1. How particular fear memories can be erased

    September 2, 2017 by Ashley

    From the University of California – Riverside press release:

    Researchers at the University of California, Riverside have devised a method to selectively erase particular fear memories by weakening the connections between the nerve cells (neurons) involved in forming these memories.

    A sight, sound, or smell we have sensed may not later trigger fear, but if the stimulus is associated with a traumatic event, such as a car accident, then fear memory is formed, and fearful responses are triggered by the stimulus.

    To survive in a dynamic environment, animals develop fear responses to dangerous situations. But not all fear memories, such as those in PTSD, are beneficial to our survival. For example, while an extremely fearful response to the sight of a helicopter is not a useful one for a war veteran, a quick reaction to the sound of a gunshot is still desirable. For survivors of car accidents, it would not be beneficial for them to relive the trauma each time they sit in a car.

    In their lab experiments, Jun-Hyeong Cho, M.D., Ph.D., an assistant professor of molecular, cell, and systems biology, and Woong Bin Kim, his postdoctoral researcher, found that fear memory can be manipulated in such a way that some beneficial memories are retained while others, detrimental to our daily life, are suppressed.

    The research, done using a mouse model and published today in Neuron, offers insights into how PTSD and specific phobias may be better treated.

    “In the brain, neurons communicate with each other through synaptic connections, in which signals from one neuron are transmitted to another neuron by means of neurotransmitters,” said Cho, who led the research. “We demonstrated that the formation of fear memory associated with a specific auditory cue involves selective strengthening in synaptic connections which convey the auditory signals to the amygdala, a brain area essential for fear learning and memory. We also demonstrated that selective weakening of the connections erased fear memory for the auditory cue.”

    In the lab, Cho and Kim exposed mice to two sounds: a high-pitch tone and a low-pitch tone. Neither tone produced a fear response in the mice. Next, they paired only the high-pitched tone with a mild footshock administered to the mice. Following this, Cho and Kim again exposed the mice to the two tones. To the high-pitch tone (with no accompanying footshock), the mice responded by ceasing all movement, called freezing behavior. The mice showed no such response to the low-pitch sound (with no accompanying footshock). The researchers found that such behavioral training strengthened synaptic connections that relay the high-pitch tone signals to the amygdala.

    The researchers then used a method called optogenetics to weaken the synaptic connection with light, which erased the fear memory for the high-pitch tone.

    “In the brain, neurons receiving the high- and low-pitch tone signals are intermingled,” said Cho, a member of the Center for Glial-Neuronal Interactions in the UC Riverside School of Medicine. “We were able, however, to experimentally stimulate just those neurons that responded to the high-pitch sound. Using low-frequency stimulations with light, we were able to erase the fear memory by artificially weakening the connections conveying the signals of the sensory cue — a high-pitch tone in our experiments — that are associated with the aversive event, namely, the footshock.”

    Cho explained that for adaptive fear responses to be developed, the brain must discriminate between different sensory cues and associate only relevant stimuli with aversive events.

    “This study expands our understanding of how adaptive fear memory for a relevant stimulus is encoded in the brain,” he said. “It is also applicable to developing a novel intervention to selectively suppress pathological fear while preserving adaptive fear in PTSD.”

    The researchers note that their method can be adapted for other research, such as “reward learning” where stimulus is paired with reward. They plan next to study the mechanisms involved in reward learning which has implications in treating addictive behaviors.

    The research, which builds on earlier work by Cho and Kim, was funded by the Initial Complement Funds to Cho from UCR.


  2. Adult brains produce new cells in previously undiscovered area

    August 31, 2017 by Ashley

    From the University of Queensland press release:

    A University of Queensland discovery may lead to new treatments for anxiety, depression and post-traumatic stress disorder (PTSD). UQ Queensland Brain Institute scientists have discovered that new brain cells are produced in the adult amygdala, a region of the brain important for processing emotional memories.

    Disrupted connections in the amygdala, an ancient part of the brain, are linked to anxiety disorders such as PTSD.

    Queensland Brain Institute director Professor Pankaj Sah said the research marked a major shift in understanding the brain’s ability to adapt and regenerate.

    “While it was previously known that new neurons are produced in the adult brain, excitingly this is the first time that new cells have been discovered in the amygdala,” Professor Sah said.

