Generating artificial sensations with

spinal cord stimulation in primates and

rodents Amol P. Yadav & Shuangyan Li
& Max O. Krucoff & Mikhail A. Lebedev
& Muhammad M. Abd-El-Barr & Miguel
A.L. Nicolelis
Visit to download the full and correct content document:
https://ebookmass.com/product/generating-artificial-sensations-with-spinal-cord-stimu
lation-in-primates-and-rodents-amol-p-yadav-shuangyan-li-max-o-krucoff-mikhail-a-le
bedev-muhammad-m-abd-el-barr-miguel-a-l-nicolel/
 Brain Stimulation 14 (2021) 825e836

Contents lists available at ScienceDirect

Brain Stimulation
journal homepage: http://www.journals.elsevier.com/brain-stimulation

Generating artificial sensations with spinal cord stimulation in

primates and rodents
Amol P. Yadav a, b, *, Shuangyan Li e, m, n, Max O. Krucoff j, k, Mikhail A. Lebedev d, l,
Muhammad M. Abd-El-Barr c, Miguel A.L. Nicolelis c, d, e, f, g, h, i
a
Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
b
Paul and Carole Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
c
Department of Neurosurgery, Duke University, Durham, NC, 27710, USA
d
Center for Neuroengineering, Duke University, Durham, NC, 27710, USA
e
Department of Neurobiology, Duke University, Durham, NC, 27710, USA
f
Department of Biomedical Engineering, Duke University, Durham, NC, 27710, USA
g
Department of Psychology and Neuroscience, Duke University, Durham, NC, 27710, USA
h
Department of Neurology, Duke University, Durham, NC, 27710, USA
i
Edmond and Lily Safra International Institute of Neuroscience, Natal, 59066060, Brazil
j
Department of Neurosurgery, Medical College of Wisconsin & Froedtert Health, Wauwatosa, WI, 53226, USA
k
Department of Biomedical Engineering, Marquette University & Medical College of Wisconsin, Milwaukee, WI, 53233, USA
l
Skolkovo Institute of Science and Technology, 30 Bolshoy Bulvar, Moscow, 143026, Russia
m
State Key Laboratory of Reliability and Intelligence of Electrical Equipment, School of Electrical Engineering, Tianjin, 300130, PR China
n
Tianjin Key Laboratory Bioelectromagnetic Technology and Intelligent Health, Hebei University of Technology, Tianjin, 300130, PR China

a r t i c l e i n f o a b s t r a c t

Article history: For patients who have lost sensory function due to a neurological injury such as spinal cord injury (SCI),
Received 24 December 2020 stroke, or amputation, spinal cord stimulation (SCS) may provide a mechanism for restoring somatic
Received in revised form sensations via an intuitive, non-visual pathway. Inspired by this vision, here we trained rhesus monkeys
1 April 2021
and rats to detect and discriminate patterns of epidural SCS. Thereafter, we constructed psychometric
Accepted 30 April 2021
Available online 18 May 2021
curves describing the relationship between different SCS parameters and the animal's ability to detect
SCS and/or changes in its characteristics. We found that the stimulus detection threshold decreased with
higher frequency, longer pulse-width, and increasing duration of SCS. Moreover, we found that monkeys
Keywords:
Spinal cord stimulation
were able to discriminate temporally- and spatially-varying patterns (i.e. variations in frequency and
Neuroprosthetics location) of SCS delivered through multiple electrodes. Additionally, sensory discrimination of SCS-
Somatosensation induced sensations in rats obeyed Weber's law of just-noticeable differences. These findings suggest
Artificial sensory feedback that by varying SCS intensity, temporal pattern, and location different sensory experiences can be
Non-human primates evoked. As such, we posit that SCS can provide intuitive sensory feedback in neuroprosthetic devices.
© 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction stimulating these brain areas requires surgical implantation of deep

Lack of sensory feedback from a brain-controlled actuator or
prosthetic device is a major hindrance to successful integration of
the neuroprosthesis in activities of daily life and rehabilitative
protocols [1e3]. The somatosensory cortex (S1) and thalamus have
been proposed as potential targets for neurostimulation that could
produce naturalistic somatosensory percepts [4e10]. However,
* Corresponding author. Department of Neurological Surgery, Indiana University
School of Medicine, Indianapolis, IN, 46202, USA.
E-mail address: apyadav@iu.edu (A.P. Yadav).
intracranial electrodes e a procedure associated with significant
risks. While peripheral nerve stimulation provides a less invasive
alternative, sensations evoked with this method are highly local-
ized, and thus limited in their applicability as a general-purpose
sensory input pathway to the brain [11e13]. Previously, in a
proof-of-concept study it was demonstrated that electrical stimu-
lation of the dorsal surface of the spinal cord can be used to
transmit sensory information between multiple rodent brains [14].
Building on this previous work, here we explored whether
nonhuman primates can learn to detect and discriminate artificial
sensations generated with dorsal thoracic epidural spinal cord

https://doi.org/10.1016/j.brs.2021.04.024
1935-861X/© 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/
).
A.P. Yadav, S. Li, M.O. Krucoff et al. Brain Stimulation 14 (2021) 825e836

stimulation (SCS). To understand the relationship between SCS
parameters and sensory detection e which is critical for the
development of novel neuroprosthetic devices e we performed a
robust psychophysical evaluation of the animals' ability to detect
sensations while SCS parameters were altered. We also examined
how sensory discrimination changes when SCS parameters are
varied in both rodent and primate models, and we asked whether
animals can learn to discriminate sensations generated by SCS
patterns that vary in frequency and spatial location. After training
the animals to discriminate SCS patterns, we determined whether
artificial sensations evoked by SCS of variable frequency follow
Weber's law of just-noticeable differences (JND) - a critical property
defining sensory discrimination.
Results
We implanted three rhesus monkeys with percutaneous
epidural SCS electrodes at the dorsal thoracic spinal level and
trained them to perform a two-alternative forced choice task
(2AFC) using a joystick-controlled cursor (Fig. 1a, Supplementary
Figure 1). In a typical experimental session, a monkey was seated
in a chair in front of a monitor that displayed task-related cues. The
animals moved a hand-held joystick to control a cursor on a screen
(Fig. 1b).
A typical trial consisted of a brief 1 s center hold period after
which two targets appeared. After a brief preparatory period of
100e1000 ms during which a trial cue was presented, the monkeys
had to move the cursor into one of the targets to obtain a juice
reward. Monkeys were initially trained to identify the correct target
using a visual cue; however, during the experimental sessions, no
visual cues were presented, and they selected a target by inter-
preting SCS cues alone. In the detection task, monkeys had to select
the left target if SCS was delivered during the preparatory period
and right target if no SCS was delivered (Fig. 1c). In the
discrimination task, monkeys had to select the left target for the
100 Hz stimuli and right target for the 200 Hz stimuli (frequency
discrimination) and the left target for electrode pair 1 and right
target for electrode pair 2 (spatial discrimination).
Monkeys learned to detect SCS stimuli
Monkeys M, O, and K learned to detect SCS-induced sensory
percepts evoked using percutaneous dorsal thoracic epidural
electrodes (T7 for monkey M, T5-T6 for monkey O, T5-T6 for
monkey K). Performance of all monkeys started below chance
levels of 50% and reached above 90% after learning (Fig. 2a). Mon-
key M started detection performance at 49% and reached a
maximum of 93% in 16 days; monkey O started at 49% and reached
a maximum of 97% in 10 days; and monkey K started at 41% and
reached a maximum of 90% in 8 days.
Electrode thresholds and electrode mapping
Once the monkeys learned to detect SCS sensations, we used
psychometric analysis to determine the detection thresholds for
different electrode combinations (Fig. 2b). We observed that the
detection thresholds varied from 315.6 mA to 340 mA for monkey O
and 197 mAe748 mA for monkey K for different cathode-anode
electrode pairs (Fig. 2c, right). Once electrode thresholds were
determined, we mapped the bipolar electrode pairs to locations on
the monkey's body by stimulating at suprathreshold amplitudes
and observing stimulation-induced minor muscle twitches or skin
flutter. We observed that muscle twitches/skin flutter were elicited
in the trunk and abdomen area only at suprathreshold values but
not at sensory threshold values (Fig. 2c). We also noted that in both
monkeys K and O experimentally determined sensory thresholds
were always lower than the observed motor thresholds for each
cathode-anode electrode pair (Supplementary Figure 3b).

Fig. 1. Surgery and experimental task setup. a) We implanted three non-human primates (rhesus monkeys) with SCS percutaneous leads over the T6-T10 dorsal epidural surface of
the spinal cord. Leads were externalized from the lower back area and secured inside a custom plastic housing. Leads were manually accessed by the experimenter for daily training
and connected to a custom pulse stimulator. b) Monkeys were seated in a primate chair in front of a computer monitor with access to a hand-controlled joystick. They participated
in a two-alternative forced choice task (2AFC) by moving the joystick controlling a cursor on the screen in order to receive a juice reward. c) On each trial, monkeys had to hold the
cursor inside the center circle for 1 s. After that, targets appeared on the left and right side of the center. Monkeys were presented with ‘SCS-ON’ (biphasic, 100 Hz, 200 ms, 1 s) cue or
‘SCS-OFF’ cue when the targets appeared. After a brief, variable hold period (100e1000 ms), the center circle disappeared which indicated them to move the joystick. Monkeys had
to move the cursor inside the left target on ‘SCS-ON’ trials and inside the right target on ‘SCS-OFF’ trials. Correct response resulted in juice reward. In the SCS discrimination task,
stimulation was delivered at 200 ms for 1 s. Monkeys had to select left target for 100 Hz stimulus and right target for 200 Hz stimulus in the frequency discrimination task. For spatial
discrimination task, monkeys had to choose left target when stimulation was delivered at electrode pair 1 and right target for stimulation at electrode pair 2.

