OSCAR Celebration of Student Scholarship and Impact
Categories
College of Engineering and Computing OSCAR

Multi Expert Debate (MED): An LLM Framework for Analysis

Author(s): Jacob Sheikh

Mentor(s): Ozlem Uzuner, Information Systems and Technology

Abstract
In this work, we introduce Multi-Expert-Debate (MED): An LLM Framework for Analysis. Analysis is an open ended problem; given the same facts, different people draw different conclusions (based on their background, their personality, their beliefs, etc.). In MED, LLM agents are each initialized with their own personas. Agents are all provided the same problem and same knowledge, and, after coming to their own individual solution, debate with other agents, until the ensemble produces a singular, refined idea. We also present SumRAG: a summary-based retrieval method to augment LLM generation. We believe this work will establish a valuable baseline to measure other approaches to reasoning against.
Audio Transcript
Hello. Today, I want to talk about explicit and implicit reasoning in language models. I want to guide this discussion with the question: How can you construct representations of the world in such a way that some agent can navigate those representations to solve problems? In other words, how can you construct an artificial general intelligence?
The first step in answering this question—and what we addressed in our work—was understanding how to navigate representations of knowledge, which is essentially how to reason. There are two approaches to reasoning in language models today: explicit reasoning and implicit reasoning. In our work, we focused on explicit reasoning.
Language models like ChatGPT have shown the ability to improve their responses through reasoning. Shown here is one example technique called chain of thought. On the left, the language model does not reason through its answer and simply outputs “11,” which is incorrect. On the right, the model verbalizes its thought process—explicit reasoning—and arrives at a more accurate answer. Explicit reasoning, therefore, is the process of articulating thoughts step by step to improve the final output. It has proven to be very effective.
The goal of our work was to synthesize explicit reasoning with other emerging techniques in language models, including retrieval-augmented generation (RAG)—querying a database—and multi-agent systems, where multiple LLMs interact. We aimed to combine all three into a unified framework to create the best of what’s currently available in LLM-based explicit reasoning.
Our work hopes to produce a framework called Multi-Expert Debates (MED). In MED, we initialize multiple agents (LLMs), each with their own opinions and personas, given access to the same information via the same RAG setup. These agents debate and defend their decisions until they converge on a single, agreed-upon output.
This work was done in the context of medical care—specifically, decision support systems to assist clinicians in diagnosis. To support this, we implemented a summarization-based RAG pipeline using a dataset that includes foundational medical knowledge, case studies, and procedural guidance.
While the system is still under development, we aim to compare its performance with models that use implicit reasoning. In implicit reasoning, the model reasons internally without verbalizing steps. For example, given the question “Find the capital of the state containing Dallas,” the model might internally reason: “Dallas is in Texas, the capital of Texas is Austin,” and output “Austin” without showing its steps. This form of reasoning has been observed but is not always reliable.
The broader objective of our research is to explore implicit reasoning further. For now, we are building a strong explicit reasoning framework as a baseline for future comparison. We’ve also found interesting connections with neuroscience, particularly regarding disentangled representations, which play a key role in how reasoning may be structured.
We are hopeful our work will provide a valuable foundation for evaluating and developing implicit reasoning approaches in the future.
Categories
College of Humanities and Social Science College of Science OSCAR

Use of a Novel In-Vivo Acetylcholine Sensor, GRABACh3.0, to Quantify the Temporal Dynamics of Acetylcholine (ACh) Release in the Cornu Ammonis 1 (CA1) Hippocampus Sub-Region

Author(s): Muhammad Shah

Mentor(s): Holger Dannenberg, Interdisciplinary Program in Neuroscience

****Warning Video Contain Graphic Images****

Abstract
Ongoing research aims to uncover how the brain processes spatial information, with the
long-term goal of informing therapies for spatial memory dysfunctions seen in
dementias. One key neuronal substrate is the place cell—neurons located in the Cornu
Ammonis 1 (CA1) subregion of the hippocampus that exhibit spatially tuned firing.
Recent studies suggest that acetylcholine (ACh), released into CA1 from the medial
septum, modulates place cell activity. Investigating how ACh modulates hippocampal
circuits during real-time behavior is essential to understanding its role in spatial
encoding.

The recent development of the fluorescent ACh sensor GRABACh3.0 enables real-time
measurement of cortical ACh activity in animal models. Using this sensor, we aim to
quantify the temporal dynamics of ACh release in the CA1 region during free-roaming
behavior in mice. To accomplish this, we will perform a stereotaxic injection of an
adeno-associated virus (rAAV) encoding GRABACh3.0 into CA1, followed by
implantation of an optic fiber above the injection site to permit fluorescence-based
recording via fiber photometry.

