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Anosognosia for hemianaesthesia: a voxel-based lesion-symptom mapping study
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DOI:10.1016/j.cortex.2014.08.006
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Anosognosia for hemianaesthesia: A voxel-based
lesion-symptom mapping study
Lorenzo Pia
, Lucia Spinazzola , Francesca Garbarmi , Giulia Bellan ,
Alessandro Piedimonte , Carlotta Fossataro , Alessandro Live Ili ,
Dalila Burin and Anna Berti
A B S T R A C T
B rain-dam aged p atien ts affected by h e m ia n a e sth e sia (i.e., th e loss o f tactile sen sibility on th e co n tralesio n al side o f th e body) m ay deny th eir d eficits (i.e., an osognosia for tactile deficits) ev en rep orting tactile exp erien ce w h en stim u li are delivered on th e im paired side. So far, d escriptive analysis on sm all sam p les o f p atien ts reported th a t th e in su lar co rtex, th e in tern a l/ex tern a l cap su le, th e b asal ganglia and th e periven tricu lar w hite m a tte r would su bserve ano so gn osia for h e m ian aesth esia. Here, w e aim ed at exam in in g in d epth th e a n a to m o -fu n ctio n al n atu re o f an osognosia for h e m ia n a e sth e sia by m e a n s o f a voxelw ise sta tistica l analysis. W e com pared tw o groups o f le ft hem iplegic p atien ts due to right brain d am ages d iffering on ly for th e p re sen ce/a b sen ce o f ano so gn osia for le ft h e m ian aesth esia. Our findings show ed a lesio n al clu ster confined m ain ly to th e anterio r p art o f th e putam en. A ccording to th e cu rren t a n ato m ical evid en ce o n th e n eu ral basis o f sen so ry ex p e ctan cies, w e suggested th a t ano so g n osia for h e m ia n a e sth e sia m igh t b e explained as a failure to d etect th e m ism a tch betw een exp ected and actu al ta ctile stim u lation .
1.
Introduction
A n o so g n o s ia (fro m th e G reek nosos d is e a s e a n d gnosis k n o w l ed ge; a n - /a - is a n e g a tiv e p refix) is th e la c k o f a w a r e n e s s for n e u ro lo g ic a l/n e u ro p sy c h o lo g ic a l d e ficits fo llo w in g fo c a l b ra in le s io n s . S u c h a d e n ia l b e h a v io r h a s b e e n re p o rte d s e le c tiv e ly fo r m o to r (e.g., h e m ip le g ia ), s e n s o ry (co rtic a l b lin d n e s s , h e m ia n o p ia , h e m ia n a e s th e s ia ), a n d c o g n itiv e d e ficits (se e
P rig a ta n o , 2 0 1 0 fo r a rev iew ), a n d it h a s b e e n ta k e n a s e v id e n c e o f m o d a lity -s p e c ific d iso rd e rs o f c o n s c io u s n e s s . In d eed , w h e n d iffe re n t s y m p to m s a re sim u lta n e o u s ly p r e s e n t d ue to a b r a in d a m a g e , p a tie n ts m a y b e u n a w a re o f o n e o f th e m b u t a w a re o f a n o th e r re v e a lin g t h a t th e m o n ito r in g o f d iffe re n t a s p e c ts o f b e h a v io r is u n d e rp in n e d b y d is c re te b r a in m e c h a n is m s (see B erti, L ad av as, & D ella C o rte, 1 9 9 6 fo r d e ta ils o n th is p o in t).
W ith in th e s e n s o r y d o m a in , a n o s o g n o s ia fo r h e m i a n a e s t h e s ia (h e re in a fte r AHA) is d ia g n o se d w h e n p a tie n ts are
p e rsu a d e d t h a t th e y a re still a b le to p e rc e iv e c o n tra le s io n a l t a c tile stim u li d e sp ite t h e f a c t th a t, d u rin g th e sta n d a rd n e u ro lo g ic a l e x a m in a tio n w ith e y e c lo s e d th e y n e v e r re p o rt o f b e in g to u c h e d o n t h e a ffe c te d sid e (B o ttin i e t al., 2 009; M arcel, 2 0 04; M arcel, T e g n e r, & N im m o -S m ith , 2 004; V a lla r, B o ttin i, & P a u lesu , 2 003, V a lla r, B o ttin i, & S te rz i, 2003). AHA p a tie n ts m a y a lso re p o rt a n a c tu a l t a c tile s e n s a tio n w h e n th e y s e e a s tim u lu s d eliv ered to t h e ir a n e s th e tic b o d y p a rts (Pia, G arb arin i, F o s sa ta ro , F o rn ia , & B erti, 2 0 1 3 ; R o m a n o , G an d ola, B o ttin i, & M a ra v ita , 2014). S u c h a s u b je c tiv e r e p o rt s e e m s to r e fle c t a re a l su b je c tiv e e x p e r ie n c e o f to u c h r a th e r th a n a m e re v e rb a l c o n fa b u la tio n a n d /o r a b ia s to sim p ly re p o rt w h a t is s e e n , b e c a u s e AHA p a tie n ts m a y sh o w n o rm a l p h y sio lo g ica l re a c tio n s (i.e., sk in c o n d u c ta n c e r e s p o n s e to in c o m in g stim u li d eliv ered to th e ir a n e s t h e t ic b o d y p a rt; R o m a n o e t al., 2014). In te re stin g ly , t a c tile s e n s a tio n s a ris e w h e n t h e p h y s ic a l c o u n te r p a rt is a b s e n t (Pia, G arb arin i, e t al., 2 0 1 3 ; R o m a n o e t al., 2014).
T o t h e b e s t o f o u r k n o w led g e, o n ly tw o stu d ie s h a v e d ire ctly e x a m in e d AHA (M arcel e t al., 2 0 0 4 ; S p in a z z o la , Pia, F o le g a tti, M a rc h e tti, & B erti, 2008). B o th o f t h e m d e m o n s tr a te d t h a t w h e n h e m ia n a e s th e s ia (h e r e in a fte r HA) c o -o c c u r w ith h e m ip le g ia (i.e., t h e c o m p le te p a ra ly sis o f th e c o n tr a le s io n a l sid e o f t h e b o d y; h e r e in a fte r HP), AHA c a n b e d is s o c i a te d fro m u n a w a r e n e s s o f HP (h e r e in a fte r AHP). In o th e r w o rd s, p a tie n ts c a n d e n y t h e ir c o n tr a le s io n a l s o m a to s e n s o r y d e ficits b u t n o t th e ir c o n tr a le s io n a l m o to r d e ficits a n d v ice v e rs a . A d d itio n ally , S p in a z z o la a n d co w o rk e rs (S p in a z z o la e t al., 2008) a n a ly z e d th e in d iv id u al le s io n a l p a tte r n o f fo u r p a tie n ts a ffe c te d b y AHA re p o rtin g t h a t le s io n s to th e in s u la r c o r te x a n d to th e b a s a l g an g lia w e re c r u c ia lly a s s o c ia te d to AHA (se e a lso (R o m a n o e t al., 2014) fo r s im ila r fin d in gs). It w a s su g g e ste d (S p in a z z o la e t al., 2008) t h a t b r a in d a m a g e w ou ld im p a ir t h e a b ility to d is tin g u ish b e tw e e n a n in te r n a l r e p r e s e n ta tio n o f th e s e n s a tio n a n d t h e a c tu a l p e r c e p tio n o f th e p h y s ic a l s tim u lu s. T h e fa ls e b e lie f o f b e in g still a b le to p e rc e iv e t a c tile s tim u li w ou ld a ris e fro m th e in t a c t b r a in a c tiv ity w ith in sp a re d a r e a s o f th e s o m a to s e n s o r y sy s te m .
