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Attention, working memory, and executive control are commonly considered distinct cognitive functions with important reciprocal interactions. Yet, longstanding evidence from lesion studies demonstrated both overlap and dissociation in their behavioural expression and anatomical underpinnings, suggesting that a lower dimensional framework could be employed to further identify processes supporting goal-directed behaviour. Here, we describe the anatomical and functional correspondence between attention, working memory, and executive control by providing an overview of cognitive models as well as recent data from lesion studies and both invasive and noninvasive multimodal neuroimaging and brain stimulation. We emphasize the benefits of considering converging evidence from multiple methodologies centred on the identification of brain mechanisms supporting goal-driven behaviour. We propose that expanding on this approach should enable the construction of a comprehensive anatomo-functional framework with testable new hypotheses, and aid clinical neuroscience to understand and treat neuropathologies of executive functions.

White matter bundles linking gray matter nodes are key anatomical players to fully characterize associations between brain systems and cognitive functions. Here we used a multivariate lesion inference approach grounded in coalitional game theory (multiperturbation Shapley value analysis, MSA) to infer causal contributions of white matter bundles to visuospatial orienting of attention. Our work is based on the characterization of the lesion patterns of 25 right hemisphere stroke patients and the causal analysis of their impact on three neuropsychological tasks: line bisection, letter cancellation, and bells cancellation. We report that, out of the 11 white matter bundles included in our MSA coalitions, the optic radiations, the inferior fronto‐occipital fasciculus and the anterior cingulum were the only tracts to display task‐invariant contributions (positive, positive, and negative, respectively) to the tasks. We also report task‐dependent influences for the branches of the superior longitudinal fasciculus and the posterior cingulum. By extending prior findings to white matter tracts linking key gray matter nodes, we further characterize from a network perspective the anatomical basis of visual and attentional orienting processes. The knowledge about interactions patterns mediated by white matter tracts linking cortical nodes of attention orienting networks, consolidated by further studies, may help develop and customize brain stimulation approaches for the rehabilitation of visuospatial neglect., We inferred causal contributions of white matter bundles to visuo‐spatial attention. We observed that the optic radiations and the inferior fronto‐occipital fasciculus exerted task‐invariant positive contributions to spatial attention, whereas the anterior cingulum provided task‐invariant negative ‐hindering‐ contributions. The superior longitudinal fasciculus and the corpus callosum displayed task‐dependent contributions. These results may inform future uses of brain stimulation approaches in visuospatial attention rehabilitation.

