):281-304.
It has been proposed that anomia following left inferior temporal lobe lesions may have two different underlying mechanisms with distinct neural substrates. Specifically, naming impairment following damage to more posterior regions (BA 37) has been considered to result from a disconnection between preserved semantic knowledge and phonological word forms (pure anomia), whereas anomia following damage to anterior temporal regions (BAs 38, 20/21) has been attributed to the degradation of semantic representations (semantic anomia). However, the integrity of semantic knowledge in patients with pure anomia has not been demonstrated convincingly, nor were lesions in these cases necessarily confined to BA 37. Furthermore, evidence of semantic anomia often comes from individuals with bilateral temporal lobe damage, so it is unclear whether unilateral temporal lobe lesions are sufficient to produce significant semantic impairment.
The main goals of this study were to determine whether anomia following unilateral left inferior temporal lobe damage reflected a loss of semantic knowledge or a post-semantic deficit in lexical retrieval and to identify the neuroanatomical correlates of the naming impairment.
Methods & Procedures
Eight individuals who underwent left anterior temporal lobectomy (L ATL) and eight individuals who sustained left posterior cerebral artery strokes (L PCA) completed a battery of language measures that assessed lexical retrieval and semantic processing, and 16 age- and education-matched controls also completed this battery. High-resolution structural brain scans were collected to conduct lesion analyses.
Outcomes & Results
Performance of L ATL and L PCA patients was strikingly similar, with both groups demonstrating naming performance ranging from moderately impaired to unimpaired. Anomia in both groups occurred in the context of mild deficits to semantic knowledge, which manifested primarily as greater difficulty in naming living things than nonliving things and greater difficulty in processing visual/perceptual as opposed to functional/associative semantic attributes. Lesion analyses indicated that both patient groups sustained damage to anterior inferior temporal lobe regions implicated in semantic processing.
These results contribute to a better understanding of the cognitive mechanism of naming impairment in patients with temporal lobe damage and support the notion that pure anomia and semantic anomia represent two endpoints along a continuum of semantic impairment. Unilateral left temporal lobe lesions in our patients resulted in relatively mild semantic deficits that were apparent primarily in lexical production tasks, whereas severe semantic impairment likely requires bilateral temporal lobe damage.
PMCID: PMC2743433  PMID: 19756227
11.  Category-Specific Naming and Recognition Deficits in Temporal Lobe Epilepsy Surgical Patients 
Neuropsychologia  2007;46(5):1242-1255.
Based upon Damasio's “Convergence Zone” model of semantic memory, we predicted that epilepsy surgical patients with anterior temporal lobe (TL) seizure onset would exhibit a pattern of category-specific naming and recognition deficits not observed in patients with seizures arising elsewhere.
We assessed epilepsy patients with unilateral seizure onset of anterior TL or other origin (n = 22), pre- or postoperatively, using a set of category-specific items and a conventional measure of visual naming (Boston Naming Test: BNT).
Category-specific naming deficits were exhibited by patients with dominant anterior TL seizure onset/resection for famous faces and animals, while category-specific recognition deficits for these same categories were exhibited by patients with nondominant anterior TL onset/resection. Patients with other seizure onset did not exhibit category-specific deficits. Naming and recognition deficits were frequently not detected by the BNT, which samples only a limited range of stimuli.
Consistent with the “convergence zone” framework, results suggest that the nondominant anterior TL plays a major role in binding sensory information into conceptual percepts for certain stimuli, while dominant TL regions function to provide a link to verbal labels for these percepts. Although observed category-specific deficits were striking, they were often missed by the BNT, suggesting that they are more prevalent than recognized in both pre- and postsurgical epilepsy patients. Systematic investigation of these deficits could lead to more refined models of semantic memory, aid in the localization of seizures, and contribute to modifications in surgical technique and patient selection in epilepsy surgery to improve neurocognitive outcome.
PMCID: PMC2474808  PMID: 18206185
semantic memory; temporal lobe epilepsy; category-specific deficits; epilepsy surgery; naming deficits
12.  Non-verbal sound processing in the primary progressive aphasias 
Brain  2009;133(1):272-285.
