Dissociating the functional roles of arcuate fasciculus subtracts in speech production.

Recent tractography and microdissection studies have shown that the left arcuate fasciculus (AF)-a fiber tract thought to be crucial for speech production-consists of a minimum of 2 subtracts directly connecting the temporal and frontal cortex. These subtracts link the posterior superior temporal gyrus (STG) and middle temporal gyrus (MTG) to the inferior frontal gyrus. Although they have been hypothesized to mediate different functions in speech production, direct evidence for this hypothesis is lacking. To functionally segregate the 2 AF segments, we combined functional magnetic resonance imaging with diffusion-weighted imaging and probabilistic tractography using 2 prototypical speech production tasks, namely spoken pseudoword repetition (tapping sublexical phonological mapping) and verb generation (tapping lexical-semantic mapping). We observed that the repetition of spoken pseudowords is mediated by the subtract of STG, while generating an appropriate verb to a spoken noun is mediated by the subtract of MTG. Our findings provide strong evidence for a functional dissociation between the AF subtracts, namely a sublexical phonological mapping by the STG subtract and a lexical-semantic mapping by the MTG subtract. Our results contribute to the unraveling of a century-old controversy concerning the functional role in speech production of a major fiber tract involved in language.

Comparing human and chimpanzee temporal lobe neuroanatomy reveals modifications to human language hubs beyond the frontotemporal arcuate fasciculus.

The biological foundation for the language-ready brain in the human lineage remains a debated subject. In humans, the arcuate fasciculus (AF) white matter and the posterior portions of the middle temporal gyrus are crucial for language. Compared with other primates, the human AF has been shown to dramatically extend into the posterior temporal lobe, which forms the basis of a number of models of the structural connectivity basis of language. Recent advances in both language research and comparative neuroimaging invite a reassessment of the anatomical differences in language streams between humans and our closest relatives. Here, we show that posterior temporal connectivity via the AF in humans compared with chimpanzees is expanded in terms of its connectivity not just to the ventral frontal cortex but also to the parietal cortex. At the same time, posterior temporal regions connect more strongly to the ventral white matter in chimpanzees as opposed to humans. This pattern is present in both brain hemispheres. Additionally, we show that the anterior temporal lobe harbors a combination of connections present in both species through the inferior fronto-occipital fascicle and human-unique expansions through the uncinate and middle and inferior longitudinal fascicles. These findings elucidate structural changes that are unique to humans and may underlie the anatomical foundations for full-fledged language capacity.

The Diagnostic Value of Language Screening in Primary Progressive Aphasia: Validation and Application of the Sydney Language Battery.

PURPOSE: The three variants of primary progressive aphasia (PPA) differ in clinical presentation, underlying brain pathology, and clinical course, which stresses the need for early differentiation. However, brief cognitive tests that validly distinguish between all PPA variants are lacking. The Sydney Language Battery (SYDBAT) is a promising screening instrument that can be used as a first step in a comprehensive neuropsychological assessment to distinguish PPA subtypes, but evidence on its validity and reliability is to date limited. In the current study, the validation and diagnostic value of the SYDBAT are described for discriminating PPA subtypes as well as distinguishing PPA from mild cognitive impairment (MCI) or Alzheimer's dementia (AD). METHOD: Forty-five patients with PPA (13 with semantic PPA, 20 with logopenic PPA, and 12 with nonfluent/agrammatic PPA), 25 MCI patients, 13 AD patients, and 50 cognitively unimpaired controls were included in this study. Both patients and controls completed the SYDBAT-NL (Dutch version). Performance on and predictive ability of the four subtests (i.e., Naming, Word Comprehension, Repetition, and Semantic Association) were assessed. In addition, construct validity and internal consistency were examined. RESULTS: Different SYDBAT performance patterns were found across PPA and non-PPA patient groups. While a discriminant function analysis based on SYDBAT subtest scores could predict PPA subtype with 78% accuracy, it was more difficult to disentangle PPA from non-PPA patients based on SYDBAT scores alone. For assisting in clinical interpretation, simple rules were set up and translated into a diagnostic decision tree for subtyping PPA, which was capable of diagnosing a large proportion of the cases. Satisfying validity and reliability measures were found. CONCLUSIONS: The SYDBAT is an easy-to-use and promising screen for assessing single-word language processes, which may contribute to the differential diagnostic process of PPA and the assessment of language impairment in MCI and AD. It can be easily implemented for initial screening of patients in a memory clinic.

