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Summary: The cerebral representation of laughter is dissociated. The emotional aspects seem to be processed in the temporal lobe; whereas the motor features apparently rely on the frontal cortex. In a few prior studies of patients in whom laughter was elicited by electrical stimulation (ES), it always was associated with mirth. We report a patient in whom ES in the right cingulate gyrus elicited smile and laughter, but no mirth. At low voltages, smiling was seen first contralaterally and became bilateral with increasing currents. Our observation supports the concept of the motor representation of laughter in the mesial frontal cortex.
Study of the neurobiologic bases of laughter has interested researchers for centuries, because laughter is an essential part of our daily behavior, and it contributes significantly to our well-being (1). It has been postulated that laughter includes two components: the mirth or merriment and the motor aspect. The feeling of mirth seems to be related to temporal and frontal neocortical functions, whereas the sequential movements (diaphragm, larynx/pharynx, facial musculature) associated with laughter depend on the limbic system and brainstem (2). The evidence for this hypothesis comes mainly from patients with various cerebral insults, such as extensive structural lesions from stroke or brain tumor, or epileptic seizures. Electrical stimulation (ES) provides an important source of information, allowing the determination of the relation between the irritated zone and the behavioral effect. A few reports exist in patients with epilepsy (2–5) and with movement disorders (6–8), in whom ES provoked laughter. In all cases, the laughter was associated with a feeling of mirth. Here we report of a patient in whom ES in the right cingulate gyrus provoked a smile and laughter, but without associated mirth.
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This 21-year-old, developmentally delayed, right-handed man had predominantly nocturnal intractable seizures with onset at age 13 years. Most commonly, the patient's seizures were preceded by acoustic auras of incomprehensible voices, followed by loss of contact and sometimes manual automatisms. His neurologic examination was normal. Ictal EEG recordings suggested left temporoparietal onset. Interictally, only rare left and right frontocentral sharp waves were noted. High-resolution magnetic resonance imaging (MRI) did not reveal any focal abnormalities. The fluorodeoxyglucose–positron emission tomography (FDG-PET) examination showed a diffuse left hemispheric hypometabolism, however, with predominance in the left temporoparietal region and to a lesser degree in the left frontoorbital cortex. An ictal 99mTc-ECD single-photon emission computed tomography (SPECT) indicated maximal hyperperfusion in the left lateral posterior temporal cortex. The interictal neuropsychological examinations revealed difficulties in verbal memory tasks and executive functions, indicating left frontotemporal impairment in the context of a discrete mental delay. A formal psychiatric evaluation confirmed the absence of any psychiatric disorder. The patient was treated with topiramate, 350 mg/d, and lamotrigine, 600 mg/d. Several months later, he underwent implantation with depth electrodes covering bilaterally the cingulate, orbitofrontal, and lateral frontal structures, as well the left amygdala, into left anterior, mid and posterior hippocampus, left lateral temporal neocortex, left superior posterior temporal lobe, and left inferior parietal cortex, providing a total of 110 recording sites (Fig. 1). The ictal and interictal recordings suggested two independent foci in the left posterior lateral temporal and left anterior mesial temporal structures.
Figure 1. The 3D reconstruction of the patient's brain and the electrode site in right anterior cingulate region (CD 2-3, 3-4) where electrical stimulation evoked pure “motor laughter” without any sensation of mirth. Patient's right side is on the left.
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Electrical stimulation was done to delineate vital cortex, with special emphasis on motor and language functions (bipolar stimulation, 50 Hz; pulse duration, 300 μs; train duration, 2–5 s; intensity, 1–12 mA). Stimulation of contacts in the right cingulate cortex (electrodes CD 2-3, 3-4) induced laughter. Stimulation at this site at low current strength (4 mA, 2 s) induced only a smile, predominating in the left side of the face, whereas at higher currents (5–10 mA, 2 s), smiling followed by symmetrical laughter involving both sides of the face was induced. The duration and intensity of laughter increased with the level of stimulation current. ES of these contacts was repeated the following day, also with longer ES duration (5 s), leading to the same phenomena. The laughter was never accompanied by a sensation of merriment or mirth. The patient expressed a depressed mood during most of his stay in the hospital, rating his mood as 2–3 on a 10-point scale, with 10 the best mood. Another psychiatric consultation confirmed the presence of a diminished mood, but no evidence of a major depression or any other psychiatric disorder was found. His mood did not change during the ES of the cingulate cortex. The patient specifically related that he still felt sad, and that his smiles and laughs were involuntary. In contrast to his emotional state, the smile and laughter appeared to be quite natural, inducing infectious laughter among the attending staff as well.
During stimulation of contacts CD 2-3, 3-4, a variety of tasks were performed including naming objects, reading a paragraph of text, counting, and rapid alternating movements of the upper limbs and tongue, but ES did not interfere with these activities. ES of any other contact did not induce laughter or mirth.
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The present study is the first report of ES-induced laughter without mirth (i.e., only the motor component of laughter and smile was elicited by ES of the right anterior cingulate cortex). Only few ES reports exist of laughter evoked by electrical stimulation at cortical sites. These have included the left supplementary motor cortex (4), orbitofrontal cortex (3), and the inferior temporal lobe (2,5). ES of these areas induced laughter, always with a sensation of mirth or, more rarely, the feeling of mirth alone. In an early ES study (3), laughter was elicited with ES of the anterior cingulate cortex and orbitofrontal cortex; however, the emotional component was difficult to evaluate, given that most of the patients had significant psychiatric comorbidities. In three case reports, laughter and merriment were induced by subcortical stimulations [thalamus, subthalamic nucleus, nucleus accumbens (6–8)], indicating that these structures are implicated in laughter either by distinct additional subcortical representations of a motor-limbic network or close connections with the aforementioned cortical regions (Table 1).
