Evolving Systems (2017) 8:203–210
DOI 10.1007/s12530-017-9176-x
ORIGINAL PAPER
Design of spiking neural networks for blood pressure prediction
during general anesthesia: considerations for optimizing results
Go Hamano1 · Andrew Lowe1 · David Cumin2
Received: 7 April 2016 / Accepted: 23 January 2017 / Published online: 7 March 2017
© Springer-Verlag Berlin Heidelberg 2017
Abstract The ability to predict blood pressure changes
during general anesthesia would assist anesthetists mini-
mize the risk of complications due to hypotensive events.
However, such prediction is not trivial. Evolving spiking
neural networks are a relatively new computational method
that may have application to this problem. ­NeuCubeST con-
sists of a 3-dimensional network of locally connected neu-
rons called a Spiking Neural Network reservoir (SNNr)
and can be used to classify time series data for prediction.
There are a number of design considerations when using
­NeuCubeST as a classifier of time-series data: what pre-
processing of the raw data is required (pre-processing),
how to convert the time-series data into a spike train (input-
encoding), which neurons the data are connected to (input-
mapping), and how many nearest neighbours to use in clas-
sification (classification). However, it is still unclear how
sensitive ­NeuCubeST-based systems are to perturbations
of any of the above. In this paper we evaluate the contri-
bution of these design factors to blood pressure prediction
using ­NeuCubeST. 6000 possible combinations of those
­NeuCubeST options were tested for each of 100 patients
and for each a Signal to Noise Ratio was obtained. All four
investigated design factors showed significant contribution
to SNR. Intra-operative MAP prediction using ­NeuCubeST
can be effective but performance is sensitive to the design
choices.
* David Cumin
d.cumin@auckland.ac.nz
1
Institute of Biomedical Technologies, Auckland University
of Technology, Private Bag 92006, Auckland 1142,
New Zealand
2 Attempts at predicting MAP have included an adaptive
Department of Anaesthesiology, Faculty of Medical
and Health Sciences, The University of Auckland, Private
Bag 92019, Auckland 1142, New Zealand
Keywords NeuCube · Spiking neural network ·
Anesthesia · Prediction · Blood pressure
1 Background
In the late 1980s, it was estimated that, over a given day,
there was more information contained in the records
of a typical 700-bed hospital than in the London Stock
Exchange (Weiss et al. 1995). Some physiologic data, such
as mean arterial pressure (MAP) and heart rate (HR) are
now routinely and automatically collected during general
anesthesia in many hospitals. However, beyond the imme-
diate surgical case, these data are seldom utilized. One area
where such “big data” could be of great value is in predict-
ing future physiological states. In this work, we are inter-
ested in predicting mean arterial blood pressure (MAP) as
it is essential to keep MAP within relatively narrow limits
during anesthesia (Gordon and Russell 2005; Rivers et al.
2001). Intraoperative hypotensive (low MAP) events, for
example, are common and associated with adverse events
(Morris et al. 2005).
There are a variety of techniques that could be applied to
physiological time-series data for prediction. Some exam-
ples of the approaches are mathematical modeling of the
cardiovascular system (Heldt et al. 2006), applications of
wavelet analysis (Saeed and Mark 2000), fuzzy inference
(Lowe et al. 1999), and fuzzy inference (Versaci and Mora-
bito 2003). Various attempts at estimating hemodynamic
status have been made but the complex and nonlinear
nature of hemodynamic parameters (Wo et al. 1993) makes
a solution non-trivial.
network fuzzy inference system (FIS) using HR, previous
MAP values, fraction of inspired isoflurane, and end-tidal
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204
­ O2 concentration (­EtCO2) as inputs (Jensen and Nebot
C predict time series data in much the same way as classifica-
1998). The algorithm was tested on five patients to predict
MAP 70 s ahead. Mean squared prediction errors ranged
from 41 to 170% (Jensen and Nebot 1998).
Severity of hemorrhage has been predicted using dis-
crete wavelet transformation and Support Vector Machines
(SVMs) using the electrocardiogram (ECG), arterial blood
pressure, and thoracic impedance signals (Ji et al. 2009).
