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Clinical commentaryEpileptic Disord 2013; 15 (1): 72-5

Crying with sorrow evokedby electrocortical stimulationTyson Burghardt 1, Maysaa M Basha 1, Darren Fuerst 1,Sandeep Mittal 2

1 Department of Neurology2 Department of Neurosurgery, Wayne State University, and Detroit Medical Center,Detroit, MI, USA

Received September 15, 2012; Accepted January 9, 2013

ABSTRACT – Dacrystic seizures are rare and have been reported inpatients with hypothalamic hamartoma as well as fronto-temporal epilepsy,involving the non-dominant hemisphere. We describe the first reportedcase of cortical stimulation of the left posterior orbito-frontal gyrus, gene-rating consistent and reproducible crying with affective content in a

tractable left temporal lobe epilepsy,anial video-EEG monitoring for resec-

perative intracranial video-EEG, sub-stimulation

cerebral hemisphere. Ictal cryinghas also been reported in a patientwith left mesial temporal lobeepilepsy and reproduced duringleft hemispheric injection on Wadatesting (Tatum and Loddenkemper,2010).There are scant reports of weep-ing and/or crying with or with-out emotional substrate evoked bydirect electrocortical stimulation; awidely accepted method for localis-ing symptomatogenic zones andcortical functions. Nevertheless, aspecific putative crying centre hasyet to be discovered.We report a case in which directelectrical stimulation of subduralelectrodes overlying the left pos-

41-year-old woman with medically inwho underwent extraoperative intracrtive non-lesional epilepsy surgery.

Key words: dacrystic seizures, extraodural electrode implantation, cortical

Little is known about the pathwaysinvolved in laughter and crying,or the associated emotional sub-strates. Ictal laughter and, much lesscommonly, ictal crying (dacrysticepisodes), with or without a cor-responding affective component,can rarely manifest during epilep-tic seizures. The most common caseis that of hypothalamic hamartoma(Blumberg et al., 2012), classicallygiving rise to emotionless laughter,but also reported to produce ictalcrying. The mechanism is secondaryto intrinsic epileptogenicity ofthe hamartoma although the rela-tionship with cortical pathways isunclear (Kahane et al., 2003; Mittal etal., 2008). Epileptic seizures which

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.2013.0559

2 Epileptic Disord, Vol. 15, No. 1, March 2013

orrespondence:andeep Mittalepartment of Neurosurgeryayne State University

160 John R Street, Suite 930etroit, MI 48201, USAsmittal@med.wayne.edu>

manifest as weeping and cryinghave also been seen in patientswith a posterior quadrant seizurefocus (Offen et al., 1976) and witha fronto-temporal focus (Lucianoet al., 1993; Wang et al., 1995), pre-dominantly in the non-dominant

terior orbito-frontal gyrus (Broad-mann area 11) induced crying withan affective component, as partof the standard evaluation of apatient undergoing two-stage corti-cal resection for pharmacoresistantepilepsy.

Epileptic Disord, Vol. 15, No. 1, March 2013 73

Cortical stimulation-induced crying

Case study

A 41-year-old, right-handed woman presented withnon-lesional, medically-refractory, left temporal lobeepilepsy. She had automotor seizures with derange-ment of consciousness and occasional secondarygeneralisation since the age of 30. Infrequently, mildright-sided hemiparesis was noted, postictally. Seizurefrequency and severity remained unchanged despiteincreasing doses of phenytoin and gabapentin, andaddition of levetiracetam. She had episodes of depres-sion, crying, and tearfulness, triggered by thoughtsabout death of a loved one, which were believed to beworse following bouts of seizures. General and neuro-logical examination was normal.Scalp video-EEG monitoring revealed her typicalseizures with electrographic onset in the left temporalregion with maximum discharge at electrodes T3, Sp1,and F7. High-resolution MRI with epilepsy protocolwas normal and FDG-PET showed hypometabolism ofthe left anterior temporal, bilateral superior temporal,and right parietal cortices. Intracarotid amobarbi-

