Welcome to another edition of Neural Frontiers! This is a little different from how I’ve published posts before, but I’m really excited about it.  Previously, I’ve worked on these by myself with minimal input from friends in the industry.  I’ve been open to the idea of collaborating on a post with other industry friends, but this is the first time I’ve done it.  It’s been enjoyable to throw ideas around and work alongside someone with a valuable perspective.

That’s why I’m happy to share that this edition of Neural Frontiers is brought to you in collaboration with Rolf Lee Dixon. Rolf is a fellow NeuroTech explorer and enthusiast who has been a subscriber for most of the year. We’ve gotten together a few times to talk content and the future of this ever-expanding arena.  Given how fun this was to work on with someone else, I’d love to produce more collaborative pieces in the future.  Please reach out with all of your ideas and feedback – the famous quote goes – “If you want to go fast, go alone.  If you want to go far, go together”.

The Hardware Trap

What if the most considerable risk in brain tech isn’t the science—it’s being stuck with 2025’s hardware in your skull in 2035? It’s the fundamental challenge facing each company building invasive neural interfaces today, and it’s why the smart money in neurotech is quietly shifting strategies.

Let’s start with the basics: neuromodulation refers to using electrical, magnetic, ultrasound, light or chemical signals to influence brain activity. Think of it like a pacemaker for your brain, except instead of regulating heartbeat, it’s controlling chronic pain, depression, focus, or movement disorders. The field splits into two camps: invasive solutions requiring surgery to implant devices directly into your brain or nervous system, and non-invasive approaches using external devices, nasal delivery systems, or wearables that never break the skin.

VCs are pouring billions into neurotech, but the invasive players like Neuralink and Synchron dominate headlines while non-invasive solutions are quietly capturing market share, FDA approvals, and patient adoption. This post breaks down why timing, technology lifecycles, and regulatory pathways make non-invasive neuromodulation the better bet for most investors in 2025. We’ll review market data, examine a breakthrough case study, and provide you with a practical checklist for evaluating neurotech deals.

The Tale of Two Markets: Invasive vs Non-Invasive

By the numbers, these markets look deceptively similar until you examine the underlying dynamics. Invasive neurotech—dominated by deep brain stimulation (DBS) and spinal cord stimulation—is a mature $8-10 billion market growing at 8-10% annually. Non-invasive neuromodulation is smaller today at roughly $3-5 billion but growing at 15-20% CAGR with dramatically lower barriers to entry. The critical insight for investors: invasive technologies target tens of thousands of severe cases annually (Parkinson’s patients willing to undergo brain surgery, for example), while non-invasive solutions can potentially serve millions of patients with moderate conditions who would never consider surgery.

Here’s what separates these markets from an investment timing perspective:

Factor	Invasive	Non-Invasive
Surgical Risk	Brain surgery required	Zero surgery
Time to Market	5-10 years	2-4 years
Hardware Lifecycle	10-15 years (permanent)	Replaceable/upgradeable
Patient Acceptance	<30% when offered surgery	>70% trial rate
Regulatory Path	PMA (most stringent)	De novo or 510(k)
Competition Level	5-10 major players	50+ startups + Big Medtech

Translation for investors: non-invasive means faster returns, lower development risk, and broader addressable markets. But it also means significantly more competition. The question becomes whether you’d rather fight for a slice of a small, protected market or compete aggressively for a much larger opportunity with faster feedback cycles.

Why Non-Invasive is Winning: Three Catalysts

Non-invasive neuromodulation is expanding beyond its original depression and chronic pain indications at a remarkable speed. Recent FDA clearances and clinical trials now validate use cases ranging from menstrual cramps to overactive bladder to PTSD. TMS (transcranial magnetic stimulation) therapy now shows 50-60% remission rates in treatment-resistant depression—statistically comparable to invasive options but with zero surgery, zero recovery time, and zero permanent hardware. Companies like Livia and Ovira have FDA clearance for menstrual pain relief using transcutaneous electrical nerve stimulation. The lower barrier to running trials means clinical evidence accumulates faster, which accelerates both physician adoption and insurance reimbursement decisions.

Here’s the elephant in the room for invasive tech: permanent implants represent a zero-sum game in an era of 2-year technology refresh cycles. AI chips, battery technology, and signal processing algorithms are advancing so rapidly that hardware designed in 2025 will be functionally obsolete by 2030—yet that hardware is surgically implanted and designed to last 10-15 years. Imagine having a 2015 iPhone permanently installed in your brain in 2025—no software updates, no new features, stuck with decade-old processing power and battery life. Would you want that device making critical decisions about your dopamine levels or motor control? Non-invasive technologies sidestep this entirely. When better technology emerges, patients simply switch devices. Even more promising: emerging solutions like dissolvable neural interfaces (think daily-wear contact lenses for your brain) or nasal nanoparticle delivery systems could offer the best of both worlds—targeted brain delivery without permanent hardware commitment.

