Cognitive functional MRI in temporal lobe epilepsy

Anterior temporal lobe resections (ATLR) provide an effective treatment option for patients with medically refractory temporal lobe epilepsy (TLE) rendering up to 70% of them seizure free. The goal of epilepsy surgery is to remove the brain areas generating the seizures without causing neuropsychological deficits such as language or memory dysfunction. Furthermore up to 60% of patients with TLE suffer from emotional disturbances following surgery. The principle aim of the work presented in this thesis was to improve presurgical evaluation of patients with TLE by using cognitive functional MRI (fMRI) to non-invasively localise brain areas that are essential for processing cognitive function such as language and memory function and emotional and social behaviour. 150 consecutive patients and 40 healthy controls were included in our experiments. Different fMRI paradigms for the evaluation of cognitive functions have been implemented on a 3 Tesla scanner. All subjects underwent language and memory fMRI and standard neuropsychological assessment; those patients who proceeded to have temporal lobe surgery were reinvestigated 4 months following ATLR. We studied the efficiency of reorganisation of language and memory function due to the underlying disease and in particular following ATLR. Amygdala fMRI was used to investigate potential implications on emotional and social outcome. A major part of the work included in this thesis has concentrated on the use of fMRI for the exploration and prediction of postoperative complications such as language and memory impairment but also emotional disturbances. When used in concert with other MR imaging modalities the results of these methods can be used to improve surgical strategies tailored to individual patients with regard to functional outcome, by virtue of definition of epileptic cerebral areas that need to be resected and eloquent areas that need to be spared

Memory reorganization following anterior temporal lobe resection: a longitudinal functional MRI study

Anterior temporal lobe resection controls seizures in 50-60% of patients with intractable temporal lobe epilepsy but may impair memory function, typically verbal memory following left, and visual memory following right anterior temporal lobe resection. Functional reorganization can occur within the ipsilateral and contralateral hemispheres. We investigated the reorganization of memory function in patients with temporal lobe epilepsy before and after left or right anterior temporal lobe resection and the efficiency of postoperative memory networks. We studied 46 patients with unilateral medial temporal lobe epilepsy (25/26 left hippocampal sclerosis, 16/20 right hippocampal sclerosis) before and after anterior temporal lobe resection on a 3 T General Electric magnetic resonance imaging scanner. All subjects had neuropsychological testing and performed a functional magnetic resonance imaging memory encoding paradigm for words, pictures and faces, testing verbal and visual memory in a single scanning session, preoperatively and again 4 months after surgery. Event-related analysis revealed that patients with left temporal lobe epilepsy had greater activation in the left posterior medial temporal lobe when successfully encoding words postoperatively than preoperatively. Greater pre- than postoperative activation in the ipsilateral posterior medial temporal lobe for encoding words correlated with better verbal memory outcome after left anterior temporal lobe resection. In contrast, greater postoperative than preoperative activation in the ipsilateral posterior medial temporal lobe correlated with worse postoperative verbal memory performance. These postoperative effects were not observed for visual memory function after right anterior temporal lobe resection. Our findings provide evidence for effective preoperative reorganization of verbal memory function to the ipsilateral posterior medial temporal lobe due to the underlying disease, suggesting that it is the capacity of the posterior remnant of the ipsilateral hippocampus rather than the functional reserve of the contralateral hippocampus that is important for maintaining verbal memory function after anterior temporal lobe resection. Early postoperative reorganization to ipsilateral posterior or contralateral medial temporal lobe structures does not underpin better performance. Additionally our results suggest that visual memory function in right temporal lobe epilepsy is affected differently by right anterior temporal lobe resection than verbal memory in left temporal lobe epilepsy

The impact of brain-derived neurotrophic factor Val66Met polymorphism on cognition and functional brain networks in patients with intractable partial epilepsy

INTRODUCTION: Medial temporal lobe epilepsy (mTLE) is the most common refractory focal epilepsy in adults. Around 30%-40% of patients have prominent memory impairment and experience significant postoperative memory and language decline after surgical treatment. BDNF Val66Met polymorphism has also been associated with cognition and variability in structural and functional hippocampal indices in healthy controls and some patient groups. AIMS: We examined whether BDNF Val66Met variation was associated with cognitive impairment in mTLE. METHODS: In this study, we investigated the association of Val66Met polymorphism with cognitive performance (n = 276), postoperative cognitive change (n = 126) and fMRI activation patterns during memory encoding and language paradigms in 2 groups of patients with mTLE (n = 37 and 34). RESULTS: mTLE patients carrying the Met allele performed more poorly on memory tasks and showed reduced medial temporal lobe activation and reduced task-related deactivations within the default mode networks in both the fMRI memory and language tasks than Val/Val patients. CONCLUSIONS: Although cognitive impairment in epilepsy is the result of a complex interaction of factors, our results suggest a role of genetic factors on cognitive impairment in mTLE

Imaging language networks before and after anterior temporal lobe resection: results of a longitudinal fMRI study.

