An Aha! moment for touch sensitivity in autism?

The social symptoms get all the press in autism, but the sensory symptoms may be the most important.   Now researchers are narrowing in on how those symptoms arise.

         “Where is fancy bred?  In the heart or in the head?”

One day you turn on your TV and find the picture is filled with static.  What is happening?

There are two big possibilities.  Perhaps there’s a problem with your TV itself, in which case you need to call for TV repair.

But maybe there’s a problem with the signal your TV is getting – maybe the antenna is askew, the satellite dish is blocked, or the cable is on the fritz.   In this case, the solution is to call your provider, not waste your time with TV repair.

Now researchers have found that in at least one kind of autism, the problem begins in the signal itself.   They added a gene associated with Rett Syndrome the touch receptor cells of mice.  These mice had ‘normal’ brains, but “autistic”  touch receptors.   And this alone was sufficient to trigger the sensory symptoms.

It will be fascinating to see if how much this holds up across the rest of the autistic spectrum.

An important ray of hope, thanks to:   Autism may affect not just brain but sensory nerves, mouse study suggests

Can MDMA help the autistic—and other medically underserved populations—cope with their anxiety?

“Psychologist Alicia Danforth invited a dozen or so autistic adults to a treatment room at the Harbor-UCLA Medical Center.”
“Autistic MDMA users had a distinct way of talking about newfound mental clarity. They said things like, “My thoughts straightened out,” “I had laser focus” or “the thought loops stopped.” They usually described it as something very pleasant or very rare, a kind of inner calm and a break from a lot of mental chaos.

 

Neurons have WiFi!?! Electric fields used to send signals in the brain

wifiscream

Unbelievable results out of Case Western’s Neural Engineering Center.

Authors observed brain waves moving very unusually slowly – just a tenth of a meter per second.   That’s incredibly slow compared to other nerves which can conducted signals as fast of 432 km/h or 275 miles per hour!

As scientists struggled to understand what could be propagating these signals, they ruled out all known transmission mechanisms: synapses, gap junctions, and diffusion.  Their astonishing best guess:  that the signals are being sent directly through the electric field!

We’ve long known that neurons can send signals through axons, the “wires”.   But if Case Western’s geniuses are right, then neurons also have “wireless”.    They can literally communicate, cell-to-cell, through the electric field!

If true, this would be a genuine Game-Changer for our understanding of communication in the brain.

This puzzle piece, submitted for your approval:   “Can Neural Activity Propagate by Endogenous Electrical Field?” (Chen Qiu, Rajat S. Shivacharan, Mingming Zhang, and Dominique M. Durand)

 

 

MacGuyvering a Stuck Switch: GABA functioning restored in Rett Syndrome neurons

260px-Apollo16LM

The first men on the moon almost didn’t make it home – all because of a stuck switch.

While heading out for a moonwalk, Buzz Aldrin accidentally bumped the control panel, breaking off a  switch.   No just any switch, either.   It was a very important switch, specifically the one that that powered the engines – the very engines they were relying on to get them back home.   The switch was now stuck.  If they didn’t fix it, they would die on the moon sitting atop a rocket that couldn’t be ignited.

With ingenuity that would make MacGuyver proud,  the astronauts found a solution.   They able to restore functioning to the stuck switch – using a felt-tipped pen.

Now scientists have discovered the genetic ‘stuck switch’ is behind Rett syndrome.  And these molecular MacGuyvers have even figured out a way to restore functioning to the affected systems.


InRodWeTrustRett syndrome,  an autism-like condition, is caused by mutations in the gene MECP2 (methyl CpG binding protein 2).   The protein MECP2 is present in the nucleus where is involved in switching other genes on or off (via the process of DNA methylation.)

One of the genes regulated by MECP2 is the Cloride potassium supporter (KCC2) which is found in neurons.    Scientists took cells from patients with Rett’s, turned them into stem cells, and then turned those stem cells into neurons.    Unlike control neurons, the neurons from patients with Rett’s exhibited a lack of KCC2. This lack of KCC2 delays the switch of the neurotransmitter GABA from having an excitatory  role to an inhibitory role.

In this study, overexpression of KCC2 restored the GABA functioning.  Researchers used insulin-like growth factor 1 (IGF1) which increased the levels of KCC2, thus restoring GABA function. This leads the authors to speculate  that “restoring KCC2 function in Rett neurons may lead to a potential treatment for Rett syndrome.”