International audience; The ‘Sprague Effect’ described in the seminal paper of James Sprague (Science 153:1544 e1547, 1966a) is an unexpected paradoxical effect in which a second brain lesion reversed functional deficits induced by an earlier lesion. It was observed initially in the cat where severe and permanent contralateral visually guided attentional deficits generated by the ablation of large areas of the visual cortex were reversed by the subsequent removal of the superior colliculus (SC) opposite to the cortical lesion or by the splitting of the collicular commissure. Physiologically, this effect has been explained in several ways-most notably by the reduction of the functional inhibition of the ipsilateral SC by the contralateral SC, and the restoration of normal interactions between cortical and midbrain structures after ablation. In the present review, we aim at reappraising the ‘Sprague Effect’ by critically analyzing studies that have been conducted in the feline and human brain. Moreover, we assess applications of the ‘Sprague Effect’ in the rehabilitation of visually guided atten- tional impairments by using non-invasive therapeutic approaches such as transcranial magnetic stimulation (TMS) and transcranial direct-current stimulation (tDCS). We also review theoretical models of the effect that emphasize the inhibition and balancing be- tween the two hemispheres and show implications for lesion inference approaches. Last, we critically review whether the resulting inter-hemispheric rivalry theories lead toward an efficient rehabilitation of stroke in humans. We conclude by emphasizing key challenges in the field of ‘Sprague Effect’ applications in order to design better therapies for brain-damaged patients.; L’effet Sprague décrit dans le document fondateur de James Sprague (Science 153: 1544 e1547, 1966a) est un effet paradoxal inattendu dans lequel une deuxième lésion cérébrale inversait les déficits fonctionnels induits par une lésion antérieure. Il a été observé initialement chez le chat où les déficits attentionnels controlatéraux sévères et permanents générés par l'ablation de grandes zones du cortex visuel ont été inversés par l'ablation ultérieure du colliculus supérieur (SC) opposé à la lésion corticale ou par la division de la commissure colliculaire. Physiologiquement, cet effet a été expliqué de plusieurs façons, notamment par la réduction de l'inhibition fonctionnelle de la SC ipsilatérale par la SC controlatérale et la restauration des interactions normales entre les structures corticales et du mésencéphale après l'ablation. Dans la présente revue, nous visons à réévaluer «l’effet Sprague» en analysant de manière critique les études qui ont été menées sur le cerveau félin et humain. De plus, nous évaluons les applications de «l’effet Sprague» dans la réadaptation des troubles de l’attention guidés visuellement en utilisant des approches thérapeutiques non invasives telles que la stimulation magnétique transcrânienne (TMS) et la stimulation transcrânienne à courant continu (tDCS). Nous passons également en revue les modèles théoriques de l'effet qui mettent l'accent sur l'inhibition et l'équilibre entre les deux hémisphères et montrent les implications pour les approches d'inférence des lésions. Enfin, nous examinons de manière critique si les théories de rivalité interhémisphérique qui en résultent conduisent à une réhabilitation efficace de l'AVC chez l'homme. Nous concluons en mettant l’accent sur les principaux défis dans le domaine des applications de «l’effet Sprague» afin de concevoir de meilleures thérapies pour les patients atteints de lésions cérébrales.

International audience; Spatial neglect usually concerns left-sided events after right-hemisphere damage. Its anatomical correlates are debated, with evidence suggesting an important role for fronto-parietal white matter disconnections in the right hemisphere. Here, we describe the less frequent occurrence of neglect for right-sided events, observed in three right-handed patients after a focal stroke in the left hemisphere. Patients were tested 1 month and 3 months after stroke. They performed a standardized paper-and-pencil neglect battery and underwent brain MRI with both structural and diffusion tensor (DT) sequences, in order to assess both grey matter and white matter tracts metrics. Lesions were manually reconstructed for each patient. Patients presented signs of mild right-sided neglect during visual search and line bisection. One patient also showed pathological performance in everyday life. Structural MRI demonstrated left parietal strokes in two patients, in the region extending from the postcentral gyrus to the temporo-parietal junction. One of these two patients also had had a previous occipital stroke. The remaining patient had a left frontal stroke, affecting the precentral, the postcentral gyri and the basal ganglia. DT MRI tractography showed disconnections in the fronto-parietal regions, concerning principally the superior longitudinal fasciculus (SLF). These results suggest an important role for left SLF disconnection in right-side neglect, which complements analogous evidence for right SLF disconnection in left-side neglect.

Although action slowing is the main cognitive impairment in stroke survivors, its mechanisms and determinants are still poorly understood. The objectives of the present study were to determine the mechanisms of post-stroke action slowing (using validated, highly specific simple reaction time (SRT) and tapping tests) and identify its imaging determinants (using multivariate lesion-symptom mapping (mLSM)).Action speed in the GRECogVASC cohort was assessed using finger tapping and SRT tests performed with both hands and analyzed using previously validated indices. Imaging determinants were identified using validated mLSM analyses and disconnection analysis and compared to those of an fMRI activation meta-analytic database.Both the tapping time and SRT were 10.7% slower for the 394 patients (p = 0.0001) than for the 786 controls, without a group × test interaction (p = 0.2). The intra-individual distribution curve was characterized by a rightward shift with an unaltered attentional peak. The mLSM analyses showed tapping to be associated with lesions in the frontostriatal tract (p = 0.0007). The SRT was associated with lesions in the frontostriatal tract (p = 0.04) and the orbital part of F3 (p = 0.0001). The SRT-tapping index was associated with lesions in the orbital part of F3 (p = 0.0001). All lesions were located in the right hemisphere only and were responsible for the disconnection of several structures involved in motor preparation, initiation, and speed. A comparison with fMRI activation meta-analytic data highlighted mostly the same regions, including the orbital part of F3, the ventral and dorsal parts of F1, and the premotor and cingulate regions in the right hemisphere.Our results confirm the marked impairment of action speed in stroke and show that the primary mechanism is motor slowing and that it is related to lesions in the right frontostriatal tract. A deficit in sustained alertness accounted for action slowing in the subgroup with lesions in the right orbital part of F3. Our SRT and mLSM results were in accordance with the fMRI activation data. Thus, stroke induces slowing in the broad network associated with SRT tasks by disrupting the frontostriatal tract and, to a lesser extent, other sites involved in attention.

