A cautionary tale on the effects of different covariance structures in linear mixed effects modeling of fMRI data.

With the steadily increasing abundance of longitudinal neuroimaging studies with large sample sizes and multiple repeated measures, questions arise regarding the appropriate modeling of variance and covariance. The current study examined the influence of standard classes of variance-covariance structures in linear mixed effects (LME) modeling of fMRI data from patients with pediatric mild traumatic brain injury (pmTBI; N = 181) and healthy controls (N = 162). During two visits, participants performed a cognitive control fMRI paradigm that compared congruent and incongruent stimuli. The hemodynamic response function was parsed into peak and late peak phases. Data were analyzed with a 4-way (GROUP×VISIT×CONGRUENCY×PHASE) LME using AFNI's 3dLME and compound symmetry (CS), autoregressive process of order 1 (AR1), and unstructured (UN) variance-covariance matrices. Voxel-wise results dramatically varied both within the cognitive control network (UN>CS for CONGRUENCY effect) and broader brain regions (CS>UN for GROUP:VISIT) depending on the variance-covariance matrix that was selected. Additional testing indicated that both model fit and estimated standard error were superior for the UN matrix, likely as a result of the modeling of individual terms. In summary, current findings suggest that the interpretation of results from complex designs is highly dependent on the selection of the variance-covariance structure using LME modeling.

Decomposition in early stages of learning novel morphologically derived words: The impact of linear vs. non-linear structure.

We examined whether morphological decomposition takes place in early stages of learning a novel language, and whether morphological structure (linear vs. non-linear) influences decomposition. Across four sessions, 41 native-Hebrew speakers learned morphologically derived words in a novel morpho-lexicon, with two complex conditions: linear and non-linear; and a third simple condition with monomorphemic words. Participants showed faster learning of trained words in the linear condition, and better generalization to untrained words for both complex conditions compared to the simple condition, with better performance for linear than non-linear morphology. Learning the root morpheme, which provides a concrete meaning, was better than learning template/suffix morphemes, which are more abstract. Overall, our results suggest that saliency of discrete units plays an important role in decomposition in early stages of learning derived words, even for speakers highly familiar with the non-linear structure in their L1.

Start shallow and grow deep: The development of a Hebrew reading brain.

Brain plasticity implies that readers of different orthographies can have different reading networks. Theoretical models suggest that reading acquisition in transparent orthographies relies on mapping smaller orthographic units to phonology, than reading opaque orthographies; but what are the neural mechanisms underlying this difference? Hebrew has a transparent (pointed) script used for beginners, and a non-transparent script used for skilled readers. The current study examined the developmental changes in brain regions associated with phonological and orthographic processes during reading pointed and un-pointed words. Our results highlight some changes that are universal in reading development, such as a developmental increase in frontal involvement (in bilateral inferior frontal gyrus (IFG) pars opercularis), and increase in left asymmetry (in IFG pars opercularis and superior temporal gyrus, STG) of the reading network. Our results also showed a developmental increase in activation in STG, which stands in contrast to previous studies in other orthographies. We further found an interaction of word length and diacritics in bilateral STG and the visual word form area (VWFA) across both groups. These findings suggest that children slightly adjust their reading depending on orthographic transparency, relying on smaller units when reading a transparent script and on larger units when reading an opaque script. Our results also showed that phonological abilities across groups correlated with activation in the VWFA, regardless of transparency, supporting the continued role of phonology at all levels of orthographic transparency. Our findings are consistent with multiple route reading models, in which both phonological and orthographic processing of multiple size units continue to play a role in children's reading of transparent and opaque scripts during reading development. The results further demonstrate the importance of taking into account differences between orthographies when constructing neural models of reading acquisition.

Training flexible conceptual retrieval in post-stroke aphasia.

Semantic therapy in post-stroke aphasia typically focusses on strengthening links between conceptual representations and their lexical-articulatory forms to aid word retrieval. However, research has shown that semantic deficits in this group can affect both verbal and non-verbal tasks, particularly in patients with deregulated retrieval as opposed to degraded knowledge. This study, therefore, aimed to facilitate semantic cognition in a sample of such patients with post-stroke semantic aphasia (SA) by training the identification of both strong and weak semantic associations and providing explicit pictorial feedback that demonstrated both common and more unusual ways of linking concepts together. We assessed the effects of this training on (i) trained and untrained items; and (ii) trained and untrained tasks in eleven individuals with SA. In the training task, the SA group showed improvement with practice, particularly for trained items. A similar untrained task using pictorial stimuli (Camel and Cactus Test) also improved. Together, these results suggest that semantic training can be beneficial in patients with SA and may show some degree of generalization to untrained situations. Future research should seek to understand which patients are most likely to benefit from this type of training.

Intrinsic connectivity of left ventrolateral prefrontal cortex predicts individual differences in controlled semantic retrieval.

