Biology subjects

M. Aghajan, Z.

Publications and source records attributed to M. Aghajan, Z..

6 recordsLinked to original sources

bioRxiv2026

Brain dynamics supporting high cognitive performance reorganize after midlife

Quantifying functional brain aging trajectories at scale remains a fundamental challenge due to the scanner-bound limitations of traditional neuroimaging. Here, we deploy whole-head Time-Domain functional Near-Infrared Spectroscopy (TD-fNIRS) to map task-evoked cortical dynamics during a 30-minute cognitive battery across the adult lifespan (N = 302, age 18-87, 45% racial or ethnic minority). We developed a robust General Cognitive Factor (GCF) tracking age-related performance decline (r = -0.57, p < 0.0001). Analysis of brain activity patterns revealed systemic, age-dependent neural dedifferentiation, highlighting a distinct neurocognitive inflection point around age 55. Prior to this threshold, high performers exhibit more variable neural activation across tasks; post-age 55, high performance is sustained through reduced spatial differentiation, signaling a compensatory strategy. Furthermore, subjective anxiety and depression disrupt these compensatory mechanisms, and subjective cognitive complaints register as distinct neural signatures before behavioral GCF decline manifests. Together, these findings establish a scalable framework for mapping functional brain health across the human lifespan, uncovering the neural mechanics of cognitive resilience and vulnerability before behavioral decline manifests.

neuroscience↗

bioRxiv2023

Change in brain asymmetry reflects level of acute alcohol intoxication and impacts on inhibitory control

Alcohol is one of the most commonly used substances and frequently abused, yet little is known about the neural underpinnings driving variability in inhibitory control performance after ingesting alcohol. This study was a single-blind, placebo-controlled, randomized design with participants (N=48) completing three study visits. At each visit participants received one of three alcohol doses; namely, a placebo dose (equivalent Blood Alcohol Concentration (BAC) = 0.00%), a low dose of alcohol (target BAC=0.04%), or a moderate dose of alcohol (target BAC=0.08%). To measure inhibitory control, participants completed a Go/No-go task paradigm twice during each study visit, once immediately before dosing and once after, while their brain activity was measured with time-domain functional near-infrared spectroscopy (TD-fNIRS). BAC and subjective effects of alcohol were also assessed. We report decreased behavioral performance for the moderate dose of alcohol, but not the low or placebo doses. We observed right lateralized inhibitory prefrontal activity during go-no-go blocks, consistent with prior literature. Using standard and novel metrics of lateralization, we were able to significantly differentiate between all doses. Lastly, we demonstrate that these metrics are not only related to behavioral performance during inhibitory control, but also provide complementary information to the legal gold standard of intoxication (i.e. BAC).

neuroscience↗

bioRxiv2023

Acute effects of subanesthetic ketamine on cerebrovascular hemodynamics in humans: A TD-fNIRS neuroimaging study

Quantifying neural activity in natural conditions (i.e. conditions comparable to the standard clinical patient experience) during the administration of psychedelics may further our scientific understanding of the effects and mechanisms of action. This data may facilitate the discovery of novel biomarkers enabling more personalized treatments and improved patient outcomes. In this single-blind, placebo-controlled study with a non-randomized design, we use time-domain functional near-infrared spectroscopy (TD-fNIRS) to measure acute brain dynamics after intramuscular subanesthetic ketamine (0.75 mg/kg) and placebo (saline) administration in healthy participants (n = 15, 8 females, 7 males, age 32.4 {+/-} 7.5 years) in a clinical setting. We found that the ketamine administration caused an altered state of consciousness and changes in systemic physiology (e.g. increase in pulse rate and electrodermal activity). Furthermore, ketamine led to a brain-wide reduction in the fractional amplitude of low frequency fluctuations (fALFF), and a decrease in the global brain connectivity of the prefrontal region. Lastly, we provide preliminary evidence that a combination of neural and physiological metrics may serve as predictors of subjective mystical experiences and reductions in depressive symptomatology. Overall, our studies demonstrated the successful application of fNIRS neuroimaging to study the physiological effects of the psychoactive substance ketamine and can be regarded as an important step toward larger scale clinical fNIRS studies that can quantify the impact of psychedelics on the brain in standard clinical settings.