Little is known about the processing of non-verbal sounds in the primary progressive aphasias. Here, we investigated the processing of complex non-verbal sounds in detail, in a consecutive series of 20 patients with primary progressive aphasia [12 with progressive non-fluent aphasia; eight with semantic dementia]. We designed a novel experimental neuropsychological battery to probe complex sound processing at early perceptual, apperceptive and semantic levels, using within-modality response procedures that minimized other cognitive demands and matching tests in the visual modality. Patients with primary progressive aphasia had deficits of non-verbal sound analysis compared with healthy age-matched individuals. Deficits of auditory early perceptual analysis were more common in progressive non-fluent aphasia, deficits of apperceptive processing occurred in both progressive non-fluent aphasia and semantic dementia, and deficits of semantic processing also occurred in both syndromes, but were relatively modality specific in progressive non-fluent aphasia and part of a more severe generic semantic deficit in semantic dementia. Patients with progressive non-fluent aphasia were more likely to show severe auditory than visual deficits as compared to patients with semantic dementia. These findings argue for the existence of core disorders of complex non-verbal sound perception and recognition in primary progressive aphasia and specific disorders at perceptual and semantic levels of cortical auditory processing in progressive non-fluent aphasia and semantic dementia, respectively.
PMCID: PMC2801322  PMID: 19797352
auditory perception; non-verbal sound; agnosia; dementia; environmental sounds
13.  The neural correlates of verbal and non-verbal semantic processing deficits in neurodegenerative disease 
To investigate the neural correlates of verbal and non-verbal semantic processing in neurodegenerative disease.
Semantic memory is often impaired in neurodegenerative disease. Neuropsychological and functional neuroimaging studies suggest that the semantic processing of verbal and non-verbal stimuli may depend on partially distinct brain networks.
We examined this possibility using voxel-based morphometry to correlate performance on verbal and non-verbal versions of a semantic association task with regional gray matter atrophy in 144 individuals with a variety of neurodegenerative diseases.
Results showed that, regardless of stimulus type, semantic processing correlated with atrophy in both temporal lobes. In addition, material-specific correlations were found in left temporal regions for verbal stimuli and the right fusiform gyrus for non-verbal stimuli.
These results provide evidence for a differential role of the left and right hemispheres in the extraction of semantic information from verbal and pictorial representations. Areas in the right inferior temporal lobe may be necessary to access structural descriptions of visually presented objects.
PMCID: PMC2754058  PMID: 19506422
14.  Verbal Fluency Performance in Amnestic MCI and Older Adults with Cognitive Complaints 
Verbal fluency tests are employed regularly during neuropsychological assessments of older adults, and deficits are a common finding in patients with Alzheimer’s disease (AD). Little extant research, however, has investigated verbal fluency ability and subtypes in preclinical stages of neurodegenerative disease. We examined verbal fluency performance in 107 older adults with amnestic mild cognitive impairment (MCI, n = 37), cognitive complaints (CC, n = 37) despite intact neuropsychological functioning, and demographically-matched healthy controls (HC, n = 33). Participants completed fluency tasks with letter, semantic category, and semantic switching constraints. Both phonemic and semantic fluency were statistically (but not clinically) reduced in amnestic MCI relative to cognitively intact older adults, indicating subtle changes in both the quality of the semantic store and retrieval slowing. Investigation of the underlying constructs of verbal fluency yielded two factors: Switching (including switching and shifting tasks) and Production (including letter, category, and action naming tasks), and both factors discriminated MCI from HC albeit to different degrees. Correlational findings further suggested that all fluency tasks involved executive control to some degree, while those with an added executive component (i.e., switching and shifting) were less dependent on semantic knowledge. Overall, our findings highlight the importance of including multiple verbal fluency tests in assessment batteries targeting preclinical dementia populations and suggest that individual fluency tasks may tap specific cognitive processes.
PMCID: PMC2743541  PMID: 18339515
Mild cognitive Impairment; Verbal Fluency; Assessment; Cognition
15.  Words and objects at the tip of the left temporal lobe in primary progressive aphasia 
Brain  2013;136(2):601-618.
