|Year : 2017 | Volume
| Issue : 2 | Page : 139-143
Neuroanatomical changes in brain structures related to cognition in epilepsy: An update
K Saniya1, BG Patil2, Madhavrao D Chavan3, KG Prakash1, Kumar Sai Sailesh4, R Archana5, Minu Johny4
1 Department of Anatomy, Azeezia Institute of Medical Sciences, Kollam, Kerala, India
2 Department of Anatomy, Shri B. M. Patil Medical College, Bijapur, Karnataka, India
3 Department of Pharmacology, Azeezia Institute of Medical Sciences, Kollam, Kerala, India
4 Department of Physiology, Little Flower Institute of Medical Sciences and Research, Angamaly, Kerala, India
5 Department of Anatomy, Saveetha Medical College, Saveetha University, Chennai, Tamil Nadu, India
|Date of Web Publication||10-Jul-2017|
Department of Anatomy, Azeezia Institute of Medical Sciences, Meeyyannoor, Kollam, Kerala
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Understanding the microanatomical changes in brain structures is necessary for developing innovative therapeutic approaches to prevent/delay the cognitive impairment in epilepsy. We review here the microanatomical changes in the brain structures related to cognition in epilepsy. Here, we have presented the changes in major brain structures related to cognition, which helps the clinicians understand epilepsy more clearly and also helps researchers develop new treatment procedures.
Keywords: Brain structures, cognition, epilepsy, Neuro-Anatomical changes
|How to cite this article:|
Saniya K, Patil B G, Chavan MD, Prakash K G, Sailesh KS, Archana R, Johny M. Neuroanatomical changes in brain structures related to cognition in epilepsy: An update. J Nat Sc Biol Med 2017;8:139-43
|How to cite this URL:|
Saniya K, Patil B G, Chavan MD, Prakash K G, Sailesh KS, Archana R, Johny M. Neuroanatomical changes in brain structures related to cognition in epilepsy: An update. J Nat Sc Biol Med [serial online] 2017 [cited 2018 May 20];8:139-43. Available from: http://www.jnsbm.org/text.asp?2017/8/2/139/210016
| Introduction|| |
Epilepsy (also called “Seizures”) is characterized by uncontrolled excessive activity of either part or all of the central nervous system. Although epilepsy is not a specific disease, it is considered as a group of syndromes as a result of chronic neurological disorders. Epilepsy can be classified into three major types: grand mal epilepsy, petit mal epilepsy, and focal epilepsy. Global prevalence of epilepsy is approximately 0.5% affecting predominantly early childhood and late adulthood resulting in psychological and social consequences. The causes and treatment protocols vary widely. In India, over 10 million patients suffer from epilepsy, which equates to a prevalence rate of 1%. Impairment of cognition is a common condition in epilepsy, and the features include mental slowness and memory and attention deficits in adults. Learning disabilities, poor academic outcome, behavioral problems, and language stagnation or deterioration are additional features observed in children. Underlying cause of cognition impairment may be lesion in particular brain area consequence to seizures or epileptic dysfunction, with age-associated increase in the vulnerability. However, seizures in children have reported to cause long-term adverse effects. Further, the extent of brain damage also depends on number, duration, and severity of seizures. Understanding the microanatomical changes in brain structures may lead to innovative therapeutic approaches to prevent/delay the cognitive impairment in epilepsy. Hence, we aimed to review the microanatomical changes in the brain structures related to cognition in epilepsy.
| Materials and Methods|| |
A detailed literature review was performed between February 2016 and August 2016, through MEDLINE, Google, PubMed, Scopus, British Medical Journal, Medline, Eric, Frontiers, and other online journals using the terms “epilepsy,” “micro-anatomical changes,” “basal ganglia,” “cerebellum,” “brain volume,” “thalamus,” “hypothalamus,” “limbic system,” “locus coeruleus,” and “cerebral cortex.” Article selection was based on their relevance to the present topic.