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Spotlight: The Subsense Case Study

Why This Startup Matters

Subsense represents the frontier of non-invasive brain delivery: nanoparticles administered nasally that cross the blood-brain barrier to deliver therapeutic payloads directly to brain tissue. No surgery, no permanent hardware, and crucially, no direct competitors in their specific delivery mechanism. They’re essentially creating a new category—invasive-level targeting with non-invasive administration.

The Innovation

The breakthrough isn’t just the delivery mechanism—it’s the flush-out system using organic chemistry principles. The nanoparticles naturally clear from the system on a predictable timeline, solving both long-term safety concerns and the obsolescence problem that plagues permanent implants. Patients can upgrade to next-generation formulations as the science advances, just like switching prescription medications. From a regulatory perspective, this positions them closer to pharmaceuticals than medical devices, which could be either an advantage or a complication depending on their exact pathway.

The Investor Dilemma

Subsense faces a 5-10 year commercialization timeline—significantly longer than typical non-invasive plays that might reach market in 2-4 years. The investment question isn’t “Does this technology work?” but rather “Will someone crack nasal brain delivery faster, or will an entirely different approach make this obsolete before launch?” Their IP position around nanoparticle chemistry and delivery mechanisms is strong today, but in neurotech, a decade is enough time for multiple disruptive entrants. This is classic deep-tech investing: massive upside if they establish the category and get there first, significant risk if the market moves before they can commercialize. The strategic tension is real—they’re solving exactly the problems we’ve identified (no surgery, upgradeable, targeted delivery) but taking long enough that the competitive landscape could shift entirely.

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The Investment Thesis: Where the Smart Money is Moving

Follow the capital, and the pattern becomes clear. Non-invasive neuromodulation companies raised over $2 billion across 150+ deals in 2023-2024, up approximately 40% from the previous two-year period. Notable exits include BrainsWay (NASDAQ: BWAY) maintaining a market cap around $150-200M post-IPO, and Flow Neuroscience raising significant Series A funding for their at-home depression headset. More telling: major medical device players like Abbott, Boston Scientific, and Nevro—companies with decades of experience in invasive neuromodulation—are aggressively entering non-invasive spaces through acquisition and internal development. Boston Scientific’s acquisition of Relievant Medsystems for $850 million signaled that even spinal intervention giants see the writing on the wall. Why? Because these companies see the same fundamental math investors do—bigger addressable markets, faster commercialization cycles, and dramatically easier patient adoption curves.

The most interesting money is coming from wellness tech giants. Oura raised $900M. WHOOP has comparable war chests. These companies have cracked consumer adoption at scale and are now moving upmarket into medical-adjacent territory. Watch the pattern: Oura and WHOOP already monitor estrogen levels and menstrual cycles, diagnosing problems for millions of users. Companies like Samphire Neuroscience use non-invasive neuromodulation to solve those problems—alleviating menstrual pain through targeted stimulation. The vertical integration play is obvious: wellness giants acquire medical solution companies, gaining FDA-cleared therapeutic capabilities, insurance reimbursement pathways, and defensible IP. For investors, this creates dual exit optionality—sell to traditional medtech (Abbott, Boston Scientific) or to consumer wellness platforms with billions in dry powder and millions of users already experiencing the problems your device solves.

The strategic insight for VCs: non-invasive neuromodulation serves as the bridge technology between basic wellness wearables (Muse headbands, Oura rings tracking sleep) and advanced neural implants requiring neurosurgery. It normalizes the concept of “brain optimization” for mainstream consumers while simultaneously building robust clinical evidence for more sophisticated interventions. Companies that establish brand trust and clinical credibility in non-invasive spaces create optionality to expand into adjacent markets as technology and regulations evolve. For investors, this creates asymmetric upside—you’re backing teams positioned to scale from $100M markets addressing specific medical conditions to potential billion-dollar markets in general cognitive enhancement and mental health. The companies that nail non-invasive solutions today are building the distribution, clinical relationships, and consumer trust needed to dominate whatever comes next in neurotech.

Your Investment Checklist: Five Questions That Matter

1. Can competitors replicate this in under 2 years?

If the answer is yes, you need a clear understanding of the defensible moat. Strong patents on mechanisms (not just applications), proprietary clinical datasets, or significant head-starts in expensive clinical trials all qualify. For example, Subsense’s specific nanoparticle chemistry and flush-out mechanism represent genuine IP protection, while a company building “a better TMS coil” faces dozens of competitors with similar capabilities. The key distinction: are you protecting novel science or just good execution?

