This toolbox performs several different analyses on the local field potentials (LFP) generated from multichannel recording electrodes. After performing spike sorting the LFP of a channel can be acquired by low-pass filtering the recorded data. This then allows the relationship between the LFP and neural spiking to be investigated.
Phase Locking
Phase locking describes the relationship between the timing of neural spiking and the phase of the LFP, at a given frequency. If a neuron is phase locked it means it has a preferred phase angle at which it is more likely to fire. If the neuron is not phase locked it fires more uniformly across all of the phase angles.
By using a continuous wavelet transform we can determine the phase of the LFP at a given frequency as a function of time allowing us to identify the phase of the LFP at each spike time of a specified neuron. From which we can build a distribution of the phase angles for the neurons.
Example distribution for a phase locked neuron, red arrow represents the preferred angle.
Example distribution for a non phase locked neuron with no preferred angle.
By calculating the circular mean of the distribution of the phase angles and testing for the deviation from uniformity using a Rayleigh test we can determine if the neuron is phase locked or not. This can be repeated for different frequencies to determine which frequency or frequency band has a stronger relationship with the neuron spike timing.
There is also an option in the toolbox to calculate the phase locking with a time offset between the neuron spike action potential and the LFP to allow analysis of whether the LFP leads or lags the action potential.
The effects of either increased [1] or disrupted [2] phase locking our results have shown have an impact on learning and memory.
Examples of significance of phase locking across frequency for two different neurons.
Spike-Field Coherence
Similarly to phase locking the spike-field coherence (SFC) is a relationship between the neural spiking action potentials and the phase of the local field potential. SFC measures the phase synchronization between the action potentials and field potential oscillations.
To compute the SFC for each spike a segment of the LFP data centered on the spike is extracted. These sections are then averaged to calculate the spike-triggered average (STA). The frequency spectrum of the STA (fSTA) can then be calculated. In the toolbox this is achieved using multitaper analysis to give estimates of the PSD. The same method is then used to calculate the frequency spectra of each of the segments of LFP data individually the average of which is the spike triggered power (STP(f)).
Finally the spike field coherence is the fSTA over the STP(f) expressed as a percentage.
Similarly to the phase locking our results have shown changes in SFC specifically in the theta frequency band have impacts on learning and memory [1], [3].
Examples of spike field coherence pre and post vagal nerve stimulation.
Example of changes in the spike field coherence in different frequency bands pre and post vagal nerve stimulation.
Amplitude Cross-Correlation
The amplitude cross-correlation is a relationship between two different LFPs, often between two different regions of the brain.
To calculate the amplitude cross-correlation both sets of LFP data are filtered into the frequency band of interest. From this the instantaneous amplitude is calculated using the Hilbert transform. The cross-correlation of the instantaneous amplitude is then calculated and the lag at which the maximum correlation occurs determined.
To ensure the significance of the results a bootstrap procedure is used, shifting the data by a random amount and repeating to allow a confidence interval to be determined. If the result from the original cross-correlation is greater than the 95% confidence interval from the bootstrapped values then the result is considered significant.
Example of amplitude cross-correlation in the theta frequency band (peak marked with red star).
Example of amplitude cross-correlation in the gamma frequency band.
Histograms of peak lag times for several rats (theta band top, gamma band bottom).
Code
The Matlab code for the toolbox can be found here: LFP_Analysis The phase locking and spike field coherence code is based on the methods described by Rutishauser et al..
References
Vagus Nerve Stimulation Alters Phase Synchrony of the Anterior Cingulate Cortex and Facilitates Decision Making in Rats
B. Cao, J. Wang, M. Shahed, B. Jelfs, R. H. M. Chan, and Y. Li
Vagus nerve stimulation (VNS) can enhance memory and cognitive functions in both rats and humans. Studies have shown that VNS influenced decision-making in epileptic patients. However, the sites of action involved in the cognitive-enhancement are poorly understood. By employing a conscious rat model equipped with vagus nerve cuff electrode, we assess the role of chronic VNS on decision-making in rat gambling task (RGT). Simultaneous multichannel-recordings offer an ideal setup to test the hypothesis that VNS may induce alterations of in both spike-field-coherence and synchronization of theta oscillations across brain areas in the anterior cingulate cortex (ACC) and basolateral amygdala (BLA). Daily VNS, administered immediately following training sessions of RGT, caused an increase in ‘good decision-maker’ rats. Neural spikes in the ACC became synchronized with the ongoing theta oscillations of local field potential (LFP) in BLA following VNS. Moreover, cross-correlation analysis revealed synchronization between the ACC and BLA. Our results provide specific evidence that VNS facilitates decision-making and unveils several important roles for VNS in regulating LFP and spike phases, as well as enhancing spike-phase coherence between key brain areas involved in cognitive performance. These data may serve to provide fundamental notions regarding neurophysiological biomarkers for therapeutic VNS in cognitive impairment.
