Smartphone-based differential pulse amperometry system for real-time monitoring of levodopa with car

Parkinson's disease caused by lack of dopamine in brain is a common neurodegenerative disorder. The traditional treatment is to replenish levodopa since it could pass through blood brain barrier and form dopamine. However, its accumulation can cause patients’ movement disorders and uncontrollable emotion. Therefore, it is critical to control the levodopa dosage accuracy to improve the curative effect in clinical. In this study, a smartphone-based electrochemical detection system was developed for rapid monitoring of levodopa. The system involved a disposable sensor, a hand-held electrochemical detector, and a smartphone with designed application. Single-wall carbon nanotubes and gold nanoparticles modified screen-printed electrodes were used to convert and amplify the electrochemical current signals upon presence of levodopa molecules. The electrochemical detectors were used to generate electrochemical excitation signals and detect the resultant currents. Smartphone was connected to the detector, which was used to control the detector, calculate data, and plot graph in real-time. The smartphone-based differential pulse amperometry system was demonstrated to monitor levodopa at concentrations as low as 0.5 μM in human serum. Furthermore, it has also been verified to be able to distinguish levodopa from other representative substances in the body. Therefore, its performance was more sensitive and rapid than electrochemical workstation. With these advantages, the system can be used in the field of point-of-care testing (POCT) to detect levodopa and provide the possibility to solve clinical demand for levodopa detection.

Ji,D.Xu, N., Liu, Z., Shi, Z., Low, S.S., Liu, J., Cheng, C., Zhu, J., Zhang, T., Xu, H., Yu X, Liu Q.. (2018).Smartphone-based differential pulse amperometry system for real-time monitoring of levodopa with carbon nanotubes and gold nanoparticles modified screen-printing electrodes. Biosensors & bioelectronics.

Frequency-Dependent Stimulus-Specific Adaptation and Regularity Sensitivity in the Rat Auditory Thal

Recent electrophysiological studies in animals using oddball stimuli have demonstrated that neurons along the auditory pathway from the inferior colliculus to the auditory cortex (AC) have a strong response to rarely presented stimuli. This phenomenon is termed stimulus-specific adaptation (SSA), which is regarded as novelty detection. However, in the medial geniculate body (MGB), it is not clear whether SSA is frequency dependent or if neurons in the MGB are sensitive to the regularity of the stimuli. In this present study, we analyzed the relationship between stimulus frequency and SSA, as well as explored regularity sensitivity using extracellular recordings in the MGBs of rats with regular and irregular oddball stimuli. It was found MGB neurons exhibited strong SSA when the pure-tone stimulus of the oddball stimulus deviated far from the characteristic frequency, even in the ventral region of the MGB, suggesting that the MGB may contribute to SSA in the primary AC. Moreover, we found the neuronal population in the MGB was sensitive to high-order sound structure, where deviant responses were smaller and standard responses were stronger for irregular oddball stimuli. We conclude that regularity detection occurs in the MGB, but in a manner distinct from the AC. 2018 IBRO. Published by Elsevier

2018-10-15

Rui,Y.Y., He J., Y.Y. Zhai, Z.H. Sun and X. Yu* (2018), Frequency Dependent Stimulus-Specific Adaptation and Regularity Sensitivity in the Auditory Thalamus of Rat. Neuroscience

Smartphone-based integrated voltammetry system for simultaneous detection of ascorbic acid, dopamine

Ascorbic acid, dopamine, and uric acid are important electroactive biomolecules for health monitoring and they coexist in serum or urine. Their quantitative determination by electrochemistry could provide the accurate reference for diseases diagnosis and treatment. However, the traditional electrochemical workstations are too large for on-field inspection. Hence, the design of handheld electrochemical system for the detection of biomolecules is significant for point-of-care testing (POCT). In this paper, a smartphone-based integrated voltammetry system using modified electrode was developed for simultaneous detection of biomolecules. The system contained a disposable sensor, a coin-size detector, and a smartphone equipped with application program. Screen-printed electrodes were used as sensors for the detection, on which reduced graphene oxide and gold nanoparticles were electrochemically deposited by the system. The detector was used with voltammetric methods, in which excitation voltage was applied on the sensors and subsequent current responses were detected.

The smartphone is the core component to communicate with the detector, calculate data, and plot voltammograms in real-time. Then, the system was applied to detect standard solutions of the biomolecules and their mixtures as examples. The results showed that the peak currents of each substance increased with higher concentration and the method allowed the discrimination of the different potentials of the studied species. Finally, the practical applications of the system were tested through detections of the biomolecules in artificial urine. The results exhibited that the system could be used to detect electrochemical activity of biomolecules with linear, high sensitivity, and specific responses in point-of-care testing.

Ji D, Liu Z, Liu L, Low SS, Lu Y, Yu X, Zhu L, Li C & Liu Q. (2018). Smartphone-based integrated voltammetry system for simultaneous detection of ascorbic acid, dopamine, and uric acid with graphene and gold nanoparticles modified screen-printed electrodes. Biosensors & bioelectronics 119, 55-62.

