Coupling of the cortical hemodynamic response
to cortical and thalamic neuronal activity
Anna Devor*†, Istvan Ulbert*‡§, Andrew K. Dunn*, Suresh N. Narayanan*, Stephanie R. Jones*, Mark L. Andermann*¶,
David A. Boas*, and Anders M. Dale*?
*Massachusetts General Hospital NMR Center and¶Program in Biophysics , Harvard Medical School, Charlestown, MA 02129;‡Institute for Psychology
of the Hungarian Academy of Sciences, Budapest 1068, Hungary; and?Departments of Neurosciences and Radiology, University of California at San Diego,
La Jolla, CA 92093
Edited by Marcus E. Raichle, Washington University School of Medicine, St. Louis, MO, and approved January 25, 2005 (received for review
October 20, 2004)
Accurate interpretation of functional MRI (fMRI) signals requires
knowledge of the relationship between the hemodynamic re-
sponse and the neuronal activity that underlies it. Here we address
the question of coupling between pre- and postsynaptic neuronal
activity and the hemodynamic response in rodent somatosensory
(Barrel) cortex in response to single-whisker deflection. Using
full-field multiwavelength optical imaging of hemoglobin oxygen-
ation and electrophysiological recordings of spiking activity and
local field potentials, we demonstrate that a point hemodynamic
measure is influenced by neuronal activity across multiple cortical
columns. We demonstrate that the hemodynamic response is a
spatiotemporal convolution of the neuronal activation. Therefore,
positive hemodynamic response in one cortical column might be
explained by neuronal activity not only in that column but also in
the neighboring columns. Thus, attempts at characterizing the
neurovascular relationship based on point measurements of elec-
trophysiology and hemodynamics may yield inconsistent results,
that the hemodynamic signal observed at a given location is a
helps explain a previously observed increase of local vascular
response beyond the saturation of local neuronal activity. We also
demonstrate that the oxy- and total-hemoglobin hemodynamic
responses can be well approximated by space–time separable
functions with an antagonistic center-surround spatial pattern
extending over several millimeters. The surround ‘‘negative’’ he-
modynamic activity did not correspond to observable changes in
neuronal activity. The complex spatial integration of the hemody-
Barrel cortex ? blood oxygenation ? intrinsic signals ? optical imaging
hemodynamic ‘‘activation’’ in the human brain under a variety of
conditions (1, 2). However, the indirect and poorly understood
nature of the coupling between these hemodynamic signals and
the underlying neuronal activity has greatly limited the inter-
pretability of neuroimaging results. Recently, several groups
have attempted to characterize this coupling in the form of a
linear or nonlinear neurovascular ‘‘transfer function’’ (3–8). In
principle, if such a function could be defined, it would provide
a basis for inferring time-averaged local neuronal activity based
on hemodynamic measurements. Furthermore, it would permit
more accurate integration of hemodynamic imaging methods
with noninvasive electrophysiological recordings such as elec-
troencephalography and magnetoencephalography (9, 10).
In a previous publication (3), using simultaneous spectro-
scopic optical imaging and electrophysiological measurements in
rodent somatosensory cortex during brief and spatially localized
hemodynamic and neuronal signals. Specifically, our results
showed that with an increase in stimulus amplitude, the hemo-
he advent of noninvasive imaging methods such as functional
MRI (fMRI) has made it possible to obtain spatial maps of
dynamic response recorded from the region of interest (ROI)
surrounding the recording electrode increased beyond the sat-
uration of electrical activity as reflected in multiple unit activity
(MUA) and local field potential (LFP) measurements. Subse-
quently, other groups have produced consistent results in the
same system by using both tactile and electrical stimuli (4, 8).
This apparent mismatch between neuronal and hemodynamic
behavior may result from neuronal processes, such as a neuro-
transmitter release from presynaptic thalamic terminals, unde-
tected by the electrophysiological recording methods used (11–
13). Here we present data showing that the hemodynamic
response within a cortical column (a principal barrel in Barrel
cortex) increases beyond saturation of the thalamic input to the
same column. It is therefore likely that the hemodynamic
response measured in the principal barrel column is driven at
least in part by neuronal activity outside the column. Indeed, the
neuronal response in neighboring barrels was observed to in-
crease throughout the stimulus range, thus providing a potential
explanation for monotonically increasing hemodynamic re-
sponse within a principal barrel beyond saturation of the local
The methods are described in detail in ref. 3.
