Autism: The Answer May Be Reflected in the Mirror Neuron

Anyone who listens to Imus in the Morning on WNBC radio (660 AM, weekdays) heard about autism during the last months of 2005. Reports of a possible association between autism and children's vaccines spurred devotion of hours of airtime to increasing public awareness of autism.---Concerns about autism are well-placed: governmental statistics indicate that its incidence is increasing by a startling 10% to 17% per year.1 Its prevalence has been steadily increasing as well, from 3.5 per 10,000 births in 1982 to 18.3 per 10,000 births in 1990-a 55% increase.2 Autism, it appears, is here to stay.Autism falls under the designation of pervasive developmental disorders (PDD), a category of neurologic disorders that includes:- Autistic disorder.- Asperger syndrome.- Childhood disintegrative disorder.- Rett syndrome.- PDD not otherwise specified.Each of these conditions is characterized by severe and pervasive deficits in several developmental areas, including imitation, pragmatic language, theory of mind, and empathy. The diagnostic criteria for autism and these other disorders, as specified by the Diagnostic and Statistical Manual of Mental Disorders, are listed in Tables 1 and 2, respectively.3Autism has several constant features, yet it can be somewhat of a chameleon, because affected persons may exhibit any combination of autistic behaviors in any degree of severity (Table 3).4 Also, the nature of the impairment in social interaction may change over time and may vary with the child's developmental level. About 10% of autistic children are savants-gifted in math, music, or art.5 Autism cannot be outgrown, although symptoms may lessen as the child matures and receives treatment. Boys are affected about 3 times more often than girls.5POSSIBLE CAUSESAutism has not been linked to any one particular causative mechanism. Several variables may contribute to autism, including environmental toxins (the discovery of "autism clusters" in Leominster, Massachusetts, and Brick Township, New Jersey, points to pollutants or toxins as possible culprits); gestational problems, such as exposure to rubella virus during the first trimester; viral infections; and metabolic imbalances. The occurrence of autism and related disabilities in some families and the higher incidence of autism observed in identical twins than in fraternal twins suggest that genetics may contribute.The possible relationship between autism and vaccines-especially the measles component of the measles-mumps-rubella vaccine, the pertussis component of the diphtheria-pertussis-tetanus vaccine, and the thimerosal preservative contained in many vaccines-is still being explored. The Institute of Medicine, reporting in 2001 and again in 2004, found no relationship between vaccines and autism but could not discount the possibility that the vaccine caused autism in a small number of children.6 More research is needed.LINK TO AUTISMRecently, investigators have found evidence that mirror neuron dysfunction is a strong contributor to autism. Mirror neurons are brain cells in the premotor cortex that fire when a person performs a goal-directed action and when he or she observes that same action performed by others. Activation of the mirror neurons is accompanied by activity in the limbic system, the brain area associated with emotion. The mirror neuron system allows a person to understand the actions, intentions, and emotions of another person and is thought to participate in such higher cognitive processes as language, imitation, and empathy.Vilayanur S. Ramachandran, MD, PhD, director of the Center for Brain and Cognition at the University of California, San Diego (UCSD), in La Jolla, and his colleagues, Eric Altschuler, MD, a former UCSD postdoctoral researcher who is now at the Mount Sinai School of Medicine in New York City, and Jaime Pineda, PhD, director of the Cognitive Neuroscience Laboratory at UCSD, became intrigued with mirror neurons after reviewing experimental research by teams led by neuroscientist Giacomo Rizzolatti, MD, PhD, director of the Department of Neuroscience at the University of Parma, Italy.7 The Italian researchers found that mirror neurons fired not only when a monkey performed a specific action but also when it observed that same action performed by another monkey.7"When I read this," said Ramachandran, "it struck me that these mirror neurons could be involved in a host of mental abilities regarded as being quintessentially human . . . such as our extraordinary ability to emulate our teachers or transmit our culture from generation to generation by imitation. These mirror neurons may contribute to our ability to empathize or understand another person's point of view.Some of the main symptoms of autism-the inability to empathize, to imitate, or to understand the emotions and intentions behind certain actions-are the same things that are mediated by the mirror neuron system," explained Ramachandran. "My colleagues and I