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For today's episode, we will talk all about Audition.
This will be an episode about autism and the
auditory processes. We should begin in 1961 from
Von Bekesee, who's a Nobel winner prize in Physiology
or Medicine, and he was a biophysicist. In the
spiral cochlea, it's a fluid -filled tunnel about
the width of pencil lead, and sound is not simply
just vibrate the entire structure uniformly.
Instead it generates a traveling wave along the
basilar membrane which is a 35 millimeter ribbon
type that varies in stiffness from its base to
its apex. High frequency sounds such as a whistle
at 8 ,000 hertz cause the waves to peak near
the stiff narrow base within 0 .3 milliseconds
of entering this oval window. Low frequency sounds
like the deep bass drum at 100 hertz. Travel
the length to the peak at the floppy and the
wide apex near the helicotrema. I know, lots
of dense and strange words here, but we're going
to make it. This mechanical frequency The separation
is a tonotopy. Motion is the first act of the
auditory coding. At the wave's peak, thousands
of little hair cells bend in unison, while outer
hair cells powered by electromotility amplify
the motion by up to one thousand fold. While
the inner hair cells transduce it into neural
signals via glutamate, which remember is excitation,
at a ribbon synapsis onto type 1 spiral ganglion
neurons. This is a lot, but we're going to parse
this out into different kind of sections and
understanding. This process occurs within one
millisecond of sound onset. The stria vascular,
a three layered Epithelial structure lining the
lateral wall is the underrated process, unknown
process of hearing. This biological battery generates
the plus 80 millivolt endocochlear potential.
This is the highest DC voltage in the entire
human body. This potential is not just a passive
by -product but an actively maintained electrochemical
gradient essential for auditory sensitivity.
The endo -limp that bays in the hair cells contains
150 millimolar potassium ions and sits at plus
80 millivolts while the pero -limp has only 5
millimolar of potassium ion and is only plus
5 millivolts. Big contrast there. The hair cell
interior rests at negative 70 millivolts and
thus a total driving force across the gradient
is plus 150 millivolts and this enables the potassium
ion to rush through mechanically gated channels
with explosive speed upon deflection. This ion
influx depolarizes the inner hair cells and triggers
a calcium -dependent glutamate. Remember excitation
release at this so -called ribbon synapsis. There's
lots of melanin here. The stria's marginal cells
secrete the potassium ions in specific channels
and the intermediate cells. These so -called
melanocytes that we're going to get into buffer
ions and provide antioxidant protection and transduction.
And the basal cells pump out this potassium ion
in a sodium potassium chloride co -transporter.
Remember the episode with Dr. Ezekiel Ben -Ari.
He's talked about these so -called pumps in quite
detail with the excitation and inhibition cells.
This is what we're going to talk about a lot
because once again, the autistic phenotype is
loaded with this excitation and inhibition. mismatch,
this imbalance. There's lots of melanin here
in the stria vascularis. See, Jack Cruz on this,
he really highlights this better than anybody,
I think, with melanin's role in auditory processes.
This is a bioelectrical gradient that powers
hearing transduction, a place of semi -conduction
with little blood brain barrier. So that means
There's lots of water here. See Decentralized
Medicine 36 from Cruise's Patreon. Cruise's Patreon
is probably the best $5 you can spend per month.
Water is the key player here. It's a silent medium.
Endo Lymph is 99 % H2O. This serves as both a
solvent for the ion transport and hydraulic medium
for the traveling wave. Without this water -based
potassium ion, melanocyte stabilized 80 plus
millivolts of bioelectrical gradient. There is
no cochlear amplifier. There is no sound or wave
transduction. There's no movement. There's no
hearing, only silence. From the cochlea, the
signal races up to the eighth cranial nerve.
as glutamate driven action potentials by only
1 .6 milliseconds. The distal eighth nerve generates
auditory brainstem response wave one. We have
a little whiteboard series on auditory brainstem
responses. Remember wave one is the first wave
and this is recorded via EEGs on the scalp. by
2 .7 milliseconds, the proximal nerve fires wave
two. And the first central synapse occurs in
the cochlear nucleus, where bushy cells in the
ventral division, the ventral cochlear nucleus,
we mentioned this in the video, receive N bulb
of held inputs and phase lock them to sound cycles
below three kilohertz. And this is preserving
time differences. Meanwhile, during this process,
destilete cells. Remember the star -shaped shells
we talked about in many columns? They're only
in layer four of the many columns. These are
cells that are shaped like stars. These release
GABA to create sideband inhibition and sharpen
the frequency tuning in the dorsal cochlear nucleus.
