Data-driven classification of cognitively normal and mild cognitive impairment subtypes predicts progression in the NACC dataset.

INTRODUCTION: Data-driven neuropsychological methods can identify mild cognitive impairment (MCI) subtypes with stronger associations to dementia risk factors than conventional diagnostic methods. METHODS: Cluster analysis used neuropsychological data from participants without dementia (mean age = 71.6 years) in the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (n = 26,255) and the "normal cognition" subsample (n = 16,005). Survival analyses examined MCI or dementia progression. RESULTS: Five clusters were identified: "Optimal" cognitively normal (oCN; 13.2%), "Typical" CN (tCN; 28.0%), Amnestic MCI (aMCI; 25.3%), Mixed MCI-Mild (mMCI-Mild; 20.4%), and Mixed MCI-Severe (mMCI-Severe; 13.0%). Progression to dementia differed across clusters (oCN < tCN < aMCI < mMCI-Mild < mMCI-Severe). Cluster analysis identified more MCI cases than consensus diagnosis. In the "normal cognition" subsample, five clusters emerged: High-All Domains (High-All; 16.7%), Low-Attention/Working Memory (Low-WM; 22.1%), Low-Memory (36.3%), Amnestic MCI (16.7%), and Non-amnestic MCI (naMCI; 8.3%), with differing progression rates (High-All < Low-WM = Low-Memory < aMCI < naMCI). DISCUSSION: Our data-driven methods outperformed consensus diagnosis by providing more precise information about progression risk and revealing heterogeneity in cognition and progression risk within the NACC "normal cognition" group.

Evidence of Impaired Remote Experience-near Semantic Memory in Medial Temporal Lobe Amnesia.

Neuropsychological research suggests that "experience-near" semantic memory, meaning knowledge attached to a spatiotemporal or event context, is commonly impaired in individuals who have medial temporal lobe amnesia. It is not known if this impairment extends to remotely acquired experience-near knowledge, which is a question relevant to understanding hippocampal/medial temporal lobe functioning. In the present study, we administered a novel semantic memory task designed to target knowledge associated with remote, "dormant" concepts, in addition to knowledge associated with active concepts, to four individuals with medial temporal lobe amnesia and eight matched controls. We found that the individuals with medial temporal lobe amnesia generated significantly fewer experience-near semantic memories for both remote concepts and active concepts. In comparison, the generation of abstract or "experience-far" knowledge was largely spared in the individuals with medial temporal lobe amnesia, regardless of whether the targets for retrieval were remote or active concepts. We interpret these findings as evidence that the medial temporal lobes may have a sustained role in the retrieval of semantic memories associated with spatiotemporal and event contexts, which are cognitive features often ascribed to episodic memory. These results align with recent theoretical models proposing that the hippocampus/medial temporal lobes support cognitive processes that are involved in, but not exclusive to, episodic memory.

Common predictors of spoken and written language performance in aphasia, alexia, and agraphia.

Language performance requires support from central cognitive/linguistic abilities as well as the more peripheral sensorimotor skills to plan and implement spoken and written communication. Both output modalities are vulnerable to impairment following damage to the language-dominant hemisphere, but much of the research to date has focused exclusively on spoken language. In this study we aimed to examine an integrated model of language processing that includes the common cognitive processes that support spoken and written language, as well as modality-specific skills. To do so, we evaluated spoken and written language performance from 87 individuals with acquired language impairment resulting from damage to left perisylvian cortical regions that collectively constitute the dorsal language pathway. Comprehensive behavioral assessment served to characterize the status of central and peripheral components of language processing in relation to neurotypical controls (n = 38). Performance data entered into principal components analyses (with or without control scores) consistently yielded a strong five-factor solution. In line with a primary systems framework, three central cognitive factors emerged: semantics, phonology, and orthography that were distinguished from peripheral processes supporting speech production and allographic skill for handwriting. The central phonology construct reflected performance on phonological awareness and manipulation tasks and showed the greatest deficit of all the derived factors. Importantly, this phonological construct was orthogonal to the speech production factor that reflected repetition of words/non-words. When entered into regression analyses, semantics and phonological skill were common predictors of language performance across spoken and written modalities. The speech production factor was also a strong, distinct predictor of spoken naming and oral reading, in contrast to allographic skills which only predicted written output. As expected, visual orthographic processing contributed more to written than spoken language tasks and reading/spelling performance was strongly reliant on phonological and semantic abilities. Despite the heterogeneity of this cohort regarding aphasia type and severity, the marked impairment of phonological skill was a unifying feature. These findings prompt greater attention to clinical assessment and potential treatment of underlying phonological skill in individuals with left perisylvian damage.

