Cross-Frequency Coupling Based Neuromodulation for Treating Neurological Disorders

Synchronous, rhythmic changes in the membrane polarization of neurons form oscillations in local field potentials. It is hypothesized that high-frequency brain oscillations reflect local cortical information processing, and low-frequency brain oscillations project information flow across larger cortical networks. This provides complex forms of information transmission due to interactions between oscillations at different frequency bands, which can be rendered with cross-frequency coupling (CFC) metrics. Phase-amplitude coupling (PAC) is one of the most common representations of the CFC. PAC reflects the coupling of the phase of oscillations in a specific frequency band to the amplitude of oscillations in another frequency band. In a normal brain, PAC accompanies multi-item working memory in the hippocampus, and changes in PAC have been associated with diseases such as schizophrenia, obsessive-compulsive disorder (OCD), Alzheimer disease (AD), epilepsy, and Parkinson’s disease (PD). The purpose of this article is to explore CFC across the central nervous system and demonstrate its correlation to neurological disorders. Results from previously published studies are reviewed to explore the significant role of CFC in large neuronal network communication and its abnormal behavior in neurological disease. Specifically, the association of effective treatment in PD such as dopaminergic medication and deep brain stimulation with PAC changes is described. Lastly, CFC analysis of the electrocorticographic (ECoG) signals recorded from the motor cortex of a Parkinson’s disease patient and the parahippocampal gyrus of an epilepsy patient are demonstrated. This information taken together illuminates possible roles of CFC in the nervous system and its potential as a therapeutic target in disease states. This will require new neural interface technologies such as phase-dependent stimulation triggered by PAC changes, for the accurate recording, monitoring, and modulation of the CFC signal

Neuronal Spike Train Analysis in Likelihood Space

Conventional methods for spike train analysis are predominantly based on the rate function. Additionally, many experiments have utilized a temporal coding mechanism. Several techniques have been used for analyzing these two sources of information separately, but using both sources in a single framework remains a challenging problem. Here, an innovative technique is proposed for spike train analysis that considers both rate and temporal information.Point process modeling approach is used to estimate the stimulus conditional distribution, based on observation of repeated trials. The extended Kalman filter is applied for estimation of the parameters in a parametric model. The marked point process strategy is used in order to extend this model from a single neuron to an entire neuronal population. Each spike train is transformed into a binary vector and then projected from the observation space onto the likelihood space. This projection generates a newly structured space that integrates temporal and rate information, thus improving performance of distribution-based classifiers. In this space, the stimulus-specific information is used as a distance metric between two stimuli. To illustrate the advantages of the proposed technique, spiking activity of inferior temporal cortex neurons in the macaque monkey are analyzed in both the observation and likelihood spaces. Based on goodness-of-fit, performance of the estimation method is demonstrated and the results are subsequently compared with the firing rate-based framework.From both rate and temporal information integration and improvement in the neural discrimination of stimuli, it may be concluded that the likelihood space generates a more accurate representation of stimulus space. Further, an understanding of the neuronal mechanism devoted to visual object categorization may be addressed in this framework as well

Study of Denoising in TEOAE Signals Using an Appropriate Mother Wavelet Function

Background and Aim: Matching a mother wavelet to class of signals can be of interest in signal analy­sis and denoising based on wavelet multiresolution analysis and decomposition. As transient evoked otoacoustic emissions (TEOAES) are contaminated with noise, the aim of this work was to pro­vide a quantitative approach to the problem of matching a mother wavelet to TEOAE signals by us­ing tun­ing curves and to use it for analysis and denoising TEOAE signals. Approximated mother wave­let for TEOAE signals was calculated using an algorithm for designing wavelet to match a specified sig­nal.Materials and Methods: In this paper a tuning curve has used as a template for designing a mother wave­let that has maximum matching to the tuning curve. The mother wavelet matching was performed on tuning curves spectrum magnitude and phase independent of one another. The scaling function was calcu­lated from the matched mother wavelet and by using these functions, lowpass and highpass filters were designed for a filter bank and otoacoustic emissions signal analysis and synthesis. After signal analyz­ing, denoising was performed by time windowing the signal time-frequency component.Results: Aanalysis indicated more signal reconstruction improvement in comparison with coiflets mother wavelet and by using the purposed denoising algorithm it is possible to enhance signal to noise ra­tio up to dB.Conclusion: The wavelet generated from this algorithm was remarkably similar to the biorthogonal wave­lets. Therefore, by matching a biorthogonal wavelet to the tuning curve and using wavelet packet analy­sis, a high resolution time-frequency analysis for the otoacoustic emission signals is possible

Changes in corticospinal excitability during reach adaptation in force fields

Both abrupt and gradually imposed perturbations produce adaptive changes in motor output, but the neural basis of adaptation may be distinct. Here, we measured the state of the primary motor cortex (M1) and the corticospinal network during adaptation by measuring motor-evoked potentials (MEPs) before reach onset using transcranial magnetic stimulation of M1. Subjects reached in a force field in a schedule in which the field was introduced either abruptly or gradually over many trials. In both groups, by end of the training, muscles that countered the perturbation in a given direction increased their activity during the reach (labeled as the on direction for each muscle). In the abrupt group, in the period before the reach toward the on direction, MEPs in these muscles also increased, suggesting a direction-specific increase in the excitability of the corticospinal network. However, in the gradual group, these MEP changes were missing. After training, there was a period of washout. The MEPs did not return to baseline. Rather, in the abrupt group, off direction MEPs increased to match on direction MEPs. Therefore, we observed changes in corticospinal excitability in the abrupt but not gradual condition. Abrupt training includes the repetition of motor commands, and repetition may be the key factor that produces this plasticity. Furthermore, washout did not return MEPs to baseline, suggesting that washout engaged a new network that masked but did not erase the effects of previous adaptation. Abrupt but not gradual training appears to induce changes in M1 and/or corticospinal networks.status: publishe

