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Biomedical subjects

N V Thakor

Publications and source records attributed to N V Thakor.

At least 19 recordsLinked to original sources

Monitoring of global cerebral ischemia using wavelet entropy rate of change.

In this paper, the subband wavelet entropy (SWE) and its time difference are proposed as two quantitative measures for analyzing and segmenting the electroencephalographic (EEG) signals. SWE for EEG subbands, namely Delta, Theta, Alpha, Beta, and Gamma, is calculated and segmented using wavelet analysis. In addition, a time difference entropy measure was calculated because it does not require a baseline and equals to zero in all clinical bands as the initial condition. Visual and quantitative results were obtained from 11 rodents that were subjected to 3, 5, and 7 min of global ischemic brain injury by asphyxic cardiac arrest. We found that the time difference of SWE is capable of amplifying the variations between clinical bands during the various stages of the recovery process and may serve as a novel analytical approach to grade and classify brain rhythms during global ischemic brain injury and recovery.

Algorithms↗

Detection of asphyxia using heart rate variability.

The long-term aims of this study are to find a parameter derived from the ECG that has a high sensitivity and specificity to asphyxia and, once we know or suspect that asphyxia occurred, to estimate how severe it was. We carried out a pilot study in which 24 adult Wistar rats were anaesthetised and subjected to controlled asphyxia for specified durations. We measured the pH, 'neurological score' and the ECG, extracting from this heart rate and heart rate variability (HRV). We have developed a technique capable of detecting asphyxia in less than 1 min, based on monitoring the ECG and estimating HRV by measuring the standard deviation of normal RR intervals (the RR interval is the time interval between two consecutive R-points of the QRS complex). In all cases the heart rate decreased and HRV increased, by an average of 46 +/- 33 ms in relation to the baseline, at the onset of asphyxia. The comparison of the base level of HRV after and before asphyxia shows promise for the estimation of the severity of the episode; however, the limitations of this study should be noted as they include the small size of the cohort and the methods of analysis.

Animals↗

Vulnerability of the thalamic somatosensory pathway after prolonged global hypoxic-ischemic injury.

The aim of this study was to test the hypothesis that under prolonged global ischemic injury, the somatosensory thalamus and the cortex would manifest differential susceptibility leading to varying degrees of thalamo-cortical dissociation. The thalamic electrical responses displayed increasing suppression with longer durations of ischemia leading to a significant thalamo-cortical electrical dissociation. The data also point to a selective vulnerability of the network oscillations involving the thalamic relay and reticular thalamic neurons. An adult rat model of asphyxial cardiac arrest involving three cohorts with 3 min (G1, n=5), 5 min (G2, n=5) and 7 min (G3, n=5) of asphyxia respectively was used. The cortical evoked response, as quantified by the peak amplitude at 20 ms in the cortical evoked potential, recovers to more than 60% of baseline in all the cases. The multi-unit responses to the somatosensory stimuli recorded from the thalamic ventral posterior lateral (VPL) nuclei consists typically of three components: (1). the ON response (<30 ms after stimulus), (2). the OFF response (period of inhibition, from 30 ms to 100 ms after stimulus) and (3). rhythmic spindles (beyond 100 ms after stimulus). Asphyxia has a significant effect on the VPL ON response at 30 min (P<0.025), 60 min (P<0.05) and 90 min (P<0.05) after asphyxia. Only animals in G3 show a significant suppression (P<0.05) of the VPL ON response when compared to the sham group at 30 min, 60 min and 90 min after asphyxia. There was no significant reduction in somatosensory cortical N20 (negative peak in the cortical response at 20 ms after stimulus) amplitude in any of the three groups with asphyxia indicating a thalamo-cortical dissociation in G3. Further, rhythmic spindle oscillations in the thalamic VPL nuclei that normally accompany the ON response recover either slowly after the recovery of ON response (in the case of G1 and G2) or do not recover at all (in the case of G3).We conclude that there is strong evidence for selective vulnerability of thalamic relay neurons and its network interactions with the inhibitory interneurons in the somatosensory pathway leading to a thalamo-cortical dissociation after prolonged durations of global ischemia.