Anterior temporal lobe resection (ATLR) controls seizures in up to 70% of patients with intractable temporal lobe epilepsy (TLE) but, in the language dominant hemisphere, may impair language function, particularly naming. Functional reorganization can occur within the ipsilateral and contralateral hemispheres. We investigated reorganization of language in left-hemisphere-dominant patients before and after ATLR; whether preoperative functional magnetic resonance imaging (fMRI) predicts postoperative naming decline; and efficiency of postoperative language networks

Brezin-Gross-Witten model as "pure gauge" limit of Selberg integrals

The AGT relation identifies the Nekrasov functions for various N=2 SUSY gauge theories with the 2d conformal blocks, which possess explicit Dotsenko-Fateev matrix model (beta-ensemble) representations the latter being polylinear combinations of Selberg integrals. The "pure gauge" limit of these matrix models is, however, a non-trivial multiscaling large-N limit, which requires a separate investigation. We show that in this pure gauge limit the Selberg integrals turn into averages in a Brezin-Gross-Witten (BGW) model. Thus, the Nekrasov function for pure SU(2) theory acquires a form very much reminiscent of the AMM decomposition formula for some model X into a pair of the BGW models. At the same time, X, which still has to be found, is the pure gauge limit of the elliptic Selberg integral. Presumably, it is again a BGW model, only in the Dijkgraaf-Vafa double cut phase.Comment: 21 page

Branes, U-folds and hyperelliptic fibrations

We construct a class of supersymmetric vacua of type IIB string theory describing systems of three- and seven-branes non-perturbatively completed by brane instantons. The vacua are specified by a set of holomorphic functions defined over a complex plane up to non-trivial U-duality monodromies around the brane locations. In the simplest setting, the solutions can be seen as a generalization of F-theory elliptic fibrations, where the torus fiber is replaced by a genus two Riemann surface with periods encoding the information on the axio-dilaton, the warp factor and the NS-NS and R-R fluxes.Comment: 49 pages, including 22 pages of Appendix, 2 figures. Minor change

Pattern Classification of Large-Scale Functional Brain Networks: Identification of Informative Neuroimaging Markers for Epilepsy

The accurate prediction of general neuropsychiatric disorders, on an individual basis, using resting-state functional magnetic resonance imaging (fMRI) is a challenging task of great clinical significance. Despite the progress to chart the differences between the healthy controls and patients at the group level, the pattern classification of functional brain networks across individuals is still less developed. In this paper we identify two novel neuroimaging measures that prove to be strongly predictive neuroimaging markers in pattern classification between healthy controls and general epileptic patients. These measures characterize two important aspects of the functional brain network in a quantitative manner: (i) coordinated operation among spatially distributed brain regions, and (ii) the asymmetry of bilaterally homologous brain regions, in terms of their global patterns of functional connectivity. This second measure offers a unique understanding of brain asymmetry at the network level, and, to the best of our knowledge, has not been previously used in pattern classification of functional brain networks. Using modern pattern-recognition approaches like sparse regression and support vector machine, we have achieved a cross-validated classification accuracy of 83.9% (specificity: 82.5%; sensitivity: 85%) across individuals from a large dataset consisting of 180 healthy controls and epileptic patients. We identified significantly changed functional pathways and subnetworks in epileptic patients that underlie the pathophysiological mechanism of the impaired cognitive functions. Specifically, we find that the asymmetry of brain operation for epileptic patients is markedly enhanced in temporal lobe and limbic system, in comparison with healthy individuals. The present study indicates that with specifically designed informative neuroimaging markers, resting-state fMRI can serve as a most promising tool for clinical diagnosis, and also shed light onto the physiology behind complex neuropsychiatric disorders. The systematic approaches we present here are expected to have wider applications in general neuropsychiatric disorders

Contending with Spiritual Reductionism: Demons, Shame, and Dividualising Experiences Among Evangelical Christians with Mental Distress

The belief that mental distress is caused by demons, sin, or generational curses is commonplace among many evangelical Christian communities. These beliefs may have positive or negative effects for individuals and groups. Phenomenological descriptions of these experiences and the subjective meanings associated with them, however, remain somewhat neglected in the literature. The current study employed semi-structured interviews with eight evangelical Christians in order to idiographically explore their experiences of mental distress in relation to their faith and wider communities. Through an interpretative phenomenological analysis, two superordinate themes were constructed: negative spiritualisation and negotiating the dialectic between faith and the lived experience of mental distress. Participants variously experienced a climate of negative spiritualisation, whereby their mental distress was demonised and dismissed, and they were further discouraged from seeking help in secular institutions and environments. Participants often considered such dismissals of their mental distress as unhelpful and stigmatising and experienced heightened feelings of shame and suffering as a result. Such discouragement also contributed to the process of othering and relational disconnection. Alongside a rejection of church teachings, which exclusively spiritualised psychological distress, participants negotiated a nuanced personal synthesis of faith, theology, and distress, which assumed a localised and idiographic significance. This synthesis included advocating for the uptake of aetiological accounts, which contextualised mental distress in terms of the whole person and resisted de-politicised, dichotomised, and individualistic narratives. Results are discussed in relation to a broad range of literature in the field, while further research suggestions are provided.N/