Reafference Cancellation in Brainstem Vestibular Neurons:
Implications for Motion Sickness Etiology
Charles M. Oman and Kathleen E. Cullen
Massachusetts Institute of Technology, Cambridge , MA 02139 USA and
Department of Physiology, McGill University, Montreal, Quebec, Canada
 Summary
Tra d itio n a l th e o rie s a ttrib u te d m o tio n sickn e ss to ve stib u la r
o ve rstim la tio n o r in te rm o d a lity se n so ry co n flict (R e a so n & B ra n d ,
1 9 7 5 , F ig 1 ). H o w e ve r, in fo rm a l m o d e ls n o w re fe rre d to a s th e
“se n so ry-m o to r co n flict th e o ry”, R e a so n ,(1 9 7 8 , F ig 2 ) a n d O m a n
(1 9 8 2 , F ig 3 ) a rg u e d th a t th e e sse n tia l co n flict m u st b e b e tw e e n
a ctu a l a n d a n ticip a te d se n so ry cu e s. Ve stib u la r e xp e cta n cy co n flict
sig n a ls co u ld a lso re su lt fro m co m p e llin g visu a l stim u la tio n (e .g .
C in e ra m a sickn e ss), a n d se rve a s e rro r sig n a ls in h e a d a n d b o d y
p o stu ra l co n tro l p a th w a ys, q u ickly trig g e rin g co rre ctive re fle xe s in
re sp o n se to p a ssive m o ve m e n t (e .g . sh ip m o tio n ). S u sta in e d
co n flicts w e re h yp o th e size d to in itia te se n so ry-m o to r le a rn in g via
ce re b e lla r in te rn a l m o d e l u p d a tin g . A ve stib u la r-e m e tic lin ka g e w a s
p o stu la te d , b u t w ith d yn a m ics to o slo w to b e a ctiva te d d u rin g n o rm a l
a ctive m o ve m e n ts. T h e th e o ry (O m a n , 1 9 9 0 ) p re d icte d th a t
ve stib u la r co n flict n e u ro n s e xh ib itin g re a ffe re n ce ca n ce lla tio n w o u ld
e ve n tu a lly b e fo u n d in b ra in ste m o r ce re b e llu m . A lth o u g h th e th e o ry
h a s b e e n w id e ly a cce p te d , e co lo g ica l p sych o lo g ists (e .g . S to ffre g e n ,
1 9 9 1 ) d e b a te d th e e xiste n ce o f in te rn a l m o d e ls a n d e xp e cta n cy
co n flict sig n a ls. O th e rs a rg u e d th e e sse n tia l co n flict w a s n o t a t th e
first sta g e o f ve stib u la r p ro ce ssin g , b u t re la te d to co n flicts b e tw e e n
th e se n se d a n d p e rce ive d ve rtica l (B le s,1 9 9 8 ) .
R e ce n t p h ysio lo g ica l stu d ie s in a le rt b e h a vin g rh e su s p rim a te s
co m p a rin g th e re sp o n se s o f ve stib u la r u n its in b ra in ste m a n d
ce re b e llu m (F ig s 4 -6 , C u lle n a n d co w o rke rs, 2 0 0 1 , 2 0 0 4 , 2 0 0 9 , 2 0 1 2 ,
2 0 1 3 ) h a ve sh o w n th a t d u rin g a ctive m o ve m e n t, ve stib u la r in p u t
(“re a ffe re n ce ”, vo n H o lst, 1 9 5 0 ) is ca n ce lle d a t th e first sta g e o f
b ra in ste m p ro ce ssin g , In th e b ra in ste m , th e ca n ce lla tio n is b e lie ve d
to re su lt fro m “e ffe re n ce co p y” sig n a ls o rig in a tin g in a ce re b e lla r
“in te rn a l m o d e l” (F ig 7 .) th a t n o rm a lly p re d icts th e ve stib u la r se n so ry
co n se q u e n ce s o f se lf-g e n e ra te d m o ve m e n t. T h e se n e u ro n s a re
b e lie ve d to p a rticip a te in re fle x sta b iliza tio n o f th e h e a d a n d b o d y
d u rin g p a ssive m o ve m e n t, w h e re a s th e re a ffe re n ce ca n ce lla tio n
p e rm its u n im p e d e d a ctive m o ve m e n t. T h e y a lso p ro je ct to ve stib u la r
th a la m u s a n d o n to co rte x a n d m a y co n trib u te to o rie n ta tio n a n d
m o tio n p e rce p tio n . O th e r cla sse s o f b ra in ste m a n d ce re b e lla r
ve stib u la r n e u ro n s h a ve b e e n id e n tifie d th a t h e lp sta b ilize g a ze , a n d
co n trib u te to a u to n o m ic o rth o sta tic re g u la tio n , b u t th e y d o n o t e xh ib it
th e sa m e typ e o f re a ffe re n ce ca n ce lla tio n .
