# Layer-specific manipulation to test feedforward/feedback cortical circuitry

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2024 · $293,487

## Abstract

The cortex must filter out the bulk of sensory inputs. Not enough or too much filtering may underlie a
variety of disorders like autism and schizophrenia. Mounting evidence suggests that this depends on
alpha/beta (~8-30 Hz) oscillations vs gamma (>35 Hz) with associated spiking. They are ubiquitous in
cortex and anti-correlated. Gamma/spiking is high during sensory inputs while alpha/beta is high (and
spiking is low) during conditions requiring top-down control. The central idea is alpha/beta (~8-30 Hz)
rhythms in deep cortical layers inhibit the superficial layer activity (spiking and gamma, >35 Hz) that feed
forward sensory inputs. Our testbed will be a model of Predictive Coding in which alpha/beta carries the
top-down predictions from higher cortex that inhibit the feeding forward of bottom-up sensory inputs of
predicted stimuli. We will test this hypothesis via direct cause-and-effect experiments, by manipulating
the alpha/beta prediction rhythms in monkeys.
We made this possible by developing a new ultra-fast latency (<10 ms) closed-loop system that can read
the brain’s endogenous rhythms and phase-match electrical stimulation to them. We will also employ
high-density “laminar” electrodes to record from all cortical layers and target stimulation to superficial
vs deep layers. Laminar electrodes with injection ports will also allow selective pharmacological
manipulation of deep vs superficial cortical layers. Monkeys will perform a local and global (patterned)
oddball detection task. Our model makes specific predictions on how attenuating vs amplifying
alpha/beta prediction signals will affect local physiological as well as feedforward vs feedback signaling
of predictions and oddballs to higher vs lower cortex. Understanding neurophysiological properties,
functions and interactions between cortical layers and their different dynamics can provide key insight
into the control of cortical processing and the disorders that come from its dysfunction.

## Key facts

- **NIH application ID:** 10769832
- **Project number:** 5R01MH131715-02
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** EARL K MILLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $293,487
- **Award type:** 5
- **Project period:** 2023-02-01 → 2027-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10769832

## Citation

> US National Institutes of Health, RePORTER application 10769832, Layer-specific manipulation to test feedforward/feedback cortical circuitry (5R01MH131715-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10769832. Licensed CC0.

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