How the speed of word finding depends on ventral tract integrity in primary progressive aphasia.

Primary progressive aphasia (PPA) is a clinical neurodegenerative syndrome with word finding problems as a core clinical symptom. Many aspects of word finding have been clarified in psycholinguistics using picture naming and a picture-word interference (PWI) paradigm, which emulates naming under contextual noise. However, little is known about how word finding depends on white-matter tract integrity, in particular, the atrophy of tracts located ventrally to the Sylvian fissure. To elucidate this question, we examined word finding in individuals with PPA and healthy controls employing PWI, tractography, and computer simulations using the WEAVER++ model of word finding. Twenty-three individuals with PPA and twenty healthy controls named pictures in two noise conditions. Mixed-effects modelling was performed on naming accuracy and reaction time (RT) and fixel-based tractography analyses were conducted to assess the relation between ventral white-matter integrity and naming performance. Naming RTs were longer for individuals with PPA compared to controls and, critically, individuals with PPA showed a larger noise effect compared to controls. Moreover, this difference in noise effect was differentially related to tract integrity. Whereas the noise effect did not depend much on tract integrity in controls, a lower tract integrity was related to a smaller noise effect in individuals with PPA. Computer simulations supported an explanation of this paradoxical finding in terms of reduced propagation of noise when tract integrity is low. By using multimodal analyses, our study indicates the significance of the ventral pathway for naming and the importance of RT measurement in the clinical assessment of PPA.

Episodic and working memory function in Primary Progressive Aphasia: A meta-analysis.

OBJECTIVE: The distinction between Primary Progressive Aphasia (PPA) variants remains challenging for clinicians, especially for the non-fluent (nfv-PPA) and the logopenic variants (lv-PPA). Previous research suggests that memory tests might aid this differentiation. This meta-analysis compares memory function among PPA variants. METHOD: Effects sizes were extracted from 41 studies (N = 849). Random-effects models were used to compare performance on episodic and working memory tests among PPA patients and healthy controls, and between the PPA variants. RESULTS: Memory deficits were frequently observed in PPA compared to controls, with large effect sizes for lv-PPA (Hedges' g = -2.04 [-2.58 to -1.49]), nfv-PPA (Hedges' g = -1.26 ([-1.60 to -0.92], p < .001)), and the semantic variant (sv-PPA; Hedges' g = -1.23 [-1.50 to -0.97]). Sv-PPA showed primarily verbal memory deficits, whereas lv-PPA showed worse performance than nfv-PPA on both verbal and non-verbal memory tests. CONCLUSIONS: Memory deficits were more pronounced in lv-PPA compared to nfv-PPA. This suggests that memory tests may be helpful to distinguish between these PPA variants.

Intellectual development in Noonan syndrome: a longitudinal study.

INTRODUCTION: Although cognitive impairments in adults with Noonan syndrome seem to be limited to a low-average intelligence and slower processing speed, studies in children with Noonan syndrome have demonstrated more extensive cognitive problems. These include deficits in language skills, memory, attention, and executive functioning. This longitudinal study is the first to investigate intellectual development in a group of individuals with Noonan syndrome. METHODS: Sixteen patients with Noonan syndrome underwent intelligence assessment both in childhood and in adulthood, using Wechsler's intelligence scales. IQ scores and Wechsler standard scores achieved in childhood and adulthood were compared. Subsequently, verbal and performance IQ in childhood were used as predictors for adult IQ and index scores. RESULTS: Compared with childhood scores, adult full-scale IQ and performance IQ significantly increased. Adult performance IQ was higher than verbal IQ. Childhood performance IQ and verbal IQ together predicted all adult IQ and index scores, except for the processing speed index. DISCUSSION: Childhood IQ was a significant predictor of adult intelligence in patients with Noonan syndrome. Performance IQ advanced to a normal level in adulthood, while verbal IQ did not develop proportionately, resulting in a discrepancy between adult performance IQ and verbal IQ. This finding could suggest a delay in the development of executive functioning in patients with Noonan syndrome, which seems to be outgrown in adulthood.