Eleven of 69 prospectively enrolled primary progressive aphasics were selected for this study because of peak atrophy sites located predominantly or exclusively within the anterior left temporal lobe. Cortical volumes in these areas were reduced to less than half of control values, whereas average volume elsewhere in the left hemisphere deviated from control values by only 8%. Failure to name objects emerged as the most consistent and severe deficit. Naming errors were attributed to pure retrieval failure if the object could not be named even when the denoting word was understood, the object recognized and the two accurately matched. Surprisingly many of the naming errors reflected pure retrieval failures, without discernible semantic or associative component. The remaining set of errors had associative components. These errors reflected the inability to define the word denoting the object more often than the inability to define the nature of the pictured object. In a separate task where the same object had to be linked to verbal or non-verbal associations, performance was abnormal only in the verbal format. Excessive taxonomic interference was observed for picture–word, but not picture–picture, matching tasks. This excessive interference reflected a blurring of intra- rather than inter-category distinctions as if the acuity of word–object associations had been diminished so that correspondences were easier to recognize at generic than specific levels. These dissociations between verbal and non-verbal markers of object knowledge indicate that the reduced neural mass at peak atrophy sites of the left temporal tip, accounting for half or more of the presumed premorbid volume, was unlikely to have contained domain-independent semantic representations of the type that would be expected in a strictly amodal hub. A more likely arrangement entails two highly interactive routes—a strongly left lateralized temporosylvian language network for verbal concepts, and a presumably more bilateral or right-sided inferotemporal/fusiform object recognition network, which remained relatively spared because peak atrophy sites were concentrated on the left. The current results also suggest that the left anterior temporal neocortex should be inserted into the language network where it is likely to play a major role in selecting verbal labels for objects and mediating the progression of word comprehension from generic to specific levels of precision.
PMCID: PMC3572925  PMID: 23361063
dementia; semantic; language; naming; frontotemporal
16.  Nature and extent of person recognition impairments associated with Capgras syndrome in Lewy body dementia 
Patients with Capgras syndrome (CS) adopt the delusional belief that persons well-known to them have been replaced by an imposter. Several current theoretical models of CS attribute such misidentification problems to deficits in covert recognition processes related to the generation of appropriate affective autonomic signals. These models assume intact overt recognition processes for the imposter and, more broadly, for other individuals. As such, it has been suggested that CS could reflect the “mirror-image” of prosopagnosia. The purpose of the current study was to determine whether overt person recognition abilities are indeed always spared in CS. Furthermore, we examined whether CS might be associated with any impairments in overt affective judgments of facial expressions. We pursued these goals by studying a patient with Dementia with Lewy bodies (DLB) who showed clear signs of CS, and by comparing him to another patient with DLB who did not experience CS, as well as to a group of healthy control participants. Clinical magnetic resonance imaging scans revealed medial prefrontal cortex (mPFC) atrophy that appeared to be uniquely associated with the presence CS. We assessed overt person recognition with three fame recognition tasks, using faces, voices, and names as cues. We also included measures of confidence and probed pertinent semantic knowledge. In addition, participants rated the intensity of fearful facial expressions. We found that CS was associated with overt person recognition deficits when probed with faces and voices, but not with names. Critically, these deficits were not present in the DLB patient without CS. In addition, CS was associated with impairments in overt judgments of affect intensity. Taken together, our findings cast doubt on the traditional view that CS is the mirror-image of prosopagnosia and that it spares overt recognition abilities. These findings can still be accommodated by models of CS that emphasize deficits in autonomic responding, to the extent that the potential role of interoceptive awareness in overt judgments is taken into account.
PMCID: PMC4173644  PMID: 25309399
Capgras syndrome; Lewy body dementia; interoceptive awareness; person recognition; affect perception
17.  The emergence of semantic categorization in early visual processing: ERP indices of animal vs. artifact recognition 
BMC Neuroscience  2007;8:24.
Neuroimaging and neuropsychological literature show functional dissociations in brain activity during processing of stimuli belonging to different semantic categories (e.g., animals, tools, faces, places), but little information is available about the time course of object perceptual categorization. The aim of the study was to provide information about the timing of processing stimuli from different semantic domains, without using verbal or naming paradigms, in order to observe the emergence of non-linguistic conceptual knowledge in the ventral stream visual pathway. Event related potentials (ERPs) were recorded in 18 healthy right-handed individuals as they performed a perceptual categorization task on 672 pairs of images of animals and man-made objects (i.e., artifacts).
Behavioral responses to animal stimuli were ~50 ms faster and more accurate than those to artifacts. At early processing stages (120–180 ms) the right occipital-temporal cortex was more activated in response to animals than to artifacts as indexed by posterior N1 response, while frontal/central N1 (130–160) showed the opposite pattern. In the next processing stage (200–260) the response was stronger to artifacts and usable items at anterior temporal sites. The P300 component was smaller, and the central/parietal N400 component was larger to artifacts than to animals.
