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Saalmann, Y. B.

Publications and source records attributed to Saalmann, Y. B..

11 recordsLinked to original sources

A ubiquitous spectrolaminar motif across independent studies, including in the Mackey et al. dataset

Our study (Mendoza-Halliday et al., 2024) made two contributions: (1) discovery of a ubiquitous cortical motif and (2) a tool derived from it--the Frequency-based Layer Identification Procedure (FLIP and vFLIP). Mackey et al. critique the tool, questioning its advantage over classic current source density (CSD) analysis, and reason backwards to challenge the motifs ubiquity. In our rebuttal, we confirm the spectrolaminar motif in diverse cortical areas using data from multiple research groups (who joined us in this rebuttal) as well as Mackey et al.s own dataset. Additionally, we introduce vFLIP2, an improved version of our tool that addresses their comments. It reliably identified and localized the motif in our data and Mackey et al.s data. Our findings reaffirm the motifs ubiquity. We value Mackey et al.s comments, which helped refine our tool.

neuroscience↗

Thalamic Control Over Laminar Cortical Dynamics Across Conscious States

The human brain must support both stable and flexible neural dynamics in order to adapt to changing contexts that are inherently non-linear. The thalamus has been linked to the coordination of these opposing dynamical regimens in the cerebral cortex, however existing methodological approaches have not integrated sufficient neurobiological details with a sensitive measure of neural dynamics that permits sensitivity to time-series non-linearities. Inspired by the field of fluid dynamics, we use a novel approach to show that spontaneous fMRI data exhibits non-trivial fluctuations in predictability over time, akin to a river that has sections of smooth and predictable (laminar) versus rough and unpredictable (non-laminar) fluid flow. We use a combination of pharmacological fMRI, macaque electrophysiology and a large-scale biophysical model of the thalamocortical system to provide robust evidence that the thalamus provides versatile control over globally linear dynamics in the cerebral cortex that characterize conscious states.

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Layer-specific reorganization of mnemonic representations in primate retrosplenial cortex during learning

Rapid learning of associations between co-occurring stimuli is essential for episodic memory formation. The retrosplenial cortex (RSC) is strongly interconnected with the hippocampus, and in rodents, the RSC has been shown to support spatial navigation and fear conditioning. Although lesion and neuroimaging studies in humans and macaques have further implicated the RSC in episodic memory, it is unclear how memory representations form and evolve in the RSC. Here we show that representations of memorized contexts in primate RSC form within minutes. These initial representations reorganize as the memory matures, with a shift in the weight of neuronal contributions from superficial to deep RSC layers across an hour and increased local connectivity between deep layer neurons. Because RSC superficial and deep layers represent input and output layers respectively, it suggests that hippocampal inputs provide context information to superficial layers during early learning, and this context information consolidates in deep RSC layers.

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Primate thalamic nuclei select abstract rules and shape prefrontal dynamics

Flexible behavior depends on abstract rules to generalize beyond specific instances, and outcome monitoring to adjust actions. Cortical circuits are posited to read out rules from high-dimensional representations of task-relevant variables in prefrontal cortex (PFC). We instead hypothesized that converging inputs from PFC, directly or via basal ganglia (BG), enable thalamus to select rules. We measured activity across PFC and connected thalamic nuclei of monkeys applying rules. Abstract rule information first appeared in ventroanterior thalamus (VA) - the main thalamic hub between BG and PFC. Mediodorsal thalamus (MD) also represented rule information before PFC, persisting to help maintain activation of relevant PFC cell ensembles. MD, a major recipient of midbrain dopamine input, was first to represent information about behavioral outcomes. A PFC-BG-thalamus model reproduced key findings, and thalamic-lesion modeling disrupted PFC rule representations. This suggests that thalamus selects high-level cognitive information from PFC and monitors behavioral outcomes of these selections.

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Traveling waves shape neural population dynamics enabling predictions and internal model updating

The brain generates predictions based on statistical regularities in our environment. However, it is unclear how predictions are optimized through iterative interactions with the environment. Because traveling waves (TWs) propagate across the cortex shaping neural excitability, they can carry information to serve predictive processing. Using human intracranial recordings, we show that anterior-to-posterior alpha TWs correlated with prediction strength. Learning about priors altered neural state space trajectories, and how much it altered correlated with trial-by-trial prediction strength. Learning involved mismatches between predictions and sensory evidence triggering alpha-phase resets in lateral temporal cortex, accompanied by stronger alpha phase-high gamma amplitude coupling and high-gamma power. The mismatch initiated posterior-to-anterior alpha TWs and change in the subsequent trials state space trajectory, facilitating model updating. Our findings suggest a vital role of alpha TWs carrying both predictions to sensory cortex and mismatch signals to frontal cortex for trial-by-trial fine-tuning of predictive models.

