Francesca Bonini

Action Monitoring and Medial Frontal Cortex: Leading Role of Supplementary Motor Area

Oops, Thats Not Right… Evaluating our actions, and detecting our errors, is crucial for adaptive behavior. These fundamental executive functions are intensively studied in cognitive and social neuroscience, but their anatomical basis remains poorly characterized. Using intracerebral electroencephalography in patients being prepared for epilepsy surgery, Bonini et al. (p. 888) found that, contrary to what is widely assumed, the supplementary motor area, and not the anterior cingulate cortex, plays a leading role in these processes. The data provide a precise spatio-temporal description of the cortical network underlying action monitoring and error processing. Detection of a core brain region for performance monitoring and error detection in humans is shown. The capacity to evaluate the outcomes of our actions is fundamental for adapting and optimizing behavior and depends on an action-monitoring system that assesses ongoing actions and detects errors. The neuronal network underlying this executive function, classically attributed to the rostral cingulate zone, is poorly characterized in humans, owing to the limited number of direct neurophysiological data. Using intracerebral recordings, we show that the leading role is played by the supplementary motor area (SMA), which rapidly evaluates successful and erroneous actions. The rostral part of medial prefrontal cortex, driven by the SMA, was activated later and exclusively in the case of errors. This suggests a hierarchical organization of the different frontal regions involved in implementation of action monitoring and error processing.

Frontal lobe seizures: From clinical semiology to localization

Frontal lobe seizures are difficult to characterize according to semiologic and electrical features. We wished to establish whether different semiologic subgroups can be identified and whether these relate to anatomic organization.

Rapid detection of generalized anxiety disorder and major depression in epilepsy: Validation of the GAD-7 as a complementary tool to the NDDI-E in a French sample

OBJECTIVE Generalized anxiety disorder (GAD) in people with epilepsy (PWE) is underdiagnosed and undertreated. The GAD-7 is a screening questionnaire to detect GAD. However, the usefulness of the GAD-7 as a screening tool in PWE remains to be validated. Thus, we aimed to: (1) validate the GAD-7 in French PWE and (2) assess its complementarity with regard to the previously validated screening tool for depression, the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E). METHODS This study was performed under the auspices of the ILAE Commission on Neuropsychiatry. People with epilepsy >18 years of age were recruited from the specialist epilepsy unit in Marseille, France. The Mini-International Neuropsychiatric Interview (MINI) was performed as gold standard, and the Penn State Worry Questionnaire (PSWQ) and the NDDI-E were performed for external validity. Data were compared between PWE with/without GAD using Chi(2) test and Students t-test. Internal structural validity, external validity, and receiver operator characteristics were analyzed. A principal component factor analysis with Varimax rotation was performed on the 13 items of the GAD-7 (7 items) plus the NDDI-E (6 items). RESULTS Testing was performed on 145 PWE: mean age = 39.38 years old (SD=14.01, range: 18-75); 63.4% (92) women; 75.9% with focal epilepsy. Using the MINI, 49 (33.8%) patients had current GAD. Cronbachs alpha coefficient was 0.898, indicating satisfactory internal consistency. Correlation between GAD-7 and the PSQW scores was high (r (145)=.549, P<.0001), indicating good external validity. Factor analysis shows that the anxiety investigated with the GAD-7 and depression investigated with the NDDI-E reflect distinct factors. Receiver operator characteristic analysis showed area under the curve of 0.899 (95% CI 0.838-0.943, P < 0.0001) indicating good capacity of the GAD-7 to detect GAD (defined by MINI). Cutoff for maximal sensitivity and specificity was 7. Mean GAD-7 score in PWE with GAD was 13.22 (SD = 3.99), and that without GAD was 5.17 (SD = 4.66). SIGNIFICANCE This study validates the French language version of the GAD-7 screening tool for generalized anxiety in PWE, with a cutoff score of 7/21 for GAD, and also confirms that the GAD-7 is a short and easily administered test. Factor analysis shows that the GAD-7 (screening for generalized anxiety disorder) and the NDDI-E (screening for major depression) provide complementary information. The routine use of both GAD-7 and NDDI-E should be considered in clinical evaluation of patients with epilepsy.

