A. David Redish

Adaptive behavior under threat requires balancing reward pursuit against the risk of harm. During approach-avoidance conflict, animals often pause at decision points, but whether these pauses reflect a unified process or distinct decision states remains unclear. Here, we replicate and extend findings from Calvin et al.1 by analyzing hippocampal activity in rats performing a pseudo-predator foraging task across two cohorts. We compared mid-track aborts (MTAs), mid-track continues (MTCs), and retreats. Behaviorally, MTAs and MTCs emerged from a shared pause state but diverged in outcome, whereas retreats reflected rapid escape following attack. Despite similar endpoints, retreats and MTAs differed in movement dynamics and neural activity. During retreats, hippocampal representations remained biased toward the attack location. In contrast, representations during MTAs shifted toward safe locations. During pauses, representations differed according to subsequent behavior: pauses preceding MTAs showed greater decoded probability near the attack region, whereas pauses preceding MTCs showed greater decoded probability to goal locations. These differences were present during the outbound approach, suggesting decision-related processes emerged early on in the journey. Together, these findings dissociate hippocampal representations associated with reactive escape from those underlying anticipatory, anxiety-like decision-making, suggesting that the hippocampus dynamically tracks behaviorally relevant features to guide decisions under threat.

Spatial navigation involves neural computations in distributed regions of the brain. Little is known about how activity across cortical regions is coordinated when animals navigate novel spatial environments or how that coordination changes as environments become familiar. We recorded mesoscale calcium (Ca ²⁺ ) dynamics across large swathes of the dorsal cortex in male mice solving the Barnes maze, a 2D spatial navigation task where mice used random, serial, and spatial search strategies to navigate to the goal. Cortical dynamics exhibited patterns of repeated calcium activity with rapid and abrupt shifts between cortical activation patterns at subsecond timescales. When mice used serial or spatial search strategies to navigate to the goal, the frontal regions of the cortex were reliably activated for prolonged durations of time (>1 s) shortly after trial initiation. These frontal cortex activation events coincided with mice approaching the edge of the maze from the center and were preceded by temporal sequences of cortical activation patterns that were distinct for serial and spatial search strategies. In serial search trials, frontal cortex activation events were preceded by activation of the posterior regions of the cortex followed by lateral activation of one hemisphere. In spatial search trials, frontal cortical events were preceded by activation of posterior regions of the cortex followed by broad activation of the lateral regions of the cortex. Our results suggest that different sequences of cortical state activations precede goal-directed navigation in spatial versus serial strategies, with exploratory analysis identifying State 3 as potentially important in spatial search.

Summary / The GABA _A positive allosteric modulator diazepam is taken systemically by millions of people daily. GABA _A signaling is essential for hippocampal circuit function, but the effects of systemic diazepam on hippocampal information processing during behavior has not been studied. To answer this question, large neural ensembles were recorded from rats running a linear track under systemic diazepam administration. A cross-correlation of spiking activity revealed significantly increased inhibition from interneurons, aligned with the timescale of GABA _A , suggesting a direct effect on local circuits. Local field potentials (LFP) showed an increase in theta and lo-gamma (30-50 Hz) power but a decrease in hi-gamma (80-120 Hz) power. We also found decreased amplitude and rate of sharp wave ripple (SWR) events and a reduction of firing rate and proportion of cells recruited to the SWRs. An autocorrelation of single-cell spike trains revealed a decrease and shift from shorter to longer timescales, aligning differently with theta frequencies. Phase coupling measurements showed decreased cellular coupling to theta and increased coupling to lo-gamma and hi-gamma. Finally, entropy of decoding along the track was increased, suggesting less precise spatial representations under diazepam. These changes suggest mechanisms that would likely disrupt hippocampal memory storage and consolidation processes under systemic diazepam.

