At Starfish, we’re constantly evaluating how we can best contribute to the world, be it through our own efforts or by enabling others to innovate on their own, opening doors in areas and ways that have yet to be imagined.

Transcranial Magnetic Stimulation (TMS) has been shown to be a safe and effective method of non-invasive brain stimulation. However, current clinical applications of TMS are not personalized, in that the stimulation protocol is not adapted to the needs of each patient. At Starfish, we are developing methods for enhancing the spatial and temporal precision of TMS to deliver more effective, personalized care. These efforts include:

• Optimized targeting: TMS treatment typically involves manual (hand-held) placement of the stimulation coil based on approximate skull measurements. We believe that precise and robust identification of cortical targets is an essential component of TMS therapies, helping to ensure that stimulation is delivered to the brain networks of interest while avoiding off-target effects. To this end, we are developing a multi-pronged approach for TMS targeting that leverages robotics and personalized functional readouts to more accurately guide stimulation.
• Closed-loop stimulation protocols: Current stimulation protocols—including state-of-the-art accelerated intermittent theta burst stimulation (iTBS) used for the treatment of major depressive disorder (MDD)—are applied in a manner that is agnostic to the cortical state of the patient.  However, foundational neuroscience research has shown that mechanisms of plasticity in the brain are highly dependent on the timing of stimulation with respect to ongoing neural activity. We are investigating how real-time readouts of neural activity, combined with advanced machine learning techniques, can be leveraged to more effectively promote plasticity. As part of this effort, we are pursuing development of minimally-invasive sensing technologies designed to be used in conjunction with TMS.

By combining technological advancements in hardware and machine learning, grounded in rigorous neuroscientific research, we believe we can significantly enhance the effectiveness of TMS. In doing so, we hope to deliver improved therapies for a variety of neurological conditions, from mood disorders to stroke and beyond.

Distributed neural interfaces hold great promise for future therapies. Existing approaches to interfacing with the brain predominantly focus on interacting with a single brain region (for example, deep brain stimulation for Parkinson’s disease). However, there is increasing evidence that a number of neurological disorders involve circuit-level dysfunction, in which the interactions between brain regions may be misregulated.

Developing better therapies for these disorders will require distributed neural interfaces capable of interacting with the brain at the circuit level; that is, reading and writing to multiple connected parts of the brain at once. In doing so, they will enable closed-loop therapies that are brain-state-aware, and plasticity-centric therapies that manipulate connectivity between brain regions. Such interfaces do not yet exist clinically, and existing interfaces are not straightforward to parallelize because of their bulky physical footprints, power and communication bandwidth needs, and surgical burden.

As a result, we’re doing some things differently, for example:

• Focusing on miniaturization and power optimization within a single device with moderate channel counts, rather than emphasizing scaling up channel counts in a single device
• Reducing size surgical burden risk by making battery-free devices powered by external wearables
• Minimizing tissue damage by reducing the cross-section of an implant, to the point of “1-D” implants
• Optimizing electrode designs to enable multi-scale recordings (single-neuron-level to local field potentials), and precisely spatially targeted stimulation exceeding current clinical capabilities with typical segmented leads

This is not a complete list, and we’re ultimately after impact over technology, so we focus on innovation where it’s most needed towards reaching the potential of distributed neural interfaces and the therapies they will enable. 

Our targeted hyperthermia device is an example of how the minimally invasive, wireless technology under development at Starfish may be used in unexpected ways. By application of the fundamental principles of our Implantables program, namely wireless power and data coupled with low surgical burden, we are developing technology to help target and eliminate solid tumors, even those deep within the body. 

The therapeutic use of heat in cancer treatment, from acute ablation with temperatures above 50°C to lower-temperature, repeated hyperthermia with moderate temperature increases of up to 45°C is well documented. Our unique approach is to utilize one or more injectable devices which would be surgically placed at the onset of a therapeutic regimen then utilized in repeat visits to an outpatient setting such as a standard chemo infusion center with minimal additional equipment.

Each implant will have a wirelessly programmable maximum temperature as well as be able to communicate wirelessly to the external antenna to ensure thermal dose delivery. This approach's simplicity and control stand out compared to other hyperthermia methods, such as high-intensity focused ultrasound (HIFU), which may require MRI for targeting and temperature control, or light-activated nanoparticles, which are limited to shallow tumors and lack precise temperature control. 

We envision the technology used in multiple ways, from direct, repeated thermal dosing with/without standard chemo or radiation or with temperate activated chemical and biological therapies which are specifically designed to be activated at regions of increased temperature. We believe that proper localization of therapy could dramatically reduce off-target effects and achieve improved outcomes.