826
A.P. Yadav, S. Li, M.O. Krucoff et al. Brain Stimulation 14 (2021) 825e836

Sensitivity to detection of sensory percepts in primates
Thereafter, we investigated the psychophysical relationship
between stimulation parameters and detection of sensory percepts
by varying stimulation amplitudes along with stimulation fre-
quency, pulse-width, or duration of stimulation while keeping the
other two parameters constant.
We varied amplitude from 50 mA to 800 mA for pulse-widths of
50 ms, 100 ms, 200 ms, and 400 ms for monkey K, and pulse-widths of
100 ms, 200 ms, and 400 ms for monkey O. Frequency and duration of
stimulation were held constant (Fig. 3a and 3e, and Supplementary
Figure 2a). We observed that stimulus detection threshold signifi-
cantly decreased with increasing stimulation pulse-width (p < 0.05,
repeated measures one-way ANOVA) for both animals (Fig. 3h).
We varied amplitude from 50 mA to 800 mA for frequencies of
10 Hz, 20 Hz, 50 Hz, 100 Hz, 200 Hz, and 500 Hz for monkey K, and
frequencies of 20 Hz, 50 Hz, 100 Hz, 200 Hz, and 500 Hz for monkey
O while keeping pulse-width and duration of stimulation constant
(Fig. 3b and 3f, and Supplementary Figure 2b). We observed that
stimulation detection threshold significantly decreased with
increasing stimulation frequency (p < 0.05, repeated measures one-
way ANOVA) for both animals (Fig. 3i).
We varied amplitude from 50 mA to 600 mA for duration of
50 ms, 100 ms, 500 ms, and 1000 ms for monkey K, and amplitude
between 50 mA and 700 mA for duration of 50 ms, 100 ms, and
500 ms for monkey O, while keeping pulse-width and frequency of
stimulation constant (Fig. 3c and 3g, and Supplementary Figure 2c).
We observed that stimulation detection threshold significantly
decreased with increasing stimulation duration (p < 0.05, repeated
measures one-way ANOVA) for both animals (Fig. 3j).
In monkey K, we varied both frequency and duration of stimu-
lation while keeping amplitude and pulse-width of stimulation
constant. We observed that as the frequency of stimulation
increased, the duration of stimulation to reach detection threshold
decreased (Fig. 3d and 3k). Monkey K was able to detect a sensory
percept generated by merely two stimulation pulses delivered at
1000 Hz.
Sensitivity to detection of sensory percepts in rats
In a proof-of-principle study, we previously showed that rats
learn to detect sensations generated by SCS delivered at T2 spinal
level [14]. In order to study the psychophysical performance of rats
pertaining to sensory detection, initially we trained rats to detect

Fig. 2. Monkeys learned to detect SCS stimuli. a) Learning curves (sigmoidal fits) for monkeys M, O, and K showing behavioral performance (fraction correct trials) as a function of
training days. b) Psychometric function showing fraction trials detected as a function of stimulation amplitude in monkey O. Detection threshold is defined as amplitude at which
monkeys achieved 75% performance on detection task. c) Mapping of bipolar electrode pairs (as indicated by pairs of±signs) on monkey K's body where stimulation on right-side
electrode at suprathreshold amplitude elicited minor muscle twitches or skin flutter. Mapped area is color coded by electrode pairs and corresponding sensory thresholds shown on
right. Monkey body shape is adapted from Ref. [15].

827
A.P. Yadav, S. Li, M.O. Krucoff et al. Brain Stimulation 14 (2021) 825e836

Fig. 3. Psychophysical evaluation of SCS sensory detection with varying stimulation parameters in primates. Once monkeys learned to detect SCS stimuli at the standard parameters
(frequency: 100 Hz, pulse width: 200 ms, duration: 1 s), we allocated different blocks of sessions where (pulse width & amplitude; panels ‘a’ and ‘e’); (frequency & amplitude; panels
‘b’ and ‘f’); and (duration & amplitude; panels ‘c’ and ‘g’) were varied while keeping other parameters constant. In monkey K, in a separate block, frequency and duration was varied
with other parameters constant (pulse width: 200 msec and amplitude: 325 mA). Psychometric curves in a-g are sigmoidal fits. Panels aed represent psychometric curves for monkey
K, while panels eeg represent psychometric curves fitted to data averaged across monkeys K and O (circles and error bars are mean ± sem). Panels h, i, j, indicate normalized

828
A.P. Yadav, S. Li, M.O. Krucoff et al.
SCS stimuli using a 2-AFC task in a slightly modified behavioral
chamber (Fig. 4a and 4b). We trained five rats to detect SCS stimuli
delivered at the T3 spinal level (frequency: 100 Hz, pulse-width:
200 ms, duration: 1 sec, biphasic pulses at 243.7±57.9 mA, Fig. 4c).
Once rats learned the basic detection task, we varied stimulation
parameters such as: pulse width (50e400 ms); frequency
(10e500 Hz); and duration (50e1000 ms) independently with
stimulation amplitude (Fig. 5a, 5d e pulse width; 5b, 5e e fre-
quency; and 5c, 5f e duration). Similar to the results in monkeys,
we observed that stimulation detection thresholds significantly
decreased with increasing pulse-width (Fig. 5g, p < 0.0001,
repeated measures one-way ANOVA), frequency (Fig. 5h,
p < 0.0001, repeated measures one-way ANOVA) and duration
(Fig. 5i, p < 0.05, repeated measures one-way ANOVA) for all rats.
Sensory discrimination in primates
We then trained monkeys K and O to discriminate SCS that
varied in frequency as well as location of stimulation. On frequency
discrimination (100 Hz vs 200 Hz, Fig. 6a), monkey O's performance
improved from 29% on day 1 to 96% on day 17 of training, while
monkey K's performance improved from 74% on day 1to 81% on day
11 (Fig. 6b). Spatial discrimination was achieved by stimulating
electrode pair 1 versus electrode pair 2 (Fig. 6c), where monkey O's
performance improved from 46% on day 1to 97% on day 11 and
monkey K's performance improved from 74% on day 1to 86% on day
7 (Fig. 6d).
Sensory discrimination and Weber's law in rats
In a proof-of-principle study, we had previously shown that rats
can learn to discriminate up to four different patterns of stimula-
tion [14]. In our current work, we trained rats to systematically
discriminate SCS stimuli with specific frequencies using the same
behavioral setup that was used for the detection task
(Supplementary Figure 5a). In the basic training, rats learned to
discriminate between 10 Hz and 100 Hz of stimulation delivered at
pulse-width of 200 msec, and duration of 1 s (Supplementary
Figure 5b). Thereafter, we studied whether discrimination of sen-
sations induced by different stimulation frequencies follows the
rules of Weber's law [16], which states that Just-Noticeable Differ-
ences (JNDs) between a standard frequency and comparison fre-
quency should linearly increase with the standard frequency of
stimulation. To this end, we determined JNDs at different standard
frequencies (10e100 Hz) where the comparison frequency was
higher than the standard (Fig. 7a). We observed that JNDs had a
significant linearly increasing relationship with the standard fre-
quency of stimulation (Fig. 7b, p < 0.0001, linear regression test).
After that, we kept the standard as a higher frequency value
(100e400 Hz) and decreased the comparison frequency randomly
from that value (Fig. 7c). In this case also, we observed that the JNDs
for lower frequency comparison significantly increased linearly as
the standard frequency increased (Fig. 7d, p < 0.0001, linear
regression test). These results suggest that the JND rule defined by
Weber's law holds true for sensory discrimination of SCS
frequencies.
detection thresholds (normalized by maximum amplitude used in the experiment block of each individual monkey) averaged across both monkeys (mean ± sem). Detection
threshold were calculated as 75% fraction detected at the stimulation parameters shown in panels aec (monkey K) and Supplementary Fig. 2 a-c (monkey O). P-values were
calculated using repeated measures one-way ANOVA. Panel k shows threshold duration obtained as 75% detection from curves in panel d as a function of frequency.
829
Brain Stimulation 14 (2021) 825e836
Discussion
In this study, we found that rhesus monkeys and rats can learn
to detect and discriminate artificial sensations induced by SCS
following several days of exposure. The threshold for detecting SCS
decreases with increasing pulse width, frequency, and duration of
the stimulus. We also documented the ability of monkeys to
discriminate sensations that are generated by stimulation pulses
with varying frequency and spatial location. In rats, we showed that
the just-noticeable differences (JNDs) from a perceivable stimulus
frequency were linearly related to the perceivable frequency when
it was compared with a stimulus that had either higher or lower
frequency. These results demonstrated the unique ability of SCS as a
novel transmission channel to the brain to encode highly contex-
tual sensory information.
Our results on behavioral sensitivity to detection of sensation in
rodents and primates were comparable to those observed with
Intracortical Microstimulation (ICMS) of S1 [5,17]. Notably, sensi-
tivity to stimulus amplitude increased with increasing pulse width,
frequency, and duration of stimulation. However, longer pulses
needed significantly higher charge to reach threshold in both pri-
mates (Supplementary Fig. 4a, 4b, and 4c, p < 0.05 e repeated
measures one-way ANOVA) and rodents (Supplementary Fig. 4d,
4e, and 4f, p < 0.0001 e repeated measures one-way ANOVA),
similar to that observed in the ICMS study [5]. ICMS amplitude
using currently FDA-approved UTAH arrays is usually restricted
below ~100 mA due to the possibility of brain tissue damage, which
limits the amplitude range for neuroprosthetic applications be-
tween detection thresholds of 20e50 mA and maximum allowable
safe amplitude of ~100 mA. In our SCS study, detection thresholds
had a wider range from 200 to 800 mA at different stimulation
settings and all detection thresholds were consistently on the non-
damaging side of the boundary between damaging and non-
damaging stimulation delineated by Shannon equation
[log(D) ¼ k e log (Q), with k ¼ 1.85] on log charge density versus log
charge per phase plot (Supplementary Figure 3a) [18]. Assuming a
commercially accepted maximum charge density of 30 mC/cm2 and
minimum pulse-width of 50 ms [19], it could be estimated that
maximum SCS current of ~80 mA in monkeys and ~3 mA in rats
could be delivered using electrode contacts (monkeys: 0.1319 cm2;
rats: 0.005 cm2) reported in our study without causing tissue
damage.
Frequency modulation has been historically considered a
promising method for providing sensory feedback with several
studies showing that animals are capable of discriminating ICMS
frequencies and that frequency modulation obeys Weber's law.
[4,20e22], While ICMS amplitude modulation in monkeys failed to
follow Weber's law [5], experiments in rats showed that modula-
tion of perceived intensity by amplitude and pulse-width modu-
lation followed Weber's law [17]. In our study, we investigated
whether rats and monkeys could learn to discriminate SCS fre-
quencies. Although monkeys O and K learned to discriminate
100 Hz SCS from 200 Hz, after taking a closer look at their learning
curves it was evident that they displayed different learning be-
haviors in the frequency discrimination task (Fig. 6b). Monkey O
started at lower discrimination performance at earlier training
sessions but reached higher level of performance toward the end of
training, whereas monkey K's performance started higher than
chance and improved marginally as the training progressed. These
A.P. Yadav, S. Li, M.O. Krucoff et al. Brain Stimulation 14 (2021) 825e836