    “Our discovery has enormous implications for understanding the amygdala’s role in regulating fear and fearful memories.”

    Researcher Dr Dhanisha Jhaveri said the amygdala played a key role in fear learning — the process by which we associate a stimulus with a frightening event.

    “Fear learning leads to the classic flight or fight response — increased heart rate, dry mouth, sweaty palms — but the amygdala also plays a role in producing feelings of dread and despair, in the case of phobias or PTSD, for example,” Dr Jhaveri said.

    Finding ways of stimulating the production of new brain cells in the amygdala could give us new avenues for treating disorders of fear processing, which include anxiety, PTSD and depression.”

    Previously new brain cells in adults were only known to be produced in the hippocampus, a brain region important for spatial learning and memory.

    The discovery of that process, called neurogenesis, was made by Queensland Brain Institute founding director Professor Perry Bartlett, who was also involved in the latest research.

    “Professor Bartlett’s discovery overturned the belief at the time that the adult brain was fixed and unable to change,” Professor Sah said. “We have now found stem cells in the amygdala in adult mice, which suggests that neurogenesis occurs in both the hippocampus and the amygdala. “The discovery deepens our understanding of brain plasticity and provides the framework for understanding the functional contribution of new neurons in the amygdala,” Professor Sah said.

    The research, led by Professor Sah, Professor Bartlett and Dr Jhaveri, is published in Molecular Psychiatry.


  3. Stress heightens fear of threats from the past

    August 25, 2017 by Ashley

    From the University of Texas at Austin press release:

    Recognizing threats is an essential function of the human mind — think “fight or flight” — one that is aided by past negative experiences. But when older memories are coupled with stress, individuals are likely to perceive danger in harmless circumstances, according to a paper published today in the Proceedings of the National Academy of Sciences.

    The findings by researchers from Dell Medical School at The University of Texas at Austin, New York University and McGill University shed light on fear generalization, a core component of anxiety and stress-related disorders.

    “The human mind uses cues to danger learned over time for self-defense, but certain circumstances can cause people to misidentify those cues,” said Joseph Dunsmoor, lead study author and assistant professor of psychiatry at Dell Med. “Our research reveals that stress levels and the amount of time since an adverse event promote this type of overgeneralization.”

    Dunsmoor conducted the research as a postdoc in the lab of Elizabeth Phelps, professor of psychology and neural science at New York University (NYU). Ross Otto, assistant professor of psychology at McGill University, also worked on the study as a postdoc at NYU.

    Post-Traumatic Stress Disorder (PTSD) — which affects about 8 million adults every year — is one disorder characterized by the inability to discriminate threat from safety. Fear is triggered by harmless stimuli such as a car backfiring because they serve as reminders of trauma. By understanding how the mind identifies and responds to such triggers, scientists can develop better treatments for mental illnesses and disorders.

    “These findings provide important laboratory data that helps explain why PTSD symptoms are often exacerbated during times of stress, and how repeated stress and trauma in the battlefield may lead to increased risk for PTSD,” said Suzannah Creech, an associate professor of psychiatry at Dell Medical School, who was not involved in the study, but has spent her career working with veterans recovering from trauma.

    “The research may help improve PTSD treatment outcomes for veterans in part by helping us understand how we may be able to prevent it in the first place,” she said.

    In the study, the researchers tested the effects of stress and time on a person’s ability to correctly identify a cue associated with a negative outcome. Study participants heard two tones with one followed by a shock, set by the participant at the level of “highly annoying but not painful.” Then, researchers played tones in the range of the two frequencies and gauged participants’ expectations of shock by self-report and data on skin responses that indicate emotional arousal. When testing the range of tones, half of the participants were methodically primed to have higher cortisol levels through an arm ice bath, and half received a control arm bath with room temperature water.

    Researchers performed the test on two groups. One group took the shock expectancy test immediately after the initial shock. The second group took the test 24 hours after the initial shock. Both groups underwent the stress/control priming activity just before the shock expectancy test.

