High-Functioning Autism: a neural phenotype in the cingulate cortex

A review by Chris and Uta Frith discusses and important paper in Neuron from Montague's group in Houston, who:

...have measured brain activity (using fMRI) while volunteers, who are classified as being at the high-functioning end of the autistic spectrum, were engaged in a simple social interaction. The task was an iterated trust game in which two subjects take turns as investor or trustee. The investor chooses how much to money to invest. This chosen amount is tripled on its way to the trustee, and the trustee then chooses how much to repay to the investor. Read Montague and his colleagues have studied this game extensively in large groups of volunteers and have observed a characteristic pattern of brain activity in the anterior cingulate cortex. When making an investment (self phase), transient increases in activity are seen in an area of mid cingulate cortex (−7 <>A graphic from the Chiu et al paper showing the diminished "self" response in autism spectrum patients:


...the results suggest that the abnormality associated with autism is restricted to only one phase of the interactive game: the point where the autistic volunteer makes an investment, not the point where the autistic volunteer is told about the repayment made by their partner. Additional results from Read Montague's group give further clues as to the implications of this result. First, the same pattern of activity in cingulate cortex is observed when volunteers are shown pictures of people engaged in athletic activities and asked to imagine themselves taking part. This is further evidence as to the nature of the cognitive process associated with this pattern of activity: it involves thinking about the self acting in a social context. Second, the characteristic patterns of activity in the cingulate cortex are only observed when the trust game is played with a human partner. No such distinct patterns emerge when the game is played in the absence of a responsive social partner...At least part of the imagining must involve thinking about how one would fit in with the group, and how other group members would evaluate one's performance. Actually, this is a question about the kind of reputation one might gain in the eyes of the others. Likewise, in the self phase of the trust game, the amount one invests can be seen as a measure of how much one trusts one's partner. It is not just giving an amount of money; it is giving a signal to the other person: “trust me” and “I trust you.”
In other words, at the point of investment we are predicting what the effect of our investments is going to be on the behavior of our partners. In the other phase of the game, we are also evaluating a signal. But there is a difference. The evaluation is after the fact. We know what the investment is. We are not at this point trying to build our reputation in the other player's eyes.

Impairment of action chains in autism.

When we observe the start of an action sequence that can end in two possible ways (in the figure shown a piece of food is placed in the mouth or in a container on the shoulder) appropriate sympathetic muscle EMG signals are detected at the start of the sequence. Thus, if the sequence will end in food to the mouth, activity is observed in the mouth-opening mylohyoid (MH) muscle at the onset. Rizzolatti and collaborators find that typically developing children show an activation of their MH muscle already when they observe the experimenter's initial motor act, food reaching. This activation reflects their understanding of the final goal of the observed action. In children with autism this action-understanding motor activation is lacking. Further, when typically developing children actually perform the observed action, MH muscle activation is observed at the very beginning of the sequence, while in children with autism, the activation is not observed until immediately before the muscle is actually used.

Figure - Schematic representation of the tasks. (Upper) The individual reaches for a piece of food located on a touch-sensitive plate, grasps it, brings it to the mouth, and finally eats it. (Lower) The individual reaches for a piece of a paper located on the same plate, grasps it, and puts into a container placed on the shoulder.

They suggest that high-functioning autistic children may understand the intentions of others cognitively but lack the mechanism for understanding them experientially because they lack the chains of action-constrained neurons that code specific motor acts (e.g., grasping) according to the final goal of the action in which the motor act is embedded.

Plasticity and learning in the human mirror neuron system

I pass on a review by Welberg of an interesting study by Catmur et al. [Catmur, C., Walsh, V. & Heyes, C. Sensorimotor learning configures the human mirror system. Curr. Biol. 17, 1527–1531 (2007)]:

Neurons in the frontoparietal mirror system fire when one performs an action and when one observes someone else performing that same action. This system is thought to have a role in social cognition and, perhaps, in language acquisition. How the mirror neurons map sensory input onto its motor representation is unknown, but Catmur et al. demonstrate that these representations are not innate and can be altered by training.

The authors used transcranial magnetic stimulation (TMS) to stimulate the motor cortex of volunteers who were watching a video of a hand. When the volunteers watched the hand's index finger move, the TMS-induced motor-evoked potential (MEP) was greater in the abductor muscle of their own index finger than when they watched the little finger move; conversely, the MEP of their little finger's abductor muscle was greatest when they watched the little finger move. In other words, a muscle showed MEP enhancement when its owner watched a movement that is normally performed by that muscle; this 'mirror effect' is thought to reflect activity of the mirror neuron system.

Half of the volunteers then underwent incongruent training trials, in which they were asked to extend their little finger if the video showed a hand extending the index finger, and vice versa. People in congruent trials simply had to repeat the movement they saw in the video. The incongruent trials were assumed to train the mirror system to associate an observed finger movement with movement of a different finger of the volunteer's own hand.

Measuring TMS-induced MEPs after training, the authors found that volunteers who had undergone the incongruent training now showed greater MEPs in the muscle of one finger when watching the 'wrong' finger move in the video, indicating that a reversal of muscle-specific MEP enhancement during action observation had taken place.

This study shows that the 'mirror properties' of the mirror system are not innate. Rather, they can be trained, through sensorimotor experience, to transform observation into action. These findings imply that insufficient social interaction and consequent inadequate sensory experience might affect the development of the mirror neuron system, for example, in children with autism.

Self-Referential Cognition in Autism

Individuals with autism spectrum conditions (ASC) have profound impairments in the interpersonal social domain, but it is unclear if individuals with ASC also have impairments in the intrapersonal self-referential domain. Lombardo et. al. give an interesting introductory discussion of the "absent self" model of Frith. They then evaluate performance of 30 subjects and:

"conclude that individuals with ASC have broad impairments in both self-referential cognition and empathy. These two domains are also intrinsically linked and support predictions made by simulation theory. Our results also highlight a specific dysfunction in ASC within cortical midlines structures of the brain such as the medial prefrontal cortex."

