BR A IN RE S EA RCH 1 1 75 ( 20 0 7 ) 7 6 –84
a v a i l a b l e a t w w w. s c i e n c e d i r e c t . c o m
w w w. e l s e v i e r. c o m / l o c a t e / b r a i n r e s
Research Report
On-line grasp control is mediated by the
contralateral hemisphere
Nichola J. Ricea,b , Eugene Tunika,c , Emily S. Crossa , Scott T. Graftona,d,⁎
a
HB 6162 Moore Hall, Department of Psychological and Brain Sciences, Center for Cognitive Neuroscience, Dartmouth College,
Hanover, New Hampshire, 03755, USA
b
Volen Center for Complex Systems, Brandeis University, MS013, 415 South Street, Waltham, MA 02454-9110, USA
c
Department of Physical Therapy, New York University, NY, USA
d
Sage Center for the Study of Mind and the Department of Psychology, Psychology East,
Room 3837, UC Santa Barbara, Santa Barbara, CA 93106, USA
A R T I C LE I N FO
AB S T R A C T
Article history:
Electrophysiological recordings from monkeys, as well as functional imaging and
Accepted 6 August 2007
neuropsychological work with humans, have suggested that a region in the anterior
Available online 10 August 2007
portion of the intraparietal sulcus (aIPS) is involved in prehensile movements. With recent
methodological advances using transcranial magnetic stimulation (TMS), we can now
Keywords:
causally attribute anatomy with function to more precisely determine the specific
Transcranial magnetic stimulation
involvement of aIPS in grasping. It has recently been demonstrated that aIPS is specifically
TMS
involved in executing a grasp under conditions of both constant target requirements, as well
Motor control
as in correcting a movement under conditions in which a target perturbation occurs. In the
Intraparietal sulcus
present study, we extend these findings by determining the differential contribution of the
Lateralization
left and right hemisphere to executing a grasping movement with the left and right hands.
Transient disruption of left aIPS at movement onset impairs grasping with the right but not
the left hand, and disruption of right aIPS impairs grasping with the left but not the right
hand. We conclude that grasping is a lateralized process, relying exclusively on the
contralateral hemisphere, and discuss the implications of these findings in relationship to
models of hemispheric dominance for motor control.
© 2007 Elsevier B.V. All rights reserved.
1.
Introduction
A skill fundamental to human behaviour is our ability to
interact with objects in the environment. One such skill that
has received considerable attention from researchers interested in motor control is grasping behaviour. Research from
both non-human primates (Gallese et al., 1994; Sakata et al.,
1995; Murata et al., 2000; Fogassi et al., 2001; Gardner et al.,
2006, 2007; Raos et al., 2006) and humans, including studies
with patients (Binkofski et al., 1998), functional imaging
(Binkofski et al., 1998; Culham et al., 2003; Frey et al., 2005)
and transcranial magnetic stimulation (TMS) (Glover et al.,
⁎ Corresponding author. Sage Center for the Study of Mind and the Department of Psychology, Psychology East, Room 3837, UC Santa
Barbara, Santa Barbara, CA 93106, USA. Fax: +1 805 893 4303.
E-mail address: grafton@psych.ucsb.edu (S.T. Grafton).
Abbreviations: LaIPS, left anterior intraparietal sulcus; RaIPS, right anterior intraparietal sulcus; MTt, transport movement time; PVt,
transport peak velocity; %TPVt, percentage transport time of peak velocity; MGAg, maximum grip aperture; %TMGAg, percentage time of
maximum grip aperture; PVg, grasp peak velocity; %TPVg, percentage grasp time of peak velocity
0006-8993/$ – see front matter © 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.brainres.2007.08.009
BR A IN RE S E A RCH 1 1 75 ( 20 0 7 ) 7 6 –8 4
2005; Tunik et al., 2005; Rice et al., 2006), have identified a
network of fronto-parietal brain regions involved in this
behaviour. Within this grasping network lies the anterior
intraparietal sulcus (aIPS), the region that is most consistently
identified to play a functional role in grasping. aIPS is located
most commonly at the junction between the postcentral
sulcus and in the intraparietal sulcus (IPS) (for review see
Tunik et al., 2007).