Largely intact memory for spatial locations during navigation in an individual with dense amnesia.

Spatial navigation and event memory (termed episodic memory) are thought to be heavily intertwined, both in terms of their cognitive processes and underlying neural systems. Some theoretical models posit that both memory for places during navigation and episodic memory depend on highly overlapping brain systems. Here, we assessed this relationship by testing navigation in an individual with severe retrograde and anterograde amnesia; the amnesia stemmed from bilateral lesions in the medial temporal lobes from two separate strokes. The individual with amnesia and age-matched controls were tested on their memories for the locations of previously seen objects relative to distal mountain cues in an immersive virtual environment involving free ambulation. All participants were tested from both repeated and novel start locations and when a single distal mountain cue was unknowingly moved to determine if they relied on a single (beacon) cue to a greater extent than the collection of all distal cues. Compared to age-matched controls, the individual with amnesia showed no significant deficits in navigation from either the repeated or novel start points, although both the individual with amnesia and controls performed well above chance at placing objects near their correct locations. The individual with amnesia also relied on a combination of distal cues in a manner comparable to age-matched controls. Despite largely intact memory for locations using distal cues, the individual with amnesia walked longer paths, rotated more, and took longer to complete trials. Our findings suggest that memory for places during navigation and episodic memory may involve partially dissociable brain circuits and that other brain regions outside of the medial temporal lobe partially support some aspects of navigation. At the same time, the fact that the individual with amnesia walked more circuitous paths and had dense amnesia for autobiographic events supports the idea that the hippocampus may be important for binding information as part of a larger role in memory.

Autobiographical memory unknown: Pervasive autobiographical memory loss encompassing personality trait knowledge in an individual with medial temporal lobe amnesia.

Autobiographical memory consists of distinct memory types varying from highly abstract to episodic. Self trait knowledge, which is considered one of the more abstract types of autobiographical memory, is thought to rely on regions of the autobiographical memory neural network implicated in schema representation, including the ventromedial prefrontal cortex, and critically, not the medial temporal lobes. The current case study introduces an individual who experienced bilateral posterior cerebral artery strokes resulting in extensive medial temporal lobe damage with sparing of the ventromedial prefrontal cortex. Interestingly, in addition to severe retrograde and anterograde episodic and autobiographical fact amnesia, this individual's self trait knowledge was impaired for his current and pre-morbid personality traits. Yet, further assessment revealed that this individual had preserved conceptual knowledge for personality traits, could reliably and accurately rate another person's traits, and could access his own self-concept in a variety of ways. In addition to autobiographical memory loss, he demonstrated impairment on non-personal semantic memory tests, most notably on tests requiring retrieval of unique knowledge. This rare case of amnesia suggests a previously unreported role for the medial temporal lobes in self trait knowledge, which we propose reflects the critical role of this neural region in the storage and retrieval of personal semantics that are experience-near, meaning autobiographical facts grounded in spatiotemporal contexts.

Functional neuroanatomy of reading in Czech: Evidence of a dual-route processing architecture in a shallow orthography.