Background and Purpose: We used differential actigraphy as a novel, objective method to quantify motor neglect (a clinical condition whereby patients mimic hemiplegia even in the absence of sensorimotor deficits), whose diagnosis is at present highly subjective, based on the clinical observation of patients’ spontaneous motor behavior. Methods: Patients wear wristwatch-like accelerometers, which record spontaneous motor activity of their upper limbs during 24 hours. Asymmetries of motor behavior are then automatically computed offline. On the basis of normal participants’ performance, we calculated cutoff scores of left/right motor asymmetry. Results: Differential actigraphy showed contralesional motor neglect in 9 of 35 patients with unilateral strokes, consistent with clinical assessment. An additional patient with clinical signs of motor neglect obtained a borderline asymmetry score. Lesion location in a subgroup of 25 patients was highly variable, suggesting that motor neglect is a heterogenous condition. Conclusions: Differential actigraphy provides an ecological measure of spontaneous motor behavior, and can assess upper limb motricity in an objective and quantitative manner. It thus offers a convenient, cost-effective, and relatively automatized procedure for following-up motor behavior in neurological patients and to assess the effects of rehabilitation.

International audience; A recent tasked-based fMRI study unveiled a network of areas implicated in the process of visuo-proprioceptive integration of the right hand. In this study, we report a case of a patient operated on in awake conditions for a glioblastoma of the left superior parietal lobule. When stimulating a white matter site in the anterior wall of the cavity, the patient spontaneously reported a discrepancy between the visual and proprioceptive perceptions of her right hand. Using several multimodal approaches (axono-cortical evoked potentials, tractography, resting-state functional connectivity), we demonstrated converging support for the hypothesis that tumor-induced plasticity redistributed the left-lateralized network of right-hand visuo-proprioceptive integration towards its right-lateralized homolog.

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Objectives The ability of voxel-based lesion-symptom mapping (VLSM) to define the functional anatomy of the human brain has not been fully assessed. With a view to assessing VLSM's validity, the present study analyzed the technique's ability to determine the known clinical-anatomic correlates of hemiparesis in stroke patients. Design Lesions (damaged in at least 5 patients) associated with transformed limb motor score (after adjustment on lesion volume) at 6 months were examined in 272 patients using VLSM. The value of additional multivariable linear, logistic and Bayesian analyses was examined. Results We first checked that motor hemiparesis was fully accounted for by corticospinal tract (CST) lesions (sensitivity = 100%; p = 0.0001). Conventional VLSM analysis flagged up 2 regions corresponding to the CST, but also 8 regions located outside the CST. All 10 brain regions achieving statistical significance in the VLSM analysis were submitted to 3 additional analyses. The backward linear regression analysis selected 5 regions, one only corresponding to the CST (R2: 0.03, p = 0.0008). The logistic regression analysis selected correctly the CST (OR: 2.39, 95%CI: 1.44–3.96; 0.001). The Bayesian network analysis selected regions including the CST (in 92% of 3000 bootstrap replications) and identified the source of multicollinearity. These lesions evaluated by structural equation modeling resulted in an excellent fit (p-value = 0.228, chi/df = 1.19, RMSEA = 0.032, CFI = 0.999). Analyses of confusion factors showed that conventional VLSM analyses were strongly influenced by lesion frequency (R2 = 0.377; p = 0.0001) and multicollinearity. Conclusions Conventional VLSM analyses are sensitive but weakened by a type I error due to the combined effects of multicollinearity and lesion frequency. We demonstrate that the addition of a Bayesian network analysis, and to a lesser extent of logistic regression, controlled for this type I error and constituted a reliable means of defining the functional anatomy of the motor system in stroke patients.