    When tested immediately after the initial shock, stress level did not significantly affect the participants fear of shock and accuracy in identifying the associated tone. However, when tested 24 hours later, stress level did heighten participants’ fear response and negatively impacted their ability to identify the tone associated with shock. The group tested 24 hours later without raised cortisol levels only had slightly heightened fear responses and retained the ability to identify the associated tone.

    “The effects of stress and memory on how humans generalize fear is largely unexamined,” Dunsmoor said. “This study provides new data that will help us care for people with disordered patterns of fear and worry.”


  4. Study suggests PTSD may have a physical component as well

    August 4, 2017 by Ashley

    From the American Academy of Neurology press release:

    The part of the brain that helps control emotion may be larger in people who develop post-traumatic stress disorder (PTSD) after brain injury compared to those with a brain injury without PTSD, according to a study released today that will be presented at the American Academy of Neurology’s Sports Concussion Conference in Jacksonville, Fla., July 14 to 16, 2017.

    “Many consider PTSD to be a psychological disorder, but our study found a key physical difference in the brains of military-trained individuals with brain injury and PTSD, specifically the size of the right amygdala,” said Joel Pieper, MD, MS, of University of California, San Diego. “These findings have the potential to change the way we approach PTSD diagnosis and treatment.”

    In the brain there is a right and left amygdala. Together, they help control emotion, memories, and behavior. Research suggests the right amygdala controls fear and aversion to unpleasant stimuli.

    For this study, researchers studied 89 current or former members of the military with mild traumatic brain injury. Using standard symptom scale ratings, 29 people were identified with significant PTSD. The rest had mild traumatic brain injury without PTSD.

    The researchers used brain scans to measure the volume of various brain regions. The subjects with mild traumatic brain injury and PTSD had 6 percent overall larger amygdala volumes, particularly on the right side, compared to those with mild traumatic brain injury only.

    No significant differences in age, education or gender between the PTSD and control groups were found.

    “People who suffered a concussion and had PTSD demonstrated a larger amygdala size, so we wonder if amygdala size could be used to screen who is most at risk to develop PTSD symptoms after a mild traumatic brain injury,” said Pieper. “On the other hand, if there are environmental or psychological cues that lead to brain changes and enlargement of the amygdala, then maybe such influences can be monitored and treated.”

    “Further studies are needed to better define the relationship between amygdala size and PTSD in mild traumatic brain injury,” said Pieper. “Also, while these findings are significant, it remains to be seen whether similar results may be found in those with sports-related concussions.”

    He pointed out that these participants’ brain injuries were caused mostly by blast injuries as opposed to sports-related concussions. The study also shows only an association and does not prove PTSD causes structural changes in the amygdala.


  5. Some patients with dementia may experience delayed-onset PTSD

    July 27, 2017 by Ashley

    From the Wiley press release:

    Delayed-onset post-traumatic symptoms in the elderly may be misdiagnosed as falling under the umbrella of behavioural and psychological symptoms of dementia (BPSD), according to a recent review.

    The review describes three cases where post-traumatic stress disorder (PTSD) symptoms are experienced by patients suffering with dementia long after the original traumatic event.

    Considering PTSD in individuals with dementia is important because PTSD is usually associated with working-age adults and is infrequently diagnosed in the elderly. In the early stages of dementia, recognising early life trauma may enable patients to access psychological therapy prior to significant cognitive decline. In patients with more advanced dementias, an awareness of earlier trauma exposure can help clinicians differentiate between delayed PTSD and BPSD in patients suffering with emotional and behavioural disturbances.

    “Every patient with dementia has a unique narrative, which if captured in the earlier stages of the disease, enables clinicians and their families to understand the origin of their distress. Therefore, it is important to look for a history of previous trauma in patients with BPSD as this could be due to delayed onset PTSD,” said Dr. Tarun Kuruvilla, senior author of the Progress in Neurology & Psychiatry review.


  6. Some patients with dementia may experience delayed-onset PTSD

    July 21, 2017 by Ashley

    From the Wiley press release:

    Delayed-onset post-traumatic symptoms in the elderly may be misdiagnosed as falling under the umbrella of behavioural and psychological symptoms of dementia (BPSD), according to a recent review.

    The review describes three cases where post-traumatic stress disorder (PTSD) symptoms are experienced by patients suffering with dementia long after the original traumatic event.