In a series of recent studies from our laboratory, we showed
that transient disruption of aIPS with TMS impairs grasping
behaviour (Tunik et al., 2005; Rice et al., 2006). In the first of
these studies, it was found that single-pulse TMS to aIPS
disrupted grasping under conditions in which the object was
perturbed (in either size or orientation), highlighting the role
of aIPS in dynamic online control of actions. Further, it was
shown that this disruption is goal- rather than effectordependent (i.e. a perturbation in size affected grasp aperture,
whereas a perturbation in orientation affected hand orientation). Finally, it was proposed that aIPS may have a specific
role in error detection because effects were only elicited
within 65 ms after object perturbation (Tunik et al., 2005). In a
follow-up study (Rice et al., 2006), deficits in grasping could
also be demonstrated in conditions where the object remained
stable in the environment. By tightly controlling viewing
conditions and applying TMS at specific time intervals, it was
possible to dissociate planning or detection of a change in the
motor goal, from execution or the on-line adjustment of a
movement. Thus, we could assess the specific contribution of
aIPS in the planning and execution components of prehensile
movements. This experiment revealed that the effect of TMS
to aIPS on grasping was present for both grasp execution and
online correction of movements. TMS had no effect on
grasping when it was delivered during the motor planning
phase (i.e. prior to movement onset), or during the detection in
a change of task goal (i.e. when subjects could see that the
target had changed size). Having established the role of the left
hemisphere aIPS in dynamic control of right-handed grasp, we
now ask whether the left and right aIPS (LaIPS and RaIPS,
respectively) control the contralateral hand or whether this
role is specialized to the left hemisphere.
In the abovementioned TMS studies, stimulation was
limited to the LaIPS as subjects grasped with their right
hand. Evidence from functional imaging studies is inconclusive regarding the lateralized specialization of aIPS for grasp,
with right-handed grasping being associated with bilateral
(Culham et al., 2003) as well as contralateral (Frey et al., 2005)
activation in aIPS. In a combined lesion and fMRI study,
Binkofski et al. (1998) found evidence to suggest that patients
with parietal lobe damage that encompasses aIPS are impaired at grasping with the hand contralateral to the lesion.
However, their imaging data in healthy individuals showed
bilateral activation in aIPS during grasping movements,
though the activation was stronger in the contralateral
hemisphere. Finally, the laterality issue has received attention
in an action observation fMRI study (Shmuelof and Zohary,
2005) in which participants viewed pictures of prehensile
movements performed with the left or right hand. The authors
reported that LaIPS activation was greater when viewing righthanded grasp and RaIPS activation was greater when viewing
left-handed grasping.
77
It remains unclear, therefore, whether the contribution of
aIPS to grasp is lateralized or not. First, inferences from prior
fMRI studies are limited because grasp was exclusively
performed with the right hand. Second, data from patients
with isolated anterior parietal lesions are rare and the role of
post-lesion neural reorganization is unknown. Third, because
action observation is inherently different from dynamic
control of prehension, it remains unclear whether Shmuelof
and Zohary's (2005) grasping observation data can be extended to dynamic control of self-generated prehension. Fourth,
any existing fMRI data offers only correlative evidence and
does not imply a causal relationship between anatomy and
function. We therefore sought to determine the lateralization
of aIPS involvement in dynamic control of prehensile movements by applying TMS to healthy individuals. Subjects were
required to grasp an object with their left or right hand while
TMS was applied to their LaIPS or RaIPS at the initiation of the
reach-to-grasp movement. To our knowledge this is the first
study to use TMS to reconcile the ambiguity of prehensile
lateralization in aIPS generated by functional imaging and
patient studies. We hypothesize that transient disruption of
left aIPS will impair grasping with the right hand only and
that disruption of right aIPS will impair grasping with the left
hand only. In addition, we predict that the effects observed
will be restricted to the grasp but not the transport
component of the movement based on previous findings
(Tunik et al., 2005; Rice et al., 2006).
2.
Results
Kinematic data were analyzed separately for the transport and
grasp components of the movement. Transport-related dependent measures included: movement time (MTt), peak
velocity (PVt), and percentage time of peak velocity (%TPVt).
These dependent measures were included as control measures, it was predicted that no significant findings would be
found for transport-related measured. A demonstration of no
significant effects on transport related measures is necessary
to make any specific comments regarding the grasping
component of the movement, as it is critical to illustrate that
grasping deficits cannot be accounted for by an overall
impairment in the reaching movement. Grasp-related dependent measures included: maximum grip aperture (MGAg),
percentage time of MGAg (%TMGAg), peak velocity of grip
aperture (PVg), and percentage time of peak velocity (%TPVg).
All data are presented in Table 1; for conciseness, only
significant findings are reported below.
