Causal hierarchy within the thalamo-cortical network in spike and wave discharges

Background: Generalised spike wave (GSW) discharges are the electroencephalographic (EEG) hallmark of absence seizures, clinically characterised by a transitory interruption of ongoing activities and impaired consciousness, occurring during states of reduced awareness. Several theories have been proposed to explain the pathophysiology of GSW discharges and the role of thalamus and cortex as generators. In this work we extend the existing theories by hypothesizing a role for the precuneus, a brain region neglected in previous works on GSW generation but already known to be linked to consciousness and awareness. We analysed fMRI data using dynamic causal modelling (DCM) to investigate the effective connectivity between precuneus, thalamus and prefrontal cortex in patients with GSW discharges. Methodology and Principal Findings: We analysed fMRI data from seven patients affected by Idiopathic Generalized Epilepsy (IGE) with frequent GSW discharges and significant GSW-correlated haemodynamic signal changes in the thalamus, the prefrontal cortex and the precuneus. Using DCM we assessed their effective connectivity, i.e. which region drives another region. Three dynamic causal models were constructed: GSW was modelled as autonomous input to the thalamus (model A), ventromedial prefrontal cortex (model B), and precuneus (model C). Bayesian model comparison revealed Model C (GSW as autonomous input to precuneus), to be the best in 5 patients while model A prevailed in two cases. At the group level model C dominated and at the population-level the p value of model C was ∼1. Conclusion: Our results provide strong evidence that activity in the precuneus gates GSW discharges in the thalamo-(fronto) cortical network. This study is the first demonstration of a causal link between haemodynamic changes in the precuneus - an index of awareness - and the occurrence of pathological discharges in epilepsy. © 2009 Vaudano et al

An unaware agenda: interictal consciousness impairments in epileptic patients.

Consciousness impairments have been described as a cornerstone of epilepsy. Generalized seizures are usually characterized by a complete loss of consciousness, whereas focal seizures have more variable degrees of responsiveness. In addition to these impairments that occur during ictal episodes, alterations of consciousness have also been repeatedly observed between seizures (i.e. during interictal periods). In this opinion article, we review evidence supporting the novel hypothesis that epilepsy produces consciousness impairments which remain present interictally. Then, we discuss therapies aimed to reduce seizure frequency, which may modulate consciousness between epileptic seizures. We conclude with a consideration of relevant pathophysiological mechanisms. In particular, the thalamocortical network seems to be involved in both seizure generation and interictal consciousness impairments, which could inaugurate a promising translational agenda for epilepsy studies

Cortical thickness and sulcal depth: insights on development and psychopathology in paediatric epilepsy.

BackgroundThe relationship between cortical thickness (CThick) and sulcal depth (SDepth) changes across brain regions during development. Epilepsy youth have CThick and SDepth abnormalities and prevalent psychiatric disorders.AimsThis study compared the CThick-SDepth relationship in children with focal epilepsy with typically developing children (TDC) and the role played by seizure and psychopathology variables.MethodA surface-based, computational high-resolution three-dimesional (3D) magnetic resonance image analytic technique compared regional CThick-SDepth relationships in 42 participants with focal epilepsy and 46 TDC (6-16 years) imaged in a 1.5 Tesla scanner. Psychiatric interviews administered to each participant yielded psychiatric diagnoses. Parents provided seizure-related information.ResultsThe TDC group alone demonstrated a significant negative medial fronto-orbital CThick-SDepth correlation. Focal epilepsy participants with but not without psychiatric diagnoses showed significant positive pre-central and post-central CThick-SDepth associations not found in TDC. Although the history of prolonged seizures was significantly associated with the post-central CThick-SDepth correlation, it was unrelated to the presence/absence of psychiatric diagnoses.ConclusionsAbnormal CThick-SDepth pre-central and post-central associations might be a psychopathology biomarker in paediatric focal epilepsy.Declaration interestNone.Copyright and usage© 2015 The Royal College of Psychiatrists. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence

Temporal Lobe Epilepsy Alters Auditory-motor Integration For Voice Control

Temporal lobe epilepsy (TLE) is the most common drug-refractory focal epilepsy in adults. Previous research has shown that patients with TLE exhibit decreased performance in listening to speech sounds and deficits in the cortical processing of auditory information. Whether TLE compromises auditory-motor integration for voice control, however, remains largely unknown. To address this question, event-related potentials (ERPs) and vocal responses to vocal pitch errors (1/2 or 2 semitones upward) heard in auditory feedback were compared across 28 patients with TLE and 28 healthy controls. Patients with TLE produced significantly larger vocal responses but smaller P2 responses than healthy controls. Moreover, patients with TLE exhibited a positive correlation between vocal response magnitude and baseline voice variability and a negative correlation between P2 amplitude and disease duration. Graphical network analyses revealed a disrupted neuronal network for patients with TLE with a significant increase of clustering coefficients and path lengths as compared to healthy controls. These findings provide strong evidence that TLE is associated with an atypical integration of the auditory and motor systems for vocal pitch regulation, and that the functional networks that support the auditory-motor processing of pitch feedback errors differ between patients with TLE and healthy controls

Network Connectivity in Epilepsy: Resting State fMRI and EEG-fMRI Contributions.