Control processes allow us to constrain the retrieval of semantic information from long-term memory so that it is appropriate for the task or context. Control demands are influenced by the strength of the target information itself and by the circumstances in which it is retrieved, with more control needed when relatively weak aspects of knowledge are required and after the sustained retrieval of related concepts. To investigate the neurocognitive basis of individual differences in these aspects of semantic control, we used resting-state fMRI to characterise the intrinsic connectivity of left ventrolateral prefrontal cortex (VLPFC), implicated in controlled retrieval, and examined associations on a paced serial semantic task, in which participants were asked to detect category members amongst distractors. This task manipulated both the strength of target associations and the requirement to sustain retrieval within a narrow semantic category over time. We found that individuals with stronger connectivity between VLPFC and medial prefrontal cortex within the default mode network (DMN) showed better retrieval of strong associations (which are thought to be recalled more automatically). Stronger connectivity between the same VLPFC seed and another DMN region in medial parietal cortex was associated with larger declines in retrieval over the course of the category. In contrast, participants with stronger connectivity between VLPFC and cognitive control regions within the ventral attention network (VAN) had better controlled retrieval of weak associations and were better able to sustain their comprehension throughout the category. These effects overlapped in left insular cortex within the VAN, indicating that a common pattern of connectivity is associated with different aspects of controlled semantic retrieval induced by both the structure of long-term knowledge and the sustained retrieval of related information.

Shared processes resolve competition within and between episodic and semantic memory: Evidence from patients with LIFG lesions.

Semantic cognition is supported by two interactive components: semantic representations and mechanisms that regulate retrieval (cf. 'semantic control'). Neuropsychological studies have revealed a clear dissociation between semantic and episodic memory. This study explores if the same dissociation holds for control processes that act on episodic and semantic memory, or whether both types of long-term memory are supported by the same executive mechanisms. We addressed this question in a case-series of semantic aphasic patients who had difficulty retrieving both verbal and non-verbal conceptual information in an appropriate fashion following infarcts to left inferior frontal gyrus (LIFG). We observed parallel deficits in semantic and episodic memory: (i) the patients' difficulties extended beyond verbal materials to include picture tasks in both domains; (ii) both types of retrieval benefitted from cues designed to reduce the need for internal constraint; (iii) there was little impairment of both semantic and episodic tasks when control demands were minimised; (iv) there were similar effects of distractors across tasks. Episodic retrieval was highly susceptible to false memories elicited by semantically-related distractors, and confidence was inappropriately high in these circumstances. Semantic judgements were also prone to contamination from recent events. These findings demonstrate that patients with deregulated semantic cognition have comparable deficits in episodic retrieval. The results are consistent with a role for LIFG in resolving competition within both episodic and semantic memory, and also in biasing cognition towards task-relevant memory stores when episodic and semantic representations do not promote the same response.

When comprehension elicits incomprehension: Deterioration of semantic categorisation in the absence of stimulus repetition.

Repetition improves retrieval from memory; however, under some circumstances, it can also impair performance. Separate literatures have investigated this phenomenon, including studies showing subjective loss of meaning following 'semantic satiation', slowed naming and categorisation when semantically related items are repeated and semantic 'access deficits' in aphasia. Such effects have been variously explained in terms of habituation of repeatedly accessed representations, increased interference from strongly activated competitors and long-term weight changes reflecting the suppression of non-targets on earlier trials (i.e., retrieval-induced forgetting). While studies of semantic satiation involve massed repetition of individual items, competition and weight changes at the conceptual level should elicit declining comprehension for non-repeated items: this pattern has been demonstrated for picture naming but effects in categorisation are less clear. We developed a paced serial semantic task (PSST), in which participants identified category members among distracters. Performance in healthy young adults deteriorated with ongoing retrieval for non-repeated words belonging to functional categories (e.g., picnic), taxonomic categories (e.g., animal) and feature-based categories (e.g., colour red - 'tomato', 'post box'). This decline was greatest at fast presentation speeds (when there was less time to overcome competition/inhibition) and for strongly associated targets (which may have accrued more inhibition to facilitate earlier target categorisation). Deteriorating performance was also seen across words and pictures, consistent with a conceptual locus. We observed a release from deteriorating categorisation following a switch to a new category, demonstrating that this was not a general effect of time on task. Patients with semantic aphasia, who have deficient semantic control, maintained their performance throughout the categories, unlike younger adults: this finding is hard to reconcile with accounts of declining performance that propose a build-up of competition, since the patients should have had greater difficulty resolving such competition. These results instead suggest that declining performance on our goal-driven categorisation task was linked to the use of a controlled retrieval strategy by healthy young adults. Patients may not have inhibited related non-target knowledge to facilitate initial categorisation like younger volunteers, and consequently they were less vulnerable to declining comprehension in this paradigm. Together, these results demonstrate circumstances which produce declines in continuous categorisation in healthy adults.