September 9, 2014

Fear, Autism, and An Innate Brain System

Have you ever been awake at night unable to sleep because of the sound of a dripping faucet? Or felt enraged due to someone sitting near you was chewing gum?Are you someone who would like to wear a turtle neck sweater during the cold weather but cannot because it feels as though the touch of the fabric on your neck and throat is strangling? Do you react badly by the sudden and unexpected touch of someone, even if its someone you know and love? If you are familiar with any of these experiences you then have a good idea of what sensory defensiveness or sensory overload is all about.

However, what distinguishes you from those who fit the full diagnostic category of sensory defensiveness is that there are multiple stimuli that the sensory defensive person finds intolerable. As a result, daily life is deeply affected because it is difficult or impossible to work, have a relationship or engage in social interaction with other people. The reason for these limitations is that there are so many stimulating factors in the environment that cause real irritation that the individual is distracted and therefore, incapacitated. Many of these people withdraw into social isolation and this isolation as well as the sensitivity to stimuli, are depressing.

In sensory defensiveness, multiple things are experienced as alarming, and are negatively reacted to. It is important to stress that these over stimulating items are minor and do not bother or annoy the average person. For those who with sensory overload, many or all of these things are intolerable. Commonly, there can be a startle response to irritating stimuli. Another common response is extreme anger that other people find disconcerting if not totally unacceptable.

This terrible experience of intolerance can affect everything from the taste and texture of certain foods to many types of sounds, lights and clothing fabrics and even temperature.

People with this disorder have a lot of variability with regard to what things will be overwhelming and to what degree someone is overwhelmed. It is possible to have a sensory defensiveness to a degree that is mild, moderate or severe.

It is not completely clear what causes this disorder. There is evidence that such factors as Premature Birth, Alcoholism, Drug Addiction, Autism, PTSD, ADHD and Brain Injury due to head trauma, can contribute to the start of hypersensitivity to stimuli.

Conditioning is sometimes used to help people with this condition. This means that they are exposed to very calming stimuli to help counteract the negativer response to things that are irritating. Ultimately the person must learn to use these calming strategies by themselves.

Recent research shows that the part of the brain called the Thalamus might be involved in this hypersensitivity. The Thalamus, located in the middle of the brain, is a kind of relay station for all the sensory information that is relayed via the eyes, ears and other sensory organs. If the thalamus is damaged, it may disrupt the brain’s ability to sort out and integrate all the sensory information coming into the brain. The use of fMRI technology and other types of brain scopes, are helping medical science understand what goes wrong in the brains of these people. It is hoped that this will lead to new and more effective techniques for the treatment of this disorder.

It is important to keep in mind that people with this condition are not deliberately behaving badly when they over react to something. This is not something they are choosing to do and would happily change it if they could. If you know someone who may be experiencing sensory overload, including a child, it is important that they be seen by a physician  so that the correct diagnosis can be made and treatment begun. Relaxation is an important piece to healing 

FEAR neurocircuitry in the brain generates emotions that are “characterized by generalized apprehensive tension, with a tendency toward various autonomic symptoms such as tachycardia (rapid heartbeat often with palpitations), sweating, gastrointestinal symptoms, and increased muscle tension,” writes Jaak Panksepp in Affective Neuroscience: The Foundations of Human and Animal Emotions (1998).

The electrocardiogram (ECG) image above right (links to source) is from the Merck Manual Online Medical Library’s entry for “Ventricular Tachycardia.” The top strip’s series of repeating wide uncoordinated spikes indicates a rapid heartbeat. Fear can generate this kind of heart rhythm. A normal ECG strip, with very coordinated spikes, is shown at the bottom for comparison.

The brain’s FEAR neuro circuitry:

 Like other emotive circuits we discuss in Part 2 of, the neurocircuitry for fear is genetically encoded in the mammalian brain. Panksepp writes: “The emotional experience of fear appears to arise from a conjunction of neural processes that prompt animals to hide (freeze) if danger is distant or inescapable, or to flee when danger is close but can be avoided.”

In the laboratory, intense electrode stimulation of FEAR neurocircuitry prompts an animal to try to flee. Panksepp explains that such stimulation “leads animals to run away as if they are extremely scared.” He writes: “If given the opportunity, animals will avoid environments where they have received such stimulation in the past, and if no avenue of escape is provided, they will freeze as if in the presence of a predator.”

The concept of genetically determined, innate neurocircuitry for FEAR can be demonstrated with a loss-of-function experiment using knockout mice. Such mice are engineered to lack the activity of one or more genes. Although it has since been removed from the internet, Richard Twyman created the following useful definition of knockout mice in a website about the human genome.