Fig. 4. Behavioral task setup and rats learned to detect SCS stimuli. a) The experiment task consisted of a closed behavioral chamber with two reward ports on one side of the
chamber. The ports were covered with vertical sliding doors. Five rats were implanted with bipolar stimulation electrodes on the dorsal surface of the spinal cord at the T3 spinal
level. b) Task consisted of a house light turning ‘on’, followed by sensory cues for 1 s. During the cue period SCS was either delivered or not delivered. After the cue period both
reward doors opened, and the rat had to make a nose poke response in either of the ports to receive water reward. If SCS was delivered rats had to poke inside the left port and if not
delivered, then they had to poke inside the right reward port. Poking in the correct reward poke initiated a water reward, while incorrect pokes were not rewarded. c) Rats learned
to detect SCS stimuli over a period of 15e25 days as indicated e learning curve showing task performance indicated by fraction trials detected as a function of training sessions.
Circles and error bars indicate mean ± sem.

differences in learning behavior could be attributed to the fact that
monkey O was stimulated at constant amplitude for both frequency
values (100 Hz and 200 Hz) while monkey K was stimulated at each
frequency's threshold amplitude. It is quite possible that monkey O
was discriminating differences in perceived magnitudes of the
sensory percepts while monkey K was discriminating differences in
the qualitative nature of the percepts induced. Rats are capable of
discriminating temporal patterns of SCS when the number of pulses
are kept constant but the frequency of stimulus is varied [14]. In
addition to that, our current results indicate that JNDs associated
with SCS frequency discrimination in rats clearly follow Weber's
law because JNDs linearly increased with standard stimulation
frequency (Fig. 7b and 7d). It could be surmised from Fig. 7b that
there were at least three discriminable percepts between 10 Hz and
200 Hz; first percept at 10 Hz, second percept at 60 Hz because JND
at 10 Hz was ~50 Hz; and third percept at 180 Hz since JND at 60 Hz
was ~120 Hz. It can be argued that applying frequency modulation
simultaneously with amplitude and pulse-width modulation
would potentially increase the number of distinct discriminable
percepts that are possible within the amplitude range allowed on
current SCS electrodes. Therefore, further experiments exploring
the relationship between sensory discrimination and frequency,
pulse-width, amplitude, and duration of stimulation are necessary
to understand how these parameters relate to perceived intensity
and quality of sensation evoked by SCS.
A major advantage of SCS is its ability to target multiple der-
matomes simultaneously with a single electrode array. In partic-
ular, a single, commercially available SCS lead with multiple
contacts can evoke sensations in multiple dermatomes simulta-
neously due to the bilateral sensory representation of the entire
lower body in the ascending dorsal column fibers. It is quite
apparent from our results that monkeys can learn to discriminate
the spatial location of the sensations evoked by SCS (Fig. 6d). This
suggests that we can take full advantage of the rostro-caudal
somatotopy represented in the dorsal column fibers in combina-
tion with spatiotemporal stimulation patterns to electrically induce
targeted tactile or proprioceptive sensations in the body. This view
is also supported by evidence from computational studies which
indicate that epidural SCS activates dorsal column fibers up to a
depth of 0.2e0.25 mm from the dorsal surface [23e27]. However,
additional work on miniaturizing electrode contacts and accurate
medio-lateral/rostro-caudal mapping of SCS-induced sensations
needs to be performed to be able to elicit precise sensations. In
addition, the ability of SCS to modulate neuronal activity in
supraspinal brain structures is quite desirable from a neuro-
prosthetic as well as a therapeutic application standpoint
[14,28e31,34]. A major limitation of our study is the short experi-
mental time (Supplementary Figure 1) we had available for pri-
mates e maximum of 5 months e due to the risk of infection
associated with externalized SCS leads. A fully implantable stimu-
lation system, like the one implanted in chronic pain patients could
potentially extend our study indefinitely and allow us to perform
longer experiments in monkeys. Nevertheless, in rodents we were
able to perform longer post-implant experiments because the
electrodes and their wires were fully enclosed inside the body.

830
A.P. Yadav, S. Li, M.O. Krucoff et al. Brain Stimulation 14 (2021) 825e836

Fig. 5. Psychophysical evaluation of SCS sensory detection with varying stimulation parameters in rats. Once rats learned to detect SCS stimuli at the standard parameters (fre-
quency: 100 Hz, pulse width: 200 ms, duration: 1 s), we allocated different blocks of sessions where (pulse width & amplitude; panel ‘a’); (frequency & amplitude; panel ‘b’); and
(duration & amplitude; panel ‘c’) were varied while keeping other parameters constant. a, b, c) Psychometric curves from representative rats showing a leftward shift of curves as
the pulse-width (rat 4), frequency (rat 2), and duration (rat 5) of stimulation increased. d, e, f) Psychometric curves with averaged data across five rats indicate leftward shift as
pulse-width, frequency, and duration are increased. X-axis represents relative amplitude values (for each rat raw amplitude values were subtracted by minimum amplitude and the
difference was divided by amplitude step size). Circles and error bars are mean ± sem across five rats. Curves in panels ‘a-f’ are sigmoidal fits. Panels ‘g’, ‘h’, and ‘i’ indicate
normalized detection thresholds. Thresholds were calculated as 75% fraction detected at different stimulation parameters consistent with panels ‘a-f’ and then normalized by
maximum amplitude used in the experimental block of each rat. Circles and error bars are mean ± sem across five rats. P-values were calculated using repeated measures one-way
ANOVA.

In conclusion, we have successfully demonstrated that SCS can
generate discernible sensory percepts in both rats and monkeys
and all together our study strongly shows the potential of SCS to
encode sensory information in the brain. Additionally, our behav-
ioral experiments serve as a test bed for future animal studies
which could elucidate the neural mechanisms underlying SCS-
based sensory detection and discrimination. We envision that SCS
can be developed as an artificial sensory feedback channel for
delivering targeted tactile and proprioceptive information to the
brain.

831
A.P. Yadav, S. Li, M.O. Krucoff et al. Brain Stimulation 14 (2021) 825e836

Fig. 6. Monkeys learned to discriminate SCS stimuli varying in frequency and spatial location of electrodes. a,b) Monkeys K and O learned to discriminate SCS stimuli delivered at
the same electrode location but varying in frequency (100 Hz vs 200 Hz). Monkey O was stimulated at same amplitude while monkey K was stimulated at the respective threshold
amplitude for 100 Hz and 200 Hz. c,d) Monkeys K and O learned to discriminate stimulation delivered at electrode pair 1 (T6 - T7 spinal level) vs electrode pair 2 (T7-T8 spinal level).
Curves in panels b and d indicate sigmoidal fits to fraction correct trials displayed as a function of training days.

Methods
All animal procedures were approved by the Duke University
Institutional Animal Care and Use Committee and in accordance
with National Institute of Health Guide for the Care and Use of
Laboratory Animals. Three adult rhesus macaque monkeys (Macaca
mulatta), monkeys ‘M’, ‘O’, and ‘K’ and five Long Evans rats
(300e350 g) participated in the experiments.
implanted in the epidural space, a small hole was created in the
skin off-midline to externalize the distal end of the lead. Exter-
nalized leads were enclosed in a custom plastic cap which was
sutured to the skin (Fig. 1a). The plastic cap allowed for access to the
leads by the researcher but protection from the animal. The animal
wore a protective vest after surgery and throughout the experi-
mental period which prevented its access to the plastic cap sutures
to its back.

Monkey spinal implant surgery Monkey SCS detection task

Monkeys M, K, and O were implanted with 8-contact cylindrical
percutaneous leads (Model 3186, diameter 1.4 mm, contact length
3 mm, spacing 4 mm, Abbott Laboratories) bilaterally to the spinal
mid-line in the dorsal epidural space at T6 e T8 spinal level.
Monkey M had two leads with 8 stimulation contacts each, monkey
O had two leads, one with 8 contacts (right side) and one with 4
contacts (left side, Model 3146, similar electrode contact di-
mensions as Model 3186), and monkey K had two leads with 8
stimulation contacts each. Experimental procedures for monkeys
M, O, and K lasted approximately 45, 135, and 150 days post-
implant after which the leads were explanted (Supplementary
Figure 1).
Implant surgery was performed under general anesthesia using
standard procedures typical of human implantation (for details see
supplementary information and Fig. 1a). Once leads were
832
Monkeys were trained to perform a two-alternative forced
choice task where they were seated in a chair facing a computer
monitor which indicated trial progression (Fig. 1b). On each trial a
center target appeared, and the monkey had to move a cursor
which was joystick-controlled inside the center target (Fig. 1c).
After a brief hold period of 1 s inside the center target, two targets
appeared on either side of the center target. Each monkey had to
hold the cursor inside the central target for a brief period of
100e1000 ms. During this hold period sensory cues were pre-
sented. If SCS was presented (charge-balanced, cathode-first, 200
ms biphasic square pulses at 100 Hz for 1 s using custom micro-
stimulator [32]), then the monkey had to move the cursor to the left
target to obtain a juice reward. If SCS was absent, then the monkey
had to move the cursor inside the right target. At the end of the
hold period, the center target disappeared, thus cuing the monkey
Fig. 7. Discrimination of higher and lower comparison frequency obeys Weber's Law. a) Fraction of trials correctly discriminated from standard frequency of 10 Hz, 20 Hz, 40 Hz,
60 Hz, 80 Hz, and 100 Hz, when compared to a range of higher frequency stimuli. c) Fraction of trials correctly discriminated from standard frequency of 110 Hz, 220 Hz, 310 Hz,
380 Hz, and 400 Hz, when compared to a range of lower frequency stimuli. Circles and error bars in ‘a’ and ‘c’ indicate mean ± sem. Curves indicate sigmoid fits to the data. Just-
noticeable difference (JND) is considered as the comparison frequency value that achieves 75% discrimination ability. b, d) Just-noticeable difference as a function of standard
frequency is indicated by black circles and error bars. Black line is linear regression fit to the data and pink bounds indicate 95% confidence bound of the regression line. JNDs
associated with higher frequency and lower frequency comparison were significantly linearly related with standard frequency. P-values were calculated using linear regression test.

