A Linear Structural Equation Model for Covert Verb Generation Based on Independent Component Analysis of fMRI Data from Children and Adolescents

Human language is a complex and protean cognitive ability. Young children, following well defined developmental patterns learn language rapidly and effortlessly producing full sentences by the age of 3 years. However, the language circuitry continues to undergo significant neuroplastic changes extending well into teenage years. Evidence suggests that the developing brain adheres to two rudimentary principles of functional organization: functional integration and functional specialization. At a neurobiological level, this distinction can be identified with progressive specialization or focalization reflecting consolidation and synaptic reinforcement of a network (Lenneberg, 1967; Muller et al., 1998; Berl et al., 2006). In this paper, we used group independent component analysis and linear structural equation modeling (McIntosh and Gonzalez-Lima, 1994; Karunanayaka et al., 2007) to tease out the developmental trajectories of the language circuitry based on fMRI data from 336 children ages 5–18 years performing a blocked, covert verb generation task. The results are analyzed and presented in the framework of theoretical models for neurocognitive brain development. This study highlights the advantages of combining both modular and connectionist approaches to cognitive functions; from a methodological perspective, it demonstrates the feasibility of combining data-driven and hypothesis driven techniques to investigate the developmental shifts in the semantic network

Mapping language networks and their association with verbal abilities in paediatric epilepsy using MEG and graph analysis

Recent theoretical models of language have emphasised the importance of integration within distributed networks during language processing. This is particularly relevant to young patients with epilepsy, as the topology of the functional network and its dynamics may be altered by the disease, resulting in reorganisation of functional language networks. Thus, understanding connectivity within the language network in patients with epilepsy could provide valuable insights into healthy and pathological brain function, particularly when combined with clinical correlates. The objective of this study was to investigate interactions within the language network in a paediatric population of epilepsy patients using measures of MEG phase synchronisation and graph-theoretical analysis, and to examine their association with language abilities. Task dependent increases in connectivity were observed in fronto-temporal networks during verb generation across a group of 22 paediatric patients (9 males and 13 females; mean age 14 years). Differences in network connectivity were observed between patients with typical and atypical language representation and between patients with good and poor language abilities. In addition, node centrality in left frontal and temporal regions was significantly associated with language abilities, where patients with good language abilities had significantly higher node centrality within inferior frontal and superior temporal regions of the left hemisphere, compared to patients with poor language abilities. Our study is one of the first to apply task-based measures of MEG network synchronisation in paediatric epilepsy, and we propose that these measures of functional connectivity and node centrality could be used as tools to identify critical regions of the language network prior to epilepsy surgery

Improving language mapping in clinical fMRI through assessment of grammar.

IntroductionBrain surgery in the language dominant hemisphere remains challenging due to unintended post-surgical language deficits, despite using pre-surgical functional magnetic resonance (fMRI) and intraoperative cortical stimulation. Moreover, patients are often recommended not to undergo surgery if the accompanying risk to language appears to be too high. While standard fMRI language mapping protocols may have relatively good predictive value at the group level, they remain sub-optimal on an individual level. The standard tests used typically assess lexico-semantic aspects of language, and they do not accurately reflect the complexity of language either in comprehension or production at the sentence level. Among patients who had left hemisphere language dominance we assessed which tests are best at activating language areas in the brain.MethodWe compared grammar tests (items testing word order in actives and passives, wh-subject and object questions, relativized subject and object clauses and past tense marking) with standard tests (object naming, auditory and visual responsive naming), using pre-operative fMRI. Twenty-five surgical candidates (13 females) participated in this study. Sixteen patients presented with a brain tumor, and nine with epilepsy. All participants underwent two pre-operative fMRI protocols: one including CYCLE-N grammar tests (items testing word order in actives and passives, wh-subject and object questions, relativized subject and object clauses and past tense marking); and a second one with standard fMRI tests (object naming, auditory and visual responsive naming). fMRI activations during performance in both protocols were compared at the group level, as well as in individual candidates.ResultsThe grammar tests generated more volume of activation in the left hemisphere (left/right angular gyrus, right anterior/posterior superior temporal gyrus) and identified additional language regions not shown by the standard tests (e.g., left anterior/posterior supramarginal gyrus). The standard tests produced more activation in left BA 47. Ten participants had more robust activations in the left hemisphere in the grammar tests and two in the standard tests. The grammar tests also elicited substantial activations in the right hemisphere and thus turned out to be superior at identifying both right and left hemisphere contribution to language processing.ConclusionThe grammar tests may be an important addition to the standard pre-operative fMRI testing

Neuroplasticity of language networks in aphasia: advances, updates, and future challenges

Researchers have sought to understand how language is processed in the brain, how brain damage affects language abilities, and what can be expected during the recovery period since the early 19th century. In this review, we first discuss mechanisms of damage and plasticity in the post-stroke brain, both in the acute and the chronic phase of recovery. We then review factors that are associated with recovery. First, we review organism intrinsic variables such as age, lesion volume and location and structural integrity that influence language recovery. Next, we review organism extrinsic factors such as treatment that influence language recovery. Here, we discuss recent advances in our understanding of language recovery and highlight recent work that emphasizes a network perspective of language recovery. Finally, we propose our interpretation of the principles of neuroplasticity, originally proposed by Kleim and Jones (1) in the context of extant literature in aphasia recovery and rehabilitation. Ultimately, we encourage researchers to propose sophisticated intervention studies that bring us closer to the goal of providing precision treatment for patients with aphasia and a better understanding of the neural mechanisms that underlie successful neuroplasticity.P50 DC012283 - NIDCD NIH HHSPublished versio

