Neuroscience Trend Forecasters

As 2022 draws to a close, the SNL Trend Forecasters have agreed to divulge their predictions for the most — and the least — exciting research fads for the New Year.

The Neurocritic: How do you guys predict today's most popular neuroscience trends? 

Trend Forecasters: Oh, well we have 4,000 computers, they're all big they all make charts and they beep LOUD.

TN: Let's get started!

In: posterior cingulate cortex

Hey Posterior Cingulate — we see you! You're fresh, you're mysterious, you're misunderstood. But we know you exist far beyond the default fashion mode. The new tripartite view proposes...

...that the broader PCC region contains three major subregions — the dorsal PCC, ventral PCC and retrosplenial cortex — that respectively support the integration of executive, mnemonic and spatial processing systems. This tripartite subregional view reconciles inconsistencies in prior unitary theories of PCC function and offers promising new avenues for progress.

Foster et al. (2022)

 

Out: anterior cingulate cortex

Get behind me, you tired brain region. Think you can do everything? Well the list of your supposed functions is wildly implausible. We've looked at PubMed and found mental fatigue, prediction of non-violent felony rearrest in women, amyloid-β-related increases in empathic concern, experimental odontogenic pain, gravitational perception, chronic itch, RDoC social constructs, and modulation of synaptic plasticity in exercise interventions for post-stroke pain.

 

 

In: claustrum

Claustrum, we're in love with you and it's not only because of the holidays. You're connected to everything and everyone.

Santa Claustrum

 

Initial speculation claimed you were responsible for consciousness (Crick & Koch, 2015), but subsequent studies in human epilepsy patients showed no alterations in consciousness with unilateral or bilateral electrical stimulation (Bickel & Parvizi, 2019). Instead, you're critical for cognitive control. The fresh functional model is called network instantiation in cognitive control (Madden et al., 2022).

Researchers at the University of Maryland School of Medicine ... now posit that Crick may have been incorrect: They developed a new theory — built on data — that the claustrum behaves more like a high-speed internet router, taking in executive commands from “boss” areas of the brain’s cortex that forms complex thoughts to generate “networks” in the cortex.

 

The most exciting recent work (in mice) has shown that claustro-cortical circuits are organized into functional modules (McBride et al., 2022)...

• Frontal areas are more inhibited, while posterior areas are more excited
• Upper layers are more excited, while deeper layers are more inhibited 

...and connect cortical network motifs (Qadir et al., 2022)

• Frontal cortices are synaptically connected to posterior cortices through claustrum
• Two claustrum projection neuron subtypes support trans-claustral circuits
• Trans-claustral circuits resemble a frontoposterior cortical network motif

Out: reinforcement learning and mesolimbic dopamine

 

Your superiority complex is tired, temporal difference error. We know you consider yourself the “biggest success story in computational neuroscience.” But every week a new finding prompts a mathematical tweak and an update of your impenetrable model.

‘teaching signal’ ‘learning model’ ‘model-free’ ‘cached values’ ‘ramps’ ‘bumps’ ‘belief states’ ‘vector RPE’ ‘DA dip of disappointment’

Go to bed, TD. You have to get up early. For a flight TO HELL!

 
 

In: HippoCamera

You spent years developing your brilliant smartphone app that improves memory in older adults, drawing on the basic science of hippocampal replay (e.g., speeding up 24 sec video clips by 3×).

Martin et al. (2022)

Autobiographical memory cues are created by recording an 8 sec audio cue to accompany a 24 sec video recording of a daily event, which is rated for significance. In your recent paper, fMRI scanning occurred after a two week or 10 week intervention. In comparison to baseline (non-reviewed) events, repeated replay of autobiographical memory cues enhanced episodic recollection and increased the differentiation of activity patterns in the hippocampus in older adults (Martin et al., 2022). Bravo, HippoCamera! Take a bow Barense, Honey, and Martin!