Introduction: According to the strong version of the orthographic depth hypothesis, in languages with transparent letter-sound mappings (shallow orthographies) the reading of both familiar words and unfamiliar nonwords may be accomplished by a sublexical pathway that relies on serial grapheme-to-phoneme conversion. However, in languages such as English characterized by inconsistent letter-sound relationships (deep orthographies), word reading is mediated by a lexical-semantic pathway that relies on mappings between word-specific orthographic, semantic, and phonological representations, whereas the sublexical pathway is used primarily to read nonwords. Methods: In this study, we used functional magnetic resonance imaging to elucidate neural substrates of reading in Czech, a language characterized by a shallo worthography. Specifically, we contrasted patterns of brain activation and connectivity during word and nonword reading to determine whether similar or different neural mechanisms are involved. Neural correlates were measured as differences in simple whole-brain voxel-wise activation, and differences in visual word form area (VWFA) task-related connectivity were computed on the group level from data of 24 young subject. Trial-to-trial reading reaction times were used as a measure of task difficulty, and these effects were subtracted from the activation and connectivity effects in order to eliminate difference in cognitive effort which is naturally higher for nonwords and may mask the true lexicality effects. Results: We observed pattern of activity well described in the literature mostly derived from data of English speakers - nonword reading (as compared to word reading) activated the sublexical pathway to a greater extent whereas word reading was associated with greater activation of semantic networks. VWFA connectivity analysis also revealed stronger connectivity to a component of the sublexical pathway - left inferior frontal gyrus (IFG), for nonword compared to word reading. Discussion: These converging results suggest that the brain mechanism of skilled reading in shallow orthography languages are similar to those engaged when reading in languages with a deep orthography and are supported by a universal dual-pathway neural architecture.

Structural Changes in Thalamic Nuclei Across Prodromal and Clinical Alzheimer's Disease.

BACKGROUND: Increasing evidence suggests that thalamic nuclei may atrophy in Alzheimer's disease (AD). We hypothesized that there will be significant atrophy of limbic thalamic nuclei associated with declining memory and cognition across the AD continuum. OBJECTIVE: The objective of this work was to characterize volume differences in thalamic nuclei in subjects with early and late mild cognitive impairment (MCI) as well as AD when compared to healthy control (HC) subjects using a novel MRI-based thalamic segmentation technique (THOMAS). METHODS: MPRAGE data from the ADNI database were used in this study (n = 540). Healthy control (n = 125), early MCI (n = 212), late MCI (n = 114), and AD subjects (n = 89) were selected, and their MRI data were parcellated to determine the volumes of 11 thalamic nuclei for each subject. Volumes across the different clinical subgroups were compared using ANCOVA. RESULTS: There were significant differences in thalamic nuclei volumes between HC, late MCI, and AD subjects. The anteroventral, mediodorsal, pulvinar, medial geniculate, and centromedian nuclei were significantly smaller in subjects with late MCI and AD when compared to HC subjects. Furthermore, the mediodorsal, pulvinar, and medial geniculate nuclei were significantly smaller in early MCI when compared to HC subjects. CONCLUSION: This work highlights nucleus specific atrophy within the thalamus in subjects with early and late MCI and AD. This is consistent with the hypothesis that memory and cognitive changes in AD are mediated by damage to a large-scale integrated neural network that extends beyond the medial temporal lobes.

Articulatory network reorganization in Parkinson's disease as assessed by multimodal MRI and acoustic measures.