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Thalamic deep brain stimulation as a paradigm to reduce consciousness: implications for cortico-striatal dynamics, absence epilepsy and consciousness studies

Anesthetic manipulations provide much-needed causal evidence for neural correlates of consciousness, but non-specific drug effects complicate their interpretation. Evidence suggests that thalamic deep brain stimulation (DBS) can either increase or decrease consciousness, depending on the stimulation target and parameters. The putative role of the central lateral thalamus (CL) in consciousness makes it an ideal DBS target to manipulate circuit-level mechanisms in cortico-striato-thalamic (CST) systems, thereby influencing consciousness and related processes. We used multi-microelectrode DBS targeted to CL in macaques while recording from frontal, parietal, and striatal regions. DBS induced episodes reminiscent of absence epilepsy, here termed absence-like activity (ALA), with decreased behavior and vacant staring coinciding with low-frequency oscillations. DBS modulated ALA likelihood in a frequency-specific manner. ALA events corresponded to decreases in measures of neural complexity (entropy) and integration ({Phi}*), an index of consciousness, and substantial changes to communication in CST circuits. During ALA, power spectral density and coherence at low frequencies increased across CST circuits, especially in thalamo-parietal and cortico-striatal pathways. Decreased consciousness and neural integration corresponded to shifts in cortico-striatal network configurations that dissociated parietal and subcortical structures. Overall, the features of ALA and implicated networks were similar to those of absence epilepsy. As this same multi-microelectrode DBS method - but at different stimulation frequencies - can also increase consciousness in anesthetized macaques, it can be used to flexibly address questions of consciousness with limited confounds, as well as inform clinical investigations of absence epilepsy and other consciousness disorders. SIGNIFICANCEWe use tailored, multi-microelectrode thalamic deep brain stimulation to reversibly decrease consciousness for otherwise healthy, wakeful animals in a stimulation frequency-dependent manner. This represents a bidirectional mechanism for controlling consciousness, as the same method can increase consciousness under certain conditions. Theories of consciousness debate the relative contribution of parietal and frontal lobes, and largely ignore subcortical contributions. In this study, changes in consciousness predominantly involve changes in subcortical and parietal regions, implying that they contribute more to consciousness than frontal regions. Further, decreases in consciousness (indexed by {Phi}*) coincide with decreased movement, staring, and low-frequency activity in the EEG, similar to absence epilepsy. Thus, the systems-level mechanisms for decreased consciousness in this study have broader clinical implications for absence epilepsy.

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More than just front or back: Parietal-striatal-thalamic circuits predict consciousness level

Major theories of consciousness disagree on the key neural substrates. In Global Neuronal Workspace Theory and Higher-order Theories, consciousness depends on frontal cortex, whereas Integrated Information Theory and Recurrent Processing Theory highlight posterior contributions. Most theories omit subcortical influences. To test these theories, we performed simultaneous frontal, parietal, striatal and thalamic recordings from awake, sleeping and anesthetized macaques, further manipulating consciousness with deep-brain thalamic stimulation. Information theoretic measures and machine learning approaches suggested parietal cortex, striatum and thalamus contribute more to consciousness level than frontal cortex. While these findings provide greater support for Integrated Information Theory than the others, the theory does not incorporate subcortical structures such as the striatum. We therefore propose that thalamo-striatal circuits have a cause-effect structure to generate integrated information. One Sentence SummaryParietal, but not frontal, circuits incorporating striatum and thalamus predict consciousness.