Impairment of Cognitive Function by Chemotherapy: Association with the Disruption of Phase-Locking and Synchronization in Anterior Cingulate Cortex
L. Mu, J. Wang, B. Cao, B. Jelfs, R. H. M. Chan, X. Xu, M. Hasan, X. Zhang, and Y. Li
Background Patients following prolonged cancer chemotherapy are at high risk of emotional and cognitive deficits. Research indicates that the brain neuronal temporal coding and synaptic long-term potentiation (LTP) are critical in memory and perception. We studied the effects of cisplatin on induction of LTP in the basolateral amygdala (BLA)-anterior cingulate cortex (ACC) pathway, characterized the coordination of spike timing with local theta oscillation, and identified synchrony in the BLA-ACC network integrity. Results In the study presented, the impacts of cisplatin on emotional and cognitive functions were investigated by elevated plus-maze test, Morris water maze test, and rat Iowa gambling task (RGT). Electrophysiological recordings were conducted to study long-term potentiation. Simultaneous recordings from multi-electrodes were performed to characterize the neural spike firing and ongoing theta oscillation of local field potential (LFP), and to clarify the synchronization of large scale of theta oscillation in the BLA-ACC pathway. Cisplatin-treated rats demonstrated anxiety- like behavior, exhibited impaired spatial reference memory. RGT showed decrease of the percentage of good decision-makers, and increase in the percentage of maladaptive behavior (delay-good decision-makers plus poor decision-makers). Cisplatin suppressed the LTP, and disrupted the phase-locking of ACC single neural firings to the ongoing theta oscillation; further, cisplatin interrupted the synchrony in the BLA-ACC pathway. Conclusions We provide the first direct evidence that the cisplatin interrupts theta-frequency phase-locking of ACC neurons. The block of LTP and disruption of synchronized theta oscillations in the BLA-ACC pathway are associated with emotional and cognitive deficits in rats, following cancer chemotherapy.
Impairment of Decision Making and Disruption of Synchrony Between Basolateral Amygdala and Anterior Cingulate Cortex in the Maternally Separated Rat
B. Cao, J. Wang, X. Zhang, X. Yang, D. C.-H. Poon, B. Jelfs, R. H. M. Chan, J. C.-Y. Wu, and Y. Li
Neurobiology of Learning and Memory, 2016, vol. 136, no. 32. pp. 74–85.
There is considerable evidence to suggest early life experiences, such as maternal separation (MS), play a role in the prevalence of emotional dysregulation and cognitive impairment. At the same time, optimal decision making requires functional integrity between the amygdala and anterior cingulate cortex (ACC), and any dysfunction of this system is believed to induce decision-making deficits. However, the impact of MS on decision-making behavior and the underlying neurophysiological mechanisms have not been thoroughly studied. As such, we consider the impact of MS on the emotional and cognitive functions of rats by employing the open-field test, elevated plus-maze test, and rat gambling task (RGT). Using multi-channel recordings from freely behaving rats, we assessed the effects of MS on the large scale synchrony between the basolateral amygdala (BLA) and the ACC; while also characterizing the relationship between neural spiking activity and the ongoing oscillations in theta frequency band across the BLA and ACC. The results indicated that the MS rats demonstrated anxiety-like behavior. While the RGT showed a decrease in the percentage of good decision-makers, and an increase in the percentage of poor decision-makers. Electrophysiological data revealed an increase in the total power in the theta band of the LFP in the BLA and a decrease in theta power in the ACC in MS rats. MS was also found to disrupt the spike-field coherence of the ACC single unit spiking activity to the ongoing theta oscillations in the BLA and interrupt the synchrony in the BLA-ACC pathway. We provide specific evidence that MS leads to decision-making deficits that are accompanied by alteration of the theta band LFP in the BLA-ACC circuitries and disruption of the neural network integrity. These observations may help revise fundamental notions regarding neurophysiological biomarkers to treat cognitive impairment induced by early life stress.