833
A.P. Yadav, S. Li, M.O. Krucoff et al.
to initiate cursor movement toward the reward. Incorrect target
reaches were not rewarded. Initiation of movement prior to the end
of the hold period terminated the trial without reward and a blank
screen was displayed 3 s before starting next trial. The learning
performance of monkeys was studied using percentage correct (PC)
trials.
Monkey psychometric evaluation of detection thresholds
Once monkeys were trained on the detection task and their
performance was above 85%, detection thresholds were deter-
mined for different electrode combinations using psychometric
testing. Particularly, during ‘Stimulation ON’ i.e. ‘left target rewar-
ded’ trials, the stimulation amplitude was randomly varied from
50 mA to a manually determined upper limit which was below the
motor threshold. Only left target trials were analyzed and a per-
centage correct (PC) performance at each stimulation amplitude
value was determined. A sigmoid curve was fit to the PC values and
75% was considered as detection threshold. This was repeated for
several electrode combinations.
Monkey electrode mapping
In monkey K, once sensory detection thresholds were deter-
mined, we mapped the location of electrode pairs to location on the
monkey's body by sedating the monkey and stimulating those
electrodes above the sensory threshold values. Areas on the body
surface that elicited minor muscle twitches or skin flutter were
marked (Fig. 2c, left) and the motor thresholds were noted. In
monkey O, these observations were not made under sedation but
while it was seated in the primate chair.
Monkey detection thresholds as stimulation parameters vary
During sets of consecutive sessions, we varied amplitude and
frequency or amplitude and pulse-width or amplitude and duration
of stimulation while keeping other parameters constant (for stim-
ulation parameter ranges, see Supplementary Table 1). The stan-
dard parameters that remained constant while others were varied
were frequency: 100 Hz, pulse width: 200 msec, and duration: 1 s. In
monkey K, we varied frequency (10e1000 Hz) and duration
(1e2000 ms) of stimulation simultaneously while keeping pulse
width and amplitude constant at 200 ms and 325 mA respectively.
Detection thresholds for each monkey were normalized by
maximum amplitude used in the experiment block of that monkey
before statistical analysis.
Monkey sensory discrimination
In the frequency discrimination task, each monkey was
instructed to move the cursor inside the left target for 100 Hz and
right target for 200 Hz respectively (Fig. 6a). In the spatial
discrimination task, the monkey was instructed to move the cursor
inside the left target for electrode pair 1 and inside right target for
electrode pair 2 respectively (Fig. 6c).
Rat pre-training and SCS electrode implantation
Moderately water deprived rats were placed inside the behav-
ioral chamber for 2 days to acclimatize to the behavioral environ-
ment. The behavioral chamber had two doors on one side of the
walls which enclosed water reward ports (Fig. 4a), slightly modified
from the one previously described [33]. Rats were gradually trained
to receive water reward from the ports. Initially, both reward doors
were kept open and rats learned to receive water by licking at the
834
Brain Stimulation 14 (2021) 825e836
water dispensing spout. Later, the doors were kept closed and
would open a few seconds after the house light turned on. In
subsequent sessions, left and right doors would open on alternate
trials and rats learned to obtain reward from each port alterna-
tively. The pre-surgical training period lasted approximately 8e10
days.
Thereafter custom designed SCS electrodes (1 mm  0.5 mm
contacts arranged transversely in a bipolar configuration with
0.25 mm spacing using a 0.025 mm thickness platinum foil,
Goodfellow Cambridge Limited, England) were implanted into the
epidural space under T3 vertebra as described in our previous
article [29]. After the rats recovered from the spinal surgical pro-
cedures, cathode leading stimulation pulse trains were delivered at
the SCS electrodes using a multi-channel constant current stimu-
lator (Master-8, A.M.P.I, Jerusalem, Israel) at stimulation settings
which were determined depending on the behavioral task under
consideration (Fig. 4a).
Rat sensory detection task
After recovery from surgery, rats were introduced to a two-
alternative forced choice task (2AFC) to learn detection of SCS
stimuli in the chamber (Fig. 4b). At the beginning of each trial, a
light in the chamber was turned on for 1 s as a reminder for the
animals to pay attention. After the light turned off, the rats received
a sensory cue for 1 s. The sensory cue either consisted of cathode-
leading bipolar square pulse trains (pulse width: 200 ms, Frequency:
100 Hz, duration: 1 s) or no stimulation pulses (interval: 1 s) at each
trial. After a brief delay of 0.5 s both reward doors opened, and rats
had to respond by choosing the left door for ‘SCS ON’ trials and right
door for ‘SCS OFF’ trials. Incorrect responses were not rewarded.
During the learning of this basic detection task, the intensity of the
delivered current was determined before each session and set using
procedures described before [14,29,31] (mean ± std, intensity at
100 Hz was 243.7 ±57:9 mA).
Rat sensory detection psychophysics
Once rats learned the basic sensory detection task and their
performance was above 80%, stimulation parameters were varied in
a systematic manner during the SCS-ON trials. In different experi-
mental sessions, stimulation parameters such as frequency and
amplitude, pulse-width and amplitude, and pulse train duration
and amplitude were varied while other parameters were kept
constant (standard parameters: pulse width: 200 ms; Frequency:
100 Hz; duration: 1 s), and sensory detection threshold amplitude
was determined (for stimulation parameter ranges see
Supplementary Table 1). For all the conditions, the detectable level
of the amplitude was defined as 75% accuracy of behavioral per-
formance. Detection thresholds for each rat were normalized by
maximum amplitude used in the experiment block of that rat
before statistical analysis.
Rat sensory discrimination task
In a 2AFC task, rats were presented with either a low frequency
stimulus or a high frequency stimulus during the sensory cue
period in the behavioral chamber. For either frequency, the stim-
ulus was delivered at the same amplitude (determined at each
session), pulse width (200 ms), and duration (1 s). After a brief delay
period following sensory cue presentation, rats had to choose the
left door for higher frequency stimulus and right door for lower
frequency stimulus to obtain reward (Fig. 4a). Initially, rats were
trained to discriminate between 10 Hz and 100 Hz frequency.
Incorrect trails were not rewarded.
A.P. Yadav, S. Li, M.O. Krucoff et al.
Weber's law and sensory discrimination
Once rats learned to discriminate 10 Hz stimulus from 100 Hz
stimulus, demonstrated by consistent discrimination performance
above 80%, the lower frequency (standard frequency) was kept
constant during right door trials while the higher frequency
(comparison frequency) was randomized between 20 Hz and
110 Hz during left door trials. Sensory discrimination performance
between a standard frequency and comparison frequency was
determined as the fraction of trials successfully discriminated for
that particular standard and comparison pair. Thus, fraction trials
discriminated was plotted as a function of comparison frequency to
obtain Just-Noticeable Differences (JNDs) determined as 75% value
on the curve. The same experiment was repeated for different
standard frequency values such as 20 Hz vs (40e220 Hz), 40 Hz vs
(60e240 Hz), 60 Hz vs (85e310 Hz), 80 Hz vs (110e380 Hz), and
100 Hz vs (130e400 Hz) to obtain JNDs for each standard frequency
value and to test for Weber's law.
Similarly, the experiment was repeated for discrimination of a
low-frequency comparison stimulus from a high-frequency stan-
dard stimulus. The standard frequency values were 110, 220, 310,
380, and 400 Hz, while the comparison frequency was randomized
from (100e10 Hz), (200e20 Hz), (285e60 Hz), (350e80 Hz), and
(370e100 Hz) respectively for each of the standard frequency
values. JNDs were calculated for each of the standard frequency
values as explained before to test for Weber's law.
Statistical analysis
Repeated measures one-way ANOVA was used to test the sig-
nificance of relationship between stimulation parameters and
sensory detection thresholds in both rats and monkeys (Fig. 3h, 3i,
3j, 5g, 5h, 5i, and Supplementary Fig. 4c and 4f). To test whether
JNDs were significantly linearly related to standard frequency in the
sensory discrimination task, the linear regression test was used
(Fig. 7b and 7d).
CRediT authorship contribution statement
Amol P. Yadav: Conceptualization, Methodology, Software,
Investigation, Formal analysis, Funding acquisition, Supervision,
Writing e original draft, Writing e review & editing. Shuangyan Li:
Methodology, Investigation, Formal analysis, Writing e review &
editing. Max O. Krucoff: Conceptualization, Methodology, Funding
acquisition, Writing e review & editing. Mikhail A. Lebedev:
Conceptualization, Writing e review & editing. Muhammad M.
Abd-El-Barr: Methodology, Writing e review & editing. Miguel
A.L. Nicolelis: Resources, Funding acquisition, Supervision, Writing
e review & editing.
Declaration of competing interest
The authors declare no competing financial or non-financial
interests.
Acknowledgements
We thank Gary Lehew for assistance with experimental setup,
Tamara Phillips for assistance with monkey handling, Paul
Thompson for assistance with primate task software, Laura Oliveira
and Susan Halkiotis for technical assistance, and Joseph O'Doherty
for comments on previous version of manuscript. This research was
supported by Duke Institute for Brain Sciences Germinator Award
and Duke Neurosurgery Research Support awarded to Amol P.
Yadav, NIH R25 awarded to Max O. Krucoff, RSF grant 21-75-30024
835
Brain Stimulation 14 (2021) 825e836
awarded to Mikhail A. Lebedev, and Hartwell Foundation grant
awarded to Miguel Nicolelis.
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.brs.2021.04.024.
References
[1] Lebedev MA, Nicolelis MA. Brain-Machine interfaces: from basic science to
neuroprostheses and neurorehabilitation. Physiol Rev 2017;97(2):767e837.
https://doi.org/10.1152/physrev.00027.2016. PubMed PMID: 28275048.
[2] Krucoff MO, Rahimpour S, Slutzky MW, Edgerton VR, Turner DA. Enhancing
nervous system recovery through neurobiologics, neural interface training,
and neurorehabilitation. ARTN 584 Front Neurosci 2016;10. https://doi.org/
10.3389/fnins.2016.00584. PubMed PMID: WOS:000390598100001.