| Changes in Hippocampus in Epilepsy|| |
Hippocampus plays a crucial role in cognition and it is involved in minute-to-minute cognitive processing. Hippocampus and associated areas were reported to be affected critically in epilepsy, especially temporal lobe epilepsy, which is more common in adults. It was reported that recurrent seizures might cause hippocampus damage throughout the lifetime of the patient. Structural (histological) and functional changes occur in hippocampus in epilepsy. Histological changes include selective and extensive hippocampal neuronal loss in CA1 and CA3 regions and around the end folium where the cells of CA2 region are spared.,,,, In other types of epilepsy, neuronal loss can be observed in all hippocampal areas. Apart from neuronal loss and gliosis, granule cell dispersion in dentate gyrus is also observed in epilepsy. Atrophied hippocampus is reported to be responsible for seizures, and surgical removal of hippocampus is reported to improve the condition.,
| Changes in Basal Ganglia in Epilepsy|| |
The role of basal ganglia in cognitive functions is well established. Earlier studies hypothesized that basal ganglia functions as a part of a modulatory control system over seizures rather than a propagation pathway. Although no specific epileptic electroencephalography changes were observed in basal ganglia, involvement of basal ganglia in distribution of epileptic activity was reported. Dopamine is reported to involve in the control of seizures related to the type of epilepsy. Sufficiently, sustained seizures cause damage of substantia nigra pars reticulate (SNR) and globus pallidus. Interestingly, epilepsy has been reported to have inverse relationship with Parkinson's disease as incidence of seizures is less in patients with Parkinson's disease., Seizures may lead to progressive microanatomical changes in putamen of both hemispheres. As the SNR plays a major role in the modulation of seizures, the seizures may be treated with high-frequency stimulation of SNR.,,
| Changes in Piriform Cortex in Epilepsy|| |
Cortical, subcortical neuronal networks play a key role in generation, maintenance, and spread of epileptic activity. The piriform cortex (PC) and amygdala generate seizures in response to chemical and electrical stimulation and as an amplifier of epileptic activity when seizures are generated elsewhere. Structural abnormalities were observed in PC in frontal lobe epilepsy.
MR imaging reported that the PC amygdala is extensively damaged in chronic temporal lobe epilepsy patients, particularly in those with hippocampal atrophy. Changes in the PC are responsible for complex partial seizures, i.e., the most common type of seizures in human epilepsy.,,,
| Changes in Gray Matter in Epilepsy|| |
It was reported that gray matter volume was associated with cognitive functions. Decreased gray matter was observed in epileptic patients.,,,, Most important area where gray matter abnormalities occurs is hippocampus. Other areas include thalamus, parietal lobe, and cingulate gyrus. Changes have also been described in the parahippocampal gyrus, middle temporal gyrus, superior temporal gyrus, inferior temporal gyrus, fusiform gyrus, temporal pole, entorhinal cortex, amygdala, and perirhinal cortex.,,, It was reported that abnormalities of gray matter are essential to produce reductions in episodic memory recall. Most commonly seen cognitive dysfunctions due to gray matter abnormalities in children are decline in verbal intelligence quotient, freedom from distractibility, and executive function and mental slowness, memory impairment and attention deficits in commonly observed among adults.,,
| Changes in Glial Cells in Epilepsy|| |
Defects in the glial cells, especially astrocytes, may cause epilepsy as they play an important role in regulation of transmission and extracellular ions., Indeed, alterations in distinct astrocyte membrane channels, receptors, and transporters have all been associated with the epileptic state.
| Changes in Hypothalamus in Epilepsy|| |
The relationships between the hypothalamic mass and the different types of seizures remain unknown. Sex steroid hormone axis abnormalities occur more commonly in people with epilepsy. Release of sex steroid hormones is controlled by the hypothalamic–pituitary–gonadal axis; the medications used to treat epilepsy can have direct effects on regulation of these hormonal systems. The changes in the hormone may lead to hypogonadism and sexual dysfunction and are linked to polycystic ovary syndrome, decrease in fertility and childbirth rate, premature menopause, and thyroid disorders. It may also cause hormonal contraceptive interaction. Endogenous hormones can influence seizure severity and frequency, resulting in catamenial patterns of epilepsy., Women who are taking antiepileptic drugs have increased risk of maternal and fetal complication; hence, good planning and effective caring is necessary during and after the pregnancy. Epilepsy and sleep have reciprocal relationships, lack of sleep may lead to seizures, and seizures adversely affect the sleep pattern. Treating sleep disorders, which are potentially caused by or contributed to by autism, may impact favorably on seizure control and on daytime behavior. In nearly one-third of patients, the occurrence of seizures was during the sleep state. This is caused by an intimate relationship between the physiological state of sleep and the pathological process underlying epileptic seizures. Hence, control of seizure can improve sleep. Seizures, antiepileptic drugs, and vagus nerve stimulation all influence sleep quality, daytime alertness, and neurocognitive function. Cold and shiver and piloerection are rare ictal signs in focal epilepsies and are often associated with an epileptic seizure focus within the temporal lobe. Hypothalamic lesions can impact thermoregulation; hence, temperature dysregulation is commonly observed during epileptic condition.