postulated that perhaps the mirror neurons are simply dysfunctional in autistic persons."Ramachandran and coinvestigators8 studied electroencephalographic (EEG) recordings of 10 autistic persons (all of whom had an IQ above 80 as well as age-appropriate verbal comprehension and production) and 10 controls as they moved their own hands and while they watched videos of visual white noise (baseline), bouncing balls (nonbiologic motion), and a moving hand.The investigators analyzed the EEG tracings for mu rhythm suppression. "This mu wave normally gets suppressed when a person performs a volitional action or watches someone else perform the same activity-grabbing a lever, for instance. It correlates with mirror neuron activity," explained Ramachandran. The study findings showed that mu waves were suppressed in controls when they moved and when they watched another person move. This was no surprise, of course. However, the mirror neurons of the autistic persons responded only to their own movement, not to that of others. "This supported our hunch that autistic children have a problem with mirror neurons," commented Ramachandran.Ramachandran noted that although other kinds of brain dysfunction are being studied as possible causes for autism, none explains the symptoms found in autism. "You can see cerebellar changes in autistic children, sure. But when the cerebellum is damaged, the child gets very specific symptoms-intention tremor, nystagmus, ataxis. None of these is characteristic of autism. As neurologists, we try to find an abnormality that can explain the symptoms that are unique to autism.We found it with mirror neuron dysfunction."SUBSEQUENT RESEARCHRamachandran and his team were the first to link mirror neuron deficiency specifically to autism. Other investigators have since taken up the baton and are finding corroborative evidence:- Assistant Professor Mirella Dapretto, PhD, and colleagues,9 working at the Semel Institute for Neuroscience and Human Behavior at the University of California, Los Angeles, used functional MRI (fMRI) to measure brain activity in 10 high-functioning autistic and 10 nonautistic children. Brain scanning was performed as the children imitated and observed 80 photographs showing different emotions (anger, fear, sadness, happiness). Symptom severity of each autistic child was tested with 2 independent measures.The autistic children had no brain activity in the pars opercularis of the inferior frontal gyrus, a key part of the mirror neuron system. Furthermore, the level of mirror neuron activity was inversely related to symptom severity in the social domain. The autistic children also showed reduced limbic activity. This may explain why the children could imitate facial expressions but could not understand the corresponding emotional state, said the researchers.- A group led by Helen Tager-Flusberg, PhD, professor of anatomy, neurobiology, and psychology at Boston University, compared the cerebral cortex thickness of 14 high-functioning autistic adults with that of age, sex, handedness, and intelligence-matched controls.10 The autistic persons had local decreases of gray matter in the areas belonging to the mirror neuron system as well as in areas important to emotion recognition and social cognition. The extent of cortical thinning correlated with symptom severity. In another study, Tager-Flusberg and colleagues11 found that the mirror neuron systems of autistic persons fired fewer times than those of controls when watching hand movements of other persons.- A team from Aberdeen University, led by Senior Lecturer in Child Psychology Justin H. G. Williams, MRCPsych, compared fMRI results in 16 adolescent autistic boys with matched controls.12 Brain activity in the mirror neuron area was reduced in the autistic group and was absent during nonimitative actions. The differences in brain activity between autistic persons and controls were most marked at the right temporoparietal junction, the area associated with "theory of mind" function. Unlike the controls, the autistic boys had no modulation of left amygdala activity during imitation. These abnormal patterns of brain activity could be related to poor integration between areas serving visual, motor, proprioceptive, and emotional functions and could block the development of theory of mind.For now, the cause of mirror neuron deficiency remains elusive. Genetic predisposition might be responsible-or perhaps a virus attacks the motor neurons. Ramachandran referred to a theory considered by himself and collaborator and frequent coauthor, William Hirstein, PhD, chair of the Department of Philosophy at Elmhurst College in Chicago: "Bill Hirstein and I postulated a few years ago that sensory input to the medulla could get distorted by mini seizures that trigger autonomic storms, affecting the child's ability to discriminate and respond appropriately to events of differing intensity levels.13 But that's a whole other story."CLINICAL IMPLICATIONS"We're still a ways off from