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OPINION: How Simons Foundation and Allen Institute Lost at Neuroscience Research

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By David Stephen

Nobody knows how the brain works is a neuroscientific imprimatur for research misdirection. What does neuroscience want? How the brain works. What does neuroscience need? An explanation of brain states to delineate several common and troubling brain disorders. Is it possible to do this without absolutely knowing how the brain works? Maybe. What does neuroscience have? Tons of evidence in brain anatomy and physiology. What can neuroscience do? Extricate components from evidence, postulate their mechanisms and explain how a mental state is different from another, defining a new description for mental disorders—minimizing the present global opacity. But what has neuroscience done? More of the same—or being unable to leap—sticking with neurons, identified more than a hundred and thirty years ago. Neuroscience has amassed a ton of data. But what can neuroscience use? What parts of the data can be used to explain brain states? Now, neuroscience research is undergoing serious funding cuts. Neuroscience never achieved deterrent status, against cuts, for the lack of major public results. Psychiatry remains a key failure of neuroscience. Also, with AI, neuroscience has no concept [within evidence] of how human intelligence works. No neuroscience to evaluate or develop benchmarks for AI based on human intelligence, to shape AI safety and alignment. Neuroscience does not just feel absent at the front, it seems weak, irrelevant and disconnected from reality.

All research is not progress. This is what neuroscience has shown. All studies do not contribute to knowledge. There are several published neuroscientific papers that have no relevance to solutions. For some, it may be unintentional because the mission is to find out how the brain works, but that may not be necessary for what can be used to explain mental states.

Whatever a depression is can be ascribed as a mental state, from when there is no depression. Or, a type of depression from another type are different mental states. What in the brain can be used as a baseline to say this [or these], act as such in this state and otherwise in that state?

The total details of how the brain does what it does may not be clear, but the mechanisms of particular components for brain states could be used to explain conditions, in a way to at least know what is happening within, from rigorous evidence on sound neuroscience research. This, extended across disorders and several brain states, would have been useful in shaping answers as the world grapples with changes, emerging trends and challenges. This would exceed neuroimaging [observed changes] to all possible conditions, not a few.

The one job of any major neuroscience institute is to find answers for mental states. This is tad different from how the brain works. Criticisms for neuroscience are common, like those for neuroimaging, neurogenetics, psychiatry and so forth. However, both the critics and the criticized hardly present something, within the cranium that can be used, to define brain states.

There is the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision [DSM-5-TR], which can be described as more of a psychological dictionary than a neuroscientific literature. It should be appalling that at this point, in the trajectory of natural philosophy, it is not even possible to say that these components move this way in an anxiety disorder and not in another.

If an institute is focused on brain atlases, how does it show brain states for respective disorders, with significance for contemporaneous care? If an institute is focused on others, what does it say about brain states?

Why are brain states important? Because they can tell of what the brain is doing and how [by the isolated components], for several answers that are sought globally in mental health, addictions, intelligence, learning, disorders, consciousness and so forth. The components would be cardinal to everything else, at least for applications, presently.

Now, say the objective is to show brain states, what are the options in the brain, for components? The likeliest are neurons, given robust evidence. Astrocytes and others contribute, but neurons would have to be ruled out, by any other component, to be credible.

So, how do neurons work? It is established that they are in clusters and have signals [electrical and chemical]. Therefore, the options to model neurons would include in clusters and then, by their signals. How can this be shown, for every condition in the DSM-5-TR? How can that be approached?

This is where theoretical neuroscience wields might.

Theoretical Neuroscience 

Why do neurons communicate? This question means that why would neurons communicate to each other for the purpose of being neurons? What is the need or survival necessity of one neuron communicating with another neuron? What are they saying to each other that is relevant to what they are? Neurons are cells, why would they need to communicate in such an elaborate manner, but several other cell types do not, yet thrive?

What can be postulated is that neurons do not communicate to each other, using signals, at least for the purpose of being neurons. This indicates that neurons are structures for signals to do what they do, but signals are not for the purpose of neurons, to communicate. This rules out the assumption that signals are for communication or that some signals are transmitters.

So, electrical and chemical signals can be described as the basis of functions, but they use neurons as the runway to taxi across. Simply, signals cannot move without neurons, but signals are of objectives—external to neurons—like jetliners are to runways.

Signals [or impulses] can now be inferred to be inadequate to describe them. Instead there can be called configurators: electrical and chemical configurators. Simply, all functions of the brain are configured electrochemically. Electrical and chemical configurators interact, in sets, in clusters of neurons, to specify respective functions. [They can be collectively referred to as neuroconfigurators]. The properties of neuroconfigurators at the time of the interactions determine the extents to which they interact. This interaction is electrical configurators, striking at chemical configurators, such that the formation [or architecture, representation, event, assembly, or construct] that defines a function is obtainable in that instance. This detours from the conclusion that electrical signals are triggering chemical signals. Chemical configurators have an almost ready configuration for which electrical signals strike to fit or complete for the function. [This is something that neuroscience can use now, to make progress].

There are several possible attributes of electrical configurators and those of chemical configurators. These attributes can be used to explain every mental state. Splits of electrical configurators are postulated to be some going ahead of others in a set to interact [or fit] with chemical configurators, as they have done before, to provide initial interpretations. If it matches, the incoming one does the same, and if not, the incoming one goes in another direction, correcting the error. This explains the labels predictive coding, processing and prediction error. It is [scientifically] based on saltatory conduction where electrical signals travel faster in myelinated axons. It is plausible that some go ahead, conceptually. Splits can explain intelligence, aspects of attention problems, intrusive thoughts and so forth. Several attributes can explain other states. 

What Can Neuroscience Use Now?

Nobody knows how the brain works is a refrain of the confused, who should have nothing to do with science. The assumption that it is only when how the brain works is known that it would be possible to answer unknowns about the brain are the machinations of dawdlers.

What can neuroscience use amid evidence? If there is a mood disorder, what is different for configurators from when there isn’t? This answer is ready. What else is possible to model? Genes? The human genome is already mapped. During neural functions, genes are expressed, but can genes be modeled for the human mind? What can neuroscience use is a question for progress. Mapping the brain is fine, if it is immediately possible to use it to explain mental state differences. Nobody knows how the brain works is a conclusion from those who are not in science for progress.

There is a recent [28 May 2025] report in The TransmitterMultisite connectome teams lose federal funding as result of Harvard cuts  stating that, “The Trump administration has canceled two grants—among the slew of U.S. federal grants terminated at Harvard University in recent months—that together provided more than $4 million in funding to map more of the mouse brain than ever before. The grants were awarded by the National Institutes of Health’s BRAIN Initiative Connectivity Across Scales program, which launched in 2023 to scale up connectomic capabilities. They funded two Harvard-led teams to develop advanced electron microscopy tools to image each cell and synaptic connection within 10 cubic millimeters of mouse brain tissue—10 times the volume previously studied at that resolution.”

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