Action Potentials↗

Transcranial magnetic stimulation in the rat.

Transcranial magnetic stimulation (TMS) allows for quantification of motor system excitability. While routinely used in humans, application in other species is rare and little is known about the characteristics of animal TMS. The unique features of TMS, i.e., predominantly interneuronal stimulation at low intensity and non-invasiveness, are particularly useful in evaluating injury and recovery in animal models. This study was conducted to characterize the rodent motor evoked potential to TMS (MEPTMS) and to develop a methodology for reproducible assessment of motor excitability in the rat. MEPTMS were compared with responses evoked by electrical stimulation of cervical spinal cord (MEPCES) and peripheral nerve. MEP were recorded by subcutaneous electrodes implanted bilaterally over the calf. Animals remained under propofol infusion and restrained in a stereotactic frame while TMS followed by CES measurements were obtained before and after 2 h of idle time. TMS was applied using a 5-cm-diameter figure-of-eight coil. MEPTMS had onset latencies of 6.7+/-1.3 ms. Latencies decreased with higher stimulation intensity (r=-0.7, P<0.05). Two morphologies, MEPTMS, 1 and MEPTMS, 2, were distinguished by latency of the first negative peak (N1), overall shape, and amplitude. MEPTMS, 2 were more frequent at higher stimulation intensity. While recruitment curves for MEPTMS, 1 followed a sigmoid course, no supramaximal response was reached for MEPTMS, 2. Mid-cervical spinal transection completely abolished any response to TMS. MEPCES showed a significantly shorter latency (5.29+/-0.24, P<0.0001). Two types of MEPCES resembling MEPTMS, 1 and 2 were observed. Neither MEPTMS nor MEPCES changed on repeat assessment after 2 h. This study demonstrates the feasibility and reproducibility of TMS in the rat. Sigmoid recruitment curves for MEPTMS, 1 suggest input-output properties similar to those of the human corticospinal system. Latency differences between CES and TMS point to a supraspinal origin of the MEPTMS. The two morphologies likely reflect different cortical or subcortical origins of MEPTMS.

Anesthetics↗

Detection of non-linearity in the EEG of schizophrenic patients.

OBJECTIVE: The aim of this study is to detect non-linearity in the EEG of schizophrenia with a modified method of surrogate data. We also want to identify if dimension complexity (correlation dimension using spatial embedding) could be used as a discriminating statistic to demonstrate non-linearity in the EEG. The difference between the attractor dimension of healthy subjects and schizophrenic subjects is expected to be interpreted as reflecting some mechanisms underlying brain wave by views of non-linear dynamics analysis may reflect mechanistic differences. METHODS: EEGs were recorded with 14 electrodes in 18 healthy male subjects (average age: 26.3; range: 20--35) and 18 male schizophrenic patients (average age: 30.6; range: 24--40) during a resting eye-closed state. Neither of two groups was taking medicines. All artificial epochs in the EEG records were rejected by an experienced doctor's visual inspection. RESULTS: Testing non-linearity with modified surrogate data, we showed that correlation dimension of EEG data of schizophrenia does refuse the null hypothesis that the data were resulted from a linear dynamic system. A decrease of dimension complexity was found in the EEG of schizophrenia compared with controls. We interpreted it as the result of the psychopath's dysfunction overall brain. The surrogating procedure results in a significant increase in D(s). CONCLUSIONS: Non-linearity of the EEG in schizophrenia was proven in our study. We think the correlation dimension with spatial embedding as a good discriminating statistic for testing such non-linearity. Moreover, schizophrenic patients' EEGs were compared with controls and a lower dimension complexity was found. The results of our study indicate the possibility of using the methods of non-linear time series analysis to identify the EEGs of schizophrenic patients.