Figure:. Image showing the overlap in peaks of activation from studies of self-referential cognition, other-referential cognition, and theory of mind within the medial prefrontal cortex and posterior cingulate/precuneus.

Boundaries are 16mm from within midline. All peaks are taken from exemplary studies in the literature. Brain is depicted on a representative sagittal slice of the Montreal Neurological Institute (MNI) template

Savant Autism - part 1

I thought this two part sequence on autism was worth passing on....

Savant Autism - part 2

An Autistic Savant - The Living Camera

Steven is an autistic savant living in London who did not speak until he was five and now has great difficulty with language as an adult. When he was eleven he drew a perfect aerial view of London after flying over it only once. Here is a windows media player movie describing his Rome flyover and drawing.

A "mind reading" prosthesis for autistic people?

Another clip from the NYTimes Magazine "Ideas" issue:

"The Emotional-Social Intelligence Prosthesis, developed by Rana el Kaliouby and Rosalind Picard, consists of a small camera mounted on a cap or glasses that monitors a conversation partner’s facial expressions and feeds the data into a hand-held computer. Software tracks the movement of facial features and classifies them using a coding system developed by the psychologist Paul Ekman, which is then correlated with a second taxonomy of emotional states created by the Cambridge autism researcher (and Ali G cousin) Simon Baron-Cohen. Almost instantaneously, the computer crunches each raised eyebrow and pucker of the lips, giving a whispered verdict about how the person is feeling. (Another version of the device, meant to be used separately, points back at users, allowing them to better understand — and perhaps modify — the face they present to the world.)" (CLICK to enlarge image below).

A striking difference in brain function in autism: Failure to deactivate.

Kennedy et al report interesting functional magnetic resonance imaging (fMRI) data on normal compared with autistic brains. From their article:

Internally directed processes, such as self-reflective thought and most higher-order social and emotional processes, consistently activate a medial cortical network involving several brain regions, namely, the medial prefrontal cortex (MPFC) and adjacent rostral anterior cingulate cortex (rACC), posterior cingulate cortex (PCC), and precuneus (PrC). Interestingly, this network is active when normal subjects are passively resting, leading many to speculate that these internally directed thoughts dominate the resting state. Self-reports from subjects while at rest further support this interpretation, wherein they typically describe "autobiographical reminiscences, either recent or ancient, consisting of familiar faces, scenes, dialogues, stories, and melodies". Conversely, activity in this midline "resting network" is reduced when subjects perform externally directed, attention-demanding, goal-oriented tasks (such as the Stroop task or math calculations), and the resulting "deactivation" of this network is thought to be an indicator of an interruption of ongoing internally directed thought processes. Thus, measuring deactivation provides a means by which rest-associated functional activity can be quantitatively examined.

Applying this approach to autism, Kennedy et al found that the autism group failed to demonstrate this deactivation effect. Furthermore, there was a strong correlation between a clinical measure of social impairment and functional activity within the ventral medial prefrontal cortex. They speculate that the lack of deactivation in the autism group is indicative of abnormal internally directed processes at rest, which may be an important contribution to the social and emotional deficits of autism.

Autistic children insensitive to emotional expressions in others also show decreased activity in their brain's 'mirror neuron' system.

Systems of mirror neurons in our brains are active during our actions and feelings and also when we observe those actions or feelings in others (see the Feb. 9 posting in this blog). Dapretto et al. now show that mirror neuron system activity during observation of emotional expressions in typically developing children is much greater than in autistic children. This suggests that a dysfunctional mirror neuron system may underlie the social deficits observed in autism.

Legend: Mirror neuron system activity during observation of emotional expressions. The right pars opercularis showed significantly greater activity in typically developing children than in children with ASD (t > 1.83, P < 0.05, small volume corrected). Credit: Nature Neuroscience

Mirror or Empathy Neurons, the DNA of psychology?

Our brains have multiple mirror neuron systems that are active not only during our own actions and emotions, but also when we are observing similar actions, emotions, or intentions in others.

Quoting V.S. Ramachandran : "Researchers at UCLA found that cells in the human anterior cingulate, which normally fire when you poke the patient with a needle ("pain neurons"), will also fire when the patient watches another patient being poked. The mirror neurons, it would seem, dissolve the barrier between self and others. [1] I call them "empathy neurons" or "Dalai Llama neurons". (I wonder how the mirror neurons of a masochist or sadist would respond to another person being poked.) Dissolving the "self vs. other" barrier is the basis of many ethical systems, especially eastern philosophical and mystical traditions. This research implies that mirror neurons can be used to provide rational rather than religious grounds for ethics (although we must be careful not to commit the is/ought fallacy)."
See: Grasping the Intentions of Others with One's Own Mirror Neuron System
Marco Iacoboni et al. 2005.

Quoting from the Jan 10, 2006 NYTimes article "Cells that Read Minds" by Sandra Blakeslee , an interview with the discoverer of mirror cells:

"We are exquisitely social creatures," Dr. Rizzolatti said. "Our survival depends on understanding the actions, intentions and emotions of others."

He continued, "Mirror neurons allow us to grasp the minds of others not through conceptual reasoning but through direct simulation. By feeling, not by thinking."

The discovery is shaking up numerous scientific disciplines, shifting the understanding of culture, empathy, philosophy, language, imitation, autism and psychotherapy.

Everyday experiences are also being viewed in a new light. Mirror neurons reveal how children learn, why people respond to certain types of sports, dance, music and art, why watching media violence may be harmful and why many men like pornography.