[3] Bensmaia SJ, Miller LE. Restoring sensorimotor function through intracortical
interfaces: progress and looming challenges. Nat Rev Neurosci 2014;15(5):
313e25. https://doi.org/10.1038/nrn3724. PubMed PMID: 24739786.
[4] O'Doherty JE, Lebedev MA, Ifft PJ, Zhuang KZ, Shokur S, Bleuler H, Nicolelis MA.
Active tactile exploration using a brain-machine-brain interface. Nature
2011;479(7372):228e31. https://doi.org/10.1038/nature10489. PubMed
PMID: 21976021; PMCID: 3236080.
[5] Kim S, Callier T, Tabot GA, Gaunt RA, Tenore FV, Bensmaia SJ. Behavioral
assessment of sensitivity to intracortical microstimulation of primate so-
matosensory cortex. 49. In: Proceedings of the national academy of Sciences of
the United States of America. vol. 112; 2015. p. 15202e7. https://doi.org/
10.1073/pnas.1509265112. PubMed PMID: 26504211; PMCID: 4679002.
[6] Tabot GA, Dammann JF, Berg JA, Tenore FV, Boback JL, Vogelstein RJ,
Bensmaia SJ. Restoring the sense of touch with a prosthetic hand through a
brain interface. P Natl Acad Sci USA 2013;110(45):18279e84. https://doi.org/
10.1073/pnas.1221113110. PubMed PMID: WOS:000326550800062.
[7] Flesher SN, Collinger JL, Foldes ST, Weiss JM, Downey JE, Tyler-Kabara EC,
Bensmaia SJ, Schwartz AB, Boninger ML, Gaunt RA. Intracortical micro-
stimulation of human somatosensory cortex. Epub 2016/11/01 Sci Transl Med
2016;8(361):361ra141. https://doi.org/10.1126/scitranslmed.aaf8083.
PubMed PMID: 27738096.
[8] Heming E, Sanden A, Kiss ZH. Designing a somatosensory neural prosthesis:
percepts evoked by different patterns of thalamic stimulation. J Neural Eng
2010;7(6):064001. https://doi.org/10.1088/1741-2560/7/6/064001. PubMed
PMID: 21084731.
[9] Swan BD, Gasperson LB, Krucoff MO, Grill WM, Turner DA. Sensory percepts
induced by microwire array and DBS microstimulation in human sensory
thalamus. Brain Stimul 2018;11(2):416e22. https://doi.org/10.1016/
j.brs.2017.10.017. PubMed PMID: 29126946; PMCID: PMC5803348.
[10] Dadarlat MC, O'Doherty JE, Sabes PN. A learning-based approach to artificial
sensory feedback leads to optimal integration. Epub 2014/11/25 Nat Neurosci
2015;18(1):138e44. https://doi.org/10.1038/nn.3883. PubMed PMID:
25420067; PMCID: PMC4282864.
[11] Strauss I, Valle G, Artoni F, D'Anna E, Granata G, Di Iorio R, Guiraud D,
Stieglitz T, Rossini PM, Raspopovic S, Petrini FM, Micera S. Characterization of
multi-channel intraneural stimulation in transradial amputees. Epub 2019/12/
19 Sci Rep 2019;9(1):19258. https://doi.org/10.1038/s41598-019-55591-z.
PubMed PMID: 31848384; PMCID: PMC6917705.
[12] Petrini FM, Valle G, Bumbasirevic M, Barberi F, Bortolotti D, Cvancara P,
Hiairrassary A, Mijovic P, Sverrisson AO, Pedrocchi A, Divoux JL, Popovic I,
Lechler K, Mijovic B, Guiraud D, Stieglitz T, Alexandersson A, Micera S, Lesic A,
Raspopovic S. Enhancing functional abilities and cognitive integration of the
lower limb prosthesis. Epub 2019/10/04 Sci Transl Med 2019;11(512). https://
doi.org/10.1126/scitranslmed.aav8939. PubMed PMID: 31578244.
[13] Petrini FM, Bumbasirevic M, Valle G, Ilic V, Mijovic P, Cvancara P, Barberi F,
Katic N, Bortolotti D, Andreu D, Lechler K, Lesic A, Mazic S, Mijovic B,
Guiraud D, Stieglitz T, Alexandersson A, Micera S, Raspopovic S. Sensory
feedback restoration in leg amputees improves walking speed, metabolic cost
and phantom pain. Epub 2019/09/11 Nat Med 2019;25(9):1356e63. https://
doi.org/10.1038/s41591-019-0567-3. PubMed PMID: 31501600.
[14] Yadav AP, Li D, Nicolelis MAL. A brain to spine interface for transferring
artificial sensory information. Epub 2020/01/23 Sci Rep 2020;10(1):900.
https://doi.org/10.1038/s41598-020-57617-3. PubMed PMID: 31964948.
[15] Bellanca RU, Lee GH, Vogel K, Ahrens J, Kroeker R, Thom JP, Worlein JM.
A simple alopecia scoring system for use in colony management of laboratory-
housed primates. Epub 2014/02/28 J Med Primatol 2014;43(3):153e61.
https://doi.org/10.1111/jmp.12107. PubMed PMID: 24571509; PMCID:
PMC4438708.
[16] Ekman G. Weber law and related functions. J Psychol 1959;47(2):343e52.
https://doi.org/10.1080/00223980.1959.9916336. PubMed PMID: WOS:
A1959CAK1200020.
[17] Bjanes DA, Moritz CT. A robust encoding scheme for delivering artificial
sensory information via direct brain stimulation. Epub 2019/08/24 IEEE Trans
Neural Syst Rehabil Eng 2019;27(10):1994e2004. https://doi.org/10.1109/
TNSRE.2019.2936739. PubMed PMID: 31443035.
A.P. Yadav, S. Li, M.O. Krucoff et al.
[18] Merrill DR, Bikson M, Jefferys JG. Electrical stimulation of excitable tissue:
design of efficacious and safe protocols. Epub 2005/01/22 J Neurosci Methods
2005;141(2):171e98. https://doi.org/10.1016/j.jneumeth.2004.10.020.
PubMed PMID: 15661300.
[19] Cogan SF, Ludwig KA, Welle CG, Takmakov P. Tissue damage thresholds
during therapeutic electrical stimulation. Epub 2016/01/23 J Neural Eng
2016;13(2):021001. https://doi.org/10.1088/1741-2560/13/2/021001.
PubMed PMID: 26792176; PMCID: PMC5386002.
[20] Romo R, Hernandez A, Zainos A, Brody CD, Lemus L. Sensing without
touching: psychophysical performance based on cortical microstimulation.
Neuron 2000;26(1):273e8. PubMed PMID: 10798410.
[21] O'Doherty JE, Shokur S, Medina LE, Lebedev MA, Nicolelis MAL. Creating a
neuroprosthesis for active tactile exploration of textures. 43. In: Proceedings
of the national academy of Sciences of the United States of America. vol. 116;
2019. p. 21821e7. https://doi.org/10.1073/pnas.1908008116. Epub 2019/10/
09, PubMed PMID: 31591224; PMCID: PMC6815176.
[22] Callier T, Brantly NW, Caravelli A, Bensmaia SJ. The frequency of cortical
microstimulation shapes artificial touch. 2. In: Proceedings of the national
academy of Sciences of the United States of America. vol. 117; 2020.
p. 1191e200. https://doi.org/10.1073/pnas.1916453117. Epub 2019/12/28,
PubMed PMID: 31879342; PMCID: PMC6969512.
[23] Holsheimer J, Barolat G. Spinal geometry and paresthesia coverage in spinal
cord stimulation. Neuromodulation : J. Int. Neuromod. Soc. 1998;1(3):
129e36. https://doi.org/10.1111/j.1525-1403.1998.tb00006.x. PubMed PMID:
22150980.
[24] Barolat G, Massaro F, He J, Zeme S, Ketcik B. Mapping of sensory responses to
epidural stimulation of the intraspinal neural structures in man. Epub 1993/
02/01 J Neurosurg 1993;78(2):233e9. https://doi.org/10.3171/
jns.1993.78.2.0233. PubMed PMID: 8421206.
[25] Holsheimer J, Buitenweg JR. Review: bioelectrical mechanisms in spinal cord
stimulation. discussion 70 Neuromodulation : J. Int. Neuromod. Soc.
2015;18(3):161e70. https://doi.org/10.1111/ner.12279. PubMed PMID:
25832787.
[26] North RB, Sieracki JM, Fowler KR, Alvarez B, Cutchis PN. Patient-interactive,
microprocessor-controlled neurological stimulation system. Epub 1998/10/01
836
Brain Stimulation 14 (2021) 825e836
Neuromodulation : J. Int. Neuromod. Soc. 1998;1(4):185e93. https://doi.org/
10.1111/j.1525-1403.1998.tb00015.x. PubMed PMID: 22151030.
[27] Holsheimer J. Which neuronal elements are activated directly by spinal cord
stimulation. Epub 2002/01/01 Neuromodulation : J. Int. Neuromod. Soc.
2002;5(1):25e31. https://doi.org/10.1046/j.1525-1403.2002._2005.x. PubMed
PMID: 22151778.
[28] Yadav AP, Nicolelis MAL. Electrical stimulation of the dorsal columns of the
spinal cord for Parkinson's disease. Mov Disord 2017;32(6):820e32. https://
doi.org/10.1002/mds.27033. PubMed PMID: 28497877.
[29] Yadav AP, Fuentes R, Zhang H, Vinholo T, Wang CH, Freire MA, Nicolelis MA.
Chronic spinal cord electrical stimulation protects against 6-
hydroxydopamine lesions. Sci Rep 2014;4:3839. https://doi.org/10.1038/
srep03839. PubMed PMID: 24452435; PMCID: 3899601.
[30] Yadav AP, Borda E, Nicolelis MA. Closed loop spinal cord stimulation restores
locomotion and desynchronizes corticostriatal beta oscillations [abstract].
Mov Disord 2018;33.
[31] Pais-Vieira M, Yadav AP, Moreira D, Guggenmos D, Santos A, Lebedev M,
Nicolelis MA. A closed loop brain-machine interface for epilepsy control using
dorsal column electrical stimulation. Sci Rep 2016;6:32814. https://doi.org/
10.1038/srep32814. PubMed PMID: 27605389; PMCID: PMC5015048.
[32] Hanson TL, Omarsson B, O'Doherty JE, Peikon ID, Lebedev MA, Nicolelis MA.
High-side digitally current controlled biphasic bipolar microstimulator. Epub
2012/02/14 IEEE Trans Neural Syst Rehabil Eng 2012;20(3):331e40. https://
doi.org/10.1109/TNSRE.2012.2187219. PubMed PMID: 22328184; PMCID:
PMC3502026.
[33] Pais-Vieira M, Chiuffa G, Lebedev M, Yadav A, Nicolelis MA. Building an
organic computing device with multiple interconnected brains. Sci Rep
2015;5:11869. https://doi.org/10.1038/srep11869. PubMed PMID: 26158615;
PMCID: 4497302.
[34] Rahimpour S, Gaztanaga W, Yadav AP, Chang SJ, Krucoff MO, Cajigas I, et al.
Freezing of Gait in Parkinson’s Disease: Invasive and Noninvasive Neuro-
modulation. Neuromodulation: Technol Neural Interfac 2020. https://doi.org/
10.1111/ner.13347. Pubmed PMID: 33368872.
Another random document with
no related content on Scribd:
adjutant were already transferred to new regiments, and their places
were not yet filled. The three months of the enlistment expired a few
days after the battle.
In the fall of 1861, the old artillery company of this town was
reorganized, and Captain Richard Barrett received a commission in
March, 1862, from the state, as its commander. This company,
chiefly recruited here, was later embodied in the Forty-seventh
Regiment, Massachusetts Volunteers, enlisted as nine months’ men,
and sent to New Orleans, where they were employed in guard duty
during their term of service. Captain Humphrey H. Buttrick, lieutenant
in this regiment, as he had been already lieutenant in Captain
Prescott’s company in 1861, went out again in August, 1864, a
captain in the Fifty-ninth Massachusetts, and saw hard service in the
Ninth Corps, under General Burnside. The regiment being formed of
veterans, and in fields requiring great activity and exposure, suffered
extraordinary losses; Captain Buttrick and one other officer being the
only officers in it who were neither killed, wounded nor captured.[190]
In August, 1862, on the new requisition for troops, when it was
becoming difficult to meet the draft,—mainly through the personal
example and influence of Mr. Sylvester Lovejoy, twelve men,
including himself, were enlisted for three years, and, being soon after
enrolled in the Fortieth Massachusetts, went to the war; and a very
good account has been heard, not only of the regiment, but of the
talents and virtues of these men.
After the return of the three months’ company to Concord, in 1861,
Captain Prescott raised a new company of volunteers, and Captain
Bowers another. Each of these companies included recruits from this
town, and they formed part of the Thirty-second Regiment of
Massachusetts Volunteers. Enlisting for three years, and remaining
to the end of the war, these troops saw every variety of hard service
which the war offered, and, though suffering at first some