 Knockout mice contain the same, artificially introduced mutation in every cell, abolishing the activity of a preselected gene. The resulting mutant phenotype (appearance, biochemical characteristics, behaviour etc.) may provide some indication of the gene’s normal role in the mouse, and by extrapolation, in human beings. Knockout mouse models are widely used to study human diseases caused by the loss of gene function.

Researchers Chong Chen et. al knocked out just one copy of a particular gene and created a knock-out mouse with unusual characteristics related to fear. In Animals in Translation: Using the Mysteries of Autism to Decode Animal Behavior (2005), Temple Grandin and Catherine Johnson recount how researchers “discovered that they hadn’t just knocked out some aspect of learning; they’d also knocked out fear. A normal mouse, with a normal amount of fear, does not fight to the death. He fights until he’s beaten, or sees he’s going to lose, and then he yields. Fear keeps him alive. The knockout mice were almost fearless, and they fought to the death.” Grandin and Johnson write: “The researchers would come to the lab first thing in the morning and find dead mice in the cages. Their backs were broken and there was blood everywhere.”

In normal animals, Panksepp notes in Affective Neuroscience that with “very weak stimulation, animals exhibit … a freezing response, common when animals are placed in circumstances where they have previously been hurt or frightened. Humans stimulated in these same brain areas report being engulfed by intense anxiety.” Panksepp provides examples of such human reactions. One patient reports: “Somebody is now chasing me, I am trying to escape from him.” Another had “an abrupt feeling of uncertainty just like entering into a long, dark tunnel.” Another sensed being near the sea with “surf coming from all directions.”

Fear progresses from the amygdala to the hypothalamus to the periaqueductal gray area of the midbrain to lower regions of the spinal cord where an autonomic response is generated. In terms of general trajectory, FEAR circuitry runs parallel to and most certainly interacts with RAGE neurocircuitry, contributing to, as Panksepp puts it “the balance between fight and flight reactions.” It is in lower, more primal, regions of the brain, specifically the periaqueductal gray (PAG) that the FEAR neurocircuitry is most easily aroused. Panksepp explains that fear is aroused with electrical stimulation of “lateral and central zones of the amygdala, the anterior and medial hypothalamus, and, most clearly (and at the lowest current levels), within specific PAG areas of the midbrain.”

FEAR neurocircuitry projects even farther “down to specific autonomic and behavioral output components of the lower brain stem and spinal cord,” which Panksepp explains control physiological processes including increased heart rate, increased blood pressure, the startle response, elimination, and perspiration. In the amygdala, FEAR circuitry and RAGE circuitry “are fairly clearly segregated, with FEAR being more lateral and RAGE more medial,” explains Panksepp.

Panksepp points out that benzodiazepines (e.g., diazepam, trade name Valium) couple with receptors along the FEAR circuit that “are closely coupled to gamma-aminobutyric acid (GABA) function in the brain.” He writes: “Just as glutamate is the brain’s most prolific excitatory transmitter, its metabolic product GABA, via one decarboxylation step, is the most pervasive inhibitory transmitter and is capable of suppressing fear as well as many other emotional and motivational processes.” In other words, benzodiazepines facilitate GABA activity and thereby reduce fear. Later in this narrative, we will talk about another drug, carbamazepine, that also facilitates GABA activity and reduces fear.

Glutamate chemical structure and its metabolic product, gamma-aminobutyric acid (GABA).

It is interesting, as Panksepp points out, that “animals and humans do not focus on their bodily injuries when they are scared ….” Fear-induced analgesia emerges in part, “from arousal of pain-inhibition pathways such as serotonin and endogenous opioids, near the PAG… .”

Many animals have innate fears. Panksepp writes: “External stimuli that have consistently threatened the survival of a species during evolutionary history often develop the ability to unconditionally arouse brain fear systems.” For example, laboratory rats that have never before encountered a cat or ferret exhibit “increased freezing and inhibition of other motivated behaviors” when the odor of a cat or ferret is introduced into their environment. Panksepp notes that the fear response is species-specific. For example, rats prefer to enter dark holes but show reduced social activity when exposed to bright lights. Benzodiazepines counter the anxiety rats display when exposed to bright lights.