In th e co n te xt o f th e m o tio n sickn e ss se n so ry-m o to r co n flict th e o ry, it
m a ke s se n se to p ro p o se th a t p ro lo n g e d stim u la tio n o f th e se u n its
a lso ca u se s n a u se a a n d vo m itin g . W e e xp e ct th a t o th e r typ e s o f
“se n so ry re a rra n g e m e n ts” ca n b e sh o w n to a ctiva te th e se n e u ro n s.
U ltim a te ly it w ill b e e sse n tia l to sh o w th a t th e y p ro je ct to a d ja ce n t
b ra in ste m a re a s im p lica te d in n a u se a a n d vo m itin g (e .g . P B N a n d
LT F, Ya te s a n d co w o rke rs, 2 0 1 2 ,), a n d a ssu m in g th e y d o , w h a t th e
p h ysio lo g y a n d p u rp o se o f th e lin ka g e is.
Fig. 1: In te rm o d a lity S e n so ry C o n flict
H yp o th e sis (R e a so n a n d B ra n d ,
1 9 7 5 ).
Supported in part by the National Space
Biomedical Research Institute
through NASA NCC 9-58
Fig. 2: “N e u ra l M ism a tch ” M o tio n
S ickn e ss M o d e l (R e a so n 1 9 7 8 )
b a se d o n R e a ffe re n ce P rin cip le (Vo n
H o lst, 1 9 5 0 ) a n d a sch e m a p ro p o se d
b y H e ld (1 9 6 1 ).
Fig. 3: C o m p u ta b le “O b se rve r” M o d e l fo r
P o stu ra l C o n tro l, S e n so ry E xp e cta n cy
C o n flict a n d E m e tic L in ka g e (O m a n ,1 9 9 0 ,
1 9 9 1 ).
+
+
.
x
ne
B
+
u
x
∫ dt
+
S
+
na
Body and sense organs
CNS Orientation Estimator
& Movement Controller
Sensory conflict
Emetic linkage
+
a
A
Re-identification of ˆA, ˆB,ˆ S
Re-calculation of K, C
ˆ
B
m
-
C
ˆ
x
+
xd
∫ dt
Fig 5: R e a ffe re n ce C a n ce la tio n in R h e su s
B ra in ste m O to lith V O N e u ro n s (C a rrio t &
C u lle n , 2 0 1 3 )
ˆ.
x+
+
+
K
K
(60s +1)2 +
+
+
c
-
K
(600s+1)2 +
+
ˆ
A
ˆ
S
Fig 4: R e a ffe re n ce C a n ce la tio n in R h e su s
B ra in ste m S e m icircu la r C a n a l V O (“Ve stib u la r
O n ly”) N e u ro n s (C u lle n e t a l 2 0 0 9 )
cTT c
aˆ
G I, C T Z in p u ts
Fig 6: R e a ffe re n ce C a n ce la tio n in R h e su s
C e re b e lla r R o stra l F a stig ia l N u cle u s U n im o d a l
C e lls (B ro o ks & C u lle n 2 0 1 3 )
C u lle n e t a l (1 9 9 9 ,
2 0 0 4 , 2 0 0 9 ) sh o w e d
th a t a ctive a n d
p a ssive re sp o n se s
o f rh e su s m o n ke y
•
se m icircu la r
ca n a l a ffe re n ts
(le ft co lu m n ) a re
id e n tica l, b u t
•
b ra in ste m
“Ve stib u la r-O n ly”
(V O ) n e u ro n s
(rig h t co lu m n )
re sp o n d o n ly to
p a ssive
m o ve m e n t.
Fig 7: H yp o th e size d M e ch a n ism fo r R e a ffe re n ce
C a n ce la tio n via ce re b e lla r in te rn a l m o d e l (C u lle n , 2 0 1 2 )
M o to r co m m a n d to n e ck m u scle
ca u se s n e ck p ro p rio ce pto r a n d
ve stib u la r re a ffe re n ce .
•
•
•
After: Cullen TINS 2012
Neural mechanism for
vestibular reafference
cancellation:
References
Corollary discharge
Internal Model
Efference copy
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In te rn a l m o d e l e m p lo ys
p ro p rio ce ptive cu e s a n d m o to r
co m m a n d to p re d ict e xp e cte d
ve stib u la r sig n a l (e ffe re n ce co p y).
•
E ffe re n ce co p y ca n ce ls re a ffe re nce,
so V O n e u ro n s p rim a rily re sp o n d to
p a ssive co m p o n e n t o f b o d y
m o ve m e n t (“e xa fferen ce ”).
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