Current Biology 20, 1–7, April 27, 2010 ª2010 Elsevier Ltd All rights reserved DOI 10.1016/j.cub.2010.02.045
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Single-Neuron Responses
in Humans during Execution
and Observation of Actions
Roy Mukamel,1,2,3,* Arne D. Ekstrom,1,5 Jonas Kaplan,2,3,6
Marco Iacoboni,2,3,4 and Itzhak Fried1,3,4,7
1Department of Neurosurgery
2Ahmanson-Lovelace Brain Mapping Center
3Semel Institute for Neuroscience and Human Behavior
4Brain Research Institute
David Geffen School of Medicine, University of California, Los
Angeles (UCLA), Los Angeles, CA 90095, USA
5Center for Neuroscience, 1544 Newton Court, University of
California, Davis, Davis, CA 95618, USA
6Brain and Creativity Institute and Department of Psychology,
University of Southern California, Los Angeles, CA, 90098, USA
7Functional Neurosurgery Unit, Tel Aviv Medical Center and
Sackler School ofMedicine, Tel Aviv University, Tel Aviv 69978,
Israel
Summary
Direct recordings in monkeys have demonstrated that
neurons in frontal and parietal areas discharge during
execution and perception of actions [1–8]. Because these
discharges ‘‘reflect’’ the perceptual aspects of actions of
others onto the motor repertoire of the perceiver, these
cells have been called mirror neurons. Their overlapping
sensory-motor representations have been implicated in
observational learning and imitation, two important forms
of learning [9]. In humans, indirect measures of neural
activity support the existence of sensory-motor mirroring
mechanisms in homolog frontal and parietal areas [10, 11],
other motor regions [12–15], and also the existence of
multisensory mirroring mechanisms in nonmotor regions
[16–19]. We recorded extracellular activity from 1177 cells
in humanmedial frontal and temporal cortices while patients
executed or observed hand grasping actions and facial
emotional expressions. A significant proportion of neurons
in supplementary motor area, and hippocampus and envi-
rons, responded to both observation and execution of these
actions. A subset of these neurons demonstrated excitation
during action-execution and inhibition during action-obser-
vation. These findings suggest that multiple systems in
humansmay be endowed with neural mechanisms ofmirror-
ing for both the integration and differentiation of perceptual
and motor aspects of actions performed by self and others.
Results
We recorded extracellular activity from a total of 1177 neurons
in 21 patients while they observed and executed grasping
actions and facial gestures. In the observation conditions,
subjects observed various actions presented on a laptop
screen. In the execution conditions, the subjects were cued
to perform an action by a visually presented word. In a control
task, the same words were presented and the patients were
instructed not to execute the action (see Experimental Proce-
dures and Figure S1A available online). In the medial frontal
cortex, we recorded from 652 neurons (369 single units, and
283 multiunits) in the supplementary motor area (SMA; both
SMA proper and pre-SMA), and anterior cingulate cortex
(ACC; both the dorsal and rostral aspects [20]). In the medial
temporal lobe we recorded from 525 neurons (296 single units,
and 229multiunits) in the amygdala, hippocampus, parahippo-
campal gyrus (PHG), and entorhinal cortex (EC) (see Fig-
ure S1B for anatomical location of electrodes). The number
of cells recorded in each region is provided in Table 1A.
Significant changes in firing rate were tested with a two-
tailed paired t test between the firing rate during baseline
(21000 ms to 0 ms relative to trial onset) and a window of
+200 to +1200 ms after stimulus onset (see Experimental
Procedures). For each action (smile, frown, precision grip, or
wholehand grip) we examined the neural response during
action-observation and action-execution. A response to
action-execution was considered only if there was no signifi-
cant response to the corresponding control task.
After examination of the cell’s response to each action sepa-
rately, the cell was classified as follows:
Action-observation neuron: a cell responding only during
one or more action-observation conditions and not during
any of the action-execution conditions (e.g., a cell respond-
ing to smile observation and frown observation).
Action-execution neuron: a cell responding only during one
or more action-execution conditions and not during any of
the action-observation conditions (e.g., a cell responding to
precision-grip execution).