In the laboratory, fear responses can be learned when neutral stimuli are paired with electric shock. This kind of fear arousal is called a “conditioned response.” In humans for example, when pain or other threatening stimuli occurs in the context of other specific external events, thereafter the external events, although nonthreatening in and of themselves, can trigger arousal in FEAR neurocircuitry. Regarding post-traumatic stress disorder (PTSD), Panksepp concludes that “deep subcortical networks” can “become sensitized and can operate independently of your higher cognitive faculties.”

Panksepp explains that when the central nucleus of the amygdala “is lesioned on both sides of the brain, animals no longer exhibit increased heart rates to stimuli they had learned to fear. It is now becoming clear that the central nucleus is one major brain area where conditional synaptic control of fear is created.” As Panksepp points out, “damage to the amygdala can reduce fear conditioning in humans just as it does in animals… .” In addition to reduced fear, Panksepp reports that “such brain-damaged individuals are no longer able to recognize the facial expressions of emotions.”

The polyvagal theory, autism, and PTSD:

 As we discussed above, Panksepp notes that FEAR neurocircuitry projects to “autonomic and behavioral output components of the lower brain stem and spinal cord.” As we discussed in Part 1 of, the vagus nerve is part of the autonomic nervous system and arises from the lower brainstem, specifically the medulla, and innervates the viscera—the internal organs of the body including the lungs, heart, liver, and intestine—with autonomic sensory and motor fibers.

In an interview with Ravi Dykema of Nexus: Colorado’s Healthy-Living Connection, March/April 2006, Stephen W. Porges, Professor and Director of the Brain-Body Center in the College of Medicine at the University of Illinois at Chicago, explains that the vagus nerve—the primary nerve for the parasympathetic nervous system—has two major branches: an ancient unmyelinated branch that we share with reptiles and a more recently evolved myelinated branch unique to mammals that “is linked to the cranial nerves that control facial expression and vocalization.”

Porges’s polyvagal theory proposes an automatic-response hierarchy emphasizing that when mammals detect they are in a safe environment, their bodies automatically activate the more recently developed myelinated branch of the vagus nerve that promotes “calm states, to self-soothe and to engage.” What Porges calls the social engagement system determines the quality of interpersonal exchanges, regulating “the features that we show other people, the facial expression, the intonation of our voice, the head nods, even the hand movements….”

 Porges points out that “when we’re stressed or anxious, we use our facial muscles, which include the ears. We eat or drink, we listen to music, and we talk to people to calm down.” He emphasizes: “We forget that listening is actually a ‘dotor’ act and involves tensing muscles in the middle ear. The middle ear muscles are regulated by the facial nerve, a nerve that also regulates eyelid lifting. When you are interested in what someone is saying, you lift your eyelids and simultaneously your middle ear muscles tense. Now you are prepared to hear their voice, even in noisy environments.”

When circumstances change and one detects danger, Porges explains that our automatic defense system employs either “the sympathetic-adrenal system to mobilize for fight and flight behaviors,” or, when circumstances are perceived to be so dire that fight or flight is useless, the ancient unmyelinated vagal system immobilizes us, just like an animal freezes when escape from a predator is impossible.

 In a 2010 interview with Lauren Culp of the Global Association for Interpersonal Neurobiology Studies (GAINS), Porges says: “By not moving, the mammal would not be detected by [the] predator and, as a byproduct of this strategy, consciousness might be lost or for humans states of dissociation may occur.” In “The Polyvagal Theory for Treating Trauma,” a National Institute for the Clinical Application of Behavioral medicine (nicabm) teleseminar, Porges explains that “If a life threat triggers a biobehavioral response that puts a human into this state, it may be very difficult to reorganize to become ‘normal ‘ again.”

To put Porges’s polyvagal theory in more academic terms, I consulted a chapter that Porges authored in The Integrative Neurobiology of Affiliation, edited by Carol Sue Carter, I. Iza Lederhendler, and Brian Kirkpatrick (Massachusetts Institute of Technology, 1999). When the more recently evolved myelinated vagal system is active (what Porges identifies as the VVC—ventral vagal complex), we have “the ability to communicate via facial expressions, vocalizations, and gestures.” When this system is inactive, “the sympathetic nervous system is unopposed and easily expressed to support mobilization such as fight or flight behaviors.” In terrifying circumstances, when the ancient unmyelinated vagal system (what Porges identifies as the DVC—dorsal ventral complex) kicks in, “immobilization and potentially life-threatening bradycardia [slowed heart action], apnea, and cardiac arrhythmias occur.” Porges explains that such immobilization is “the vestige from the reptilian vagal control of the heart and lung. In contrast to reptiles, mammals have a great demand for oxygen and are vulnerable to any depletion in oxygen resources. The metabolic demand for mammals is approximately five times greater than that for reptiles of equivalent body weight. Thus, reptilian dependence on this system provides a shutdown of metabolic activity to conserve resources during diving or death feigning.”