Data analysis revealed that LaIPS mediates grasping with
the right hand only, and RaIPS mediates grasping with the left
hand only, as predicted this effect was restricted to grasp
dependent measures. This was revealed by a significant TMS
by hand interaction for the variable %TPVg (F(2,16) = 4.349,
p = 0.031); no other interactions were significant for any of the
other dependent variables tested. A series of paired sample
t-tests, comparing each TMS condition to the corresponding
no TMS condition (each subsequently collapsed across object
size, as there were no observed size effects or interactions)
revealed that this interaction can be accounted for by a
significant difference between no TMS and RaIPS TMS for the
78
BR A IN RE S EA RCH 1 1 75 ( 20 0 7 ) 7 6 –84
Table 1 – Results
MTt
No TMS
Left hand
Right hand
LaIPS TMS
Left hand
Right hand
RaIPS TMS
Left hand
Right hand
5
6
7
8
5
6
7
8
5
6
7
8
5
6
7
8
5
6
7
8
5
6
7
8
cm
cm
cm
cm
cm
cm
cm
cm
cm
cm
cm
cm
cm
cm
cm
cm
cm
cm
cm
cm
cm
cm
cm
cm
907.55
915.57
913.86
933.91
812.54
820.02
815.52
808.60
971.53
994.29
976.69
977.16
850.99
846.04
857.89
859.39
968.30
969.08
967.65
975.66
843.05
839.74
847.69
821.27
(167.50)
(137.63)
(149.79)
(160.26)
(130.08)
(128.15)
(125.59)
(104.02)
(197.43)
(218.62)
(199.12)
(204.17)
(92.57)
(107.21)
(112.38)
(133.63)
(199.22)
(211.25)
(214.94)
(230.49)
(129.91)
(125.74)
(139.27)
(115.34)
PVt
1079.90
1109.10
1084.79
1104.13
1218.39
1223.03
1220.75
1223.91
1060.88
1025.39
1058.06
1067.51
1164.31
1200.94
1187.78
1186.51
1111.30
1112.48
1116.56
1100.54
1169.60
1187.17
1168.78
1195.70
(158.79)
(157.54)
(131.07)
(149.06)
(180.09)
(155.42)
(163.76)
(157.86)
(136.46)
(157.70)
(179.24)
(154.38)
(175.54)
(166.25)
(174.35)
(179.91)
(145.27)
(162.37)
(152.81)
(195.27)
(152.36)
(139.11)
(148.64)
(147.58)
%TPVt
34.87
34.13
34.92
33.40
34.45
34.66
34.52
35.14
33.76
33.28
32.71
34.04
33.87
34.40
32.39
33.99
34.96
34.48
32.77
33.47
34.41
34.94
34.88
34.76
(4.83)
(4.11)
(5.73)
(5.40)
(3.04)
(3.79)
(3.42)
(3.86)
(5.95)
(5.74)
(5.66)
(6.98)
(4.74)
(2.53)
(3.71)
(4.10)
(6.44)
(6.23)
(7.00)
(6.88)
(2.91)
(1.70)
(2.18)
(2.35)
MGAg
60.49
64.68
67.85
76.69
66.42
71.12
77.08
81.96
58.57
63.32
66.96
70.47
68.34
72.87
77.05
82.39
64.17
65.68
69.09
73.80
68.39
71.48
77.53
82.83
(20.46)
(19.67)
(20.22)
(20.94)
(7.02)
(6.89)
(8.82)
(8.90)
(14.51)
(15.46)
(16.46)
(17.21)
(8.77)
(6.99)
(7.65)
(7.76)
(19.22)
(19.34)
(18.85)
(21.08)
(8.94)
(7.95)
(7.07)
(8.24)
%TMGAg
68.50
69.80
69.54
72.17
69.58
71.09
73.08
73.09
71.37
68.92
70.40
72.58
68.51
68.55
68.12
68.67
63.18
64.25
68.13
71.58
68.72
68.84
70.75
72.69
(13.69)
(11.72)
(11.16)
(8.35)
(6.62)
(7.21)
(8.26)
(9.26)
(11.47)
(12.43)
(10.82)
(12.38)
(14.41)
(8.21)
(9.69)
(11.88)
(14.70)
(13.40)
(11.24)
(15.01)
(8.15)
(8.31)
(8.69)
(8.59)
PVg
192.65
204.84
212.36
249.73
218.88
232.62
253.81
275.55
184.20
204.88
216.61
231.60
232.01
247.75
270.25
289.25
220.68
230.67
232.00
260.39
223.76
239.60
257.27
291.49
(74.58)
(70.69)
(74.57)
(81.83)
(31.03)
(27.24)
(44.04)
(48.41)
(46.05)
(58.99)
(56.82)
(65.76)
(51.77)
(46.04)
(51.49)
(44.31)
(71.98)
(75.60)
(74.12)
(87.26)
(38.12)
(38.96)
(33.93)
(54.91)
%TPVg
25.95
26.23
26.60
24.97
29.55
30.20
30.34
28.20
25.62
24.21
24.30
25.45
25.77
24.45
23.52
23.80
22.37
21.03
24.18
20.40
26.48
27.17
27.22
27.66
(5.40)
(4.04)
(5.09)
(4.21)
(7.10)
(6.91)
(6.57)
(4.69)
(8.00)
(6.51)
(6.55)
(7.64)
(6.00)
(5.43)
(5.05)
(6.50)
(5.42)
(6.11)
(8.49)
(4.64)
(7.48)
(7.15)
(7.00)
(6.27)
Table depicts mean and standard deviations (shown in parentheses) for all the dependent variables, including movement time (MTt), peak
velocity of wrist (PVt), time of peak velocity of wrist (%TPVt), maximum grip aperture (MGAg), time of maximum grip aperture (%TMGAg), peak
velocity of grasp (PVg) and time of peak velocity of grasp (%TPVg). It is notable that MGAg for the 8-cm object is slightly smaller than the actual
object size, we account for this by the placement of the markers on the index finger and thumb, which when the fingers are fully extended (as is
necessary to grasp the larger objects) causes MGA to be smaller than actual object size.