Seizure-onset patterns in focal cortical dysplasia and neurodevelopmental tumors: Relationship with surgical prognosis and neuropathologic subtypes.

The study of intracerebral electroencephalography (EEG) seizure‐onset patterns is crucial to accurately define the epileptogenic zone and guide successful surgical resection. It also raises important pathophysiologic issues concerning mechanisms of seizure generation. Until now, several seizure‐onset patterns have been described using distinct recording methods (subdural, depth electrode), mostly in temporal lobe epilepsies or with heterogeneous neocortical lesions.

18FDG-PET in different subtypes of temporal lobe epilepsy: SEEG validation and predictive value.

The objective of the study was to characterize interictal 18‐fluorodeoxyglucose–positron emission tomography (18FDG‐PET) whole‐brain voxel‐based metabolic patterns among distinct subtypes of temporal lobe epilepsy (TLE), as defined by stereo–electroencephalography (SEEG) and to determine predictive value of PET result on postoperative outcome.

Does the Thalamo-Cortical Synchrony Play a Role in Seizure Termination?

The mechanisms underlying seizure termination are still unclear despite their therapeutic importance. We studied thalamo-cortical connectivity and synchrony in human mesial temporal lobe seizures in order to analyze their role in seizure termination. Twenty-two seizures from 10 patients with drug-resistant mesial temporal lobe epilepsy undergoing pre-surgical evaluation were analyzed using intracerebral recordings [stereoelectroencephalography (SEEG)]. We performed a measure of SEEG signal interdependencies (non-linear correlation), to estimate the functional connectivity between thalamus and cortical regions. Then, we derived synchronization indices, namely global, thalamic, mesio-temporal, and thalamo-mesio temporal index at the onset and the end of seizures. In addition, an estimation of thalamic “outputs and inputs” connectivity was proposed. Thalamus was consistently involved in the last phase of all analyzed seizures and thalamic synchronization index was significantly more elevated at the end of seizure than at the onset. The global synchronization index at the end of seizure negatively correlated with seizure duration (p = 0.045) and in the same way the thalamic synchronization index showed an inverse tendency with seizure duration. Six seizures out of twenty-two displayed a particular thalamo-cortical spike-and-wave pattern at the end. They were associated to higher values of all synchronization indices and outputs from thalamus (p = 0.0079). SWP seizures displayed a higher and sustained increase of cortical and thalamo-cortical synchronization with a stronger participation of thalamic outputs. We suggest that thalamo-cortical oscillations might contribute to seizure termination via modulation of cortical synchronization. In the subgroup of SWP seizures, thalamus may exert a control on temporal lobe structures by inducing a stable hypersynchronization that ultimately leads to seizure termination.

Dynamic Reconfiguration of Visuomotor-Related Functional Connectivity Networks

Cognitive functions arise from the coordination of large-scale brain networks. However, the principles governing interareal functional connectivity dynamics (FCD) remain elusive. Here, we tested the hypothesis that human executive functions arise from the dynamic interplay of multiple networks. To do so, we investigated FCD mediating a key executing function, known as arbitrary visuomotor mapping, using brain connectivity analyses of high-gamma activity recorded using MEG and intracranial EEG. Visuomotor mapping was found to arise from the dynamic interplay of three partly overlapping cortico-cortical and cortico-subcortical functional connectivity (FC) networks. First, visual and parietal regions coordinated with sensorimotor and premotor areas. Second, the dorsal frontoparietal circuit together with the sensorimotor and associative frontostriatal networks took the lead. Finally, cortico-cortical interhemispheric coordination among bilateral sensorimotor regions coupled with the left frontoparietal network and visual areas. We suggest that these networks reflect the processing of visual information, the emergence of visuomotor plans, and the processing of somatosensory reafference or actions outcomes, respectively. We thus demonstrated that visuomotor integration resides in the dynamic reconfiguration of multiple cortico-cortical and cortico-subcortical FC networks. More generally, we showed that visuomotor-related FC is nonstationary and displays switching dynamics and areal flexibility over timescales relevant for task performance. In addition, visuomotor-related FC is characterized by sparse connectivity with density <10%. To conclude, our results elucidate the relation between dynamic network reconfiguration and executive functions over short timescales and provide a candidate entry point toward a better understanding of cognitive architectures. SIGNIFICANCE STATEMENT Executive functions are supported by the dynamic coordination of neural activity over large-scale networks. The properties of large-scale brain coordination processes, however, remain unclear. Using tools combining MEG and intracranial EEG with brain connectivity analyses, we provide evidence that visuomotor behaviors, a hallmark of executive functions, are mediated by the interplay of multiple and spatially overlapping subnetworks. These subnetworks span visuomotor-related areas, the cortico-cortical and cortico-subcortical interactions of which evolve rapidly and reconfigure over timescales relevant for behavior. Visuomotor-related functional connectivity dynamics are characterized by sparse connections, nonstationarity, switching dynamics, and areal flexibility. We suggest that these properties represent key aspects of large-scale functional networks and cognitive architectures.