2. What’s the regulatory pathway and realistic timeline?

Understanding FDA pathways isn’t optional. De novo classification (for truly new technologies with no predicate devices) typically requires 18-36 months and extensive clinical data, but lets you establish a new category. The 510(k) pathway (demonstrating substantial equivalence to existing devices) moves faster at 6-12 months but confines you to existing, often smaller markets. An additional wrinkle: devices that only read and display biomarkers usually face minimal regulatory burden, while anything making medical intervention claims faces significantly stricter scrutiny.

The strategic opportunity: as wellness companies move into medical territory, they’re building regulatory precedents that benefit the entire non-invasive category—and eventually invasive devices too. The FDA is developing institutional knowledge around wellness-medical hybrids in real-time, which should accelerate future approvals. This represents a regulatory learning curve where each category (wellness → non-invasive → invasive) validates safety standards and clinical endpoints that inform the next level. Companies positioned at these transitions are potentially de-risking the entire neurotech stack for future innovators.

3. What’s the hardware upgrade strategy?

Permanent implants with no upgrade path face existential obsolescence risk. Look for companies building: dissolvable or biodegradable interfaces that naturally clear after treatment periods, subscription or rental models for external devices that allow hardware swaps, or software-upgradeable platforms where the critical IP lives in algorithms rather than physical components. Red flag: any pitch centered on “10-year implant” without addressing what happens when the technology improves in year three. Green flag: business models that benefit from technology advancement rather than being threatened by it.

4. How does this create or expand market categories?

The best investments don’t just capture existing markets—they create new ones or dramatically expand addressable populations. Does this technology enable use cases that weren’t previously feasible? More importantly, does it convert “non-consumers”—people who would never consider brain surgery—into potential customers? A device that helps severe Parkinson’s patients without surgery is interesting; a device that allows millions of people with moderate focus issues to manage their condition is transformative. Look for technologies that change the adoption equation, not just the technical implementation.

5. What’s the commercialization timeline vs. disruption risk?

This is the “Subsense dilemma” in large. Longer development timelines provide more opportunity for fast followers or adjacent technologies to disrupt your position before you reach market. A company with breakthrough science but a 7-year path to commercialization faces a genuine risk that the market landscape will shift entirely during that period. Balance the defensibility of IP and technical barriers against the speed-to-market of potential competitors. Sometimes, “pretty good technology that ships in 2 years” beats “revolutionary technology that ships in 6 years” from a pure investment returns perspective.

6. What’s the reimbursement strategy beyond FDA clearance?

FDA clearance opens the door, but CMS reimbursement codes are what actually generate revenue—and this is where many non-invasive neuromodulation companies are currently hitting a wall. The pathway from regulatory approval to sustainable commercialization requires navigating the complex coding system to secure appropriate CPT codes and payer coverage. Without this, even FDA-cleared technology becomes a cash-pay product with limited market penetration. Ask: Does the company have a reimbursement strategy mapped out before FDA submission? Are they pursuing existing codes (faster, lower reimbursement) or novel codes (slower, potentially more lucrative)? Do they have health economics data proving cost-effectiveness? Companies treating reimbursement as an afterthought face painful post-approval stalls. Winners engage payers early and have a clear line of sight to sustainable reimbursement within 12-18 months of clearance.

Positioning for 2030

The next five years will separate category winners from expensive science experiments. Here’s what to expect: FDA-cleared non-invasive devices for anxiety and focus disorders (essentially non-pharmaceutical Adderall alternatives), insurance reimbursement expanding well beyond current depression and chronic pain coverage, and consumer brain-optimization devices successfully crossing into medical-grade territory. The winning products won’t look like hospital equipment—they’ll look like AirPods. Discreet, designed for daily use, covered by insurance, and as socially acceptable as wearing prescription glasses or contacts. We’re moving from “medical device you use in a clinic” to “health tool you use at home,” and that shift changes everything about market size, adoption rates, and defensibility.

For investors and entrepreneurs positioning for this wave, track three specific signals. First, monitor clinical trial results for novel indications beyond the traditional neuromodulation targets—each new validated use case expands the addressable market and de-risks the entire category. Second, watch FDA regulatory pathway trends closely: are de novo approvals accelerating as the agency builds institutional knowledge? Are there patterns in which types of mechanisms get faster clearance? Third, pay attention to hardware lifecycle innovations—dissolvable interfaces, nasal delivery systems, and software-first platforms represent potential discontinuities that could reshape competitive dynamics overnight. The next category-defining neurotech company won’t just have great science. They’ll have cracked the commercialization timing, patient adoption curve, and hardware refresh problem simultaneously. That convergence is your signal to move capital aggressively.