In the Nexus interview, Porges reminds us that people suffering from PTSD, autism, panic disorder, or any other hypervigilant state are unconscious of the neurobiological process behind their symptoms, which are, Porges explains, an “adaptation to a situation” that his/her nervous system has “evaluated as dangerous.” He points out that strategies to reason with or negotiate with a patient frequently do not work to improve engagement and interaction with others. Porges says “to make people calmer, we talk to them softly, modulate our voices and tones to trigger listening behaviors, and ensure that the individual is in a quieter environment in which there are no loud background noises.”

Porges notes in the GAINS interview: “At least 60% of individuals with autism have auditory hypersensitivities.” In working and interacting with individuals, he emphasizes the importance of “respecting the physiological state of the other and respecting the sensory world of the other person….” In working with trauma victims, Porges advises therapists to encourage their clients to “celebrate the success of their bodies in navigating and negotiating extraordinary dangerous situations” and respect “how their body and their nervous system put them in a state in which they could survive.”

In dealing with stress, Porges recommends to everyone to remember what it is to be a human. He tells Nexus readers: “Part of being a human is to be dependent upon another human. Not all the time, of course. Similar to most mammals, we come into the world with great dependence on our caregivers, and that need to connect and be connected to others remains throughout our lives.” He emphasizes the need to create safe environments for ourselves in which we can socially engage.

Fear processing, PTSD, and kindling:

A March 2009 report from the Society for Neuroscience, “Post Traumatic Stress Disorder,” aligns with Amy F.T. Arnsten’s ideas about how stress can produce impairments in the prefrontal cortex (see Stress, attention, learning, memory, and ADHD). The Society for Neuroscience reports: “Patients with PTSD have heightened levels of norepinephrine, a chemical involved in arousal and stress. High levels of this chemical strengthen the emotional reactions of the amygdala, a brain region involved in the fear response, while weakening the rational functions of the prefrontal cortex, which normally allows us to suppress troubling memories and thoughts.”

There is interesting evidence of a mechanism within the human brain that helps suppress troubling memories and thoughts in a way that is healing. In Animals in Translation, Grandin and Johnson draw attention to Ruth Lanius et al., “The Nature of Traumatic Memories: A 4-T fMRI Functional Connectivity Analysis.” During the study, brain scans were conducted for eleven people with PTSD as a result of sexual abuse, assault, or car crashes as well as for thirteen people who had suffered the similar experiences without developing PTSD. Those who suffered from PTSD remembered their trauma visually, more like a flashback, while those without PTSD remembered their trauma as a verbal narrative. In a summary of this research, titled “Brain Activation May Explain PTSD Flashbacks,” Joan Arehart-Treichel quotes Bessel van der Kolk, M.D., a professor of psychiatry at Boston University and medical director of the Trauma Center there.

Dr. Lanius has elegantly demonstrated how people’s brain function differs when they are in dissociate states.… We always suspected that when people go into these states, there is a decrease in activation of the left inferior prefrontal cortex—meaning that people are less capable of taking in new information and being curious about the world out there—and that the brain shifts to a more right posterior activation—more to a state of fear and flight.”

 If language helps humans suppress fear, it is easier to understand why animals do not possess the same ability to suppress fear as people do. Grandin, who has made a career working with animals, asserts: “I do know that once an animal has become traumatized it’s impossible to un-traumatize him. Animals never unlearn a bad fear.” Grandin and Johnson point out that animals are aware of tiny details in their environments and can become afraid of these tiny details. The authors describe this as “hyper-specific” fear. “It comes from autism research, because autistic people are extremely hyper-specific. You see the trees better than the forest. A lot of times you might not see the forest at all. Just trees, trees, and more trees.” The authors point out that animals will react fearfully to any stimulus that resembles, in terms of sensory perception, an initial fearful experience. They describe a dog’s encounter with a red hot-air balloon which severely frightened the animal. Subsequently, the dog reacted fearfully to any red, circular object, even the read aerial markers that draw attention to power lines.

In Affective Neuroscience, Jaak Panksepp notes that PTSD is “characterized by permanent personality changes, including frequent moods of intense fear and anger.” The Society for Neuroscience reports that PTSD symptoms may “include intrusive memories, emotional numbness, and insomnia.”