Animal Preparation. Male Sprague–Dawley rats (n ? 17, 250–350
g, Taconic Farms) were used. All experimental procedures were
approved by the Massachusetts General Hospital Subcommittee
on Research Animal Care. Rats were initially anesthetized with
1.5% halothane and ventilated with ?1% halothane in a mixture
of air and oxygen. Halothane was discontinued, and anesthesia
was maintained with a 50-mg?kg?1i.v. bolus of ?-chloralose
followed by continuous i.v. infusion at 40 mg?kg?1?h?1. Heart
rate, blood pressure, blood gas, and body temperature were
An area of skull overlying the primary somatosensory cortex
was exposed and then thinned until soft and transparent (?100
?m). A well of petroleum jelly was built and filled with mineral
oil (Sigma). A small hole was made in the thinned skull over the
center of a barrel, as determined by optical imaging, and the
recording electrode was introduced through the dura mater. For
This paper was submitted directly (Track II) to the PNAS office.
Freely available online through the PNAS open access option.
fMRI, functional MRI; Hb, deoxyhemoglobin; HbO, oxyhemoglobin; HbT, total hemoglo-
bin; VPM, ventral posteriomedial thalamic nucleus; POm, medial division of the posterior
†To whom correspondence should be addressed. E-mail: firstname.lastname@example.org.
§I.U. recently founded and is the majority owner of Neurotrack, a company that develops
and markets laminar electrophysiology equipment for animal research.
© 2005 by The National Academy of Sciences of the USA
March 8, 2005 ?
vol. 102 ?
recordings involving laminar probes, the thinned skull and dura
mater were removed.
Spectroscopic Optical Imaging. To illuminate the cortex, light from
a mercury xenon arc lamp was directed through a six-position
rotating filter wheel (560, 570, 580, 590, 600, and 610 nm)
coupled to a 12-mm fiber bundle. Images of a 4.5- to 6-mm2area
were acquired by a cooled 12-bit charge-coupled device camera
(Coolsnap, Photometrics, Tucson, AZ). Image acquisitions were
triggered at ?15 Hz by individual filters in the filter wheel
passing through an optic sensor (14). The spectral data were
converted to percent change maps for deoxyhemoglobin (Hb),
modified Beer–Lambert law (14). Differential pathlength cor-
rection was applied to adjust for the differential optical path-
length through the tissue at different wavelengths. The point-
spread function for the optical signal was estimated as 100 ?m
in the lateral plane at a depth of 400 ?m from the cortical
Electrophysiological Recordings. Electrophysiological recordings
were performed by using either single metal microelectrodes
[FHC (Bowdoinham, ME), 5–7 M?] or linear array multielec-
trodes with 24 contacts spaced at 100 ?m (15). Layer IV was
identified by depth and a selective response to the principal
based on a contact number when contact no. 1 was positioned at
the cortical surface by using visual control. A contact with the
strongest selectivity was identified by listening to an audio
monitor while stimulating different whiskers. The signals were
amplified and filtered between 500 and 5,000 Hz to record MUA
and between 0.1 and 500 Hz to record LFP. The MUA signals
were rectified on the time axis before averaging. Averaged LFP
curves were rectified on the time axis before integration. In
cortex, the microelectrodes were positioned in lower layer II?III
(400–500 ?m). The ventral posteriomedial thalamic nucleus
(VPM) and the medial division of the posterior thalamic nucleus
(POm) were targeted by using stereotactic coordinates (VPM,
AP ?3.6 to ?3.0, ML 2.0 to 3.5, and DV 5.0 to 7.0; POm, AP
?4.3 to ?3.5, ML 1.5 to 2.5, and DV 5.0 to 6.5).
Stimulation Paradigm. Single whiskers were deflected upward by
a wire loop coupled to a computer controlled piezoelectric
stimulator. We used a fast randomized event-related stimulus
presentation paradigm analogous to that used in event-related
fMRI studies. The stimulus sequence was optimized for event-
related response estimation efficiency by using the approach
described by Dale (16). The stimulation paradigm consisted of
single deflections of varying amplitude with an interstimulus
interval of 1 sec. We used 27 stimulus amplitudes. Intervening
amplitudes were spaced with equal increments on a linear scale.