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Dynamics of coherent activity between cortical areas defines a two-stage process of selective attention

Analysing a visual scene requires the brain to briefly keep in memory potentially relevant parts and then direct attention to their locations for detailed processing. To reveal the neuronal basis of the underlying working memory and top-down attention processes, we trained macaques to match two patterns presented with a delay between them. As the above processes are likely to require communication between brain regions, and the parietal cortex is involved in spatial attention, we simultaneously recorded neuronal activities from the interconnected parietal and middle temporal areas. We found that mnemonic information about the first pattern was retained in coherent oscillating activity between the areas in high-frequency bands, followed by coherent activity in low-frequency bands that mediate top-down attention on the relevant location. ONE SENTENCE SUMMARYGamma coherence allows retaining object features in a saliency map while lower frequency coherence facilitates attention.

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Receptors, circuits and neural dynamics for prediction

Learned associations between stimuli allow us to model the world and make predictions, crucial for efficient behavior; e.g., hearing a siren, we expect to see an ambulance and quickly make way. While there are theoretical and computational frameworks for prediction, the circuit and receptor-level mechanisms are unclear. Using high-density EEG, Bayesian modeling and machine learning, we show that inferred "causal" relationships between stimuli and frontal alpha activity account for reaction times (a proxy for predictions) on a trial-by-trial basis in an audio-visual delayed match-to-sample task which elicited predictions. Predictive beta feedback activated sensory representations in advance of predicted stimuli. Low-dose ketamine, a NMDA receptor blocker - but not the control drug dexmedetomidine - perturbed behavioral indices of predictions, their representation in higher-order cortex, feedback to posterior cortex and pre-activation of sensory templates in higher-order sensory cortex. This study suggests predictions depend on alpha activity in higher-order cortex, beta feedback and NMDA receptors, and ketamine blocks access to learned predictive information.

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Central thalamus modulates consciousness by controlling layer-specific cortical interactions

Consciousness is the capacity to experience ones environment and internal states. The minimal mechanisms sufficient to produce this experience, the neural correlates of consciousness (NCC), are thought to involve thalamocortical and intracortical interactions, but the key operations and circuit paths are unclear. We simultaneously recorded neural activity in central thalamus and across layers of fronto-parietal cortex in awake, sleeping and anesthetized macaques. Spiking activity was selectively reduced in deep cortical layers and thalamus during unconsciousness, as were intracolumnar and interareal interactions at alpha and gamma frequencies. Gamma-frequency stimulation, when focused on the central lateral thalamus of anesthetized macaques, counteracted these neural changes and restored consciousness. These findings suggest that the NCC involve both corticocortical feedforward and feedback pathways coordinated with intracolumnar and thalamocortical loops.\n\nSummaryStimulation of central lateral thalamus counters anesthesia to restore wake cortical dynamics and consciousness.

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Pulvinar influences parietal delay activity and information transmission between dorsal and ventral visual cortex in macaques

The fronto-parietal attention network represents attentional priorities and provides feedback about these priorities to sensory cortical areas. Sustained spiking activity in the posterior parietal cortex (PPC) carries such prioritized information, but how this activity is sustained in the absence of feedforward sensory information, and how it is transmitted to the ventral visual cortical pathway, is unclear. We hypothesized that the higher-order thalamic nucleus, the pulvinar, which is connected with both the PPC and ventral visual cortical pathway, influences information transmission within and between these cortical regions. To test this, we simultaneously recorded from the pulvinar, lateral intraparietal area (LIP) and visual cortical area V4 in macaques performing a selective attention task. Here we show that LIP influenced V4 during the delay period of the attention task, and that the pulvinar regulated LIP-V4 information exchange. Pulvino-cortical effects were consistent with the pulvinar supporting sustained activity in LIP. Taken together, these results suggest that pulvinar regulation of cortical functional connectivity generalizes to dorsal and ventral visual cortical pathways. Further, the pulvinars role in sustaining parietal delay activity during selective attention implicates the pulvinar in other cognitive processes supported by such delay activity, including decision-making, categorization and oculomotor functions.\n\nSignificance StatementA network of areas on the brains surface, in frontal and parietal cortex, allocate attention to behaviorally relevant information around us. Such areas in parietal cortex show sustained activity during maintained attention and transmit behaviorally relevant information to visual cortical areas to enhance sensory processing of attended objects. How this activity is sustained and how it is transmitted to visual areas supporting object perception is unclear. We show that a subcortical area, the pulvinar in the thalamus, helps sustain activity in the cortex and regulates the information transmitted between the fronto-parietal attention network and visual cortex. This suggests that the thalamus, classically considered as a simple relay for sensory information, contributes to higher-level cognitive functions.

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