Biology subjects

Stoll, F. M.

Publications and source records attributed to Stoll, F. M..

12 recordsLinked to original sources

bioRxiv2026

Dynamic geometry remapping of neural activity within frontal and subcortical areas during decision-making

Decision-making involves dynamic evaluation of competing options. Recording 16,495 neurons across nine frontal and subcortical areas in macaques revealed brain-wide fluctuations between encoding the attributes of available options. These dynamic representations track deliberation and scale with decision difficulty. Instead of binding attribute information of different options together, our analyses show that these representations are associated with dynamic area- and attribute-specific changes in neural geometry.

neuroscience↗

bioRxiv2026

Prefrontal mechanisms of goal progress inference and monitoring in macaque monkeys

Primates pursue goals over extended periods and over multiple steps. The ability to track progress and its rate is critical for such pursuit, yet the neural mechanisms of this tracking are unclear. We recorded single-unit activity from macaque midcingulate cortex (MCC) and lateral prefrontal cortex (LPFC) whilst animals worked for immediate rewards and checked a gauge showing progress towards a larger reward. MCC expressed a temporally extended progress rate signal linked to the long timescale neurons in the region. LPFC expressed progress rate only when inferences on that property were required. In MCC, independent feedback-valence information was also preserved, enabling both readout of work success and rate-specific progress updating. An RNN trained under the same constraints showed that progress rate representations emerge spontaneously, and are critical for tracking goal progress. These results demonstrate a frontal mechanism for inferring and predicting goal progress by extracting progress rate information.

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bioRxiv2024

Consistent hierarchies of single-neuron timescales in mice, macaques and humans

The intrinsic timescales of single neurons are thought to be hierarchically organized across the cortex. This conclusion, however, is primarily based on analyses of neural responses from macaques. Whether hierarchical variation in timescales is a general brain organizing principle across mammals remains unclear. Here we took a cross-species approach and estimated neuronal timescales of thousands of single neurons recorded across multiple areas in mice, monkeys, and humans using a task-agnostic method. We identify largely consistent hierarchies of timescales in frontal and limbic regions across species: hippocampus had the shortest timescale whereas anterior cingulate cortex had the longest. Within this scheme, variability across species was found, most notably in amygdala and orbitofrontal cortex. We show that variation in timescales is not simply related to differences in spiking statistics nor the result of cytoarchitectonic features such as cortical granularity. Thus, hierarchically organized timescales are a consistent organizing principle across species and appear to be related to a combination of intrinsic and extrinsic factors. HighlightsO_LISimilar hierarchies of single neuron timescales exist across humans, macaques, and mice C_LIO_LIHumans diverge from an otherwise conserved hierarchy in amygdala and OFC C_LIO_LITimescale variability in ventral frontal cortex is not entirely related to cytoarchitecture C_LI

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bioRxiv2024

Decision-making shapes dynamic inter-areal communication within macaque ventral frontal cortex

Macaque ventral frontal cortex is comprised of a set of anatomically heterogeneous and highly interconnected areas. Collectively these areas have been implicated in many higher-level affective and cognitive processes, most notably the adaptive control of decision-making. Despite this appreciation, little is known about how subdivisions of ventral frontal cortex dynamically interact with each other during decision-making. Here we assessed functional interactions between areas by analyzing the activity of thousands of single neurons recorded from eight anatomically defined subdivisions of ventral frontal cortex in macaques performing a visually guided two-choice probabilistic task for different fruit juices. We found that the onset of stimuli and reward delivery globally increased communication between all parts of ventral frontal cortex. Inter-areal communication was, however, temporally specific, occurred through unique activity subspaces between areas, and depended on the encoding of decision variables. In particular, areas 12l and 12o showed the highest connectivity with other areas while being more likely to receive information from other parts of ventral frontal cortex than to send it. This pattern of functional connectivity suggests a role for these two areas in integrating diverse sources of information during decision processes. Taken together, our work reveals the specific patterns of inter-areal communication between anatomically connected subdivisions of ventral frontal cortex that are dynamically engaged during decision-making.