Altered synchrony and loss of consciousness during frontal lobe seizures

OBJECTIVE Loss of consciousness (LOC) in frontal lobe epilepsy (FLE) has been rarely specifically studied until now. In this study we evaluated the LOC in a population of patients with FLE and studied the relationship between changes in synchrony and degree of LOC. METHODS 24 patients undergoing stereoelectroencephalography (SEEG) during pre-surgical evaluation of FLE were studied. The LOC intensity was scored using the Consciousness Seizure Scale (CSS). For each studied seizure (n=52), interdependencies between signals recorded from 5 brain regions were estimated as a function of time by using non-linear regression analysis (h(2) coefficient). RESULTS Seizures were divided into 3 groups according to the CSS scale: group A (no LOC) with a score ⩽2, group B (intermediate or partial LOC) with a score ranging from 3 to 5, and group C (maximal LOC) with a score ⩾6. The majority of seizures in FLE patients disclosed significant LOC, particularly for patients with prefrontal lobe seizures. Mean correlation values were significantly different between groups A and C (p<0.001), the maximal values of synchrony being observed in group C. Differences were significant for interaction affecting the external prefrontal cortex (p=0.004) (p=0.01) and the parietal cortex. In addition, a significant correlation was found between CSS scores and correlations values (h(2)) of the prefrontal and the parietal region but not with the premotor cortex. CONCLUSIONS This study indicates that in FLE, prefrontal seizures frequently alter consciousness. As in other focal seizures, LOC appears to be related to changes in synchrony in prefrontal and parietal associative cortices. SIGNIFICANCE LOC in FLE is frequent and as in other focal epilepsies is related to an alteration of prefrontal-parietal network.

Natural evolution from idiopathic photosensitive occipital lobe epilepsy to idiopathic generalized epilepsy in an untreated young patient

Idiopathic photosensitive occipital lobe epilepsy (IPOE) is an idiopathic localization-related epilepsy characterized by age-related onset, specific mode of precipitation, occipital photic-induced seizures--frequently consisting of visual symptoms--and good prognosis. This uncommon epilepsy, which usually starts in childhood or adolescence, has rarely been observed in families in which idiopathic generalized epilepsy also affects other members. We describe a nuclear family in which the proband showed electro-clinical features of idiopathic photosensitive occipital lobe epilepsy in childhood, which subsequently evolved into absences and a single generalized tonico-clonic seizure in early adolescence. His mother had features suggestive of juvenile myoclonic epilepsy. This case illustrates a continuum between focal and generalized entities in the spectrum of the so-called idiopathic (genetically determined) epileptic syndromes.

How does vagal nerve stimulation (VNS) change EEG brain functional connectivity

An effect of vagal nerve stimulation (VNS) on cortical synchronization has been postulated but remains to be verified. In this study we investigated the impact of VNS on functional connectivity (Fc) using direct intracerebral recordings (stereotactic EEG, SEEG). Five patients with epilepsy who underwent SEEG recordings during ongoing VNS therapy were investigated. Interdependencies between twenty-six selected bipolar SEEG channels were estimated by nonlinear regression analysis during ON and OF periods of stimulation. In comparison with OFF periods, the ON periods disclosed higher values for four patients (P1, P3, P4, P5) and lower values for one patient (P2). From thresholded graphs, we observed increased connections between several brain regions in P1 and P5 and decreased connections in P2. Finally, the only decreased Fc occurring during VNS corresponded to the responder patient, suggesting that therapeutic impact might be related to this mechanism.