| Date post: | 19-Aug-2015 |
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Health & Medicine |
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The Mesial Temporal Structures & Behavior - Towards a Neurobiological Nexus
Neurokrish | Neurosciences India Group
Neurokrish Consulting
Dr. Ennapadam S KrishnamoorthyMD., DCN, PhD, FRCP (Lond, Glas, Edin),
FIPS, MAMSFounder & Director
@Neurokrish | [email protected]
Vivek MisraB.Tech (Genetic Engg), M.S. (Clin Neuro)
Research Associate@iVivekMisra
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What Is The Problem ?
“Indeed, symptom-based diagnosis, once common in other areas of medicine, has been largely replaced in the past half century as
we have understood that symptoms alone rarely indicate the best choice of treatment.
Patients with mental disorders deserve better.”
~ Tom Insel, M.D., Director of the National Institute of Mental Health
Neurokrish Consulting
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Mesial Temporal Structures
Neurokrish Consulting
Intraventricular Structures• Hippocampus;• Fimbria;• Amygdala ; and • Choroidal fissure.
Extraventricular Structures• Uncus;• Parahippocampal Gyrus; • Dentate Gyrus.
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Types of Temporal Lobe Epilepsy
• MTLE with Hippocampal Sclerosis – Primary– Secondary ? Dual Pathology– Familial
• Other Mesial temporal lesion• Benign nonfamilial temporal lobe epilepsy• Partial epilepsy with auditory features• Lateral temporal lobe epilepsy
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The Mesial Temporal Syndrome Epilepsy - The Trimble Construct
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Features of the Affective Somatoform spectrum
Changes in the structureOf the AHC
Features of the Geschwind syndrome
Psychotic features specific to epilepsy
AEDs
Seizures
NeuropsychologicalSymptoms
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Epilepsy and Mesial Temporal Lobe
• While the amygdala is widely regarded as the seat of human emotion, the hippocampus is well recognized as being the storehouse of memories.
• Number of studies have shown change in MTS volumes (Bernasoni, 2003a); entorhinal cortex involvement (Bernasconi, 2003b; Bartlomei, 2005); involvement of hippocampus, amygdala and entorhinal cortex and progressive but differential volume loss (Bernasconi, 2005);
• There may be a differential role for the amygdala, hippocampus and possibly other temporal structures, in the development and/or the expression of psychopathology.
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Mesial Temporal Structure Volumes And Psychopathology• With the advancement in imaging technology, there is a evolving focus on
volumetric studies of ROI.
• While the amygdala is widely regarded as the seat of human emotion, the hippocampus is well recognised as being the storehouse of memories. Both structures have pivotal role across Neuropsychiatric Disorders.
• Studies have highlighted the volumetric changes in both Amygdala and Hippocampus in several affective disorder such as unipolar major depression, psychosis, schizophreniform affective disorder. (Briellmann 2007, Velakoulis 2006)
• More recent finding suggests the role of MTS in various behavioral outcomes such as – Viscosity, Hyposexuality, Religiosity, Hypergraphia etc in Temporal Lobe & Refractory Epilepsy.
Krishnamoorthy ES: JNNP: 2007 Nov; 78(11): 1165–1166.
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Put on the Clinician’s Hat
Is it Degenerative ?Is it Neoplastic ?Is it Metabolic ? Is it Vascular ?Is it Developmental ?Is it Trauma ?
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What is the Pathophysiology ?
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Metabolic Degenerative
Developmental
Genetic Predisposition
Environmental Factors Gene – Environment
Interactions
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Mesial Temporal Structures
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Hippocampus Amygdala
Structurally Functionally
DevelopmentalEpileptogenesis
Enlarged / Atrophied Hyper / Hypo Activation
Memory Complaints Behavioral Complaints
REST BDNFmTOR
Back
tran
slati
on Translation
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Focus - Epileptogenesis: A Convergence On Neural Circuit Dysfunction
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Goldberg & Coulter 2013
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Focus – Brain Derived Neurotrophic Factor
• Brain Derived Neurotrophic Factor (BDNF) provides a potential mechanism for the observed up-regulation in Epilepsy.
• BDNF's vital role in the development of the landscape of the brain and up-regulated levels of both BDNF mRNA and BDNF protein suggest its role in epilepsy, (Gall et al., 1991) by:
– modulating excitatory and inhibitory synaptic transmission by inhibiting GABAA-receptor-mediated post-synaptic currents. (Tanaka et al., 1997)
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The Network - Transcriptomic Profiling of Medial Temporal Lobe Epilepsy
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Red shows Upregulated and Green indicates Downregulation. Venugopal et al., 2012
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Our Proposition
• A diagnostic approach based on the biology as well as the symptoms must not be constrained by the current DSM categories.
• Mental disorders are biological disorders involving brain circuits that implicate specific domains of cognition, emotion, or behavior.
• Each level of analysis needs to be understood across a dimension of function.
• Mapping the cognitive, circuit, and genetic aspects of mental disorders will yield new and better targets for treatment.
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What is The Future ?
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The Research Domain Criteria (RDoC) Project: NIMH
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Take Home Message• Neuropsychiatry is a complex specialty that requires integration of knowledge
about structure and function.
• The MTS is a region of interest from a neurobiological perspective for epilepsy, schizophrenia and depression: common genetic mechanisms for these myriad yet linked conditions need to be understood.
• Complex Neuropsychiatric syndromes like the Mesial Temporal Epilepsy syndrome deserve our attention.
• The Old: Dissect in Anatomy, Experiment in Physiology, Follow the body to autopsy (Boyd's Pathology)
• The New: Detail orientate the clinical syndrome (phenotype), image the brain (region of interest), follow it up in the laboratory (genetic & biochemical studies)
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