 

Out: Brain Behavior Quantification and Synchronization (BBQS)

BRAIN Initiative,² you're so far behind the times that YOU ARE OUT. Didn't you get the memo that Neuroscience Needs Behavior back in 2017? Or read the review on Quantifying Behavior [in worms and flies] to Solve Sensorimotor Transformations, which covered papers going back to 2008 and earlier? The patented HippoCamera was developed behind your back with funding from the Canadian government and private foundations. And the clever use of remote memories recorded by the 1 Second Everyday app (Bainbridge & Baker, 2022) was funded by NIH Intramural funds. The fact that you waited until 2023 to fully announce BBQS projects in humans and non-humans speaks volumes to the value you place on understanding behavior. GO TO BED!

In: neuropeptide maps of human prefrontal cortex

One recent uptick in human brain complexity was revealed from analysis of postmortem tissue in 17 subregions of prefrontal cortex (PFC). Zhong and colleagues (2022) found that 60 neuropeptides and 60 neuropeptide receptors are expressed in at least one of the PFC subregions. The data are freely available and incorporated into the Human Protein Atlas — which has about 5 million individual web pages. The authors encouraged efforts to explore these neuropeptide receptors as potential targets for drug development in neurology and psychiatry, which has been neglected by pharmaceutical companies in recent years.


Out: functional neuroimaging in psychiatry 

You're a failure, psychiatric neuroimaging!! Nour, Liu, and Dolan wrote a 20 page paper detailing your many shortcomings and faults. For instance, explanatory aspirations in resting-state studies are laughable:

“...bridging a gap between descriptive accounts of neural data and psychopathology requires a model that relates network properties ... to specific computational processes. Absent such a model, we argue that further large-scale data collection will be insufficient to yield breakthroughs in probing a fundamental understanding of cognition or psychiatric illness.”

 We needn't go further than listing other direct quotes from their paper:

• “...functional neuroimaging plays no role in clinical decision making.”

• “While the computational psychiatry literature has identified associations between model-informed neural activity and psychiatric variables, effective clinical translation has been lacking.” 
  

• “Casting a cold eye on the psychiatric neuroimaging literature invites a conclusion that despite 30 years of intense research and considerable technological advances, this enterprise has not delivered a neurobiological account (i.e., a mechanistic explanation) for any psychiatric disorder, nor has it provided a credible imaging-based biomarker of clinical utility.”

 

Ouch! You've done nothing for us, psychiatric neuroimaging. You haven't even embraced the correct level of analysis (i.e. manifolds). GO TO BED!

[In again: manifolds]

In: Synchron

Synchron, all the other billionaires are backing you, to the tune of $75 million! In a remarkable advance towards greater independence for paralyzed persons, the Stentrode, an endovascular brain computer interface (BCI), received Breakthrough Device designation from the FDA in August 2021. 

 

Stentrode™ (endovascular implant)

 

The minimally invasive BCI was developed with funding from DARPA (among others), and initial results from sheep were reported in Nature Biotechnology (Oxley et al., 2016). Its placement in the superior sagittal sinus (via the jugular vein) produces high-fidelity recordings from motor cortex without the need for risky cranial surgery. The brain.io™ motor neuroprosthesis transmits cortical signals from the Stentrode to a receiver implanted in the chest, and a machine learning algorithm decodes the neural activity and translates the signals to digital commands.

 

Oxley et al. (2021)

 

Two paralyzed participants with ALS achieved typing click selection accuracy of 93% within 86 days and 71 days of machine-learning supervised training (Oxley et al., 2021). Typing rate was relatively slow (13.8 and 20.1 correct characters per minute, respectively) in comparison to some other BCI cases, but those all entailed craniotomies.¹ Nonetheless, both participants were able to text, e-mail, browse the internet, shop online, and manage finances (Oxley et al., 2021). The COMMAND Early Feasibility Study is an ongoing clinical trial of the Synchron device that will enroll six patients.

In: Mastodon

Because everyone needs an alternative social media site.

Out: Neuralink

Neuralink, you're out! So go back to hell. Stop flaunting your wealth, Neuralink. We all know you have to die for your hubris. You think you'll have FDA approval in six months, but that's what you said in 2019. Many of your claims are sheer fantasy, like you'll be able to cure everything from addiction to strokes.

from Neuralink Progress Update, Summer 2020

 

Your Fall 2022 update was more technically impressive, but still claimed your device will be able to restore vision — prompting eminent vision scientist Brian Wandell to call out this BS:

He [Musk] specifically said this would work for the congenitally blind because they still have a visual cortex.