    Considering PTSD in individuals with dementia is important because PTSD is usually associated with working-age adults and is infrequently diagnosed in the elderly. In the early stages of dementia, recognising early life trauma may enable patients to access psychological therapy prior to significant cognitive decline. In patients with more advanced dementias, an awareness of earlier trauma exposure can help clinicians differentiate between delayed PTSD and BPSD in patients suffering with emotional and behavioural disturbances.

    “Every patient with dementia has a unique narrative, which if captured in the earlier stages of the disease, enables clinicians and their families to understand the origin of their distress. Therefore, it is important to look for a history of previous trauma in patients with BPSD as this could be due to delayed onset PTSD,” said Dr. Tarun Kuruvilla, senior author of the Progress in Neurology & Psychiatry review.


  7. Snail study suggests select memories can be erased

    July 11, 2017 by Ashley

    From the Columbia University Medical Center press release:

    Different types of memories stored in the same neuron of the marine snail Aplysia can be selectively erased, according to a new study by researchers at Columbia University Medical Center (CUMC) and McGill University and published today in Current Biology.

    The findings suggest that it may be possible to develop drugs to delete memories that trigger anxiety and post-traumatic stress disorder (PTSD) without affecting other important memories of past events.

    During emotional or traumatic events, multiple memories can become encoded, including memories of any incidental information that is present when the event occurs. In the case of a traumatic experience, the incidental, or neutral, information can trigger anxiety attacks long after the event has occurred, say the researchers.

    “The example I like to give is, if you are walking in a high-crime area and you take a shortcut through a dark alley and get mugged, and then you happen to see a mailbox nearby, you might get really nervous when you want to mail something later on,” says Samuel Schacher, PhD, a professor of neuroscience in the Department of Psychiatry at CUMC and co-author of the paper. In the example, fear of dark alleys is an associative memory that provides important information — e.g., fear of dark alleys — based on a previous experience. Fear of mailboxes, however, is an incidental, non-associative memory that is not directly related to the traumatic event.

    “One focus of our current research is to develop strategies to eliminate problematic non-associative memories that may become stamped on the brain during a traumatic experience without harming associative memories, which can help people make informed decisions in the future — like not taking shortcuts through dark alleys in high-crime areas,” Dr. Schacher adds.

    Brains create long-term memories, in part, by increasing the strength of connections between neurons and maintaining those connections over time. Previous research suggested that increases in synaptic strength in creating associative and non-associative memories share common properties. This suggests that selectively eliminating non-associative synaptic memories would be impossible, because for any one neuron, a single mechanism would be responsible for maintaining all forms of synaptic memories.

    The new study tested that hypothesis by stimulating two sensory neurons connected to a single motor neuron of the marine snail Aplysia; one sensory neuron was stimulated to induce an associative memory and the other to induce a non-associative memory.

    By measuring the strength of each connection, the researchers found that the increase in the strength of each connection produced by the different stimuli was maintained by a different form of a Protein Kinase M (PKM) molecule (PKM Apl III for associative synaptic memory and PKM Apl I for non-associative). They found that each memory could be erased — without affecting the other — by blocking one of the PKM molecules.

    In addition, they found that specific synaptic memories may also be erased by blocking the function of distinct variants of other molecules that either help produce PKMs or protect them from breaking down.

    The researchers say that their results could be useful in understanding human memory because vertebrates have similar versions of the Aplysia PKM proteins that participate in the formation of long-term memories. In addition, the PKM-protecting protein KIBRA is expressed in humans, and mutations of this gene produce intellectual disability.

    “Memory erasure has the potential to alleviate PTSD and anxiety disorders by removing the non-associative memory that causes the maladaptive physiological response,” says Jiangyuan Hu, PhD, an associate research scientist in the Department of Psychiatry at CUMC and co-author of the paper. “By isolating the exact molecules that maintain non-associative memory, we may be able to develop drugs that can treat anxiety without affecting the patient’s normal memory of past events.”

    “Our study is a ‘proof of principle’ that presents an opportunity for developing strategies and perhaps therapies to address anxiety,” said Dr. Schacher. “For example, because memories are still likely to change immediately after recollection, a therapist may help to ‘rewrite’ a non-associative memory by administering a drug that inhibits the maintenance of non-associative memory.”

