Journal Articles

  • Hypothermia Amplifies Somatosensory-evoked Potentials in Uninjured Rats JOURNAL OF NEUROSURGICAL ANESTHESIOLOGY Madhok, J., Wu, D., Xiong, W., Geocadin, R. G., Jia, X. 2012; 24 (3): 197-202


    Temperature fluctuations significantly impact neurological injuries in intensive care units. As the benefits of therapeutic hypothermia continue to unfold, many of these discoveries are generated by studies in animal models undergoing experimental procedures under the influence of anesthetics. We studied the effect of induced hypothermia on neural electrophysiological signals of an uninjured brain in a rodent model while under isoflurane. Fourteen rats were divided into 2 groups (n=7 each), on the basis of electrode placement at either frontal-occipital or primary somatosensory cortical locations. Neural signals were recorded during normothermia (T=36.5 to 37.5°C), mild hypothermia (T=32 to 34°C), and hyperthermia (T=38.5 to 39.5°C). The burst-suppression ratio was used to evaluate electroencephalography (EEG), and amplitude-latency analysis was used to assess somatosensory-evoked potentials (SSEPs). Hypothermia was characterized by an increased burst-suppression ratio (mean±SD) of 0.58±0.06 in hypothermia versus 0.16±0.13 in normothermia, P<0.001 in frontal-occipital; and 0.30±0.13 in hypothermia versus 0.04±0.04 in normothermia, P=0.006 in somatosensory. There was potentiation of SSEP (2.89±1.24 times the normothermic baseline in hypothermia, P=0.02) and prolonged peak latency (N10: 10.8±0.4 ms in hypothermia vs. 9.1±0.3 ms in normothermia; P15: 16.2±0.8 ms in hypothermia vs. 13.7±0.6 ms in normothermia; P<0.001), whereas hyperthermia was primarily marked by shorter peak latencies (N10: 8.6±0.2 ms, P15: 12.6±0.4 m; P<0.001). In the absence of brain injury in a rodent model, hypothermia induces significant increase to the SSEP amplitude while increasing SSEP latency. Hypothermia also suppressed EEGs at different regions of the brain by different degrees. The changes to SSEP and EEG are both reversible with subsequent rewarming.

    View details for DOI 10.1097/ANA.0b013e31824ac36c

    View details for Web of Science ID 000305272400005

    View details for PubMedID 22441433

  • Study of the origin of short- and long-latency SSEP during recovery from brain ischemia in a rat model NEUROSCIENCE LETTERS Wu, D., Anastassios, B., Xiong, W., Madhok, J., Jia, X., Thakor, N. V. 2010; 485 (3): 157-161


    Somatosensory evoked potentials (SSEPs) have been established as an electrophysiological tool for the prognostication of neurological outcome in patients with hypoxic-ischemic brain injury. The early and late responses in SSEPs reflect the sequential activation of neural structures along the somatosensory pathway. This study reports that the SSEP can be separated into early (short-latency, SL) and late (long-latency, LL) responses using independent component analysis (ICA), based on the assumption that these components are generated from different neural sources. Moreover, this source separation into the SL and LL components allows analysis of electrophysiological response to brain injury, even when the SSEPs are severely distorted and SL and LL components get mixed. With the help of ICA decomposition and corrected peak estimation, the latency of LL-SSEP is shown to be predictive of long-term neurological outcome. Further, it is shown that the recovery processes of SL- and LL-SSEPs follow different dynamics, with the SL-SSEP restored earlier than LL-SSEP. We predict that the SL- and LL-SSEPs reflect the timing of the progression of evoked response through the thalamocortical pathway and as such respond differently depending upon injury and recovery of the thalamic and cortical regions, respectively.

