A cortical neural prosthesis for restoring and enhancing memory

Abstract

A primary objective in developing a neural prosthesis is to replace neural circuitry in the brain that no longer functions appropriately. Such a goal requires artificial reconstruction of neuron-to-neuron connections in a way that can be recognized by the remaining normal circuitry, and that promotes appropriate interaction. In this study, the application of a specially designed neural prosthesis using a multi-input/multi-output (MIMO) nonlinear model is demonstrated by using trains of electrical stimulation pulses to substitute for MIMO model derived ensemble firing patterns. Ensembles of CA3 and CA1 hippocampal neurons, recorded from rats performing a delayed-nonmatch-to-sample (DNMS) memory task, exhibited successful encoding of trial-specific sample lever information in the form of different spatiotemporal firing patterns. MIMO patterns, identified online and in real-time, were employed within a closed-loop behavioral paradigm. Results showed that the model was able to predict successful performance on the same trial. Also, MIMO model-derived patterns, delivered as electrical stimulation to the same electrodes, improved performance under normal testing conditions and, more importantly, were capable of recovering performance when delivered to animals with ensemble hippocampal activity compromised by pharmacologic blockade of synaptic transmission. These integrated experimental-modeling studies show for the first time that, with sufficient information about the neural coding of memories, a neural prosthesis capable of real-time diagnosis and manipulation of the encoding process can restore and even enhance cognitive, mnemonic processes.

Likelihood Methods for Point Processes with Refractoriness

“…These techniques have been used for basic neuroscience research (Kass et al, 2011;Okatan et al, 2005;Eldawlatly et al, 2009;Berger et al, 2011;Jenison et al, 2011;So et al, 2012), to improve biophysical neural models (Ahrens et al, 2008;Meng et al, 2011;Mensi et al, 2012), or to design better BMIs (Shoham et al, 2005;Srinivasan et al, , 2007Truccolo et al, 2008;Wang and Principe, 2010;Saleh et al, 2012).…”

Deep brain stimulation: a mechanistic and clinical update

“…Hippocampal stimulation, for example, has been found to both disrupt 72,105 and enhance memory. The fact that memory enhancement requires the stimulation to be spatially and temporally matched to existing hippocampal input activity 18,75 suggests that some sort of oscillatory coupling mechanism is involved and that DBS can augment this mechanism. In the medial temporal lobe, increases in the amplitude of q band (3-8 Hz) LFP oscillations can predict whether an experience is encoded in memory, 70,113 and reinforcing these q oscillations with DBS has been shown to improve spatial working memory.…”

Neuromodulation for restoring memory

“…61 Recording ensembles of hippocampal CA1 and CA3 neurons enable pre diction of memory task outcome, and stimulation alters memory task performance. 5 Hippocampal stimulation delivered in a spatial and temporal task-specific pattern determined from prior recordings restored memory-dependent conditioned behavior in rats treated with hippocampal infusion of an NMDA channel blocker, a treatment that blocks hippocampal-dependent memory performance. 4 Medial temporal DBS has shown some promise in a rodent dementia model.…”

“…16 These oscillations can occur at a wide range of frequencies. Two frequencies that play a particularly important role in memory are gamma (30-100 Hz) and theta (3)(4)(5)(6)(7)(8). Theta-frequency oscillations predominate hippocampal activity and play a vital role in memory, in part by contributing to the transfer of information between the hippocampus and other regions involved in memory.…”