| Changes in Thalamus in Epilepsy|| |
Anterior thalamus influences memory processing and spatial navigation through its interactions with hippocampus and cortex. Other studies reported that intralaminar thalamic nucleus, the parafascicular thalamus, also contributes to behavioral flexibility, whereas the mediodorsal thalamic nucleus plays a key role in acquiring goal-directed behavior. Thalamic lesions in patients with seizure disorders are wider and are associated with atrophy of limbic system. Prolonged partial status epilepticus may lead to thalamic diffusion-weighted imaging hyperintense lesions, and thalamus is likely to participate in the evolution and propagation of partial seizures. Further, it was observed that selective reductions in gamma-aminobutyric acid receptor subunits in thalamus may play a role in pathophysiology of absence epilepsy.
| Changes in Cerebellum in Epilepsy|| |
Role of cerebellum in cognition and behavior is well documented. Cerebellar atrophy was reported in patients with epilepsy. Although peri-ictal changes in cerebellar perfusion was observed in epilepsy, its contribution to cerebellar atrophy was minimum. Cerebellar stimulation especially in anterior lobe and thalamic region is reported to be effective in patients with seizures.,
| Changes in Olfactory Cortex in Epilepsy|| |
Primary olfactory cortex (piriform cortex) is central to olfactory identification and is an epileptogenic structure. Epilepsy appears to cause a generalized decrease in olfactory functioning although increased sensitivity may occur in some epileptic patients at some time in the pre-ictal period. Other sensory modalities are also affected by the epileptic process which, in some cases, involve limbic-related temporal lobe structures. Many of the olfactory deficits previously attributed to temporal lobe resection actually exist preoperatively. Confusions in taste and unpleasant auras are associated with hyperresponsiveness of neurons, which may explain why most epilepsy-related olfactory auras are described as bad. Interesting parallels exist between the effects of the neuroendocrine system on seizure activity and olfactory function.
| Changes in Amygdala in Epilepsy|| |
Following stimulation of amygdale, a full spectrum of experiential symptoms is observed in patients with temporal lobe epilepsy. Selective amygdalotomy has proved to be an effective treatment for temporal lobe epilepsy. Lateral amygdala is a nucleus of the amygdala that projects to the temporal neocortex and hippocampus. Rodent studies have shown that spontaneous discharges occur in the lateral amygdala of epileptics. In two patients, interictal spikes, spike-wave, and polyspike complexes were observed intraoperatively in the amygdala; however, evidence of its origin from the amygdale is lacking. Recent research in humans have indicated that amygdala lesions may impair selective domains of affect and cognition, which are related to the appraisal of emotional and social significance of sensory events. Damage to the amygdala may cause a wide range of deficits in the appraisal of emotional and social significance of sensory events although these deficits are often variable and still poorly understood.
| Conclusion|| |
We have presented the gross changes in major brain structures related to cognition deficits associated with epilepsy, which we hope will help the clinicians and biomedical researcher to further understand the epilepsy.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Dawda Y, Ezewuzie N. Epilepsy: Clinical features and diagnosis. Clin Pharm2010;2:86-8.
Vaz M, Kurpad A, Raj T. Guyton and Hall Textbook of Medical Physiology. A South Asian Edition. New Delhi: Reed Elsevier India Private Limited; 2013. p. 818.
Selvaraj N, Adhimoolam M, Perumal DK, Rajamohammed MA. Neuroprotective effect of lercanidipine – A novel calcium channel blocker in albino mice. J Clin Diagn Res 2015;9:FF01-5.
Goyal A, Bhadravathi MC, Kumar A, Narang R, Gupta A, Singh H. Comparison of dental caries experience in children suffering from epilepsy with and without administration of long term liquid oral medication. J Clin Diagn Res 2016;10:ZC78-82.
