Insights on cognitive reorganization after hemispherectomy in Rasmussen's encephalitis. A narrative review.

Rasmussen's encephalitis is a rare neurological pathology affecting one cerebral hemisphere, therefore, posing unique challenges. Patients may undergo hemispherectomy, a surgical procedure after which cognitive development occurs in the isolated contralateral hemisphere. This rare situation provides an excellent opportunity to evaluate brain plasticity and cognitive recovery at a hemispheric level. This literature review synthesizes the existing body of research on cognitive recovery following hemispherectomy in Rasmussen patients, considering cognitive domains and modulatory factors that influence cognitive outcomes. While language function has traditionally been the focus of postoperative assessments, there is a growing acknowledgment of the need to broaden the scope of language investigation in interaction with other cognitive domains and to consider cognitive scaffolding in development and recovery. By synthesizing findings reported in the literature, we delineate how language functions may find support from the right hemisphere after left hemispherectomy, but also how, beyond language, global cognitive functioning is affected. We highlight the critical influence of several factors on postoperative cognitive outcomes, including the timing of hemispherectomy and the baseline preoperative cognitive status, pointing to early surgical intervention as predictive of better cognitive outcomes. However, further specific studies are needed to confirm this correlation. This review aims to emphasize a better understanding of mechanisms underlying hemispheric specialization and plasticity in humans, which are particularly important for both clinical and research advancements. This narrative review underscores the need for an integrative approach based on cognitive scaffolding to provide a comprehensive understanding of mechanisms underlying the reorganization in Rasmussen patients after hemispherectomy.

Finding the Words: How Does the Aging Brain Process Language? A Focused Review of Brain Connectivity and Compensatory Pathways.

As people age, there is a natural decline in cognitive functioning and brain structure. However, the relationship between brain function and cognition in older adults is neither straightforward nor uniform. Instead, it is complex, influenced by multiple factors, and can vary considerably from one person to another. Reserve, compensation, and maintenance mechanisms may help explain why some older adults can maintain high levels of performance while others struggle. These mechanisms are often studied concerning memory and executive functions that are particularly sensitive to the effects of aging. However, language abilities can also be affected by age, with changes in production fluency. The impact of brain changes on language abilities needs to be further investigated to understand the dynamics and patterns of aging, especially successful aging. We previously modeled several compensatory profiles of language production and lexical access/retrieval in aging within the Lexical Access and Retrieval in Aging (LARA) model. In the present paper, we propose an extended version of the LARA model, called LARA-Connectivity (LARA-C), incorporating recent evidence on brain connectivity. Finally, we discuss factors that may influence the strategies implemented with aging. The LARA-C model can serve as a framework to understand individual performance and open avenues for possible personalized interventions.

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.

When Age Tips the Balance: a Dual Mechanism Affecting Hemispheric Specialization for Language.

Aging engenders neuroadaptations, generally reducing specificity and selectivity in functional brain responses. Our investigation delves into the functional specialization of brain hemispheres within language-related networks across adulthood. In a cohort of 728 healthy adults spanning ages 18 to 88, we modeled the trajectories of inter-hemispheric asymmetry concerning the principal functional gradient across 37 homotopic regions of interest (hROIs) of an extensive language network, known as the Language-and-Memory Network. Our findings reveal that over two-thirds of Language-and-Memory Network hROIs undergo asymmetry changes with age, falling into two main clusters. The first cluster evolves from left-sided specialization to right-sided tendencies, while the second cluster transitions from right-sided asymmetry to left-hemisphere dominance. These reversed asymmetry shifts manifest around midlife, occurring after age 50, and are associated with poorer language production performance. Our results provide valuable insights into the influence of functional brain asymmetries on language proficiency and present a dynamic perspective on brain plasticity during the typical aging process.

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.

Cognitive outcome after left functional hemispherectomy on dominant hemisphere in patients with Rasmussen encephalitis: beyond the myth of aphasia. Patient series.

BACKGROUND: Rasmussen encephalitis is a rare chronic neurological pathology frequently treated with functional hemispherectomy (or hemispherotomy). This surgical procedure frees patients of their severe epilepsy associated with the disease but may induce cognitive disorders and notably language alterations after disconnection of the left hemisphere. OBSERVATIONS: The authors describe longitudinally 3 cases of female patients with Rasmussen encephalitis who underwent left hemispherotomy in childhood and benefited from a favorable cognitive outcome. In the first patient, the hemispherotomy occurred at a young age, and the recovery of language and cognitive abilities was rapid and efficient. The second patient benefited from the surgery later in childhood. In addition, she presented a reorganization of language and memory functions that seem to have been at the expense of nonverbal ones. The third patient was a teenager during surgery. She benefited from a more partial cognitive recovery with persistent disorders several years after the surgery. LESSONS: Recovery of cognitive functions, including language, occurs after left hemispherotomy, even when performed late in childhood. Therefore, the surgery should be considered as early as possible to promote intercognitive reorganization.