The effect of animal and artifact categorization emerged at ~150 ms over the right occipital-temporal area as a stronger response of the ventral stream to animate, homomorphic, entities with faces and legs. The larger frontal/central N1 and the subsequent temporal activation for inanimate objects might reflect the prevalence of a functional rather than perceptual representation of manipulable tools compared to animals. Late ERP effects might reflect semantic integration and cognitive updating processes. Overall, the data are compatible with a modality-specific semantic memory account, in which sensory and action-related semantic features are represented in modality-specific brain areas.
PMCID: PMC1852317  PMID: 17411424
18.  Congenital prosopagnosia: multistage anatomical and functional deficits in face processing circuitry 
Journal of Neurology  2010;258(5):770-782.
Face recognition is a primary social skill which depends on a distributed neural network. A pronounced face recognition deficit in the absence of any lesion is seen in congenital prosopagnosia. This study investigating 24 congenital prosopagnosic subjects and 25 control subjects aims at elucidating its neural basis with fMRI and voxel-based morphometry. We found a comprehensive behavioral pattern, an impairment in visual recognition for faces and buildings that spared long-term memory for faces with negative valence. Anatomical analysis revealed diminished gray matter density in the bilateral lingual gyrus, the right middle temporal gyrus, and the dorsolateral prefrontal cortex. In most of these areas, gray matter density correlated with memory success. Decreased functional activation was found in the left fusiform gyrus, a crucial area for face processing, and in the dorsolateral prefrontal cortex, whereas activation of the medial prefrontal cortex was enhanced. Hence, our data lend strength to the hypothesis that congenital prosopagnosia is explained by network dysfunction and suggest that anatomic curtailing of visual processing in the lingual gyrus plays a substantial role. The dysfunctional circuitry further encompasses the fusiform gyrus and the dorsolateral prefrontal cortex, which may contribute to their difficulties in long-term memory for complex visual information. Despite their deficits in face identity recognition, processing of emotion related information is preserved and possibly mediated by the medial prefrontal cortex. Congenital prosopagnosia may, therefore, be a blueprint of differential curtailing in networks of visual cognition.
Electronic supplementary material
The online version of this article (doi:10.1007/s00415-010-5828-5) contains supplementary material, which is available to authorized users.
PMCID: PMC3090571  PMID: 21120515
Congenital prosopagnosia; Fusiform gyrus; Emotion; Functional MRI; Voxel-based morphometry
19.  Behavioral evidence for inter-hemispheric cooperation during a lexical decision task: a divided visual field experiment 
HIGHLIGHTS The redundant bilateral visual presentation of verbal stimuli decreases asymmetry and increases the cooperation between the two hemispheres.The increased cooperation between the hemispheres is related to semantic information during lexical processing.The inter-hemispheric interaction is represented by both inhibition and cooperation.
This study explores inter-hemispheric interaction (IHI) during a lexical decision task by using a behavioral approach, the bilateral presentation of stimuli within a divided visual field experiment. Previous studies have shown that compared to unilateral presentation, the bilateral redundant (BR) presentation decreases the inter-hemispheric asymmetry and facilitates the cooperation between hemispheres. However, it is still poorly understood which type of information facilitates this cooperation. In the present study, verbal stimuli were presented unilaterally (left or right visual hemi-field successively) and bilaterally (left and right visual hemi-field simultaneously). Moreover, during the bilateral presentation of stimuli, we manipulated the relationship between target and distractors in order to specify the type of information which modulates the IHI. Thus, three types of information were manipulated: perceptual, semantic, and decisional, respectively named pre-lexical, lexical and post-lexical processing. Our results revealed left hemisphere (LH) lateralization during the lexical decision task. In terms of inter-hemisphere interaction, the perceptual and decision-making information increased the inter-hemispheric asymmetry, suggesting the inhibition of one hemisphere upon the other. In contrast, semantic information decreased the inter-hemispheric asymmetry, suggesting cooperation between the hemispheres. We discussed our results according to current models of IHI and concluded that cerebral hemispheres interact and communicate according to various excitatory and inhibitory mechanisms, all which depend on specific processes and various levels of word processing.
PMCID: PMC3694293  PMID: 23818879
asymmetry; cooperation; inhibition; divided visual field; redundant; bilateral; lexical decision
20.  Topographic amnesia: spatial memory disorder, perceptual dysfunction, or category specific semantic memory impairment? 