This piece of the puzzle brought to you by: “KCC2 rescues functional deficits in human neurons derived from patients with Rett syndrome

Deep brain stimulation in the basolateral amygdala improves symptoms of autism

Amygdala

A 2012 case study reports that “Deep Brain Stimulation in the basolateral amygdala improves symptoms of autism and related self-injurious behavior

A team from Germany reports on the case of a 13-year old boy with autism who was engaging in life-threatening self-injurious behavior.    Doctors implanted a stimulator that could provide inputs to multiple different brain sites (“the paralaminar, the basolateral (BL), the central amygdala as well as the supra-amygdaloid projection system”).

After the surgery, no improvement was seen – at first.   But then they turned on the stimulator.

Parents and clinicians found that stimulating one of those sites, the basolateral amygdala, improved a wide variety of symptoms associated with autism.

The patient experienced a marked decrease in self-injurious behavior.   AND what’s more, he experienced improvements in social behavior,  emotion regulation, and sleep cycle regulation.

After 6 months, he began to utter single words (“Papa”, “Mama”) or sing along with music — actions that would have been impossible before the stimulation.

His dosage of Abilify  could be reduced, his dosage of Lorazepam eliminated.

Researchers conclude that “the amygdala has an important part in the etiopathogenesis of autism” and that the basoloateral nucleus of the amygdala “appears to be pivotal”.    Not only did they find the deep-brain stimulation  to be effective, but they also found it “did not evoke any side-effects”.

 

Another  brick in the wall, thanks to:

Sturm V, Fricke O, Bührle CP, Lenartz D, Maarouf M, Treuer H, Mai JK and Lehmkuhl G (2013) DBS in the basolateral amygdala improves symptoms of autism and related self-injurious behavior: a case report and hypothesis on the pathogenesis of the disorder. Front. Hum. Neurosci. 6:341. doi: 10.3389/fnhum.2012.00341

The painful squeal of chalk on a blackboard

#ds31 - Nails on a Chalk Board

The squeal of chalk on a blackboard” feels painful to almost everyone.   Scientists speculate that nails screeching on a blackboard sounds like primate distress calls.

But for many people with sensory processing difficulties, the hiss of running water or the roar of a vacuum cleaner can sound just as unpleasant as nails on a blackboad.   So maybe it makes sense to look at just how typical brains decide nails on the chalkboard is such a painful sound.  Maybe the same equipment is involved in autistic sensory pain to noises.

To learn about the processing of painful (“aversive”) sounds, we turn to:

A Dynamic System for the Analysis of Acoustic Features and Valence of Aversive Sounds in the Human Brain

Sukhbinder Kumar, Katharina von Kriegstein, Karl J. Friston,and Timothy D. Griffiths

Researchers had previously found that a spectral analysis of a sound could predict its relative unpleasantness.   Now they embarked on an even greater adventure — to see if this spectral analysis could be used to predict functional MRI data of people listening to painful sounds.

Dynamic Causal Modeling of misophonia 2

First fMRI was acquired from 13 subjects as they listened to 74 different sounds.  Subjects rated each sound on its unpleasantness.

Analysis revealed activity in both amygdala were correlated to the acoustic features, but only the  right basolateral amygdala was found to be correlated to the unpleasantness of the sound.  The authors discuss how the basolateral nucleus acts as the amygdala’s “sensory interface”, receiving signals from the both the auditory thalamus and the association areas of the auditory cortex“.

Acoustic features correlated with activity in the auditory cortex (specifically the anterior Superior Temporal Gyrus and the “upper bank” of the Superior Temporal Sulcus).     The unpleasantness of the sound was correlated only with the right Superior Temporal Gyrus.

Dynamic Causal Modeling of misophonia 1
Red = Acoustic features , Blue = Valence

 

Researchers conclude that the audio signal is first processed  in the auditory cortex (superior temporal gyrus), after which it is passed to the amygdala which evaluates the signal’s unpleasantness.    That value judgment is the passed back to the auditory cortex.

Why do the vacuum cleaners or showers elicit fear or pain in people with sensory issues? If it’s for similar reasons to chalkboard scraping, then perhaps we should look to the right basolateral amygdala.