memory task

Working memory tasks for functional mapping of the prefrontal cortex in common marmosets

Hippocampal network dynamics during impaired working memory in epileptic mice

Memory impairment is a common cognitive deficit in temporal lobe epilepsy (TLE). The hippocampus is severely altered in TLE exhibiting multiple anatomical changes that lead to a hyperexcitable network capable of generating frequent epileptic discharges and seizures. In this study we investigated whether hippocampal involvement in epileptic activity drives working memory deficits using bilateral LFP recordings from CA1 during task performance. We discovered that epileptic mice experienced focal rhythmic discharges (FRDs) while they performed the spatial working memory task. Spatial correlation analysis revealed that FRDs were often spatially stable on the maze and were most common around reward zones (25 ‰) and delay zones (50 ‰). Memory performance was correlated with stability of FRDs, suggesting that spatially unstable FRDs interfere with working memory codes in real time.

Neural Circuit Mechanisms of Pattern Separation in the Dentate Gyrus

The ability to discriminate different sensory patterns by disentangling their neural representations is an important property of neural networks. While a variety of learning rules are known to be highly effective at fine-tuning synapses to achieve this, less is known about how different cell types in the brain can facilitate this process by providing architectural priors that bias the network towards sparse, selective, and discriminable representations. We studied this by simulating a neuronal network modelled on the dentate gyrus—an area characterised by sparse activity associated with pattern separation in spatial memory tasks. To test the contribution of different cell types to these functions, we presented the model with a wide dynamic range of input patterns and systematically added or removed different circuit elements. We found that recruiting feedback inhibition indirectly via recurrent excitatory neurons proved particularly helpful in disentangling patterns, and show that simple alignment principles for excitatory and inhibitory connections are a highly effective strategy.

Functional segregation of rostral and caudal hippocampus in associative memory

It has long been established that the hippocampus plays a crucial role for episodic memory. As opposed to the modular approach, now it is generally assumed that being a complex structure, the HC performs multiplex interconnected functions, whose hierarchical organization provides basis for the higher cognitive functions such as semantics-based encoding and retrieval. However, the «where, when and how» properties of distinct memory aspects within and outside the HC are still under debate. Here we used a visual associative memory task as a probe to test the hypothesis about the differential involvement of the rostral and caudal portions of the human hippocampus in memory encoding, recognition and associative recall. In epilepsy patients implanted with stereo-EEG, we show that at retrieval the rostral HC is selectively active for recognition memory, whereas the caudal HC is selectively active for the associative memory. Low frequency desynchronization and high frequency synchronization characterize the temporal dynamic in encoding and retrieval. Therefore, we describe here anatomical segregation in the hippocampal contributions to associative and recognition memory.

Targeted Activation of Hippocampal Place Cells Drives Memory-Guided Spatial Behaviour

The hippocampus is crucial for spatial navigation and episodic memory formation. Hippocampal place cells exhibit spatially selective activity within an environment and have been proposed to form the neural basis of a cognitive map of space that supports these mnemonic functions. However, the direct influence of place cell activity on spatial navigation behaviour has not yet been demonstrated. Using an ‘all-optical’ combination of simultaneous two-photon calcium imaging and two-photon holographically targeted optogenetics, we identified and selectively activated place cells that encoded behaviourally relevant locations in a virtual reality environment. Targeted stimulation of a small number of place cells was sufficient to bias the behaviour of animals during a spatial memory task, providing causal evidence that hippocampal place cells actively support spatial navigation and memory. Time permitting, I will also describe new experiments aimed at understanding the fundamental encoding mechanism that supports episodic memory, focussing on the role of hippocampal sequences across multiple timescales and behaviours.