    Future studies in preclinical models are needed to better understand how PKMs are produced and localized at the synapse before researchers can determine which drugs may weaken non-associative memories.


  8. Identified brain circuitry bridges neural and behavioral roles in PTSD

    July 6, 2017 by Ashley

    From the NYU Langone Medical Center / New York University School of Medicine press release:

    Specific cerebral circuitry bridges chemical changes deep in the brain and the more outward behavioral expressions associated with post-traumatic stress disorder (PTSD), which could lead to more objective biomarkers for the disorder, according to a comprehensive review of rapidly changing data published June 22 in the New England Journal of Medicine.

    In this latest, comprehensive review, the authors — from the Steven and Alexandra Cohen Veterans Center (CVC) in the Department of Psychiatry at NYU Langone Medical Center and the University of Michigan/Veterans Affairs Ann Arbor Health Systems Mental Health Service — have identified four neural-behavioral models associated with PTSD. These models pinpoint specific circuits in the brain that “mediate” between chemical changes — which are being examined as possible PTSD biomarkers — and the expression of certain characteristics often associated with PTSD. These include fear responses, avoidance of trauma reminders, impaired emotional balance and the persistence of defensive responses despite a safe environment.

    “These neural-behavioral models account for, and help further explain, many of the peripheral findings in PTSD,” says study co-author Israel Liberzon, MD, professor of Psychiatry, Psychology and Neuroscience from University of Michigan. “These models will be valuable roadmaps in examining whether certain PTSD-related behaviors have particular chemical roots. This, in turn, could advance the identification of objective biomarkers for PTSD.”

    The authors point out that one of the major challenges with PTSD is that it is painstakingly difficult to objectively profile and diagnose. PTSD sufferers come from a wide swath of society, with higher rates of illness among socially disadvantaged individuals, younger persons, women, military personnel, police officers, firefighters and first responders to trauma. It also is prevalent in victims of physical and sexual assault, and those requiring assistance from first responders.

    The American Psychiatric Association recently updated its diagnostic criteria for PTSD in the fifth edition of its Diagnostic and Statistical Manual of Mental Disorders. But the co-authors point out that even when examining these changes comparatively with the APA’s prior criteria as well as criteria from the World Health Organization, there is only a 30% overlap in those meeting diagnostic criteria across the three measurements.

    “There continues to be major concerns with diagnosing PTSD,” says co-author Charles R. Marmar, MD, the Lucius Littauer Professor and chair of psychiatry at NYU Langone and director of the CVC. “While biomarker research continues — and we are making important strides — clinicians need to be alerted to the differences between criteria meant to index PTSD and the broader array of symptoms.”

    Study Includes Guidelines to Help Identify PTSD

    To address this, the authors included in their review detailed and easy-to-follow tables that provide information to better recognize signs and symptoms of PTSD for healthcare providers like primary care physicians, often the first point of contact for patients.

    “We know a lot more about PTSD and related conditions than in the past,” says co-author Arieh Shalev, MD, the Barbara Wilson Professor in the Department of Psychiatry at NYU Langone and a co-director of the CVC. “Our goal is to provide a highly precise and concise summary of all of the evidence-based findings thus far for understanding, diagnosing and treating PTSD.”

    The authors also say that there are more therapeutic options to offer patients, including cognitive behavior therapy, such as prolonged exposure and cognitive processing therapies; eye movement desensitization and reprocessing therapy; stress management; and medication. The review also includes data about the effectiveness of neurofeedback; transcranial magnetic stimulation; and endocannabinoid modulators, such as marijuana-derived medications.

    PTSD remains the most prevalent psychological consequence of trauma. An estimated 70 percent of adults worldwide will experience a traumatic event in their lifetime, and approximately 10 percent will develop the disorder. According to the U.S. Department of Veterans Affairs National Center for PTSD, approximately eight million American adults suffer from PTSD in a given year.


  9. Amygdala activity predicts posttraumatic stress disorder

    June 22, 2017 by Ashley

    From the Elsevier press release:

    Neuroimaging measures of emotional brain function after acute trauma may help predict whether a person will develop posttraumatic stress disorder (PTSD), according to a new study in Biological Psychiatry. Led by senior author Dr. Kerry Ressler of Emory University in Georgia and Harvard Medical School and McLean Hospital in Massachusetts, the study reports an association between the activity of two key brain regions involved in emotional regulation, the amygdala and anterior cingulate cortex (ACC), shortly after trauma and symptoms of PTSD that emerged within the following year.