A 60 year old patient, SE, who presented with a severe difficulty in finding his way around previously familiar environments and a mild prosopagnosia is described. SE had herpes simplex encephalitis resulting in selective right temporal lobe damage. He showed normal spatial learning, but was severely imparied in his ability to recognise pictures of buildings and landmarks. The disorder was not confined to the visual modality, but rather involved a loss of knowledge about famous buildings and landmarks when tested from their spoken name. SE was contrasted with a more severely prosopagnosic patient, PHD, who showed normal ability to recognise buildings and landmarks, indicating that recognition of people dissociates from recognition of buildings/landmarks. It is concluded that SE's failure of place knowledge represents a category specific supramodal semantic memory impairment.
PMCID: PMC1073857  PMID: 8609511
21.  The Neural Correlates of Visual and Verbal Cognitive Styles 
It has long been thought that propensities for visual or verbal learning styles influence how children acquire knowledge successfully and how adults reason in everyday life. There is no direct evidence to date, however, linking these cognitive styles to specific neural systems. In the present study, visual and verbal cognitive styles are measured by self-report survey and cognitive abilities are measured by scored tests of visual and verbal skills. Specifically, we administered the Verbalizer-Visualizer Questionnaire (VVQ) and modality-specific subtests of the Wechsler Adult Intelligence Scale (WAIS) to 18 subjects who subsequently participated in a functional magnetic resonance imaging experiment. During the imaging session, participants performed a novel psychological task involving both word-based and picture-based feature matching conditions that was designed to permit the use of either a visual or a verbal processing style during all conditions of the task. Results demonstrated a pattern of activity in modality-specific cortex that distinguished visual from verbal cognitive styles. During the word-based condition, activity in a functionally-defined brain region that responded to viewing pictorial stimuli (fusiform gyrus) correlated with self-reported Visualizer ratings on the VVQ. In contrast, activity in a phonologically-related brain region (supramarginal gyrus) correlated with the Verbalizer dimension of the VVQ during the picture-based condition. Scores from the WAIS subtests did not reliably correlate with brain activity in either of these regions. These findings suggest that modality-specific cortical activity underlies processing in visual and verbal cognitive styles.
PMCID: PMC2697032  PMID: 19321775
cognitive style; visualizer; verbalizer; fMRI; modality-specific; working memory
22.  Right Inferior Frontal Gyrus Activation Is Associated with Memory Improvement in Patients with Left Frontal Low-Grade Glioma Resection 
PLoS ONE  2014;9(8):e105987.
Patients with low-grade glioma (LGG) have been studied as a model of functional brain reorganization due to their slow-growing nature. However, there is no information regarding which brain areas are involved during verbal memory encoding after extensive left frontal LGG resection. In addition, it remains unknown whether these patients can improve their memory performance after instructions to apply efficient strategies. The neural correlates of verbal memory encoding were investigated in patients who had undergone extensive left frontal lobe (LFL) LGG resections and healthy controls using fMRI both before and after directed instructions were given for semantic organizational strategies. Participants were scanned during the encoding of word lists under three different conditions before and after a brief period of practice. The conditions included semantically unrelated (UR), related-non-structured (RNS), and related-structured words (RS), allowing for different levels of semantic organization. All participants improved on memory recall and semantic strategy application after the instructions for the RNS condition. Healthy subjects showed increased activation in the left inferior frontal gyrus (IFG) and middle frontal gyrus (MFG) during encoding for the RNS condition after the instructions. Patients with LFL excisions demonstrated increased activation in the right IFG for the RNS condition after instructions were given for the semantic strategies. Despite extensive damage in relevant areas that support verbal memory encoding and semantic strategy applications, patients that had undergone resections for LFL tumor could recruit the right-sided contralateral homologous areas after instructions were given and semantic strategies were practiced. These results provide insights into changes in brain activation areas typically implicated in verbal memory encoding and semantic processing.
PMCID: PMC4144959  PMID: 25157573
23.  Galactose uncovers face recognition and mental images in congenital prosopagnosia: The first case report 
Nutritional Neuroscience  2014;17(5):239-240.