Transformation of spatiotemporal dynamics in the macaque vestibular system from otolith afferents to

Abstract Sensory signals undergo substantial recoding when neural activity is relayed from
sensors through pre-thalamic and thalamic nuclei to cortex. To explore how temporal dynamics and
directional tuning are sculpted in hierarchical vestibular circuits, we compared responses of
macaque otolith afferents with neurons in the vestibular and cerebellar nuclei, as well as five
cortical areas, to identical three-dimensional translational motion. We demonstrate a remarkable
spatio-temporal transformation: otolith afferents carry spatially aligned cosine-tuned translational
acceleration and jerk signals. In contrast, brainstem and cerebellar neurons exhibit non-linear,
mixed selectivity for translational velocity, acceleration, jerk and position. Furthermore, these
components often show dissimilar spatial tuning. Moderate further transformation of translation
signals occurs in the cortex, such that similar spatio-temporal properties are found in multiple
cortical areas. These results suggest that the first synapse represents a key processing element in
vestibular pathways, robustly shaping how self-motion is represented in central vestibular circuits
and cortical areas.

Laurens J, Liu S, Yu X J, et al. Transformation of spatiotemporal dynamics in the macaque vestibular system from otolith afferents to cortex[J]. Elife, 2017, 6.

Adaptation facilitates spatial discrimination for deviant locations in the thalamic reticular nucleu

The capacity to identify unanticipated abnormal cues in a natural scene is vital for animal survival. Stimulusspecific adaptation (SSA) has been considered the neuronal correlate for deviance detection. There have been comprehensive assessments of SSA in the frequency domain along the ascending auditory pathway, but only little attention given to deviance detection in the spatial domain. We found that thalamic reticular nucleus (TRN) neurons exhibited stronger responses to a tone when it was presented rarely as opposed to frequently at a certain spatial location. Subsequently, we engaged signal detection theory to directly gauge neuronal spatial discriminability and found that discrimination of deviant locations was considerably higher than standard locations. The variability in neuronal spatial discriminability among the TRN population was directly related to response difference (RD) but not variance; meanwhile, further analyses attributed higher spatial sensitivity at deviant locations to larger RD. Astonishingly, a significant correlation was found between the amount of adaptation and deviant discriminability. Collectively, our results suggest that adaptation facilitates rare location discrimination by sharpening the response gap between two locations.2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Xu X X, Zhai Y Y, Kou X K, et al. Adaptation facilitates spatial discrimination for deviant locations in the thalamic reticular nucleus of the rat.[J]. Neuroscience, 2017, 19(10):1-11.

Neuronal thresholds and choice-related activity of otolith afferent fibers during heading perception

How activity of sensory neurons leads to perceptual decisions
remains a challenge to understand. Correlations between choices
and single neuron firing rates have been found early in vestibular
processing, in the brainstem and cerebellum. To investigate the
origins of choice-related activity, we have recorded from otolith
afferent fibers while animals performed a fine heading discrimination
task. We find that afferent fibers have similar discrimination
thresholds as central cells, and the most sensitive fibers have
thresholds that are only twofold or threefold greater than perceptual
thresholds. Unlike brainstem and cerebellar nuclei neurons,
spike counts from afferent fibers do not exhibit trial-by-trial
correlations with perceptual decisions. This finding may reflect
the fact that otolith afferent responses are poorly suited for driving
heading perception because they fail to discriminate self-motion
from changes in orientation relative to gravity. Alternatively,
if choice probabilities reflect top-down inference signals, they are
not relayed to the vestibular periphery.

Xiong-jie Yu ，J David Dickman，Gregory C Deangelis，Dora E Angelaki，Neuronal thresholds and choice-related activity of otolith afferent fibers during heading perception.，Proceedings of the National Academy of Sciences of the United States of America，2015，112（20）：6467-6472

Across-ear stimulus-specific adaptation in the auditory cortex.

The ability to detect unexpected or deviant events in natural scenes is critical for survival. In
the auditory system, neurons from the midbrain to cortex adapt quickly to repeated stimuli
but this adaptation does not fully generalize to other rare stimuli, a phenomenon called
stimulus-specific adaptation (SSA). Most studies of SSA were conducted with pure tones
of different frequencies, and it is by now well-established that SSA to tone frequency is
strong and robust in auditory cortex. Here we tested SSA in the auditory cortex to the ear
of stimulation using broadband noise. We show that cortical neurons adapt specifically to
the ear of stimulation, and that the contrast between the responses to stimulation of the
same ear when rare and when common depends on the binaural interaction class of the
neurons.