Electrodecontacts

SF 1-6

FP 1-64

IS 1-6

AD 1-6

PD 1-6

AT 1-16

PT 1-16TO 1-16

Ictal onset

Crying withstimulation

Figure 1. Three-dimensional reconstructed brain surface created by coregistration of preoperative MRI and post-implantation CTshowing placement of intracranial subdural and depth electrodes over the left hemisphere.By convention, electrode 1 is most medial. AT: anterior subtemporal; PT: posterior subtemporal; FP: fronto-parietal; SF: subfrontal;TO: temporo-occipital; AD: anterior hippocampal depth; PD: posterior hippocampal depth; IS: insular. Electrodes AT1, AD1, and PD1showed ictal onset. Electrodes SF3 and SF4 along the posterior orbito-frontal gyrus resulted in crying upon electrical stimulation(arrows). Intraoperative photograph of electrode placement is shown in the top left corner.

tal (Wada) testing demonstrated bilateral languagerepresentation and normal memory scores. Left hemi-spheric epilepsy was suspected and the patientunderwent further evaluation with the placement ofthe following subdural grids and strips with numberedplatinum contacts with 10-mm, inter-contact spacing(Ad-Tech Medical Instrument Corporation, Racine,WI): anterior subtemporal 2 × 8 grid (AT 1-16), poste-rior subtemporal 2 × 8 grid (PT 1-16), fronto-parietal4 × 8 grid (FP 1-64), subfrontal 1 × 6 strip (SF 1-6), andtemporo-occipital 2 × 8 grid (TO 1-16). In addition, two6-contact platinum depth electrodes (5-mm, contactspacing) were stereotactically implanted in the leftanterior (AD 1-6) and posterior (PD 1-6) hippocampusand one 6-contact depth electrode was laid flat in theinsular cortex after microsurgical opening of the leftSylvian fissure (IS 1-6). Figure 1 outlines the intracranialelectrodes. Three-dimensional reconstructed brainsurface was created by coregistration of the preopera-tive volumetric MRI with the post-implantation CTscan using the MPI-tool software (Advanced TomoVision, Erfstadt, Germany), 3D-tool surface rendering

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oftware (Max-Planck Institute, Cologne, Germany), asell as in-house developed software (ET/MR Imaging

aboratory, Detroit, MI). Extraoperative monitoringemonstrated her typical seizures with left hippocam-al ictal onset at AT1, AD1, and PD1 electrodes withubsequent spread to SF3 and SF4 electrodes, over-ying the posterior orbito-frontal gyrus within 20 to5 seconds. She then underwent MRI-guided volu-etric resection of anterior and medial temporal lobe

tructures. She had an uneventful recovery and hasemained seizure-free for over 24 months.rior to resective surgery, direct cortical stimulation forapping of eloquent cortex was performed extraope-

atively using a Grass S12 cortical stimulator (Astro-ed Inc., West Warwick, RI). Stimulation trains lasted

or 3 to 10 seconds, utilising 300-�s pulses at 50 Hz.ntensity varied from 1.5 to 9.5 mA in increments ofmA. Activation of the subfrontal electrodes SF3 andF4 (overlying the left posterior orbito-frontal gyrus;gure 1) consistently produced emotional crying at 4.5-.5 mA with no afterdischarges noted. The crying wasssociated with a sorrowful facial expression, sobbingody movements, and a voice inflected with sadness.hese physical manifestations ended with the termi-ation of stimulation and the patient described feelingad, but could not express the trigger for the sadnessr crying. Results were consistent and reproducible.

iscussion

he process of weeping and crying normally consistsf negative emotional substrate associated with vocali-ation, changes in facial appearance and expressions,ncreased lacrimation, and autonomic variations.everal neuroanatomical correlates are likely to be

nvolved in the process of crying (Parvizi, et al., 2001;ild et al., 2003; Arias, 2011). Given that humans are

nique to this clinical presentation, an experimen-al model is lacking and much of the informationbout the localisation of weeping and crying is basedn clues from pathological conditions which includebservations related to dacrystic seizures and limitedortical stimulation studies. Involvement of the pos-erior orbito-frontal region or Broadmann area 11 inrying has not been previously reported.acrystic epilepsy was first named by Offen and

olleagues in 1976 (Offen et al., 1976). The authorsescribed a patient with neurosyphillis and right hemi-

4

pheric focal findings who presented with episodes ofaroxysmal crying, devoid of affective content, associ-ted with right posterior quadrant, low-voltage, 2-Hz,elta rhythms on surface EEG. Although there hadeen several prior cases reporting paroxysmal cryingpisodes which were thought to be seizures, this washe first to be corroborated by simultaneous EEG.

