Robert S. Hurley

Comparison of social cognitive functioning in schizophrenia and high functioning autism: more convergence than divergence

BACKGROUND Individuals with schizophrenia and individuals with high-functioning autism (HFA) seem to share some social, behavioral and biological features. Although marked impairments in social cognition have been documented in both groups, little empirical work has compared the social cognitive functioning of these two clinical groups. METHOD Forty-four individuals with schizophrenia, 36 with HFA and 41 non-clinical controls completed a battery of social cognitive measures that have been linked previously to specific brain regions. RESULTS The results indicate that the individuals with schizophrenia and HFA were both impaired on a variety of social cognitive tasks relative to the non-clinical controls, but did not differ from one another. When individuals with schizophrenia were divided into negative symptom and paranoid subgroups, exploratory analyses revealed that individuals with HFA may be more similar, in terms of the pattern of social cognition impairments, to the negative symptom group than to the paranoia group. CONCLUSIONS Our findings provide further support for similarities in social cognition deficits between HFA and schizophrenia, which have a variety of implications for future work on gene-brain-behavior relationships.

Words and objects at the tip of the left temporal lobe in primary progressive aphasia

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.

Primary progressive aphasia and the evolving neurology of the language network

Primary progressive aphasia (PPA) is caused by selective neurodegeneration of the language-dominant cerebral hemisphere; a language deficit initially arises as the only consequential impairment and remains predominant throughout most of the course of the disease. Agrammatic, logopenic and semantic subtypes, each reflecting a characteristic pattern of language impairment and corresponding anatomical distribution of cortical atrophy, represent the most frequent presentations of PPA. Such associations between clinical features and the sites of atrophy have provided new insights into the neurology of fluency, grammar, word retrieval, and word comprehension, and have necessitated modification of concepts related to the functions of the anterior temporal lobe and Wernickes area. The underlying neuropathology of PPA is, most commonly, frontotemporal lobar degeneration in the agrammatic and semantic forms, and Alzheimer disease (AD) pathology in the logopenic form; the AD pathology often displays atypical and asymmetrical anatomical features consistent with the aphasic phenotype. The PPA syndrome reflects complex interactions between disease-specific neuropathological features and patient-specific vulnerability. A better understanding of these interactions might help us to elucidate the biology of the language network and the principles of selective vulnerability in neurodegenerative diseases. We review these aspects of PPA, focusing on advances in our understanding of the clinical features and neuropathology of PPA and what they have taught us about the neural substrates of the language network.

Neural Mechanisms of Object Naming and Word Comprehension in Primary Progressive Aphasia

Primary progressive aphasia (PPA) is a neurodegenerative syndrome that causes a gradual atrophy of the left hemisphere language network, leading to impairments of object naming (anomia) and word comprehension. In 33 human subjects with PPA, object naming and word comprehension were explored with N400 potentials elicited by picture–word or picture–picture matching tasks. Two mechanisms of impairment were identified. In one group of patients, where the object name could be recognized but not retrieved during verbal naming, N400s in picture–word trials were also abnormal, revealing an associative basis for retrieval anomia. In these patients, a putative prephonological signal (i.e., lemma) evoked by the object picture appears to have become too weak to elicit retrieval, but not necessarily too weak to support the informationally less taxing process of recognition. A second group of PPA patients showed more severe naming deficits—the object name was neither verbalized nor recognized. Furthermore, nouns of the same category (but not those of other object categories) could not be identified as mismatches. This blurring of intracategory but not intercategory differentiation of word meaning was correlated with anterior temporal atrophy, predominantly in the left hemisphere, especially along the superior temporal gyrus. Although not part of the classic language network, this area appears critical for proceeding from generic to specific levels of word comprehension and object naming. N400 abnormalities emerged for lexical (picture–word) but not nonverbal (picture–picture) associations, supporting a dual-route rather than amodal organization of object concepts.