left hand condition (t = 2.415, p = 0.042), and a significant difference between no TMS and LaIPS TMS for the right hand
condition (t = 4.017, p = 0.004) (Fig. 1a). These data were also
expressed as a %TMS effect, and again collapsed across object
size (as previous analysis revealed no effects or interactions
of object size on this variable). One sample t-tests comparing
each TMS condition to zero, revealed a significant TMS effect
for both the LaIPS, Right hand condition (t = −4.112, p = 0.003),
and the RaIPS, Left hand condition (t = − 2.471, p = 0.039),
no other significant differences were observed; these data
are depicted in Fig. 1b. A significant main effect of TMS
was also observed for %TPVg (F(2,16) = 6.006, p = 0.011), with
time of peak velocity occurring later in the no TMS condition
relative to both TMS conditions (No TMS = 27.75, LaIPS = 27.71,
RaIPS = 27.46). This difference was significant for both the
left (t = 3.045, p = 0.016) and right (t = 2.970, p = 0.018) hemisphere (when compared to the no TMS condition), and
unlikely accounts for the observed interactions described
above.
A significant effect of object size was observed for MGAg
(F(3,24) = 31.025, p < 0.001), with grip aperture increasing as
object size increases (5 cm = 64.40 mm, 6 cm = 68.19 mm,
7 cm = 72.59 mm, 8 cm = 78.02 mm). A significant effect of
object size was also observed for PVg (F(3,24) = 21.962, p < 0.001),
with velocity increasing as object size increases (5 cm =
212.03 mm/s, 6 cm = 226.73 mm/s, 7 cm = 240.38 mm/s,
8 cm = 266.33 mm/s). This significant effect of object size for
these grasp dependent measures may account for the failure
to find any significant effects or interactions with TMS on
these variables, as this effect on object size increases the
variability for these measures.
For the transport variables, as predicted, no significant
effects or interaction with TMS were found. A significant
effect of hand was observed for MTt (F(1,8) = 9.918, p = 0.014).
This can be accounted for by subjects moving slower when
grasping with their left hand (955.94 mm/s) than their right
hand (835.23 mm/s). Such a finding supports the rationale
for expressing temporal measures as a percentage of movement time. No other significant effects or interactions were
observed.
3.
Discussion
In the present study, we used TMS to transiently disrupt LaIPS
and RaIPS to assess the contribution of each hemisphere to
the execution of prehensile movements with the right and the
left hand. We revealed that TMS to LaIPS disrupts grasping
with the right hand but not the left, and that TMS to RaIPS
disrupts grasping with the left hand but not the right. Our
results therefore limit the now established role of aIPS in
dynamic control of prehension (Tunik et al., 2005; Rice et al.,
2006) to the contralateral hand.
Our findings are in accord with previous data showing that
TMS to aIPS disrupts grasp (and not transport) kinematics on
tasks that manipulate grasp-related parameters (Tunik et al.,
2005; Rice et al., 2006). It is important to note that the transport
kinematics were used as control variables, as we did not
BR A IN RE S E A RCH 1 1 75 ( 20 0 7 ) 7 6 –8 4
Fig. 1 – Significant results. Graphs depicting significant
findings for (a) Time of peak velocity, expressed as a
percentage of movement time, and (b) %TMS effect for
time of peak velocity. Bars indicate means, with standard
errors, *p < 0.05, **p < 0.01.
predict any significant effect of TMS on these components of
the movement. To make claims regarding the role of aIPS in
the control of grasp, it is important to first establish that
effects cannot be accounted for by an overall impairment of
the reaching movement. One notable difference in the
significant findings observed in this study and in previous
investigations (Binkofski et al., 1998; Tunik et al., 2005; Rice et
al., 2006) is that the effects observed in the present study are
limited to the temporal aspects of the grasping movement. In
previous investigations, it has been reported that disruption of
aIPS resulted in deficits in grasp-related variables in both the
spatial (maximum grip aperture) and temporal (time of
maximum grip aperture and peak velocity of grip aperture)
dimensions. To reconcile such a finding it is important to
consider what an earlier time of peak velocity of grasp
represents in behavioral terms. An earlier time of peak
velocity represents a shortening of the acceleration phase of
the movement and a lengthening of the deceleration phase.