Sridharan R, Murthy BN. Prevalence and pattern of epilepsy in India. Epilepsia 1999;40:631-6.
van Rijckevorsel K. Cognitive problems related to epilepsy syndromes, especially malignant epilepsies. Seizure 2006;15:227-34.
Helmstaedter C. The impact of epilepsy on cognitive function. J Neurol Neurosurg Psychiatry2013;84:e1.
Haut SR, Velísková J, Moshé SL. Susceptibility of immature and adult brains to seizure effects. Lancet Neurol 2004;3:608-17.
Sutula T, Pitkänen A. Do seizures damage the brain? Prog Brain Res 2002;135:1-520.
Lado FA, Laureta EC, Moshé SL. Seizure-induced hippocampal damage in the mature and immature brain. Epileptic Disord 2002;4:83-97.
Sweatt JD. Hippocampal function in cognition. Psychopharmacology (Berl) 2004;174:99-110.
Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV. Jasper's Basic Mechanisms of the Epilepsies. (Contemporary Neurology Series 80). 4th
ed. USA: Oxford University Press; 2012.
Kälviäinen R, Salmenperä T, Partanen K, Vainio P, Riekkinen P, Pitkänen A. Recurrent seizures may cause hippocampal damage in temporal lobe epilepsy. Neurology 1998;50:1377-82.
Bruton CJ. The Neuropathology of Temporal Lobe Epilepsy. Oxford: Oxford University Press; 1988.
Meldrum BS, Bruton CJ. Epilepsy. In: Adams JH, Duchen LW, editors. Greenfield's Neuropathology. New York: Oxford University Press; 1992. p. 1246-83.
Sendrowski K, Sobaniec W. Hippocampus, hippocampal sclerosis and epilepsy. Pharmacol Rep 2013;65:555-65.
Schiffer D, Cordera S, Tereni A. Neuropathological findings in surgical specimens of temporal lobe epilepsy. Crit Rev Neurosurg 1994;4:339-50.
Thom M. Hippocampal sclerosis: Progress since Sommer. Brain Pathol 2009;19:565-72.
Blümcke I, Thom M, Wiestler OD. Ammon's horn sclerosis: A Maldevelopmental disorder associated with temporal lobe epilepsy. Brain Pathol 2002;12:199-211.
Spencer SS, Spencer DD. Entorhinal-hippocampal interactions in medial temporal lobe epilepsy. Epilepsia 1994;35:721-7.
Spencer SS. Substrates of localization-related epilepsies: Biologic implications of localizing findings in humans. Epilepsia 1998;39:114-23.
Leisman G, Braun-Benjamin O, Melillo R. Cognitive-motor interactions of the basal ganglia in development. Front Syst Neurosci 2014;8:16.
Dematteis M, Kahane P, Vercueil L, Depaulis A. MRI evidence for the involvement of basal ganglia in epileptic seizures: An hypothesis. Epileptic Disord 2003;5:161-4.
Rektor I, Kuba R, Brázdil M. Interictal and ictal EEG activity in the basal ganglia: An SEEG study in patients with temporal lobe epilepsy. Epilepsia 2002;43:253-62.
Bouilleret V, Semah F, Biraben A, Taussig D, Chassoux F, Syrota A, et al.
Involvement of the basal ganglia in refractory epilepsy: An 18F-fluoro-L-DOPA PET study using 2 methods of analysis. J Nucl Med 2005;46:540-7.
Inamura K, Smith ML, Hansen AJ, Siesjö BK. Seizure-induced damage to substantia nigra and globus pallidus is accompanied by pronounced intra- and extracellular acidosis. J Cereb Blood Flow Metab 1989;9:821-9.
Vercueil L. Parkinsonism and epilepsy: Case report and reappraisal of an old question. Epilepsy Behav 2000;1:128-30.
Vercueil L, Hirsch E. Seizures and the basal ganglia: A review of the clinical data. Epileptic Disord 2002;4 Suppl 3:S47-54.
Gerdes JS, Keller SS, Schwindt W, Evers S, Mohammadi S, Deppe M. Progression of microstructural putamen alterations in a case of symptomatic recurrent seizures using diffusion tensor imaging. Seizure 2012;21:478-81.
Iadarola MJ, Gale K. Substantia nigra: Site of anticonvulsant activity mediated by gamma-aminobutyric acid. Science 1982;218:1237-40.