The Cerebellum\u27s Relationship to Language Function Following Perinatal Stroke

While recent studies have demonstrated the association between the cerebellum and higher-order cognitive functioning, it is still unclear how volumetric differences of specific regions of interests within the cerebellum across typical and atypical development are related to language function. We have done so by measuring the volume of cerebellar subregions of healthy controls, and compared the volume to behavioral measures of language function. We then followed with an analysis of the cerebellum’s relationship to language function following perinatal stroke, which provides us with a greater knowledge of the impact of a cortical injury on cerebellar development and the cognitive outcomes of such changes by again measuring and comparing the volume of cerebellar subregions to language measures. We report several novel findings that contribute to the growing understanding of the cerebellum’s relationship to language function. We found that greater right laterality of lobules IV and VIIb predicted performance on expressive language measures in typical development. We also found that following an early injury to the cerebral cortex\u27s left hemisphere, there was a bilateral association of cerebellar lobules to language measures. Specifically, we found greater right laterality of the cerebellar cortex, lobule IV, and Crus I predicted higher scores on the Expressive Vocabulary Test. While greater left lateralization of lobule VI predicted expressive language and lobule VIIIa predicted grammatical judgment, especially early in development, and greater left lateralization of lobule IX predicted receptive vocabulary. Implications of the findings of volumetric association to language function and poststroke development within the cerebellum are discussed

Multivariate patterns of brain-behavior associations across the adult lifespan

The nature of brain-behavior covariations with increasing age is poorly understood. In the current study, we used a multivariate approach to investigate the covariation between behavioral-health variables and brain features across adulthood. We recruited healthy adults aged 20–73 years-old (29 younger, mean age = 25.6 years; 30 older, mean age = 62.5 years), and collected structural and functional MRI (s/fMRI) during a resting-state and three tasks. From the sMRI, we extracted cortical thickness and subcortical volumes; from the fMRI, we extracted activation peaks and functional network connectivity (FNC) for each task. We conducted canonical correlation analyses between behavioral-health variables and the sMRI, or the fMRI variables, across all participants. We found significant covariations for both types of neuroimaging phenotypes (ps = 0.0004) across all individuals, with cognitive capacity and age being the largest opposite contributors. We further identified different variables contributing to the models across phenotypes and age groups. Particularly, we found behavior was associated with different neuroimaging patterns between the younger and older groups. Higher cognitive capacity was supported by activation and FNC within the executive networks in the younger adults, while it was supported by the visual networks’ FNC in the older adults. This study highlights how the brain-behavior covariations vary across adulthood and provides further support that cognitive performance relies on regional recruitment that differs between older and younger individuals

Theta-Modulated Gamma-Band Synchronization Among Activated Regions During a Verb Generation Task

Expressive language is complex and involves processing within a distributed network of cortical regions. Functional MRI and magnetoencephalography (MEG) have identified brain areas critical for expressive language, but how these regions communicate across the network remains poorly understood. It is thought that synchronization of oscillations between neural populations, particularly at a gamma rate (>30 Hz), underlies functional integration within cortical networks. Modulation of gamma rhythms by theta-band oscillations (4–8 Hz) has been proposed as a mechanism for the integration of local cell coalitions into large-scale networks underlying cognition and perception. The present study tested the hypothesis that these oscillatory mechanisms of functional integration were present within the expressive language network. We recorded MEG while subjects performed a covert verb generation task. We localized activated cortical regions using beamformer analysis, calculated inter-regional phase locking between activated areas, and measured modulation of inter-regional gamma synchronization by theta phase. The results show task-dependent gamma-band synchronization among regions activated during the performance of the verb generation task, and we provide evidence that these transient and periodic instances of high-frequency connectivity were modulated by the phase of cortical theta oscillations. These findings suggest that oscillatory synchronization and cross-frequency interactions are mechanisms for functional integration among distributed brain areas supporting expressive language processing

Convergent and divergent fMRI responses in children and adults to increasing language production demands

In adults, patterns of neural activation associated with perhaps the most basic language skill—overt object naming—are extensively modulated by the psycholinguistic and visual complexity of the stimuli. Do children's brains react similarly when confronted with increasing processing demands, or they solve this problem in a different way? Here we scanned 37 children aged 7–13 and 19 young adults who performed a well-normed picture-naming task with 3 levels of difficulty. While neural organization for naming was largely similar in childhood and adulthood, adults had greater activation in all naming conditions over inferior temporal gyri and superior temporal gyri/supramarginal gyri. Manipulating naming complexity affected adults and children quite differently: neural activation, especially over the dorsolateral prefrontal cortex, showed complexity-dependent increases in adults, but complexity-dependent decreases in children. These represent fundamentally different responses to the linguistic and conceptual challenges of a simple naming task that makes no demands on literacy or metalinguistics. We discuss how these neural differences might result from different cognitive strategies used by adults and children during lexical retrieval/production as well as developmental changes in brain structure and functional connectivity