The amygdala is a region of the brain known for its connections to emotional responses and fear memories, and hyperreactivity of the amygdala is associated with symptoms of PTSD (post-traumatic stress disorder). That said, it’s quite a leap to design neurosurgical ablation of the amygdala to address someone’s PTSD. This type of irreversible intervention could only be considered because of the presence of another brain disorder: epilepsy.
In a case series published in Neurosurgery, Emory investigators describe how for their first patient with both refractory epilepsy and PTSD, observations of PTSD symptom reduction were fortuitous. However, in a second patient, before-and-after studies could be planned. In both, neurosurgical ablation of the amygdala significantly reduced PTSD symptoms as well as reducing seizure frequency.
Stage fright: don’t get over it, get used to it, advises Emory neuroscientist Anwesha Banerjee in her recent talk at TEDx Decatur. Many can feel empathy with the situation Banerjee describes. It was her first public presentation eight years ago, facing “a room full of scientists, who for whatever reason, did not look very happy that day.”
“What if I fail in front of the crowd? What if everybody thinks I’m an idiot?”
That feeling of scrutiny might have an evolutionary relationship to the fear of being eaten by a predator, she speculates.
Through participating in Toastmasters International, she has made public speaking more of a habit. She contrasts the two parts of the brain: the amygdala, tuner of emotional responses, with the basal ganglia, director of habits.
“I still get stage fright,” she says. “In fact, I have it right now, thinking how all you predators might try to eat me up! But my brain pays less attention to it.”
Banerjee is a postdoctoral scientist in cell biologist Gary Bassell’s lab, studying myotonic dystrophy. In 2017, she was funded by the Myotonic Dystrophy Foundation to create a mouse model of the neurological/sleep symptoms of myotonic dystrophy.
To investigate the functions of regions within the brain, developmental neuroscience studies have often relied on permanent lesions. As an alternative to permanent lesions, scientists at Yerkes National Primate Research Center sought to test whether chemogenetic techniques could be applied to produce a transient inhibition of the amygdala, well known for regulating emotional responses, in infant non-human primates.
Their findings were recently published online by eNeuro, an open access journal of the Society for Neuroscience.
Amygdala — image from NIMH
Chemogenetics is a way of engineering cells so that they selectively respond to designer drugs, which have minimal effects elsewhere in the brain. It involves injection of a viral vector carrying genes encoding receptors responsive to the designer drug – in this case, clozapine-N-oxide, a metabolite of the antipsychotic clozapine. The technique has mostly been tested in rodents.
“This proof-of-principle study is the first to demonstrate that chemogenetic tools can be used in young infant nonhuman primates to address developmental behavioral neuroscience questions,” says Jessica Raper, PhD, first author of the eNeuro paper and a research associate at Yerkes. “Considering its reversibility and reduced invasiveness, this technique holds promise for developmental studies in which more invasive techniques cannot be employed.” Read more
A recent paper in Neuropsychologia got a lot of attention on Twitter and at the Cognitive Neuroscience Society meeting in Boston over the weekend. It discusses what can happen when the amygdala, a region of the brain known for regulating emotional responses, receives direct electrical stimulation. A thrill ride – but for only one study participant. Two of nine people noticed the electrical stimulation. One individual reported (a video is included in the paper):
“It was, um, it was terrifying, it was just…it was like I was about to get attacked by a dog. Like the moment, like someone unleashes a dog on you, and it’s just like it’s so close…
He also spontaneously reported “this is fun.” He further explained that he could distinguish feelings in his body that would normally be associated with fear recognized and the absence of an actual threat, making the experience “fun”.
But wait, why were Emory neuroscientists Cory Inman, Jon Willie and Stephan Hamann and colleagues doing this? Read more
Low estrogen levels may make women more susceptible to the development of post-traumatic stress disorder (PTSD) at some points in their menstrual cycles or lifetimes, while high estrogen levels may be protective.
New research from Emory University School of Medicine and Harvard Medical School provides insight into how estrogen changes gene activity in the brain to achieve its protective effects.
The findings, published in Molecular Psychiatry, could inform the design of preventive treatments aimed at reducing the risk of PTSD after someone is traumatized.
The scientists examined blood samples from 278 women from the Grady Trauma Project, a study of low-income Atlanta residents with high levels of exposure to violence and abuse. They analyzed maps of DNA methylation, a modification to the shape of DNA that is usually a sign of genes that are turned off.
The group included adult women of child-bearing age, in which estrogen rises and falls with the menstrual cycle, and women that had gone through menopause and had much lower estrogen levels.
“We knew that estrogen affects the activity of many genes throughout the genome,” says Alicia Smith, PhD, associate professor and vice chair of research in the Department of Gynecology and Obstetrics at Emory University School of Medicine. “But if you look at the estrogen-modulated sites that are also associated with PTSD, just one pops out.”