In t h e p r e s e n t p a p er, w e a im e d a t o b ta in in g a c le a re r a n a to m ic a l p ic tu re o f AHA in o rd er to b e tt e r u n d e r s ta n d th e n a tu r e o f t h e u n a w a r e n e s s b e h a v io r. A s first, w e co m p a re d th e le s io n a l p a tte r n s o f g ro u p s o f rig h t b r a in d a m a g e d p a tie n ts d iffe rin g o n ly fo r t h e p r e s e n c e /a b s e n c e o f AHA. S e co n d ly , on th e b a s e s o f th e a n a to m ic a l p a tte r n w e d raw in fe r e n c e s a b o u t th e fu n c tio n a l m e a n in g o f t h e d a m a g ed a re a s .
2.
Materials and methods
2.1.
Participants
W e re tro s p e c tiv e ly s e le c te d t h e p a rtic ip a n ts o f o u r stu d y fro m a s e r ie s o f s tro k e p a tie n ts w ith rig h t h e m is p h e r ic le s io n s (d o c u m e n te d b y c o m p u te riz e d to m o g ra p h y ) a n d n o h is to ry o f s u b s ta n c e a b u se /p re v io u s n e u ro lo g ic a l d is e a s e s , a d m itte d to d iffe re n t re h a b ilita tio n c e n te r s fro m 2005 to 2 0 1 3 . T h e p re re q u is ite to b e in clu d e d in t h e stu d y w a s t h e p r e s e n c e o f HA. A d d itio n ally , in o rd er to fo c u s e x c lu siv e ly o n th e n e u ra l c o r r e la te s AHA, p a tie n ts a ffe c te d b y AHP w e re n o t in clu d e d . A s a re s u lt, tw e n ty -s e v e n p a tie n ts (te n w o m e n ) a ffe c te d b y HA
(s ix te e n w ith a n d e le v e n w ith o u t AHA), p a rtic ip a te d in th e stu d y a p p ro v ed b y t h e lo c a l e th ic c o m m itte e a fte r sig n in g a w r itte n in fo r m e d c o n s e n t. In o rd e r to p e r fo rm t h e a n a to m ic a l c o m p a r is o n s , HA p a tie n ts w e re d ivid ed in to th r e e su b g ro u p s: th o s e w h o su ffe re d fro m HP (h e r e in a fte r HA_HP grou p ; n = 11), th o s e w h o su ffe re d fro m b o th HP a n d AHA (h e re in a fte r AHA_HP group; n = 11), a n d th o s e w h o su ffe re d fro m AHA o n ly (AHA group; n = 5). T h e th r e e gro u p s did n o t d iffe r (M an n W h itn e y U T e s t o r S tu d e n t's t te s t) in te r m s o f age (AHA = m e a n 69, SD = 7.54; AHA_HP = m e a n 6 5 .7 2 , SD = 7.86; HA_HP = m e a n 6 4 .0 9 , SD = 1 3 .4 1 . AHA us AHA_HP, p = .61; AHA us HA_HP, p = .9; AHA_HP us HA_HP, p = .73), e d u c a tio n a l lev el (AHA = m e a n 9.8 , SD = 4 .6 ; AHA_HP = m e a n 8 .5 4 , SD = 4 .6 9 ; HA_HP = m e a n 1 0 .0 9 , SD = 4 .1 . AHA us AHA_HP, p = .46; AHA us HA_HP, p = .9; AHA_HP us HA_HP, p = .42) a n d illn e s s o n s e t (AHA = m e a n 55, SD = 37 .1 ; AHA_HP = m e a n 4 6 .6 3 , SD = 12.97; HA_HP = m e a n 6 0 .2 7 , SD = 33.8. AHA us AHA_HP, p = .9; AHA us HA_HP, p = .65; AHA_HP us HA_HP, p = .22).
2.2.
Neurological and neuropsychological assessm en tC o n tra le s io n a l v isu a l, m o to r a n d t a c tile d e fic its w e re a s s e s s e d a c c o rd in g to a sta n d a rd iz e d p ro to co l (B isia ch , P a ttin i, R u sco n i, R icci, & B e rn a rd in i, 1 997; B is ia ch , V a lla r, P e ra n i, P ap ag n o , & B erti, 1986) in w h ic h s c o r e s ra n g e fro m 0 (no d eficit) to 3 (s e v e re d eficit). W h a t fo llo w s is p a rt o f t h e ro u tin e n e u ro lo g ic a l d ia g n o sis o f HA. P a tie n ts b lin d fo ld e d first r e c e iv e te n sin g le lig h t to u c h stim u li ap p lied o n th e d o rsa l su rfa c e o f e ith e r th e h a n d s o r t h e f e e t (in ra n d o m o rd er). T h e y h a v e to re p o rt th e to u c h b y a n s w e rin g '‘rig h t" or "le ft". T h e s c o re is a ss ig n e d on t h e b a s is o f th e p e r fo r m a n c e o f h e a lth y p a rtic ip a n ts (100% o f d e te c tio n s ) a s fo llo w s: s c o re 3 = 3 to 0 stim u li a re re p o rte d on t h e c o n tr a le s io n a l lim b ; s c o re 2 = 7 to 4 stim u li a re re p o rte d on t h e c o n tr a le s io n a l lim b . W h e n p a tie n ts s c o re 2 (i.e., w h o r e p o rte d s o m e c o n tr a le s io n a l stim u li), t h e y a re a d m in is te re d t e n d o u b le (s y m m e tric a l a n d s im u lta n e o u s ) stim u li ('‘rig h t", "le ft" o r "rig h t a n d le ft" a n s w e rs). T h e y r e c e iv e t h e s c o re 1 if th e y re p o rt 7 to 0 s tim u li o n th e c o n tr a le s io n a l lim b , a n d 0 if th e y re p o rt 8 to 10.