A woman in her early 40s with congenital prosopagnosia and attention deficit hyperactivity disorder observed for the first time sudden and extensive improvement of her face recognition abilities, mental imagery, and sense of navigation after galactose intake. This effect of galactose on prosopagnosia has never been reported before. Even if this effect is restricted to a subform of congenital prosopagnosia, galactose might improve the condition of other prosopagnosics. Congenital prosopagnosia, the inability to recognize other people by their face, has extensive negative impact on everyday life. It has a high prevalence of about 2.5%. Monosaccharides are known to have a positive impact on cognitive performance. Here, we report the case of a prosopagnosic woman for whom the daily intake of 5 g of galactose resulted in a remarkable improvement of her lifelong face blindness, along with improved sense of orientation and more vivid mental imagery. All these improvements vanished after discontinuing galactose intake. The self-reported effects of galactose were wide-ranging and remarkably strong but could not be reproduced for 16 other prosopagnosics tested. Indications about heterogeneity within prosopagnosia have been reported; this could explain the difficulty to find similar effects in other prosopagnosics. Detailed analyses of the effects of galactose in prosopagnosia might give more insight into the effects of galactose on human cognition in general. Galactose is cheap and easy to obtain, therefore, a systematic test of its positive effects on other cases of congenital prosopagnosia may be warranted.
PMCID: PMC4096494  PMID: 24164936
Monosaccharide; Galactose; Congenital prosopagnosia; Developmental prosopagnosia; Face blindness; Face recognition; Mental imagery; ADHD
24.  Motor cortex pre-activation by standing facilitates word retrieval in aphasia 
Background and Objectives
A tight link between linguistic functions and activation of motor areas has been consistently reported, indicating that the two systems share functional neural resources. However, little efforts have been made to explore whether this knowledge could aid the rehabilitation of neurological conditions affecting language functions (e.g., aphasia). Moreover, the few previous studies that assessed the impact of motor-language interactions in aphasia used manual gestures, which are an integral component of language comprehension and production.
In the present study we assessed whether pre-activation of the leg-motor cortex, during standing vs. sitting, can facilitate language production in chronic aphasia. In a cross-over within-subject design, we assessed performance on a picture naming task and controlled for effects on processing speed and simple verbal reaction time.
We found that standing compared to sitting had a beneficial effect on the number of semantic self-corrections that resulted in correct naming. In the absence of effects on motor or general processing speed, this points to a specific effect on lexical retrieval and selection. This was further corroborated by an error pattern analysis. Successful semantic self-corrections during standing were only found when there was already partial activation of the target semantic network, i.e., when self-corrections were preceded by an incorrect, but semantically associated naming response.
Our findings show that pre-activation of the motor system, that extends beyond the intrinsic link between manual gestures and language, can facilitate lexical access in chronic aphasia and may open new directions in aphasia rehabilitation.
PMCID: PMC3594773  PMID: 20966157
Aphasia; Stroke; Anomia; Motor System; Word-retrieval
25.  Deficits in Concept Formation in Amyotrophic Lateral Sclerosis 
Neuropsychology  2012;26(4):422-429.
Amyotrophic Lateral Sclerosis (ALS) is associated with impaired executive control. The aim of the current research was to test the hypothesis that concept formation deficits associated with an extra-motor neurocognitive network involving executive and semantic resources can be found in some ALS patients.
Forty-one patients with clinically-definite ALS were assessed with Delis Kaplan Executive Function System Sorting Test (D-KEFS), a measure of concept formation requiring patients to manipulate verbal and visual semantic information and neuropsychological tests measuring naming, semantic memory, and executive control. Using D-KEFS scale scores, a k-mean cluster analysis specifying a 3-group solution was able to classify ALS patients into groups presenting with mildly impaired, average, and above average sorting test performance. High resolution T1 structural MRI was used to examine cortical thickness in a subset of 16 ALS patients.
Step-wise regression analyses related free and recognition sorting test performance to measures of action naming, single word semantic knowledge, and mental search/working memory. MRI studies found widespread cortical thinning involving bilateral frontal, temporal and parietal regions. Regression analyses related recognition sorting performance to reduced MRI cortical thickness involving the left prefrontal and left parietal cortex.
An extra-motor cognitive network is associated with impaired concept formation in ALS.
PMCID: PMC3516292  PMID: 22612577
Amyotrophic Lateral Sclerosis (ALS); executive control; prefrontal cortex; neuropsychology; Delis-Kaplan Executive Function System (D-KEFS) Sorting Test

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