The stimulus angular velocity increased from 203° per sec
(vertical displacement of 240 ?m, amplitude 1) to 969° per sec
(vertical displacement of 1,200 ?m, amplitude 27). For each
stimulus condition, we averaged 240 trials for each animal.
The Barrel cortex in the rat is well suited for studying localized
cortical activations due to precise mapping of each one of the
large facial vibrissae (whiskers) onto a specific cortical area,
called a barrel (17). In agreement with previous reports, tactile
stimulation of a single facial whisker produced spatially localized
optical signals centered on the principal barrel and extending
well beyond one cortical column (18). Fig. 1 shows activation
maps of HbO, Hb, and HbT as a function of time after deflection
time-resolved spectral optical measurements obtained with a
rotating filter wheel (see Methods). In agreement with our
previous report (3), an initial increase (‘‘initial dip’’) in Hb was
accompanied by an initial decrease in HbO, both preceding an
increase in HbT (Fig. 1; see also Fig. 7, which is published as
supporting information on the PNAS web site). These early
changes may correspond to a local increase in oxygen consump-
tion preceding an increase in blood flow (19, 20). A subsequent
increase in HbT (reflecting an increase in blood volume under
the assumption of constant hematocrit) was accompanied by a
reversal of sign in both Hb and HbO signals, presumably
corresponding to washout of Hb by increased blood flow (21).
The hemodynamic signals always exhibited an antagonistic cen-
ter-surround spatial pattern. The increase in HbO and HbT
centered on the principal barrel was always accompanied by
corresponding decreases in the surround. Similarly, a decrease in
amplitudes) were calculated from six wavelength data. Each image represents an individual frame (average of ?1,400 trials). Time between consecutive images
is 200 msec. (b) A continuation of the time series shown in a. The signal for Hb and HbO is expressed in percent change relative to its own baseline concentration
(40 and 60 ?M, respectively, were assumed for all animals). HbT was calculated as a sum of Hb and HbO.
Spatiotemporal evolution of the hemodynamic reponse. (a) Full-field time series of HbO, Hb, and HbT signals (an average of the six strongest stimulus
Devor et al.PNAS ?
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Hb in the center was always accompanied by an increase in the
A comparison of the center-surround pattern of the HbO
response at the peak of activation (Fig. 2a) to an estimated size
of the Barrel cortex (Fig. 2c) shows that the center ‘‘positive’’
activity covers approximately the entire Barrel cortex, whereas
the surround ‘‘negativity’’ is present outside Barrel cortex, and
even outside the primary somatosensory cortex (22). The
hemodynamic response as a function of stimulus intensity was
investigated in the regions corresponding to the principal
barrel and the surround ‘‘negativity’’ (Fig. 2). The first ROI
was defined as a 300 ? 300-?m area around the electrode used
to record spiking (MUA) and synaptic (LFP) neuronal activity
from the principal barrel. Taking into account the distance
between the adjacent barrels of ?500 ?m (23), this ROI
reflected the hemodynamic response in the principal barrel
column. The second ROI was defined as all pixels at least 3 mm
away from the recording electrode, reflecting the region of
surround negativity well outside the Barrel cortex. An ampli-
tude of the hemodynamic response increased with an increase
in stimulus intensity in both the center and surround ROIs
(Fig. 2b), with a surround amplitude in average ?10% of that
in the center. A comparison of hemodynamic responses aver-
aged from 300 ? 300-?m ROIs around recording electrodes
with electrophysiological recordings showed no change in
neuronal activity in the surround region (Fig. 2 d and e; see also
Fig. 8, which is published as supporting information on the
PNAS web site). Thus, the surround negative response did not
correspond to local neuronal inhibition, as measured by our
methods. The spatiotemporal pattern of the hemodynamic
activity including the biphasic spatial pattern is also evident in
our previous data using a different anesthesia agent, urethane,
which indicates a conservation of the phenomenon across
anesthesia conditions and rules out a possibility that the
center-surround pattern is an artifact of ?-chloralose (3).