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rying as a manifestation of epileptic seizures haseen considered to be rare and rather a prominent

eature of paroxysmal non-epileptic spells (Bergennd Ristanovic, 1993). However, several reports haveemonstrated a higher incidence of epileptic crying

han expected. Luciano et al. reported seven patientsho presented with crying episodes with ictal activity

nd reviewed 11 other previously published casesLuciano et al., 1993). Crying was described in the ictalr immediate postictal state, with or without coexist-

ng negative emotions, with or without preservation ofonsciousness, fronto-temporal in localisation, right-ided in origin, and presumably non-dominant inateralisation (Luciano et al., 1993). The non-dominantateralisation of negative emotional states is supportedy observations that lesions and strokes yield patho-

ogical crying when the left hemisphere is affected andaughter when the right hemisphere is affected, via lossf function (Sackeim et al., 1982; Starkstein et al., 1987).pisodic crying behaviour has also been described inpatient with left temporal complex partial seizures

nd reproduced during left intracarotid sodium amo-arbital testing (Tatum and Loddenkemper, 2010). Aecent review of nine patients with dacrystic seizuresescribed the underlying aetiology to be hypothalamicamartoma in five cases, left mesial temporal sclerosis

n four, and a left frontal glioblastoma in one patientBlumberg et al., 2012).n human stimulation studies, there are several cases ofathological crying, based on therapeutic neurostimu-

ation of subcortical structures such as the thalamus,imbic structures, pons, and/or cerebellum (Okun etl., 2004; Wojtecki et al., 2007). The latter structure haseen implicated in motoric crying displays, includingssociated facial expression and lacrimation (Parvizi etl., 2001). Stimulation of the right superior temporalyrus at the margin of the Sylvian fissure, inferior to therecentral gyrus, resulted in fear, distress, and weeping

n a patient with a right temporal glioma (Penfield andasper, 1954).rying and weeping, with and without emotional sub-

trate, may be similar to laughter which can occur withnd without mirth due to, presumably, distinct path-ays for emotional qualia and the motoric expressionf such (Arroyo et al., 1993). In addition, stimulationtudies suggest that laughter without mirth is likelyo be localised to the anterior cingulate and superiorrontal gyrus of both hemispheres, and the sensa-ion of mirth may be represented in the temporal and

Epileptic Disord, Vol. 15, No. 1, March 2013

rontal lobes of the dominant hemisphere close toanguage and negative motor areas (Fernandez-Bacaaca et al., 2011). Remarkably, direct stimulation ofypothalamic hamartomas can reproduce both laugh-

ng and crying spells in the same patient (Kahane etl., 1997; Kahane et al., 2003). It has been hypothesizedhat pathological crying and laughter may be due to

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isruption of the inhibitory cortical pathways to theypothalamus and brainstem (Wild et al., 2003; Wortzelt al., 2008).oreover, functional studies of emotion, particularly

n patients suffering from treatment-resistant depres-ion, can help elucidate the pathways implicated inrying. The subcallosal (subgenual) cingulate gyrusBroadmann area 25) appears to play a critical rolen major depression and has been the target foreep brain stimulation in order to treat treatment-esistant depression (Phan et al., 2002; Lozano et al.,012). Interestingly, the proximity and possible inter-lay between the orbito-frontal gyrus and subcallosalingulate gyrus may provide additional insight into theeuroanatomical substrate for emotional processing.

n our case, we used direct cortical stimulation todentify the posterior orbito-frontal gyrus as a key com-onent of the pathways producing sorrowful crying.revious assignment of crying and negative emo-ions to the non-dominant hemisphere is challengedy lateralisation of our case to the left, however,ominance could not be clearly established in ouratient since there was a presence of bilateral language

unction, as evidenced by intracarotid sodium amytalesting and functional MRI. Furthermore, ictal dis-harge reached this region within 20-25 seconds anday have been contributory to the overall depressedood of this patient and her worsening of depression

ostictally. �

isclosures.one of the authors have any conflict of interest to disclose.