Comparing the selectivity of vowel representations in cortical auditory vs. motor areas: A repetition-suppression study.

A computational model of speech perception, COSMO (Laurent et al., 2017), predicts that speech sounds should evoke both auditory representations in temporal areas and motor representations mainly in inferior frontal areas. Importantly, the model also predicts that auditory representations should be narrower, i.e. more focused on typical stimuli, than motor representations which would be more tolerant of atypical stimuli. Based on these assumptions, in a repetition-suppression study with functional magnetic resonance imaging data, we show that a sequence of 4 identical vowel sounds produces lower cortical activity (i.e. larger suppression effects) than if the last sound in the sequence is slightly varied. Crucially, temporal regions display an increase in cortical activity even for small acoustic variations, indicating a release of the suppression effect even for stimuli acoustically close to the first stimulus. In contrast, inferior frontal, premotor, insular and cerebellar regions show a release of suppression for larger acoustic variations. This "auditory-narrow motor-wide" pattern for vowel stimuli adds to a number of similar findings on consonant stimuli, confirming that the selectivity of speech sound representations in temporal auditory areas is narrower than in frontal motor areas in the human cortex.

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.

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.

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.

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.

Lateropulsion After Hemispheric Stroke: A Form of Spatial Neglect Involving Graviception.

OBJECTIVE: To test the hypothesis that lateropulsion is an entity expressing an impaired body orientation with respect to gravity in relation to a biased graviception and spatial neglect. METHODS: Data from the DOBRAS cohort (ClinicalTrials.gov: NCT03203109) were collected 30 days after a first hemisphere stroke. Lateral body tilt, pushing, and resistance were assessed with the Scale for Contraversive Pushing. RESULTS: Among 220 individuals, 72% were upright and 28% showed lateropulsion (tilters [14%] less severe than pushers [14%]). The 3 signs had very high factor loadings (>0.90) on a same dimension, demonstrating that lateropulsion was effectively an entity comprising body tilt (cardinal sign), pushing, and resistance. The factorial analyses also showed that lateropulsion was inseparable from the visual vertical (VV), a criterion referring to vertical orientation (graviception). Contralesional VV biases were frequent (44%), with a magnitude related to lateropulsion severity: upright -0.6° (-2.9; 2.4), tilters -2.9° (-7; 0.8), and pushers -12.3° (-15.4; -8.5). Ipsilesional VV biases were less frequent and milder (p < 0.001). They did not deal with graviception, 84% being found in upright individuals. Multivariate, factorial, contingency, and prediction analyses congruently showed strong similarities between lateropulsion and spatial neglect, the latter encompassing the former. CONCLUSIONS: Lateropulsion (pusher syndrome) is a trinity constituted by body tilt, pushing, and resistance. It is a way to adjust the body orientation in the roll plane to a wrong reference of verticality. Referring to straight above, lateropulsion might correspond to a form of spatial neglect (referring to straight ahead), which would advocate for 3D maps in the human brain involving the internal model of verticality.

TractLearn: A geodesic learning framework for quantitative analysis of brain bundles.

Deep learning-based convolutional neural networks have recently proved their efficiency in providing fast segmentation of major brain fascicles structures, based on diffusion-weighted imaging. The quantitative analysis of brain fascicles then relies on metrics either coming from the tractography process itself or from each voxel along the bundle. Statistical detection of abnormal voxels in the context of disease usually relies on univariate and multivariate statistics models, such as the General Linear Model (GLM). Yet in the case of high-dimensional low sample size data, the GLM often implies high standard deviation range in controls due to anatomical variability, despite the commonly used smoothing process. This can lead to difficulties to detect subtle quantitative alterations from a brain bundle at the voxel scale. Here we introduce TractLearn, a unified framework for brain fascicles quantitative analyses by using geodesic learning as a data-driven learning task. TractLearn allows a mapping between the image high-dimensional domain and the reduced latent space of brain fascicles using a Riemannian approach. We illustrate the robustness of this method on a healthy population with test-retest acquisition of multi-shell diffusion MRI data, demonstrating that it is possible to separately study the global effect due to different MRI sessions from the effect of local bundle alterations. We have then tested the efficiency of our algorithm on a sample of 5 age-matched subjects referred with mild traumatic brain injury. Our contributions are to propose: 1/ A manifold approach to capture controls variability as standard reference instead of an atlas approach based on a Euclidean mean. 2/ A tool to detect global variation of voxels' quantitative values, which accounts for voxels' interactions in a structure rather than analyzing voxels independently. 3/ A ready-to-plug algorithm to highlight nonlinear variation of diffusion MRI metrics. With this regard, TractLearn is a ready-to-use algorithm for precision medicine.