disadvantage from change of commanders, and from severe losses,
they grew at last, under the command of Colonel Prescott, to an
excellent reputation, attested by the names of the thirty battles they
were authorized to inscribe on their flag, and by the important
position usually assigned them in the field.
 I have found many notes of their rough experience in the march
and in the field. In McClellan’s retreat in the Peninsula, in July, 1862,
“it is all our men can do to draw their feet out of the mud. We
marched one mile through mud, without exaggeration, one foot
deep,—a good deal of the way over my boots, and with short rations;
on one day nothing but liver, blackberries, and pennyroyal tea.”—“At
Fredericksburg we lay eleven hours in one spot without moving,
except to rise and fire.” The next note is, “cracker for a day and a
half,—but all right.” Another day, “had not left the ranks for thirty
hours, and the nights were broken by frequent alarms. How would
Concord people,” he asks, “like to pass the night on the battle-field,
and hear the dying cry for help, and not be able to go to them?” But
the regiment did good service at Harrison’s Landing, and at
Antietam, under Colonel Parker; and at Fredericksburg, in
December, Lieutenant-Colonel Prescott loudly expressed his
satisfaction at his comrades, now and then particularizing names:
“Bowers, Shepard and Lauriat are as brave as lions.”[191]
At the battle of Gettysburg, in July, 1863, the brigade of which the
Thirty-second Regiment formed a part, was in line of battle seventy-
two hours, and suffered severely. Colonel Prescott’s regiment went
in with two hundred and ten men, nineteen officers. On the second of
July they had to cross the famous wheat-field, under fire from the
rebels in front and on both flanks. Seventy men were killed or
wounded out of seven companies. Here Francis Buttrick, whose
manly beauty all of us remember,[192] and Sergeant Appleton, an
excellent soldier, were fatally wounded. The Colonel was hit by three
bullets. “I feel,” he writes, “I have much to be thankful for that my life
is spared, although I would willingly die to have the regiment do as
well as they have done. Our colors had several holes made, and
were badly torn. One bullet hit the staff which the bearer had in his
hand. The color-bearer is brave as a lion; he will go anywhere you
say, and no questions asked; his name is Marshall Davis.” The
Colonel took evident pleasure in the fact that he could account for all
his men. There were so many killed, so many wounded,—but no
missing. For that word “missing” was apt to mean skulking. Another
incident: “A friend of Lieutenant Barrow complains that we did not
treat his body with respect, inasmuch as we did not send it home. I
think we were very fortunate to save it at all, for in ten minutes after
he was killed the rebels occupied the ground, and we had to carry
him and all our wounded nearly two miles in blankets. There was no
place nearer than Baltimore where we could have got a coffin, and I
suppose it was eighty miles there. We laid him in two double
blankets, and then sent off a long distance and got boards off a barn
to make the best coffin we could, and gave him burial.”
After Gettysburg, Colonel Prescott remarks that our regiment is
highly complimented. When Colonel Gurney, of the Ninth, came to
him the next day to tell him that “folks are just beginning to
appreciate the Thirty-second Regiment: it always was a good
regiment, and people are just beginning to find it out;” Colonel
Prescott notes in his journal,—“Pity they have not found it out before
it was all gone. We have a hundred and seventy-seven guns this
morning.”
Let me add an extract from the official report of the brigade
commander: “Word was sent by General Barnes, that, when we
retired, we should fall back under cover of the woods. This order was
communicated to Colonel Prescott, whose regiment was then under
the hottest fire. Understanding it to be a peremptory order to retire
then, he replied, ‘I don’t want to retire; I am not ready to retire; I can
hold this place;’ and he made good his assertion. Being informed
that he misunderstood the order, which was only to inform him how
to retire when it became necessary, he was satisfied, and he and his
command held their ground manfully.” It was said that Colonel
Prescott’s reply, when reported, pleased the Acting-Brigadier-
General Sweitzer mightily.
After Gettysburg, the Thirty-second Regiment saw hard service at
Rappahannock Station; and at Baltimore, in Virginia, where they
were drawn up in battle order for ten days successively: crossing the
Rapidan, and suffering from such extreme cold, a few days later, at
Mine Run, that the men were compelled to break rank and run in
circles to keep themselves from being frozen. On the third of
December, they went into winter quarters.
 I must not follow the multiplied details that make the hard work of
the next year. But the campaign in the Wilderness surpassed all their
worst experience hitherto of the soldier’s life. On the third of May,
they crossed the Rapidan for the fifth time. On the twelfth, at Laurel
Hill, the regiment had twenty-one killed and seventy-five wounded,
including five officers. “The regiment has been in the front and centre
since the battle begun, eight and a half days ago, and is now
building breastworks on the Fredericksburg road. This has been the
hardest fight the world ever knew. I think the loss of our army will be
forty thousand. Every day, for the last eight days, there has been a
terrible battle the whole length of the line. One day they drove us; but
it has been regular bull-dog fighting.” On the twenty-first, they had
been, for seventeen days and nights, under arms without rest. On
the twenty-third, they crossed the North Anna, and achieved a great
success. On the thirtieth, we learn, “Our regiment has never been in
the second line since we crossed the Rapidan, on the third.” On the
night of the thirtieth,—“The hardest day we ever had. We have been
in the first line twenty-six days, and fighting every day but two; whilst
your newspapers talk of the inactivity of the Army of the Potomac. If
those writers could be here and fight all day, and sleep in the
trenches, and be called up several times in the night by picket-firing,
they would not call it inactive.” June fourth is marked in the diary as
“An awful day;—two hundred men lost to the command;” and not
until the fifth of June comes at last a respite for a short space, during
which the men drew shoes and socks, and the officers were able to
send to the wagons and procure a change of clothes, for the first
time in five weeks.
But from these incessant labors there was now to be rest for one
head,—the honored and beloved commander of the regiment. On
the sixteenth of June, they crossed the James River, and marched to
within three miles of Petersburg. Early in the morning of the
eighteenth they went to the front, formed line of battle, and were
ordered to take the Norfolk and Petersburg Railroad from the rebels.
In this charge, Colonel George L. Prescott was mortally wounded.
After driving the enemy from the railroad, crossing it, and climbing
the farther bank to continue the charge, he was struck, in front of his
command, by a musket-ball which entered his breast near the heart.
He was carried off the field to the division hospital, and died on the
following morning. On his death-bed, he received the needless
assurances of his general that “he had done more than all his
duty,”—needless to a conscience so faithful and unspotted. One of
his townsmen and comrades, a sergeant in his regiment, writing to
his own family, uses these words: “He was one of the few men who
fight for principle. He did not fight for glory, honor, nor money, but
because he thought it his duty. These are not my feelings only, but of
the whole regiment.”
On the first of January, 1865, the Thirty-second Regiment made
itself comfortable in log huts, a mile south of our rear line of works
before Petersburg. On the fourth of February, sudden orders came to
move next morning at daylight. At Dabney’s Mills, in a sharp fight,
they lost seventy-four in killed, wounded and missing. Here Major
Shepard was taken prisoner. The lines were held until the tenth, with
more than usual suffering from snow and hail and intense cold,
added to the annoyance of the artillery fire. On the first of April, the
regiment connected with Sheridan’s cavalry, near the Five Forks,
and took an important part in that battle which opened Petersburg
and Richmond, and forced the surrender of Lee. On the ninth, they
marched in support of the cavalry, and were advancing in a grand
charge, when the white flag of General Lee appeared. The brigade
of which the Thirty-second Regiment formed part was detailed to
receive the formal surrender of the rebel arms. The homeward
march began on the thirteenth, and the regiment was mustered out
in the field, at Washington, on the twenty-eighth of June, and arrived
in Boston on the first of July.
Fellow citizens: The obelisk records only the names of the dead.
There is something partial in this distribution of honor. Those who
went through those dreadful fields and returned not deserve much
more than all the honor we can pay. But those also who went
through the same fields, and returned alive, put just as much at
hazard as those who died, and, in other countries, would wear
distinctive badges of honor as long as they lived. I hope the disuse of
such medals or badges in this country only signifies that everybody
knows these men, and carries their deeds in such lively
remembrance that they require no badge or reminder. I am sure I
need not bespeak your gratitude to these fellow citizens and
neighbors of ours. I hope they will be content with the laurels of one
war.
But let me, in behalf of this assembly, speak directly to you, our
defenders, and say, that it is easy to see that if danger should ever
threaten the homes which you guard, the knowledge of your
presence will be a wall of fire for their protection. Brave men! you will
hardly be called to see again fields as terrible as those you have
already trampled with your victories.
There are people who can hardly read the names on yonder
bronze tablet, the mist so gathers in their eyes. Three of the names
are of sons of one family.[193] A gloom gathers on this assembly,
composed as it is of kindred men and women, for, in many houses,
the dearest and noblest is gone from their hearth-stone. Yet it is
tinged with light from heaven. A duty so severe has been
discharged, and with such immense results of good, lifting private
sacrifice to the sublime, that, though the cannon volleys have a
sound of funeral echoes, they can yet hear through them the
benedictions of their country and mankind.

