‘Electronic adderall’: A breakthrough in brain science could unlock new possibilities

In an article published alongside the new paper, neuroscientists Noah S. Philip and Kevin S. LaBar write that the amygdala “is one of the core neural circuits associated with depression, anxiety, and posttraumatic stress disorder.” Drugs and other therapies for those conditions often target the small, almond-shaped part of the brain. Philip and LaBar say the new study is important because it “elegantly maps out how we might improve amygdala targeting,” with an eye to developing therapies for people who doctors can’t help with the tools that are currently available.

Neuroscientist James Giordano tells IE that he’s particularly interested in the work for two reasons. Number one, the technology involves “wearable forms of brain stimulation versus implantables.” And number two, these experiments point to a wide array of potential use cases. “This method of superficial stimulation can conduct specific forms of current and change the relative activity of deeper layers of the brain, such as those that are involved in activation, arousal, and passivity,” he says. That’s a big deal because some of those deeper layers are involved in “our underlying emotions and behaviors [and] may also be involved in certain psychiatric and neurological conditions.”

Interesting Engineering sat down with Professor Giordano to talk about this study and what it could mean for the future of neuroscience.

This interview has been edited for length and clarity.

Interesting Engineering: What have these scientists done?

James Giordano: These scientists are employing a form of transcranial stimulation that utilizes a low-level magnetic pulse. This is called transcranial magnetic stimulation. Characteristically, this form of stimulation only engages and modulates the uppermost or outermost layers of the brain surface, referred to as the cortical mantle.

What is so interesting about this particular study is that direct activation of a key area of the brain’s cortex, the prefrontal cortex, seems to directly engage a network that causes a change in the activity of a much deeper brain structure called the amygdala, which is part of the limbic system, which is involved in the regulation of arousal states, passivity, aggressiveness, behavior, lack activation, and focus.

The interesting component of this study is that by utilizing a transcranial form of stimulation, they’re able to evoke an effect in deeper brain structures in ways that are valid, viable, reproducible, apparently reliable, and therefore valuable.

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IE: So, this method offers access to structures that were previously out of reach for transcranial stimulation?

Giordano: Correct. In the past, one of the concerns with transcranial forms of stimulation — whether it was transcranial magnetic stimulation or transcranial electrical stimulation — was what is referred to as the spatial limitation.

In other words, the available current — either electrical or magnetic — will only penetrate through the scalp, the musculature, the skull, and the protective membranes of the brain deep enough to affect the outermost layer of the brain, the cortical layer. And while that cortical layer certainly is involved in a variety of higher cognitive and behavioral and motor functions, it’s important to understand that the brain operates as a networked system. So, the cortex does not function independently but rather functions as a system with other nodes and networks of the brain that lie deeper, deeper within.

Therefore, the limitation of many of these transcranial neuromodulatory approaches was their constrained ability to directly, reproducibly, and reliably affect deeper brain structures that are part of those functional networks. In other words, the current would diffuse to such an extent that you were not getting the particularity and specificity of effect at key targets deeper within the brain that would therefore modulate the activities of key nodes and networks that are involved in various thoughts, emotions, behaviors, etc.

What this study demonstrates is that by directly stimulating an area of the prefrontal cortex, utilizing very precise and particular parameters, we can activate a direct pathway, a direct network link to the amygdala, and in this way, modulate the functional activity of the amygdala in direct and directional ways.

IE: The amygdala comes up a lot in conversations about the brain. What is that region of the brain responsible for?

Giordano: I think it’s important to recognize that the amygdala is not a single structure, but rather a mosaic of substructures that have very diverse connections within the various nodes and networks of the brain. There are a lot of inputs to the various amygdaloid nuclei and various outputs from the amygdaloid nuclei.

So, the amygdala can be seen as both a relay and a sub-control node in those brain networks that function in arousal, interest, and behavioral activation and that modulate certain aspects of passivity and aggression. So, the ability to modulate amygdaloid activity directly by stimulating a very superficial area of the cortex transcranially allows an increased capability to modify the activity of certain areas of the amygdala in what may be directable ways.

IE: What could the ability to affect those processes look like in practical terms?

Giordano: The most direct, the most explicit way to think about this is that by modulating the prefrontal cortex utilizing transcranial magnetic stimulation, we can now identify a direct pathway to modulate or modify the activity of the amygdala.

Now, it remains to be seen how specific amygdala modulation is. In other words, can we fine-tune the modulation — that is, fine-tune the activity of the amygdala — by fine-tuning the input to the cortex? But this is an important first step that affords, if you will, a vector and nexus to access the amygdala. And in this way, perhaps affect amygdala functions that are as involved or contributory to various cognitive states, emotional states, and behavioral outputs.