Adult↗

A short-time multifractal approach for arrhythmia detection based on fuzzy neural network.

We have proposed the notion of short-time multifractality and used it to develop a novel approach for arrhythmia detection. Cardiac rhythms are characterized by short-time generalized dimensions (STGDs), and different kinds of arrhythmias are discriminated using a neural network. To advance the accuracy of classification, a new fuzzy Kohonen network, which overcomes the shortcomings of the classical algorithm, is presented. In our paper, the potential of our method for clinical uses and real-time detection was examined using 180 electrocardiogram records [60 atrial fibrillation, 60 ventricular fibrillation, and 60 ventricular tachycardia]. The proposed algorithm has achieved high accuracy (more than 97%) and is computationally fast in detection.

Algorithms↗

Coherence-weighted Wiener filtering of somatosensory evoked potentials.

In this paper, we present a Wiener filtering (WF) approach for extraction of somatosensory evoked potentials (SEPs) from the background electroencephalogram (EEG), with sweep-to-sweep variations in its signal power. To account for the EEG power variations, WF is modified by iteratively weighting the power spectrum using the coherence function. Coherence-weighted Wiener filtering (CWWF) is able to extract SEP waveforms, which have a greater level of detail as compared with conventional time-domain averaging (TDA). Using CWWF, the components of the SEP show significantly less variability. As such, CWWF should be useful as an important diagnostic tool able to detect minimal changes in the SEP. In an experimental study of cerebral hypoxia, CWWF is shown to be more responsive to detection of injury than WF or TDA.

Electroencephalography↗

Optical light scatter imaging of cellular and sub-cellular morphology changes in stressed rat hippocampal slices.

Optical imaging, such as transmission imaging, is used to study brain tissue injury. Transmission imaging detects cellular swelling via an increase in light transmitted by tissue slices due to a decrease in scattering particle concentration. Transmission imaging cannot distinguish sub-cellular particle size changes from cellular swelling or shrinkage. We present an optical imaging method, based on Mie scatter theory, to detect changes in sub-cellular particle size and concentration. The system uses a modified inverted microscope and a 16-bit cooled CCD camera to image tissue light scatter at two angles. Dual-angle scatter ratio imaging successfully discriminated latex microsphere suspensions of differing sizes (0.6, 0.8, 1 and 2 microm) and concentrations. We applied scatter imaging to hippocampal slices treated with 100 microM N-methyl-D-aspartate (NMDA) to model excitotoxic injury or -40 mOsm hypotonic perfusion solution to cause edema injury. We detected light scatter decreases similar to transmission imaging in the CA1 region of the hippocampus for both treatments. Using our system, we could distinguish between NMDA and hypotonic treatments on the basis of statistically significant (P<0.0003) differences in the scatter ratio measured in CA1. Scatter imaging should be useful in studying tissue injuries or activity resulting in brain tissue swelling as well as morphological changes in sub-cellular organelles such as mitochondrial swelling.

Animals↗

Early electrophysiological and histologic changes after global cerebral ischemia in rats.