International audience; Visual neglect is a disabling consequence of right hemisphere damage, whereby patients fail to detect left-sided objects. Its precise mechanisms are debated, but there is some consensus that distinct component deficits may variously associate and interact in different patients. Here we used a touch-screen based procedure to study two putative component deficits of neglect, rightward "magnetic" attraction of attention and impaired spatial working memory, in a group of 47 right brain-damaged patients, of whom 33 had signs of left neglect. Patients performed a visual search task on three distinct conditions, whereby touched targets could (1) be tagged, (2) disappear or (3) show no change. Magnetic attraction of attention was defined as more left neglect on the tag condition than on the disappear condition, where right-sided disappeared targets could not capture patients' attention. Impaired spatial working memory should instead produce more neglect on the no change condition, where no external cue indicated that a target had already been explored, than on the tag condition. Using a specifically developed analysis algorithm, we identified significant differences of performance between the critical conditions. Neglect patients as a group performed better on the disappear condition than on the no change condition and also better in the tag condition comparing with the no change condition. No difference was found between the tag condition and the disappear condition. Some of our neglect patients had dissociated patterns of performance, with predominant magnetic attraction or impaired spatial working memory. Anatomical results issued from both grey matter analysis and fiber tracking were consistent with the typical patterns of fronto-parietal and occipito-frontal disconnection in neglect, but did not identify lesional patterns specifically associated with one or another deficit, thus suggesting the possible co-localization of attentional and working memory processes in fronto-parietal networks. These findings give support to the hypothesis of the co-occurrence of distinct cognitive deficits in visual neglect and stress the necessity of multi-component models of visuospatial disorders.

Behavioral and electrophysiological studies in humans and non-human primates have correlated frontal high-beta activity with the orienting of endogenous attention and shown the ability of the latter function to modulate visual performance. We here combined rhythmic transcranial magnetic stimulation (TMS) and diffusion imaging to study the relation between frontal oscillatory activity and visual performance, and we associated these phenomena to a specific set of white matter pathways that in humans subtend attentional processes. High-beta rhythmic activity on the right frontal eye field (FEF) was induced with TMS and its causal effects on a contrast sensitivity function were recorded to explore its ability to improve visual detection performance across different stimulus contrast levels. Our results show that frequency-specific activity patterns engaged in the right FEF have the ability to induce a leftward shift of the psychometric function. This increase in visual performance across different levels of stimulus contrast is likely mediated by a contrast gain mechanism. Interestingly, microstructural measures of white matter connectivity suggest a strong implication of right fronto-parietal connectivity linking the FEF and the intraparietal sulcus in propagating high-beta rhythmic signals across brain networks and subtending top-down frontal influences on visual performance.

