Biological neurons act as generalization filters in reservoir computing.

Reservoir computing is a machine learning paradigm that transforms the transient dynamics of high-dimensional nonlinear systems for processing time-series data. Although the paradigm was initially proposed to model information processing in the mammalian cortex, it remains unclear how the nonrandom network architecture, such as the modular architecture, in the cortex integrates with the biophysics of living neurons to characterize the function of biological neuronal networks (BNNs). Here, we used optogenetics and calcium imaging to record the multicellular responses of cultured BNNs and employed the reservoir computing framework to decode their computational capabilities. Micropatterned substrates were used to embed the modular architecture in the BNNs. We first show that the dynamics of modular BNNs in response to static inputs can be classified with a linear decoder and that the modularity of the BNNs positively correlates with the classification accuracy. We then used a timer task to verify that BNNs possess a short-term memory of several 100 ms and finally show that this property can be exploited for spoken digit classification. Interestingly, BNN-based reservoirs allow categorical learning, wherein a network trained on one dataset can be used to classify separate datasets of the same category. Such classification was not possible when the inputs were directly decoded by a linear decoder, suggesting that BNNs act as a generalization filter to improve reservoir computing performance. Our findings pave the way toward a mechanistic understanding of information representation within BNNs and build future expectations toward the realization of physical reservoir computing systems based on BNNs.

Suppression of hypersynchronous network activity in cultured cortical neurons using an ultrasoft silicone scaffold.

The spontaneous activity pattern of cortical neurons in dissociated culture is characterized by burst firing that is highly synchronized among a wide population of cells. The degree of synchrony, however, is excessively higher than that in cortical tissues. Here, we employed polydimethylsiloxane (PDMS) elastomers to establish a novel system for culturing neurons on a scaffold with an elastic modulus resembling brain tissue, and investigated the effect of the scaffold's elasticity on network activity patterns in cultured rat cortical neurons. Using whole-cell patch clamp to assess the scaffold effect on the development of synaptic connections, we found that the amplitude of excitatory postsynaptic current, as well as the frequency of spontaneous transmissions, was reduced in neuronal networks grown on an ultrasoft PDMS with an elastic modulus of 0.5 kPa. Furthermore, the ultrasoft scaffold was found to suppress neural correlations in the spontaneous activity of the cultured neuronal network. The dose of GsMTx-4, an antagonist of stretch-activated cation channels (SACs), required to reduce the generation of the events below 1.0 event per min on PDMS substrates was lower than that for neurons on a glass substrate. This suggests that the difference in the baseline level of SAC activation is a molecular mechanism underlying the alteration in neuronal network activity depending on scaffold stiffness. Our results demonstrate the potential application of PDMS with biomimetic elasticity as cell-culture scaffold for bridging the in vivo-in vitro gap in neuronal systems.

Rise of oligodendroglioma hypermutator phenotype from a subclone harboring TP53 mutation after TMZ treatment.

Oligodendrogliomas characterized and defined by 1p/19q co-deletion are slowly growing tumors showing better prognosis than astrocytomas. TP53 mutation is rare in oligodendrogliomas while the vast majority of astrocytomas harbor the mutation, making TP53 mutation mutually exclusive with 1p/19q codeletion in lower grade gliomas virtually. We report a case of 51-year-old woman with a left fronto-temporal oligodendroglioma that contained a small portion with a TP53 mutation, R248Q, at the initial surgery. On a first, slow-growing recurrence 29 months after radiation and nitrosourea-based chemotherapy, the patient underwent TMZ chemotherapy. The recurrent tumor responded well to TMZ but developed a rapid progression after 6 cycles as a malignant hypermutator tumor with a MSH6 mutation. Most of the recurrent tumor lacked typical oligodendroglioma morphology that was observed in the primary tumor, while it retained the IDH1 mutation and 1p/19q co-deletion. The identical TP53 mutation observed in the small portion of the primary tumor was universal in the recurrence. This case embodied the theoretically understandable clonal expansion of the TP53 mutation with additional mismatch repair gene dysfunction leading to hypermutator phenotype. It thus indicated that TP53 mutation in oligodendroglioma, although not common, may play a critical role in the development of hypermutator after TMZ treatment.

Middle Cerebral Artery Aneurysm Associated with Moyamoya Disease.

BACKGROUND: We report a rare case of unruptured middle cerebral artery aneurysm associated with moyamoya disease. CASE DESCRIPTION: A 48-year-old woman with an 8-year history of moyamoya disease developed a de novo aneurysm at the bifurcation of the right middle cerebral artery. The aneurysm showed rapid enlargement in size in 1 year and surgical treatment was performed. Preoperative images could not clearly define the anatomical relationship between the aneurysm and the surrounding vessels. Intraoperative findings indicated that segmental occlusion of normal arteries that was not visualized made it difficult to define the vascular anatomy. In addition, those occlusions accompanied by improved M1 flow after administration of cilostazol was speculated to have increased hemodynamic stress, leading to the relatively rapid progress of the aneurysm. CONCLUSIONS: Understanding the complexity of such process may be valuable in proper decision-making in the management of moyamoya disease patients.

Ultrasoft Silicone Gel as a Biomimetic Passivation Layer in Inkjet-Printed 3D MEA Devices.

Multielectrode arrays (MEAs) are versatile tools that are used for chronic recording and stimulation of neural cells and tissues. Driven by the recent progress in understanding of how neuronal growth and function respond to scaffold stiffness, development of MEAs with a soft cell-to-device interface has gained importance not only for in vivo but also for in vitro applications. However, the passivation layer, which constitutes the majority of the cell-device interface, is typically prepared with stiff materials. Herein, a fabrication of an MEA device with an ultrasoft passivation layer is described, which takes advantage of inkjet printing and a polydimethylsiloxane (PDMS) gel with a stiffness comparable to that of the brain. The major challenge in using the PDMS gel is that it cannot be patterned to expose the sensing area of the electrode. This issue is resolved by printing 3D micropillars at the electrode tip. Primary cortical neurons are grown on the fabricated device, and effective stimulation of the culture confirms functional cell-device coupling. The 3D MEA device with an ultrasoft interface provides a novel platform for investigating evoked activity and drug responses of living neuronal networks cultured in a biomimetic environment for both fundamental research and pharmaceutical applications.