Table 1. Summary of ES studies in which laughter was induced by electrical stimulation
|Reference||Electrode type||Appearance||Anatomic localization||Stimulation parameters||Mirth sensation|
|Hassler et al., 1961 (6)||Depth electrode||Schizophrenia, Dystonia||Thalamus (medial V.o.i.)||50 Hz, no other details given||Yes|
|Sem-Jacobsen, 1968 (3)||Intracranial electrodes||Psychotic patients||Anterior cingulate gyrus and orbitofrontal regions||0.5–5 mA, 60 Hz, 0.5 s||Yes|
|Arroyo et al., 1993, Pat2 (2)||Subdural electrodes||Epilepsy||Left fusiform and parahippocampal gyrus||13 mA, 50 Hz, 0.3 ms, 1 s||Yes|
|Arroyo et al., 1993, Pat3 (2)||Subdural electrodes||Epilepsy||Left fusiform and parahippocampal gyrus||15 mA, 50 Hz, 0.3 ms, 1–5 s||Yes|
|Fried et al., 1998 (4)||Subdural electrodes||Epilepsy||Left superior frontal gyrus (borders SMA)||1–12 mA, 50 Hz, 0.3 ms, 1–5 s||Yes|
|Krack et al., 2001 (7)||Intracranial electrodes||Parkinson||Anterodorsal and lateral portion of STN||3.6V, 60 μs, 160 Hz||Yes|
|Satow et al., 2003 (5)||Subdural electrodes||Epilepsy||Left basal inferior temporal gyrus||5–15 mA, 1–5 s||Yes|
|Okun et al, 2004 (8)||Intracranial electrodes||OCD||Left and right nucleus accumbens||0–8 V, 210 μs, 130 Hz||Yes|
|Sperli et al., 2005 (this article)||Intracranial electrodes||Epilepsy||Right cingulate cortex (CD 2-3 to CD 3-4)||1–11 mA, 50 Hz, 0.3 ms, 2–5 s||No|
The cingulate cortex plays an important role in the control of movement initiation, affect, response selection, and adequate social behaviors (9). Electrical stimulation of the anterior cingulate cortex in 83 patients with epilepsy resulted in complex movement sequences (other than consistently evoked laughter), affecting also the oropharygeal region (10) and seemed to represent archaic movements (e.g., thumb sucking, licking). Stimulus-initiated movements most often were carried out contralateral to the stimulation site (84%) (11). ES in our patient also evoked a smiling response starting contralateral to the stimulated cortex, which became bilateral with increasing stimulus intensity. Close projections exist between this area and the contralateral lateral aspect of the facial nucleus, which innervates the lower facial muscles (12). The convergence of limbic input and the control of facial muscles may explain the role of the anterior cingulate cortex in nonvoluntary facial movements. Our case suggests the existence of an anatomic subdivision within this area, given that only the motor component could be elicited in our patient. It is speculated that the limbic component involves more-anterior aspects, including subgenual components of the cingulate cortex, as indicated by promising results of deep-brain stimulation of patients with treatment-resistant depressions (13).
Stereotyped laughter is a well-known feature in gelastic seizures and pseudobulbar laughter. Pseudobulbar laughter is defined as inappropriate and uncontrollable laughter, detached from any stimulus, and a well-known feature of widespread cortical and subcortical injury (12). Gelastic seizures due to hypothalamic hamartoma are rare, and most often are seen in young children, in whom the emotional component is difficult to evaluate. However, in well-documented adult cases, a feeling of an urge to laugh, but without an associated feeling of mirth, was reported (14). Depth recording and ES of the hamartoma suggested a strong relation between the hamartoma and the cingulate gyrus (15), and it is suggested that the “mechanical” laughter is an expression of propagation to discrete sites of the cingulate cortex. Although the epileptic activity during the gelastic seizures seemed to be maximal or even confined to the hamartoma, in some of the patients studied with depth electrodes simultaneously in the hamartoma and cingulate gyrus, rapid recruitment or even onset in the cingulate gyrus was suspected (see Fig. 6 in ref. 15). Moreover, a few patients have had frank laughter during seizures originating from the cingulate gyrus (16). These observations further corroborate the role of the cingulate gyrus in the motor expression of laughter.
Conversely, mirth seemed to rely primarily on temporal lobe structures, not necessarily related to the laughter act. ES in the left inferior temporal lobe led to a feeling of mirth without frank laughter (5). We are not aware of other reports in which ES induced strong positive feelings, albeit some of the experiential phenomena described in the context of ES may also have a pleasant character (17). However, numerous reports exist of seizures preceded by spiritual or orgasmic/erotic auras, experienced as very positive feelings, and the focus is almost always in the temporal lobe (18).
Laughter and smile are universally present social gestures, partially present already in the newborn, involving a complex sequence of facial, pharyngeal, and diaphragmatic muscle contractions. They allow rapid establishment of a friendly interaction with another person. In this context, an inborn cortical representation is mandatory for the survival of our species. Our observation suggests that its cortical representation is in the anterior cingulate cortex. Furthermore, our report supports the hypothesis of dissociation in the cortical mechanisms of laughter (2): whereas the temporal cortical structures are involved in the processing of the emotional component, the mesial frontal cortex, or more specifically, the anterior cingulate gyrus, is relevant for the motor aspects of laughter.