A fte r th e m o to r a n d s o m a to s e n s o r y e x a m in a tio n , AHA an d AHP w e re e v a lu a te d a cc o rd in g to a s ta n d a rd p ro to co l (Pia, G arb arin i, e t al., 2 013; R o m a n o e t al., 2 014; S p in a z z o la , B ella n , P ia, & B erti, 2014). F o r t h e d ia g n o sis o f AHA, HA p a tie n ts w e re fir s t a s s e s s e d w ith fo u r q u e s tio n s re la te d to ta c tile p e r c e p tio n (se e S p in a z z o la e t al., 2 0 1 4 fo r d eta ils), tw o fo r th e u p p er lim b (How is s e n s a tio n in y o u r a rm ? , A re y o u a b le to p e rc e iv e a lig h t to u c h o n y o u r le ft h a n d ? ) a n d tw o fo r t h e lo w er lim b (How is s e n s a tio n in y o u r leg ?; A re y o u a b le to p e rc e iv e a lig h t to u c h o n y o u r le f t fo o t?). F o r e a c h q u e s tio n , HA p a tie n ts h a d to r a te t h e ir ow n p e r c e p tu a l a b ilitie s b y m e a n s o f a v e rb a l ju d g m e n t: n o rm a l p e r c e p tio n , p e r c e p tio n w ith d ifficu ltie s, n o p e r c e p tio n . A w a re n e s s o f th e p o te n tia l a b ility to fe e l s e n s a tio n s w a s sc o re d c o m p a r in g th e e x a m in e r 's ju d g m e n t w ith th e p a tie n t's se lf-e v a lu a tio n , a s fo llo w s: n o AHA (sco re 0, full a c c o rd in all q u e stio n s), m o d e ra te AHA (sco re 1, d is a g r e e m e n t in o n e o r tw o q u e stio n s), se v e re AHA (sco re 2, d is a g r e e m e n t in all q u e stio n s). AHA w a s d ia g n o se d w ith s c o re 1 o r 2 (0 w a s t h e c u t- o f f s c o re s in c e h e a lth y p a rtic ip a n ts a n d p a tie n ts w ith o u t HA do n o t sh o w a n y d is a g r e e m e n t; S p in a z z o la e t al., 2014).
A d d itio n ally , t h e a b ility to re p o rt t a c tile stim u li d eliv ered to t h e a ffe c te d sid e w a s e v a lu a te d (y e s/n o a n s w e rs) a lso w ith e y e s o p en . T h e s a m e s e q u e n c e o f lig h t to u c h stim u li a p p lied to b o th th e lim b s (te n tr ia ls e a ch ) o f th e n e u ro lo g ic a l e x a m w a s a d m in iste re d . T h e d is c re p a n c y b e tw e e n t h e a b ility to p e rce iv e stim u li w ith o p e n o r c lo s e d e y e s w a s sc o re d s u b tra c tin g th e n u m b e r o f re p o rte d s tim u li d u rin g th e e y e c lo se d e v a lu a tio n fro m th o s e o f t h e e y e s o p e n e v a lu a tio n a s fo llo w s: 0 = n o p o sitiv e d iffe re n c e , 1 = d iffe re n c e o n e to five, 2 = d iffe re n c e five to te n . T h e r e w a s a fu ll h ig h c o n s is te n c y b e tw e e n t h e s e sc o r e s a n d th o s e o b ta in e d fro m t h e in te rv ie w , n a m e ly e a c h p a r tic ip a n t o b ta in e d t h e s a m e s c o re w ith th e fo u r q u e s tio n s an d w ith t h e o n -lin e e v a lu a tio n (i.e., w ith o p e n eyes).
H a n d e d n e ss w a s a s s e s s e d w ith th e E d in b u rg in v e n to ry (Oldfield, 1971), w h e r e a s p a tie n ts ' s c r e e n in g fo r global co g n itiv e fu n c tio n in g w a s e v a lu a te d w ith th e Ita lia n v e rs io n o f t h e M ini M e n ta l S ta te E x a m in a tio n (M easso e t al., 1993). L eft e x tr a p e rs o n a l a n d p e r s o n a l n e g le c t w e re a s s e s s e d w ith t h e b e h a v io ra l/c o n v e n tio n a l s c a le s o f th e B eh a v io ra l In a tte n tio n T e s t (W ilso n , C o ck b u rn , & H alligan , 1987) a n d w ith th e B is ia c h a n d co -w o rk e rs p ro ce d u re (B isia ch , P e ra n i, V a lla r, & B erti, 1986), re s p e c tiv e ly . T h e th r e e g ro u p s (i.e., AHA, AHA_HP a n d HA_HP) did n o t d iffe r (M an n W h itn e y U T e s t o r S tu d e n t's t te st) in te rm s o f M M SE s c o re (AHA = 26 .0 3 , SD = 2.37; AHA_HP = m e a n 26.93, SD = 2.81; HA_HP = m e a n 25 .7 6 , SD = 3.2. AHA us AHA_HP,
p = .45; AHA us HA_HP, p = .81; AHA_HP us HA_HP, p = .37), BITC
s c o re (AHA = m e a n 9 4 .6 , SD = 57 .0 5 ; AHA_HP = m e a n 95 .3 6 , SD = 4 8 .1 6 ; HA_HP = m e a n 9 1 .1 8 , SD = 5 0 .94. AHA us AHA_HP,
p = .82; AHA us HA_HP, p = .94; AHA_HP us HA_HP, p = 84), BITB
s c o re (AHA = m e a n 52.8, SD = 2 8 .22; AHA_HP = m e a n 51.9, SD = 2 5 .64; HA_HP = m e a n 4 9 .7 2 , SD = 28.6. AHA us AHA_HP,
p = .95; AHA us HA_HP, p = .95; AHA_HP us HA_HP, p = .85) an d
B is ia c h s c o re (AHA m e a n = 0, SD = 0; AHA_HP = m e a n 72, SD = 1.1; HA_HP = m e a n 6 3, SD = 1.2. AHA us AHA_HP, p = .15; AHA us HA_HP, p = .24; AHA_HP us HA_HP, p = .78) (D em o- g ra p h ica l, n e u ro lo g ic a l a n d n e u ro p sy c h o lo g ic a l d a ta o f p a tie n ts a re re p o rte d in T a b le 1).
2.3.