taking these findings from the lab to the clinic," mused Ramachandran. He envisions a time when the discovery of mirror neuron deficiency in a child could be applied to earlier diagnosis of autism-especially in younger siblings. Typically, autism is not identified until a child is aged 3 or 4 years, sometimes older. If younger siblings of high-functioning autistic persons could be tested and identified, they could be treated earlier.One possible treatment approach uses the mu rhythm in a biofeedback mechanism. Humans can learn to increase or decrease the strength of the mu signal at will so that they can better imitate others and control their own movements. As Ramachandran hypothesized, "We might be able to feed the mu wave suppression back to the child-perhaps by having affected children watch themselves in a mirror-and see if they can use biofeedback to enhance it. It certainly represents one line of treatment that may prove to be helpful in the future." Until then, parents and caregivers can continue to rely on traditional methods of treatment and to seek help from available resources. A list of resources for families affected by autism will appear in the online version of this article on www.appneurology.comREFERENCES1. US Department of Education. Autism incidence rates. Available at: www.pedal4acure.org. Accessed February 1, 2006.2. Newschaffer CJ, Falb MD, Gurney JG. National autism prevalence trends from United States special education data. Pediatrics. 2005;115:e277-e282.3. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Arlington, Va: American Psychiatric Association; 2000:70-84.4. Autism Society of America. Understanding autism. Learning the signs. Available at: www.autism-society.org/ site/PageServer?pagename=WhatisAutism. Accessed March 10, 2006.5. Edelson SM. Overview of autism. Center for the Study of Autism. Available at: www.autism.org/ overview.html. Accessed March 10, 2006.6. Institute of Medicine. Immunization safety review: vaccines and autism. May 2004. Available at: www.cdc.gov/nip/news/iom. Accessed February 3, 2006.7. Ferrari PF, Gallese V, Rizzoletti G, Fogassi L. Mirror neurons responding to the observation of ingestive and communicative mouth actions in the monkey ventral premotor cortex. Eur J Neurosci. 2003;17:1703-1714.8. Oberman LM, Hubbard EM, McCleery JP, et al. EEG evidence for mirror neuron dysfunction in autism spectrum disorders. Brain Res Cogn Brain Res. 2005;24:190-198.9. Dapretto M, Davies MS, Pfeifer JH, et al. Understanding emotions in others: mirror neuron dysfunction in children with autism spectrum disorders. Nat Neurosci. 2005;9:28-30.10. Hadjikhani N, Joseph RM, Snyder J, Tager-Flusberg H. Anatomical differences in the mirror neuron system and social cognition network in autism. Cereb Cortex. 2005 Nov 23;[Epub ahead of print].11. Theoret H, Halligan E, Kobayashi M, et al. Impaired motor facilitation during action observation in individuals with autism spectrum disorder. Curr Biol. 2005;15:R84-R85.12. Williams JH, Waiter GD, Gilchrist A, et al. Neural mechanisms of imitation and "mirror neuron" functioning in autistic spectrum disorder. Neuropsychologia. 2006;44:610-621.13. Hirstein W, Iversen P, Ramachandran VS. Autonomic responses of autistic children to people and objects. Proc Biol Sci. 2001;268:1883-1888.COLLEEN B. LITOF is a freelance medical writer in Redding, Connecticut.---Table 1 Diagnostic criteria for autistic disorder4A. A total of 6 or more items from (1), (2), and (3), with at least 2 from (1) and 1 each from (2) and (3):(1) Qualitative impairment in social interaction manifested by at least 2 of the following:a. Marked impairment in the use of multiple nonverbal behaviors, such as eye-to-eye gaze, facial expression, body postures, and gestures to regulate social interactionb. Failure to develop peer relationships appropriate to developmental levelc. Lack of spontaneous seeking to share enjoyment, interests, or achievements with other people (ie, by a lack of showing, bringing, or pointing out objects of interest)d. Lack of social or emotional reciprocity(2) Qualitative impairments in communication as manifested by at least 1 of the following:a. Delay in, or total lack of, the development of spoken language (not accompanied by an attempt to compensate through alternative modes of communication such as gesture or mime)b. In persons with adequate speech, marked impairment in the ability to initiate or sustain a conversation with othersc. Stereotyped and repetitive use of language or idiosyncratic languaged. Lack of varied, spontaneous make-believe play or social imitative play appropriate to developmental level(3) Restricted repetitive and stereotyped patterns of behavior, interests, and activities manifested by at least 1 of the following:a. Preoccupation with 1 or more stereotyped and restricted patterns of interest that is abnormal either in intensity or focusb. Apparently inflexible adherence to specific, nonfunctional routines or ritualsc. Stereotyped and repetitive