Functional signature of recovering cortex: dissociation of local field potentials and spiking activity in somatosensory cortices of spinal cord injured monkeys

Abstract

After disruption of dorsal column afferents at high cervical spinal levels in adult monkeys, somatosensory cortical neurons recover responsiveness to tactile stimulation of the hand; this reactivation correlates with a recovery of hand use. However, it is not known if all neuronal response properties recover, and whether different cortical areas recover in a similar manner. To address this, we recorded neuronal activity in cortical area 3b and S2 in adult squirrel monkeys weeks after unilateral lesion of the dorsal columns. We found that in response to vibrotactile stimulation, local field potentials remained robust at all frequency ranges. However, neuronal spiking activity failed to follow at high frequencies (≥15 Hz). We suggest that the failure to generate spiking activity at high stimulus frequency reflects a changed balance of inhibition and excitation in both area 3b and S2, and that this mismatch in spiking and local field potential is a signature of an early phase of recovering cortex (<two months).

Keywords: Local field potential; Neuron spikes; Primates; Somatosensory cortex; Spinal cord injury; Touch.

Figure 1. Spatial correspondence of pre-lesion and post-lesion fMRI and electrophysiology maps of input - deprived digit regions in Area 3b in two representative monkeys (SM-D: A–D and SM-C: E–H)

SM-D: (A & E) Pre-lesion fMRI activation map to D3 stimulation (thresholded at p<10⁻⁴). Scale bar: p value range for each fMRI image. (B & F) Post-lesion (eight-week) fMRI activation map to same D3 stimulation (thresholded at p<10⁻⁴). (C&G) Post-lesion digit representation maps defined by dense microelectrode recording/mapping (detailed map from this animal see Figures in Qi et al 2011). Red dot indicates the recording site from where electrophysiology data (Figures 2 – 5) were taken. Scale bar: 1 mm. a: anterior; p: posterior; m: middle; l: lateral. D1–D5: digits. P1& PTH: palm. Wr: wrist. Dotted black line: border between Area 3b and area 1. Double blue line: hand-face border. (D&H) Spatial relationships among pre-lesion fMRI (pink outline), post-lesion fMRI (purple outline), electrophysiologically defined post-lesion D3 (orange patch), and one of the recording sites (red dot). fMRI activation was generated by the same protocol used in pre-lesion fMRI session (stimulating site on distal finger pad of D3 is shown by the violet dot on hand insert).

Figure 2. Spiking activity in Area 3b of normal (A–B) and input-deprived cases (C–D)

(A & C) Raster plots of typical single neuron spiking responses of area 3b in normal (A) and input-deprived (C) cortex. Five columns represent spiking activity recorded from the same site in response to vibrotactile stimuli with various frequencies (from left to right: 2, 8, 15, 30, and 50 Hz). Each row in the raster stands for one stimulus trial (60 trials total), 4.0 s long, and the colored dots represent the action potentials of area 3b neurons. Black bars indicate the duration of the stimulus training. (B & D) Peristimulus time histograms (PSTH) plots of corresponding area 3b neuron spiking responses in normal (B) and input-deprived cortex (D). Five columns represent spiking activity recorded from the same site in response to vibrotactile stimuli with various frequencies (from left to right: 2, 8, 15, 30, and 50 Hz). All the PSTHs (calculated with 10 ms bin size) ubiquitously exhibited dramatic increase in firing rate at stimulus onset of each trial (indicated by red arrows) and sustained periodic discharge pattern, entrainment to vibratory frequency under control condition.

Figure 3. LFPs activity in area 3b regions of normal (A–B) and input-deprived cases (C–D)

(A & C) Plots of somatically evoked local potentials (LFPs) recorded simultaneously from the same electrode as the spikes of (Figure 2A&2C) in normal (A) and input-deprived (C) area 3b. Five columns represent distinct frequencies of stimuli. Each panel shows typical traces of stimulus-evoked LFP in amplitude (mV), which was averaged from 60 trials within one recording session. Black bars indicate the duration of the stimulus training. (B & D) Corresponding spectrograms of A and C. Each panel shows response of stimulus-evoked LFP in the time-frequency domain decomposed by the wavelet transform (averaged from 60 trials within one recording session). The spectrograms show that the ON responses consist of a wide band of frequencies (red arrows), and bands at the stimulus frequencies as well as higher harmonics occur during the stimulation epoch (light blue arrows). The color bar shows the LFP power in dB unit.