Lesion
m apping and analysisP a tie n ts ' le s io n lo c a tio n s w e re id e n tifie d th ro u g h MRI or CT s c a n s . L e sio n s w e re m a p p e d o n to th e 1 m m 3 M N I152 sta n d a rd s p a c e th ro u g h a c o m p u te riz e d te c h n iq u e . Im a g e m a n ip u la tio n s w e re a c h ie v e d w ith t h e so ftw a re M R Icron (R o rd en & B re tt, 2000). F irst, t h e MNI te m p la te w a s r o ta te d o n c o ro n a l, s a g itta l a n d h o riz o n ta l p la n e s a cc o rd in g to t h e p a tie n t's s c a n a n g le. S e c o n d , a sk illed r a te r (LP), m a n u a lly m a p p e d th e le s io n o n to e a c h c o rre s p o n d e n t te m p la te s lic e , w h e r e a s a s e c o n d sk ille d r a t e r (AP) d o u b le -c h e c k e d fo r th e a c c u r a c y o f th e tra c in g s fo r e a c h p a tie n t (in th e o n ly o n e c a s e o f
Table 1 - Demographical, neurological and neuropsychological data. Id = patients' Identification number. Gen = Gender
(M = Male, F = Female). Edu = Education (years of formal education). Aet = Etiology (H = hemorrhage, I = ischemia,
M = meningioma). Ons = Onset (days between the disease and the first day of the assessment). MMSE = Mini Mental State
Examination (0-30). BITC = Behavioral Inattention Test-Conventional subtest (0-146, cut off 129). BITB Behavioral
Inattention Test-Behavioral subtest (0-81, cut off 67). Flu = Bisiach test (0-3, cut off 2). Vis = Visual deficits (0-3, cut off 2, the
two values refer to the upper and lower quadrant, respectively). Mot = Motor deficits (0-3, cut off 2, the two values refer to
the upper and lower limb, respectively). Som = Somatosensory deficits (0-3, cut off 2, the two values refer to the upper and
lower limb, respectively). AHA = Anosognosia for hemianaesthesia (0-2, cut off 1, the two values refer to the upper and
lower limb, respectively), n.a. = not available.
Id G roup A ge G en Edu A et O ns M M SE BITC BITB B is ia c h V is M o t S o m AHA
l AHA 76 F 7 E 51 26.7 134 69 0 1-1 0-0 2-2 1-1 2 AHA 61 M 18 I 26 22.46 140 76 0 3-3 0-0 2-3 1-2 3 AHA 64 M 8 E 23 26.49 17 8 0 0-0 0-0 3-0 2-0 4 AHA 66 M 8 I 115 25.53 132 69 0 3-3 0-0 2-0 1-0 5 AHA 78 M 8 I 60 29 50 42 0 0-0 0-0 3-3 2-2 6 AHA_HP 61 M 4 I 28 20.27 145 81 2 n.a. 3-3 3-3 2-2 7 AHA_HP 65 M 8 I 30 30 133 68 0 0-0 3-3 3-2 0-1 8 AHA_HP 70 F 8 E 60 30 23 16 1 0-0 3-3 3-3 2-1 9 AHA_HP 50 F 18 I 40 29 139 79 0 0-0 3-3 3-3 2-2 10 AHA_HP 82 M 8 I 45 27 89 46 0 0-0 3-3 2-2 2-2 11 AHA_HP 72 F 5 I 60 28 66 60 0 0-0 3-3 3-3 2-2 12 AHA_HP 62 F 8 I 40 28 64 48 0 0-0 3-3 3-3 2-2 13 AHA_HP 64 M 5 I 40 26 141 76 0 0-0 3-3 2-2 2-2 14 AHA_HP 68 M 5 I 70 25 14 1 3 3-3 3-3 3-3 2-2 15 AHA_HP 64 M 17 I 50 25 135 40 2 3-3 3-3 3-3 2-2 16 AHA_HP 65 M 8 I 50 28 100 56 0 0-0 3-3 3-3 2-2 17 HA_HP 66 M 8 E 55 28.53 19 6 0 0-0 3-2 3-3 0-0 18 HA_HP 67 M 8 I 131 26 133 68 0 0-0 3-3 2-0 0-0 19 HA_HP 77 F 17 E 35 28 140 73 0 0-0 3-3 3-3 0-0 20 HA_HP 55 M 5 I 30 17.9 17 8 3 0-0 3-3 3-3 0-0 21 HA_HP 37 F 18 I 50 30 91 53 0 0-0 3-3 3-3 0-0 22 HA_HP 68 M 8 I 30 28 131 79 1 0-0 3-3 2-2 0-0 23 HA_HP 79 F 13 I 112 24 141 80 0 3-3 3-3 3-3 0-0 24 HA_HP 70 F 8 I 70 25 51 37 3 3-3 3-3 3-3 0-0 25 HA_HP 64 M 9 E 41 25 94 45 0 0-0 3-3 3-3 0-0 26 HA_HP 45 M 8 I 72 26 41 20 0 3-3 3-3 3-3 0-0 27 HA_HP 77 F 9 E 37 25 145 78 0 0-0 2-2 3-3 0-0
d is a g r e e m e n t, a n in te r s e c tio n le s io n m a p w a s u sed ). T h ird , th e m a p s w e re b a c k r o ta te d in to th e sta n d a rd sp a c e .
W e fir s t c re a te d tw o s e p a ra te le s io n s o v erlap , n a m e ly AHA_HP a n d HA_HP gro u p s. T h e n , w e s u b tra c te d HA_HP fro m AHA_HP. T h e c o m p a r is o n b e tw e e n t h e tw o g ro u p s w a s o b ta in e d b y m e a n s o f a v o x e l-b y -v o x e l L ie b e rm e is te r t e s t (p < .01 FDR c o rre c tio n ) a s im p le m e n te d in t h e NPM in clu d e d in MRI- c ro n (R o rd en , K a rn a th , & B o n ilh a , 2007).
S e c o n d , w e p u t in c o n fr o n t th e o b ta in e d r e s u lts w ith th e le s io n s o v erla p o f t h e five p u re AHA p a tie n ts (AHA p a tie n ts w ith o u t HP). Q u a n tita tiv e e s t im a t e s o f g rey a n d w h ite m a tt e r re g io n s in v o lv e m e n t w e re o b ta in e d b y s u p e rim p o s in g th e A n a to m ic a l L a b elin g m a p te m p la te AAL (T z o u rio -M a z o y er e t al., 2002) a n d t h e JH U -w h ite m a tt e r te m p la te (Hua e t al., 2008).
3.
Results
Fig. 1A a n d B sh o w t h e le s io n o v e rla p p in g o f AHA_HP an d HA_HP gro u p s, re s p e c tiv e ly , w h e r e a s T a b le 2A a n d B re p o rt t h e ir q u a n tita tiv e e s tim a te . T h e AHA_HP group sh o w e d a le s io n a l p a tte r n m a in ly in v o lv in g th e in s u la , t h e c a u d a te n u c le u s , t h e p o s te rio r lim b o f in te r n a l c a p s u le , t h e p u ta m e n , th e su p e rio r c o ro n a ra d ia ta , t h e su p e rio r fro n to -o c c ip ita l f a s c ic u lu s a n d th e su p e rio r lo n g itu d in a l fa s c ic u lu s . T h e HA_HP group d isp la y ed a le s io n a l p a tte r n m a in ly in v o lv in g th e in s u la , th e su p e rio r c o ro n a ra d ia ta a n d t h e su p e rio r lo n g itu d in a l fa s c ic u lu s .