The Challenge and Opportunities of Mapping Cortical Layer Activity and Connectivity with fMRI

In this talk I outline the technical challenges and current solutions to layer fMRI. Specifically, I describe our acquisition strategies for maximizing resolution, spatial coverage, time efficiency as well as, perhaps most importantly, vascular specificity. Novel applications from our group, including mapping feedforward and feedback connections to M1 during task and sensory input modulation and S1 during a sensory prediction task are be shown. Layer specific activity in dorsal lateral prefrontal cortex during a working memory task is also demonstrated. Additionally, I’ll show preliminary work on mapping whole brain layer-specific resting state connectivity and hierarchy.

Human Single-Neuron recordings reveal neuronal mechanisms of Working Memory

Working memory (WM) is a fundamental human cognitive capacity that allows us to maintain and manipulate information stored for a short period of time in an active form. Thanks to a unique opportunity to record activity of neurons in humans during epilepsy monitoring we could test neuronal mechanisms of this cognitive capacity. We showed that firing rate of image selective neurons in Medial Temporal Lobe persists through maintenance periods of working memory task. This activity was behaviorally relevant and formed attractors in its state-space. Furthermore, we showed that firing rate of those neurons phase lock to ongoing slow-frequency oscillations. The properties of phase locking are dependent on memory content and load. During high memory loads, the phase of the oscillatory activity to which neurons phase lock provides information about memory content not available in the firing rate of the neurons.

Emergent scientists discuss Alzheimer's disease

This seminar is part of our “Emergent Scientists” series, an initiative that provides a platform for scientists at the critical PhD/postdoc transition period to share their work with a broad audience and network. Summary: These talks cover Alzheimer’s disease (AD) research in both mice and humans. Christiana will discuss in particular the translational aspects of applying mouse work to humans and the importance of timing in disease pathology and intervention (e.g. timing between AD biomarkers vs. symptom onset, timing of therapy, etc.). Siddharth will discuss a rare variant of Alzheimer’s disease called “Logopenic Progressive Aphasia”, which presents with temporo-parietal atrophy yet relative sparing of hippocampal circuitry. Siddharth will discuss how, despite the unusual anatomical basis underlying this AD variant, degeneration of the angular gyrus in the left inferior parietal lobule contributes to memory deficits similar to those of typical amnesic Alzheimer’s disease. Christiana’s abstract: Alzheimer’s disease (AD) is a debilitating neurodegenerative disorder that causes severe deterioration of memory, cognition, behavior, and the ability to perform daily activities. The disease is characterized by the accumulation of two proteins in fibrillar form; Amyloid-β forms fibrils that accumulate as extracellular plaques while tau fibrils form intracellular tangles. Here we aim to translate findings from a commonly used AD mouse model to AD patients. Here we initiate and chronically inhibit neuropathology in lateral entorhinal cortex (LEC) layer two neurons in an AD mouse model. This is achieved by over-expressing P301L tau virally and chronically activating hM4Di DREADDs intracranially using the ligand dechloroclozapine. Biomarkers in cerebrospinal fluid (CSF) is measured longitudinally in the model using microdialysis, and we use this same system to intracranially administer drugs aimed at halting AD-related neuropathology. The models are additionally tested in a novel contextual memory task. Preliminary findings indicate that viral injections of P301L tau into LEC layer two reveal direct projections between this region and the outer molecular layer of dentate gyrus and the rest of hippocampus. Additionally, phosphorylated tau co-localize with ‘starter cells’ and appear to spread from the injection site. Preliminary microdialysis results suggest that the concentrations of CSF amyloid-β and tau proteins mirror changes observed along the disease cascade in patients. The disease-modifying drugs appear to halt neuropathological development in this preclincial model. These findings will lead to a novel platform for translational AD research, linking the extensive research done in rodents to clinical applications. Siddharth’s abstract: A distributed brain network supports our ability to remember past events. The parietal cortex is a critical member of this network, yet, its exact contributions to episodic remembering remain unclear. Neurodegenerative syndromes affecting the posterior neocortex offer a unique opportunity to understand the importance and role of parietal regions to episodic memory. In this talk, I introduce and explore the rare neurodegenerative syndrome of Logopenic Progressive Aphasia (LPA), an aphasic variant of Alzheimer’s disease presenting with early, left-lateralized temporo-parietal atrophy, amidst relatively spared hippocampal integrity. I then discuss two key studies from my recent Ph.D. work showcasing pervasive episodic and autobiographical memory dysfunction in LPA, to a level comparable to typical, amnesic Alzheimer’s disease. Using multimodal neuroimaging, I demonstrate how degeneration of the angular gyrus in the left inferior parietal lobule, and its structural connections to the hippocampus, contribute to amnesic profiles in this syndrome. I finally evaluate these findings in the context of memory profiles in other posterior cortical neurodegenerative syndromes as well as recent theoretical models underscoring the importance of the parietal cortex in the integration and representation of episodic contextual information.