Figure 4. Spiking activity in S2 of normal (A–B) and input-deprived cortex (C–D)

(A & C) Raster plots of typical single neuron spiking responses of S2 in normal (A) and input-deprived (C) cortex. Five columns represent spiking activity recorded from the same site in response to vibrotactile stimuli with various frequencies (from left to right: 2, 8, 15, 30, and 50 Hz). Each row in the raster stands for one stimulus trial (60 trials total), 4.0 s long, and the colored dots represent the action potentials of S2 neurons. Black bars indicate the onset and offset of the stimulus training. (B & D) Peristimulus time histograms (PSTH) plots of corresponding S2 neuron spiking responses in normal (B) and input-deprived cortex (D). Five columns represent spiking activity recorded from the same site in response to vibrotactile stimuli with various frequencies (from left to right: 2, 8, 15, 30, and 50 Hz). All the PSTHs (calculated with 10 ms bin size) ubiquitously exhibited dramatic increase in firing rate at stimulus onset of each trial (indicated by red arrows) and sustained periodic discharge pattern, entrainment to vibratory frequency under control condition.

Figure 5. LFPs activity in S2 regions of normal (A–B) and input-deprived cortex (C–D)

(A & C) Plots of somatically evoked local potentials (LFPs) recorded simultaneously from the same electrode as the spikes of (Figure 2A&2C) in normal (A) and input-deprived (C) S2. Five columns represent distinct frequencies of stimuli. Each panel shows typical traces of stimulus-evoked LFP in amplitude (mV), which was averaged from 60 trials within one recording session. Black bars indicate the onset and offset of the stimulus training. (B & D) Corresponding spectrograms of A and C. Each panel shows response of stimulus-evoked LFP in the time-frequency domain decomposed by the wavelet transform (averaged from 60 trials within one recording session). The spectrograms show that the ON responses consist of a wide band of frequencies (red arrows), and bands at the stimulus frequencies as well as higher harmonics occur during the stimulation epoch (light blue arrows). The color bar shows the LFP power in dB unit.

Figure 6. Group analysis of Spiking and LFP responses in Area 3b and S2 as function of stimulus frequency (A–D) and summary of percentage of spike-LFP dissociation in control and plasticity cases (E)

(A) Plot of the Response Efficacy (RE, solid lines) and firing rate (dotted lines) spiking activity as a function frequency in area 3b. The mean RE from declined progressively in control cases that were statistically significant higher than those of plasticity cases (* p < 0.05, except for 2 Hz stimulus). But the mean RE of plasticity cases dropped nearly to zero at higher flutter stimuli. The differences in firing rates between normal and deafferentated cortex were also significant. (B) Similar decaying trend of RE and firing rate was observed in S2, besides that significant difference between control and plasticity was found at all stimulus conditions (p < 0.05). (C) The mean power of evoked LFP in Area 3b also decreased with increasing stimulus frequency. The LFP signal was persistently and robustly modulated by the tactile stimulation under all conditions, and there is no difference between signals in normal versus deafferentated cortex (p>0.05). (D) Similar response pattern of evoked LFP is presented in S2 as well. * p<0.05.

Figure 7

Plots of the number of penetrations of related (A, D), dissociated (B, E) and absence (C, F) of spiking activity and LFP power as a function of different stimulus frequencies in control (blue bars) and plasticity (input-deprived, red bars) cortex of area 3b and S2. (G) Summary of spike-LFP dissociation as function of stimulus frequency in area 3b and S2 of normal and input-deprived (plasticity subjects). With increasing stimulation frequency, the LFP response became more frequently dissociated with spiking activity in plasticity cases, which was quantified by the percentage of total recording sites (red line: from 4.8% to 62.5% of recording sites in area 3b and dark line: from 4.8% to 72.0% in S2). Particularly at higher frequencies of stimulation (15, 30, 50 Hz), the numbers of recording sites where the dissociation were robustly observed in plasticity cases is significantly higher than those in control cases (dash lines).