Fuciform cells integrate spectral cues while
cartwheel cells use GABA to suppress the echoes.
GABA is inhibition. So, we need this to suppress
echoes and this is the excitation inhibition
balance. This is where EI comes into play most
notably. Glutamate drives forward GABA carves
clarity. Remember, the living organism, the human,
our default is go. So the waves coming into the
ear are wanting to go. It's the GABA that is
used here to kind of channel them and help filter
out any unwanted, unnecessary sounds. At the
superior olivary complex, and this is the first
brainstem station for this binaural processing,
this binaural hearing. The medial superior olive
uses glutamate to detect from both ears to code
the time differences with microsecond precision,
while the lateral superior olive compares level
differences. via ipsilateral glutamate excitation,
which means only one side and contralateral glycine
plus GABA inhibition from the medial nucleus
of the trapezoid body, sometimes called MNTB.
So glycine is something we haven't discussed
that much of or any. but this is acting as also
extra inhibition. Glycine is sometimes inhibition.
The calyx of held, which is the largest synapses
in the brain, ensure sub -millisecond timing.
And this is all happening before 3 .8 milliseconds.
At 3 .8 milliseconds, the auditory brainstem
response weight three. reflects this superior
olive complex activity. And then the medial nucleus
of the trapezoid body to the lateral superior
olive pathway will co -release glycine, which
is fast acting, and GABA, which is more slower
acting, to shape and balance the excitatory and
inhibitory profile. which is critical for sound,
localization, and noise. When you speak, the
brain activates the medial olivocochlear reflex
via a corollary discharge from vocal motor areas.
Corollary discharge is something in sensations,
sensory neurons, sensory processes that is providing
some prediction. so your sensory organs can predict
kind of what happens next. They can be on alert
and be prepared. This is big with the superior
colliculus to the frontal eye fields as well
for vision. The medial olivocochlear efferents
release acetylcholine and this is very fast acting.
Angaba for more sustained inhibition. This is
hyperpolarizing them and reduces cochlear gain
by 10 to 20 decibels. This prevents self -defining
and allows you to hear others. The lateral olivocochlear
system will activate during listening and use
GABA to inhibit various dendrites and unmask
speech transients in background noise. This efferent
feedback is the first line of defense against
listening dissonance. We'll parse out listening
dissonance in a little bit. Upwards to the midbrain,
the inferior colliculus. The auditory hub. Remember
inferior colliculus is to auditory as superior
colliculus is to vision. These are relay stations.
The inferior colliculus receives 95 % of ascending
fibers. In humans, one inferior colliculus contains
approximately 13 .5 million cells, and 40 % of
these are disc -shaped excitatory neurons. 9
% of these are cellette cells, the star shapes,
and 18 % are gabaergic. Out of the 18 % GABAergic,
a majority of those are parvalbium interneurons.
And then about half of many are somatostatin
interneurons, and only roughly 2 % of those are
vaso -intestinal peptide, the VIP. And then the
inferior colliculus also has about 30 % glia
cells. By 5 .6 milliseconds, the ABR, auditory
brain stem response wave 5, marks the first inferior
colliculus spike and is specifically from the
central nucleus of the inferior colliculus. Glutamate
from the lateral laminscus activate the noise
while GABAergic from local interneurons creates
duration tuning. Sideband suppression, so background
noise and this EI response. High gamma oscillations
of 70 to approximately 150 Hertz emerge here.
So typically in sensory processing, gamma is
risky and a lot of autistic phenotypes live in
gamma. But in hearing, gamma is required because
high gamma oscillations reflect local computation.
So we're in the midbrain. Remember the inferior
colliculus. Okay, the relay station for auditory.
Remember the midbrain, the inferior colliculus,
and the superior colliculus for vision. They
are spatially relationship here. They can just
reach out and high five the thalamus. The medial
geniculate body of the thalamus receives the
auditory. This is the relay station for the thalamus.
Okay. So from the inferior culliculus to the
medial geniculate nucleus, we're looking at now
we're at six to upwards to nine milliseconds.
Myelinated axons of the inferior culliculus carry
glutamate signals up. Remember just to high five
each other. The fusion tensor imaging Remember
we've we've talked about this with sensory processing
measurements and distal connection measurements.