Revealing the neural basis of human memory with direct recordings of place and grid cells and traveling waves

The ability to remember spatial environments is critical for everyday life. In this talk, I will discuss my lab’s findings on how the human brain supports spatial memory and navigation based on our experiments with direct brain recordings from neurosurgical patients performing virtual-reality spatial memory tasks. I will show that humans have a network of neurons that represent where we are located and trying to go. This network includes some cell types that are similar to those seen in animals, such as place and grid cells, as well as others that have not been seen before in animals, such as anchor and spatial-target cells. I also will explore the role of network oscillations in human memory, where humans again show several distinctive patterns compared to animals. Whereas rodents generally show a hippocampal oscillation at ~8Hz, humans have two separate hippocampal oscillations, at low and high frequencies, which support memory and navigation, respectively. Finally, I will show that neural oscillations in humans are traveling waves, propagating across the cortex, to coordinate the timing of neuronal activity across regions, which is another property not seen in animals. A theme from this work is that in terms of navigation and memory the human brain has novel characteristics compared with animals, which helps explain our rich behavioural abilities and has implications for treating disease and neurological disorders.

The role of gamma oscillations in stimulus encoding during a sequential memory task in the human Medial Temporal Lobe

Bernstein Conference 2024

Dissecting emergent network noise compensation mechanisms in working memory tasks

COSYNE 2022

Inter-areal patterned microstimulation selectively drives PFC activity and behavior in a memory task

COSYNE 2022

Inter-areal patterned microstimulation selectively drives PFC activity and behavior in a memory task

COSYNE 2022

Connectome-constrained cortical circuits optimized for visual function and working memory tasks

COSYNE 2023

Phase remembers: trained RNNs develop phase-locked limit cycles in a working memory task

COSYNE 2023

Claustrum lesions lead to changes in behavioural strategy during reversal learning in a spatial memory task

Correlation patterns in working-memory tasks: fMRI fractal and spectral analysis

Evaluating the modular hypothesis: Comparison of cerebellar medial nucleus and lateral nucleus activity in a rewarded spatial memory task

From recency effects to contraction bias - a neural network model for history effects in Parametric Working Memory tasks

Latency peak of early visual evoked potential is modified by age and novelty during visual memory task

Long-term stability of medial prefrontal cortex pyramidal cell ensembles in an olfaction guided working memory task

Non-linear functional co-activations in short-term memory task

In vivo two-photon imaging of hippocampal neurons during the forced alternation working memory task in 5xFAD Alzheimer mouse model

Auditory cortex activity during sound memory retention in an auditory working memory task

FENS Forum 2024

Context representation in mouse frontal cortex during a short-term memory task

FENS Forum 2024

Cortical-hippocampal interaction in the context of memory task

FENS Forum 2024

Emergence of different spatial cognitive maps in CA1 for rats performing an episodic memory task using egocentric and allocentric navigational strategies

FENS Forum 2024

The GlyT1 inhibitor bitopertin improves choice accuracy during a touchscreen-based working memory task in mice

FENS Forum 2024

Involvement of entorhinal input to the hippocampus in processing “what” and “where” information in twin variants of a memory task

FENS Forum 2024