Laughing During Brain Surgery
By Patrick Magahis
When people think of brain surgery, they immediately conjure images of a sedated, helpless patient lying on a stretcher while teams of neurosurgeons tirelessly operate within millimeter-scale precision on the body’s most delicate organ. However, certain neurosurgical procedures must be performed while patients are awake. A classic example is a craniotomy, during which the surgeon removes lesions near “eloquent” parts of the brain, a procedure that can cause noticeable motor, sensory, or linguistic disability [1]. In a process known as functional-anatomical correlation, patients are left awake and fully monitored, allowing the surgical team to communicate with them, test their language abilities, and detect any impairments that may arise from the resection.
However, “awake surgery” poses a major risk: When patients are too anxious to tolerate the procedure, constant fidgeting can be distracting to the surgery team. In the worst case, the psychological stress experienced during surgery may induce a life-threatening panic attack. On the other hand, performing the surgery under general anesthesia may fail to prevent collateral brain damage. Therefore, a non-sedative method that helps patients tolerate awake, functional-anatomical correlation would be a transformative breakthrough in the field of neurosurgery [1].
In a 2018 article published in the Journal of Clinical Investigation, a team of neuroscientists at the Emory University School of Medicine led by Kelly R. Bijanki took steps to achieve this goal.
Bijanki worked with an epilepsy patient undergoing neuro-monitoring to diagnose seizures. The team discovered a focal pathway in the brain that, when electrically stimulated, caused immediate laughter, followed by a sense of calm and happiness. These effects were even observed during awake brain surgery. The researchers later harnessed these effects to assist the patient through a separate awake brain surgery two days later.
How could a physically invasive experience like surgery possibly cause a patient to laugh? The answer lies in the structure and organization of the brain. The cingulum bundle is a white matter tract that lies under the brain’s cortex and curves around the midbrain. It is a logical target for treatment because it serves a crossroads for white matter connecting several lobes of the brain and is directly involved in coordinating complex emotional responses [2,3]. It is also the key to experiencing laughter, even during our most stressful moments.
Bijanki and her team used cingulum bundle stimulation on a patient with epilepsy undergoing diagnostic intracranial electroencephalography (iEEG). In this procedure, electrodes are temporarily implanted in the brain to localize the onset of seizures before surgical therapies are performed [4]. Figure 1 shows the location of electrode contacts within the patient’s cingulum bundle. Using data from the iEEG, Bijanki and her team generated maps of white matter and the volume of tissues activated (VTAs) by the electrical stimulation in order to elucidate the most likely pathways of brain activation [2]. One pair of electrode contacts was found to evoke the strongest positive behavioral response; it also exclusively engaged the cingulum bundle. By contrast, other pairs were not associated with any behavioral response and were shown to engage only minimally with the cingulum bundle.
Initial electrical stimulation to the left anterior cingulum bundle white matter immediately elicited mirthful behavior within the patient: smiling, laughing, and generally positive affect. The patient reported an involuntary urge to laugh, which evolved into a pleasant, relaxed feeling over the course of a few seconds. Figure 2 depicts an EEG record and its associated images of the patient’s face, showing the progression of the patient’s emotional response over time. When the stimulation was turned off, the positive sensation dissipated over the course of a few seconds.
Bijanki and her team were also able to influence the strength of the laughter pathway by altering the strength of the stimulation. When the stimulation amplitudes were increased, the patient reported feeling similar but more intense experiences [1]. Other patients undergoing the same technique smiled, reported mood elevation and pain relief, and even laughed when higher levels of current were applied.
To measure the patient’s mood and thought processes objectively, Bijanki subjected the patient to a facial affective bias task, a test in which patients are asked to rate the mood and intensity of a series of images of emotional facial expressions. In addition to raising the patient’s own positivity, cingulum bundle stimulation produced a strong positive shift in the patient’s ratings of the facial expressions—all the faces were interpreted as happier during stimulation than during no stimulation [1]. This result presents a potential use for cingulum stimulation in treating depression, since this effect on the patient’s emotion ratings—“affective bias”—is known to correspond with reduced depressive symptoms.
How does cingulum stimulation fare in a real surgery scenario? Bijanki and her team put the procedure to the test during an actual awake brain surgery to see if it would reduce the risk of a panic attack. The patient first underwent a standard surgical procedure under deep sedation, followed by a resection during which the patient was brought awake. Initially, the patient reported significant anxiety and fear. However, when increasing levels of cingulum stimulation were applied, the patient reported feeling more relaxed and began to smile and laugh. When stimulation was briefly discontinued, the patient reported feeling more pain in her scalp, became aware of the use of electrocautery, and expressed unease.