For example, in the no TMS right hand condition, subjects
achieve time of peak velocity on average at 29.57% of
movement time, meaning that they spend approximately
the first 30% of the movement accelerating, and the
remaining 70% decelerating. In the LaIPS right hand condi-
79
tion, subjects achieve time of peak velocity on average at
24.39% of the movement, meaning that subjects now spend
approximately 24% of the movement accelerating, and 76%
of the movement decelerating. We believe that this lengthening of the deceleration phase represents an overall
impairment in the movement, which subjects attempt to
compensate for by allowing more time for the hand to home
in on the target. As variables such as MGAg and %TMGAg
occur within this deceleration phase of the movement, we
propose that this longer deceleration phase allows subjects
to compensate for deficits that may have been elicited within
this time window.
The results of the present study extend the observations
that patients with damage to LaIPS and RaIPS have contralesional grasping deficits (Binkofski et al., 1998). Because of
the often broad extent of the lesion and the potential for
post-stroke reorganization, the interpretation of that data
may have limitations in establishing laterality of grasp
control. In addition, our results settle the dispute regarding
the contradictory findings within the functional imaging
literature involving grasping with the right hand (see Introduction), and extend these findings to grasping with the left
hand. The bilateral activation in aIPS during right handed
grasp that was observed by Binkofski et al. (1998) and Culham
et al. (2003) may perhaps be the result of some interhemispheric resonance that may automatically occur in anticipation of bilateral actions. Another possibility is that the
bilateral fMRI activations observed in aIPS are related to
processing occurring later in the movement. Whatever the
basis for such bilateral activation, our TMS data clearly show
an absence of a causal relationship between the aIPS
ipsilateral to the grasping hand and the execution of a prehensile movement.
Our results are unlikely to be accounted for by transitory
interference due to the fact that the second TMS pulse was
applied at approximately the same time as %TPVg for
several reasons. First, our TMS pulses were applied at 0
and 100 ms after movement onset, and absolute time of
peak velocity of the grasp occurred at an average time of
231.51 ms after movement onset for the no TMS condition.
As such, the second TMS pulse was delivered more than
100 ms before the peak velocity of the grasp, making it
unlikely that the effects can be accounted for by transitory
interference of the second pulse. Second, our effects were
observed only when subjects were grasping with the hand
contralateral to the TMS pulse, if the effects were due to an
interference from the TMS pulse itself then we would expect
the effects to be observed for both hands for this variable.
Third, if the effects can be accounted for by transitory interference then we would expect TMS effects to be observed
for other variables occurring at approximately the same time
as %TPVg, such as %TPVt (which occurred on average
295.82 ms after movement onset in the no TMS condition)
yet no significant effects of TMS were observed for this
variable.
Our data, taken in light of recent fMRI evidence that
observation of prehensile movements (Shmuelof and Zohary,
2005; Hamilton and Grafton, 2006), viewing and naming tools
(Chao and Martin, 2000), and imagining or pantomiming a
grasping movement (Shikata et al., 2003) are associated with
80
BR A IN RE S EA RCH 1 1 75 ( 20 0 7 ) 7 6 –84
activation in and around the aIPS, suggest that aIPS may be
equally important during action observation and dynamic
control (see also, Tunik et al., 2007). What remains unknown is
whether a causal role of aIPS for action observation is likewise
limited to the hemisphere contralateral to the observed hand,
is specialized to one hemisphere, or is bilateral. This question
is currently under investigation in our laboratory.
The results of our study rule out a left hemisphere
dominance model for the prehension system. This provides
evidence for a dissociation between the prehension and the
praxis system. Research from patients with apraxia have
shown that lesions to the inferior and superior parietal cortex
(within and adjacent to the left intraparietal sulcus), and the
left middle frontal gyrus cause difficulty with performance of
complex skilled actions (Haaland et al., 2000). Such a finding is
supported by imaging studies with healthy individuals,
showing a distributed left hemisphere network of regions
involved during the viewing and naming of tools (Chao and
Martin, 2000), as well as planning and executing tool-use
gestures with both the left and right hand (Johnson-Frey et al.,
2005). Our results provide further support for a distinction
between the parieto-frontal anatomy of the praxis system and
the prehension system (Johnson-Frey, 2003; Johnson-Frey
et al., 2005) by suggesting that unlike the praxis system
(which is dominated by the left hemisphere), the prehension
system is lateralized depending exclusively on the contralateral hand.
One difference between this study and those of previous
investigations within our laboratory (Tunik et al., 2005; Rice
et al., 2006) is the fact that we did not include a perturbation
condition. The reason for this difference between the present
study and our prior investigations is that Rice et al. (2006)
revealed that aIPS is involved in grasping independent of
whether a perturbation occurs, making a perturbation an
unnecessary manipulation in the current design. The results
of the present study support this finding. Further, it was not
clear from the previous investigation if the deficits we observed
were confounded by processes related to predicting whether a
perturbation would occur or not. The present design eliminates
this possibility suggesting that aIPS is involved in grasping
under conditions in which a perturbation will never occur. We
included 4 different object sizes in the present design to ensure
that the task was a difficult one. We argue in our previous study
(Rice et al., 2006) that the previously reported lack of TMS effects
under conditions of no perturbation (Tunik et al., 2005) may be
accounted for by the fact that the task was too easy, perhaps
permitting subjects to execute a default movement.