In Part 1 of, we discuss kindling (see Kindling and stress—how experience affects the brain). In our discussion of FEAR neurocircuitry here, Panksepp explains in more specific detail the experimental procedure known as kindling in which “animals are induced to exhibit epileptic states by the periodic application of localized electrical stimulation to specific areas of the brain.” Panksepp points out that the “amygdala, an emotion-mediating brain area, is an ideal site for kindling studies, since seizure activity can be induced here most rapidly.” Citing a wide range of research studies, Panksepp succinctly describes the kindling procedure:

The procedure consists simply of applying a burst of brain stimulation through indwelling electrodes for a period of one second, once a day, for a week or two. After the first brief ESB [electrical stimulation to the brain], nothing special happens, unless one observes the EEG, where one will note a momentary seizure immediately after the brain stimulation. This induced epileptic fit gets larger and larger as the days pass, and after a few days, the ESB begins to provoke brief periods of outright convulsive activity. After a week or so, the brief stimulation produces a full-blown motor fit, unambiguous both behaviorally and in the poststimulation EEG. Thereafter, the animal will always have a seizure when it receives this burst of brain stimulation. Gradually even other stimuli become capable of triggering seizures, especially loud sounds and flashing lights.

Giving animals seizure-inducing drugs every several days or even exposing them to very loud auditory stimulation also induces kindling, sometimes provoking fits in certain sensitive strains of animals. The induction of these epileptic states reflects a functional reorganization of the nervous system, since no structural changes have been found to result from kindling procedures.

Panksepp observes that “the emotional personality of these animals seems to change as they become kindled. Cats tend to become temperamental and irritable. In female rats, we have observed a form of ‘nymphomania’.” Panksepp says that normal female rats are sexually receptive “for only a couple of hours every four days, but after kindling many females remain in constant estrus. They are willing to have sex with males at all times. It is as if their hormonal receptivity cycle has been locked in overdrive.”

“The severity of PTSD can be diminished with antiseizure medications, such as carbamazepine,” notes Panksepp. He points out that carbamazepine facilitates the inhibitory activity of gamma-aminobutyric acid (GABA) and blocks the effects of previous kindling. In Part 3 of, regarding obsessions and compulsions, we also discuss the inhibitory neurotransmitter GABA along with the nucleus accumbens, which is intricately connected with the easily kindled amygdala,

Fear, autism, splitting, and savantry:

As you may know, Temple Grandin is autistic and has made a career working with animals, especially in improving conditions for farm animals raised for food. She writes: “This is what I have in common with animals. Our fear system is ‘turned on’ in a way a normal person’s is not. … If I hadn’t gone on medication I couldn’t have had a life at all. I certainly wouldn’t have been able to have a career.”

In Animals in Translation, Grandin and Johnson write: “It seems likely that animals and autistic people both have hyper-fear systems in large part because their frontal lobes are less powerful compared to the frontal lobes in typical folks. The prefrontal cortex gives humans some freedom of action in life, including some freedom from fear. As a rule, normal people have more power to suppress fear, and to make decisions in the face of fear, than animals or (most) autistic people.”

 Regarding the frontal lobes, Grandin and Johnson write: “The frontal lobes fight fear in two ways. First, the frontal lobes are the brakes. The frontal lobes tamp down the [action of the] amygdala …. The amygdala tells the pituitary to pump out stress hormones such as cortisol; the prefrontal cortex tells the pituitary to slow down.” The position of the amygdalae within the temporal lobes can be seen in the MRI to the right (image links to NIH source). The MRI shows fMRI activation of the amygdalae highlighted in red.

Grandin and Johnson point to a core difference between animals and autistic people on the one hand, and normal people on the other. “Animals and autistic people are splitters. They see the differences between things more than the similarities. In practice this means animals don’t generalize very well.”

Regarding savantry, Grandin and Johnson point to the research of Allen Snyder and D. John Mitchell who propose that “all the different autistic savant abilities come from the fact that autistic people don’t process what they see and hear into unified wholes, or concepts, rapidly the way normal people do.” Grandin and Johnson explain that a normal person doesn’t become conscious of what he’s looking at until after his brain has composed the sensory eces into wholes. The authors point out that an autistic savant is conscious of the bits and pieces. They note Snyder’s and Mitchell’s conclusion that “the reason autistic people see the pieces of things is that they have privileged access to lower levels of raw information.” Snyder’s article, “Explaining and Inducing Savant Skills: Privileged Access to Lower Level, Less-Processed Information,” is available on the web.