INTRODUCTION: Cerebral anoxia is fundamental to morbidity and mortality after resuscitation from cardiac arrest. With no proven effective primary therapy for post-anoxic brain injury, the goal of neurologic care are supportive, to provide prognosis and prevention of further complications. With the multifaceted approach using electroencephalography (EEG), somatosensory evoked potentials (SEP), multiunit recordings, behavioral and histologic assessment, we investigated the hyperacute recovery period after resuscitation from cardiac arrest in a rat model to define the value of EEG and SEP in assessing neurologic injury. METHODS: Two cohorts of rats were subjected to sham and graded asphyxic-cardiac arrest. EEG was collected during baseline, at injury, and 90 minutes into recovery in the first rat cohort. EEG bursting during the first 90 minutes of recovery was visually analyzed and correlated with the neurologic recovery at 24 hours after injury. The neurologic recovery was assessed using a neurodeficit score (NDS) with 80 as normal and 0 as brain dead. The next rat cohort subjected to asphyxic-cardiac arrest was studied using SEP and multiunit recording in the VPL; brain histologic studies were performed at 4 hours after the asphyxia. RESULTS: The first rat cohort subjected to graded asphyxic-cardiac arrest emerged from EEG isoelectricity by burst-suppression pattern during the first 90 minutes after asphyxia. Six rats in the good outcome group (NDS >60) showed increased frequency of bursting, leading to return of EEG background activity. Six rats with a bad outcome (NDS <60) had low-intensity and persistent bursting without return of EEG background activity within 90 minutes of observation. Visual assessment showed increased EEG peak burst counts during the first 90 minutes of recovery for the rats with a good outcome compared with the rats with a bad outcome. In the second cohort, the rats were subjected to 3 minutes, 5 minutes, and 7 minutes of asphyxia. The N20 recovered to 60% of baseline in all three cases. The recovery profile of VPL is similar to that of cortical N2O for the animal with 3 minutes of asphyxia. However, VPL response is suppressed after 7 minutes of asphyxia leading to a divergence in the rate of recovery of the cortical N20 and VPL response. In both the animals (with mild and intermediate injury) in which the early response in VPL recovered to more than 50% of baseline, the recovery profile was similar to the N20 in cortical evoked potential (EP). The rats were killed 4 hours after asphyxia and the hematoxylin and eosin stain performed on the brains showed evidence of neuronal injury in the thalamic reticular nucleus (TRN) which seemed to correlate with the duration of asphyxia. CONCLUSION: We present a multimodality assessment of early neurologic recovery following resuscitation from cardiac arrest. The recovery of bursting and high-frequency oscillations may be regulated by interneurons in the TRN. The early selective vulnerability of these interneurons in the TRN may be crucial to the early neurologic recovery as assessed by EP, multiunit recording, EEG, and neurologic behavioral recovery.

Animals↗

Wavelet analysis and time-frequency distributions of the body surface ECG before and after angioplasty.

In a pilot study, electrocardiographic (ECG) recordings of patients with left and right coronary stenosis taken before and after angioplasty were analyzed using the continuous wavelet transform. Time-frequency distributions were obtained for different leads in order to examine the dynamics of the QRS-spectrum and establish features specific of ischemia in the time-frequency domain. We found relevant changes in the mid-frequency range, reflecting the ECG's response to percutaneous transluminal coronary angioplasty (PTCA). The changes appeared in ECG leads close to ischemic zones of the myocardium. Time-frequency distributions of the ECG during the QRS may thus become another electrocardiographic indicator of ischemia, alternative to ST-level in standard ECG or body surface mapping. The paper demonstrates the ability of the continuous wavelet transform to detect short lasting events of low amplitude superimposed on large signal deflections.

Angioplasty, Balloon, Coronary↗

A novel quantitative EEG injury measure of global cerebral ischemia.

OBJECTIVE: To develop a novel quantitative EEG (qEEG) based analysis method, cepstral distance (CD) and compare it to spectral distance (SD) in detecting EEG changes related to global ischemia in rats. METHODS: Adult Wistar rats were subjected to asphyxic-cardiac arrest for sham, 1, 3, 5 and 7 min (n=5 per group). The EEG signal was processed and fitted into an autoregressive (AR) model. A pre-injury baseline EEG was compared to selected data segments during asphyxia and recovery. The dissimilarities in the EEG segments were measured using CD and SD. A segment measured was considered abnormal when it exceeded 30% of baseline and its duration was used as the index of injury. A comprehensive Neurodeficit Score (NDS) at 24 h was used to assess outcome and was correlated with CD and SD measures. RESULTS: A higher correlation was found with CD and asphyxia time (r=0.81, P<0.001) compared to SD and asphyxia time (r=0.69, P<0.001). Correlation with cardiac arrest time (MAP<10 mmHg) showed that CD was superior (r=0.71, P<0.001) to SD (r=0.52, P=0.002). CD obtained during global ischemia and 90 min into recovery correlated significantly with NDS at 24 h after injury (Spearman coefficient=-0.83, P<0.005), and was more robust than the traditional SD (Spearman coefficient=-0.63, P<0.005). CONCLUSION: The novel qEEG-based injury index from CD was superior to SD in quantifying early cerebral dysfunction after cardiac arrest and in providing neurological prognosis at 24 h after global ischemia in adult rats. Studying early qEEG changes after asphyxic-cardiac arrest may provide new insights into the injury and recovery process, and present opportunities for therapy.