Velísková J, Claudio OI, Galanopoulou AS, Kyrozis A, Lado FA, Ravizza T, et al.
Developmental aspects of the basal ganglia and therapeutic perspectives. Epileptic Disord 2002;4 Suppl 3:S73-82.
Velísková J, Moshé SL. Update on the role of substantia nigra pars reticulata in the regulation of seizures. Epilepsy Curr 2006;6:83-7.
Centeno M, Vollmar C, Stretton J, Symms MR, Thompson PJ, Richardson MP, et al.
Structural changes in the temporal lobe and piriform cortex in frontal lobe epilepsy. Epilepsy Res 2014;108:978-81.
Gonçalves Pereira PM, Insausti R, Artacho-Pérula E, Salmenperä T, Kälviäinen R, Pitkänen A. MR volumetric analysis of the piriform cortex and cortical amygdala in drug-refractory temporal lobe epilepsy. AJNR Am J Neuroradiol 2005;26:319-32.
Löscher W, Ebert U. The role of the piriform cortex in kindling. Prog Neurobiol 1996;50:427-81.
Zimmerman ME, Brickman AM, Paul RH, Grieve SM, Tate DF, Gunstad J, et al.
The relationship between frontal gray matter volume and cognition varies across the healthy adult lifespan. Am J Geriatr Psychiatry 2006;14:823-33.
Keller SS, Roberts N. Voxel-based morphometry of temporal lobe epilepsy: An introduction and review of the literature. Epilepsia 2008;49:741-57.
Bernasconi N, Bernasconi A, Andermann F, Dubeau F, Feindel W, Reutens DC. Entorhinal cortex in temporal lobe epilepsy: A quantitative MRI study. Neurology 1999;52:1870-6.
Bernasconi N, Duchesne S, Janke A, Lerch J, Collins DL, Bernasconi A. Whole-brain voxel-based statistical analysis of gray matter and white matter in temporal lobe epilepsy. Neuroimage 2004;23:717-23.
Bonilha L, Rorden C, Halford JJ, Eckert M, Appenzeller S, Cendes F, et al.
Asymmetrical extra-hippocampal grey matter loss related to hippocampal atrophy in patients with medial temporal lobe epilepsy. J Neurol Neurosurg Psychiatry 2007;78:286-94.
Keller SS, Wilke M, Wieshmann UC, Sluming VA, Roberts N. Comparison of standard and optimized voxel-based morphometry for analysis of brain changes associated with temporal lobe epilepsy. Neuroimage 2004;23:860-8.
Bonilha L, Rorden C, Castellano G, Pereira F, Rio PA, Cendes F, et al.
Voxel-based morphometry reveals gray matter network atrophy in refractory medial temporal lobe epilepsy. Arch Neurol 2004;61:1379-84.
Keller SS, Mackay CE, Barrick TR, Wieshmann UC, Howard MA, Roberts N. Voxel-based morphometric comparison of hippocampal and extrahippocampal abnormalities in patients with left and right hippocampal atrophy. Neuroimage 2002;16:23-31.
Pail M, Brázdil M, Marecek R, Mikl M. An optimized voxel-based morphometric study of gray matter changes in patients with left-sided and right-sided mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE/HS). Epilepsia 2010;51:511-8.
Bonilha L, Rorden C, Castellano G, Cendes F, Li LM. Voxel-based morphometry of the thalamus in patients with refractory medial temporal lobe epilepsy. Neuroimage 2005;25:1016-21.
Keller SS, Cresswell P, Denby C, Wieshmann U, Eldridge P, Baker G, et al
. Persistent seizures following left temporal lobe surgery are associated with posterior and bilateral structural and functional brain abnormalities. Epilepsy Res 2007;74:131-9.
Mueller SG, Laxer KD, Cashdollar N, Buckley S, Paul C, Weiner MW. Voxel-based optimized morphometry (VBM) of gray and white matter in temporal lobe epilepsy (TLE) with and without mesial temporal sclerosis. Epilepsia 2006;47:900-7.
Nelissen N, Van Paesschen W, Baete K, Van Laere K, Palmini A, Van Billoen H, et al.
Correlations of interictal FDG-PET metabolism and ictal SPECT perfusion changes in human temporal lobe epilepsy with hippocampal sclerosis. Neuroimage 2006;32:684-95.