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bioRxiv2024

Dissociable representations of decision variables within subdivisions of macaque orbitofrontal and ventrolateral frontal cortex

Ventral frontal cortex (VFC) in macaques is involved in many affective and cognitive processes and has a key role in flexibly guiding reward-based decision-making. VFC is composed of a set of anatomically distinct subdivisions that are within the orbitofrontal cortex, ventrolateral prefrontal cortex, and anterior insula. In part, because prior studies have lacked the resolution to test for differences, it is unclear if neural representations related to decision-making are dissociable across these subdivisions. Here we recorded the activity of thousands of neurons within eight anatomically defined subregions of VFC in macaque monkeys performing a two-choice probabilistic task for different fruit juices outcomes. We found substantial variation in the encoding of decision variables across these eight subdivisions. Notably, ventrolateral subdivision 12l was unique relative to the other areas that we recorded from as the activity of single neurons integrated multiple attributes when monkeys evaluated the different choice options. Activity within 12o, by contrast, more closely represented reward probability and whether reward was received on a given trial. Orbitofrontal area 11m/l contained more specific representations of the quality of the outcome that could be earned later on. We also found that reward delivery encoding was highly distributed across all VFC subregions, while the properties of the reward, such as its flavor, were more strongly represented in areas 11m/l and 13m. Taken together, our work reveals the diversity of encoding within the various anatomically distinct subdivisions of VFC in primates. SIGNIFICANCE STATEMENTVentral frontal cortex (VFC) is essential for flexible decision-making and is composed of many anatomically defined subdivisions. How neural representations related to decision-making vary or not between these subdivisions is unclear. Here we recorded single neuron activity from eight anatomically distinct subdivisions of VFC while macaques made choices between stimuli based on the probability of receiving different flavored fruit juices. We report that neural representations across these subdivisions were dissociable. Area 12l exhibiting the most integrated representations of decision variables at the level of single neurons. By contrast, activity in area 12o was closely related to reward probability whereas activity in area 11m/l and 13m represented juice flavor. Thus, neural representations are distinct across anatomically separable parts of VFC.

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bioRxiv2023

Comparative basolateral amygdala connectomics reveals dissociable single-neuron projection patterns to frontal cortex in macaques and mice

Short abstractThe basolateral amygdala (BLA) projects to the frontal cortex (FC) in both rodents and primates, but the comparative organization of single-neuron BLA-FC projections is unknown. Using a barcoded connectomic approach, we found that BLA neurons are more likely to project to multiple distinct parts of FC in mice than in macaques. Further, while single BLA neuron projections to nucleus accumbens are similarly organized in mice and macaques, BLA-FC connections differ.

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bioRxiv2023

The neural basis of resting-state fMRI functional connectivity in fronto-limbic circuits revealed by chemogenetic manipulation

Measures of fMRI resting-state functional connectivity (rs-FC) are an essential tool for basic and clinical investigations of fronto-limbic circuits. Understanding the relationship between rs-FC and neural activity in these circuits is therefore vital. Here we introduced inhibitory designer receptors exclusively activated by designer drugs (DREADDs) into the macaque amygdala and activated them with a highly selective and potent DREADD agonist, deschloroclozapine. We evaluated the causal effect of activating the DREADD receptors on rs-FC and neural activity within circuits connecting amygdala and frontal cortex. Interestingly, activating the inhibitory DREADD increased rs-FC between amygdala and ventrolateral prefrontal cortex. Neurophysiological recordings revealed that the DREADD-induced increase in fMRI rs-FC was associated with increased local field potential coherency in the alpha band (6.5-14.5Hz) between amygdala and ventrolateral prefrontal cortex. Thus, our multi-disciplinary approach reveals the specific signature of neuronal activity that underlies rs-FC in fronto-limbic circuits.

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bioRxiv2023

Preferences reveal separable valuation systems in prefrontal-limbic circuits

Individual preferences for the flavor of different foods and fluids exert a strong influence on behavior. Most current theories posit that preferences are integrated with other state variables in orbitofrontal cortex (OFC), which is thought to derive the relative subjective value of available options to drive choice behavior. Here we report that instead of a single integrated valuation system in OFC, another separate one is centered in ventrolateral prefrontal cortex (vlPFC) in macaque monkeys. Specifically, we found that OFC and vlPFC preferentially represent outcome flavor and outcome probability, respectively, and that preferences are separately integrated into these two aspects of subjective valuation. In addition, vlPFC, but not OFC, represented the outcome probability for the two options separately, with the difference between these representations reflecting the degree of preference. Thus, there are at least two separable valuation systems that work in concert to guide choices and that both are biased by preferences.