Asymmetric connectivity between the anterior temporal lobe and the language network

The anterior temporal lobe (ATL) sits at the confluence of auditory, visual, olfactory, transmodal, and limbic processing hierarchies. In keeping with this anatomical heterogeneity, the ATL has been implicated in numerous functional domains, including language, semantic memory, social cognition, and facial identification. One question that has attracted considerable discussion is whether the ATL contains a mosaic of differentially specialized areas or whether it provides a domain-independent amodal hub. In the current study, based on task-free fMRI in right-handed neurologically intact participants, we found that the left lateral ATL is interconnected with hubs of the temporosylvian language network, including the inferior frontal gyrus and middle temporal gyrus of the ipsilateral hemisphere and, to a lesser extent, with homotopic areas of the contralateral hemisphere. In contrast, the right lateral ATL had much weaker functional connectivity with these regions in either hemisphere. Together with evidence that has been gathered in lesion-mapping and event-related neuroimaging studies, this asymmetry of functional connectivity supports the inclusion of the left ATL within the language network, a relationship that had been overlooked by classic aphasiology. The asymmetric domain selectivity for language of the left ATL, together with the absence of such an affiliation in the right ATL, is inconsistent with a strict definition of domain-independent amodal functionality in this region of the brain.

Anatomic, clinical, and neuropsychological correlates of spelling errors in primary progressive aphasia

This study evaluates spelling errors in the three subtypes of primary progressive aphasia (PPA): agrammatic (PPA-G), logopenic (PPA-L), and semantic (PPA-S). Forty-one PPA patients and 36 age-matched healthy controls were administered a test of spelling. The total number of errors and types of errors in spelling to dictation of regular words, exception words and nonwords, were recorded. Error types were classified based on phonetic plausibility. In the first analysis, scores were evaluated by clinical diagnosis. Errors in spelling exception words and phonetically plausible errors were seen in PPA-S. Conversely, PPA-G was associated with errors in nonword spelling and phonetically implausible errors. In the next analysis, spelling scores were correlated to other neuropsychological language test scores. Significant correlations were found between exception word spelling and measures of naming and single word comprehension. Nonword spelling correlated with tests of grammar and repetition. Global language measures did not correlate significantly with spelling scores, however. Cortical thickness analysis based on MRI showed that atrophy in several language regions of interest were correlated with spelling errors. Atrophy in the left supramarginal gyrus and inferior frontal gyrus (IFG) pars orbitalis correlated with errors in nonword spelling, while thinning in the left temporal pole and fusiform gyrus correlated with errors in exception word spelling. Additionally, phonetically implausible errors in regular word spelling correlated with thinning in the left IFG pars triangularis and pars opercularis. Together, these findings suggest two independent systems for spelling to dictation, one phonetic (phoneme to grapheme conversion), and one lexical (whole word retrieval).

Electrophysiology of Object Naming in Primary Progressive Aphasia

Primary progressive aphasia (PPA), a selective neurodegeneration of the language network, frequently causes object naming impairments. We examined the N400 event-related potential (ERP) to explore interactions between object recognition and word processing in 20 PPA patients and 15 controls. Participants viewed photographs of objects, each followed by a word that was either a match to the object, a semantically related mismatch, or an unrelated mismatch. Patients judged whether word–object pairs matched with high accuracy (94% PPA group; 98% control group), but they failed to exhibit the normal N400 category effect (N400c), defined as a larger N400 to unrelated versus related mismatch words. In contrast, the N400 mismatch effect (N400m), defined as a larger N400 to mismatch than match words, was observed in both groups. N400m magnitude was positively correlated with neuropsychological measures of word comprehension but not fluency or grammatical competence, and therefore reflected the semantic component of naming. After ERP testing, patients were asked to name the same set of objects aloud. Trials with objects that could not be named were found to lack an N400m, although the name had been correctly recognized at the matching stage. Even accurate overt naming did not necessarily imply normal semantic processing, as shown by the absent N400c. The N400m was preserved in one patient with postsemantic anomia, who could write the names of objects she could not verbalize. N400 analyses can thus help dissect the multiple cognitive mechanisms that contribute to object naming failures in PPA.