Animals↗

Effects of anodal vs. cathodal pacing on the mechanical performance of the isolated rabbit heart.

Previous studies have suggested that anodal pacing enhances electrical conduction in the heart near the pacing site. It was hypothesized that enhanced conduction by anodal pacing would also enhance ventricular pressure in the heart. Left ventricular pressure measurements were made in isolated, Langendorff-perfused rabbit hearts by means of a Millar pressure transducer with the use of a balloon catheter fixed in the left ventricle. The pressure wave was analyzed for maximum pressure (Pmax) generated in the left ventricle and the work done by the left ventricle (Parea). Eight hearts were paced with monophasic square-wave pulses of varying amplitudes (2, 4, 6, and 8 V) with 100 pulses of each waveform delivered to the epicardium. Anodal stimulation pulses showed statistically significant improvement in mechanical response at 2, 4, and 8 V. Relative to unipolar cathodal pacing, unipolar anodal pacing improved Pmax by 4.4 +/- 2.3 (SD), 5.3 +/- 3.1, 3.5 +/- 4.9, and 4.8 +/- 1.9% at 2, 4, 6, and 8 V, respectively. Unipolar anodal stimulation also improved Parea by 9.0 +/- 3.0, 12.0 +/- 6.0, 10.1 +/- 7.7, and 11.9 +/- 6.0% at 2, 4, 6, and 8 V, respectively. Improvements in Pmax and Parea indicate that an anodally paced heart has a stronger mechanical response than does a cathodally paced heart. Anodal pacing might be useful as a novel therapeutic technology to treat mechanically impaired or failed hearts.

Animals↗

Somatosensory stimulus entrains spindle oscillations in the thalamic VPL nucleus in barbiturate anesthetized rats.

This study reports the effect of external stimuli on spindle oscillations in the somatosensory thalamus of barbiturate anesthetized rats. Multi-unit responses to somatosensory stimuli were measured from the contralateral thalamic ventral posterior lateral (VPL) nucleus at different stimulus strengths and periods. Spindle oscillations could be entrained by the somatosensory stimuli at periods between 2 and 5 s. A resonance phenomenon described as a quiescent pre-stimulus period followed by entrained post-stimulus oscillations, was observed for somatosensory stimuli above the threshold for eliciting cortical evoked potentials and a stimulus period between 2 and 5 s. This study demonstrates an ascending pathway for localized modulation of spindle oscillations.

Anesthesia↗

Higher-order spectral analysis of burst patterns in EEG.

Burst suppression patterns in electroencephalograms (EEG's) have been observed in a variety of situations including recovery of a subject from a traumatic brain injury. They are associated with grave prognostic outcomes in neonates. We study power spectral parameters and bispectral parameters of the EEG at baseline, during early recovery from an asphyxic arrest (EEG burst patterns) and during late recovery after EEG evolves into a more continuous activity. The bicoherence indexes, which indicate the degree of phase coupling between two frequency components of a signal, are significantly higher within the delta-theta band of the EEG bursts than in the baseline or late recovery waveforms. The bispectral parameters show a more detectable trend than the power spectral parameters. In the second part of the study, we looked into the possibility of higher (> 2)--order nonlinearities in the EEG bursts using the diagonal slices of the polyspectrum. The diagonal elements of the polyspectrum reveal the presence of self-frequency and self-phase coupling of orders higher than two in majority of the EEG bursts studied. The bicoherence indexes and the diagonal elements of the polyspectrum strongly indicate the presence of nonlinearities of order two and in many cases higher, in the EEG generator during episodes of bursting. This indication of nonlinearity in EEG signals provides a novel quantitative measure of brain's response to injury.

