# Neurophysiological Characterization of Thalamic Nuclei in Epileptic Anaesthetized Patients

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## Abstract

**:**

## 1. Introduction

## 2. Materials and Methods

#### 2.1. Patients and Surgery

#### 2.2. Somatosensory Evoked Potentials

#### 2.3. Reconstruction of the Trajectory

#### 2.4. Analysis of Discharge Properties

- Amplitude of the AP, measured from peak to peak (in µV). This property is not a tonic property, but is commonly used in clinical practice; therefore, we included it in this group.
- Mean frequency and standard deviation of the raw trace and for every neuron. Both values were obtained from the inverse of the instant frequency.
- Density, defined as the number of cells recorded by every electrode at one position. AP sorting was performed by clustering by using the Mahalanobis distances (see below) of several properties of the AP (e.g., amplitude and duration of positive and negative phases and maximum and minimum value of the first derivative). The maximum number of cells allowed to be identified by this mean was chosen as 5.
- Probability density functions (pdf) of the inter-spike interval (ISI) for every neuron. Relative frequency was computed for 1 ms bins, and the probability/bin (p
_{i}) was calculated with the following expression:$${p}_{i}=\frac{{f}_{i}}{{{\displaystyle \sum}}_{j=1}^{N}{f}_{j}}$$_{i}is the frequency for the i-bin and N is the total number of bins.

- Burst index (BI) is defined as the ratio between the number of ISI < 10 ms and the number of ISIs > 10 ms. It represents the number of bursts of discharges with respect to individual discharges, and is calculated as follows:$$BI=\frac{{N}_{ISI<10ms}}{{N}_{ISI>10ms}}$$
- Pause index (PI), defined as the ratio between the number of ISIs > 50 ms and the number of ISIs < 50 ms, is calculated as follows:$$PI=\frac{{N}_{ISI>50ms}}{{N}_{ISI<50ms}}$$
- Pause ratio (PR), defined as the total duration of pauses (ISI > 50 ms) divided by the total duration of no-pauses (ISI < 50 ms). Although similar in name, the information obtained is different from that of the PI, and the PR is calculated as follows:$$PR=\frac{{{\displaystyle \sum}}_{i=1}^{N}IS{I}_{>50ms}^{i}}{{{\displaystyle \sum}}_{j=1}^{N}IS{I}_{50ms}^{j}}$$

#### 2.5. Evaluation of Global Similarity

#### 2.6. Statistics

## 3. Results

#### Tonic Properties

## 4. Discussion

## 5. Conclusions

## Author Contributions

## Funding

## Acknowledgments

## Conflicts of Interest

## Appendix A

**Figure A1.**Identification of thalamic nuclei. (

**a**) Raw MER (left) and high frequency oscillations (HFO) obtained by SSEP (right); (

**b**) reconstruction of the trajectory from one patient, showing microelectrode (anterior = blue, central = green, posterior = red, and lateral = purple) positions at different depths superimposed onto an SW map. The numbers on the left indicate the true distance to the target.

**Figure A2.**Recordings from different nuclei and positions identified by reconstruction. Raw traces from MER are in the left column, and different planes from the Schaltenbrand–Wahren (SW) atlas are in the right column. Horizontal calibration bar: 5 s for the upper traces and 167 ms for the lower traces. (

**a**) Ce.mc (pale red), asterisk indicates the location of the recording, (

**b**) Ce.pc. (strong red), the dot shows the location of the recording, (

**c**) V.im (blue), asterisk indicates the location of the recording, and (

**d**) V.c (green), indicated by a dot. Numbers show the distance for every axis from the mid-intercommissural AC-PC line.

## Appendix B

**Figure A3.**Representation of both parts of double exponential functions for Ce.pc (red), Ce.mc (blue), V.im (green), and V.c (yellow). Continuous lines represent the first part of equations ($\beta {e}^{-\gamma x}$ ) and discontinuous ones the second parts ($\delta {e}^{-\epsilon x}$) of Equation (2).

