Modeling the neurocognitive dynamics of language across the lifespan.

Healthy aging is associated with a heterogeneous decline across cognitive functions, typically observed between language comprehension and language production (LP). Examining resting-state fMRI and neuropsychological data from 628 healthy adults (age 18-88) from the CamCAN cohort, we performed state-of-the-art graph theoretical analysis to uncover the neural mechanisms underlying this variability. At the cognitive level, our findings suggest that LP is not an isolated function but is modulated throughout the lifespan by the extent of inter-cognitive synergy between semantic and domain-general processes. At the cerebral level, we show that default mode network (DMN) suppression coupled with fronto-parietal network (FPN) integration is the way for the brain to compensate for the effects of dedifferentiation at a minimal cost, efficiently mitigating the age-related decline in LP. Relatedly, reduced DMN suppression in midlife could compromise the ability to manage the cost of FPN integration. This may prompt older adults to adopt a more cost-efficient compensatory strategy that maintains global homeostasis at the expense of LP performances. Taken together, we propose that midlife represents a critical neurocognitive juncture that signifies the onset of LP decline, as older adults gradually lose control over semantic representations. We summarize our findings in a novel synergistic, economical, nonlinear, emergent, cognitive aging model, integrating connectomic and cognitive dimensions within a complex system perspective.

Complex visual discrimination is impaired after right, but not left, anterior temporal lobectomy.

The prevailing view in human cognitive neuroscience associates the medial temporal lobes (MTLs) with declarative memory. Compelling experimental evidence has, however, demonstrated that these regions are specialized according to the representations processed, irrespective of the cognitive domain assessed. This account was supported by the study of patients with bilateral medial temporal amnesia, who exhibit impairments in perceptual tasks involving complex visual stimuli. Yet, little is known regarding the impact of unilateral MTL damage on complex visual abilities. To address this issue, we administered a visual matching task to 20 patients who underwent left (N = 12) or right (N = 8) anterior temporal lobectomy for drug-resistant epilepsy and to 38 healthy controls. Presentation viewpoint was manipulated to increase feature ambiguity, as this is critical to reveal impairments in perceptual tasks. Similar to control participants, patients with left-sided damage succeeded in all task conditions. In contrast, patients with right-sided damage had decreased accuracy compared with that of the other two groups, as well as increased response time. Notably, the accuracy of those with right-sided damage did not exceed chance level when feature ambiguity was high (i.e., when stimuli were presented from different viewpoints) for the most complex classes of stimuli (i.e., scenes and buildings, compared with single objects). The pattern reported in bilateral patients in previous studies was therefore reproduced in patients with right, but not left, resection. These results suggest that the complex visual-representation functions supported by the MTL are right-lateralized, and raise the question as to how the representational account of these regions applies to representations supported by left MTL regions.

Prediction of the clinical and naming status after anterior temporal lobe resection in patients with epilepsy.

By assessing the cognitive capital, neuropsychological evaluation (NPE) plays a vital role in the perioperative workup of patients with refractory focal epilepsy. In this retrospective study, we used cutting-edge statistical approaches to examine a group of 47 patients with refractory temporal lobe epilepsy (TLE), who underwent standard anterior temporal lobectomy (ATL). Our objective was to determine whether NPE may represent a robust predictor of the postoperative status, two years after surgery. Specifically, based on pre- and postsurgical neuropsychological data, we estimated the sensitivity of cognitive indicators to predict and to disentangle phenotypes associated with more or less favorable outcomes. Engel (ENG) scores were used to assess clinical outcome, and picture naming (NAM) performance to estimate naming status. Two methods were applied: (a) machine learning (ML) to explore cognitive sensitivity to postoperative outcomes; and (b) graph theory (GT) to assess network properties reflecting favorable vs. less favorable phenotypes after surgery. Specific neuropsychological indices assessing language, memory, and executive functions can globally predict outcomes. Interestingly, preoperative cognitive networks associated with poor postsurgical outcome already exhibit an atypical, highly modular and less densely interconnected configuration. We provide statistical and clinical tools to anticipate the condition after surgery and achieve a more personalized clinical management. Our results also shed light on possible mechanisms put in place for cognitive adaptation after acute injury of central nervous system in relation with surgery.

Hubs disruption in mesial temporal lobe epilepsy. A resting-state fMRI study on a language-and-memory network.

