At the Cutting Edge

Cecelia Ky-Lan Do
May 5
13 min read

by John Pierre Alkhoury

art by Kristen Chun

Flesh is meant to meet flesh. Every time we hug one another, we feel a warmth that can only belong to another living thing. However, when a patient lies on the operating table, metal replaces flesh. For now, it exists only as a tool, a sterile passage to a successful operation. Whether signified by technology’s increasing involvement in surgery or by looming fears of artificial intelligence replacing the surgeon, metal is becoming more than a tool.

This is particularly pressing in a field like neurosurgery, which operates on a sensitive and integral part of our identity. However, understanding neurosurgery as a general practice requires more pages than one article offers. As a result, it is better to narrow the focus through the lens of a particular condition: Parkinson’s disease (PD). Being one of the most common neurological conditions, PD serves as a backdrop for neurosurgery’s advancement. As neurosurgery integrates more technology, it will bring both unprecedented progress in curing/treating disease and also a threat to our identity, our physical autonomy, and our privacy [1].

Neurosurgery in the Early 20th Century: Lesions, Pallidotomies, and the (not) Seat of Consciousness The history of neurosurgery and PD did not converge at some recent point but was rather intertwined from the very beginning. A disease like PD represented a threat to every facet of livelihood at the time. Understanding what we know about it today gives clarity to this anxiety. PD is a neurological condition characterized by the loss of dopamine within the substantia nigra pars compacta, a section of the midbrain responsible for motor control, reward-seeking, and cognitive function. Consequently, dopamine loss disrupts the motor signalling between brain and body that neurosurgeons have spent decades studying. PD manifests in its characteristic tremor but can also cause bradykinesia (slow movement), depression, and cognitive decline [2].

Mere decades ago, surgeons saw the same symptoms but did not yet have knowledge of the underlying mechanisms, which was reflected in how they treated PD. In the 20th century, neurosurgery mainly involved inflicted lesions, or damage to tissue, intended to disrupt communication in the brain or remove a target structure altogether [3]. One such lesion-based operation was the pallidotomy, in which the globus pallidus internus (GPi) was destroyed. In 1939, neurosurgeon Russel Meyers met a young woman with damaged basal ganglia, a cluster of nuclei in the brain primarily responsible for motor control [4]. Upon observing this damage, Meyers realized that lesions of the basal ganglia did not necessarily entail catastrophic harm or death to the individual. This was especially relevant to his work with PD because of the GPi’s role.

In a healthy brain, the GPi inhibits the thalamus, a section of the brain that receives signals from the cerebellum to fine-tune movement, in order to filter out unwanted motor signals [4]. However, the dopaminergic neuron loss in PD can result in an overactive GPi. As a result, the thalamus becomes unable to distinguish real motor signals from the noise of the commands from the GPi to stop the signalling. This leads to the bradykinesia characteristic of PD [5].

Knowing this, Meyers sought to perform the first basal ganglia surgery. More specifically, he removed the head of the caudate, a part of the basal ganglia that processes sensory & cognitive information to regulate voluntary movement [6]. This procedure was revolutionary beyond PD treatment for both medical and philosophical reasons. The striatum, the part of the basal ganglia containing the caudate, was considered the “seat of consciousness and the soul.” Johns Hopkins neurosurgeon Walter Dandy had miscorrelated damage to the striatum with irreversible comas and deemed it inaccessible [7]. As a result, surgeons were extremely averse to operating on it. Meyer’s operation altered the landscape of neurosurgery because he showed that much more of the brain could be operated on than was thought before.

Nonetheless, Meyer’s surgery still posed a risk, and neurosurgeons continued to seek techniques that would reduce danger to the patient, which led to the development of the stereotactic technique [8]. Before, “open” brain surgery was limited by its imprecision and risk of damage. To address this, surgeons developed a device attached to the skull that divided the brain into a 3D map. The stereotactic technique involved using Cartesian structures to pinpoint brain regions and guiding a thin electrode towards them, and bombarding the region of interest with heat until it was destroyed. In its initial stages, this technique demanded pneumoencephalography, an infamously painful process in which air is pumped into the skull for better X-ray visibility, and would highlight the need for better methods of imaging the brain [9].