INTRODUCTION: Hypokinetic dysarthria (HD) is common in Parkinson's disease (PD). Our objective was to evaluate articulatory networks and their reorganization due to PD pathology in individuals without overt speech impairment using a multimodal MRI protocol and acoustic analysis of speech. METHODS: A total of 34 PD patients with no subjective HD complaints and 25 age-matched healthy controls (HC) underwent speech task recordings, structural MRI, and reading task-induced and resting-state fMRI. Grey matter probability maps, task-induced activations, and resting-state functional connectivity within the regions engaged in speech production (ROIs) were assessed and compared between groups. Correlation with acoustic parameters was also performed. RESULTS: PD patients as compared Tto HC displayed temporal decreases in speech loudness which were related to BOLD signal increases in the right-sided regions of the dorsal language pathway/articulatory network. Among those regions, activation of the right anterior cingulate was increased in PD as compared to HC. We also found bilateral posterior superior temporal gyrus (STG) GM loss in PD as compared to HC that was strongly associated with diadochokinetic (DDK) irregularity in the PD group. Task-induced activations of the left STG were increased in PD as compared to HC and were related to the DDK rate control. CONCLUSIONS: The results provide insight into the neural correlates of speech production control and distinct articulatory network reorganization in PD apparent already in patients without subjective speech impairment.

The role of the striatum in visuomotor integration during handwriting: an fMRI study.

This study investigates the role of the dorsal/sensorimotor striatum in visuomotor integration (i.e., the transformation of internal visual information about letter shapes into motor output) during handwriting. Twenty healthy participants underwent fMRI scanning with tasks consisting of self-paced handwriting of alphabetically ordered single letters and simple dots, with both tasks performed without visual feedback. Functional connectivity (FC) from these two tasks was compared to demonstrate the difference between coordinated activity arising during handwriting and the activity during a simpler motor condition. Our study focused upon the writing-specific cortico-striatal network of preselected regions of interest consisting of the visual word form area (VWFA), anterior intraparietal sulcus/superior parietal lobule, striatum, premotor cortex/Exner's area, and primary and supplementary motor regions. We observed systematically increased task-induced cortico-striatal and cortico-cortical FC. This increased synchronization of neural activity between the VWFA, i.e., the visual cortical area containing information about letter shapes, and the frontoparietal motor regions is mediated by the striatum. These findings suggest the involvement of the striatum in integrating stored letter-shape information with motor planning and execution during handwriting.

Face Recognition.

PURPOSE OF REVIEW: Functional imaging studies, intracranial recordings, and lesion-deficit correlations in neurological patients have produced unique insights into the cognitive mechanisms and neural substrates of face recognition. In this review, we highlight recent advances in the field and integrate data from these complementary lines of research to propose a functional neuroanatomical model of face identity recognition. RECENT FINDINGS: Rather than being localized to a single specialized cortical region, face recognition is supported by a distributed neural network. Core components of the network include face-selective visual areas in the ventral occipito-temporal cortex, whereas the extended network is comprised of anterior temporal lobe structures involved in the retrieval of multimodal identity-specific knowledge about familiar individuals, the amygdala responsible for generating emotional responses to faces, and prefrontal regions that provide top-down executive control of the recognition process. Damage to different network components results in neuropsychological disorders of face identity processing manifested either as impaired recognition of familiar faces (prosopagnosia, person recognition disorders) or as false recognition/misidentification of unfamiliar faces. Face identity recognition requires the coordinated activity of a large-scale neural network. Neurological damage can compromise the structural/functional integrity of specific network nodes or their connections and give rise to face recognition disorders with distinct clinical features and underlying cognitive mechanisms determined primarily by the location of the lesion.

The contribution of the left anterior ventrolateral temporal lobe to the retrieval of personal semantics.