Visual neglect is a heterogeneous, multi-component syndrome resulting from right hemisphere damage. Neglect patients do not pay attention to events occurring on their left side, and have a poor functional outcome. The intra-hemispheric location of lesions producing neglect is debated, because studies using different methods reported different locations in the grey matter and in the white matter of the right hemisphere. These reported locations show various patterns of overlapping with the fronto-parietal attention networks demonstrated by functional neuroimaging. We explored the anatomical correlates of neglect patients' performance on distinct tests of neglect. For the first time in neglect anatomy studies, we individually assessed 25 patients with subacute strokes in the right hemisphere, by using a combined structural and diffusion tensor deterministic tractography approach, with separate analyses for each neglect test. The results revealed that lesions in nodes of the ventral attention network (angular and supramarginal gyri) were selectively associated with deficits in performance on all the tests used; damage to other structures correlated with impaired performance on specific tests, such as the bells test (middle and inferior frontal gyri), or the reading test (temporal regions). Importantly, however, white matter damage proved crucial in producing neglect-related deficits. Voxel-based lesion-symptom mapping (VLSM) and tractography consistently revealed that damage to the ventral branch of the superior longitudinal fasciculus (SLF III) and to the inferior fronto-occipital fasciculus (IFOF) predicted pathological scores on line bisection/drawing copy and on the bells test, respectively. Moreover, damage to distinct sectors of SLF III, or combined SLF/IFOF damage, gave rise to different performance profiles. Our results indicate that both grey and white matter lesion analysis must be taken into account to determine the neural correlates of neglect-related deficits. They also suggest that damage to distinct portions of white matter tracts may give rise to distinct clinical signs of neglect, presumably by inducing dysfunction of partly overlapping, but distinct networks.

Anatomical studies conducted in neurological conditions have developed our understanding of the causal relationships between brain lesions and their clinical consequences. The analysis of lesion patterns extended across brain networks has been particularly useful in offering new insights on brain-behavior relationships. Here we applied multiperturbation Shapley value Analysis (MSA), a multivariate method based on coalitional game theory inferring causal regional contributions to specific behavioral outcomes from the characteristic functional deficits after stroke lesions. We established the causal patterns of contributions and interactions of nodes of the attentional orienting network on the basis of lesion and behavioral data from 25 right hemisphere stroke patients tested in visuo-spatial attention tasks. We calculated the percentage of damaged voxels for five right hemisphere cortical regions contributing to attentional orienting, involving seven specific Brodmann Areas (BA): Frontal Eye Fields, (FEF-BA6), Intraparietal Sulcus (IPS-BA7), Inferior Frontal Gyrus (IFG-BA44/BA45), Temporo-Parietal Junction (TPJ-BA39/BA40), and Inferior Occipital Gyrus (IOG-BA19). We computed the MSA contributions of these seven BAs to three behavioral clinical tests (line bisection, bells cancellation, and letter cancelation). Our analyses indicated IPS as the main contributor to the attentional orienting and also revealed synergistic influences among IPS, TPJ, and IOG (for bells cancellation and line bisection) and between TPJ and IFG (for bells and letter cancellation tasks). The findings demonstrate the ability of the MSA approach to infer plausible causal contributions of relevant right hemisphere sites in poststroke visuo-spatial attention and awareness disorders. Hum Brain Mapp 38:3454-3471, 2017. © 2017 Wiley Periodicals, Inc.

We studied the neural correlates of target omissions in five patients with right hemisphere damage and varying signs of left spatial neglect. Benefiting from the high temporal resolution of magneto-encephalography, we directly compared brain regional synchrony events of detected and omitted left-sided targets. Results showed that before stimulus presentation, a low beta synchronization activity was specifically increased within left frontal areas before pathological response omissions of left-sided targets. In the same pre-stimulus period, there were no such beta oscillations when patients correctly detected the target, or when no target was presented. Our findings emphasize the importance of neural activity during the pre-stimulus period on subsequent stimulus processing, and highlight the consequences of episodic interruptions of large-scale interhemispheric networks on target detection. Furthermore, our data suggest that prefrontal activity is not necessarily beneficial to target detection, but can be detrimental to it.