Principal component analysis revealed one dominant compo-
nent explaining most of the variance for the HbO and HbT
spatiotemporal observations and, to a lesser extent, Hb (Table 1;
see also Fig. 9, which is published as supporting information on
the PNAS web site). The more complex behavior of Hb may
reflect a combination of competing effects of oxygen consump-
tion, blood volume changes, and washout process at different
timescales. The stimulus dependence of the surround negativity
(Fig. 2b) and the results of principal component analysis indicate
space–time separability of HbO and HbT hemodynamic activa-
tion, where the response at every time point and stimulus
amplitude represents a scaling version of a fixed center-surround
Consistent with our previous results (3), the hemodynamic
response within the principal barrel continued to increase be-
(Fig. 3; see also Fig. 10, which is published as supporting
information on the PNAS web site). The hemodynamic response
in the principal barrel increased monotonically throughout the
stimulus range. An approximately linear relationship was ob-
spatial pattern. (a) An image of HbO at the peak of the response. (b) Integral
HbO (red) and HbT (black) responses as a function of stimulus intensity in the
center (principal barrel, ROI?in) and surround (?3 mm away from the record-
ing electrode, ROI?out). Data from five animals were averaged, and all am-
plitudes are shown. The error bars reflect the intersubject standard error. The
the maximal response amplitude in the center ROI for that animal before
averaging the data across animals. Note that the magnitude of the negative
surround response is on average ?10% of that in the center. (c) The locations
of electrophysiological recordings are superimposed on the image of the
vasculature corresponding to the functional map in a. Recordings from loca-
electrodes are visible on the image). The indicated approximate location of
the Barrel field was determined by fitting the position, size, and orientation
of a typical histology sample based on the locations of two identified barrel
columns (C3 and D1). (d) Time courses of HbT response averaged from 300 ?
300 ?m ROIs around recording electrodes. The locations are color coded in a
and c. (e) MUA recorded from the locations marked in c. Responses to seven
top and bottom plots in d and e differ by factor of 5. The arrow denotes
The hemodynamic response has an antagonistic center-surround
Table 1. Percent variance explained by the first principal
component analysis for HbO, Hb, and HbT signals
Each row represents one case (one animal). ID, identification.
neuronal activity. (a) Integral HbO (red) and HbT (black) responses averaged
from 300 ? 300 ?m ROI around the electrode recording from the principal
barrel as a function of stimulus intensity. Data from eight animals were
standard error. (b) MUA (Left), LFP (Right) peak (red), and integral (black)
responses as a function of stimulus amplitude. The data were averaged across
the same subjects as in a. The curves were fitted by using the function
www.pnas.org?cgi?doi?10.1073?pnas.0407789102Devor et al.
served between the hemodynamic response, measured as the
integral under the timecourse curve, and the stimulus amplitude
(Fig. 3a). Note that the conserved spatiotemporal pattern of the
hemodynamic response for HbO and HbT (Fig. 9) implies that
a time course averaged from any other ROI will behave as a
scaled version of that from the principal barrel ROI. In contrast
to the hemodynamic response, spiking and synaptic neuronal
activity recorded from the principal barrel as MUA and LFP,
respectively, exhibited saturation with an increase in stimulus
intensity. LFP measures a weighted sum of transmembrane
currents due to synaptic and dendritic activity (24, 25), whereas
MUA measures population spiking activity (26, 27). We esti-
mated a total evoked neuronal activity by using the integral
under the curve and peak values for MUA and LFP. All
measures showed pronounced saturation with an increase in
stimulus intensity (Fig. 3b).
Sensory inputs from the whisker pad reach Barrel cortex via
two parallel pathways: lemniscal (via the VPM) and paralemnis-
cal (via the medial division of the posterior thalamic nucleus,
POm) (28–30). In the VPM, each facial vibrissa is mapped onto
a cluster of cells (a barreloid) that sends its output to the
corresponding cortical barrel (31). The POm has more diffuse
maps, longer latencies, and a strong dependence on cortical
feedback (32). To test whether the apparent mismatch between
neuronal and hemodynamic behavior results from a presynaptic
(thalamic) process, we performed simultaneous measurements
from corresponding locations in the cortex and thalamus. Si-
multaneous measurements from the corresponding barreloid in
the VPM showed that the input cortical layer (layer IV) followed
closely the thalamic input. Fig. 4 shows the MUA response in
thalamus (Fig. 4a1) and cortical input layer IV (Fig. 4a2). Fig.