neuroscience↗

bioRxiv2022

Periodic Time Cells in Human Entorhinal Cortex

Grid cells in the entorhinal cortex demonstrate spatially periodic firing patterns, which are thought to provide a map of space on behaviorally relevant length scales. It is unknown, however, whether such periodicity exists for behaviorally relevant time scales in the human brain. Here we investigated neuronal firing during a temporally continuous uninterrupted experience by presenting fourteen neurosurgical patients with an audiovisual video while recording single neuron activity from multiple brain regions. We report on a set of units that modulate their activity in a strikingly periodic manner across different timescales--from seconds to many minutes. These cells were most prevalent in the entorhinal cortex. Time within the video could be decoded from their population activity. Furthermore, these cells remapped their dominant periodicity to shorter timescales during a subsequent recognition memory task. When the audiovisual sequence was presented at two different speeds (regular and faster), a significant percentage of these temporally periodic cells (TPCs) maintained their timescales, suggesting a degree of invariance with respect to the narrative content. The temporal periodicity of TPCs may complement the spatial periodicity of grid cells Whether these cells provide scalable spatiotemporal metrics for encoding and retrieval of human experience warrants future investigations.

neuroscience↗

bioRxiv2021

Decoding of human identity by computer vision and neuronal vision

Extracting meaning from a dynamic and variable flow of incoming information is a major goal of both natural and artificial intelligence. Computer vision (CV) guided by deep learning (DL) has made significant strides in recognizing a specific identity despite highly variable attributes1,2. This is the same challenge faced by the nervous system and partially addressed by the concept cells--neurons exhibiting selective firing in response to specific persons/places, described in the human medial temporal lobe (MTL)3-6. Yet, access to neurons representing a particular concept is limited due to these neurons sparse coding. It is conceivable, however, that the information required for such decoding is present in relatively small neuronal populations. To evaluate how well neuronal populations encode identity information in natural settings, we recorded neuronal activity from multiple brain regions of nine neurosurgical epilepsy patients implanted with depth electrodes, while the subjects watched an episode of the TV series "24". We implemented DL models that used the time-varying population neural data as inputs and decoded the visual presence of the main characters in each frame. Before training and testing the DL models, we devised a minimally supervised CV algorithm (with comparable performance against manually-labelled data7) to detect and label all the important characters in each frame. This methodology allowed us to compare "computer vision" with "neuronal vision"--footprints associated with each character present in the activity of a subset of neurons--and identify the brain regions that contributed to this decoding process. We then tested the DL models during a recognition memory task following movie viewing where subjects were asked to recognize clip segments from the presented episode. DL model activations were not only modulated by the presence of the corresponding characters but also by participants subjective memory of whether they had seen the clip segment, and by the associative strengths of the characters in the narrative plot. The described approach can offer novel ways to probe the representation of concepts in time-evolving dynamic behavioral tasks. Further, the results suggest that the information required to robustly decode concepts is present in the population activity of only tens of neurons even in brain regions beyond MTL.

neuroscience↗

bioRxiv2019

Modulation of human intracranial theta oscillations during freely moving spatial navigation and memory

How the human brain supports accurate navigation of a learned environment has been an active topic of research for nearly a century1-5. In rodents, the theta rhythm within the medial temporal lobe (MTL) has been proposed as a neural basis for fragmenting incoming information and temporally organizing experiences and is thus widely implicated in spatial and episodic memory6. In addition, high-frequency theta (~8Hz) is associated with navigation, and loss of theta results in spatial memory deficits in rats 7. Recently, high-frequency theta oscillations during ambulatory movement have been identified in humans8,9, though their relationship to spatial memory remains unexplored. Here, we were able to record MTL activity during spatial memory and navigation in freely moving humans immersed in a room-scale virtual reality (VR) environment. Naturalistic movements were captured using motion tracking combined with wireless VR in participants implanted with an intracranial electroencephalographic (iEEG) recording system for the treatment of epilepsy. We found that prevalence of theta oscillations across brain sites during both learning and recall of spatial locations during ambulatory navigation is critically linked to memory performance. This finding supports the reinstatement hypothesis of episodic memory--thought to underlie our ability to recreate a prior experience10-12--and suggests that theta prevalence within the MTL may act as a potential representational state for memory reinstatement during spatial navigation. Additionally, we found that theta power is hexadirectionally modulated13-15 as a function of the direction of physical movement, most prominently after learning has occurred. This effect bears a resemblance to the rodent grid cell system16 and suggests an analog in human navigation. Taken together, our results provide the first characterization of neural oscillations in the human MTL during ambulatory spatial memory tasks and provide a platform for future investigations of neural mechanisms underlying freely moving navigation in humans.

neuroscience↗