Similarities Between Somatosensory Cortical Responses Induced via Natural Touch and Microstimulation in the Ventral Posterior Lateral Thalamus in Macaques.

Lost sensations, such as touch, could be restored by microstimulation (MiSt) along the sensory neural substrate. Such neuroprosthetic sensory information can be used as feedback from an invasive brain-machine interface (BMI) to control a robotic arm/hand, such that tactile and proprioceptive feedback from the sensorized robotic arm/hand is directly given to the BMI user. Microstimulation in the human somatosensory thalamus (Vc) has been shown to produce somatosensory perceptions. However, until recently, systematic methods for using thalamic stimulation to evoke naturalistic touch perceptions were lacking. We have recently presented rigorous methods for determining a mapping between ventral posterior lateral thalamus (VPL) MiSt, and neural responses in the somatosensory cortex (S1), in a rodent model (Choi et al., 2016; Choi and Francis, 2018). Our technique minimizes the difference between S1 neural responses induced by natural sensory stimuli and those generated via VPL MiSt. Our goal is to develop systems that know what neural response a given MiSt will produce and possibly allow the development of natural "sensation." To date, our optimization has been conducted in the rodent model and simulations. Here, we present data from simple non-optimized thalamic MiSt during peri-operative experiments, where we used MiSt in the VPL of macaques, which have a somatosensory system more like humans, as compared to our previous rat work (Li et al., 2014; Choi et al., 2016). We implanted arrays of microelectrodes across the hand area of the macaque S1 cortex as well as in the VPL. Multi and single-unit recordings were used to compare cortical responses to natural touch and thalamic MiSt in the anesthetized state. Post-stimulus time histograms were highly correlated between the VPL MiSt and natural touch modalities, adding support to the use of VPL MiSt toward producing a somatosensory neuroprosthesis in humans.

Electronically induced contrast enhancement in whisker S1 cortical response fields.

The ability of an organism to specifically attend to relevant sensory information during learning and subsequent performance of a task is highly dependent on the release of the neurotransmitter Acetylcholine (ACh). Electrophysiological studies have shown that pairing endogenous ACh with specific visual or auditory stimuli induces long lasting enhancements of subsequent cortical responses to the previously paired stimulus. In this study we present data suggesting that similar effects can be elicited in the rat whisker sensory system. Specifically, we show that pairing whisker deflection with electrical stimulation of the magnocellular basal nucleus (BN: a natural source of cortical ACh) causes an increase in the center-surround contrast of the treated whisker's cortical response field (CRF). Meanwhile, deflections of whiskers distant from the treated whisker show overall increased response magnitudes, but non-significant changes in contrast between principle vs. surround barrel responses. Control trials, in which BN stimulation was not paired with whisker deflection, showed similar lack of contrast enhancement. These results indicate that BN stimulation, paired with incoming whisker information, selectively increases the paired whisker's CRF center-surround contrast, while unpaired BN stimulation causes a more general increases in S1 responsiveness, without contrast modulation. Enhanced control over whisker sensory pathway attentional mechanisms has the potential to facilitate a more effective transfer of desired information to the animal's neural processing circuitry, thereby allowing experimental evaluation of more complex behavior and cognition than was previously possible.

Erasing sensorimotor memories via PKMzeta inhibition.

Sensorimotor cortex has a role in procedural learning. Previous studies suggested that this learning is subserved by long-term potentiation (LTP), which is in turn maintained by the persistently active kinase, protein kinase Mzeta (PKMzeta). Whereas the role of PKMzeta in animal models of declarative knowledge is established, its effect on procedural knowledge is not well understood. Here we show that PKMzeta inhibition, via injection of zeta inhibitory peptide (ZIP) into the rat sensorimotor cortex, disrupts sensorimotor memories for a skilled reaching task even after several weeks of training. The rate of relearning the task after the memory disruption by ZIP was indistinguishable from the rate of initial learning, suggesting no significant savings after the memory loss. These results indicate a shared molecular mechanism of storage for declarative and procedural forms of memory.

A bio-friendly and economical technique for chronic implantation of multiple microelectrode arrays.

Many neurophysiological experiments on rodents and non-human primates involve the implantation of more than one multi-electrode array to record from many regions of the brain. So called 'floating' microelectrode arrays are implanted in cortical regions of interest and are coupled via a flexible cable to their connectors which are fixed to the skull by a cement cap or a titanium pedestal, such as the Cereport system, which has been approved for human use. The use of bone cement has several disadvantages including the creation of infection prone areas at the interface with the skull and surrounding skin. Alternatively, the more biocompatible Cereport has a limited carrying capacity and is far more expensive. In this paper, we describe a new implantation technique, which combines the biocompatibility of titanium, a high carrying capacity with a minimal skull footprint, and a decreased chance of infection, all in a relatively inexpensive package. This technique utilizes an in-house fabricated 'Nesting Platform' (NP), mounted on a titanium headpost to hold multiple connectors above the skin, making the headpost the only transcutaneous object. The use of delrin, a durable, lightweight and easily machinable material, allows easy customization of the NP for a wide variety of floating electrodes and their connectors. The ultimate result is a longer survival time with superior neural recordings that can potentially last longer than with traditional implantation techniques.