Balance, Lateropulsion, and Gait Disorders in Subacute Stroke.

OBJECTIVE: To test the hypothesis that impaired body orientation with respect to gravity (lateropulsion) would play a key role in poststroke balance and gait disorders. METHODS: Cohort study of 220 individuals consecutively admitted to a neurorehabilitation ward after a first hemisphere stroke (DOBRAS cohort [Determinants of Balance Recovery After Stroke] 2012-2018, ClinicalTrials.gov: NCT03203109), with clinical data systematically collected at 1 month, then at discharge. Primary outcomes were balance and gait disorders, quantified by the Postural Assessment Scale for Stroke and the modified Fugl-Meyer Gait Assessment, to be explained by all deficits on day 30, including lateropulsion assessed with the Scale for Contraversive Pushing. Statistics comprised linear regression analysis, univariate and multivariate analyses, and receiver operating characteristic curves. RESULTS: Lateropulsion was frequent, especially after right hemisphere stroke (RHS, D30, 48%; discharge 24%), almost always in right-handers. Among all deficits, impaired body orientation (lateropulsion) had the most detrimental effect on balance and gait. After RHS, balance disorders were proportional to lateropulsion severity, which alone explained almost all balance disorders at initial assessment (90%; 95% confidence interval [CI] [86-94], p < 0.001) and at discharge (92%; 95% CI 89-95, p < 0.001) and also the greatest part of gait disorders at initial assessment (66%; 95% CI 56-77, p < 0.001) and at discharge (68%; 95% CI 57-78, p < 0.001). CONCLUSION: Lateropulsion is the primary factor altering poststroke balance and gait at the subacute stage and therefore should be systematically assessed. Poststroke balance and gait rehabilitation should incorporate techniques devoted to misorientation with respect to gravity.

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.

Speech rehabilitation in post-stroke aphasia using visual illustration of speech articulators: A case report study.

Recent studies on the remediation of speech disorders suggest that providing visual information of speech articulators may contribute to improve speech production. In this study, we evaluate the effectiveness of an illustration-based rehabilitation method on speech recovery of a patient with non-fluent chronic aphasia. The Ultraspeech-player software allowed visualization by the patient of reference tongue and lip movements recorded using ultrasound and video imaging. This method can improve the patient's awareness of their own lingual and labial movements, which can increase the ability to coordinate and combine articulatory gestures. The effects of this method were assessed by analyzing performance during speech tasks, the phonological processes identified in the errors made during the phoneme repetition task and the acoustic parameters derived from the speech signal. We also evaluated cognitive performance before and after rehabilitation. The integrity of visuospatial ability, short-term and working memory and some executive functions supports the effectiveness of the rehabilitation method. Our results showed that illustration-based rehabilitation technique had a beneficial effect on the patient's speech production, especially for stop and fricative consonants which are targeted (high visibility of speech articulator configurations) by the software, but also on reading abilities. Acoustic parameters indicated an improvement in the distinction between consonant categories: voiced and voiceless stops or alveolar, post-alveolar and labiodental fricatives. However, the patient showed little improvement for vowels. These results confirmed the advantage of using illustration-based rehabilitation technique and the necessity of detailed subjective and objective intra-speaker evaluation in speech production to fully evaluate speech abilities.

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.

Probabilistic mapping of language networks from high frequency activity induced by direct electrical stimulation.

Direct electrical stimulation (DES) at 50 Hz is used as a gold standard to map cognitive functions but little is known about its ability to map large-scale networks and specific subnetwork. In the present study, we aim to propose a new methodological approach to evaluate the specific hypothesis suggesting that language errors/dysfunction induced by DES are the result of large-scale network modification rather than of a single cortical region, which explains that similar language symptoms may be observed after stimulation of different cortical regions belonging to this network. We retrospectively examined 29 patients suffering from focal drug-resistant epilepsy who benefitted from stereo-electroencephalographic (SEEG) exploration and exhibited language symptoms during a naming task following 50 Hz DES. We assessed the large-scale language network correlated with behavioral DES-induced responses (naming errors) by quantifying DES-induced changes in high frequency activity (HFA, 70-150 Hz) outside the stimulated cortical region. We developed a probabilistic approach to report the spatial pattern of HFA modulations during DES-induced language errors. Similarly, we mapped the pattern of after-discharges (3-35 Hz) occurring after DES. HFA modulations concurrent to language symptoms revealed a brain network similar to our current knowledge of language gathered from standard brain mapping. In addition, specific subnetworks could be identified within the global language network, related to different language processes, generally described in relation to the classical language regions. Spatial patterns of after-discharges were similar to HFA induced during DES. Our results suggest that this new methodological DES-HFA mapping is a relevant approach to map functional networks during SEEG explorations, which would allow to shift from "local" to "network" perspectives.