Our results differ from a recent study (Davare et al., 2007)
showing that bilateral inactivation of aIPS is necessary to
impair hand preshaping with the right hand, when applied
270–220 ms before object contact. Such findings differ from
observations with patients (Binkofski et al., 1998), showing
that a unilateral lesion to aIPS disrupts grasping with the
contralateral hand, and TMS investigations, showing that
transient disruption of left aIPS disrupts grasping to the right
hand (Tunik et al., 2005). We propose that the differences
between the study of Davare et al. and the studies conducted
within our lab can be accounted for by the timing of the TMS
pulses and the task employed. We recently showed that TMS
to left aIPS disrupts grasping, but only when applied simulta-
neous with hand movement execution (not during the
planning phase of the movement) (Rice et al., 2006), potentially
reflecting a role of aIPS in the computation of a difference
vector (Ulloa and Bullock, 2003). In the study of Davare et al.,
they applied the TMS pulses between 0 and 200 ms after the go
signal, and reported an average reaction time (i.e. time to
contact the object) of 268.7 ms. If we assume that the role of
aIPS in grasping involves the online computation of a
difference vector (i.e. the difference between the target and
the current state), then this computation could not be made in
the Davare et al. (2007) task until contact with the object was
made (as the task required applying a correct force to the
object to pick it up). Therefore, the timing of the pulses was
(for the most part) prior to the computation of this difference
vector, at a time when we know that left aIPS alone has no
functional role.
There are a number of other questions raised by this study
that warrant further investigation. While the present study
rules out a dominant left hemisphere model of grasp control,
this conclusion is limited to right-handers. It would be
interesting to address the role of these regions in left-handed
subjects. Evidence from a recent study (Gonzalez et al., 2006),
showing that both left- and right-handers are affected similarly
(by their left hand only) when grasping objects embedded in
visual illusions, might suggest that left-handers will show a
similar pattern of effects as that shown here. Another interesting question that warrants investigation is the contribution of
LaIPS and RaIPS to grasping in the contralateral and ipsilateral
visual fields. Investigations from imaging (Handy et al., 2003,
2005; Shmuelof and Zohary, 2005) as well as patient studies
(Perenin and Vighetto, 1988) suggest that there may be
differential hemispheric involvement when objects are presented in the contralateral or ipsilateral hemifield.
It also remains to be determined if the parietal cortex
contributes to reaching in a lateralized manner. While some
studies suggest bilateral involvement (Connolly et al., 2003),
others suggest that the involvement may be contralateral
(Desmurget et al., 1999). A good candidate for such an
investigation would be a region within the precuneus, which
has been suggested to be the human homologue of the monkey
parietal reach region (Connolly et al., 2003). We would predict,
based on a recent overlap study of patients suffering from
unilateral optic ataxia (Karnath and Perenin, 2005), that the
organization of this reaching system is contralateral in a similar
way as the organization of the grasping system.
In conclusion the results of the present study shed light on
the fronto-parietal hemispheric contribution to grasping with
the right and left hand. In particular, we show that prehensile
movements are highly lateralized with the LaIPS-mediating
grasp execution with the right hand but not the left, and the
RaIPS-mediating grasp execution with the left hand but not the
right.
4.
Experimental procedures
4.1.
Subjects
Nine healthy subjects participated in the study after providing
written informed consent (6 females, 3 males; mean age
BR A IN RE S E A RCH 1 1 75 ( 20 0 7 ) 7 6 –8 4
± standard deviation (S.D.), 24.67 ± 3.43 years old). Dartmouth
Institutional Review Board approval was granted for all
procedures. All subjects were right handed, as determined
using the Edinburgh Handedness Inventory (Oldfield, 1971).
Informed consent was obtained from each subject prior to
participation in the study in accordance with the principles of
the Declaration of Helsinki.
4.2.
Procedure
Subjects were seated at a table and instructed to place their
thumb and index finger on a start button directly in front of
them. 57 cm away from them, positioned at shoulder level,
they viewed an object mounted on the shaft of a motor
(Kollmorgen model no. S6MH4); this object comprised 4
rectangular targets offset at varying degrees, each target was
1.5 cm wide and 1 cm deep, however the length of each target
varied (8, 7, 6 or 5 cm) (Fig. 2). On a trial-by-trial basis, the
motor rotated the object so that one of the four targets was
oriented vertically. We included four different sized objects so
that, on each trial, subjects would be required to plan and
execute the movement, without relying on a default movement strategy. Visual feedback was controlled by liquid crystal
shutter glasses (Plato System, Translucent Technologies,
Canada), which were programmed to open for 200 ms at the
start of each trial, and remained opaque between each trial.
