MINOR, Lloyd, LABYRINTH and Balance, June 6, 2013

this is the last 2012-2013 Bio-X seminar of the academic year:

organizer is Channing Roberts;  mentions wanting to get
an inner ear exam and winding up on the colonoscopy table  (big laugh);

introduction by John...  (in ENT);

Lloyd Minor is Dean of the School of Medicine... 
 I chat with him before seminar begins...
mainly does admin now... hard to do research. also.
He was prev.  Provost at Johns Hopkins...

he begins:
when undergrad at Brown... became interested in math models ....

our understanding of balance disorders is primitive
 (compared to the auditory system);
hard to test it...

he is from the South (? Arkansas)

Vestibular Disorders:

vertigo caused by vestibular disorders occurs in 7% of people at some time during their life.

more than 2M Americans fall every year.  
symptoms of  vestibular-based fall are present in 80% of people who fall..

abt 50% of people over age 70 have had at least one episode of BPV.= beingn positional vertigo.

Meniere  200 cases per 100k in USA...

vestibulo-oculo reflex.... = VOR

it maintains steady gaze during head movements...

eg  move head to the R  and keep eyes  on target

fovea is only abt 5% of area of retina...  must keep images v stable on the fovea...

he shows a video... 
put a cheap video camera on driver's head on bumpy road... it's really bumpy!
(this gives you an idea of what the VOR is accomplishing: image stabilization despite head/ eye mvmts)

eyes move oppositive and compensate for head mvmt to adapt 

Overview:   insights from  RESEARCH on vestib disorders provided
new direction for clinical research...

The vestib apparaturs is located deep inside petrous  formation...
entire thing is abt the size of a dime!!!

superior semicircular canal  and  horiz  canal  and posterior canal  (that is in vertical plane)

senses acceleration  for head mvmts...

otolith organs  detect  translation motion and gravitational motion....

when at Hopkins was interested in Rapid Head Movement Test
move head to R and eyes drift back to the left...

impaired in vestibular Schwanoma... or vestib  neuritis  or aminoglycoside administration...

can lose  VOR :  first described by Michael Halagyi in 1990s...

he developed a new technique to measure the VOR:
Scleral search coil  technique

wear a contact lens with a coil in it;
 inside a  3d  oscillating magnetic field  (to induce current in the coil)

so, can record  movements of eyes...

case  66 man  1 yr after L labyrinthectomy for tumor..

he shows  lesioned side...  head mvmts 
 (no response of eyes until late when u get wild oscillations

but on intact side...  you have  almost normal gain...

gain was 0.74  on intact side

(on lesioned side it was abt 0.20 !  hugely diminshed)

does not happen with slow head mvmts  (only  with fast head mvmt)...

(with intact reflex:  the eye veloc. v nicely tracks the head movement
 in amount and in time  (without any lag)

did experiments  in  monkeys... same type head mvmts in  macaques...

monkey:  (see Minor et al  j neurophys 1999)

during rapid head mvmt  gain  = 1.1  (in nl animal)  and asymptotes down to  0.8  at end of motion...

common accel is  3,000 to 12,000 degrees per sec2.

latency of  reflex is about  5 milliseconds!!!
 (fastest  reflex in the body, by far!!!!!!!!!!!)
could not be any faster... takes abt that time to get neurotransmitter across synapse...
this reflex traverse two synapses.

but  now look at  monkey  with no VOR = vestib ocul reflex...
look at animal  with  bilat lesion:
maintaining rapid gaze is totally dependent on vestibular function...
you can model it...

he shows math model:  a transfer function...

there is a TONIC  pathway (velocity) and a phasic pathway  (acceleration) 
 but subject to inhib cutoff...

input is head velocity... output is eye velocity...

records neurons...

Lasker  J neurophys  2000

squirrel monkey... post  labyrithectomy...

recovers for rotations toward intact side but not with lesioned side...

must adjust relative weighting of  phasic pathway...
 (that  accounts for  recovery of contralesional response)

5 ms  delay... v fast  reflex...
3 groups of neurons... (two synapses)

afferents to vestib  neuron  then to oculomotor nucleus then to abducens nuclei

while you exciet the agonist you inhibit the antagonist...