Data were collected on 59 healthy humans exposed to a
hemorrhage model known as lower body negative pressure
(LBNP). Severity of shock was predicted with an accuracy
of 82% under these controlled conditions.
Hypotensive events were predicted using wavelet anal-
ysis, principal component analysis and a 3-layer artificial
neural network (ANN) with HR and systolic, diastolic,
and mean arterial blood pressure as inputs (Lee and Mark
2011). The ANN was designed to predict hypotension after
a gap of 1–4 h. The algorithm was trained with 130,325
controls and 3953 hypotensive examples from the MIMIC-
II database. Despite low positive predictive values, the best
mean area under ROC curve was 0.934.
In this research, we apply a novel spiking neural net-
work architecture, called ­ NeuCubeST (Tu et al. 2014).
Spiking neural network mimic phenomenon observed dur-
ing biologicalneural information processing (Bohte 2004).
­NeuCubeST has been successfully applied to the analysis
of spatio-temporal brain data [e.g. EEG (Kasabov 2012)]
and time-series data without spatial information [e.g. stroke
occurrence prediction using environmental data (Kasabov
et al. 2014)]. This study differs from previously reported
research by (1) using a spiking neural network technique;
(2) utilizing a relatively large number of anaesthetic
records; (3) relying on routinely collected data rather than
specialized protocols; and (4) designing prediction models
to predict MAP 5 min ahead in time.
2 NeuCubeST
NeuCubeST is comprised of a 3-dimensional network of
locally connected neurons called a Spiking Neural Network
reservoir (SNNr). Data are input to neurons in the SNNr
after conversion to spike trains. These neurons signal other
neurons, which in turn spike if thresholds are reached, and
so on throughout the network. When output neurons spike,
an output spike train is generated (Tu et al. 2014).
NeuCubeST has three main modes of operation (Kasa-
bov 2014): (1) unsupervised learning according to a Spike
Timing Dependent Plasticity (STDP) learning rule; (2)
supervised learning according to a rank order rule; and (3)
prediction or classification based on a comparison method,
such as Nearest Neighbor Search. The latter can be used to
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Evolving Systems (2017) 8:203–210
tion of aphid growth trends (Tu et al. 2014).
The size of the SNNr is defined by three parameters:
­nx, ­ny and ­nz, representing the neuron numbers along x,
y and z axis, respectively. The neurons are allocated in a
parallelepiped array ­nx × n­ y × n­ z. A neuron in the SNNr
is connected to its neighboring neurons, defined as neu-
rons to which it has a distance shorter than a set distance
parameter.
2.1 Input feature mapping
Each variable in a set of time-series data is mapped onto
the SNNr via two main categories of feature allocation
methods. The similarity-based approach maps each varia-
ble to its corresponding feature with their distance based on
a similarity matrix among those variables. The other cat-
egory of feature allocation is trial and error, which is based
on the idea that trials with cross validation after random
selections of mappings would enable a more effective map-
ping to be found.
2.2 Input encoding
NeuCubeST processes spike trains so an input encoder that
converts real value sequences to spike trains is required. We
used two methods for encoding the input signals: Address
Event Representation (AER), which has successfully
applied to a SNN (Dhoble et al. 2012), and a novel encod-
ing method combining inter-spike interval and Gaussian
receptive field encodings.
2.2.1 AER
AER is based on an idea that a significant change in a vari-
able is considered an event. Specifically, AER uses the
variable gradient with respect to time, and a bi-direction
threshold to emit a positive or negative spike. The thresh-
old is a parameter, and for instance, a threshold can be
determined in a statistical way using the sum of the mean
value and standard deviation of the signal gradient. A tun-
ing of the threshold parameter can change the significance
of each event.
2.2.2 Gaussian encoding method
We propose a novel input encoding method based on both
the Inter-Spike Interval (ISI) encoding method (Torikai
et al. 2006) and the Gaussian Receptive Field (GRF) encod-
ing method (Johnson et al. 2011). ISI is a way of represent-