That site is located in a gene called HDAC4, known to be critical for learning and memory in mice. Genetic variation in HDAC4 among the women was linked to a lower level of HDAC4 gene activity and differences in their ability to respond to and recover from fear, and also differences in “resting state” brain imaging. Women with the same variation also showed stronger connections in activation between the amygdala and the cingulate cortex, two regions of the brain involved in fear learning. Read more
A region of the brain called the hippocampus is known for its role in memory formation. Scientists at Yerkes National Primate Research Center, Emory University are learning more about another facet of hippocampal function: its importance in the regulation and expression of emotions, particularly during early development.
Using a nonhuman primate model, their findings provide insight into the mechanisms of human psychiatric disorders associated with emotion dysregulation, such as PTSD (post-traumatic stress disorder) and schizophrenia. The results were published online recently by the journal Psychoneuroendocrinology.
“Our findings demonstrate that damage to the hippocampus early in life leads to increased anxiety-like behaviors in response to an unfamiliar human,” says research associate Jessica Raper, PhD, first author of the paper. “However, despite heightened anxious behavior, cortisol responses to the social stress were dampened in adulthood.”
The hormone cortisol modulates metabolism, the immune system and brain function in response to stress. Reduced hippocampal volume and lower cortisol response to stressors have been demonstrated as features of and risk factors for PTSD, Raper says. Also, the dampened daily rhythms of cortisol seen in the nonhuman primates with hippocampal damage resemble those reported in first-episode schizophrenia patients.
Follow-up studies could involve temporary interference with hippocampus function using targeted genetic techniques, she says. Read more
The focus on PTSD co-occurring with depression. As the authors note, several studies looking at traumatized individuals found PTSD and depression together more often than they were present separately. This was true of Atlanta inner city residents in the Grady Trauma Project, veterans and survivors of the 2001 World Trade Center attack.
DICER: the gene whose activity is turned down in blood samples from people with PTSD plus depression. Its name evokes one of the three Fates in Greek mythology, Atropos, who cuts the thread of life. DICER is at the center of a cellular network of regulation, because it is part of the machinery that generates regulatory micro-RNAs.
The findings recapitulate work in mouse models of stress and its effects on the brain, with a connection to the many-tentacled Wnt signaling/adhesion protein beta-catenin.
Some past posts on the Grady Trauma Projectâ€™s scientific fruits follow. Read more
As part of reporting on neurosurgeon Robert Grossâ€™s work with patients who have drug-resistant epilepsy, I interviewed a remarkable woman, Barbara Olds. She had laser ablation surgery for temporal lobe epilepsy in 2012, which drastically reduced her seizures and relieved her epilepsy-associated depression.
Emory Medicineâ€™s editor decided to focus on deep brain stimulation, rather than ablative surgery, so Ms. Oldsâ€™ experiences were not part of the magazine feature. Still, talking with her highlighted some interesting questions for me.
In contrast to evidence that the amygdala stimulates stress responses in adults, researchers at Yerkes National Primate Research Center, Emory University have found that the amygdala has an inhibitory effect on stress hormones during the early development of nonhuman primates.
The amygdala is a region of the brain known to be important for responses to threatening situations and learning about threats. Alterations in the amygdala have been reported in psychiatric disorders such as depression, anxiety disorders like PTSD, schizophrenia and autism spectrum disorder. However, much of what is known about the amygdala comes from research on adults.
â€œOur findings fit into anÂ emerging themeÂ in neuroscience research: that during childhood, there is a switch in amygdala function and connectivity with other brain regions, particularly the prefrontal cortex,â€ says Mar Sanchez, PhD, neuroscience researcher at Yerkes and associate professor of psychiatry and behavioral sciences at Emory University School of Medicine. The first author of the paper is postdoctoral fellow Jessica Raper, PhD.
Some notableÂ links on the amygdala:
*AnÂ effort to correctÂ simplistic views of amygdala as the “fear center” of the brain
*Collection of papers mentioningÂ patient SM, an adult human with an amygdala lesion
The epilepsy patient Henry Molaison, known for most of the 20th century as H.M., is one of the most famous in neuroscience. His case played an important role in telling scientists about structures of the brain that are important for forming short-term and long-term memories.
To control H.M.â€™s epilepsy, neurosurgeon William Scoville http://www.raybandasoleit.com/ removed much of the hippocampi, amygdalae and nearby regions on both sides of his brain. After the surgery, H.M. suffered from severe anterograde amnesia, meaning that he could not commit new events to explicit memory. However, other forms of his memory were intact, such as short-term working memory and motor skills.
This classic case helps us understand the advances that neurosurgeons at Emory are achieving today. The surgeries now used to treat some medication-resistant forms of epilepsy are similar to what was performed on H.M., although they are considerably less drastic. Usually tissue on only one side of the brain is removed. Still, there can be cognitive side effects: loss of visual or verbal memory abilities, and deficiencies in the ability to name or recognize objects, places or people.