PET Mapping for Brain–Computer Interface Stimulation of the Ventroposterior Medial Nucleus of the Thalamus in Rats with Implanted Electrodes

DISCUSSION

Born as a highly multidisciplinary field, BCI research has moved at a stunning pace since the first experiment demonstrating that electrical activity generated by ensembles of cortical neurons can directly control a robotic manipulator (8). Noninvasive neuroimaging modalities for BCI systems are gaining momentum in the research arena. Although functional MRI, with its superior spatial resolution, has surfaced as the major tool for noninvasive characterization of brain function (9), PET has the advantage of tracing biochemical changes in cognitive or behavioral brain function during real-time tasks without the interference of ambient noise generated by the MRI scanner, and unlike MRI, PET is suitable for a brain with implanted metal electrodes.

In the current study, by using ¹⁸F-FDG PET imaging we found that VPM stimulation induced an increase in glucose metabolism in the paraventricular thalamic nucleus, septohippocampal nucleus, olfactory bulb, left crus II, and bilaterally in the lateral septum, amygdala, piriform cortex, endopiriform nucleus, and insular cortex but that a significantly decrease in ¹⁸F-FDG accumulation occurred in the right secondary visual cortex, right simple lobule of the cerebellum, and bilaterally in the primary somatosensory cortex. To the best of our knowledge, this was the first study using PET as a neuroimaging tool to investigate the orienting performance of BCI-based electrical stimulation in rats with electrodes implanted in the VPM.

One significant finding of our study was the increased glucose metabolism in the paraventricular thalamic nucleus, amygdala, hippocampus, and lateral septum after VPM stimulation. The paraventricular thalamic nucleus is a major source of projections to the nucleus accumbens, the bed nucleus of the stria terminalis, and the central nucleus of the amygdala, as well as to the cortical areas associated with these subcortical regions. The paraventricular thalamic nucleus participates in functional integration of limbic cortical and striatal circuitry and is notable for providing a very dense projection to the nucleus accumbens, a part of the striatum strongly associated with regulation of locomotion (10). Consequently, the paraventricular thalamic nucleus, with its direct and indirect projections to the nucleus accumbens, forms an impressive neural network that can exert control over locomotor activity (11). The amygdala is a critical component of the neural circuitry underlying fear associations and emotional learning (12). Previous work indicated an essential role for the basolateral amygdala in stimulus–reward learning and for the dorsal hippocampus in spatial learning and memory (13). Interestingly, the current study found increased glucose metabolism not only in the amygdala and paraventricular thalamic nucleus but also in the septohippocampal nucleus and bilaterally in the lateral septum—observations that are consistent with recent literature on the hippocampus–to–lateral-septum pathway (14). The optogenetic stimulation of projections from the lateral septum to the lateral hypothalamus decreased locomotion, suggesting that the lateral septum has a crucial role in controlling locomotion and arousal.

The insular cortex, a part of the neocortex located in the lateral temporal lobe, is highly interconnected with multiple brain networks (15). Electrical stimulation of the insula has been shown to elicit body movements in nonhuman primates, indicating a role in sensorimotor processing (16). The midposterior insula has also been implicated in the processing of awareness of the position, movement, and sensation of the body and thus has a role in coordinating movements effectively (17). The cerebellum has been implicated in the control of actions and the acquisition of motor skills (18). In particular, the posterolateral regions (crus I and II) have been shown to be involved in adaptations to force fields and to visuomotor perturbation (19). Taking these findings from the literature and our findings together, we suggest that the insula and cerebellum may be involved in coordination of movement and control of the turning angle.

Our finding that electrical stimulation of the VPM decreases glucose metabolism in the primary somatosensory cortex is supported by other studies. Electrical stimulation has been shown to evoke strong and long-lasting cortical inhibition that suppresses firing of neurons (20). A recent study investigating responses in the visual cortex (21) found that visual stimuli evoke fewer spikes in the awake state than in the anesthetized state and that spikes evoked in the awake state are quickly followed by a significant and long-lasting hyperpolarization, suggesting that cortical responses to sensory stimulation are dominated by synaptic inhibition in the awake cortex (21). Thus, we speculate that electrical stimulation of the VPM might lead to initial activation of the cortical pyramidal neurons; subsequently, thalamocortical input recruited by strong postsynaptic inhibition shunts the initial excitatory input within the course of the hyperpolarization, resulting in a long-lasting decrease in baseline activity of the primary somatosensory cortex. Greater insight into the effect of BCI-based stimulation on brain function may be gained by future PET studies that combine electrophysiologic recordings and electroencephalography in the same subject.