Xu XX, Yu XJ, Nelken I, He J (2014). Across-ear stimulus-specific adaptation in the

auditory cortex. Front Neural Circuits. 2014 Jul 30;8:89

Long-term deficits in motion detection thresholds and spike count variability after unilateral vesti

The vestibular system
operates in a push-pull fashion using signals from both labyrinths
and an intricate bilateral organization. Unilateral vestibular lesions
cause well-characterized motor deficits that are partially compensated
over time and whose neural correlates have been traced in the mean
response modulation of vestibular nuclei cells. Here we compare both
response gains and neural detection thresholds of vestibular nuclei and
semicircular canal afferent neurons in intact vs. unilateral-lesioned
macaques using three-dimensional rotation and translation stimuli.
We found increased stimulus-driven spike count variability and detection
thresholds in semicircular canal afferents, although mean
responses were unchanged, after contralateral labyrinth lesion. Analysis
of trial-by-trial spike count correlations of a limited number of
simultaneously recorded pairs of canal afferents suggests increased
noise correlations after lesion. In addition, we also found persistent,
chronic deficits in rotation detection thresholds of vestibular nuclei
neurons, which were larger in the ipsilesional than the contralesional
brain stem. These deficits, which persisted several months after lesion,
were due to lower rotational response gains, whereas spike count
variability was similar in intact and lesioned animals. In contrast to
persistent deficits in rotation threshold, translation detection thresholds
were not different from those in intact animals. These findings
suggest that, after compensation, a single labyrinth is sufficient to
recover motion sensitivity and normal thresholds for the otolith, but
not the semicircular canal, system.

Yu, Xiong-Jie ，Thomassen, Jakob S ，Dickman, J David，Newlands,Shawn D，Angelaki, Dora E，Long-term deficits in motion detection thresholds and spike count variability after unilateral vestibular lesion. J Neurophysiol. 2014 ,112(4):870-89

Detection thresholds of macaque otolith afferents.

The vestibular system is our sixth sense and is important for spatial perception functions, yet the sensory detection and discrimination
properties of vestibular neurons remain relatively unexplored. Herewehave used signal detection theory to measure detection thresholds
of otolith afferents using 1 Hz linear accelerations delivered along three cardinal axes. Direction detection thresholds were measured by
comparing mean firing rates centered on response peak and trough (full-cycle thresholds) or by comparing peak/trough firing rates with
spontaneous activity (half-cycle thresholds). Thresholds were similar for utricular and saccular afferents, as well as for lateral, fore/aft,
and vertical motion directions.Whencomputed along the preferred direction, full-cycle direction detection thresholds were 7.54 and 3.01
cm/s2 for regular and irregular firing otolith afferents, respectively. Half-cycle thresholds were approximately double, with excitatory
thresholds being half as large as inhibitory thresholds. The variability in threshold among afferents was directly related to neuronal gain
and did not depend on spike count variance. The exact threshold values depended on both the time window used for spike count analysis
and the filtering method used to calculate mean firing rate, although differences between regular and irregular afferent thresholds were
independent of analysis parameters. The fact that minimum thresholds measured in macaque otolith afferents are of the same order of
magnitude as human behavioral thresholds suggests that the vestibular periphery might determine the limit on our ability to detect or
discriminate small differences in head movement, with little noise added during downstream processing.

Yu, Xiong-Jie ，Dickman, J David，Angelaki, Dora E，Detection thresholds of macaque otolith afferents.，Journal of Neuroscience，2012，32（24）：8306-8316

Individual auditory thalamic reticular neurons have large and cross-modal sources of cortical and t

In the present study, the sources of thalamic and
cortical inputs of thalamic reticular nucleus (TRN) neurons
were examined by investigating the responses of the TRN
neurons to electrical stimulation of different sites in the thalamus
and the cortex of the rat. The recurrent excitation of the
corticothalamic system that is triggered by electrical stimulation
was eliminated by ablating the auditory cortex and by
temporarily inactivating the medial geniculate body (MGB),
when studying the sources of thalamic and cortical inputs,
respectively. Single TRN neurons responded to electrical
stimulation of 50–100 A of the thalamus over a large area
(dorsoventrally 1.2–2.4 mm and mediolaterally 1.0–2.3 mm,
n9). Four of 16 auditory TRN neurons responded to electrical
stimulation of the lateral geniculate nucleus. The TRN
neurons responded to cortical stimulation over a rostrocaudal
distance of 2.60.5 mm (range: 1.5–3.5 mm, n24) of the
auditory cortex. Visual or auditory TRN neurons also responded
to electrical stimulation in the auditory or visual
cortices, respectively. The present study revealed that each
TRN neuron received a wide range of inputs from both ascending
thalamic and descending cortical projections. The
projection could be cross-modal. Having a strong and lasting
inhibition on the thalamus, the TRN neurons are likely to be
involved in adjusting global states relating to awareness and
attention in the thalamocortical system. © 2011

Yu XJ, Meng X-K, Xu X-X, He J. (2011) Individual auditory thalamic reticular neurons have large and cross-modal sources of cortical and thalamic inputs.Neuroscience 193: 122-131