Epilepsy & Brain Modulation

Tuesday 13 May 2014

Karsten Mueller¹, Harald E Möller¹, Franziska Busse¹, Annette Horstmann^1,2, Jöran Lepsien¹, Matthias L Schroeter^1,3, Matthias Blüher^2,4, Michael Stumvoll⁴, Arno Villringer^1,3, and Burkhard Pleger^1,3
1Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, ²Integrated Research and Treatment Center (IFB) Adiposity Diseases, Leipzig, Germany, ³Day Clinic for Cognitive Neurology, University Hospital Leipzig, Germany, ⁴Department for Internal Medicine, University Hospital Leipzig, Germany

We investigated the effect of intense physical exercise on brain structure in relation to the brain-derived neurotrophic factor (BDNF), leptin and high-density lipoprotein (HDL) serum concentrations in 16 young overweight and obese participants. After a 3-months fitness program, we found a significant decrease of leptin and an increase of HDL and BDNF. Structural MRI was performed directly after blood withdrawal. Significant correlations were found between the intra-individual changes in serum markers concentration and grey matter density, particularly in the left hippocampus, and radial diffusivity in large white matter regions including the whole corpus callosum.

Claudia Metzler-Baddeley¹, Karen Caeyenberghs², Sonya Foley³, and Derek K Jones^3
1CUBRIC, Cardiff University, Cardiff, United Kingdom, ²University of Ghent, Ghent, Belgium, ³CUBRIC, Cardiff University, Wales, United Kingdom

Brain trainings are popular and used by many to improve mental capacity and combat age-related decline. However, the evidence for training benefits on brain structure remains limited and controversial. This research investigated the effects of a 2 months working memory training on microstructure in white matter pathways mediating cognitive control (the superior longitudinal fasciculus, the arcuate and the cingulum). Relative to an active placebo condition, training led to improvements in working memory span capacity, which were related to alterations in white matter microstructure in the cingulum and the arcuate and were dependent on inter-individual differences in baseline microstructural properties.

Thomas Mueggler¹, Michael Honer¹, Basil Künnecke¹, Andreas Bruns¹, Andrew W. Thomas², Maria-Clemencia Hernandez¹, and Markus von Kienlin^1
1Pharma Research & Early Development, DTA Neuroscience, Hoffmann-La Roche, Basel, Basel-City, Switzerland, ²Pharma Research & Early Development, Pharma Research & Early Development, Small Molecule Research, Hoffmann-La Roche, Basel, Basel-City, Switzerland

Increased GABA-mediated inhibition has been proposed as a mechanism underlying deficient cognition in the Ts65Dn (TS) mouse model of Down syndrome. Using ASL-based fMRI we reveal a region-specific perfusion phenotype in TS mice and demonstrate complete reversal after chronic treatment with RO4938581, a negative allosteric modulator (NAM) selective for the GABA_A alpha5 receptor subtype, specifically of the observed hippocampal deficits. This novel finding is in line with recently reported effects of RO4938581 to rescue hippocampal synaptic plasticity, spatial learning and memory in TS mice supporting the potential therapeutic use of selective GABA_A alpha5 NAMs to treat cognitive dysfunction in Down syndrome.

Yu-Chen Chen¹, Jian Wang^2,3, Yun Jiao¹, Richard Salvi⁴, and Gao-Jun Teng^1
1Jiangsu Key Laboratory of Molecular Imaging and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University,Nanjing,China, Nanjing, Jiangsu, China, ²Department of Physiology and Pharmacology, Medical School of Southeast University,Nanjing,China, Nanjing, Jiangsu, China, ³School of Human Communication Disorders, Dalhousie University, Halifax, Nova Scotia, Canada, Nova Scotia, Canada, ⁴Center for Hearing and Deafness, University at Buffalo, Buffalo, NY, USA, New York, United States

Recent studies suggest that low frequency neural oscillatory activity contributes to tinnitus generation. To explore this issue, we measured the amplitude of low-frequency fluctuations (ALFF) in resting-state functional magnetic resonance imaging (fMRI) during salicylate-induced tinnitus and during sound stimulation. We found that salicylate significantly increased ALFF oscillatory activity in several auditory and non-auditory regions previously implicated in tinnitus. Music stimulation tended to potentiate the salicylate-induced hyperactivity in the ALFF responses in many auditory areas. Resting-state ALFF fMRI might be used to identify the aberrant neural networks in humans who suffer from severe, debilitating tinnitus.

Peter T. Fwu¹, Elysia P. Davis², Claudia Buss², Muqing Lin¹, Kevin Head², Curt A. Sandman², and Min-Ying Lydia Su^1
1Tu & Yuen Center for Functional Onco-Imaging, Department of Radiological Sciences, University of California, Irvine, CA, United States, ²Women and Children’s Health and Well-Being Project, Department of Psychiatry & Human Behavior, University of California, Irvine, CA, United States

Hippocampal volume and shape analysis was applied to 103 children (6-10 years old) to evaluate the association with prenatal and post-partum depression of their mothers during and after pregnancy. Non-rigid registration was applied to analyze shape based on the deformation matrix. The head segment of the right hippocampus showed a significant association with prenatal depression, and the body segment of the left hippocampus showed a significant correlation with the post-partum depression. The results were similar in males and females. None of the volumetric measurements revealed significant correlations, suggesting that shape analysis may provide a more sensitive tool for subregional analysis.