There is a growing body of evidence pointing toward large-scale networks underlying the core phenomena in epilepsy, from seizure generation to cognitive dysfunction or response to treatment. The investigation of networks in epilepsy has become a key concept to unlock a deeper understanding of the disease. Functional imaging can provide valuable information to characterize network dysfunction; in particular resting state fMRI (RS-fMRI), which is increasingly being applied to study brain networks in a number of diseases. In patients with epilepsy, network connectivity derived from RS-fMRI has found connectivity abnormalities in a number of networks; these include the epileptogenic, cognitive and sensory processing networks. However, in majority of these studies, the effect of epileptic transients in the connectivity of networks has been neglected. EEG-fMRI has frequently shown networks related to epileptic transients that in many cases are concordant with the abnormalities shown in RS studies. This points toward a relevant role of epileptic transients in the network abnormalities detected in RS-fMRI studies. In this review, we summarize the network abnormalities reported by these two techniques side by side, provide evidence of their overlapping findings, and discuss their significance in the context of the methodology of each technique. A number of clinically relevant factors that have been associated with connectivity changes are in turn associated with changes in the frequency of epileptic transients. These factors include different aspects of epilepsy ranging from treatment effects, cognitive processes, or transition between different alertness states (i.e., awake-sleep transition). For RS-fMRI to become a more effective tool to investigate clinically relevant aspects of epilepsy it is necessary to understand connectivity changes associated with epileptic transients, those associated with other clinically relevant factors and the interaction between them, which represents a gap in the current literature. We propose a framework for the investigation of network connectivity in patients with epilepsy that can integrate epileptic processes that occur across different time scales such as epileptic transients and disease duration and the implications of this approach are discussed

Network Connectivity in Epilepsy: Resting State fMRI and EEG-fMRI Contributions.

There is a growing body of evidence pointing toward large-scale networks underlying the core phenomena in epilepsy, from seizure generation to cognitive dysfunction or response to treatment. The investigation of networks in epilepsy has become a key concept to unlock a deeper understanding of the disease. Functional imaging can provide valuable information to characterize network dysfunction; in particular resting state fMRI (RS-fMRI), which is increasingly being applied to study brain networks in a number of diseases. In patients with epilepsy, network connectivity derived from RS-fMRI has found connectivity abnormalities in a number of networks; these include the epileptogenic, cognitive and sensory processing networks. However, in majority of these studies, the effect of epileptic transients in the connectivity of networks has been neglected. EEG-fMRI has frequently shown networks related to epileptic transients that in many cases are concordant with the abnormalities shown in RS studies. This points toward a relevant role of epileptic transients in the network abnormalities detected in RS-fMRI studies. In this review, we summarize the network abnormalities reported by these two techniques side by side, provide evidence of their overlapping findings, and discuss their significance in the context of the methodology of each technique. A number of clinically relevant factors that have been associated with connectivity changes are in turn associated with changes in the frequency of epileptic transients. These factors include different aspects of epilepsy ranging from treatment effects, cognitive processes, or transition between different alertness states (i.e., awake-sleep transition). For RS-fMRI to become a more effective tool to investigate clinically relevant aspects of epilepsy it is necessary to understand connectivity changes associated with epileptic transients, those associated with other clinically relevant factors and the interaction between them, which represents a gap in the current literature. We propose a framework for the investigation of network connectivity in patients with epilepsy that can integrate epileptic processes that occur across different time scales such as epileptic transients and disease duration and the implications of this approach are discussed

Childhood Absence Epilepsy And Varied Effect On Performance On Attention And Motor Tasks, With Correlation To Eeg And Fmri

Childhood absence epilepsy is characterized by a distinct 3-4 Hz spike and wave discharge seen on EEG that is usually associated with a brief loss of consciousness. It is a general form of epilepsy believed to affect the entire brain. We studied children with childhood absence epilepsy with simultaneous fMRI/EEG while they were doing a behavioral test, either continuous performance task (CPT), or repetitive tapping task (RTT). We were interested in the effect seizures would have on their performance on the CPT and RTT task, an attention and motor task respectively. We found that children would be affected earlier or even before seizure onset during the CPT task, while they would be affected later on in the seizure during the RTT task. There was also worse interictal performance in runs where a seizure was recorded. When correlating this with the imaging we found there to be greater power in the frontal leads of the EEG when a child was unable to perform during a seizure, and there was decreased signal in the frontal lobe with fMRI in similarly impaired performance during seizure. This leads us to believe that the frontal lobes, through corticothalamic networks, are more greatly affected during seizure with increased impairment

Neurophysiological signatures reflect differences in visual attention during absence seizures

Objective: Absences affect visual attention and eye movements variably. Here, we explore whether the dissimilarity of these symptoms during absences is reflected in differences in electroencephalographic (EEG) features, functional connectivity, and activation of the frontal eye field. Methods: Pediatric patients with absences performed a computerized choice reaction time task, with simultaneous recording of EEG and eye-tracking. We quantified visual attention and eye movements with reaction times, response correctness, and EEG features. Finally, we studied brain networks involved in the generation and propagation of seizures. Results: Ten pediatric patients had absences during the measurement. Five patients had preserved eye movements (preserved group) and five patients showed disrupted eye movements (unpreserved group) during seizures. Source reconstruction showed a stronger involvement of the right frontal eye field during absences in the unpreserved group than in the preserved group (dipole fraction 1.02% and 0.34%, respectively, p &lt; 0.05). Graph analysis revealed different connection fractions of specific channels. Conclusions: The impairment of visual attention varies among patients with absences and is associated with differences in EEG features, network activation, and involvement of the right frontal eye field. Significance: Assessing the visual attention of patients with absences can be usefully employed in clinical practice for tailored advice to the individual patient.</p