Diffusion is just nerd speak for movement. DTIs
use a fractional antitrophy or FA and this measures
0 .55 to 0 .65 in neurotypicals but a decrease
in the autistic phenotype due to reduced myelination.
The ventral division of the medial geniculate.
Remember, ventral is bottom or floor, basement
type of thing. So it makes sense that inputs
are going to come in here because the inferior
colliculus is just below. So inputs are coming
in and multisensory kind of begins. The thalamic
reticular nucleus uses the GABAergic to sculpt
out the thalamic output. Measurement instruments
here reveal huge things about the autistic phenotype.
Auditory brainstem response can use EEGs and
it shows the wave 5 delay in the autistic phenotype.
MEGs captures reduced 40 Hz gamma. Remember in
auditory you want gamma to be higher so you can
help filter out because everything is so fast
acting. You need a lot of power here. EEG tracks
increased alpha effort. Event related potentials
show an increase in N400 mismatch. Remember N400
means roughly at 400 milliseconds, so we're much
downstream from here, but these measuring instruments
are just kind of highlighting distal connections,
the overall complete auditory processing. FMRI
maps the medial prefrontal cortex hyperactivity
and the diffusion tensor imaging that FA reveals
a reduced white matter integrity. the inferior
colliculus to the medial geniculate nucleus so
that's very close but there's already a reduced
white matter track right there. So in the neurotypicals
these systems are harmonized and glutamate drives
that while GABA the inhibition sculpts out powers
and unwanted noise. The auditory sector of the
thalamic reticular nucleus, which is a thin GABAergic
shell around the medial geniculate body, gets
thalamic output and suppressing irrelevant frequencies.
Remember the shell that is the thalamic reticular
nucleus. This is all inhibition and has crucial
roles for sensory gating and modulating signal
to noise control. The TRN here is suppressing
irrelevant or steady background sounds while
amplifying sudden or attended sounds. Noises
that you want to hear that you're sending your
attention to. This is kind of assisting you with
that. And this helps with selective attention
as well. In auditory, the thalamic reticular
nucleus is like noise -cancelling headphones.
For all of the wild and uncontrollable background
noise. From here, there's a kind of a system
highlighted throughout various brainstem regions
called the reticular activating system. And this
spans the brainstem and the membrane, which modulates
arousal and attention to the sound in hearing
norepinephrine and cholinergic inputs from the
locus aurelius and areas of the brainstem enhance
inferior colliculus and auditory cortex 1 responding
to alertness. So that leads us up to the thalamus.
So from the cochlear all the way up to the brainstem,
up the brainstem, and into the thalamus. We have
the auditory brainstem response, ABR. This is
something that's done in as soon as you're born
within one to three days of life before the baby
even leaves the hospital to go home. You can
do this. A recent study in 2021 by Delgado et
al had a subjects of 139 ,154 newborns in Florida,
only Florida. Every baby received routine universal
newborn hearing screening with an automated ABR,
auditory brainstem response. And years later
when preschool disability records were linked
back to those specific subjects in the study,
321 children who received an autism diagnosis
had already on day one, two or three of live
shown wave five latencies, prolonged by 0 .3
to 0 .5 milliseconds. Now, you might think, well,
that's not that long, but remember, it only took
us about four milliseconds from cochlear to the
thalamus. Hearing is a very powerful and fast
-acting process. That delay It's so tiny, most
clinicians wouldn't even notice it on a single
tracing. But across hundreds of thousands of
babies, it was unmistakable. There are no differences
found in wave 1, so the periphery was fine. The
problem was already central, already in the brain
stem, already present before the child ever opened
their eyes to the world or spoke their first
words. And for the first time, there was proof
that the auditory wiring differences in autism
are prenatal and that a test we had already given
in newborns in many different countries at many
different times can flag risk for the autistic
phenotype and be an early biomarker. The reticular
activating system alerts the living organism.
The thalamic reticular nucleus Fithers out noise.