Mesial temporal lobe epilepsy (mTLE) affects the brain networks at several levels and patients suffering from mTLE experience cognitive impairment for language and memory. Considering the importance of language and memory reorganization in this condition, the present study explores changes of the embedded language-and-memory network (LMN) in terms of functional connectivity (FC) at rest, as measured with functional MRI. We also evaluate the cognitive efficiency of the reorganization, that is, whether or not the reorganizations support or allow the maintenance of optimal cognitive functioning despite the seizure-related damage. Data from 37 patients presenting unifocal mTLE were analyzed and compared to 48 healthy volunteers in terms of LMN-FC using two methods: pairwise correlations (region of interest [ROI]-to-ROI) and graph theory. The cognitive efficiency of the LMN-FC reorganization was measured using correlations between FC parameters and language and memory scores. Our findings revealed a large perturbation of the LMN hubs in patients. We observed a hyperconnectivity of limbic areas near the dysfunctional hippocampus and mainly a hypoconnectivity for several cortical regions remote from the dysfunctional hippocampus. The loss of FC was more important in left mTLE (L-mTLE) than in right (R-mTLE) patients. The LMN-FC reorganization may not be always compensatory and not always useful for patients as it may be associated with lower cognitive performance. We discuss the different connectivity patterns obtained and conclude that interpretation of FC changes in relation to neuropsychological scores is important to determine cognitive efficiency, suggesting the concept of "connectome" would gain to be associated with a "cognitome" concept.

Missing links: The functional unification of language and memory (L∪M).

The field of neurocognition is currently undergoing a significant change of perspective. Traditional neurocognitive models evolved into an integrative and dynamic vision of cognitive functioning. Dynamic integration assumes an interaction between cognitive domains traditionally considered to be distinct. Language and declarative memory are regarded as separate functions supported by different neural systems. However, they also share anatomical structures (notably, the inferior frontal gyrus, the supplementary motor area, the superior and middle temporal gyrus, and the hippocampal complex) and cognitive processes (such as semantic and working memory) that merge to endorse our quintessential daily lives. We propose a new model, "L∪M" (i.e., Language/union/Memory), that considers these two functions interactively. We fractionated language and declarative memory into three fundamental dimensions or systems ("Receiver-Transmitter", "Controller-Manager" and "Transformer-Associative" Systems), that communicate reciprocally. We formalized their interactions at the brain level with a connectivity-based approach. This new taxonomy overcomes the modular view of cognitive functioning and reconciles functional specialization with plasticity in neurological disorders.

Reconfiguration dynamics of a language-and-memory network in healthy participants and patients with temporal lobe epilepsy.

Current theoretical frameworks suggest that human behaviors are based on strong and complex interactions between cognitive processes such as those underlying language and memory functions in normal and neurological populations. We were interested in assessing the dynamic cerebral substrate of such interaction between language and declarative memory, as the composite function, in healthy controls (HC, N = 19) and patients with temporal lobe epilepsy (TLE, N = 16). Our assumption was that the language and declarative memory integration is based on a language-and-memory network (LMN) that is dynamic and reconfigures according to task demands and brain status. Therefore, we explored two types of LMN dynamics, a state reconfiguration (intrinsic resting-state compared to extrinsic state assessed with a sentence recall task) and a reorganization of state reconfiguration (TLE compared to HC). The dynamics was evaluated in terms of segregation (community or module detection) and integration (connector hubs). In HC, the level of segregation was the same in both states and the mechanism of LMN state reconfiguration was shown through module change of key language and declarative memory regions with integrative roles. In TLE patients, the reorganization of LMN state reconfiguration was reflected in segregation increase and extrinsic modules that were based on shorter-distance connections. While lateral and mesial temporal regions enabled state reconfiguration in HC, these regions showed reduced flexibility in TLE. We discuss our results in a connectomic perspective and propose a dynamic model of language and declarative memory functioning. We claim that complex and interactive cognitive functions, such as language and declarative memory, should be investigated dynamically, considering the interaction between cognitive networks.

Mapping of Language-and-Memory Networks in Patients With Temporal Lobe Epilepsy by Using the GE2REC Protocol.

Preoperative mapping of language and declarative memory functions in temporal lobe epilepsy (TLE) patients is essential since they frequently encounter deterioration of these functions and show variable degrees of cerebral reorganization. Due to growing evidence on language and declarative memory interdependence at a neural and neuropsychological level, we propose the GE2REC protocol for interactive language-and-memory network (LMN) mapping. GE2REC consists of three inter-related tasks, sentence generation with implicit encoding (GE) and two recollection (2REC) memory tasks: recognition and recall. This protocol has previously been validated in healthy participants, and in this study, we showed that it also maps the LMN in the left TLE (N = 18). Compared to healthy controls (N = 19), left TLE (LTLE) showed widespread inter- and intra-hemispheric reorganization of the LMN through reduced activity of regions engaged in the integration and the coordination of this meta-network. We also illustrated how this protocol could be implemented in clinical practice individually by presenting two case studies of LTLE patients who underwent efficient surgery and became seizure-free but showed different cognitive outcomes. This protocol can be advantageous for clinical practice because it (a) is short and easy to perform; (b) allows brain mapping of essential cognitive functions, even at an individual level; (c) engages language-and-memory interaction allowing to evaluate the integrative processes within the LMN; (d) provides a more comprehensive assessment by including both verbal and visual modalities, as well as various language and memory processes. Based on the available postsurgical data, we presented preliminary results obtained with this protocol in LTLE patients that could potentially inform the clinical practice. This implies the necessity to further validate the potential of GE2REC for neurosurgical planning, along with two directions, guiding resection and describing LMN neuroplasticity at an individual level.