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bioRxiv2023

High-throughput sequencing of macaque basolateral amygdala projections reveals dissociable connectional motifs with frontal cortex

The basolateral amygdala (BLA) projects widely across the macaque frontal cortex1-4, and amygdalo-frontal projections are critical for optimal emotional responding5 and decision- making6. Yet, little is known about the single-neuron architecture of these projections: namely, whether single BLA neurons project to multiple parts of the frontal cortex. Here, we use MAPseq7 to determine the projection patterns of over 3000 macaque BLA neurons. We found that one-third of BLA neurons have two or more distinct targets in parts of frontal cortex and of subcortical structures. Further, we reveal non-random structure within these branching patterns such that neurons with four targets are more frequently observed than those with two or three, indicative of widespread networks. Consequently, these multi-target single neurons form distinct networks within medial and ventral frontal cortex consistent with their known functions in regulating mood and decision-making. Additionally, we show that branching patterns of single neurons shape functional networks in the brain as assessed by fMRI-based functional connectivity. These results provide a neuroanatomical basis for the role of the BLA in coordinating brain-wide responses to valent stimuli8 and highlight the importance of high- resolution neuroanatomical data for understanding functional networks in the brain.

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bioRxiv2020

Local inhibitory control of frontal network metastability underlies the temporal signature of cognitive states

Cortical neural dynamics organizes over multiple anatomical and temporal scales. The mechanistic origin of the temporal organization and its contribution to cognition remain unknown. Here we demonstrate the cause of this organization by studying a specific temporal signature (autocorrelogram time constant and latency) of neural activity. In monkey frontal areas, recorded during flexible cognitive decisions, temporal signatures display highly specific area-dependent ranges, as well as anatomical and cell-type distributions. Moreover, temporal signatures are functionally adapted to behaviorally relevant timescales. Fine-grained biophysical network models, constrained to account for temporal signatures, reveal that after-hyperpolarization potassium and inhibitory GABA-B conductances critically determine areas specificity. They mechanistically account for temporal signatures by organizing activity into metastable states, with inhibition controlling state stability and transitions. As predicted by models, state durations non-linearly scale with temporal signatures in monkey, matching behavioral timescales. Thus, local inhibitory-controlled metastability constitutes the dynamical core specifying the temporal organization of cognitive functions in frontal areas.

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bioRxiv2019

Investigating Confidence Judgments using Reviews in Human and Monkeys

Confidence judgments are self-assessments of the quality of ones own performance, and are a crucial aspect of metacognitive abilities. The underlying neurobiological mechanisms are poorly understood. One approach to understanding these mechanisms would be to take advantage of putative metacognitive abilities in non-human models. However, many discrepancies exist between human and non-human studies on metacognition due to the mode of reporting judgements. We here present an attempt to directly compare human and non-human primates metacognitive abilities using a protocol assessing confidence judgments. After performing a categorization test, subjects could either validate their choice or review the test. We could assess whether subjects detected their errors and how they corrected them according to their confidence, and importantly did so in both human and non-human primates. 14 humans and 2 macaque monkeys were tested. Humans showed a well-adapted use of the review option by reviewing more after incorrect choices or difficult stimuli. Non-human primates did not demonstrate a convincing use of the review or validate opportunity. In both species, reviewing did not improve performance. This study shows that decisions to review under uncertainty are not naturally beneficial to performance and is rather perturbed by biases and alternative low-cognitive cost strategies.

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bioRxiv2017

Amygdala Input Differentially Influences Prefrontal Local Field Potential And Single Neuron Encoding Of Reward-Based Decisions

Reward-guided behaviors require functional interaction between amygdala, orbital (OFC), and medial (MFC) divisions of prefrontal cortex, but the neural mechanisms underlying these interactions are unclear. Here, we used a decoding approach to analyze local field potentials (LFPs) recorded from OFC and MFC of monkeys engaged in a stimulus-choice task, before and after excitotoxic amygdala lesions. Whereas OFC LFP responses were strongly modulated by the amount of reward associated with each stimulus, MFC responses best represented which stimulus subjects decided to choose. This was counter to what we observed in the level of single neurons where their activity was closely associated with the value of the stimuli presented on each trial. After lesions of the amygdala, stimulus-reward value and choice encoding were reduced in OFC and MFC, respectively. However, while the lesion-induced decrease in OFC LFP encoding of stimulus-reward value mirrored changes in single neuron activity, reduced choice encoding in MFC LFPs was distinct from changes in single neuron activity. Thus, LFPs and single neurons represent different information required for decision-making in OFC and MFC. At the circuit-level, amygdala input to these two areas play a distinct role in stimulus-reward encoding in OFC and choice encoding in MFC.

neuroscience↗