Two hundred years of experiments on site restoration in human, and many fundamental cellular experiments of visual development and the limits of adult plasticity, show this is false.

Potential ethical concerns have been noted by UPenn Prof Anna Wexler. Finally, you're under investigation for possible animal welfare violations. Neuralink, if I see you in the street I'll stab you in the face.

 

What are your favorite neuroscience trends for 2023? What should be kicked to the curb?

 

Footnotes

¹ Most notable was BrainGate participant T5, with an astonishing 90 characters per minute. Two microelectrode arrays were implanted in the hand area of the precentral gyrus, and neural activity produced by imagined handwriting was decoded and translated into text in real time (Willett et al., 2021).

² hat tip to Drug Monkey.

References

Bainbridge, W. A., & Baker, C. I. (2022). Multidimensional memory topography in the medial parietal cortex identified from neuroimaging of thousands of daily memory videos. Nature Communications, 13(1), 1-16.

Bickel, S., & Parvizi, J. (2019). Electrical stimulation of the human claustrum. Epilepsy & Behavior, 97, 296-303.

Calhoun, A. J., & Murthy, M. (2017). Quantifying behavior to solve sensorimotor transformations: advances from worms and flies. Current opinion in neurobiology, 46, 90-98.

Crick, F. C., & Koch, C. (2005). What is the function of the claustrum?. Philosophical Transactions of the Royal Society B: Biological Sciences, 360(1458), 1271-1279.

Foster, B. L., Koslov, S. R., Aponik-Gremillion, L., Monko, M. E., Hayden, B. Y., & Heilbronner, S. R. (2022). A tripartite view of the posterior cingulate cortex. Nature Reviews Neuroscience, 01 Dec 2022.

Han, J. J. (2021). Synchron receives FDA approval to begin early feasibility study of their endovascular, brain‐computer interface device. Artificial Organs, 45, 1134-1135.

Krakauer, J. W., Ghazanfar, A. A., Gomez-Marin, A., MacIver, M. A., & Poeppel, D. (2017). Neuroscience needs behavior: correcting a reductionist bias. Neuron, 93(3), 480-490. 

Madden, M. B., Stewart, B. W., White, M. G., Krimmel, S. R., Qadir, H., Barrett, F. S., ... & Mathur, B. N. (2022). A role for the claustrum in cognitive control. Trends in Cognitive Sciences.

Martin, C. B., Hong, B., Newsome, R. N., Savel, K., Meade, M. E., Xia, A., ... & Barense, M. D. (2022). A smartphone intervention that enhances real-world memory and promotes differentiation of hippocampal activity in older adults. Proceedings of the National Academy of Sciences, 119(51), e2214285119.

McBride, E. G., Gandhi, S. R., Kuyat, J. R., Ollerenshaw, D. R., Arkhipov, A., Koch, C., & Olsen, S. R. (2022). Influence of claustrum on cortex varies by area, layer, and cell type. Neuron (Nov 4).

Nour, M. M., Liu, Y., & Dolan, R. J. (2022). Functional neuroimaging in psychiatry and the case for failing better. Neuron, 110(16), 2524-2544.

Oxley, T. J., Yoo, P. E., Rind, G. S., Ronayne, S. M., Lee, C. S., Bird, C., ... & Opie, N. L. (2021). Motor neuroprosthesis implanted with neurointerventional surgery improves capacity for activities of daily living tasks in severe paralysis: first in-human experience. Journal of neurointerventional surgery, 13(2), 102-108.

Qadir, H., Stewart, B. W., VanRyzin, J. W., Wu, Q., Chen, S., Seminowicz, D. A., & Mathur, B. N. (2022). The mouse claustrum synaptically connects cortical network motifs. Cell Reports, 41(12), 111860.

Zhong, W., Barde, S., Mitsios, N., Adori, C., Oksvold, P., Feilitzen, K. V., ... & Hökfelt, T. (2022). The neuropeptide landscape of human prefrontal cortex. Proceedings of the National Academy of Sciences, 119(33), e2123146119.