APPENDIX
In the above Address I have been compelled to suppress more
details of personal interest than I have used. But I do not like to omit
the testimony to the character of the Commander of the Thirty-
second Massachusetts Regiment, given in the following letter by one
of his soldiers:—

Near Petersburg, Virginia, June 20, 1864.

Dear Father:
With feelings of deep regret, I inform you that Colonel
Prescott, our brave and lamented leader, is no more. He was
shot through the body, near the heart, on the eighteenth day
of June, and died the following morning. On the morning of
the eighteenth, our division was not in line. Reveille was at an
early hour, and before long we were moving to the front. Soon
we passed the ground where the Ninth Corps drove the
enemy from their fortified lines, and came upon and formed
our line in rear of Crawford’s Division. In front of us, and one
mile distant, the Rebels’ lines of works could be seen.
Between us and them, and in a deep gulley, was the Norfolk
and Petersburg Railroad. Soon the order came for us to take
the railroad from the enemy, whose advance then held it. Four
regiments of our brigade were to head the charge; so the 32d
Massachusetts, 62d, 91st and 155th Pennsylvania regiments,
under command of Colonel Gregory, moved forward in good
order, the enemy keeping up a steady fire all the time. All
went well till we reached the road. The Rebels left when they
saw us advance, and, when we reached the road, they were
running away. But here our troubles began. The banks, on
each side of the road, were about thirty feet high, and, being
stiff clay, were nearly perpendicular. We got down well
enough, because we got started, and were rolled to the
bottom, a confused pile of Yanks. Now to climb the other side!
It was impossible to get up by climbing, for the side of it was
like the side of a house. By dint of getting on each other’s
shoulders and making holes for our feet with bayonets, a few
of us got up; reaching our guns down to the others, we all
finally got over. Meanwhile, a storm of bullets was rained
upon us. Through it all, Colonel Prescott was cool and
collected, encouraging the men to do their best. After we were
almost all across, he moved out in front of the line, and called
the men out to him, saying, “Come on, men; form our line
here.” The color-bearer stepped towards him, when a bullet
struck the Colonel, passed through him, and wounded the
color-bearer, Sergeant Giles of Company G. Calmly the
Colonel turned, and said, “I am wounded; some one help me
off.” A sergeant of Company B, and one of the 21st
Pennsylvania, helped him off. This man told me, last night, all
that the Colonel said, while going off. He was afraid we would
be driven back, and wanted these men to stick by him. He
said, “I die for my country.” He seemed to be conscious that
death was near to him, and said the wound was near his
heart; wanted the sergeant of Company B to write to his
family, and tell them all about him. He will write to Mrs.
Prescott, probably; but if they do not hear from some one an
account of his death, I wish you would show this to Mrs.
Prescott. He died in the division hospital, night before last,
and his remains will probably be sent to Concord. We lament
his loss in the regiment very much. He was like a father to us,
—always counselling us to be firm in the path of duty, and
setting the example himself. I think a more moral man, or one
more likely to enter the kingdom of heaven, cannot be found
in the Army of the Potomac. No man ever heard him swear, or
saw him use liquor, since we were in the service. I wish there
was some way for the regiment to pay some tribute to his
memory. But the folks at home must do this for the present.
The Thirty-second Regiment has lost its leader, and calls on
the people of Concord to console the afflicted family of the
brave departed, by showing their esteem for him in some
manner. He was one of the few men who fight for principle,—
pure principle. He did not fight for glory, honor nor money but
because he thought it his duty. These are not my feelings
only, but of the whole regiment. I want you to show this to
every one, so they can see what we thought of the Colonel,
and how he died in front of his regiment. God bless and
comfort his poor family. Perhaps people think soldiers have
no feeling, but it is not so. We feel deep anxiety for the
families of all our dear comrades.
Charles Bartlett,
Sergeant Company G, 32d Mass. Vols.[194]
 XVIII
EDITORS’ ADDRESS

MASSACHUSETTS QUARTERLY REVIEW,

DECEMBER, 1847

The old men studied magic in the flowers,

And human fortunes in astronomy,
And an omnipotence in chemistry,
Preferring things to names, for these were men,
Were unitarians of the united world,
And, wheresoever their clear eye-beams fell,
They caught the footsteps of the Same. Our eyes
Are armed, but we are strangers to the stars,
And strangers to the mystic beast and bird,
And strangers to the plant and to the mine.
The injured elements say, ‘Not in us;’
And night and day, ocean and continent,
Fire, plant and mineral say, ‘Not in us;’
And haughtily return us stare for stare.
For we invade them impiously for gain;
We devastate them unreligiously,
And coldly ask their pottage, not their love.
Therefore they shove us from them, yield to us
Only what to our griping toil is due;
But the sweet affluence of love and song,
The rich results of the divine consents
Of man and earth, of world beloved and loved,
The nectar and ambrosia are withheld.
 EDITORS’ ADDRESS
The American people are fast opening their own destiny. The
material basis is of such extent that no folly of man can quite subvert
it; for the territory is a considerable fraction of the planet, and the
population neither loath nor inexpert to use their advantages. Add,
that this energetic race derive an unprecedented material power
from the new arts, from the expansions effected by public schools,
cheap postage and a cheap press, from the telescope, the telegraph,
the railroad, steamship, steam-ferry, steam-mill; from domestic
architecture, chemical agriculture, from ventilation, from ice, ether,
caoutchouc, and innumerable inventions and manufactures.
A scholar who has been reading of the fabulous magnificence of
Assyria and Persia, of Rome and Constantinople, leaves his library
and takes his seat in a railroad-car, where he is importuned by
newsboys with journals still wet from Liverpool and Havre, with
telegraphic despatches not yet fifty minutes old from Buffalo and
Cincinnati. At the screams of the steam-whistle, the train quits city
and suburbs, darts away into the interior, drops every man at his
estate as it whirls along, and shows our traveller what tens of
thousands of powerful and weaponed men, science-armed and
society-armed, sit at large in this ample region, obscure from their
numbers and the extent of the domain. He reflects on the power
which each of these plain republicans can employ; how far these
chains of intercourse and travel reach, interlock and ramify; what
levers, what pumps, what exhaustive analyses are applied to Nature
for the benefit of masses of men. Then he exclaims, What a negro-
fine royalty is that of Jamschid and Solomon! What a substantial
sovereignty does my townsman possess! A man who has a hundred
dollars to dispose of—a hundred dollars over his bread—is rich
beyond the dreams of the Cæsars.
Keep our eyes as long as we can on this picture, we cannot stave
off the ulterior question,—the famous question of Cineas to Pyrrhus,
[195]—the where to of all this power and population, these surveys
and inventions, this taxing and tabulating, mill-privilege, roads, and
mines. The aspect this country presents is a certain maniacal
activity, an immense apparatus of cunning machinery which turns
out, at last, some Nuremberg toys. Has it generated, as great
interests do, any intellectual power? Where are the works of the
imagination—the surest test of a national genius? At least as far as
the purpose and genius of America is yet reported in any book, it is a
sterility and no genius.
One would say there is nothing colossal in the country but its
geography and its material activities; that the moral and intellectual
effects are not on the same scale with the trade and production.
There is no speech heard but that of auctioneers, newsboys, and the
caucus. Where is the great breath of the New World, the voice of
aboriginal nations opening new eras with hymns of lofty cheer? Our
books and fine arts are imitations; there is a fatal incuriosity and
disinclination in our educated men to new studies and the
interrogation of Nature. We have taste, critical talent, good
professors, good commentators, but a lack of male energy. What
more serious calamity can befall a people than a constitutional
dulness and limitation? The moral influence of the intellect is
wanting. We hearken in vain for any profound voice speaking to the
American heart, cheering timid good men, animating the youth,
consoling the defeated, and intelligently announcing duties which
clothe life with joy, and endear the face of land and sea to men.[196]
It is a poor consideration that the country wit is precocious, and, as
we say, practical; that political interests on so broad a scale as ours
are administered by little men with some saucy village talent, by deft
partisans, good cipherers; strict economists, quite empty of all
superstition.
Conceding these unfavorable appearances, it would yet be a poor
pedantry to read the fates of this country from these narrow data. On
the contrary, we are persuaded that moral and material values are
always commensurate. Every material organization exists to a moral
end, which makes the reason of its existence. Here are no books,
but who can see the continent with its inland and surrounding
waters, its temperate climates, its west-wind breathing vigor through
all the year, its confluence of races so favorable to the highest
energy, and the infinite glut of their production, without putting new
queries to Destiny as to the purpose for which this muster of nations
and this sudden creation of enormous values is made?
This is equally the view of science and of patriotism. We hesitate
to employ a word so much abused as patriotism, whose true sense
is almost the reverse of its popular sense. We have no sympathy
with that boyish egotism, hoarse with cheering for one side, for one
state, for one town: the right patriotism consists in the delight which
springs from contributing our peculiar and legitimate advantages to
the benefit of humanity. Every foot of soil has its proper quality; the
grape on two sides of the same fence has new flavors; and so every
acre on the globe, every family of men, every point of climate, has its
distinguishing virtues. Certainly then this country does not lie here in
the sun causeless; and though it may not be easy to define its
influence, men feel already its emancipating quality in the careless
self-reliance of the manners, in the freedom of thought, in the direct
roads by which grievances are reached and redressed, and even in
the reckless and sinister politics, not less than in purer expressions.
Bad as it is, this freedom leads onward and upward,—to a Columbia
of thought and art, which is the last and endless end of Columbus’s
adventure.
Lovers of our country, but not always approvers of the public
counsels, we should certainly be glad to give good advice in politics.
We have not been able to escape our national and endemic habit,
and to be liberated from interest in the elections and in public affairs.
Nor have we cared to disfranchise ourselves. We are more solicitous
than others to make our politics clear and healthful, as we believe
politics to be nowise accidental or exceptional, but subject to the
same laws with trees, earths and acids. We see that reckless and
destructive fury which characterizes the lower classes of American
society, and which is pampered by hundreds of profligate presses.
The young intriguers who drive in bar-rooms and town-meetings the
trade of politics, sagacious only to seize the victorious side, have put
the country into the position of an overgrown bully, and
Massachusetts finds no heart or head to give weight and efficacy to
her contrary judgment. In hours when it seemed only to need one
just word from a man of honor to have vindicated the rights of
millions, and to have given a true direction to the first steps of a
nation, we have seen the best understandings of New England, the
trusted leaders of her counsels, constituting a snivelling and
despised opposition, clapped on the back by comfortable capitalists
from all sections, and persuaded to say, We are too old to stand for
what is called a New England sentiment any longer. Rely on us for
commercial representatives, but for questions of ethics,—who knows
what markets may be opened? We are not well, we are not in our
seats, when justice and humanity are to be spoken for.
We have a bad war, many victories, each of which converts the
country into an immense chanticleer; and a very insincere political
opposition.[197] The country needs to be extricated from its delirium
at once. Public affairs are chained in the same law with private; the
retributions of armed states are not less sure and signal than those
which come to private felons. The facility of majorities is no
protection from the natural sequence of their own acts. Men reason
badly, but Nature and Destiny are logical.[198]
But, whilst we should think our pains well bestowed if we could
cure the infatuation of statesmen, and should be sincerely pleased if
we could give a direction to the Federal politics, we are far from
believing politics the primal interest of men. On the contrary, we hold
that the laws and governors cannot possess a commanding interest
for any but vacant or fanatical people; for the reason that this is
simply a formal and superficial interest; and men of a solid genius
are only interested in substantial things.
The State, like the individual, should rest on an ideal basis. Not
only man but Nature is injured by the imputation that man exists only
to be fattened with bread, but he lives in such connection with
Thought and Fact that his bread is surely involved as one element
thereof, but is not its end and aim. So the insight which commands
the laws and conditions of the true polity precludes forever all
interest in the squabbles of parties. As soon as men have tasted the
enjoyment of learning, friendship and virtue, for which the State
exists, the prizes of office appear polluted, and their followers
outcasts.
 A journal that would meet the real wants of this time must have a
courage and power sufficient to solve the problems which the great
groping society around us, stupid with perplexity, is dumbly
exploring. Let it now show its astuteness by dodging each difficult
question and arguing diffusely every point on which men are long
ago unanimous. Can it front this matter of Socialism, to which the
names of Owen and Fourier have attached, and dispose of that
question? Will it cope with the allied questions of Government,
Nonresistance, and all that belongs under that category? Will it
measure itself with the chapter on Slavery, in some sort the special
enigma of the time, as it has provoked against it a sort of inspiration
and enthusiasm singular in modern history? There are literary and
philosophical reputations to settle. The name of Swedenborg has in
this very time acquired new honors, and the current year has
witnessed the appearance, in their first English translation, of his
manuscripts. Here is an unsettled account in the book of Fame; a
nebula to dim eyes, but which great telescopes may yet resolve into
a magnificent system. Here is the standing problem of Natural
Science, and the merits of her great interpreters to be determined;
the encyclopædical Humboldt, and the intrepid generalizations
collected by the author of the Vestiges of Creation. Here is the
balance to be adjusted between the exact French school of Cuvier,
and the genial catholic theorists, Geoffroy St.-Hilaire, Goethe, Davy
and Agassiz. Will it venture into the thin and difficult air of that school
where the secrets of structure are discussed under the topics of
mesmerism and the twilights of demonology?
What will easily seem to many a far higher question than any other
is that which respects the embodying of the Conscience of the
period. Is the age we live in unfriendly to the highest powers; to that
blending of the affections with the poetic faculty which has
distinguished the Religious Ages? We have a better opinion of the
economy of Nature than to fear that those varying phases which
humanity presents ever leave out any of the grand springs of human
action. Mankind for the moment seem to be in search of a religion.
The Jewish cultus is declining; the Divine, or, as some will say, the
truly Human, hovers, now seen, now unseen, before us. This period
of peace, this hour when the jangle of contending churches is
hushing or hushed, will seem only the more propitious to those who
believe that man need not fear the want of religion, because they
know his religious constitution,—that he must rest on the moral and
religious sentiments, as the motion of bodies rests on geometry. In
the rapid decay of what was called religion, timid and unthinking
people fancy a decay of the hope of man. But the moral and religious
sentiments meet us everywhere, alike in markets as in churches. A
God starts up behind cotton bales also. The conscience of man is
regenerated as is the atmosphere, so that society cannot be
debauched. The health which we call Virtue is an equipoise which
easily redresses itself, and resembles those rocking stones which a
child’s finger can move, and a weight of many hundred tons cannot
overthrow.
With these convictions, a few friends of good letters have thought
fit to associate themselves for the conduct of a new journal. We have
obeyed the custom and convenience of the time in adopting this form
of a Review, as a mould into which all metal most easily runs. But
the form shall not be suffered to be an impediment. The name might
convey the impression of a book of criticism, and that nothing is to
be found here which was not written expressly for the Review; but
good readers know that inspired pages are not written to fill a space,
but for inevitable utterance; and to such our journal is freely and
solicitously open, even though everything else be excluded. We
entreat the aid of every lover of truth and right, and let these
principles entreat for us. We rely on the talents and industry of good
men known to us, but much more on the magnetism of truth, which is
multiplying and educating advocates for itself and friends for us. We
rely on the truth for and against ourselves.
 XIX
ADDRESS TO KOSSUTH