Action observation/execution nonmatching neuron: a cell
responding during action-observation in one condition
and action-execution in a different condition (e.g., a cell
responding to smile observation and frown execution).
Action observation/execution matching neuron: a cell
responding during both the execution and the observation
of the same action (e.g., a cell responding to smile observa-
tion and smile execution).
Table 1B provides the number of cells in each category
described above, according to anatomical region. Themajority
of cells responded to one dimension of the stimuli (observation
or execution). In the SMA [c2(1) = 14.5, p = 1023] and pre-SMA
[c2(1) = 4.2, p = 0.03], the proportion of responses to action-
execution relative to action-observation was significantly
higher. In the other regions examined (ACC and medial
temporal lobe) there was no significant difference between
the two conditions. Six cells responded to observation, execu-
tion, and also the control task of one action and were therefore
not considered as action observation/execution matching
cells (three cells in PHG, two in EC, and one in SMA). Within
the population of action-observation cells, there were more
responses to hand grasps (precision grip or wholehand
prehension) in PHG relative to facial gestures (smile or frown;
c2(1) = 3.9, p = 0.04), and more responses to observations of
facial gestures relative to hand grasps in ACCd [c2(1) = 4.8,
p = 0.02]. The distribution of responses within the population*Correspondence: rmukamel@ucla.edu
Please cite this article in press as: Mukamel et al., Single-Neuron Responses in Humans during Execution and Observation of Actions,
Current Biology (2010), doi:10.1016/j.cub.2010.02.045

of action-observation cells and action-execution cells is pro-
vided in Table S1.
We subsequently focused our analyses on the action obser-
vation/execution matching cells responding during both
observation and execution of particular actions. Figure 1A
displays one such cell in the SMA responding to the observa-
tion and execution of two grip types (precision and whole-
hand). This cell did not respond to the control tasks or any of
the facial gesture conditions. Figure 1B displays another cell
in entorhinal cortex responding to observation and execution
of facial gestures (smile and frown). Again, this cell did not
respond to the control tasks or to observation and execution
of the various grips.
Next, we tested whether the proportion of action observa-
tion/execution matching neurons in each anatomical region
is significantly higher than that expected by chance (chance
level set at 5%).We performed a chi-square test on the propor-
tion of such cells in each region (except for the amygdala
where we performed Fischer’s exact test due to small number
of cells). The proportion of cells in the hippocampus [c2(1) =
12.5, p = 2 3 1024], parahippocampal gyrus [c2(1) = 17.4,
p < 1024], entorhinal cortex [c2(1) = 3.3, p < 0.05], and SMA
[c2(1) = 19.4, p < 1024] was significantly higher than expected
by chance. In amygdala, pre-SMA, ACCd, and ACCr the
proportions were not significantly higher than chance. In addi-
tion to the chi-square test, we performed a bootstrap analysis
to test whether or not the number of action observation/execu-
tion matching neurons is higher than the null distribution
(see Experimental Procedures). Figure S2A displays the null
distribution (blue) together with the actual number of cells in
our data set (red arrow). In agreement with the chi-square
test described above, the number of cells in SMA (p = 0.003),
entorhinal cortex (p = 0.001), hippocampus (p < 1024), and par-
ahippocampal gyrus (p < 1024) were significantly higher than
expected by chance. In addition, we performed the same anal-
ysis, this time taking into account only cells defined as single
units and obtained similar results (SMA (p = 0.02), EC (p =
0.004), H (p = 0.02), and PHG (p = 0.007); see Figure S2B).
Furthermore, the proportion of action observation/execution
matching neurons in these regions was significantly higher
compared with Poisson generated spike trains with similar
firing rates (Figure S2C). The distribution of joint p values for
these action observation/execution matching neurons is pro-
vided in Figure S2D for the different regions.
