Fourteen-year-old girl (AB) with no previous medical illness began to notice brief but distinct episodes of guilt and distress, occasionally followed by urinary incontinence. In the beginning, the patient attributed these feelings to recent or ongoing events such as “fighting with friends” or “doing something wrong at school”. With time, she became increasingly baffled by these episodes, trying to “figure out if the situation was causing guilt” (Supplamentary Table 1). These episodes were noted by the patient to be more frequent in social-affective situations, such as standing in front of large groups or arguing with her parents. For nearly a year the patient kept these episodes to herself until she had a generalized tonic clonic seizure, leading to neurological consultation and epilepsy diagnosis. Although the patient was treated with multiple anti-seizure medications, the episodes did not abate.
MRI showed a 2.4x1.8x1.3-cm mass in the right frontal horn of the lateral ventricle, extending posteriorly to border the fornices (Fig. 1). Anteriorly, the mass bordered the rostrum and genu of the corpus callosum, and at the ventral-anterior aspect it bordered the subgenual cingulate gyrus (Brodmann area 25). Surface video-EEG suggested right temporal seizure onset. In an effort to better delineate the epileptogenic region, AB underwent stereotactic implantation of seven intracranial depth electrodes (Ad-tech, Racine, WI, USA); each electrode contained seven 1⋅57 mm platinum contacts with 5 mm intercontact distance, implanted at right anterior temporal and frontal sites, including the amygdala, hippocampus, and orbitofrontal cortex. Continuous video-EEG monitoring (NicOne LTM system, Viasys, Madison, WI, USA) identified seizure onset region in the anterior temporal lobe, lateral to the amygdala.
Fig. 1Tumor and related brain structures before and after first and second surgical laser ablations.
As part of the clinical evaluation, bipolar electrical stimulation (50 Hz frequency; 100 μsec pulse width; current range: 2–10 mA; 4 sec duration) was carried out between adjacent contacts using Nicolet Cortical Stimulator (Viasys, Madison, WI, USA). Electrical stimulation of adjacent contacts in the lateral amygdala and the uncinate fasciculus elicited feelings of intense guilt and distress, followed by an ego-dystonic feeling of separation between herself and her surroundings. The reported feeling of separation resembled a dissociative experience, as reflected in the patient's description: “I feel I'm not here, suddenly there's a world, and there's me inside something closed, like an aquarium, and I'm looking out” (Supplamentary Table 2). Stimulation of contacts in the anterior hippocampus evoked feelings of guilt and distress as well (Fig. 1). Stimulation of the more lateral pairs of contacts, both in the region of the amygdala and in the hippocampus, elicited feelings of separation without guilt or distress (Supplamentary Table 2). Electrical stimulation of these sites induced epileptic after-discharges and occasional seizures.
Surgical biopsy of the mass showed dysembryroplastic neuroepithelial tumor. Using a 0.73-mm diameter laser optical fiber within a 1.6-mm diameter polycarbonate cooling catheter (Visualase® Inc., Houston, TX), the patient underwent an MRI-guided laser thermal ablation of the tumor (Supplamentary Fig. 1), achieving destruction of the medial and posterior part of the tumor abutting the fornix. Post procedural MRI showed residual tumor in the anterior and ventral part of the lesion bordering the subgenual cingulate gyrus (Fig. 1). The patient had temporary relief but after a few weeks the guilt episodes returned. The patient then underwent a second surgery where the antero-ventral part of the tumor was ablated in the same manner. A postoperative MRI showed ablation of the tumor bordering the subcallosal cingulate (Fig. 1). Five years later, the patient remains free of these guilt episodes or any other seizure phenomena and is off anti-seizure medications.
Clinical neurosurgical cases of rare occurrence may illuminate fundamental features of the human mind in ways not afforded by any other methodology. Although extrapolation from cases involving brain pathology to normal brain mechanisms should be viewed with caution, there are several features of this case that deserve attention. As opposed to ‘primary’ emotions such as fear, anger, disgust, etc., guilt is often considered a social emotion, i.e., an affective state elicited during social interactions [
]. Indeed, the more frequent occurrence of AB's guilt episodes in social-affective situations appears to support this view. Moreover, when initially faced with spontaneously arising episodes of guilt, the patient sought for an explanation, inserting a social context for the guilt. This pursuit of an explanation is similar to a previous reported case [
] of another patient who inserted various cognitive explanations following episodes of stimulation-evoked laughter. Yet, the occurrence of these guilt episodes and the ability to elicit them in isolation by specific brain activity, in the absence of a particular cause or social context, suggest that guilt could be a distinct primary human emotion.
There are correlative neuroimaging data suggesting neuroanatomical substrates for guilt [
]. Activation of the subgenual cingulate cortex with the adjacent septal region and the anterior temporal lobe region is correlated with feelings of guilt [
]. Furthermore, there is an association between hyperconnectivity of these two regions and overgeneralized feeling of self-blame in patients with major depressive disorder [
]. Disruption of such hyperconnectivity may contribute to the reported improvement in these disorders achieved with deep brain stimulation of the subgenual cingulate region [
]. Although we found no reported seizure activity expressed as feelings of guilt, there are several reported epileptic auras of shame and embarrassment, sometime considered complex emotions that share neural substrates with guilt. Indeed, these cases involved pathology in the ventromedial frontal lobe and the region near the genu of the corpus callosum, including the anterior cingulate cortex [
]. The paucity of reports of ictal guilt or shame may be due to several factors including patients’ difficulty of assigning verbal description to such complex emotions, or rapid generalization of seizure activity close to the corpus callosum.
The present case of “before and after” goes beyond the above neuroimaging studies and clinical reports, as it presents several causal links between these anatomical structures and guilt. First, evoking distinct guilt episodes by electrical stimulation in the amygdala and the electrical activity preceding these episodes located just lateral to the amygdala, suggest recruitment of the anterior temporal lobe in the generation of guilt. Furthermore, the durable elimination of these guilt episodes by the second (and not the first) laser surgery in which the tumor bordering the subgenual cingulate was ablated, suggests that the subgenual cingulate rather than the fornix is involved in the production of guilt. The interface of the tumor with the subgenual cingulate gyrus, an area implicated in major depression [
], corroborates involvement of the neural mechanisms of guilt with those of depression. Taken together, these observations demonstrate recruitment of a distinct brain network generating the experience of guilt. This network likely involves the region of the subgenual cingulate gyrus and the medial-anterior temporal lobe, including the amygdala that is connected to the medial prefrontal region by the uncinate fasciculus.
AB's misfortune of spontaneously emerging episodes of guilt preceded by localized electrical activity, its evocation by localized electrical stimulation as well as its elimination by laser ablation procedure, represent an exceedingly rare set of circumstances offering a unique insight into one of the most allusive states of the human mind.
Funding
None.
Author contributions
IF performed electrode implantation and the two laser ablation procedures, participated in video-EEG analysis, electrical stimulation mapping and imaging data analysis and wrote the manuscript. FF performed video-EEG analysis and electrical stimulation mapping, FA performed electrical stimulation mapping, MA performed data analysis, AF performed image analysis and reconstruction, NS performed neuroimaging analysis and participated in laser ablation procedures. All authors discussed the results and commented on the manuscript.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgments
None.
Appendix A. Supplementary data
The following is/are the supplementary data to this article:
Ictal embarrassment originating from the anterior cingulate cortex confirmed by intracranial electroencephalography in a case with intractable epilepsy.
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