motor mannerisms (ie, hand or finger flapping or twisting, or complex whole-body movements)d. Persistent preoccupation with parts of objectsB. Delay or abnormal functioning in at least 1 of the following areas, with onset before age 3 years: (1) social interaction, (2) language as used in social communication, or (3) symbolic or imaginative play.C. The disturbance is not better categorized as Rett syndrome or childhood disintegrative disorder---Table 2 Characteristics of other disorders in the PDD spectrum4Disorder: Asperger syndromeTraits:- Qualitative impairment in social function manifested by at least 2 of the following: marked impairment in use of multiple nonverbal behaviors; failure to develop appropriate peer relationships; lack of spontaneous seeking to share enjoyment, interests, or achievements; lack of social or emotional reciprocity- Restricted repetitive stereotypical patterns of behavior manifested by at least 1 of the following:preoccupation with one or more stereotypical, restricted patterns of interest; inflexible adherence to specific, nonfunctional routines/rituals; stereotyped, repetitive motor mannerisms; preoccupation with parts of objects- Disturbance clinically interferes with social, occupational, or other important functional areas- No clinically significant general delay in language; cognitive development; or self-help skills, adaptive behavior, and curiosityDisorder: Childhood disintegrative disorderTraits:- Apparently normal development for the first 2 years after birth- Clinically significant loss of skills in at least 2 of the following: language, social skills or adaptive behavior, bowel/bladder control, play, motor skills- Functional abnormalities in at least 2 of the following: social interaction, communication, patterns of behavior, interests, and activitiesDisorder: Rett syndromeTraits:- Apparently normal prenatal and perinatal development, including psychomotor development (first 5 months)- Normal head circumference at birth- Deceleration of head growth between 5 and 48 months- Loss of purposeful hand skills between 5 and 30 months, with subsequent development of stereotyped hand movements- Early loss of social engagement- Onset of poorly coordinated gait or trunk movements- Severely impaired expressive and receptive language development- Severe psychomotor retardationDisorder: PDD-NOSTraits:- Severe, pervasive impairment in the development of reciprocal social interaction associated with verbal/nonverbal communication- Stereotypical behaviors, activities, or interestsPDD, pervasive developmental disorder; PDD-NOS, pervasive developmental disorder not otherwise specified.---Table 3 Autistic behaviors5-Insistence on sameness; resistance to change-Difficulty with expressing needs; using gestures or pointing instead of speaking-Repeating words or phrases in place of normal, responsive language-Laughing (or crying) for no apparent reason; showing distress for reasons not evident to others-Preference for solitude; aloofness-Tantrums-Difficulty in mixing with others-Not wanting to cuddle or be cuddled-Little or no eye contact-Unresponsiveness to normal teaching methods-Sustained odd play-Spinning objects-Obsessive attachment to objects-Apparent over- or under-sensitivity to pain-No real fear of danger-Noticeable physical over- or under-activity-Uneven gross/fine motor skills.-Nonresponsiveness to verbal cues; acts as if deaf, although hearing tests in normal rangeTABLE 4 Resources for families affected by autismCenters for Disease Control and PreventionAutism Information Center: ResourcesWeb site: www.cdc.gov/ncbdd/dd/aic/resources/index.htmNational Dissemination Center for Children With DisabilitiesThe NICHCY has resource sheets listing key programs in each state for children with developmental disabilities and their families. The lists include state agencies, state chapters of disability organizations and parent groups, and parent training/information projects.Telephone: 800-695-0285E-mail: nichcy@aed.orgWeb site: www.nichcy.org/states.htmState Children's Health Insurance ProgramEvery state has a Children's Health Insurance Program that provides free or low-cost health insurance for eligible children. The Insure Kids Now! Web site has basic information about these programs, including links to each state's insurance program.Telephone: 877-267-2323Web site: www.cms.hhs.gov/home/schip.aspNational Institute on Disability and Rehabilitation ResearchThis agency funds state projects that work to help people with disabilities gain access to adaptive technology devices and services.Telephone: 202-245-7640Web site: www.ed.gov/about/offices/list/osers/nidrr/index-html?src=mrAutism Society of AmericaContains information, answers to common questions about autism, and links to support groups. Also provides listings of local resources and a free e-mail newsletter.Telephone: 800-3AUTISM (328-8476)E-mail: A list of various e-mail addresses is provided, depending on the nature of the inquiry.Web site: www.autism-society.org