Fig. 1C sh o w s t h e le s io n p lo t su b tra c tio n b e tw e e n th e tw o gro u p s, w h e r e a s T a b le 2C d isp lay s its q u a n tita tiv e e s tim a te . T h e su b tra c tio n a n a ly s is sh o w e d t h a t th e a n te r io r lim b o f th e in te r n a l c a p s u le , th e p a llid u m , th e p u ta m e n a n d t h e u n c in a te fa s c ic u lu s w e re d a m a g ed a t le a s t t h e 50% m o re fre q u e n tly in t h e AHA_HP group r e s p e c t to HA_HP group. It is w o rth n o tic in g t h a t t h e re v e rs e s u b tra c tio n sh o w e d t h a t n o re g io n s w e re in ju r e d a t le a s t 50% m o re in t h e HA_HP, r e s p e c t to AHA_HP, gro u p s. T h e V o x e l-b y -v o x e l t e s t co m p a r in g t h e tw o gro u p s w ith b in o m ia l d a ta (Fig. 2A a n d T a b le 3A) re v e a le d a c lu s te r m a in ly in v o lv in g th e a n te r io r p u ta m e n , w ith a m in o r in v o lv e m e n t o f t h e u n c in a te fa s c ic u lu s (an d a v e ry s m a ll in v o lv e m e n t o f th e p a llid u m , p a rt o f th e le n tifo rm n u c le u s t o g e th e r w ith th e p u ta m e n ). In th e group o f five p u re AHA p a tie n ts , th e le s io n a l p a tte r n m a in ly in v o lv ed t h e in s u la , th e p o s tc e n tr a l g yru s, th e r o la n d ic o p e rcu lu m , t h e su p e rio r lo n g itu d in a l fa s c ic u lu s , th e su p ra m a rg in a l gyru s a n d th e p u ta m e n (Fig. 2B a n d T a b le 3B).
4.
Discussion
W ith t h e p r e s e n t in v e s tig a tio n , w e a im e d a t fin d in g th e n e u ra l c o r r e la te s o f a n o s o g n o s ia fo r h e m ia n a e s th e s ia . By m e a n s o f a v o x e lw is e s ta tis tic a l a n a ly s is , w e d ire ctly co m p a re d HA_HP group le s io n p lo ts to AHA_HP group le s io n p lo ts. T h e re s u lts w e re a lso e v a lu a te d in r e la tio n s h ip w ith t h e le s io n p lo ts o f a s m a ll group o f p a tie n ts a ffe c te d b y a p u re fo rm o f AHA (i.e., p a tie n ts a ffe c te d b y u n a w a r e n e s s o f th e
Fig. 1 - Overlays of regional lesion plots of the AHA_HP (A) and HA_HP (B) groups. The frequency is represented trough a
color scale ranging from black (lesion in one patient) to red (lesion in eleven patients). Subtraction of regional lesion plots (C).
Regions damaged more frequently in the AHA_HP group respect to HA_HP group are displayed in warm colors, from dark
red to white. MNI coordinates of each transverse section are reported.
Table 2 - Quantitative estimate of the regional lesion plots of the AHA_HP (A) and the HA_HP groups (B). Region overlaps in
three patients or more in at least one of the two groups are reported. For each region, the percentage of lesioned voxels
(Region %), the number of patients (Patients #) and MNI coordinates are reported, Quantitative estimate of the subtraction of
regional lesion plots (C). Only brain regions that were damaged the 50% or more frequently in the AHA_HP group respect to
HA_HP group are reported. For each region, the number of lesioned voxels (Voxels %), the percentage of lesioned voxels
(Region %), the percentage of patients (Patients %) and MNI coordinates (MNI) are reported.
G rey /W h ite m a tte r (A) AHA_HP (B) HA_HP
R egio n % P a tie n ts # MNI R egio n % P a tie n ts # MNI
X Y Z X Y Z Amygdala 67 5 31 0 - 1 2 8 2 36 3 -2 5 Angular 93 5 42 - 5 0 22 77 5 42 - 5 0 22 Anterior_cor_rad 79 6 23 20 5 33 4 25 22 9 Anterior_limb_int_cap 92 7 22 7 13 71 4 21 - 5 18 Calcarine 0 0 0 0 0 18 3 28 - 6 9 6 Caudate 54 8 21 4 21 44 5 20 - 1 2 21 Fornix 21 3 30 - 1 6 - 1 0 0 0 0 0 0 Frontal_Inf_Ope 95 6 39 17 5 97 6 48 12 0 Frontal_Inf_Orb 85 4 46 19 - 1 2 77 5 52 19 - 9 Frontal_Inf_Tri 89 5 46 21 0 87 5 47 19 3 Frontal_Mid 82 4 49 43 11 40 2 41 41 3 Frontal_Sup 80 3 24 48 23 14 2 30 3 47 Heschl 100 7 42 - 1 6 6 100 6 41 -2 1 5 Hippocampus 21 4 36 - 2 1 - 6 3 2 35 - 1 9 - 8 Insula 100 9 31 - 1 7 16 99 8 31 - 1 6 20 Occipital_Inf 3 2 49 - 7 4 - 3 8 3 33 -8 1 0 Occipital_Mid 77 4 49 - 6 7 25 80 3 33 - 8 0 0 Occipital_Sup 22 3 34 - 7 1 41 0 0 0 0 0 Olfactory 43 3 26 9 - 1 2 0 0 0 0 0 Pallidum 100 7 28 - 4 - 3 56 3 28 - 3 - 5 Parietal_Inf 92 4 52 - 4 8 38 31 3 37 - 5 0 38 Postcentral 83 4 53 - 6 25 68 5 60 - 1 6 19 Posterior_corona_rad 30 7 27 - 2 4 20 39 7 29 - 2 4 23 Posterior_limb_int_cap 86 8 26 - 1 1 18 55 6 26 - 1 2 16 Posterior_tha 29 3 37 - 5 2 - 3 62 3 27 - 7 2 5 Precentral 85 5 37 3 29 70 3 58 10 16 Putamen 100 9 24 6 4 84 6 36 1 - 2 Retrolenticular_part 66 5 26 - 2 1 2 42 3 37 - 3 4 5 Rolan dic_Oper 100 7 38 - 4 13 98 7 42 - 2 10 Sagittal_stratum 57 5 43 - 2 8 - 1 0 27 2 39 - 1 8 - 9 Superior_corona_rad 88 9 29 - 1 8 20 77 8 27 - 1 8 21 Superior_fronto-occi_fas 95 8 21 7 20 100 4 17 - 6 19 Superior_long_fas 100 8 30 - 4 19 100 8 31 - 1 6 22 SupraMarginal 91 5 47 - 4 2 22 76 6 46 -3 5 29 Temporal_Inf 46 4 56 - 1 6 - 1 8 30 3 53 - 6 -2 7 Temporal_Gyurus_Mid 92 5 48 - 8 - 1 8 88 5 46 0 - 1 6 Temporal_Pole_Mid 78 4 47 3 -1 7 75 5 52 15 - 2 2 Temporal_Pole_Sup 89 6 44 4 -1 7 87 6 54 9 0 Temporal_Gyrus_Sup 94 7 41 - 1 4 3 95 7 43 - 9 - 5 Thalamus 55 6 22 - 1 9 13 20 3 22 - 1 8 6 Uncinate_fasc 92 6 33 2 - 1 4 0 0 0 0 0
G rey /W h ite m a tte r (C) AHA_HP m in u s HA_HP
R egio n % P a tie n ts % MNI
X Y Z
Anterior_limb_int_cap 86 55 22 7 13
Pallidum 100 64 22 6 1
Putamen 98 73 24 12 0
Uncinate_fasc 92 55 33 2 - 1 4
t a c tile im p a ir m e n t w ith o u t a n y m o to r d eficits). O ur re s u lts sh o w e d t h a t t h e a n te r io r p a rt o f th e p u ta m e n , a n d , to a m u c h le s s e x t e n t t h e u n c in a te fa s c ic u lu s a n d p a llid u m , s e e m to b e c ru c ia l fo r t h e e m e rg e n c e o f a n o s o g n o s ia for h e m ia n a e s th e s ia .