Lee JH, Kim SE, Park CH, Yoo JH, Lee HW. Gray and white matter volumes and cognitive dysfunction in drug-naïve newly diagnosed pediatric epilepsy. Biomed Res Int 2015;2015:923861.
Bordey A, Sontheimer H. Properties of human glial cells associated with epileptic seizure foci. Epilepsy Res 1998;32:286-303.
Heuser K, Szokol K, Taubøll E. The role of glial cells in epilepsy. Tidsskr Nor Laegeforen 2014;134:37-41.
Binder DK, Steinhäuser C. Functional changes in astroglial cells in epilepsy. Glia 2006;54:358-68.
Munari C, Kahane P, Francione S, Hoffmann D, Tassi L, Cusmai R, et al.
Role of the hypothalamic hamartoma in the genesis of gelastic fits (a video-stereo-EEG study). Electroencephalogr Clin Neurophysiol 1995;95:154-60.
Pennell PB. Hormonal aspects of epilepsy. Neurol Clin 2009;27:941-65.
Harden CL. Interaction between epilepsy and endocrine disorder: Effect on the lifelong health of epileptic women. Review article. Adv Stud Med 2003;3:720-5.
Pennell PB. Pregnancy in women who have epilepsy. Neurol Clin 2004;22:799-820.
Malow BA. Sleep disorders, epilepsy, and autism. Ment Retard Dev Disabil Res Rev 2004;10:122-5.
Kotagal P, Yardi N. The relationship between sleep and epilepsy. Semin Pediatr Neurol 2008;15:42-9.
Stefan H, Feichtinger M, Black A. Autonomic phenomena of temperature regulation in temporal lobe epilepsy. Epilepsy Behav 2003;4:65-9.
Minamimoto T, Hori Y, Yamanaka K, Kimura M. Neural signal for counteracting pre-action bias in the centromedian thalamic nucleus. Front Syst Neurosci 2014;8:3.
Bradfield LA, Hart G, Balleine BW. The role of the anterior, mediodorsal, and parafascicular thalamus in instrumental conditioning. Front Syst Neurosci 2013;7:51.
Tschampa HJ, Greschus S, Sassen R, Bien CG, Urbach H. Thalamus lesions in chronic and acute seizure disorders. Neuroradiology 2011;53:245-54.
Katramados AM, Burdette D, Patel SC, Schultz LR, Gaddam S, Mitsias PD. Periictal diffusion abnormalities of the thalamus in partial status epilepticus. Epilepsia 2009;50:265-75.
Li H, Kraus A, Wu J, Huguenard JR, Fisher RS. Selective changes in thalamic and cortical GABAA receptor subunits in a model of acquired absence epilepsy in the rat. Neuropharmacology 2006;51:121-8.
Rapoport M, van Reekum R, Mayberg H. The role of the cerebellum in cognition and behavior: A selective review. J Neuropsychiatry Clin Neurosci 2000;12:193-8.
Liu RS, Lemieux L, Bell GS, Sisodiya SM, Bartlett PA, Shorvon SD, et al.
Cerebral damage in epilepsy: A population-based longitudinal quantitative MRI study. Epilepsia 2005;46:1482-94.
Bohnen NI, O'Brien TJ, Mullan BP, So EL. Cerebellar changes in partial seizures: Clinical correlations of quantitative SPECT and MRI analysis. Epilepsia 1998;39:640-50.
Cooper IS, Amin I, Riklan M, Waltz JM, Poon TP. Chronic cerebellar stimulation in epilepsy. Clinical and anatomical studies. Arch Neurol 1976;33:559-70.
Krauss GL, Koubeissi MZ. Cerebellar and thalamic stimulation treatment for epilepsy. Acta Neurochir Suppl 2007;97(Pt 2):347-56.
Menassa DA, Sloan C, Chance SA. Primary olfactory cortex in autism and epilepsy: Increased glial cells in autism. Brain Pathol 2016. doi: 10.1111/bpa.12415. [Epub ahead of print].
West SE, Doty RL. Influence of epilepsy and temporal lobe resection on olfactory function. Epilepsia 1995;36:531-42.
Kullmann DM. What's wrong with the amygdala in temporal lobe epilepsy? Brain J Neurol 2011;134:2800-1.
Cristinzio C, Vuilleumier P. The role of amygdala in emotional and social functions: Implications for temporal lobe epilepsy. Epileptologie 2007;24:78-89.