    “This study introduces a new potential biomarker of PTSD, highlighting new roles for neuroimaging in PTSD research,” said Dr. John Krystal, Editor of Biological Psychiatry. The identification of a PTSD biomarker has exciting implications for limiting or preventing symptoms of the disorder.

    “The search for such early biological markers of poor recovery is very important, because it will allow us to find the people who are most at risk right after a trauma, and intervene early, before the onset of disorders such as PTSD or depression,” said first author Dr. Jennifer Stevens, of Emory University.

    In the study, Stevens and colleagues used functional magnetic resonance imaging to measure brain activity of 31 people approximately one month after a traumatic incident. The trauma was non-military related and included events such as a car accident or sexual assault. While the participants observed images of fearful faces (an index of threat), the researchers measured how the neural activity reacted in the amygdala and ACC, a brain region that regulates amygdala function, and how the activity changed over time with repeated viewing. Self-reported PTSD symptoms were assessed at 1, 3, 6, and 12 months after trauma.

    People with a greater amygdala response to fearful faces had greater initial symptom severity, and were more likely to maintain PTSD symptoms over the following year. Additionally, those with a sharper drop in ventral ACC activity over repeated viewing of fearful images, called habituation, showed a poorer recovery trajectory. The findings suggest that amygdala reactivity and ventral ACC habituation to a threat predict the emergence of PTSD symptoms after trauma.

    “The findings also suggest that an over-active amygdala may be one of the causes of PTSD, and that we should try to develop treatments that reduce amygdala reactivity,” said Stevens. For example, the region could be targeted with interventions such as psychotherapy or pharmacological treatments that can be administered shortly after trauma occurs.


  10. Amygdala activity predicts posttraumatic stress disorder

    June 16, 2017 by Ashley

    From the Elsevier press release:

    Neuroimaging measures of emotional brain function after acute trauma may help predict whether a person will develop posttraumatic stress disorder (PTSD), according to a new study in Biological Psychiatry. Led by senior author Dr. Kerry Ressler of Emory University in Georgia and Harvard Medical School and McLean Hospital in Massachusetts, the study reports an association between the activity of two key brain regions involved in emotional regulation, the amygdala and anterior cingulate cortex (ACC), shortly after trauma and symptoms of PTSD that emerged within the following year.

    “This study introduces a new potential biomarker of PTSD, highlighting new roles for neuroimaging in PTSD research,” said Dr. John Krystal, Editor of Biological Psychiatry. The identification of a PTSD biomarker has exciting implications for limiting or preventing symptoms of the disorder.

    “The search for such early biological markers of poor recovery is very important, because it will allow us to find the people who are most at risk right after a trauma, and intervene early, before the onset of disorders such as PTSD or depression,” said first author Dr. Jennifer Stevens, of Emory University.

    In the study, Stevens and colleagues used functional magnetic resonance imaging to measure brain activity of 31 people approximately one month after a traumatic incident. The trauma was non-military related and included events such as a car accident or sexual assault. While the participants observed images of fearful faces (an index of threat), the researchers measured how the neural activity reacted in the amygdala and ACC, a brain region that regulates amygdala function, and how the activity changed over time with repeated viewing. Self-reported PTSD symptoms were assessed at 1, 3, 6, and 12 months after trauma.

    People with a greater amygdala response to fearful faces had greater initial symptom severity, and were more likely to maintain PTSD symptoms over the following year. Additionally, those with a sharper drop in ventral ACC activity over repeated viewing of fearful images, called habituation, showed a poorer recovery trajectory. The findings suggest that amygdala reactivity and ventral ACC habituation to a threat predict the emergence of PTSD symptoms after trauma.

    “The findings also suggest that an over-active amygdala may be one of the causes of PTSD, and that we should try to develop treatments that reduce amygdala reactivity,” said Stevens. For example, the region could be targeted with interventions such as psychotherapy or pharmacological treatments that can be administered shortly after trauma occurs.