Functional Connectivity is Reduced in Early-stage Primary Progressive Aphasia When Atrophy is not Prominent

Primary progressive aphasia (PPA) is a clinical syndrome of language decline caused by neurodegenerative pathology. Although language impairments in PPA are typically localized via the morphometric assessment of atrophy, functional changes may accompany or even precede detectable structural alterations, in which case resting state functional connectivity (RSFC) could provide an alternative approach. The goal of this study was to determine whether language network RSFC is reduced in early-stage PPA when atrophy is not prominent. We identified 10 individuals with early-stage agrammatic variant of PPA with no prominent cortical thinning compared with nonaphasic controls. RSFC between 2 nodes of the language network and 2 nodes of the default mode network were compared between agrammatic variant of PPA and healthy control participants. Language network connectivity was comparable with controls among patients with milder agrammatism, but was significantly reduced in patients with more pronounced agrammatism. No group differences were observed in default mode network connectivity, demonstrating specificity of findings. In early stages of PPA when cortical atrophy is not prominent, RSFC provides an alternative method for probing the neuroanatomic substrates of language impairment. RSFC may be of particular utility in studies on early interventions for neurodegenerative disease, either to identify anatomic targets for intervention or as an outcome measure of therapeutic efficacy.

A nonverbal route to conceptual knowledge involving the right anterior temporal lobe

ABSTRACT The semantic variant of primary progressive aphasia (PPA‐S) is diagnosed based on impaired single‐word comprehension, but nonverbal impairments in face and object recognition can also be present, particularly in later disease stages. PPA‐S is associated with focal atrophy in the left anterior temporal lobe (ATL), often accompanied by a lesser degree of atrophy in the right ATL. According to a dual‐route account, the left ATL is critical for verbal access to conceptual knowledge while nonverbal access to conceptual knowledge depends upon the integrity of right ATL. Consistent with this view, single‐word comprehension deficits in PPA‐S have consistently been linked to the degree of atrophy in left ATL. In the current study we examined object processing and cortical thickness in 19 patients diagnosed with PPA‐S, to evaluate the hypothesis that nonverbal object impairments would instead be determined by the amount of atrophy in the right ATL. All patients demonstrated inability to access conceptual knowledge on standardized tests with word stimuli: they were unable to match spoken words with their corresponding pictures on the Peabody Picture Vocabulary Test. Only a minority of patients, however, performed abnormally on an experimental thematic verification task, which requires judgments as to whether pairs of object pictures are thematically‐associated, and does not rely on auditory or visual word input. The entire PPA‐S group showed cortical thinning in left ATL, but atrophy in right ATL was more prominent in the subgroup with low verification scores. Thematic verification scores were correlated with cortical thickness in the right rather than left ATL, an asymmetric mapping which persisted when controlling for the degree of atrophy in the contralateral hemisphere. These results are consistent with a dual‐route account of conceptual knowledge: breakdown of the verbal left hemispheric route produces an aphasic syndrome, which is only accompanied by visual object processing impairments when the nonverbal right hemispheric route is also compromised. HighlightsAnterior temporal lobes have different functions in each hemisphere.Left anterior temporal lobe supports noun recognition.Right anterior temporal lobe supports recognition of object images.

Eye movements as probes of lexico-semantic processing in a patient with primary progressive aphasia

Eye movement trajectories during a verbally cued object search task were used as probes of lexico-semantic associations in an anomic patient with primary progressive aphasia. Visual search was normal on trials where the target object could be named but became lengthy and inefficient on trials where the object failed to be named. The abnormality was most profound if the noun denoting the object could not be recognized. Even trials where the name of the target object was recognized but not retrieved triggered abnormal eye movements, demonstrating that retrieval failures can have underlying associative components despite intact comprehension of the corresponding noun.