IE: What could that mean for the future of therapeutic devices?

Giordano: This may open the door to particular therapeutic interventions. For example, we may be able to use these types of transcranial magnetic — or even, perhaps, transcranial electrical stimulation — to be able to target key cortical areas that we will subsequently identify as having a direct interface with deeper brain structures that are part of the larger node and network configurations of the brain that are involved in a variety of pathological conditions: anxiety disorders, depressive disorders, perhaps even forms of psychosis. This provides yet another tool, a potential tool in the therapeutic armamentarium. 

Over and above that, it may also provide yet another pathway, another viable method for treating those cases of anxiety, depression, trauma, stress disorder, manifestations of head injury, and/or stroke that have been relatively resistant to other forms of treatments. 

But here, we must go one step further: the ability to target the cortex to affect the function of the amygdala and those “downstream” nodes and networks that are involved in the amygdala and limbic system. Participation in cognitive, emotive, and behavioral functions and outputs can also be viewed in more of a preventive-therapeutic or preventive-interventional way.

In other words, there is an aspect of preventive neuropsychiatry here. The idea is “Could we target areas of the cortex to affect the amygdala (and perhaps subsequently other deeper cerebral structures) to then modify patterns of cognitive responses, emotional responses and reactions, decisions, and behaviors?”

IE: If this technology can be used as a form of preventative medicine, could it also be used to enhance a person’s abilities?

Giordano: Clearly, not only might this have value in certain forms of preventive medicine, but might also extend that construct of prevention to include things such as optimizing certain patterns of thought, feeling, or behavior through increasing or decreasing the relative functional contribution of these brain nodes and networks in those ways that can change the way we think, the way we feel and the way we act.

In this situation, we see the possible utility in occupational optimization and enablement across a range of occupations. As well, we can see particular wellness and lifestyle applications.

And I think it is also important to recognize that although this particular study is oriented toward parameters of transcranial magnetic stimulation that are most likely to be utilized in clinical settings, the demonstrated ability to target the cortex in specific ways that can then modulate deeper brain structures might also be a value to direct to consumer, and even do-it-yourself approaches to transcranial or electrical stimulation that can then ‘opportunize’ these identified parameters and pathways to best effect.

IE: What could a direct-to-consumer version of this technology look like?

Giordano: It’s not so much a question of what we would expect to see. There is already a viable international direct-to-consumer neural modulation market. The vast majority of these devices utilize low-output transcranial electrical stimulation. At this time transcranial magnetic stimulation remains the province of clinical and research interventions, these magnetic devices are not available as direct-to-consumer, yet.

But a study such as this demonstrates a viable cortical target and the parameters for stimulating that target to be able to then engage a deeper cerebral structure, the amygdala. And although the method used was transcranial magnetic stimulation, I think it would be certainly of interest to then also evaluate whether, and under what conditions and through what parameters, transcranial electrical stimulation might also engage a similar if not identical mechanistic effect.

IE: Are you talking about an electronic Adderall?

Giordano: Yes. Much of that work has already been done. There’s already been considerable work that has addressed and focused upon the capabilities and limitations of various forms and patterns of transcranial electrical stimulation to modify the node-network activity of the brain to in some way affect patterns of thought, emotion, and also behavioral performance. In other words, the ability for attentiveness, vigilance, avoiding fatigue, increased performance in a variety of mental tasks or physical tasks, increasing coordination, decreasing reaction time, etc.

We already know that there is at least a potential capability for various types of transcranial electrical, and, of course, magnetic stimulation to do this. And so, as a result, it would be a logical extension that those approaches that are used direct-to-consumer that employ low-output transcranial electrical stimulation might seek to access those same targets, but with much lower currents that are used clinically, so as to be able to generate at least similar if not identical effects.

IE: What does this new research tell us about the state of neuroscience and the future of technologies that interact directly with the brain?

Giordano: I think it reflects the momentum and trajectory of the field in general. For at least the past decade, the identified limitation — if not constraint — of transcranial magnetic and transcranial electrical stimulation has been the relative superficiality of the modulatory effect. In other words, we know that the direct effects have been, up to this point, apparently limited to the outermost layers of the brain.

Our hope was that by affecting those layers, you might then have a “ripple effect” downstream or upstream in other brain areas that would therefore be of value to certain types of interventions and therapeutics. Here, we have a study that demonstrates that directly. It not only demonstrates that it is possible but also provides parameters and patterns by which this stimulation can reproducibly evoke such effects.

What they’ve done is they’ve opened the door for the next series of both experiments and potential translations into the clinical and perhaps para-clinical realm.