Nucleus | r | α | β | γ | δ | ε |
---|---|---|---|---|---|---|

Ce.pc | 0.9939 | 0.001 | 0.1296 | 0.5683 | 0.0135 | 0.0421 |

Ce.mc | 0.9904 | 0.001 | 0.0363 | 0.2660 | 0.0090 | 0.0285 |

V.im | 0.9929 | 0.0013 | 0.0429 | 0.7841 | 0.0193 | 0.0692 |

V.c | 0.9925 | 0.001 | 0.0356 | 0.2899 | 0.0085 | 0.0262 |

## Appendix C

Index | Pair of Thresholds (ms) | Linear Function [y(x)] | r^{2} | t | p |
---|---|---|---|---|---|

10/50 | $7.35x+0.89$ | 0.675 | 2.038 | n.s | |

BI | 20/100 | $0.87x+2.74$ | 0.040 | 0.289 | n.s |

50/200 | $0.35x+1.44$ | 0.513 | 1.451 | n.s | |

10/50 | $0.23x+0.01$ | 0.932 | 5.215 | <0.01 | |

PI | 20/100 | $0.09x+0.01$ | 0.849 | 3.347 | <0.05 |

50/200 | $0.41x+0.02$ | 0.980 | 9.900 | <0.001 | |

10/50 | $1.38x+0.12$ | 0.933 | 5.261 | <0.01 | |

PR | 20/100 | $0.04x+0.06$ | 0.757 | 2.496 | n.s |

50/200 | $0.22x+0.05$ | 0.602 | 1.739 | n.s |

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**Figure 1.**Tonic properties for the four nuclei. (

**a**) Amplitude of the action potential (AP), (

**b**) mean frequency of the raw traces, and (

**c**) density of the cells. Horizontal lines indicate statistically significant differences between pairs of nuclei based on the Kruskal–Wallis analysis of variance test.

**Figure 2.**Probability density functions pooled for (

**a**) centromedian magnocellular (Ce.mc), (

**b**) centromedian parvocellular (Ce.pc) (

**c**) ventral intermediate thalamic nucleus (V.im), and (

**d**) ventral caudal thalamic nucleus (V.c). Discontinuous lines represent ± 2.5 SEM. Insets show the details of the first 10 ms.

**Figure 3.**Examples of all the nuclei. (

**a**) Ce.pc, (

**b**) Ce.mc (

**c**) V.c, and (

**d**) V.im. For every panel, the upper row shows the raw trace obtained by the microelectrode recording (MER), the middle row shows the binary plots, and the bottom row shows the probability density functions (pdfs). Vertical calibration bars = 50 µV.

**Figure 4.**Graphs showing the values of (

**a**) burst index (BI), (

**b**) pause index (PI), and (

**c**) pause ratio (PR) for all the nuclei for different pairs of times (solid dot = 10/50 ms, empty dot = 20/100 ms, and triangles = 50/200 ms). Insets represent linear regressions for the values obtained for all the nuclei using different pairs of times (solid dots = 10/50 vs. 20/100, empty dots = 10/50 vs. 50/200 and triangles = 20/100 vs. 50/200).

**Figure 5.**Phasic properties for the four nuclei for the 20/100 ms threshold pair. (

**a**) BI, (

**b**) PI, (

**c**) PR. Horizontal lines indicate statistically significant differences between pairs of nuclei according to the Kruskal–Wallis analysis of variance test.

Pat. | Sex | Age (years) | History (years) | Etiology | v-EEG | MRI Result | VNS | AED |
---|---|---|---|---|---|---|---|---|

1 | F | 37 | 31 | Genetic ^{1} | GE | Normal | Yes | PGB, CBZ, CNZ |

2 | F | 18 | 12 | LGS | GE | Dysplasia LF | No | RUF, VPT |

3 | M | 34 | 27 | Genetic ^{2} | EG/EE | Normal | Yes | VPT, PGB, LAC, ZNS |

4 | M | 27 | 27 | LGS | GE | Normal | No | LVZ, OXC, LAC, CZM |

5 | M | 30 | 23 | Structural | GE/EE | Dysplasia biFT | Yes | TPM, VPT |

^{1}20 ring-chromosome syndrome.

^{2}Tuberous sclerosis.

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**MDPI and ACS Style**

Vega-Zelaya, L.; Torres, C.V.; Navas, M.; Pastor, J.
Neurophysiological Characterization of Thalamic Nuclei in Epileptic Anaesthetized Patients. *Brain Sci.* **2019**, *9*, 312.
https://doi.org/10.3390/brainsci9110312

**AMA Style**

Vega-Zelaya L, Torres CV, Navas M, Pastor J.
Neurophysiological Characterization of Thalamic Nuclei in Epileptic Anaesthetized Patients. *Brain Sciences*. 2019; 9(11):312.
https://doi.org/10.3390/brainsci9110312

**Chicago/Turabian Style**

Vega-Zelaya, Lorena, Cristina V. Torres, Marta Navas, and Jesús Pastor.
2019. "Neurophysiological Characterization of Thalamic Nuclei in Epileptic Anaesthetized Patients" *Brain Sciences* 9, no. 11: 312.
https://doi.org/10.3390/brainsci9110312