3  neurons  (2  synapses)... see Netter diagram...

nerve fibers that  innervate the semicircular canal
 abt 4K  afferents that innervate the horiz canal...

all  have  fast  resting discharge rate  of 80 to100 hz...

can encode  excit and inhibt.

sensory transduction:

canal has endolymph...
occluded by cupula... stereocilia...  
sheering force of  of motion of cupula  that sheers hair cells...

2 types:  type 1 and 2  hair cells.. specific organziation...

ventral zone of  calyx  strucutre  (enfold, enwrap the hair cell...
but some are bouton only  and some are dimorphic  (intermediate)

type 1 cells  with calyx-only  are irreg discharging...

adapted from Baird  in J Neuroph 1988...

regular discharging cells  are the bouton-only...

he shows  tuning curves of  3 difft morphologies of hair cells...
wrt to sensitivity and phase...
some encode  acceler, some encode velocity...

Question:
are there changes in afferent physio on the intact side following labyrith unilateral...

some effect but not enuf to account for recovery...

now look at central neurons  PVP  in vestib  nuclei...
PVP = position -vestib-pauses neurons...
eye position gets encoded,  pause is for rapid eye mvmts (or saccades)

how does physio change after labyrinthectomy...

compensation in PVP neurons...

they get neck proprioception

efference copy  is also  given to them (with volun movement of the head)

now, recording form PVP neurons...

animals body being rotated beneath the head but head is not moving...

70% of  neck sensit neurons do show better compensaiton  (more than those that do not)

clinical implication:  pts  do NOT like to move  heads... do NOT want to move head...
but these  data  suggest that head mvmt is important to promote best compensation
(ie  neck  propriocep is impt in recovery)

copy efference...

distinuishes passive mvmt vs  volitional mvmt...
tell them... go fast or slower to match the...

VOR gain  is much better with  volitional mvmt  (due to efference copy)

next look at monkeys

train monkeys to make active gaze shifts....

while recording from  PVP  neuron

(in monkeys confirmed that  PVP neurons receive and benefit frome ffer copy signal to get max VOR gain)

so,   recovery benfits from  both  effer copy signal and from neck proprioception signal...

confirms his basic overall theme:  clinical observation lead to better research  and vice versa..

****************************  new topic

begin research  in 1995... he joined  Hopkins in 1993...

oscillopsia  apparent motion of objects  that are stationary

when this 54 year old man...  had fluttering vision
 (oscillopsia when he made whistling sounds...

he shows IR  video of man...  
when a tone is played see the eye move  upward and inward tonically...

(due to R super canal  = RS  v precise  alignment btwn mvmts and canals that they innervate)

eye mvmts in patient with right SCD = superior canal dehiscence disorder...

poss due to canal dehiscence...

this was due to abnl  endolymph flow...

SCD - superior canal  dehiscence...

in 2% of bone... there is v thin  roof of  superior canal... 
that may lead to SCD  (this is NOT surgical...
it occurs spontaneously)

we saw  171 pts with SCD....  mean age was 46 years...

they had  sound induced vertigo..

how to rx it...

54 year old  ... still living with it...
but some of these sxs are   v debilitating...

he thot... mabe we can selectivley inactive just the super canal...

surgical:  he reviews tis surgery:  use a  3 cm craniotomy... 
 see dehiscence of  canal  and then they plug it...

they plug it  with fascia and with bone chips...

they then use  rapid head mvmt test...

He was Provost in 2009 at  J Hopkins... but
work in ENT  with this continues with Dr John Carey...

progress towards a 3d  vestibular  prosthesis

by Dr  Charles  Della Santina...

see Deall Santina, Migliaccio, Patel  2005... can turn it on or off  (vestib function)

must love the process of getting there (in research career) (otherwise wont get there)..
he spent 11 yars in training after med school  (with Jay Wolberg and others)...

he really does not like the term  clinical BURDEN
 to describe seeing pts in clinic by basic researchers...

Q  Chris Duffield... u showed this with yaw... does this occur   in other planes?  YES

Q  evolution of vestibular apparat... yes in lamprey and hagfish...