Strategies and cognitive reserve to preserve lexical production in aging.

In the absence of any neuropsychiatric condition, older adults may show declining performance in several cognitive processes and among them, in retrieving and producing words, reflected in slower responses and even reduced accuracy compared to younger adults. To overcome this difficulty, healthy older adults implement compensatory strategies, which are the focus of this paper. We provide a review of mainstream findings on deficient mechanisms and possible neurocognitive strategies used by older adults to overcome the deleterious effects of age on lexical production. Moreover, we present findings on genetic and lifestyle factors that might either be protective or risk factors of cognitive impairment in advanced age. We propose that "aging-modulating factors" (AMF) can be modified, offering prevention opportunities against aging effects. Based on our review and this proposition, we introduce an integrative neurocognitive model of mechanisms and compensatory strategies for lexical production in older adults (entitled Lexical Access and Retrieval in Aging, LARA). The main hypothesis defended in LARA is that cognitive aging evolves heterogeneously and involves complementary domain-general and domain-specific mechanisms, with substantial inter-individual variability, reflected at behavioral, cognitive, and brain levels. Furthermore, we argue that the ability to compensate for the effect of cognitive aging depends on the amount of reserve specific to each individual which is, in turn, modulated by the AMF. Our conclusion is that a variety of mechanisms and compensatory strategies coexist in the same individual to oppose the effect of age. The role of reserve is pivotal for a successful coping with age-related changes and future research should continue to explore the modulating role of AMF.

Dissociating facial electromyographic correlates of visual and verbal induced rumination.

Previous research showed that mental rumination, considered as a form of repetitive and negative inner speech, is associated with increased facial muscular activity. However, the relation between these muscular activations and the underlying mental processes is still unclear. In this study, we tried to separate the facial electromyographic correlates of induced rumination related to either i) mechanisms of (inner) speech production or ii) rumination as a state of pondering on negative affects. To this end, we compared two groups of participants submitted to two types of rumination induction (for a total of 85 female undergraduate students without excessive depressive symptoms). The first type of induction was designed to specifically induce rumination in a verbal modality whereas the second one was designed to induce rumination in a visual modality. Following the motor simulation view of inner speech production, we hypothesised that the verbal rumination induction should result in a higher increase of activity in the speech-related muscles as compared to the non-verbal rumination induction. We also hypothesised that relaxation focused on the orofacial area should be more efficient in reducing rumination (when experienced in a verbal modality) than a relaxation focused on a non-orofacial area. Our results do not corroborate these hypotheses, as both rumination inductions resulted in a similar increase of peripheral muscular activity in comparison to baseline levels. Moreover, the two relaxation types were similarly efficient in reducing rumination, whatever the rumination induction. We discuss these results in relation to the inner speech literature and suggest that because rumination is a habitual and automatic form of emotion regulation, it might be a particularly (strongly) internalised and condensed form of inner speech. Pre-registered protocol, preprint, data, as well as reproducible code and figures are available at: https://osf.io/c9pag/.

Interactive mapping of language and memory with the GE2REC protocol.

Previous studies have highlighted the importance of considering cognitive functions from a dynamic and interactive perspective and multiple evidence was brought for a language and memory interaction. In this study performed with healthy participants, we present a new protocol entitled GE2REC that interactively accesses the neural representation of language-and-memory network. This protocol consists of three runs related to each other, providing a link between tasks, in order to assure an interactive measure of linguistic and episodic memory processes. GE2REC consists of a sentence generation (GE) in the auditory modality and two recollecting (2REC) memory tasks, one recognition performed in the visual modality, and another one recall performed in the auditory modality. Its efficiency was evaluated in 20 healthy volunteers using a 3T MR imager. Our results corroborate the ability of GE2REC to robustly activate fronto-temporo-parietal language network as well as temporal mesial, prefrontal and parietal cortices in encoding during sentence generation and recognition. GE2REC is useful because it: (a) requires simultaneous and interactive language-and-memory processes and jointly maps their neural basis; (b) explores encoding and retrieval, managing to elicit activation of mesial temporal structures; (c) is easy to perform, hence being suitable for more restrictive settings, and (d) has an ecological dimension of tasks and stimuli. GE2REC may be useful for studying neuroplasticity of cognitive functions, especially in patients with temporal lobe epilepsy who show reorganization of both language and memory networks. Overall, GE2REC can provide valuable information in terms of the practical foundation of exploration language and memory interconnection.