4b1 shows an increase in response in thalamus (black) and
cortical layer IV (red) as a function of stimulus intensity. The
same function [ax?(1?bx)c] fits well both cortical and thalamic
VPM spiking activity. Therefore, the saturation of the MUA in
layer IV of the cortex is fully explained by saturation in the input
from the VPM. Note that the similarity in the cortical and
thalamic responses under our stimulus conditions should not be
taken as a general case. Thalamocortical response transforma-
tion can be readily demonstrated by using other stimulus para-
digms such as whisker deflections with different rise time (33),
prolong ‘‘ramp-and-hold’’ trapezoids (34) or repetitive stimula-
The results of simultaneous laminar recordings of MUA from
VPM and POm are shown in Fig. 5. In agreement with previous
reports (32), POm responses peaked later in time (Fig. 5b) and
were distributed through a number of recording electrodes
indicating diffuse mapping (data not shown). Recordings from
the electrode with the shortest delay are shown in Fig. 5. Both
VPM and POm MUA responses, measured either as peak values
or an integral under the curve (Fig. 5 Right; see also Fig. 11,
which is published as supporting information on the PNAS web
site) saturated with an increasing stimulus intensity.
Because the hemodynamic response recorded from the prin-
cipal barrel increases beyond saturation of both the pre- and
postsynaptic activity localized to the same barrel, processes
outside the principal barrel must contribute. To investigate the
MUA and LFP behavior in neighboring cortical columns, we
performed simultaneous recordings from the principal barrel
and a neighbor barrel (Fig. 6; see also Figs. 12 and 13, which are
published as supporting information on the PNAS web site). In
agreement with previous reports, MUA and LFP activity in the
neighbor barrel had a smaller amplitude and a slower rise (Fig.
6 a and b) (35). Fig. 6d shows locations of the electrode
recordings from columns corresponding to ?, D2, and D3
whiskers. The fastest saturation of the neuronal activity was
present in the principal barrel column ? (Fig. 6c, red), followed
by D2 column located two columns away (Fig. 6c, blue). In the
D3 column, located three columns away from the principal
barrel, neuronal activity increased close to linear throughout the
stimulus range (Fig. 6c, green).
Our results show that the neurovascular transfer function is
nonlocal, i.e., the hemodynamic signal observed at a given
spatial region. Thus, attempts at characterizing this function
based on point measurements of electrophysiology and hemo-
dynamics may yield inconsistent results, depending on the spatial
extent of neuronal activation. This may explain some of the
apparent discrepancies in the neurovascular relationship be-
tween the results reported while using varying stimulus frequen-
cies vs. varying stimulus amplitudes in rat Barrel cortex (5–8).
Note that the nonlocal nature of the hemodynamic point spread
(VPM) by using a single metal electrode and in the cortex by using a laminar
imposed for VPM (Upper) and cortical layer IV (a2). An input impedance of
recording electrodes, 7 M? in the VPM and 0.2 M? in the cortex, explains
differences in signal-to-noise ratio. (b1) VPM (black) and cortical layer IV (red)
peak response as a function of stimulus intensity. The curves were fitted by
and infragranule (green) peak responses as a function of stimulus amplitude.
Thalamic VPM and cortical responses saturate with an increase in
from VMP and POm by using two laminar electrode arrays. Responses for
different stimulus amplitudes (Inset) are superimposed for VPM (a) and POm
(b). The peak (black) and integral (red) response as a function of stimulus
intensity was fitted by using the function ax?(1?bx)c.
Neither lemniscal nor paralemniscal inputs increase beyond satura-
Devor et al. PNAS ?
March 8, 2005 ?
vol. 102 ?
no. 10 ?
does not necessarily preclude accurate localization of individual
columns based on the center of mass of the hemodynamic
response, e.g., due to deflection of individual whiskers (36), or
by subtracting one stimulus condition from another (37, 38).
However, it does limit the achievable resolution in terms of
two-point separation (39).
The relatively large spatial extent of the hemodynamic re-
sponse is in agreement with previous optical imaging studies
(18). Although spiking activity after a deflection of a single
whisker is largely restricted to a small number of neighboring
barrel columns (35), voltage-sensitive dye imaging shows that
neuronal activity after a brief deflection of a single whisker
spreads from the principal barrel column to cover a large part of
the Barrel cortex (23). Both extensive lateral cortico-cortical
connections (35, 40) and diffuse nonlemniscal inputs (32) might
contribute to this significant lateral spread of neuronal activity.