Autobiographical facts and personal trait knowledge are conceptualized as distinct types of personal semantics, but the cognitive and neural mechanisms that separate them remain underspecified. One distinction may be their level of specificity, with autobiographical facts reflecting idiosyncratic conceptual knowledge and personal traits representing basic level category knowledge about the self. Given the critical role of the left anterior ventrolateral temporal lobe (AVTL) in the storage and retrieval of semantic information about unique entities, we hypothesized that knowledge of autobiographical facts may depend on the integrity of this region to a greater extent than personal traits. To provide neuropsychological evidence relevant to this issue, we investigated personal semantics, semantic knowledge of non-personal unique entities, and episodic memory in two individuals with well-defined left (MK) versus right (DW) AVTL lesions. Relative to controls, MK demonstrated preserved personal trait knowledge but impaired "experience-far" (i.e., spatiotemporal independent) autobiographical fact knowledge, semantic memory for non-personal unique entities, and episodic memory. In contrast, both experience-far autobiographical facts and personal traits were spared in DW, whereas episodic memory and aspects of semantic memory for non-personal unique entities were impaired. These findings support the notion that autobiographical facts and personal traits have distinct cognitive features and neural mechanisms. They also suggest a common organizing principle for personal and non-personal semantics, namely the specificity of such knowledge to an entity, which is reflected in the contribution of the left AVTL to retrieval.

Alteration of Diffusion-Tensor Magnetic Resonance Imaging Measures in Brain Regions Involved in Early Stages of Parkinson's Disease.

Many nonmotor symptoms (e.g., hyposmia) appear years before the cardinal motor features of Parkinson's disease (PD). It is thus desirable to be able to use noninvasive brain imaging methods, such as magnetic resonance imaging (MRI), to detect brain abnormalities in early PD stages. Among the MRI modalities, diffusion-tensor imaging (DTI) is suitable for detecting changes in brain tissue structure due to neurological diseases. The main purpose of this study was to investigate whether DTI signals measured from brain regions involved in early stages of PD differ from those of healthy controls. To answer this question, we analyzed whole-brain DTI data of 30 early-stage PD patients and 30 controls using improved region of interest-based analysis methods. Results showed that (i) the fractional anisotropy (FA) values in the olfactory tract (connected with the olfactory bulb: one of the first structures affected by PD) are lower in PD patients than healthy controls; (ii) FA values are higher in PD patients than healthy controls in the following brain regions: corticospinal tract, cingulum (near hippocampus), and superior longitudinal fasciculus (temporal part). Experimental results suggest that the tissue property, measured by FA, in olfactory regions is structurally modulated by PD with a mechanism that is different from other brain regions.

The neural substrates of improved phonological processing following successful treatment in a case of phonological alexia and agraphia.

Phonological deficits are common in aphasia after left-hemisphere stroke, and can have significant functional consequences for spoken and written language. While many individuals improve through treatment, the neural substrates supporting improvements are poorly understood. We measured brain activation during pseudoword reading in an individual through two treatment phases. Improvements were associated with greater activation in residual left dorsal language regions and bilateral regions supporting attention and effort. Gains were maintained, while activation returned to pre-treatment levels. This case demonstrates the neural support for improved phonology after damage to critical regions and that improvements may be maintained without markedly increased effort.

The nature and treatment of phonological text agraphia.

Phonological alexia and agraphia are written language disorders characterised by disproportionate difficulty reading and spelling nonwords in comparison to real words. In phonological alexia, it has been shown that, despite relatively accurate reading of words in isolation, text-level reading deficits are often marked and persistent. Specifically, some individuals demonstrate difficulty reading functors and affixes in sentences, a profile referred to as phonological text alexia. In this paper, we demonstrate an analogous manifestation of the phonological impairment on text-level writing and suggest the term "phonological text agraphia". We examined four individuals with phonological alexia/agraphia who also showed disproportionate difficulty writing well-formed sentences in comparison to their grammatical competence in spoken utterances. Implementation of a phonological treatment protocol resulted in significantly improved sublexical phonology skills as well as improvements in grammatical accuracy of written narratives. These findings support the notion of a common phonological impairment underlying nonword reading/spelling deficits and sentence-level difficulties.

Neural evidence for defective top-down control of visual processing in Parkinson's and Alzheimer's disease.