    View details for DOI 10.1016/j.neulet.2010.08.086

    View details for Web of Science ID 000284017400004

    View details for PubMedID 20816917

  • Quantitative assessment of somatosensory-evoked potentials after cardiac arrest in rats: Prognostication of functional outcomes CRITICAL CARE MEDICINE Madhok, J., Maybhate, A., Xiong, W., Koenig, M. A., Geocadin, R. G., Jia, X., Thakor, N. V. 2010; 38 (8): 1709-1717


    High incidence of poor neurologic sequelae after resuscitation from cardiac arrest underscores the need for objective electrophysiological markers for assessment and prognosis. This study aims to develop a novel marker based on somatosensory evoked potentials (SSEPs). Normal SSEPs involve thalamocortical circuits suggested to play a role in arousal. Due to the vulnerability of these circuits to hypoxic-ischemic insults, we hypothesize that quantitative SSEP markers may indicate future neurologic status.Laboratory investigation.University Medical School and Animal Research Facility.: Sixteen adult male Wistar rats.None.SSEPs were recorded during baseline, during the first 4 hrs, and at 24, 48, and 72 hrs postasphyxia from animals subjected to asphyxia-induced cardiac arrest for 7 or 9 mins (n = 8/group). Functional evaluation was performed using the Neurologic Deficit Score (NDS). For quantitative analysis, the phase space representation of the SSEPs-a plot of the signal vs. its slope-was used to compute the phase space area bounded by the waveforms recorded after injury and recovery. Phase space areas during the first 85-190 mins postasphyxia were significantly different between rats with good (72 hr NDS >or=50) and poor (72 hr NDS <50) outcomes (p = .02). Phase space area not only had a high outcome prediction accuracy (80-93%, p < .05) during 85-190 mins postasphyxia but also offered 78% sensitivity to good outcomes without compromising specificity (83-100%). A very early peak of SSEPs that precedes the primary somatosensory response was found to have a modest correlation with the 72 hr NDS subscores for thalamic and brainstem function (p = .066) and not with sensory-motor function (p = .30).Phase space area, a quantitative measure of the entire SSEP morphology, was shown to robustly track neurologic recovery after cardiac arrest. SSEPs are among the most reliable predictors of poor outcome after cardiac arrest; however, phase space area values early after resuscitation can enhance the ability to prognosticate not only poor but also good long-term neurologic outcomes.

    View details for DOI 10.1097/CCM.0b013e3181e7dd29

    View details for Web of Science ID 000280116500011

    View details for PubMedID 20526197

  • Evolution of somatosensory evoked potentials after cardiac arrest induced hypoxic-ischemic injury RESUSCITATION Xiong, W., Koenig, M. A., Madhok, J., Jia, X., Puttgen, H. A., Thakor, N. V., Geocadin, R. G. 2010; 81 (7): 893-897


    We tested the hypothesis that early recovery of cortical SEP would be associated with milder hypoxic-ischemic injury and better outcome after resuscitation from CA.Sixteen adult male Wistar rats were subjected to asphyxial cardiac arrest. Half underwent 7min of asphyxia (Group CA7) and half underwent 9min (Group CA9). Continuous SEPs from median nerve stimulation were recorded from these rats for 4h immediately following CA, and at 24, 48, and 72h. Clinical recovery was evaluated using the Neurologic Deficit Scale.All rats in group CA7 survived to 72h, while only 50% of rats in group CA9 survived to that time. Mean NDS values in the CA7 group at 24, 48, and 72h after CA were significantly higher than those of CA9. The N10 (first negative potential at 10ms) amplitude was significantly lower within 1h after CA in rats that suffered longer CA durations. SEPs were also analyzed by separating the rats into good (NDS>or=50) vs. bad (NDS<50) outcomes at 72h, again showing significant difference in N10 and peak-to-peak amplitudes between the two groups. In addition, a smaller N7 potential was consistently observed to recover earlier in all rats.The diminished recovery of N10 is associated with longer CA times in rats. Higher N10 and peak-to-peak amplitudes during early recovery are associated with better neurologic outcomes. N7, which may represent thalamic activity, recovers much earlier than cortical responses (N10), suggesting failure of thalamocortical conduction during early recovery.