Despite its progress, neurosurgery had been and remained a liability. Doctors avoided it because the risk of infection outweighed the benefits. In 1951, Lars Leksell set out to tackle this issue, and he began by taking the existing stereotactic technique and incorporating a burr hole, a small hole drilled into the skull to access the brain [10]. Still dissatisfied, he developed the gamma knife, an incision-less technique using gamma rays that converge at a focal point to destroy tissue by targeted radiation [10]. Leksell’s dedication to minimally invasive surgery now casts neurosurgery in a new light, one that promises safety and addresses previously untreated conditions.

Leksell’s pallidotomy incited a renaissance. In 1992, Leksell’s former student Laitinen, brought it back to light amidst the therapeutic failure of L-DOPA, which had been the preferred, more accessible, and less invasive option for the treatment of PD [12]. L-DOPA was a crucial drug for the treatment of PD, as it is a dopamine precursor that easily crosses the barrier between the blood and the brain and subsequently converts into dopamine, the main deficiency in PD. However, it was causing long-term complications and difficulty in controlling voluntary movements. These complications made it unreliable as a long-term, single therapy [12]. When Laitinen reinstated Leksell’s pallidotomy, he essentially made no changes to Leksell’s original operation, other than a few refinements like using MRI (magnetic resonance imaging) instead of pneumoencephalography or targeting the posteromedial globus pallidus instead of the GPi due to a better understanding of basal ganglia anatomy [13]. In an ironic turn of events, Laitinen found that the pallidotomy effectively treated levodopa-induced dyskinesia, a side-effect of the same treatment that had phased out the pallidotomy in the first place [11].

Deep Brain Stimulation: a Foundation of Modern Neurosurgery

The pallidotomy represented an important leap in our understanding of neurosurgery as a practice and a science. However, it remains limited in that it's irreversible. Once you destroy tissue, you cannot get it back. Rapid technological advancement now allows us to avoid destroying it in the first place. It involves a basic principle of modern neurosurgery: modulating the brain circuit, or changing the activity and connectivity of neurons. [14].

One of the most prominent examples is Deep Brain Stimulation (DBS), a technique pioneered by a single observation that would change neurosurgery forever. In 1991, Alim Benabid, a neurosurgeon at the French University of Grenoble, was performing a thalamotomy, which is essentially a lesion of the thalamus, to treat the tremors in a PD patient. At the time, neurosurgeons located parts of the brain using electrical signals, since each region of the brain had a unique frequency, before lesioning the tissue. While performing this otherwise completely mundane task, he noticed that as he increased the frequency of this electrical signal, the tremor in the patient got better [15]. Benabid would go on to formally apply DBS for the first time to target the ventral intermediate nucleus in the thalamus. This region is also the origin of synchronized neuron “bursts” that manifest in tremors in individuals with PD [16]. Like in many other neurosurgeries, the patient was awake, since the brain does not have pain receptors, and their movement gives feedback to the surgeon on the success of the stimulation or any possible side effects as they arise [17]. The results were groundbreaking, bringing the same level of relief that would have previously required lesions [15].

Since then, DBS has drastically changed to adapt to the growing field of neurosurgery and to our growing understanding of the brain. Today, DBS essentially involves a long-term implantation of a system including electrodes in a specific configuration in the brain. This configuration is adjusted based on the target brain region and is intended to optimally deliver electrical stimulation [18]. The implanted electrodes are essentially delivering high-frequency electrical pulses of 130+ Hertz that override the abnormal signal in the target neuron. Compared to the normal firing rate of the brain of 13-35 Hertz, this new pulse is much stronger and will override it and activate the axon, a key component of transmitting electrical signals between neurons, which then allows this amplified signal to spread through a larger brain circuit [18].

Think of a static-filled, incoherent broadcasting signal being sent from the “radio tower” that is the GPi to the thalamus. As discussed before, pallidotomy essentially annihilates that tower and prevents the signal from being sent in the first place. DBS, however, acts as a second radio tower that intercepts the original signal and overwhelms it with a stronger signal that interrupts the faulty one of the GPi to the thalamus.

