Temperature significantly influences physiological processes and is implicated in various neurodegenerative diseases. While the brain's inherent thermal fluctuations are notable, diagnostic and therapeutic tools can introduce further thermal changes. Optogenetics and multi-photon microscopy, for instance, can cause considerable heating. Existing models often underestimate the in vivo temperature rise during stimulation, highlighting the need for accurate thermal monitoring. Infrared neural stimulation (INS) uses pulsed infrared light (1400–2100 nm) to create controlled temperature transients in neurons, offering advantages over optogenetics due to its ease of use and lack of genetic modifications. INS has demonstrated applications in altering GABAergic neurotransmission, pacing hearts, and activating brain regions. Infrared neural inhibition (INI), conversely, suppresses neural activity using lower radiant exposure. However, in vivo demonstrations of INI in intracortical or hippocampal targets are lacking. This study aims to address this gap by developing a multifunctional tool for simultaneous thermal stimulation and recording of neural activity.

Previous research has highlighted the impact of temperature on various aspects of neuronal function. Studies have shown that temperature influences resting potential, action potential generation, synaptic transmission, and the diffusion of molecules involved in synaptic transmission. The clinical relevance of temperature effects on brain disorders, particularly pathological hyperthermia, has been recognized, and hypothermia has shown therapeutic potential in mitigating neuronal injury in conditions such as ischemia and traumatic brain injury. Existing optical stimulation microdevices, or optrodes, primarily designed for optogenetic manipulation, could potentially induce thermal changes. While some hybrid systems combining silicon microprobes with optical fibers or integrated dielectric waveguides have been proposed, in vivo demonstrations of efficient and safe near-infrared (NIR) applications in deep tissue neuromodulation remain limited. This necessitates the development of integrated systems capable of delivering NIR light while simultaneously measuring neural activity.

The researchers designed a multifunctional silicon neural microprobe with integrated photonic and electrical components. A 5 mm long waveguide embedded within the probe shaft delivers infrared light (λ = 1550 nm) from an external laser diode. Platinum recording sites along the shaft measure neuronal action potentials and tissue temperature. The device's optical efficiency was characterized in vitro, measuring spatial temperature distribution around the probe tip and establishing a calibration curve between optical power and temperature rise. In vivo experiments were performed in rats, implanting the probe in the neocortex and hippocampus. Stimulation protocols involved 2-minute ON and 4-minute OFF periods at various optical powers. Electrophysiological recordings were analyzed to assess changes in neuronal firing patterns, and the results were validated against data from a control laminar silicon probe. The spatial and temporal dynamics of temperature changes were modeled using a multi-physical model, ensuring that observed neural responses could be correctly attributed to thermal effects.

In vitro characterization revealed that the full width at half maximum of the temperature distribution around the probe tip was 1020 ± 184 µm. In vivo experiments in rat neocortex demonstrated that IR stimulation at various optical powers (6.9, 8.5, 10.5 mW) caused significant increases in multiunit activity at 1300 µm from the probe tip. However, at 1600 µm, high optical power led to suppressed activity. In the hippocampus (CA1 pyramidal layer), high optical power stimuli (2.8, 7.1, 10.7, 13.4 mW) caused increased multiunit activity. No visible stimulation artifacts were observed in the raw data, and action potential waveforms remained unaffected, indicating no neural damage. Concurrent measurements of tissue temperature using the integrated sensor and comparison with external sensor readings helped validate the study's findings. Furthermore, changes in body temperature were minimal, suggesting that the observed neural responses were primarily due to localized heating.

The study's findings demonstrate that the developed implantable photonic microdevice successfully achieved localized thermal neuromodulation in the deep brain tissue. The ability to both stimulate and record neural activity using a single device provides a significant advancement for in vivo research. The observed excitatory and inhibitory effects of infrared light at different locations and powers underscore the complex interplay between temperature and neuronal excitability. This technology allows researchers to study the effects of precisely controlled temperature gradients on neural circuits with high spatiotemporal resolution, advancing our understanding of temperature-sensitive neuronal processes and their involvement in health and disease. The absence of stimulation artifacts and the lack of neural damage suggest the safety and reliability of this technique.

This work presents the first in vivo demonstration of an integrated microdevice capable of deep brain tissue neuromodulation using infrared light while simultaneously recording neural activity. The results validate the device's functionality and demonstrate its ability to reversibly modulate neuronal firing. The precision control over temperature and the concurrent electrophysiological recording capability position this technology as a valuable tool for advancing research in neurophysiology, paving the way for future investigations into temperature-dependent mechanisms in brain function and dysfunction.

The study was conducted in rats, and further research is needed to determine the generalizability of these findings to other species, including humans. The spatial extent of the temperature changes induced by the device is limited, and it might not be suitable for targeting large neural populations. Additionally, the long-term effects of chronic infrared stimulation on neural tissue remain to be investigated.