Animals↗

Influence of electrical coupling on early afterdepolarizations in ventricular myocytes.

Computer modeling is used to study the effect of electrical coupling between a myocardial zone where early afterdepolarizations (EAD's) can develop and the normal neighboring tissue. The effects of such coupling on EAD development and on the likelihood of EAD propagation as an ectopic beat are studied. The influence on EAD formation is investigated by approximating two partially coupled myocardial zones modeled as two active elements coupled by a junctional resistance R. For R values lower than 800 omega cm2, the action potentials are transmitted to the coupled element, and for R values higher than 850 omega cm2 they are blocked. In both ranges of R, when the electrical coupling increases, the EAD's appear at more negative takeoff potentials with higher amplitudes and upstrokes. The EAD's are not elicited if the electrical coupling is too high. In a separate model of two one-dimensional cardiac fiber segments partially coupled by a resistance R, critical R values exist, between 42 and 54 omega cm2, that facilitate EAD propagation. These results demonstrate that in myocardial zones favorable to the formation of EAD, the electrical coupling dramatically affects initiation of EAD and its spread to the neighboring tissue.

Calcium Channels↗

Modeling the relationship between concurrent epicardial action potentials and bipolar electrograms.

A signal analysis approach to building the relationship between concurrent epicardial cell action potentials (AP's) and bipolar electrograms is presented. Wavelet network, one nonlinear black-box modeling method, is used to identify the relationship between cell AP's and bipolar electrocardiograms. The electrical signals were simultaneously measured from the epicardium of isolated Langendorff-perfused rabbit hearts during three different rhythm conditions: normal sinus rhythm (NSR), normal sinus rhythm after ischemia (NSRI), and ventricular fibrillation (VF). For NSR and NSRI, the proposed modeling method successfully captures the nonlinear input-output relationship and provides an accurate output, but the method fails in case of VF. This result suggests that a time-invariant nonlinear modeling method such as wavelet network is not appropriate for VF rhythm, which is thought to be time-varying as well as chaotic, but still useful in detection of VF. A new arrhythmia detection algorithm, with potential application in implantable devices, is proposed for identifying the time of rhythmic bifurcation.

Action Potentials↗

Detecting ventricular tachycardia and fibrillation by complexity measure.

Sinus rhythm (SR), ventricular tachycardia (VT) and ventricular fibrillation (VF) belong to different nonlinear physiological processes with different complexity. In this study, we present a novel, and computationally fast method to detect VT and VF, which utilizes a complexity measure suggested by Lempel and Ziv [1]. For a specific window length (i.e., the length of data segment to be analyzed), the method first generates a 0-1 string by comparing the raw electrocardiogram (ECG) data to a selected suitable threshold. The complexity measure can be obtained from the 0-1 string only using two simple operations, comparison and accumulation. When the window length is 7 s, the detection accuracy for each of SR, VT, and VF is 100% for a test set of 204 body surface records (34 SR, 85 monomorphic VT, and 85 VF). Compared with other conventional time- and frequency-domain methods, such as rate and irregularity, VF-filter leakage, and sequential hypothesis testing, the new algorithm is simple, computationally efficient, and well suited for real-time implementation in automatic external defibrillators (AED's).

Algorithms↗

Quantification of injury-related EEG signal changes using distance measures.

Novel indicators based on distance measures are developed and compared to quantify changes in electroencephalogram signal resulting from hypoxic-asphyxic injury. An injury index is derived based on the measures. The Itakura distance-based index is found to have the highest correlation with the long-term outcome as measured by the neurological deficit scores.

Animals↗