A s w e m e n tio n e d above, so fa r o n ly tw o stu d ie s rep o rted d ata a b o u t th e n e u ra l b a s is o f a n o so g n o s ia fo r h e m ia n a e s th e s ia (R o m an o e t al., 2014; S p in a z z o la e t al., 2008). B o th o f th e m em p lo y ed t h e tra d itio n a l ov erlay le sio n p lo t te c h n iq u e o n sm all sa m p le s o f p a tie n ts. Sp ecifically, S p in a z z o la a n d co w o rk ers
Fig. 2 - (A) Brain regions significantly associated to AHA (AHA_HP group us HA_HP group). All voxels which survived to the
binomial test are displayed. The color scale represents Z-Libermesiter scores. (B) Overlays of regional lesion plots of the AHA
group. The frequency is represented trough a color scale ranging from black (lesion in one patient) to red (lesion in five
patients).
(S p in azzo la e t al., 2008) a n a ly z ed th e le sio n ov erlap o f fo u r AHA p a tie n ts. T h e y fou n d th a t all p a tie n ts h a d in c o m m o n le sio n s to th e p u ta m e n , th e in s u la r co rte x , th e in te rn a l an d th e e x te rn a l ca p su le. Sim ilarly , R o m a n o an d co w o rk ers (R o m an o e t al., 2014) a n a ly z ed t h e le sio n a l p a tte rn o f five AHA p a tie n ts an d rep o rted t h a t fo u r h a d le sio n s to t h e in s u la r co rte x , th e b a s a l gan glia and th e p e riv e n tricu la r w h ite m a tte r. It is w o rth n o tic in g t h a t S p i n a z z o la an d co w o rk ers (S p in azzo la e t al., 2008) su g gested a lso a p re lim in a ry e x p la n a tio n o f ta c tile u n a w a re n e ss o n th e b a s is o f th e in te rp re ta tio n o f u n a w a re n e s s for m o to r d eficits. It h a s b e e n su g gested th a t a n o so g n o s ia fo r h e m ip le g ia is a d o m ain sp e cific d iso rd er o f m o n ito rin g v o lu n ta ry a ctio n s . A d am ag e to th e co rtica l n e tw o rk su b serv in g m o to r a w a re n e ss in th e la te ra l p re m o to r (Berti e t al., 2005; V o ca t, S tau b , Stro p p in i, & V u illeu m ier, 2010) o r in s u la r (Berti e t al., 2005; Fotop oulou, P em ig o , M aed a, Rudd, & K o p elm an , 2010; K a rn a th , B aier, & N agele, 2005; M oro, P em ig o , Zap paroli, Cordioli, & A glioti, 2011; V o c a t e t al., 2010) c o rte x (b u t s e e also F otop ou lo u e t al., 2010 for a p re v a le n ce o f b a s a l gan glia d am ag es), w ou ld p re v e n t d istin g u ish in g b e tw e e n in te n d e d an d a ctu a l m o v e m e n t e x e c u tio n , lea d in g to u n a w a re n e s s o f th e d eficit. A d d itionally, a sp ared a ctiv ity o f th e b ra in stru c tu re s th a t im p le m e n t th e in te n tio n -p ro g ra m m in g sy s te m (see H eilm an , B arrett, & Adair, 1998 fo r t h e first m o to r in te n tio n a l th e o ry o f AHP) w ou ld in d u ce th e p a tie n ts' fa ls e b e lie f o f b e in g still ab le to m o v e (G arbarin i & Pia, 2013; G arb arini, P ied im o n te, D o tta, Pia, & B erti, 2013; Pia e t al., 2013). A cco rd in gly, S p in a z z o la an d co w o rk ers (S p in azzo la e t al., 2008) p ro p o sed th a t in AHA th e b r a in d am ag e w ou ld p re v e n t to d istin g u ish b e tw e e n an in te rn a l r e p re s e n ta tio n o f th e s e n s a tio n a risin g fro m e x p e cta tio n s/p re v io u s e x p e rie n c e o f ta c tile p e rce p tio n a n d th e re a l a ctu a l p e rce p tio n o f th e p h y sica l stim u lu s. T h e fa ls e b e lie f o f b e in g still ab le to p erceiv e ta c tile stim u li m ig h t th e n a rise fro m th e in ta c t b ra in a ctiv ity o f
t h e sp ared a re a s w ith in th e so m a to s e n s o ry sy s te m . A s fo r th e d en ia l o f m o to r d eficit, th e fa ls e b e lie f w ou ld b e ca u se d b y an actu a l n e u ra l signal.