Subjects were instructed to grasp the target (which was
oriented on the vertical dimension) as soon as the shutter
glasses opened. The object was to be grasped using a precision
grip, with their index finger and thumb. The object was not to
be removed from the motor, subjects simply had to grasp the
object briefly then release their grip and return to the start
position. Subjects grasped the target with either their left or
their right hand, while they received TMS to their left
hemisphere, right hemisphere or not at all. As such there
Fig. 2 – Experimental setup. Light grey area indicates
opening of shutter glasses, and dark grey indicates closing of
shutter glasses. The glasses are open for 200 ms at the start
of each trial, during which time subjects view the object
mounted on the motor. Here subjects would be required to
grasp the large object (shown on the vertical dimension);
with a 90° change in orientation subjects would be required
to grasp the small object. After 200 ms, the glasses close and
remain closed for the remainder of the trial. On hand
movement onset (signalled by release of the start button) the
first TMS pulse is delivered (TMS 1), followed by the second
100 ms later (TMS 2).
81
were six different conditions, presented in blocks in a
counterbalanced order: (1) No TMS, Right hand grasp; (2) No
TMS, Left hand grasp; (3) Right hemisphere TMS, Right hand
grasp; (4) Right hemisphere TMS, Left hand grasp; (5) Left
hemisphere TMS, Right hand grasp; (6) Left hemisphere TMS,
Left hand grasp. Each block consisted of 40 trials, with there
being an equal probability of each of the four target objects
being oriented on the vertical dimension on any given trial,
forcing subjects to make a movement plan during the viewing
period of each trial. In TMS trials, the TMS was delivered in
double pulses, with the first pulse (TMS 1) delivered simultaneous with the release of the start button, and the second
pulse (TMS 2) occurring 100 ms after the first (see Fig. 2). This
double-pulse sequence was used to lengthen the window
during which the TMS-induced virtual lesion affected function. This sequence has proven effective in similar TMS
paradigms carried out in our lab (Rice et al., 2006).
4.3.
Localization of brain sites and TMS:
Two cortical sites were chosen for stimulation: (1) the most
anterior region of the IPS in the left hemisphere (LaIPS) and (2)
the most anterior region of the IPS in the right hemisphere
(RaIPS). In both hemispheres, this region is located at the
junction between the anterior extent of the IPS and the inferior
postcentral sulcus (Culham et al., 2003; Frey et al., 2005) (Fig. 3).
Ear plugs were provided to dampen the noise associated with
the discharge from the TMS coil as well as the rotation of the
motor. Given that grasp was performed by left and right hands
in each subject, the left and right aIPS sites served as each
other's control condition. As an additional precaution, subjects were tested in a no-TMS condition. In previous experiments within our laboratory, we have used a range of control
sites, including primary motor cortex and the parieto-occipital
complex (Tunik et al., 2005), and a medial and a caudal portion
of the left aIPS (Rice et al., 2006). In both these studies, it has
been shown that TMS to only LaIPS disrupts grasping,
providing strong evidence to suggest that these effects can
be localized to LaIPS and the effects cannot be accounted for by
a spread of activation to nearby areas.
A high-resolution three-dimensional volumetric structural
MRI was obtained for each subject (Philips 3T MRI scanner),
and the cortical surface was displayed as a three-dimensional
representation using Brainsight Frameless Stereotaxic software (Rogue-Research, Canada). Each targeted cortical site
was demarcated on the three-dimensional image using the
same software. The position of the coil and the subject's head
were monitored using a Polaris Optical Tracking System
(Northern Digital, Inc., Canada). Positional data for both rigid
bodies were registered in real time to a common frame of
reference and were superimposed onto the reconstructed
three-dimensional MRI image of the subject using the Brainsight software (Rogue-Research, Canada). For both sites, the
TMS coil was held tangential to the surface of the skull, with
the handle pointing backwards. The coil was held to the
subjects' skull by the experimenter using one hand, with the
other hand stabilizing the head to the coil. The position of the
coil to the head was monitored continuously online using
Brainsight (Rogue-Research, Canada), and head movements
were judged to be negligible. A chin-rest was not used in this
82
BR A IN RE S EA RCH 1 1 75 ( 20 0 7 ) 7 6 –84
Fig. 3 – Localization of brain sites for TMS. A three-dimensional rendering of one subject's structural MRI, illustrating the
left and the right hemispheres. The cortical sites chosen for stimulation are indicated by the white dots, which are placed at
the junction between the most anterior region of the intraparietal sulcus, and the postcentral sulcus.
experiment in an attempt to eliminate the side effects of head,
neck and back pain, which have been reported in a previous
study in our laboratory using a similar experimental set-up,
and attributed to the use of a chin-rest (Rice et al., 2006).
A Neotonus PNS stimulator (model no. N-0233-A-110V)
(Neotonus Inc., GA) with an air cooled iron-core butterflyshaped coil was used to administer TMS. Pulse duration for
this stimulator and head coil is 180 μs (at 100% of operating
power). This stimulator generates cosine pulses, and the
magnetic field distribution of the coil is comparable to a
5 cm × 10 cm figure of eight coil (Epstein and Zangaladze, 1996).