INTRODUCTION: We used a functional MRI paradigm involving conventional vs. unconventional views of objects to assess bottom-up vs. top-down visual processing in Parkinson's disease (PD) with normal cognition, PD with mild cognitive impairment (MCI), and MCI due to Alzheimer's disease (AD) as compared to healthy controls. We particularly aimed at determining whether the task discriminated between PD with and without MCI and between two MCI groups due to distinct pathologies (AD and PD). METHODS: 116 right-handed subjects (21 MCI due to AD; 16 PD with normal cognition; 24 PD with MCI; 55 healthy controls) performed a visual object-matching task in a T MR scanner. T statistic maps were computed to contrast task-based activation during unconventional vs. conventional view conditions. One-way ANOVAs and post hoc tests were performed to assess differences across and between groups. RESULTS: Both MCI groups performed worse than controls in the unconventional views condition and showed reduced activation of right anterior cingulate cortex and right superior parietal lobule (PD with MCI), and right middle and inferior frontal gyri (MCI due to AD). Neural responses in cortical areas within the ventral and dorsal visual pathway appeared to be preserved in both MCI groups. Receiver operating characteristic analysis of MRI contrast in the right superior parietal lobule distinguished PD with and without MCI with 87.50% sensitivity and 86.98% specificity. CONCLUSIONS: Impaired recognition of objects presented in unconventional orientations in MCI due to PD and AD was associated with decreased activation of frontoparietal regions, consistent with defective top-down regulation of visual processing. Aberrant activation of superior parietal cortex may serve as an early imaging biomarker of impending cognitive impairment in PD.

Oscillatory reactivity to effortful cognitive processing in the subthalamic nucleus and internal pallidum: a depth electrode EEG study.

This study investigates how complex motor-cognitive activities are processed in the subthalamic nucleus (STN) and internal globus pallidum (GPi), as adverse neuropsychiatric effects may accompany deep brain stimulation (DBS), mainly in Parkinson's disease (PD) and STN-DBS. Dystonia patients with GPi-DBS electrodes (n = 5) and PD subjects (n = 5) with STN-DBS electrodes performed two tasks: (1) copying letters; and (2) writing any letter other than that appearing on the monitor. The cognitive load of the second task was greater than that of the first. Intracranial local field potentials (LFPs) were analysed. A beta power decrease was the main correlate of the enhanced cognitive load during the second task in both structures, with a lateralization to the left side, mainly in the GPi. A gamma power increase linked with the increased cognitive activity was observed only in the STN. Differences were also observed in the theta and alpha bandpasses. Beta ERD reactivity seems to be essential during the processing of complex motor-cognitive tasks, increases with enhanced cognitive effort, and was observed in both the STN and GPi. Oscillatory reactivity to effortful cognitive processing in other frequency bands was less consistent, with differences between the studied nuclei. Lateralization of activity related to cognitive factors was observed mainly in the GPi.

Neural substrates of sublexical processing for spelling.

We used fMRI to examine the neural substrates of sublexical phoneme-grapheme conversion during spelling in a group of healthy young adults. Participants performed a writing-to-dictation task involving irregular words (e.g., choir), plausible nonwords (e.g., kroid), and a control task of drawing familiar geometric shapes (e.g., squares). Written production of both irregular words and nonwords engaged a left-hemisphere perisylvian network associated with reading/spelling and phonological processing skills. Effects of lexicality, manifested by increased activation during nonword relative to irregular word spelling, were noted in anterior perisylvian regions (posterior inferior frontal gyrus/operculum/precentral gyrus/insula), and in left ventral occipito-temporal cortex. In addition to enhanced neural responses within domain-specific components of the language network, the increased cognitive demands associated with spelling nonwords engaged domain-general frontoparietal cortical networks involved in selective attention and executive control. These results elucidate the neural substrates of sublexical processing during written language production and complement lesion-deficit correlation studies of phonological agraphia.

Impaired personal trait knowledge, but spared other-person trait knowledge, in an individual with bilateral damage to the medial prefrontal cortex.