And distal connections like the medial prefrontal
cortex helps predict. In the autistic phenotype,
a decrease of inhibition creates a noisy and
effortful dissonance world. Where something like
porosity is lost. And noise is pain and triggers
our threats. Sounds bland and so forth. So let's
leave this to listening dissonance. We mentioned
this in the Autistic Phenotype and the Adaptive
Responses episode about the medial prefrontal
cortex. Listening dissonance is a very uncomfortable
neural friction that arises when the brain expects
a clear auditory signal, but it's receiving a
mixture of target sounds and competing background
noises. It is not a formal diagnostic term, but
very descriptive and accurate. This moment -to
-moment struggle of extracting meaningful, expected
and wanted sounds from the environment. This
conflict begins in the cochlea, where loud noise
saturates those outer hair cells and compresses
the dynamic range and reduces the effectiveness
of that plus 80 millivolt endocochlear potential
that normally powers precise transduction but
as a result of this faint cues are lost and noises
are masked and mismatched and the auditory nerve
fires less distinctively remember i say that
in noisy environments or even if it's not that
noisy but there is just multiple sources of sound
maybe the noises and sound is functional and
at healthy ranges, but there are many of them.
Sounds will start to blend and it'll start sounding
like a late Beatles track. Maybe something off
of Sergeant Pepper's in 1967 or the White Album
in 1968. They just began experimenting with different
types of noises and instruments and then blending
all of those together. They would do this later
in the song. as the song ended and just carried
on and make these funky different noises. That's
what listening to sonnets is to me. By the time
the signal reaches the brainstem, that superior
olivary complex in the inferior colliculus attempt
to suppress the mask through sideband inhibition
and the duration tuning. Remember, this is what
Gab is trying to do. And remember the autistic
phenotype has low inhibition. If it's a seesaw,
the excitation is on the high side of the seesaw.
Inhibition is low towards the ground. And this
is a frequent phenomena with the autistic phenotype
where noise floods the central nucleus of the
inferior colliculus, which is normally good for
sharpening tunes and timing. is in a conundrum.
It's a conflict. Lots of friction here. Remember,
this is the auditory brainstem response wave
five. This is what's happening here with this
abnormal wave five. It's not the lack of hearing.
It's not a hearing loss. It's hypersensitivity.
It's blended noises. This is the big finding
with the auditory brainstem response five. Okay,
so we made it up through the thalamus and we're
projecting out signals from the thalamus to things
like the auditory cortex and we mentioned the
medial prefrontal cortex. So, the auditory cortex
is a so -called hallmark of the sonus. And this
is where it becomes unmistakable. At 40 Hertz,
gamma rhythm that normally binds syllables together
collapses and phase locking weakens. Remember
we talked about phase locking in speech and language
or should be called language and speech and the
brain loses its ability to track the speech sound
and envelope, the meaning. What should be a coherent
stream is perceived as a jumble of disconnection
and fragments. And to compensate, the brain recruits
higher order regions. Frontal alpha power increases
as a marker of heightened cognitive effort. While
the beta oscillations reflect top -down predictions
from the medial prefrontal cortex. And this attempts
to fill the gaps. The anterior cingulate cortex,
the ACC, remember which is a subdivision. a little
nuclei of the medial prefrontal cortex. This
monitors the rising prediction error. Remember,
some of the roles with the ACC, like error detection,
conflict monitoring, evaluating risk reward.
And it is attempting to sustain activation of
the dorsal medial and the ventral medial prefrontal
cortex. And this appears in fMRI. and it's kind
of lit up, that effort -related glow will intensify
with every decibel the signal -to -noise ratio
falls. In the neurotypical individual, this balanced
network can restore partially and take back control,
but they do show fatigue and even elevated cortisol
to reduce things like working memory. In the
autistic phenotype, the same noisy environment
triggers an exaggerated form of dissonance. Mainly
because of parvalbum, positive GABAergic neurons
are reduced in the inferior colliculus and the
superior olive, which is inhibitory sculpting
that is weaker. Remember, this is the rose here
as the signals are being sent up through the
brainstem to the thalamus. the luminous pathway
is already slower and less synchronous. So noise
that a neurotypical listener finds merely effortful
can become overwhelming, driving frontal alpha
power even higher and often leading to sensory
shutdown and incomplete or loss of control. At
this time, Particularly, the belt regions projecting
to the amygdala, the insula, and the orbital
frontal cortex are hyperconnected, so the unresolved
auditory signal spills into emotional circuitry.