Measurements in a model head have indicated that the
isopotential contours of the induced electric field have an
oval shape, with the long axis parallel to the central windings
of the coil and the maximum electric field directly beneath the
center (Epstein et al., 1996). Double-pulse TMS (inter-stimulus
interval, 100 ms) was applied at 110% of motor threshold, to
each hemisphere. Motor threshold was determined separately
for both the left and right hemisphere, and defined as the
intensity required to produce a visible contraction of the
intrinsic contralateral hand muscles 50% of the time with the
coil positioned over the hand area of the left and right primary
motor cortex.
After completing the experiment, all participants were
required to complete a side effects questionnaire, as recommended by Machii et al. (2006). No side effects were reported
by any of the subjects. This is a notable difference when
compared to a previous TMS investigation within our laboratory using a similar experimental design and also stimulating
the intraparietal sulcus (although we note that in the previous
study, TMS was limited to left hemisphere stimulation) (Rice
et al., 2006). In this previous study, the reported side effects
included five reports of neck pain, four reports of headache,
two reports of scalp pain, and one report of difficulty
concentrating. We believe the exclusion of the chin rest can
account for the majority of the reduction in reported side
effects in the present study, and suggest this should be a
consideration in the design of future TMS studies. We note
that controlling head movements is fundamental to TMS
investigations to ensure that stimulation is being limited to
the site of interest. We, however, believe that with methodological advances, in particular, the introduction of frameless
stereotaxic software such as Brainsight (Rogue-Research,
Canada), which allows one to monitor the position of the
stimulation locus to the site of interest, it is possible to
monitor and document head movements online, and subsequently remove such data from analysis.
4.4.
Analysis and statistics
Kinematic data were obtained by localizing the threedimensional position of six infrared light-emitting diodes
(Optotrak 3020, Northern Digital Inc., Canada; sampling rate,
100 Hz) attached to the joint between the distal and
intermediate phalanges of the index finger and thumb on
the left and right hand and the metacarpophalangeal joint
(MPJ) of the index finger of the right hand, and little finger of
the left hand. The placement of the markers ensured
minimal occlusion during the grasping movement. Offline,
missing samples were interpolated and the data were filtered
at 10 Hz using custom written Labview (National Instruments, TX) software. The onset and offset of the movement
were defined as the time at which the velocity of the MPJ
marker exceeded and then fell below 50 mm/s, respectively.
Trials were excluded from analysis if missing data points due
to occlusion of the infrared light-emitting diodes prevented
the analysis of that trial. A total of 82% of data were included
in final analysis.
Kinematic data were analyzed separately for the transport
and grasp components of the movement. Based on previous
findings (Tunik et al., 2005; Rice et al., 2006), we predict that
aIPS will be involved in only the grasp component of the
movement. Transport-related dependent measures included:
MTt, defined by the time interval between movement onset
and offset; PVt, defined as the maximum value of the first
derivative of the 3D position of the MPJ marker; and %TPVt,
defined as the time interval between peak velocity and
movement onset, expressed as a percentage of movement
time. Grasp-related dependent measures included: MGAg,
defined as the three-dimensional distance between the
index and thumb markers; %TMGAg, defined as the time
interval between MGAg and movement onset, expressed as a
percentage of movement time; PVg, defined as the maximum
value of the first derivative of grip aperture; and %TPVg
defined as the time interval between peak velocity of grip
aperture and movement onset, expressed as a percentage of
BR A IN RE S E A RCH 1 1 75 ( 20 0 7 ) 7 6 –8 4
movement time. Temporal measures were always expressed
as a function of movement time as pilot data indicated that
subjects are slower at grasping with their left hand than their
right, and we wanted to ensure that any effects observed in
these variables were not a function of hand effect.
Data were analyzed using 3 × 2 × 4 repeated measures
analysis of variance (ANOVA) for each dependent measure,
with factors TMS site (LaIPS, RaIPS and No TMS), hand (Left
hand and Right hand) and object size (8, 7, 6 and 5 cm). Where
significant results were obtained pre-planned t-tests were
used for subsequent analysis. In addition, for variables
affected by TMS, data was normalized to the corresponding
no TMS condition, and expressed as a percentage TMS effect,
according to the following equation: %TMS effect = [(TMS
condition − Mean No TMS condition) / (Mean No TMS Condition)] × 100. A similar method of expressing TMS effects have
been reported elsewhere (Schenk et al., 2005). A one-sample ttest was then conducted on these data comparing each
condition to zero (with zero indicating no effect of TMS). A
significance threshold of 0.05 was adopted. For conciseness
only significant findings are discussed, however data for all
variables are presented in Table 1.
Acknowledgment
This work was supported by PHS grants NS44393 and NS33505.
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