After allowing two weeks for sensor expression, a fiber photometry system will be used
to deliver constant excitation light specific to the sensor and record resulting
fluorescence during 15-minute free-roaming trials in a novel boxed environment.
Simultaneously, mouse velocity will be estimated using DeepLabCut, a markerless AI-
based pose estimation tool. Fluorescence signals will be synchronized with velocity data
to assess their temporal relationship.

Preliminary data revealed a positive correlation (r = 0.60) between ACh sensor
fluorescence and mouse velocity during free-roaming trials—a relationship consistent
with prior literature, supporting the validity of our recorded ACh signal. Next, we aim to
replicate this model and examine ACh release in CA1 during behavioral assays of
novelty and familiarity, to further investigate the neuromodulatory role of ACh in spatial
encoding.

Audio Transcript
Hello

My name is Muhammad, and my project is “Using a Novel In-Vivo Acetylcholine Sensor, GRABACh3.0, to Quantify the Temporal Dynamics of Acetylcholine (ACh) release in the Cornu Ammonis 1 (CA1) Hippocampus Sub-Region.”

In 1971, John O’Keeffe, a Nobel Prize winning neuroscientist, probed the electrical activity of hippocampal CA1 pyramidal neurons with electrodes in mouse models. He noticed that as the mouse traversed the environment, certain populations of neurons would increase firing rates in select regions of the box, which is now known as spatially tuned firing.

Discovery of these cells offered a new insight into how individual neurons encode space, and these CA1 neuron types would cleverly be named place cells! With this discovery came renewed interest in understanding the place cells within the CA1 region, with the goal of further uncovering the mechanisms of spatial cognition to inform future treatments for spatial amnesia in patients with, for example, Alzheimer’s disease.

Recently, it was discovered through retrograde tracing that Acetylcholine or ACh is released into CA1 region from distant cholinergic afferents from the medial septum. It is believed that these cholinergic afferents play a role in either directly stimulating place cells or stimulating other surrounding interneurons to inhibit place cells in the CA1 region.

Based on the multimodal modulation of place cells by ACh, understanding the release dynamics of ACh in real-time within the CA1 during behavior is of great interest.

To accomplish this, we used a novel ACh sensor called GRABACh3.0. Its major feature of interest is its binary nature, where it is capable of emission when ACh is bound but is incapable of emission when ACh is not bound. Thus, by using this sensor, the real-time neurodynamics of ACh within neuronal circuits can be observed.

To express the ACh sensor in mouse models, it is first packaged into a viral vector and then injected into the CA1 region, as seen here. We were able to confirm the expression of the sensor through immunohistology, shown here.

A fiber optic receiver is then implanted into the same location within the CA1 as the virus injection to measure the expressed ACh sensor. Then, a fiber photometry system is used to stimulate the sensor. Fiber photometry is a powerful technique that allows both excitation light, specific to the sensor, and control light to be transmitted through the same wire into the mouse fiber optic. It also allows, from the same input wire, to receive and record any resulting emission from either excitation or control light source, respectively, thus separating their influence on fluorescence within the sample. The fluorescence data is then converted into an electric signal using a phototransducer within the system.

Here is the system on the left where you can see both of the excitation cords that go into the sample and the emission cord coming back from the sample. We record fiber data for 15 minutes in a boxed environment. We also sync the fiber system with a bird’s eye video recording of the mouse to see how ACh levels correlate with the velocity of the mouse during the free roaming trials.

This correlation is found between ACh levels and velocity data to confirm whether we truly see an ACh signal from the mouse, as prior literature has established this positive correlation. After subtracting the control signal from the ACh signal and finding the velocity data using an AI markerless pose estimator, DeepLabCut, we obtained these preliminary results.

The graphs on the left show the isolated ACh signal, the velocity data, and their superimposition. Zooming in, we can see at specific time points when the animal increases its running speed, as marked by the arrows, that ACh activity tends to increase along with it. Furthermore, the overall correlation between the two variables was 0.60, which is very unlikely to be due to chance, especially over almost 45000 data points.

These findings were very exciting, but we face the next challenge of getting replicable results. The current findings come from our most recent and successful mouse, which resulted from a series of trial and error from previous mouse models using the sensor, as it is our lab’s first time using this specific sensor within the CA1. We are currently waiting on a new cohort of mice to see if we can consistently get results similar to those seen recently.

If we achieve consistency, we hope to use our standardized procedure and combine it with other techniques, such as optogenetics or spatial behavioral assays, in the future.

I want to give a big thank you to URSP for funding, Dr. Holger Dannenberg for his mentorship, and the Spatial Cognition Lab team for their support—this project would not have been possible without them.