In the background hum, or overlapping talker,
the so -called sounds coming from the environment
that are blending and are intensified, It's just
not hard to understand. It can feel threatening
or painful. I often have times where the ears
were throbbing, it seems like. And a contribution
to the higher rates of auditory hypersensitivity
and misophonia is seen in autism. Ultimately,
listening to sonas is the audible signature of
an excitation -inhibition imbalance. under load
and it explains why a classroom or a restaurant
or family gatherings and so forth can be exhausting
intolerable for some or most when the brainstem
cannot adequately filter or the cortex can't
provide top -down control and all of this noise
is just coming and coming and coming and eventually
you just can't take it I often leave things like
family gatherings and so forth. It's just too
much. The signal to noise is sort of like the
excitation inhibition. It's just too much of
the bad kind. So let's move into the auditory
cortex 1. The primary auditory cortex, sometimes
called A1, It is the first cortical station where
raw acoustic energy is transformed into neural
representations that we consciously perceive
as sound. Remember the mini -columns. Remember
the videos and the episodes about mini -columns.
So let's build up a mini -column from the auditory
cortex. Remember, each cortex, auditory, visual,
cerebral cortex, and so forth, have different
types of layers, mainly layer 4, where inputs
are received. In layer 1, there are sparse, mostly
feedback fibers. Layers 2 and 3 contain pyramidal
neurons, sending association areas and contralateral
information. This is just like we drew out in
the whiteboard series. Lots of pyramidal neurons
in layers two and three. Remember this is where
consciousness and experiences and intelligence
and so forth live in the living organism. Layer
four has in the auditory cortex small stellette
cells that receive direct thalamic input from
the ventral medial Geniculate body. The first
cortical synapses that are roughly 12 to 16 milliseconds
after sound perceived. Layers five and six have
large pyramids projecting back to the thalamus
and to the inferior colliculus and to the superior
olive and various regions of the cortex for feedback.
The differences here mainly with these different
many columns and locations is the layer 4. Stilett
excitatory cells in layer 4 receive information
from the medial geniculate nucleus that drive
these local pyramids. Pyramidal excitatory cells
in the layers 2 and 3 and 5 and 6 handle feet
forward to belt areas and perceive neuroplasticity.
How are you going to respond? How is this living
organism equipped for this input coming in? Paralbium
interneurons are found in all layers of the auditory
cortex and this delivers fast GABA inhibition
for that sharp tuning and gamma. So we have layers
and layers of inhibition to help filter out noises
at different epochs of the cochlear all the way
up through the cortex and sensory perception,
sensation perception process. Somatostatin enter
neuron, those other GABA cells are in layers
two and three and also five. This is providing
inhibition at the dendrites and during duration
of tuning. VIP cells, the vaso -intestinal peptides,
the third kind of abundant cell type for inhibition
are found in layers two and three. And this is
providing disinhibition during attention. Remember,
VIPs are disinhibition, which means stopping
the stop signals. Inhibition of inhibition. A1
is where sounds stop being vibrations and waves
and becomes perception. Remember layers two and
three. This is where our experiences and intelligence
and memories and so forth live. This sound means
this. X equals Y. These six layered gamma rhythmic
gateways that turns the inferior colliculus's
precise timing into rich and meaningful auditory
world that we experience as individual living
organisms. Everything higher in hearing, things
like language, music, emotion, attention, is
built on the foundation of A1. at about 50 milliseconds
after sound reaches the cortex. Hearing is the
most powerful thing happening in the human body.
It's bioelectric, water -mediated, and excitation
-inhibition kind of orchestra. From people like
von Beckesies, mechanical wave, to auditory cortex
1, powered by the stria, and all of those melanocytes
and melanin. or shaped by GABA's ability to filter
out, kind of channel out, while the goal signals
go, because there's a lot of goal in hearing.
With the Autistic Phenotype, the formula is easy.
There's low GABA, low gamma, and high dissonance,
and things like high misophonia. The formula
is low inhibition plus high excitation Equals
sensory overload So whenever you hear a parent
say that their autistic child is in pain from
the sound That pain is probably real remember
Katie Asher She can be seen on the telepathy
tapes and she has her own podcast. She has books
written about this She is a very active person
for the autistic phenotype. She said that her
son Houston can hear Wi -Fi, and you should very
much believe that. If you're listening to the
podcast, listening to the episode, please feel
free to leave a review or rating. In podcasting,
reviews, ratings, and downloads are huge, and
I very much appreciate your feedback. You can
contact me on X at RPS 47586 where we can have
discussions about autism or neuroscience, neurobiology
even. You can check out the YouTube channel for
all shorts, links, and clips about the videos
and you can check out the new whiteboard series
videos that I'm doing that attempt to kind of
make this stuff easier to understand because
I know that episodes are dense but I want people
to understand the autistic phenotype and I want
to be able to teach it accurately. You can email
me info .fromthespectrum Thank you for listening
to From the Spectrum Podcast.