Gregory Harrison Turner¹, Johana Vallejo², Mohammed Abdelwahab³, Qingwei Liu¹, Lana Leung², Younghee Ahn⁴, Jong Rho⁴, and Do Young Kim^3
1Neuroimaging Research, Barrow Neurological Institute, Phoenix, AZ, United States, ²Physiology, Midwestern University, Glendale, AZ, United States,³Barrow Neurological Institute, AZ, United States, ⁴Alberta Children's Hospital, University of Calgary, Alberta, Canada

Chronic in vivo administration of BHB results in a significant anticonvulsant effect in Kcna1-null mice. Moreover, Manganese Enhanced MRI found that BHB alone appears to exert a structural neuroprotective effect in hippocampus. The combination of morphological and functional neuroprotective effects of BHB in this genetic model of epilepsy suggests that KB may be beneficial for neurological conditions other than epilepsy.

Luis Manuel Colon-Perez¹, Eric Montie², Michelle Couret³, and Thomas Mareci^1
1Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, United States, ²Natural Science, University of South Carolina Beaufort, Bluffton, SC, United States, ³University of Florida, FL, United States

Thyroid hormone (TH) deficiencies have been shown to affect the developmental process of myelination in rat brains. Thyroid hormone deficiencies induce various neurological symptoms, as cognitive deficits, sensory and motor impairments. The neurological symptoms related to TH deficiencies are also associated with changes in brain structure, which result from the reduction of white matter volume. Thyroid-hormone deficiency leads to a decrease in the strength of connectivity measures and changes in network connectivity. In order to study the effects of thyroid disruption in rat cortical networks, we acquired diffusion-weighted data, performed tractography on ex vivo rat brains and graph theory analysis

Tuukka Miettinen¹, Raimo Salo¹, Heikki Yli-Ollila¹, Teemu Laitinen¹, Juhana Sorvari¹, Asla Pitkänen^1,2, Olli Gröhn¹, and Alejandra Sierra^1
1Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland, ²Department of Neurology, Kuopio University Hospital, Kuopio, Finland

In this study, our hypothesis was that in vivo DTI is able to detect progression of microstructural alterations in the hippocampus and in other white matter and grey matter areas during the early stages of epileptogenesis. Rats were scanned using in vivo high resolution DTI before, and 10, 20, 34 and 79 days after status epilepticus induced by kainic acid or pilocarpine. We found robust and progressive changes in fractional anisotropy, axial, linear and spherical diffusivities and also in the orientation of principal diffusion direction in the hippocampus and other brain areas throughout the brain. These findings have potential to serve as predictive biomarkers for epilepsy in the future.

Peter B Barker¹, Gregory K Bergey², Huong Trinh³, Tilak Ratnanather³, He Zhu⁴, David Bonekamp⁵, and Doris D.M. Lin^5
1Radiology, JHU SOM, Baltimore, MD, United States, ²Neurology, JHU SOM, MD, United States, ³Center for Imaging Science, JHU, MD, United States,⁴Radiology, Vanderbilt University, TN, United States, ⁵Radiology, JHU SOM, MD, United States

Although MRI plays an important role in the evaluation of patients with drug-resistant partial epilepsy, it has been reported that approximately 30% of patients with mesial temporal lobe epilepsy (mTLE, the most common form) have normal scans at 1.5 or 3.0T. This study investigates the use of high resolution MRI and MRSI at 7.0T for the evaluation of mTLE. Results suggests that subtle abnormalities may be detected at 7.0T in patients with scans read as normal at 3T. 7.0T MR may therefore allow more patients to proceed directly to surgery without the need for invasive EEG monitoring.

Simon Sean Keller¹, Mark Richardson², Jan-Christoph Schoene-Bake³, Jonathan O’Muircheartaigh⁴, Christian Elger³, and Bernd Weber^3
1Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, Merseyside, United Kingdom, ²Clinical Neuroscience, Institute of Psychiatry, King's College London, London, United Kingdom, ³Department of Epileptology, University of Bonn, Bonn, Germany,⁴Neuroimaging, Institute of Psychiatry, King's College London, London, United Kingdom

We have applied multiple automated mapping methods to T1-weighted MRIs to determine the presurgical neuroanatomical correlates of persistent postoperative seizures (PPS) in patients with medically intractable temporal lobe epilepsy (TLE). We report that patients with PPS have atrophy of the mesial temporal lobe contralateral to the side of intended surgery and of the thalamus and striatum bilaterally relative to patients surgically rendered seizure free. The identification of preoperative bihemispheric hippocampo-thalamo-striatal abnormalities may indicate susceptibility to PPS in patients with intractable TLE.