D iffe re n tly fro m th e s m a ll s a m p le s o f th e tw o a b o v e- m e n tio n e d stu d ie s, h e r e w e em p lo y e d a le s io n s u b tra c tio n te c h n iq u e o n la rg e r s a m p le s o f p a tie n ts . W ith r e s p e c t to th e o v e rla y le s io n p lo t te c h n iq u e , th is a p p r o a c h c a n id e n tify th e n e u ra l c o r r e la te s o f a g iv en b e h a v io r b y c o m p a r in g t h e o v erla y le s io n p lo t o f p a tie n ts w ith , a n d p a tie n ts w ith o u t, t h e d e fic it o f in te r e s t. In o th e r w o rd s, i f gro u p s d iffe r o n ly fo r th e c ritic a l d eficit, t h e m e th o d is a b le to d is tin g u ish b e tw e e n s tru c tu re s t h a t a re o n ly o fte n d a m a g e d fro m s tr u c tu r e s t h a t a re s p e c if ic a lly re q u ire d fo r th e fu n c tio n o f in t e r e s t (R o rd en e t al., 2007). A cco rd in g ly , w e re tro s p e c tiv e ly s e le c te d p a tie n ts a ffe c te d by HA w ith o r w ith o u t AHA (b u t n o AHP). It is w o rth n o tic in g t h a t t h e g ro u p s o n w h ic h w e p e rfo rm e d a n a to m ic a l c o m p a r is o n s did n o t d iffered in te r m s o f so c io -d e m o g ra p h ic a n d t h e o th e r n e u ro p sy c h o lo g ic a l m e a s u r e s . H e n ce , e a c h v a ria b le , e x c e p t AHA, w e re b a la n c e d a m o n g g ro u p s. O ur a n a to m ic a l re s u lts a re c o n s is t e n t w ith p re v io u s lite r a tu re (R o m an o e t al., 2014; S p in a z z o la e t al., 2008). H o w ever, th e y su g g e st t h a t a sp e cific stru c tu re , n a m e ly th e a n te r io r p u ta m e n , co u ld b e t h e n e u ra l b a s is fo r th e e m e rg e n c e o f AHA.
T ra d itio n a lly , th e p u ta m e n h a s b e e n su b d iv id ed in to tw o d is tin c t re g io n s, n a m e ly t h e a n te r io r p a rt, m o re c o n n e c te d w ith th e p re m o to r c o r te x a n d t h e a n te r io r c in g u la te c o rte x , an d th e p o s te rio r p a rt, m o r e lin k e d to th e s e n s o r im o to r c o rte x an d t h e c e r e b e llu m (e.g., A le x a n d e r, D eL ong, & S trick , 1986; F e rn a n d e z -S e a ra , A z n a r e z -S a n a d o , M en g u al, L oay za, & P a sto r, 2009). A lte r a tio n o f th e a n te r io r p u ta m e n fu n c tio n in g h a s b e e n a s s o c ia te d to d iffe re n t d is e a s e s . D y s k in e sia s, for in s ta n c e , h a v e b e e n lin k e d to a s ig n ific a n t d e n s ity d e c r e a s e o f t h e d o p a m in e D2 re c e p to r s w ith in th e a n te r io r p u ta m e n
Table 3 - (A) Quantitative estimate of the brain structures
significantly associated to AHA (AHA_HP group us HA_HP
group). For each brain structure, the number of clustering
voxels, z score, and MNI coordinates of the center of mass
are reported. Quantitative estimate of the regional lesion
plots of the AHA group (B). Region overlaps in at least three
patients or more are reported. For each region, the
percentage of lesioned voxels (Region %), the number of
patients (Patients #) and MNI coordinates are reported.
(N ad eau , C o u ch , D e v a n e , & S h u k la , 1995). R ed u ced v o lu m e o f t h e a n te r io r p u ta m e n h a s b e e n re p o rte d in H u n tin g to n 's d is e a s e (B o h n e n e t al., 2000) w h e r e a s re d u ce d d e n s ity s e e m s to su b s e rv e co g n itiv e im p a ir m e n ts o fte n o b se rv e d in s p in o c e r e b e lla r a ta x ia (B rag a-N eto e t al., 2012). S u rfa c e a b n o r m a litie s o f t h e a n te r io r p u ta m e n h a v e b e e n re p o rte d in te e n a g e r s w ith A tte n tio n D e ficit H y p e ra ctiv ity D iso rd e r (B ie d e rm a n e t al., 2008). T h e a n te r io r p u ta m e n h a s b e e n fo u n d to b e in v o lv ed in d iffe re n t fu n c tio n s : s e le c tio n o f v o lu n ta ry m o v e m e n ts (G erard in e t al., 2004), m o to r le a r n in g (M iyach i, H ik o sak a, M iy a sh ita , K arad i, & R and , 1997), re a s o n in g (M elro se, P ou lin , & S te r n , 2007) c o g n itiv e /v is u o m o to r sk ill-le a rn in g , (B e a u ch a m p , D ag h er, A sto n , & D o y o n , 2 0 0 3 ; F lo y er-L ea & M a tth e w s, 2004), c o g n itiv e '‘sh ift"(M cC lu re, B e rn s , & M o n ta g u e, 2003) a n d g e n e ra l a tte n tio n (R o m o , S c a rn a ti, & S c h u ltz , 1992).
In te re stin g ly , th e a n te r io r p u ta m e n s e e m s to b e in v o lv ed a lso in p re d ic tio n e rro rs (O 'D o herty e t al., 2004), in clu d in g erro r
r e s p o n s e s to t h e u n e x p e c te d a b s e n c e o f in p u t (d en O ud en , F risto n , D aw , M c In to s h , & S te p h a n , 2009). A cco rd in g ly , a r e c e n t fMRI stu d y (L an gn er e t al., 2011) re p o rte d t h a t a n te r io r p u ta m e n w a s a c tiv a te d b y th e o m is s io n s o f e x p e c te d s e n s o ry stim u li, t a c tile , a u d ito ry o r v isu a l (in d eed , fu rth e r a c tiv a tio n s o f th e p o s te rio r p u ta m e n w e re th o u g h t to r e fle c t m o to r p re p a ra tio n , r a th e r th a n s e n s o ry e x p e c ta tio n s ). A d d itio n ally , e x p e c ta n c ie s o f t a c tile stim u li le a d e d to in c r e a s e d a c tiv itie s in th e s o m a to s e n s o r y c o r tic e s a n d d e a c tiv a tio n s in v isu a l/a u d ito ry c o rtic e s . T h e s e d a ta su g g e st t h a t th e b r a in re p r e s e n ts ta c tile - sp e cific in fo r m a tio n w ith in b o th t h e s o m a to s e n s o r y a n d o th e r s e n s o ry d o m a in s in o rd e r to p rio ritiz e t h e e la b o ra