Changes in corticospinal excitability during reach adaptation in force fields

Both abrupt and gradually imposed perturbations produce adaptive changes in motor output, but the neural basis of adaptation may be distinct. Here, we measured the state of the motor cortex (M1) and the corticospinal network during adaptation by measuring motor evoked potentials(MEPs) before reach onset using transcranial magnetic stimulation of M1. Subjects reached in a force field in a schedule in which the field was introduced either abruptly or gradually over many trials. In both groups by end of training muscles that countered the perturbation in a given direction increased their activity during the reach (labeled as on-direction for each muscle). In the abrupt group, in the period before the reach toward the on-direction, MEPs in these muscles also increased, suggesting a direction-specific increase in the excitability of corticospinal network. However, in the gradual group these MEP changes were missing. Following training there was a period of washout. The MEPs did not return to baseline. Rather, in the abrupt group the off-direction MEPs increased to match the on-direction MEPs. Therefore, we observed changes in corticospinal excitability in the abrupt but not gradual condition. Abrupt training includes repetition of motor commands, and repetition may be the key factor that produces this plasticity. Furthermore, washout did not return MEPs to baseline, suggesting that washout engaged a new network that masked but did not erase the effects of previous adaptation. Abrupt but not gradual training appears to induce changes in M1 and/or corticospinal networks

Multidimensional scaling in observation space and likelihood space.

<p>A multidimensional scaling technique is used to illustrate the capability of the likelihood space in increasing the separability of the clusters. (A) The distance measurement and multidimensional scaling results for pairs of spike trains from the human face and car stimuli in the observation space. (B) The distance measurement and multidimensional scaling results for the same spike trains after projection onto the likelihood space.</p

Projection of spike train onto likelihood space.

<p>Sample response of a single neuron to face stimulus presentation in raster plot format. This data is for the repeated trials, where each row is the spike train recorded for any individual trial. The transformation of the spike train for the single trial, from the observation space into a likelihood space, is illustrated. Based on previous observations and estimated stimuli conditional probability distribution, each point in the new space is generated by the projection of the binary vector of spike train.</p

Passive fixation task.

<p>The paradigm for the passive fixation task is illustrated. The presentation of the stimulus sequence started after the monkey maintained fixation for 300 ms. Each stimulus lasted 300 ms and was followed by another stimulus after a 700 ms interstimulus interval. The sequence stopped when 36 stimuli were presented, or when the monkey broke the gaze fixation.</p

Application of texture analysis to DAT SPECT imaging: Relationship to clinical assessments

Dopamine transporter (DAT) SPECT imaging is increasingly utilized for diagnostic purposes in suspected Parkinsonian syndromes. We performed a cross-sectional study to investigate whether assessment of texture in DAT SPECT radiotracer uptake enables enhanced correlations with severity of motor and cognitive symptoms in Parkinson's disease (PD), with the long-term goal of enabling clinical utility of DAT SPECT imaging, beyond standard diagnostic tasks, to tracking of progression in PD. Quantitative analysis in routine DAT SPECT imaging, if performed at all, has been restricted to assessment of mean regional uptake. We applied a framework wherein textural features were extracted from the images. Notably, the framework did not require registration to a common template, and worked in the subject-native space. Image analysis included registration of SPECT images onto corresponding MRI images, automatic region-of-interest (ROI) extraction on the MRI images, followed by computation of Haralick texture features. We analyzed 141 subjects from the Parkinson's Progressive Marker Initiative (PPMI) database, including 85 PD and 56 healthy controls (HC) (baseline scans with accompanying 3 T MRI images). We performed univariate and multivariate regression analyses between the quantitative metrics and different clinical measures, namely (i) the UPDRS (part III - motor) score, disease duration as measured from (ii) time of diagnosis (DD-diag.) and (iii) time of appearance of symptoms (DD-sympt.), as well as (iv) the Montreal Cognitive Assessment (MoCA) score. For conventional mean uptake analysis in the putamen, we showed significant correlations with clinical measures only when both HC and PD were included (Pearson correlation r = −0.74, p-value < 0.001). However, this was not significant when applied to PD subjects only (r = −0.19, p-value = 0.084), and no such correlations were observed in the caudate. By contrast, for the PD subjects, significant correlations were observed in the caudate when including texture metrics, with (i) UPDRS (p-values < 0.01), (ii) DD-diag. (p-values < 0.001), (iii) DD-sympt (p-values < 0.05), and (iv) MoCA (p-values < 0.01), while no correlations were observed for conventional analysis (p-values = 0.94, 0.34, 0.88 and 0.96, respectively). Our results demonstrated the ability to capture valuable information using advanced texture metrics from striatal DAT SPECT, enabling significant correlations of striatal DAT binding with clinical, motor and cognitive outcomes, and suggesting that textural features hold potential as biomarkers of PD severity and progression