Elsevier

Experimental Neurology

Volume 249, November 2013, Pages 132-143
Experimental Neurology

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

https://doi.org/10.1016/j.expneurol.2013.08.013Get rights and content

Highlights

  • Enhanced inhibitory tone in area 3b and S2 after spinal cord injury

  • Clear dissociation between spiking and LFP at high stimulus frequencies

  • We propose that this is a cortical signature during recovery of function.

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).

Introduction

After spinal cord injury, considerable recovery of sensory function often occurs over a period of days to months. These recoveries include simple hand use (Ballermann et al., 2001), tasks involving fine cutaneous touch, and temporal or spatial information processing (for reviews see Kaas and Collins (2003), Kaas and Florence (2001b) and Nathan et al. (1986)). In humans, light touch and pressure sensation often recover quickly and completely; while vibration and proprioception recover slowly and never become completely normal (Bors, 1979), suggesting differential recovery of frequency specific channels in the somatosensory pathways. A primate model with a unilateral destruction of the dorsal column pathway, although not a typical model of spinal cord injury, offers a unique experimental platform for examining the roles of cortical reactivation and reorganization in functional and behavioral recoveries after deafferentation. In this model of spinal cord injury, input-deprived brain regions in primary somatosensory cortex (S1) regain their responsiveness to stimuli (reactivation), but the somatotopy remains abnormal (reorganization) (Darian-Smith and Brown, 2000, Florence et al., 1998, Graziano and Jones, 2009, Jones, 2000, Kaas et al., 1983, Kaas et al., 2008, Manger et al., 1996). Such cortical reactivation and reorganization in S1 are believed to be crucial for the recovery of simple hand use and regaining of some forms of touch sensation (Darian-Smith and Ciferri, 2005).

The abnormal phantom sensations that develop in humans after deafferentation implicate roles of higher cortical areas beyond S1 such as second somatosensory cortex (S2) (Flor et al., 1995, Knecht et al., 1998, Tandon et al., 2009). However, to date, little is known about the neuronal basis of brain recovery following spinal cord lesion and even less about the role of higher areas such as S2, knowledge that is vital for developing new therapies aimed at functional recovery (Pons et al., 1988, Vierck, 1998, Vierck and Cooper, 1998). Little is known about the inter-areal differences during the reactivation process in earlier somatosensory cortices of area 3b and S2 in primates. By quantifying and comparing the neuronal responsiveness of simultaneously recorded area 3b and S2 neurons from reactivated cortex weeks after dorsal column section, this study examined whether area 3b and S2 cortex exhibit similar functional reactivation profiles. As the third study in the series (Chen et al., 2012, Qi et al., 2011) here we report the stimulus-frequency dependent dissociation in response efficiency between spiking and local field potentials (LFP) recorded simultaneously from the input-deprived but reactivated area 3b and S2 cortex. A better understanding of the reactivation process may lead to new therapies to aide functional recovery following spinal cord injury.

There is a growing recognition in recent years that LFPs and spiking activity reflect different aspects of neuronal processing at different spatial and temporal scales. LFP integrates predominantly synaptic input signals from a population of neurons in a relatively larger cortical region whereas spiking activity carries the output signal. To date, the precise relationship between LFP and spiking activity remains elusive (Berens et al., 2008a, Berens et al., 2008b, Boynton, 2011, Conner et al., 2011, Logothetis, 2003, Logothetis et al., 2001). There is evidence for a functional or task specific relationship between these two different types of signals (Bartolo et al., 2011, Ekstrom, 2010, Rauch et al., 2008). Furthermore, most of what we know about the reactivation properties of somatosensory cortex following spinal cord injury comes from microelectrode recordings in which only spiking activity was evaluated. To our knowledge, no study has systematically examined the cortical responsiveness of reactivated cortex after spinal cord injury by recording both spiking and LFP responses. Immunohistological evidence of altered excitatory and inhibitory neurotransmission systems, as well as our functional imaging findings, led us to hypothesize that subthreshold electrical activity plays a key role in promoting cortical reactivation, and ultimately behavioral recovery (Chen et al., 2012, Garraghty et al., 2006, Mowery and Garraghty, 2009). As a test of this hypothesis, the present study aims to 1) characterize the response properties of spiking activity and LFPs, 2) determine the relationship between changes in spiking and LFP, and 3) examine whether spiking activity and LFP response differ in input-deprived and reactivated versus normal cortical area 3b and S2. We find that the local field potential (LFP) response to skin indentations remains robust at all frequencies in both area 3b and S2; however, neuron spiking activity fails to follow at high stimulus frequencies.

Section snippets

Animal preparation and surgery

Four adult squirrel monkeys (Saimiri bolivians) and six hemispheres were included in this study. Unilateral dorsal column section between spinal cord cervical segments C4–C6 was carried out under aseptic conditions under deep anesthesia (1–3% isoflurane) (Jain et al., 1997, Jain et al., 2008, Qi et al., 2011). The monkeys with spinal cord injuries were subject to fMRI imaging before and up to four times after spinal cord lesions, as described elsewhere (Chen et al., 2012). After 8 weeks of

Spike and LFP activity in regions exhibiting altered BOLD response after lesion

We examined the response properties of spike and evoked field potentials of neurons in areas 3b and S2 eight weeks after large, but incomplete lesion of the contralateral dorsal columns at higher cervical levels. Responses obtained from these cortical areas in monkeys without dorsal column lesions served as controls. Locations of recording sites for the study of reactivated neurons were identified and validated by pre- and post-lesion fMRI activation, and by detailed neuronal response maps of

Discussion

This study aimed to determine how neurons in area 3b and S2 of somatosenosry cortex responded to repeated trains of skin indentation at different frequencies in cortex that had been reactivated after dorsal column lesion of afferents from the hand. We then mapped cortical regions of reactivation with microelectrode electrophysiology and with functional imaging (MRI and optical imaging) and confirmed the extent of the deafferentations with histological evaluations. By examining neuronal spikes

Acknowledgments

This work was supported by the Dana Foundation (to LMC), NIH NS044735 (to AWR), NS067017 (to HXQI), NS16446 (to JHK), and Vanderbilt University Center for Integrative & Cognitive Neuroscience. We thank Robert Friedman for providing the NI LabVIEW support and providing feedback on the manuscript, and Xiang Ye and Lisa Chu for their assistance of some surgeries and data collection.

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