eferences

rias M. Neurology of laughter and humour: pathologicalaughing and crying. Rev Neurol 2011; 53: 415-21.

rroyo S, Lesser RP, Gordon B, et al. Mirth, laughter and gelas-ic seizures. Brain 1993; 116: 757-80.

ergen D, Ristanovic R. Weeping as a common element ofseudoseizures. Arch Neurol 1993; 50: 1059-60.

lumberg J, Fernandez IS, Vendrame M, et al. Dacrysticeizures: demographic, semiologic, and etiologic insightsrom a multicenter study in long-term video-EEG monitoring

pileptic Disord, Vol. 15, No. 1, March 2013

nits. Epilepsia 2012; 53: 1810-9.

ernandez-Baca Vaca G, Lüders HO, Basha MM, Miller JP.irth and laughter elicited during brain stimulation. Epilepticisord 2011; 13: 435-40. doi : 10.1684/epd.2011.0480.

ahane P, Munari C, Minotti L, et al. The role of hypothalamicamartoma in the genesis of gelastic and dacrystic seizures.

Wi6

Wit

Cortical stimulation-induced crying

n: Tuxhorn I, Holthausen H, Boenigk H. Pediatric epilepsyyndromes and their surgical treatment. London: John Libbey,997: 447-61.

ahane P, Ryvlin P, Hoffmann D, Minotti L, Benabid AL.rom hypothalamic hamartoma to cortex: what can be learntrom depth recordings and stimulation? Epileptic Disord003; 5: 205-17.

ozano AM, Giacobbe P, Hamani C, et al. A multicenter pilottudy of subcallosal cingulate area deep brain stimulationor treatment-resistant depression. J Neurosurg 2012; 116:15-22.

uciano D, Devinsky O, Perrine K. Crying seizures. Neurology993; 43: 2113-7.

ittal S, Montes JL, Farmer JP, Sabbagh AJ. Hypothalamicamartomas. In: Baltuch GH, Villemure JG. Operative tech-iques in epilepsy surgery. New York: Thieme, 2008: 81-98.

ffen ML, Davidoff RA, Troost BT, Richey ET. Dacrysticpilepsy. J Neurol Neurosurg Psychiatry 1976; 39: 829-34.

kun MS, Raju DV, Walter BL, et al. Pseudobulbar cryingnduced by stimulation in the region of the subthalamicucleus. J Neurol Neurosurg Psychiatry 2004; 75: 921-3.

arvizi J, Anderson SW, Martin CO, Damasio H, Damasio AR.athological laughter and crying: a link to the cerebellum.rain 2001; 124: 1708-19.

enfield W, Jasper H. Epilepsy and the functional anatomy ofhe human brain. Boston: Little, Brown and Co., 1954.

han KL, Wager T, Taylor SF, Liberzon I. Functional neu-oanatomy of emotion: a meta-analysis of emotion activationtudies in PET and fMRI. Neuroimage 2002; 16: 331-48.

ackeim HA, Greenberg MS, Weiman AL, Gur RC, Hunger-uhler JP, Geschwind N. Hemispheric asymmetry in thexpression of positive and negative emotions. Neurologicvidence. Arch Neurol 1982; 39: 210-8.

tarkstein SE, Robinson RG, Price TR. Comparison of corticalnd subcortical lesions in the production of poststroke moodisorders. Brain 1987; 110: 1045-59.

atum WO, Loddenkemper T. Crying with left temporalobe seizures and Wada testing. Epilepsy Behav 2010; 18:03-5.

ang DZ, Steg RE, Futrell N. Crying seizures after cerebralnfarction. J Neurol Neurosurg Psychiatry 1995; 58: 380-1.

ild B, Rodden FA, Grodd W, Ruch W. Neural correlates ofaughter and humour. Brain 2003; 126: 2121-38.

75

ojtecki L, Nickel J, Timmermann L, et al. Pathological cryingnduced by deep brain stimulation. Mov Disord 2007; 22: 1314-.

ortzel HS, Oster TJ, Anderson CA, Arciniegas DB. Patholog-cal laughing and crying: epidemiology, pathophysiology andreatment. CNS Drugs 2008; 22: 531-45.