Christos Constantinidis
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cconstan.bsky.social
Christos Constantinidis
@cconstan.bsky.social
Professor of Biomedical Engineering and Neuroscience. Neural basis of cognition, cognitive development, deep brain stimulation.

https://lab.vanderbilt.edu/constantinidis-lab/home/
Our results provide a critical confirmation of the Standard Model of Working memory.

Many thanks to my students who did these challenging experiments, and particularly the co-first authors, Rana Mozumder and Zhengyang Wang (end)
December 29, 2025 at 2:41 PM
Had persistent activity truly been an artifact, the existence of gaps and off-states would have greatly degraded the performance of simultaneous populations during the delay period (14/10)
December 29, 2025 at 2:41 PM
Furthermore, this decrease was present in all task epochs, including the stimulus presentation and response periods, rather than the delay period alone. We speculate that off states are caused by variations in neuromodulatory tone (13/10)
December 29, 2025 at 2:41 PM
When we calculated decoding accuracy of populations of neurons sampled from different trials (or “pseudo-populations”, commonly used in neurophysiology) and tested them with neurons recorded simultaneously, only a subtle performance decrease was evident (12/10)
December 29, 2025 at 2:41 PM
However, we also show that such off-states are relative decreases in firing rate rather than absolute “gaps” in spiking. Activity across the network continued to maintain information about the stimulus being remembered even during off states (11/10)
December 29, 2025 at 2:41 PM
A recent study has revealed off-states in the activity of prefrontal neurons during working memory (nature.com/articles/s41...) . We replicated this finding and additionally show that such off-states are coordinated across the prefrontal and posterior parietal cortex (10/10)
Intermittent rate coding and cue-specific ensembles support working memory - Nature
By recording large populations of neurons in behaving monkeys using newly developed silicon probes, we show that intermittent periods of memorandum-specific spiking coexist with synaptic mechanis...
nature.com
December 29, 2025 at 2:41 PM
Such persistence is only evident for stimuli that are optimal for the recording site. Picking a suboptimal stimulus will not produce such asynchronously elevated firing, which is not an argument that persistent activity is not present somewhere else in the PFC (9/10)
December 29, 2025 at 2:41 PM
In this article we document “The Asynchronous State” of Working Memory. In single trials, individual neurons may not exhibit persistent activity, however populations of ~100 neurons are sufficient to generate activity elevated above the baseline for the entire delay period (8/10)
December 29, 2025 at 2:41 PM
However empirical validation was lacking until now.

Enter modern neurophysiological techniques, e.g. Neuropixel recordings from primates (7/10)
December 29, 2025 at 2:41 PM
We have argued that persistent activity does not imply a perfectly regular firing rate at the level of single neurons. The collective activity of multiple neurons is what maintains information. See this review for a more detailed explanation: www.jneurosci.org/content/38/3...
Persistent Spiking Activity Underlies Working Memory
Persistent activity generated in the PFC during the delay period of working memory tasks represents information about stimuli held in memory and determines working memory performance. Alternative mode...
www.jneurosci.org
December 29, 2025 at 2:41 PM
Alternative theories have sprung out, instead, suggesting that “activity-silent” mechanisms allow information to persist over periods when firing ceases (5/10)
December 29, 2025 at 2:41 PM
This has led to the idea that observed persistent activity is an “artifact of averaging”: it only becomes evident when firing rate from multiple trials is averaged together, creating a mere illusion of persistence (4/10)
December 29, 2025 at 2:41 PM
A thorn in the side of this theory, however, has been that the firing of cortical neurons is quite irregular; individual neurons rarely exhibit continuous, uninterrupted firing throughout the entire delay period of working memory tasks (3/10)
December 29, 2025 at 2:41 PM
The neural basis of working memory has been debated. What we like to call “The Standard Model” of working memory posits that persistent discharges generated by neurons in the prefrontal cortex constitute the neural correlate of working memory (2/10)
December 29, 2025 at 2:41 PM
Congratulations
December 19, 2025 at 3:14 PM
It looks like Congress has little appetite for continuing the DOGE capping of indirect-costs fight
December 9, 2025 at 9:41 PM