ing a real value as an inter-spike interval in spike trains and
theoretically has an ability to allow the real value itself to
propagate through a SNN. GRF is a way of delaying a spike
Evolving Systems (2017) 8:203–210
emission of a feature neuron according to a Gaussian func-
tion of the distance between a set value and a real value.
GRF was originally proposed for spatial data, rather than
for time-series data. In our method, we first calculate the
difference between the variable value and the mean of that
variable. Secondly, we define a positive or negative spike
emission delay in accordance with how close the differ-
ence is: when the difference is bigger, emit a spike earlier;
if the difference is positive, emit a positive spike; if nega-
tive, emit a negative spike. Thirdly, ensure the spike emis-
sions occur for every time point and do not overlap. Conse-
quently, this third rule gives the method features of ISI as
well as that of GRF. In other words, the interval between
two successive spikes represents the gradient between their
related time points.
In short, there are a number of design considerations
when using N ­ euCubeST as a classifier of time-series data:
what pre-processing of the raw data is required (pre-
processing), how to convert the time-series data into a
spike train (input-encoding), which neurons the data are
connected to (input-mapping), and how many nearest
neighbors to use in classification (classification). How-
ever, it is unclear from published literature how sensitive
­NeuCubeST-based systems are to perturbations of any of the
above design considerations.
3 Experimental design and results
3.1 Aim
The purpose of this work is to explore the sensitivity of
­NeuCubeST to different pre-processing, input-encoding,
input-mapping, and classification settings in predicting
blood pressure values from intra-operative records.
3.2 Methods
3.2.1 Ethics approval
Ethics approval was obtained from NZHDC (12/NTA/74)
to create a database of de-identified electronic anesthetic
records, including physiological data, from operating
rooms of a tertiary hospital in Auckland, New Zealand.
3.2.2 Prediction Models
We chose to design a model to predict the MAP 5 min
ahead from the given previous 15 min pattern of MAP,
end-tidal carbon dioxide (­ EtCO2), minimum alveolar con-
centration (MAC), heart rate (HR), peripheral capillary
oxygen saturation (­SpO2) and body temperature (BT).
All these variables are routinely measured during general
205
anesthesia as part of patient monitoring in high standard
anesthesia work stations (Chilkoti et al. 2015). The data
was sampled at 30 s intervals.
A random sample of 100 anesthetic records with
between 30 min and 45 min of overlapping data for all
physiologic variables were extracted from the database.
Training patterns were extracted from these records with
a 20 min sliding window with 5 min steps. Leave-one-out
cross validation was performed for each record, where
predictions were generated every 30 s starting from
20 min into the record.
Multiple prediction models were designed, encom-
passing every combination of options for each of the
chosen design factors on a ­NeuCubeST model of reservoir
size 6 × 6 × 6:
• Pre-processing Raw data were either pre-processed with
a 5-step median filter or encoded without the filter. A
median filter was chosen to remove outliers (Saeed
2007). An outlier may occur for clinical reasons, for
example a blood-sampling event will interfere with
the MAP reading as it uses the same cannula. Because
blood sampling and other, similar events usually take
less than 1 min (2 steps) to finish, the 5-step median fil-
ter was chosen. Thus, there were 2 options for the pre-
processing step.
• Input encoding Address event representation (AER)
(Kasabov 2012) and the newly proposed Gaussian-
receptive-field-based encoding method (see above)
were tested. For the AER, 2 different spiking thresholds
were tested. Each method was tested in forward and
reverse time order because the Rank-Order rule used in
­NeuCubeST supervised learning puts more importance
on earlier-emitted spikes than later spikes. Thus, there
were a total of 6 options for input encoding.
Fig. 1  Histogram of SNR over the 600,000 experiments
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206 Evolving Systems (2017) 8:203–210