Next, we focused on the action observation/execution
matching neurons in the anatomical regions where the propor-
tion of such cells was significant (SMA, parahippocampal
gyrus, hippocampus, and entorhinal cortex). Figure 2 displays
the responses of six additional neurons from these various
regions. The complete response details of all action observa-
tion/execution matching cells are provided in Table S2. The
majority of these cells (40 out of 68) were classified as single
units (see Experimental Procedures). Among the 68 action
observation/execution matching cells, 33 increased their firing
rate during both observation and execution of a particular
action (e.g., Figures 2A–2D). In contrast, 21 other neurons
decreased their firing rate during both conditions (Figure 2E).
These types of responses have been previously reported in
monkeys (e.g., [21]) and birds [22]. Furthermore, 14 neurons
increased their firing rate during one condition and decreased
it during the other. Themajority of these cells (n = 11) increased
their firing rate during action-execution and decreased their
firing rate during action-observation (Figure 2F), whereas the
remaining neurons did the opposite [c2(1) = 6.2, p = 0.01].
For anatomical distribution of response types see Table S3A.
Obviously, the breaking down of responses by type and
anatomical region makes it difficult to test for regional differ-
ences and therefore to draw any firm conclusion on these
distributions.
We subsequently examined the temporal profiles of neural
activity by computing the average response profile of all action
observation/execution matching neurons. This was con-
ducted separately for cells exhibiting excitation to both condi-
tions (Figure 3A), inhibition to both conditions (Figure 3B), and
cells exhibiting excitation during action-execution and inhibi-
tion during action-observation (Figure 3C). In order to accom-
modate for differences in firing rates across different cells
before averaging, similar to [21] we normalized each excitatory
response to range between 0 and +1, and each inhibitory
responses to range between 0 and 21 (see Experimental
Table 1. Location and Response Types of Recorded Cells
A. Location of Recorded Cells
Region A H EC PHG SMA Pre-SMA ACCd ACCr Total
SU/MU 11/22 92/71 102/73 91/63 82/43 79/65 66/59 142/116 665/512
Right 13 77 81 48 23 68 80 168 558
Left 20 86 94 106 102 76 45 90 619
Total 33 163 175 154 125 144 125 258 1177
B. Response Types
Region A H EC PHG SMA Pre-SMA ACCd ACCr %
Action-execution 11 (4, 7)
(33%)
36 (19, 17)
(22%)
37 (18, 19)
(21%)
39 (22, 17)
(25%)
41 (27, 14)
(33%)
34 (23, 11)
(24%)
28 (12, 16)
(22%)
50 (28, 22)
(19%)
23%
Action-observation 4 (1, 3)
(12%)
29 (18, 11)
(18%)
32 (21, 11)
(18%)
35 (19, 16)
(23%)
13 (9, 4)
(10%)
19 (11, 8)
(13%)
26 (15, 11)
(21%)
45 (25, 20)
(17%)
17%
Observation/
Execution matching
2 (1, 1)
(6%)
18 (8, 10)
(11%)
14 (9, 5)
(8%)
19 (13, 6)
(12%)
17 (10, 7)
(14%)
6 (4, 2)
(4%)
2 (2, 0)
(2%)
12 (8, 4)
(5%)
8%
Observation/Execution
nonmatching
1 (0, 1)
(3%)
16 (8, 8)
(10%)
11 (5, 6)
(6%)
11 (8, 3)
(7%)
13 (7, 6)
(10%)
10 (5, 5)
(7%)
1 (0, 1)
(1%)
14 (8, 6)
(5%)
7%
(A) Number of single units (SU) and multiunits (MU) recorded in the left and right hemispheres in various anatomical regions.
(B) Response types of cells across all recorded regions. Absolute number (single unit, multiunit) and percentages of cells (calculated from total number of
recorded cells in each region; see A). The last column represents the percentage of responses across all regions. For definitions of response types, see text.
The following abbreviations are used: A, amygdala; H, hippocampus; EC, entorhinal cortex; PHG, parahippocampal gyrus; SMA, supplementarymotor area;
ACCd, dorsal aspect of anterior cingulate; and ACCr, rostral aspect of anterior cingulate. See also Table S2.
Current Biology Vol 20 No 8
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Please cite this article in press as: Mukamel et al., Single-Neuron Responses in Humans during Execution and Observation of Actions,
Current Biology (2010), doi:10.1016/j.cub.2010.02.045