Because voltage-sensitive dye measurements are sensitive to
subthreshold neuronal activity (41, 42), this observation also
advocates a significant contribution of subthreshold synaptic
activity to hemodynamic signals.
In addition, a number of phenomena other than sub- or
suprathreshold local neuronal activity have been demonstrated
to contribute to increase the spatial spread of the hemodynamic
response. Among them are the diffusion of vasodilator sub-
stances such as NO from the active locus to nearby vessels (43,
44) after an increase in intracellular calcium (45), conducted
upstream and downstream vasodilatation (46, 47), and innerva-
tion of cortical microvessels by cholinergic fibers originating
from basal forebrain and?or 5-HT fibers originating from raphe
nuclei. Both cholinergic and 5-HT inputs have been shown to
induce significant increases in cortical perfusion upon stimula-
tion (48, 49).
The antagonistic hemodynamic changes observed in the sur-
round, in the absence of corresponding neuronal deactivation,
strongly suggest that the neurovascular transfer function has a
center-surround structure. Our measurement of MUA and LFP
in the surround area of hemodynamic activation failed to reveal
any neuronal correlate such as surround neuronal inhibition.
However, a possibility exists that a decrease in pyramidal neuron
activity in the surround area is exactly balanced by an increase
in inhibitory interneuron activity, resulting in unchanged MUA.
It is also possible that dendritic activity of inhibitory interneu-
rons would not show up on our LFP recordings due to their
closed-field configuration. Although we cannot rule out this
hypothesis based on the current data, we find it unlikely taking
into account the spatial extent of the negative hemodynamic
activation. In the present experiment, this negative surround
extends beyond the Barrel cortex and even beyond the somato-
sensory complex. To our knowledge, there have been no reports
of electrophysiological response outside of the Barrel cortex to
brief single-whisker deflection stimuli as used in this study.
Negative surround activation has also previously been reported
by using blood oxygen level-dependent fMRI in high-order
visual areas where neuronal activation rather than deactivation
is expected to occur under the stimulus conditions used (50).
The stimulus amplitude dependence of the surround negativ-
ity, along with the results of principal component analysis,
suggests a spatiotemporal separability of the neurovascular
transfer function for HbO and HbT. The corresponding analyses
for Hb, on the other hand, reveal a more complex pattern of
barrel (?) and two neighboring barrels (D2 and D3). Responses to different amplitudes are superimposed (Inset). The arrow denotes stimulus delivery. (c) MUA
(Left) and LFP (Right) peak responses as a function of stimulus amplitude. The curves were fitted by using the function ax?(1?bx)c. (d) Locations of
electrophysiological recordings are superimposed on the image of the vasculature. Recordings from barrel columns ? and D3 (the electrodes are visible on the
image) were performed after recordings from ? and D2 barrels.
Neuronal activity in neighboring cortical columns increases throughout the stimulus range. MUA (a) and LFP (b) responses are plotted for the principal
www.pnas.org?cgi?doi?10.1073?pnas.0407789102Devor et al.
results. Specifically, the spatial pattern of the Hb response varies
as a function of poststimulus latency. A detailed analysis of
spatiotemporal dynamics of Hb could provide more insight into
the competing effects of flow, volume, and oxygen consumption
(CMRO2) changes in blood oxygen level-dependent fMRI sig-
nal, because this method is primarily sensitive to changes in
A precise characterization of the neurovascular transfer
function will require full-field imaging of both electrophysio-
logical and hemodynamic parameters under different stimulus
conditions, where the location and extent of neuronal activa-
tion are systematically varied. This could be accomplished by
combining simultaneous spectroscopic and voltage-sensitive
dye imaging (52) during stimulation of different whiskers at
varying frequencies, which is known to modulate the lateral
spread of neuronal activity (53) and the hemodynamic re-
sponse (54, 55).
The complex spatial and temporal structure of the neurovas-
implications for the proper interpretation of fMRI results and
for the integration of different imaging modalities (10). In
particular, the spatial extent, center-surround organization, and
nonlinear gain of the neurovascular coupling have to be consid-
ered to draw valid inferences about neuronal activity from
This work was supported by National Institutes of Health Grants R01
EB00790, P41 RR14075, and NS44623 and by the Mental Illness and
Neuroscience Discovery (MIND) Institute.
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