In addition to helping the patient relax, cingulum stimulation allowed the surgeons to assign functional-anatomical correlation. During the surgery, a neurologist administered a language test asking the patient to name objects and animals, read statements, and answer written questions. Fortunately, the patient’s thought processes and language abilities were found to be perfectly intact.
Bijanki’s research establishes cingulum bundle stimulation as a new approach to manage patient anxiety and ensure a stable mental state during awake neurosurgical procedures [1]. Bijanki and her team even claim the applications of their study extend beyond awake brain surgery. Understanding the biological function and mechanism of this laughter pathway can directly inform efforts to better treat depression, anxiety disorders, and chronic pain via deep brain stimulation [2]. In addition, Bijanki’s use of iEEG to deconvolute the mechanism of one brain pathway serves as a model for uncovering other murky features of neurological function; with direct feedback from patients, neuroscientists may be able to assign functions to unknown brain pathways. More often than not, surgery is no laughing matter—unless, of course, laughter is a side-effect.
References
[1] Bijanki, Kelly R., et al. “Cingulum Stimulation Enhances Positive Affect and Anxiolysis to Facilitate Awake Craniotomy.” Journal of Clinical Investigation, vol. 129, no. 3, 2019, pp. 1152–1166., doi:10.1172/jci120110.
[2] Bubb, Emma J., et al. “The Cingulum Bundle: Anatomy, Function, and Dysfunction.” Neuroscience & Biobehavioral Reviews, vol. 92, 2018, pp. 104–127., doi:10.1016/j.neubiorev.2018.05.008.
[3] Riva-Posse, Patricio, et al. “Defining Critical White Matter Pathways Mediating Successful Subcallosal Cingulate Deep Brain Stimulation for Treatment-Resistant Depression.” Biological Psychiatry, vol. 76, no. 12, 2014, pp. 963–969., doi:10.1016/j.biopsych.2014.03.029.
[4] Wu, Yupeng, et al. “Segmentation of the Cingulum Bundle in the Human Brain: A New Perspective Based on DSI Tractography and Fiber Dissection Study.” Frontiers in Neuroanatomy, vol. 10, 2016, doi:10.3389/fnana.2016.00084.
When people think of brain surgery, they immediately conjure images of a sedated, helpless patient lying on a stretcher while teams of neurosurgeons tirelessly operate within millimeter-scale precision on the body’s most delicate organ. However, certain neurosurgical procedures must be performed while patients are awake. A classic example is a craniotomy, during which the surgeon removes lesions near “eloquent” parts of the brain, a procedure that can cause noticeable motor, sensory, or linguistic disability [1]. In a process known as functional-anatomical correlation, patients are left awake and fully monitored, allowing the surgical team to communicate with them, test their language abilities, and detect any impairments that may arise from the resection.
However, “awake surgery” poses a major risk: When patients are too anxious to tolerate the procedure, constant fidgeting can be distracting to the surgery team. In the worst case, the psychological stress experienced during surgery may induce a life-threatening panic attack. On the other hand, performing the surgery under general anesthesia may fail to prevent collateral brain damage. Therefore, a non-sedative method that helps patients tolerate awake, functional-anatomical correlation would be a transformative breakthrough in the field of neurosurgery [1].
In a 2018 article published in the Journal of Clinical Investigation, a team of neuroscientists at the Emory University School of Medicine led by Kelly R. Bijanki took steps to achieve this goal.
Bijanki worked with an epilepsy patient undergoing neuro-monitoring to diagnose seizures. The team discovered a focal pathway in the brain that, when electrically stimulated, caused immediate laughter, followed by a sense of calm and happiness. These effects were even observed during awake brain surgery. The researchers later harnessed these effects to assist the patient through a separate awake brain surgery two days later.
How could a physically invasive experience like surgery possibly cause a patient to laugh? The answer lies in the structure and organization of the brain. The cingulum bundle is a white matter tract that lies under the brain’s cortex and curves around the midbrain. It is a logical target for treatment because it serves a crossroads for white matter connecting several lobes of the brain and is directly involved in coordinating complex emotional responses [2,3]. It is also the key to experiencing laughter, even during our most stressful moments.
Bijanki and her team used cingulum bundle stimulation on a patient with epilepsy undergoing diagnostic intracranial electroencephalography (iEEG). In this procedure, electrodes are temporarily implanted in the brain to localize the onset of seizures before surgical therapies are performed [4]. Figure 1 shows the location of electrode contacts within the patient’s cingulum bundle. Using data from the iEEG, Bijanki and her team generated maps of white matter and the volume of tissues activated (VTAs) by the electrical stimulation in order to elucidate the most likely pathways of brain activation [2]. One pair of electrode contacts was found to evoke the strongest positive behavioral response; it also exclusively engaged the cingulum bundle. By contrast, other pairs were not associated with any behavioral response and were shown to engage only minimally with the cingulum bundle.