tio n o f t h e sp e c ific stim u li a n d o p tim iz e t h e d e te c tio n b e fo re th e ta rg e t e v e n t o c c u rs . T h e n , th e b r a in c o m p a r e s s p e c ific ity o f t h e e x p e c ta tio n s w ith t h e sp e c ific ity o f t h e a c tu a l stim u la tio n an d th e a n te r io r p u ta m e n w o u ld su b s e rv e o m is s io n -r e la te d B a y e s ia n su rp ris e a c c o rd in g to t h e s p e c ific ity o f t h e p re d ic tio n s (L an gn er e t al., 2011). In te re stin g ly , th is id e a is r e m in is c e n t o f a r e c e n t in te r p r e ta tio n o f AHP in te r m s o f im b a la n c e s b e tw e e n a c tu a l e x p e r ie n c e s o f t h e b o d y a n d p rio r e x p e c ta n c ie s o f b o d y sig n a ls (Fo to p o u lo u , 2 0 1 4 , 2012). On t h e s e b a s e s , w e p ro p o se a p o ssib le in te r p r e ta tio n o f a n o s o g n o s ia fo r h e m ia n a e s th e s ia . T a c tile -s p e c ific e x p e c t a n c ie s w ou ld b e g e n e r a te d w ith in sp a red s o m a to s e n s o r y c o rtic e s . In te re stin g ly , t h e o v e rla y s o f re g io n a l le s io n p lo t o f b o th AHA_HP (Fig. 1A a n d T a b le 2A) a n d AHA (Fig. 2B an d T a b le 3B) gro u p s sh o w e d t h a t t h e s e s tr u c tu r e s w e re in t a c t or a t le a s t p a rtia lly sp a red . T h e s u b s e q u e n t c o m p a r is o n b e tw e e n e x p e c ta n c ie s a n d (a b se n c e ) o f p e rc e iv e d stim u li w o u ld n o t b e p o ssib le d u e to a n te r io r p u ta m e n le s io n s . A cco rd in g ly , th is p a rt o f th e p u ta m e n is t h e m a in b r a in s tru c tu re e m e rg in g fro m t h e c o m p a r is o n b e tw e e n AHA_HP a n d HA_HP gro u p s (Figs. 1C a n d 2A, T a b le 2C a n d 3A). In d eed a m in o r in v o lv e m e n t w a s re p o rte d a lso fo r th e u n c in a te fa s c ic u lu s . In te re stin g ly , th e s e fib e r t r a c t h a s b e e n re la te d to im p a ire d e rro r m o n ito r in g d u rin g v isu a l lo c a tio n o f o b je c ts (M etz ler-B a d d eley , Jo n e s , B e la ro u s si, A g g leto n , & O 'S u lliv an , 2011). T h e a n te r io r p u ta m e n w a s a lso d a m a g e d in tw o AHA p a tie n ts (Fig. 2B, T a b le 3B). T h e c o n s e q u e n c e s o f n o t b e in g a b le to d e te c t t h e m is m a tc h b e tw e e n a n e x p e c te d t a c tile s e n s a tio n a n d its a c tu a l a b s e n c e w ou ld le a d p a tie n ts to re ly e n tire ly o n t h e ir t a c tile s e n s o ry e x p e c ta n c ie s (i.e., re p o rtin g ta c tile s tim u li in a b s e n c e o f ta c tile p e rce p tio n ) d e v e lo p in g a fa ls e b e lie f o f b e in g a b le to fe e l th e stim u li (se e a lso Pia, C av allo, & G a rb arin i, 2014).
W e m u s t c le a rly a ck n o w le d g e t h a t o u r in te r p r e ta tio n is still a t s p e c u la tiv e lev el. D ire c t n e u ro im a g in g e v id e n c e (e.g., fMRI o r EEG) o f a c tiv itie s d u rin g t h e e x p e c ta n c ie s o f ta c tile stim u li a re b a r e ly re q u ire d in o rd er to s tr e n g th e n o u r c o n clu s io n s . A d d itio n ally , fu tu re s tu d ie s sh o u ld a lso o b ta in m o re in d e p th d a ta a b o u t s o m a to s e n s o r y p r o c e s s in g a s, for in s ta n c e , t a c tile th r e s h o ld /d is c r im in a tio n w h e n s tim u li are d eliv ered o r n o t d eliv ered , p ro p rio ce p tio n , p a in p e r c e p tio n a n d so on . F in a lly , in o u r s a m p le o f h e m ia n a e s th e s ic p a tie n ts w ith a p u re fo rm o f a n o s o g n o s ia , t h e a n te r io r p u ta m e n w a s c le a rly d a m a g e d in tw o p a tie n ts (o u t o f five). A lth o u g h CT s c a n c a n h ig h ly u n d e r e s tim a te th e e x t e n t o f t h e su b a c u te d isru p tiv e e f fe c ts p ro d u ce d b y a s tro k e o n th e a r e a s su rro u n d in g th e le s io n (e.g., a n te r io r p u ta m e n ) o r "h id e " fu n c tio n a l d ia s c h is is (e.g., b e tw e e n sp a re d s o m a to s e n s o r y a re a s a n d a n te r io r p u t a m e n ), w e c e r ta in ly n e e d to c o lle c t m o re c a s e s o f p u re AHA in G rey /W h ite m a tte r (A) AHA_HP us HA_HP
R egio n % z s c o re X MNI Y Z Putamen 17 3.58 24 12 0 Pallidum 1 3.2 22 6 1 Uncinate_fasciculus 8 2.83 33 2 - 1 4 G rey /W h ite m a tte r (B) AHA
R egio n % P a tie n ts # MNI
X Y Z Angular 55 2 40 - 5 7 22 Anterior_limb_int_cap 42 2 13 11 - 5 Caudate 19 2 13 11 - 9 Frontal_Inf_Ope 85 2 62 14 4 Frontal_Mid 37 2 32 2 36 Heschl 99 2 43 - 1 7 5 Insula 92 3 37 - 2 8 22 Occipital_Mid 20 2 34 - 6 2 33 Pallidum 47 2 14 10 - 4 Parietal_Inf 67 2 44 - 4 5 38 Postcentral 71 3 51 - 2 1 31 Posterior_cor_rad 35 2 30 - 5 0 19 Posterior_limb_int_cap 43 2 24 - 2 2 10 Precentral 37 3 40 - 1 4 36 Putamen 91 2 16 14 - 1 0 Rectus 4 2 19 15 -1 1 Retrolenticular_part 48 2 25 - 2 4 10 Rolan dic_Oper 97 3 42 - 3 4 22 Superior_corona_rad 53 3 30 - 1 3 24 Superior_long_fas 96 3 32 - 1 9 24 SupraMarginal 71 3 46 - 3 6 23 Temporal_Mid 35 2 41 - 5 7 21 Temporal_Pole_Sup 11 2 56 5 - 3 Temporal_Sup 76 3 51 - 3 8 22 Thalamus 18 2 23 - 2 3 11
o rd e r to h a v e a fu ll a n a to m ic a l a c c o u n t o f a n o s o g n o s ia fo r h e m ia n a e s th e s ia .
Acknowledgments
T h e a u th o rs a re g ra te fu l to all p a tie n ts w h o a c c e p te d to p a rtic ip a te in th e stu d y . T h e stu d y h a s b e e n fu n d ed b y a PRIN (p ro t. 2010EN PR YE_003) a n d a S a n P aolo F o u n d a tio n (EU a c c e le r a tin g g ra n t 2012) g ra n ts.
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