a b
5.0 5.0

2.5 2.5

SNR
SNR

0.0 0.0

−2.5 −2.5

−5.0 −5.0

Raw Median filter AER 1 AER 2 Gaussian AER 1 reverse AER 2 reverse Gaussian reverse
Pre−processing Input Encoding
c d
5.0
5.0

2.5
2.5

SNR
SNR

0.0
0.0

−2.5
−2.5

−5.0
−5.0

1 20 40 60 80 10 1 10 10 weighted 50 50 weighted
Input Mapping
Classification

e
5.0

2.5
SNR

0.0

−2.5

−5.0

1 20 40 60 80 100
Patient

Fig. 2  Boxplots of SNR by Input encoding method and classification algorithm. Note these plots only show SNR in [−5,5]

• Input mapping Input feature neurons in each predic- Although graph-matching algorithms have been pro-
tion model were allocated to randomly-generated input posed (Tu et al. 2014), we applied none of them to keep
feature allocations. We used 100 such allocations. the experiments straightforward.

13
Evolving Systems (2017) 8:203–210 207

Table 1  ANOVA results of model with SNR as the dependent vari- 3.3 Results
able
F-value P-value The mean and standard deviation of SNR over the 600,000
experiments was −0.8675 ± 2.1732 dB. The distribution of
Pre-processing 909.6 <0.001
SNR are shown in Fig. 1.
Input encoding 851.9 <0.001
Univariate analysis suggests that there are significant
Input mapping 4.4 <0.001
differences between levels in all of the possible factors.
Classification 99,496.6 <0.001
These are represented graphically in Fig. 2 for input encod-
Patient 4142.3 <0.001
ing and classification only as exemplars.
The ANOVA results (Table 1) show that all design con-
siderations contribute to the SNR.
Table 2  ANOVA results of model with interactions and SNR as the Table 2 shows that interactions are all significant also:
dependent variable
The second order interactions can be visualized in Fig. 3.
F-value P-value

Pre-processing 91.3 <0.001

Input encoding 86.6 <0.001
4 Discussion
Classification 9,955.9 <0.001
Patient 241.6 <0.001
Approximately one-third (37.6%) of the experiments had
Pre-processing × input encoding 7.9 <0.001
an SNR above 0 in these experiments. This suggests some
Pre-processing × classification 35.7 <0.001
promise for using this method in predicting MAP val-
Input encoding × classification 34.3 < 0.001
ues. However, different design choices for the ­NeuCubeST
Pre-processing × input encoding × clas- 1.8 0.115
model had an effect on the results of predicting blood pres-
sification ­ euCubeST is sensitive to
sure (Fig. 3). This indicates that N
these choices and careful consideration should be given
before using the model to predict MAP.
The selection of k-NN method (that is, classification
• Classification Several k-nearest neighbor search method) has the largest main effect, and that of pre-pro-
methods were tested, specifically: non-weighted and cessing and input encoding methods the second largest.
weighted k-nearest neighbor search methods with Using more nearest neighbours for classification improves
k = 10 and 50, as well as 1-Nearest Neighbor Search. the prediction, which indicates that there are not a small
Thus there were 5 options for classification method. number of clusters in the dynamic behavior of patients. The
weighting of nearest neighbours may also be of benefit for
All 6000 possible combinations (2 × 6 × 100 × 5) of predicting blood pressure. The F-value for input mapping
­NeuCubeST design options were tested for each of the indicates the lowest variance between different schemes
100 patients. The signal-to-noise ratio (SNR) was used to as a ratio of variance within a scheme. In this work, input
measure the accuracy of the predictions. SNR is defined mapping was chosen randomly, but more work needs to be
here as 10 L­ og10 {(mean square of the increments occur- done to understand if deterministic input mapping schemes
ring in 300 s)/(mean square error of the predicted incre- perform significantly differently.
ments)}. By this definition, positive SNR means a pre- The results shown in Fig. 3 indicate that preprocessing
diction better than the naive prediction method of using the data is slightly better for prediction of MAP, although
the value of each pattern at 15 min to predict the value at there appears to be some interaction between preprocess-
20 min (i.e. a 300 s increment). ing and input encoding scheme, which is intuitively plau-
Analysis of variance (ANOVA) was used to measure sible. Gaussian input encoding leads to the best predic-
the relative contribution of each design consideration on tion in this task. Notably, a “patient” selection can affect
the SNR. The F-value can be interpreted as an indicator prediction significantly. It is likely that the best predic-
of effect-size, and the P-value is the statistical signifi- tions came from patients where the test patterns were most
cance level. Given the large data set, parametric analysis similar to the training patterns. This supports the idea that
is appropriate even though the distribution of SNR may ­NeuCubeST can become a better predictor by being specifi-
not be normal (Lumley et al. 2002). Data were analysed cally designed for a similar subject group, such as a patient
using R (v3.1.2, CRAN). group (smoking, male, more than 60 years old and with
hypertension) or stroke prediction from temporal local cli-
mate data (Kasabov et al. 2014). We did not investigate the
patient demographics.