Anatomical studies conducted in neurological conditions have developed our understanding of the causal relationships between brain lesions and their clinical consequences. The analysis of lesion patterns extended across brain networks has been particularly useful in offering new insights on brain-behavior relationships. Here we applied multiperturbation Shapley value Analysis (MSA), a multivariate method based on coalitional game theory inferring causal regional contributions to specific behavioral outcomes from the characteristic functional deficits after stroke lesions. We established the causal patterns of contributions and interactions of nodes of the attentional orienting network on the basis of lesion and behavioral data from 25 right hemisphere stroke patients tested in visuo-spatial attention tasks. We calculated the percentage of damaged voxels for five right hemisphere cortical regions contributing to attentional orienting, involving seven specific Brodmann Areas (BA): Frontal Eye Fields, (FEF-BA6), Intraparietal Sulcus (IPS-BA7), Inferior Frontal Gyrus (IFG-BA44/BA45), Temporo-Parietal Junction (TPJ-BA39/BA40), and Inferior Occipital Gyrus (IOG-BA19). We computed the MSA contributions of these seven BAs to three behavioral clinical tests (line bisection, bells cancellation, and letter cancelation). Our analyses indicated IPS as the main contributor to the attentional orienting and also revealed synergistic influences among IPS, TPJ, and IOG (for bells cancellation and line bisection) and between TPJ and IFG (for bells and letter cancellation tasks). The findings demonstrate the ability of the MSA approach to infer plausible causal contributions of relevant right hemisphere sites in poststroke visuo-spatial attention and awareness disorders. Hum Brain Mapp 38:3454-3471, 2017. © 2017 Wiley Periodicals, Inc.

In visual search tasks, neglect patients tend to explore and repeatedly re-cancel stimuli on the ipsilesional side, as if they did not realize that they had previously examined the rightward locations favoured by their lateral bias. The aim of this study was to explore the hypothesis that a spatial working memory deficit explains these ipsilesional re-cancellation errors in neglect patients. For the first time, we evaluated spatial working memory and re-cancellation through separate and independent tasks in a group of patients with right hemisphere damage and a diagnosis of left neglect. Results showed impaired spatial working memory in neglect patients. Compared to the control group, neglect patients cancelled fewer targets and made more re-cancellations both on the left side and on the right side. The spatial working memory deficit appears to be related to re-cancellations, but only for some neglect patients. Alternative interpretations of re-exploration of space are discussed.

International audience; Posterior cortical atrophy (PCA) is rare neurodegenerative dementia, clinically characterized by a progressive decline in higher-visual object and space processing. After a brief review of the literature on the neuroimaging in PCA, here we present a study of the brain structural connectivity in a patient with PCA and progressive isolated visual and visuo-motor signs. Clinical and cognitive data were acquired in a 58-years-old patient (woman, right-handed, disease duration 18 months). Brain structural and diffusion tensor (DT) magnetic resonance imaging (MRI) were obtained. A voxel-based morphometry (VBM) study was performed to explore the pattern of gray matter (GM) atrophy, and a fully automatic segmentation was assessed to obtain the hippocampal volumes. DT MRI-based tractography was used to assess the integrity of long-range white matter (WM) pathways in the patient and in six sex- and age-matched healthy subjects. This PCA patient had a clinical syndrome characterized by left visual neglect, optic ataxia, and left limb apraxia, as well as mild visuo-spatial episodic memory impairment. VBM study showed bilateral posterior GM atrophy with right predominance; DT MRI tractography demonstrated WM damage to the right hemisphere only, including the superior and inferior longitudinal fasciculi and the inferior fronto-occipital fasciculus, as compared to age-matched controls. The homologous left-hemisphere tracts were spared. No difference was found between left and right hippocampal volumes. These data suggest that selective visuo-spatial deficits typical of PCA might not result from cortical damage alone, but by a right-lateralized network-level dysfunction including WM damage along the major visual pathways.

Unilateral spatial neglect is a disabling condition, frequently observed after right-hemisphere damage (RHD), and associated with poor functional recovery. Clinical and experimental evidence indicates that attentional impairments are prominent in neglect. Recent brain imaging and behavioral studies in neglect patients and healthy individuals have provided insights into the mechanisms of attention and have revealed interactions between putative attentional networks. We recruited 16 RHD patients and 16 neurologically intact observers to perform a lateralized version of the Attention Network Test devised by Posner and co-workers (Fan et al., 2002). The results showed evidence of interaction between attentional networks during conflict resolution. Phasic alertness improved the orienting deficit to left-sided targets, reducing the interference of distracters in the neglected visual field, thus facilitating conflict resolution in the majority of patients. Modulating alertness may be an important way of improving basic deficits associated with neglect, such as those affecting spatial orienting.