AT CONCORD, MAY 11, 1852

God said, I am tired of kings,

I suffer them no more;
Up to my ear the morning brings
The outrage of the poor.

My angel,—his name is Freedom,—

Choose him to be your king;
He shall cut pathways east and west,
And fend you with his wing.

ADDRESS TO KOSSUTH
Sir,—The fatigue of your many public visits, in such unbroken
succession as may compare with the toils of a campaign, forbid us to
detain you long. The people of this town share with their countrymen
the admiration of valor and perseverance; they, like their
compatriots, have been hungry to see the man whose extraordinary
eloquence is seconded by the splendor and the solidity of his
actions. But, as it is the privilege of the people of this town to keep a
hallowed mound which has a place in the story of the country; as
Concord is one of the monuments of freedom; we knew beforehand
that you could not go by us; you could not take all your steps in the
pilgrimage of American liberty, until you had seen with your eyes the
ruins of the bridge where a handful of brave farmers opened our
Revolution. Therefore, we sat and waited for you.
And now, Sir, we are heartily glad to see you, at last, in these
fields. We set no more value than you do on cheers and huzzas. But
we think that the graves of our heroes around us throb to-day to a
footstep that sounded like their own:—

“The mighty tread

Brings from the dust the sound of liberty.”[199]

Sir, we have watched with attention your progress through the

land, and the varying feeling with which you have been received, and
the unvarying tone and countenance which you have maintained.
We wish to discriminate in our regard. We wish to reserve our honor
for actions of the noblest strain. We please ourselves that in you we
meet one whose temper was long since tried in the fire, and made
equal to all events; a man so truly in love with the greatest future,
that he cannot be diverted to any less.
It is our republican doctrine, too, that the wide variety of opinions is
an advantage. I believe I may say of the people of this country at
large, that their sympathy is more worth, because it stands the test of
party. It is not a blind wave; it is a living soul contending with living
souls. It is, in every expression, antagonized. No opinion will pass
but must stand the tug of war. As you see, the love you win is worth
something; for it has been argued through; its foundation searched; it
has proved sound and whole; it may be avowed; it will last, and it will
draw all opinion to itself.
We have seen, with great pleasure, that there is nothing accidental
in your attitude. We have seen that you are organically in that cause
you plead. The man of Freedom, you are also the man of Fate. You
do not elect, but you are elected by God and your genius to the task.
We do not, therefore, affect to thank you. We only see in you the
angel of freedom, crossing sea and land; crossing parties,
nationalities, private interests and self-esteems; dividing populations
where you go, and drawing to your part only the good. We are afraid
that you are growing popular, Sir; you may be called to the dangers
of prosperity. But, hitherto, you have had in all centuries and in all
parties only the men of heart. I do not know but you will have the
million yet. Then, may your strength be equal to your day. But
remember, Sir, that everything great and excellent in the world is in
minorities.[200]
Far be from us, Sir, any tone of patronage; we ought rather to ask
yours. We know the austere condition of liberty—that it must be
reconquered over and over again; yea, day by day; that it is a state
of war; that it is always slipping from those who boast it to those who
fight for it: and you, the foremost soldier of freedom in this age,—it is
for us to crave your judgment; who are we that we should dictate to
you? You have won your own. We only affirm it. This country of
workingmen greets in you a worker. This republic greets in you a
republican. We only say, ‘Well done, good and faithful.’—You have
earned your own nobility at home. We admit you ad eundem (as they
say at College). We admit you to the same degree, without new trial.
We suspend all rules before so paramount a merit. You may well sit
a doctor in the college of liberty. You have achieved your right to
interpret our Washington. And I speak the sense not only of every
generous American, but the law of mind, when I say that it is not
those who live idly in the city called after his name, but those who, all
over the world, think and act like him, who can claim to explain the
sentiment of Washington.
Sir, whatever obstruction from selfishness, indifference, or from
property (which always sympathizes with possession) you may
encounter, we congratulate you that you have known how to convert
calamities into powers, exile into a campaign, present defeat into
lasting victory. For this new crusade which you preach to willing and
to unwilling ears in America is a seed of armed men. You have got
your story told in every palace and log hut and prairie camp,
throughout this continent. And, as the shores of Europe and America
approach every month, and their politics will one day mingle, when
the crisis arrives it will find us all instructed beforehand in the rights
and wrongs of Hungary, and parties already to her freedom.
 XX
WOMAN

A LECTURE READ BEFORE THE WOMAN’S

RIGHTS CONVENTION, BOSTON, SEPTEMBER
20, 1855

The politics are base,

The letters do not cheer,
And ’tis far in the deeps of history,
The voice that speaketh clear.

Yet there in the parlor sits

Some figure in noble guise,—
Our Angel in a stranger’s form;
Or Woman’s pleading eyes.

“Lo, when the Lord made North and South,

And sun and moon ordained he,
Forth bringing each by word of mouth
In order of its dignity,
Did man from the crude clay express
By sequence, and, all else decreed,
He formed the woman; nor might less
Than Sabbath such a work succeed.”

Coventry Patmore.
 WOMAN
Among those movements which seem to be, now and then,
endemic in the public mind,—perhaps we should say, sporadic,—
rather than the single inspiration of one mind, is that which has urged
on society the benefits of action having for its object a benefit to the
position of Woman. And none is more seriously interesting to every
healthful and thoughtful mind.
In that race which is now predominant over all the other races of
men, it was a cherished belief that women had an oracular nature.
They are more delicate than men,—delicate as iodine to light,—and
thus more impressionable. They are the best index of the coming
hour. I share this belief. I think their words are to be weighed; but it is
their inconsiderate word,—according to the rule, ‘take their first
advice, not the second:’ as Coleridge was wont to apply to a lady for
her judgment in questions of taste, and accept it; but when she
added—“I think so, because—” “Pardon me, madam,” he said,
“leave me to find out the reasons for myself.” In this sense, as more
delicate mercuries of the imponderable and immaterial influences,
what they say and think is the shadow of coming events. Their very
dolls are indicative. Among our Norse ancestors, Frigga was
worshipped as the goddess of women. “Weirdes all,” said the Edda,
“Frigga knoweth, though she telleth them never.” That is to say, all
wisdoms Woman knows; though she takes them for granted, and
does not explain them as discoveries, like the understanding of man.
Men remark figure: women always catch the expression. They
inspire by a look, and pass with us not so much by what they say or
do, as by their presence. They learn so fast and convey the result so
fast as to outrun the logic of their slow brother and make his
acquisitions poor.[201] ’Tis their mood and tone that is important.
Does their mind misgive them, or are they firm and cheerful? ’Tis a
true report that things are going ill or well. And any remarkable
opinion or movement shared by woman will be the first sign of
revolution.
Plato said, Women are the same as men in faculty, only less in
degree. But the general voice of mankind has agreed that they have