    View details for DOI 10.1016/j.resuscitation.2010.03.030

    View details for Web of Science ID 000279758500025

    View details for PubMedID 20418008

Conference Proceedings

  • Characterization of Neurologic Injury using Novel Morphological Analysis of Somatosensory Evoked Potentials Madhok, J., Iyer, S., Thakor, N. V., Maybhate, A. IEEE. 2010: 2798-2801


    This paper describes an innovative, easy-to-interpret, clinically translatable tool for analysis of Somatosensory Evoked Potentials (SSEPs). Unlike traditional analysis, which involves peak-to-peak amplitude and latency calculation, this method, phase space analysis, analyzes the overall morphology of the SSEP, and includes greater information. The SSEP is plotted in phase space (x-dot vs. x), which leads to an approximately spiral curve. The area swept out by this curve is termed the Phase Space Area (PSA). As PSA calculation involves numerical differentiation, we present a comparison of two different approaches to combat noise amplification: finite-window smoothing, and total variation regularization (TVR) of the numerical derivative. These methods are applied to simulated SSEPs. The efficacy of these methods in performing noise-reduction is assessed and compared with ensemble averaging. While TVR gives a reasonably robust approximation of the derivative, Gaussian smoothing of the derivative offers the best trade-off between the number of signal sweeps required to be averaged, close approximation of the SSEP derivative, and optimal estimation of the PSA. We validate this method by analyzing non-characteristic SSEPs that have indistinguishable peaks as is frequently seen in cases of underlying neurologic injury such as hypoxic-ischemic encephalopathy.

    View details for Web of Science ID 000287964003051

    View details for PubMedID 21095700

  • Information Theoretical Assessment of Neural Spiking Activity with Temperature Modulation Madhok, J., Jia, X., Choi, Y., Zhang, D., Thakor, N. IEEE. 2009: 4990-4993


    Previous research has shown that hypothermia immediately after Cardiac Arrest (CA) improves neurological outcomes. In order to study how hypothermia affects neural spiking, cortical and subcortical neural activity was recorded from rodents. Consistent with previous findings, preliminary results show that the firing rate is proportional to the temperature. We also studied the information coded in the spike-timing information of individual neurons and observed that information content varies with temperature. Furthermore, there is an increased dependence between the cortex and sub-cortical structures such as the Thalamus during hypothermia. The latter is most likely an indicator of coupling between these highly connected structures in response to temperature manipulation leading to arousal after global cerebral ischemia.

    View details for Web of Science ID 000280543603340

    View details for PubMedID 19965028

  • Honors Biomedical Instrumentation - A Course Model for Accelerated Design Madhok, J., Smith, R. J., Thakor, N. V. IEEE. 2009: 2015-2018


    A model for a 16-week Biomedical Instrumentation course is outlined. The course is modeled in such a way that students learn about medical devices and instrumentation through lecture and laboratory sessions while also learning basic design principles. Course material covers a broad range of topics from fundamentals of sensors and instrumentation, guided laboratory design experiments, design projects, and eventual protection of intellectual property, regulatory considerations, and entry into the commercial market. Students eventually complete two design projects in the form of a 'Challenge' design project as well as an 'Honors' design project. Sample problems students solve during the Challenge project and examples of past Honors projects from the course are highlighted.

    View details for Web of Science ID 000280543601236

    View details for PubMedID 19964766

  • Neural Signals in Cortex and Thalamus during Brain Injury from Cardiac Arrest in Rats Zhang, D., Choi, Y., Madhok, J., Jia, X., Koenig, M., Thakor, N. IEEE. 2009: 5946-5949


    Previous research has shown that a characteristic burst-suppression (BS) pattern appears in EEG during the early recovery period following cardiac arrest (CA). To study cortical and subcortical neural activity underlying BS, extracellular activity in the parietal cortex and the centromedian nucleus of the thalamus and extradural EEG were recorded in a rodent CA model. Preliminary results show that during the BS, the cortical firing rate is extraordinarily high, and that bursts in EEG correlate to dense spikes in cortical neurons. An unexpected and novel observation is that 1) thalamic activity reappears earlier than cortical activity following CA, and 2) the correlation coefficient of cortical and thalamic activity rises during BS period. These results will help elucidate the mechanism of brain recovery after CA injury.

    View details for Web of Science ID 000280543604212

    View details for PubMedID 19965064

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