Alongside the electrodes, the setup of DBS includes a pulse generator, as well as a patient and clinician programmer that allows them to optimize the settings on it [19]. The electrodes allow clinicians to identify and locate local field potentials (LFP), which encapsulate the summed electrical activity of neurons near that particular electrode tip [21]. Clinicians can use LFPs in tandem with observed clinical response to optimize therapy [22].

Surgeons and researchers can actually observe the effects of DBS happening in real time. New adaptive DBS (aDBS) technology is able to simultaneously stimulate the target region while also recording LFP signals. As the electrodes deliver electrical pulses, they record a reduction in beta signals. This is important because the suppression of beta signals can be correlated with a restoration of motor function [19]. The adaptability of the DBS system through LFPs can be used to find the ideal settings to bring the optimal beta suppression.

Technology always threatens to override what is in place, to make conventions obsolete. What distinguishes DBS is that the core concept of modulation is so fundamental to brain intervention, meaning technology can only expand it. This is exemplified by the recent invention of rechargeable internal pulse generators (IPGs), a device that allows the recharging of DBS electrodes remotely, without the need for an incision [24]. Using this device addresses many drawbacks of non-rechargeable electrodes: additional costs, additional surgeries, and risk of infection [23].

Brain-Computer Interfaces as a Threat to the Self

Neurosurgery has advanced down a gradient: Pallidotomy was completely performed by humans, whereas DBS has increasingly leveraged technology to improve results and assist in an otherwise human-facilitated process. So what is at the other end of this scale? Imagine that this same flesh is now completely detached from something familiar. The metal instrument no longer acts as a medium, but as the operator itself. This is what the advent of artificial intelligence and technological autonomy seems to be striving towards. However, the reality is much more nuanced and holds the key to major medical advancements, serious ethical risks, and a challenge to what it fundamentally means to be human.

The primary example of this future is the brain-computer interface (BCI). This is an operation involving the implantation of a tiny chip in the brain that can both receive and send signals to the brain. Researchers insert a stentrode, a very small mesh tube typically used for clearing arteries, through the femoral vein, where it connects the brain to a device in the chest called the implantable receiver transmitter unit (IRTU), which essentially reads this signal and turns it into data to be sent to an external device (like a phone) via Bluetooth [25]. This signal is then translated by the external device into an executable, whilst the system simultaneously sends these results back to the user. Essentially, the BCI is reading your imagination through electrical signals, then translating them into the language necessary to actually do the things you think about [26].

When it comes to a disease like PD, the implications are obvious: this technology is overcoming the major motor challenge of PD. In fact, researchers are currently working on a helmet-shaped BCI that would monitor the brain for erratic electrical signals in the basal ganglia characteristic of PD. The BCI would be able to determine the need for treatment and calculate the exact frequency needed to counteract the malfunctioning units. While it is not as precise or permanent as DBS, this technology does not require surgery and would thus be less invasive [27].

However, the use of BCIs does not stop at medicine. Defense contracts are currently being concentrated in neurotechnology that would give soldiers enhanced durability, cognition, and motor function. These grants or contracts are usually issued under the guise of therapeutic research, mostly for traumatic brain injury, but their discoveries are inherently dual-use. Beyond the ethical concern of engineering supersoldiers, the innate use of technology in such sensitive ways involves saving and processing neural data unique to an individual. The question then becomes, who owns the data? In most cases, it is likely going to be the military itself. Does that mean they own the individuals, too?

The object of ownership is not some vague code corresponding to the individual; it is neural data: the scientific essence of how we think. It is natural to question how we retain selfhood or free will, but what does that actually mean here? Derek Parfit’s Reasons and Persons offers a useful definition of identity that we can go off of. As he defines it, identity is not innate. That is, it is simply a matter of continuity. If I am able to remember my family’s name or if I am able to live a life with a coherent, pervading sense of purpose, that becomes a hallmark of my identity. In a situation where BCIs are used for PD or a similar disease, identity is actually solidified as the individual is now able to act on their thoughts: there is continuity between thought and action. By the same process, that same continuity can be severed. Imagine instead a scenario where a timid man flies a plane overhead. He thinks of all the lives he’ll take and shivers at the thought of the annihilation he’ll cause. His eyes fixate on the big, bad button, but he has no room to hesitate. At the slightest hint of insubordination, somewhere a toggle will turn on, and what was once that man will wreak havoc. Is there continuity there?

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