Painful stimuli evoke potentials recorded from the medial temporal lobe in humans

Abstract

The role of human medial temporal structures in fear conditioning has led to the suggestion that neurons in these structures might respond to painful stimuli. We have now tested the hypothesis that recordings from these structures will demonstrate potentials related to the selective activation of cutaneous nociceptors by a painful laser stimulus (laser evoked potential, LEP) (Kenton B, Coger R, Crue B, Pinsky J, Friedman Y, Carmon A (1980) Neurosci Lett 17:301-306). Recordings were carried out through electrodes implanted bilaterally in these structures for the investigation of intractable epilepsy. Reproducible LEPs were commonly recorded both bilaterally and unilaterally, while LEPs were recorded at contacts on the left (9/14, P=0.257) as commonly as on the right (5/14), independent of the hand stimulated. Along electrodes traversing the amygdala the majority of LEPs were recorded from dorsal contacts near the central nucleus of the amygdala and the nucleus basalis. Stimulus evoked changes in theta activity were observed at contacts on the right at which isolated early negative LEPs (N2*) responses could be recorded. Contacts at which LEPs could be recorded were as commonly located in medial temporal structures with evidence of seizure activity as on those without. These results demonstrate the presence of pain-related inputs to the medial temporal lobe where they may be involved in associative learning to produce anxiety and disability related to painful stimuli.

Figure 1

Stereotactic technique for placing depth electrodes. Panel A is a T2 weighted coronal image through the amygdala in which the oblique targeting lines define the center of the stereotactic coordinate system, the horizontal line indicates the medial-lateral coordinate, and the vertical line indicates the vertical coordinate. Ventral and dorsal white dots indicate the location of electrodes 4 and 5 on the amygdala electrode in panel A (labeled), and panel B shows the location of the corresponding hippocampal electrode (unlabelled). Panel C is a fluoroscopic image showing the centering crosshairs aligned with the target. See methods section on ‘Surgical Technique’.

Figure 2

Reproducible LEPs and estimated electrode locations for subject 4. LEPs are shown for the left (A) and right (B) hippocampus and for the left amygdala (C). The reproducibility of these potentials is shown by the overlay of tracings from two separate runs, one colored black and the other red. The peaks are indicated by the position (latency) of the corresponding label (N2* or P2**) along the horizontal axis, and by an arrow in A4, A5, and B5. The contact at which the potential was recorded is indicated to the left of each potential. The voltage (mV) and time scales (ms), and the polarity of the potentials, indicated in panel B, apply to all three panels.

Figure 3

Time-frequency map of hippocampal changes in energy for the local field potential response to the laser stimulus. The horizontal scale is time following the laser stimulus (s), the vertical scale is frequency (Hz), and the color scale is change in energy relative to baseline in logarithmic scale. The color dimension indicates significant increases (hot colors) or decreases in energy (cold colors) in (dB) after laser stimulation relative to baseline. The green background represents time-frequency regions with no significant change relative to baseline. For example, a pixel with the maximum temperature color of 10 dB represents a significant increase in energy which is 10 dB greater than baseline for a given time and frequency.