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208 Evolving Systems (2017) 8:203–210

a −0.6 b
0

−0.7

−1
encoding
−0.8 k_knn
AER 1
1

Mean SNR
Mean SNR

AER 2
10
Gaussian
10 weighted
AER 1 reverse
50
−0.9 AER 2 reverse
50 weighted
Gaussian reverse −2

−1.0

−3

−1.1

Pre−processing Pre−processing

c
0

−1

k_knn
1
Mean SNR

10
10 weighted
−2 50
50 weighted

−3

AER 1 AER 2 Gaussian AER 1 reverse AER 2 reverse Gaussian reverse

Input encoding

Fig. 3  Interaction plots for each of the second order interactions

NeuCubeST has potential to be an effective predictor of
MAP using the proposed methodology. However, all four
investigated design factors showed highly significant con-
tribution to SNR when controlling for patient selection.
Many other parameters such as training algorithms or other
algorithm settings may also impact results but were not
investigated. In this research, patient records were chosen
at random. More work is required to determine the applica-
bility of these results to specific patient groups and surgical
or anaesthetic procedures. Such work will lead to a better
understanding of how to optimize experimental designs for
improved prediction results.
Although it is a natural question to ask which com-
bination is best for predicting MAP, it was not the inten-
tion of this research to answer that question, which will be
the subject of future work. Similarly, we did not use other
methods for prediction of MAP as this was outside the
scope of the research. Such comparisons could be the focus
of future work.
5 Conclusion
This research found that MAP prediction was particularly
sensitive to output classification method. Notably, the use
of larger numbers of nearest neighbours was associated
with better performance (higher SNR), on average. Opti-
mal choice of output classification (that is, the number of
nearest neighbours) is likely to be dependent on the clus-
tering characteristics of the application and these results

13
Evolving Systems (2017) 8:203–210
indicate that there is a wide variety of dynamic behaviors
within patient time series. Median filtering as a method of
preprocessing was also found to have a significant effect
on prediction performance. Application of median filter-
ing improved the upper quartile of predictor performance,
but also reduced the lower quartile. These results indicate
that feature extraction, particularly that which affects tem-
poral information contained in the data, affects the ease
with which the temporal network can distinguish between
relevant and irrelevant patterns. The effect of filtering also
showed interaction with input encoding method, which,
although intuitively reasonable, is a further indication of
the optimization complexity facing a system designer.
Nevertheless, some configurations of ­NeuCubeST in this
research demonstrated MAP prediction performance sub-
stantially greater than a naïve approach, which is promising
evidence for both the existence of a relationship between
the measured variables and future MAP, and the ability of
spiking neural networks to discover this relationship.
In summary, intra-operative MAP prediction using
­NeuCubeST can be effective but performance is sensitive
to pre-processing, input encoding, input mapping and clas-
sification methods. Such design choices must be carefully
considered by anyone wishing to utilize ­NeuCubeST for this
purpose.
Acknowledgements The work is sponsored by the Knowledge
Engineering and Discovery Research Institute, Auckland University
of Technology, New Zealand. We are grateful for the assistance of
Prof. Chris Triggs, Statistics, University of Auckland, for his advice
regarding the analysis of these data.
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