Functional neuroimaging has revealed that in healthy adults retrieval of personal trait knowledge is associated with increased activation in the medial prefrontal cortex (mPFC). Separately, neuropsychology has shown that the self-referential nature of memory can be disrupted in individuals with mPFC lesions. However, it remains unclear whether damage to the mPFC impairs retrieval of personal trait knowledge. Therefore, in this neuropsychological case study we investigated the integrity of personal trait knowledge in J.S., an individual who sustained bilateral damage to the mPFC as a result of an anterior communicating artery aneurysm. We measured both accuracy and consistency of J.S.'s personal trait knowledge as well as his trait knowledge of another, frequently seen person, and compared his performance to a group of healthy adults. Findings revealed that J.S. had severely impaired accuracy and consistency of his personal trait knowledge relative to control participants. In contrast, J.S.'s accuracy and consistency of other-person trait knowledge was intact in comparison to control participants. Moreover, J.S. showed a normal positivity bias in his trait ratings. These results, albeit based on a single case, implicate the mPFC as critical for retrieval of personal trait knowledge. Findings also cast doubt on the likelihood that the mPFC, in particular the ventral mPFC, is necessary for storage and retrieval of trait knowledge of other people. Therefore, this case study adds to a growing body of evidence that mPFC damage can disrupt the link between self and memory.

Treatment for Alexia With Agraphia Following Left Ventral Occipito-Temporal Damage: Strengthening Orthographic Representations Common to Reading and Spelling.

PURPOSE: Damage to left ventral occipito-temporal cortex can give rise to written language impairment characterized by pure alexia/letter-by-letter (LBL) reading, as well as surface alexia and agraphia. The purpose of this study was to examine the therapeutic effects of a combined treatment approach to address concurrent LBL reading with surface alexia/agraphia. METHOD: Simultaneous treatment to address slow reading and errorful spelling was administered to 3 individuals with reading and spelling impairments after left ventral occipito-temporal damage due to posterior cerebral artery stroke. Single-word reading/spelling accuracy, reading latencies, and text reading were monitored as outcome measures for the combined effects of multiple oral re-reading treatment and interactive spelling treatment. RESULTS: After treatment, participants demonstrated faster and more accurate single-word reading and improved text-reading rates. Spelling accuracy also improved, particularly for untrained irregular words, demonstrating generalization of the trained interactive spelling strategy. CONCLUSION: This case series characterizes concomitant LBL with surface alexia/agraphia and demonstrates a successful treatment approach to address both the reading and spelling impairment.

Processing deficits for familiar and novel faces in patients with left posterior fusiform lesions.

Pure alexia (PA) arises from damage to the left posterior fusiform gyrus (pFG) and the striking reading disorder that defines this condition has meant that such patients are often cited as evidence for the specialisation of this region to processing of written words. There is, however, an alternative view that suggests this region is devoted to processing of high acuity foveal input, which is particularly salient for complex visual stimuli like letter strings. Previous reports have highlighted disrupted processing of non-linguistic visual stimuli after damage to the left pFG, both for familiar and unfamiliar objects and also for novel faces. This study explored the nature of face processing deficits in patients with left pFG damage. Identification of famous faces was found to be compromised in both expressive and receptive tasks. Discrimination of novel faces was also impaired, particularly for those that varied in terms of second-order spacing information, and this deficit was most apparent for the patients with the more severe reading deficits. Interestingly, discrimination of faces that varied in terms of feature identity was considerably better in these patients and it was performance in this condition that was related to the size of the length effects shown in reading. This finding complements functional imaging studies showing left pFG activation for faces varying only in spacing and frontal activation for faces varying only on features. These results suggest that the sequential part-based processing strategy that promotes the length effect in the reading of these patients also allows them to discriminate between faces on the basis of feature identity, but processing of second-order configural information is most compromised due to their left pFG lesion. This study supports a view in which the left pFG is specialised for processing of high acuity foveal visual information that supports processing of both words and faces.