Initial electrical stimulation to the left anterior cingulum bundle white matter immediately elicited mirthful behavior within the patient: smiling, laughing, and generally positive affect. The patient reported an involuntary urge to laugh, which evolved into a pleasant, relaxed feeling over the course of a few seconds. Figure 2 depicts an EEG record and its associated images of the patient’s face, showing the progression of the patient’s emotional response over time. When the stimulation was turned off, the positive sensation dissipated over the course of a few seconds.
Bijanki and her team were also able to influence the strength of the laughter pathway by altering the strength of the stimulation. When the stimulation amplitudes were increased, the patient reported feeling similar but more intense experiences [1]. Other patients undergoing the same technique smiled, reported mood elevation and pain relief, and even laughed when higher levels of current were applied.
To measure the patient’s mood and thought processes objectively, Bijanki subjected the patient to a facial affective bias task, a test in which patients are asked to rate the mood and intensity of a series of images of emotional facial expressions. In addition to raising the patient’s own positivity, cingulum bundle stimulation produced a strong positive shift in the patient’s ratings of the facial expressions—all the faces were interpreted as happier during stimulation than during no stimulation [1]. This result presents a potential use for cingulum stimulation in treating depression, since this effect on the patient’s emotion ratings—“affective bias”—is known to correspond with reduced depressive symptoms.
How does cingulum stimulation fare in a real surgery scenario? Bijanki and her team put the procedure to the test during an actual awake brain surgery to see if it would reduce the risk of a panic attack. The patient first underwent a standard surgical procedure under deep sedation, followed by a resection during which the patient was brought awake. Initially, the patient reported significant anxiety and fear. However, when increasing levels of cingulum stimulation were applied, the patient reported feeling more relaxed and began to smile and laugh. When stimulation was briefly discontinued, the patient reported feeling more pain in her scalp, became aware of the use of electrocautery, and expressed unease.
In addition to helping the patient relax, cingulum stimulation allowed the surgeons to assign functional-anatomical correlation. During the surgery, a neurologist administered a language test asking the patient to name objects and animals, read statements, and answer written questions. Fortunately, the patient’s thought processes and language abilities were found to be perfectly intact.
Bijanki’s research establishes cingulum bundle stimulation as a new approach to manage patient anxiety and ensure a stable mental state during awake neurosurgical procedures [1]. Bijanki and her team even claim the applications of their study extend beyond awake brain surgery. Understanding the biological function and mechanism of this laughter pathway can directly inform efforts to better treat depression, anxiety disorders, and chronic pain via deep brain stimulation [2]. In addition, Bijanki’s use of iEEG to deconvolute the mechanism of one brain pathway serves as a model for uncovering other murky features of neurological function; with direct feedback from patients, neuroscientists may be able to assign functions to unknown brain pathways. More often than not, surgery is no laughing matter—unless, of course, laughter is a side-effect.
References
[1] Bijanki, Kelly R., et al. “Cingulum Stimulation Enhances Positive Affect and Anxiolysis to Facilitate Awake Craniotomy.” Journal of Clinical Investigation, vol. 129, no. 3, 2019, pp. 1152–1166., doi:10.1172/jci120110.
[2] Bubb, Emma J., et al. “The Cingulum Bundle: Anatomy, Function, and Dysfunction.” Neuroscience & Biobehavioral Reviews, vol. 92, 2018, pp. 104–127., doi:10.1016/j.neubiorev.2018.05.008.
[3] Riva-Posse, Patricio, et al. “Defining Critical White Matter Pathways Mediating Successful Subcallosal Cingulate Deep Brain Stimulation for Treatment-Resistant Depression.” Biological Psychiatry, vol. 76, no. 12, 2014, pp. 963–969., doi:10.1016/j.biopsych.2014.03.029.
[4] Wu, Yupeng, et al. “Segmentation of the Cingulum Bundle in the Human Brain: A New Perspective Based on DSI Tractography and Fiber Dissection Study.” Frontiers in Neuroanatomy, vol. 10, 2016, doi:10.3389/fnana.2016.00084.
Figure 1. Location of implanted electrodes within various regions of patient’s brain. A: Postimplantation skull radiograph depicting relative positions of the intracranial electrodes. B–D: Postimplantation MRI demonstrating positions of stimulated cingulate contacts.
Figure 2. Feelings of happiness induced by acute cingulum stimulation in the patient. Continuous intracranial EEG record and associated sequential still images of patient’s face showing temporal progression of facial expression (smiling, laughter) during a 6-second period of acute cingulum bundle stimulation (3.0 mA).