Introduction Signs of left unilateral neglect often occur after damage to the right hemisphere and entail a left–right imbalance in stimulus processing. Typically, neglect patients deviate rightward when bisecting lines. An underestimation of the left portion of the line and/or a right overestimation could explain this effect. Methods Here we dissected their respective contribution by asking participants to compare a vertical segment to a horizontal segment, either on the left or on the right. We also tested whether neglect patients exhibited the symmetry law, whereby normal participants underestimate symmetrically bisected lines as compared to asymmetrically bisected lines. Results Controls and patients underestimated symmetric figures. Depending on the degree of left–right horizontal competition, neglect patients underestimated left-sided stimuli or overestimated right-sided stimuli. Conclusions We concluded that two independent deficits contribute to neglect signs: a deficit in attentional orienting to the left, which can be worsened by left hemianopia, perhaps depending on impaired functioning of right-hemisphere attentional networks, and a tendency for attention to be captured by right-sided stimuli, possibly resulting from the activity of an isolated left hemisphere. Finally, the symmetry law was preserved in neglect patients, and thus appears to be driven by pre-attentive mechanisms.

International audience; The study of brain-function relationships is undergoing a conceptual and methodological transformation due to the emergence of network neuroscience and the development of multivariate methods for lesion-deficit inferences. Anticipating this process, in 1998 Godefroy and co-workers conceptualized the potential of four elementary typologies of brain-behaviour relationships named 'brain modes' (unicity, equivalence, association, summation) as building blocks able to describe the association between intact or lesioned brain regions and cognitive processes or neurological deficits. In the light of new multivariate lesion inference and network approaches, we critically revisit and update the original theoretical notion of brain modes, and provide real-life clinical examples that support their existence. To improve the characterization of elementary units of brain-behavioural relationships further, we extend such conceptualization with a fifth brain mode (mutual inhibition/masking summation). We critically assess the ability of these five brain modes to account for any type of brain-function relationship, and discuss past versus future contributions in redefining the anatomical basis of human cognition. We also address the potential of brain modes for predicting the behavioural consequences of lesions and their future role in the design of cognitive neurorehabilitation therapies.; L'étude des relations cerveau-fonction subit une transformation conceptuelle et méthodologique due à l'émergence des neurosciences de réseau et au développement de méthodes multivariées pour les inférences déficit-lésion. Anticipant ce processus, en 1998, Godefroy et ses collègues ont conceptualisé le potentiel de quatre typologies élémentaires de relations cerveau-comportement appelées «modes cérébraux» (unicité, équivalence, association, sommation) comme éléments constitutifs capables de décrire l'association entre cerveau intact ou lésé. régions et processus cognitifs ou déficits neurologiques. À la lumière de nouvelles inférences de lésions multivariées et de nouvelles approches en réseau, nous revisitons et mettons à jour de manière critique la notion théorique originale des modes cérébraux et fournissons des exemples cliniques réels qui soutiennent leur existence. Pour améliorer encore la caractérisation des unités élémentaires des relations cerveau-comportement, nous étendons cette conceptualisation avec un cinquième mode cérébral (inhibition mutuelle / sommation de masquage). Nous évaluons de manière critique la capacité de ces cinq modes cérébraux à prendre en compte tout type de relation cerveau-fonction, et discutons des contributions passées et futures dans la redéfinition de la base anatomique de la cognition humaine. Nous abordons également le potentiel des modes cérébraux pour prédire les conséquences comportementales des lésions et leur rôle futur dans la conception de thérapies de neuroréhabilitation cognitives.