Microfinance institutions (MFIs) are commonly understood to succeed through structural mechanisms such as group lending, joint liability, peer monitoring, and repayment incentives. However, these explanations fail to account for the wide variation in outcomes among institutions employing similar contractual structures. We propose a new theoretical framework that reconceptualizes microfinance success as fundamentally dependent on the institutional cultivation of trust. Drawing on emerging neuroeconomic models of decision-making and cooperation, we argue that MFIs operate as assurance systems in which repayment and continued lending depend on mutually reinforced expectations of cooperation between borrowers and institutions. Within this framework, trust functions not as a byproduct of preexisting social capital, but as a psychological precursor to cooperative decision-making that can be intentionally structured through institutional design. We identify three distinct but interacting forms of trust—deliberative, instinctual, and procedural—through which institutions shape borrower expectations and stabilize cooperative equilibria. Through comparative analysis of major MFIs including Grameen Bank, BRAC, ASA, BancoSol, Bank Rakyat Indonesia, Equity Bank Kenya, and SKS Microfinance, we find that long-term institutional success is better explained by trust-generating architectures than by lending modality alone. Current global microfinance datasets inadequately capture these institutional dimensions, limiting the field’s ability to explain institutional resilience, scaling, and failure. Reframing microfinance through the lens of trust and neuroeconomic decision-making offers new implications for institutional design, financial inclusion policy, and the evaluation of development interventions under conditions of uncertainty.

Several electroencephalography-based metrics have been proposed to index excitation/inhibition balance (E/I). We used single-unit and local field potential recordings from rat medial prefrontal and orbitofrontal cortex and mouse visual cortex and hippocampus to evaluate four candidate metrics against empirically-measured E/I. While 1/f slope and gamma oscillations showed region and context dependencies, broadband (6-80 Hz) and high gamma (80-150 Hz) power consistently correlated with E/I, supporting their use as proxy measures. If at least 30 minutes' data from medial prefrontal cortex were used per animal, broadband power could rank the animals by their E/I ratio, suggesting it could be used as an individual differences measure.

Planning entails running simulations forward to identify possible outcomes. It is useful for situations where outcomes are uncertain, costly or dangerous to pursue. A growing body of literature is finding that during theta states in the rodent hippocampus, sequences run forward along possible futures, enabling 'episodic future thinking' that can be used within a neural circuit for planning. Emerging data suggest that the prelimbic cortex initiates these simulations, an entorhinal-hippocampal interaction generates them and valuation systems in the ventral striatum (nucleus accumbens) and orbitofrontal cortex evaluate them, enabling downstream decision-making processes to take action. Within the hippocampus, each theta cycle carries activity representing the present followed by explorations of possible paths ahead of the animal. These representations occur serially and sequentially. These theta sweeps are not mere reflections of movement but dynamic cognitive simulations whose length, direction and content shift with learning, confidence and experience. Individual theta cycles change in length and representation from cycle to cycle, suggesting a cognitive role. In this review, we bring together that body of literature and identify open questions and controversies for future research, including questions regarding how sweeps are structured, how they shift between exploration and commitment, and how threat-related representations interface with avoidance circuits. This article is part of the theme issue 'The role of hippocampal predictions in cognition: bridging perception and memory'.

Precise measurement of individual variation in psychiatric symptoms is essential for developing scalable tools that can ultimately inform treatment development and clinical care. Individuals performing the same cognitive task often adopt qualitatively distinct strategies that may reflect differences in underlying neural processes and psychiatric symptom dimensions. Yet most cognitive paradigms implicitly assume that all individuals rely on the same cognitive strategy, attributing behavioral variability to differences along a shared computational axis. This assumption may obscure meaningful cognitive heterogeneity that cuts across traditional diagnostic categories, which themselves group phenotypically and biologically diverse individuals. Even dimensional approaches may fail to capture distinct computational profiles if they assume a common underlying cognitive process across participants. To test this hypothesis, we combined a computationally grounded Context Generalization task involving different visual stimuli (color, shape, texture, size) with standardized self-report psychiatric questionnaires. We tested how distinct cognitive strategies relate to symptom dimensions commonly observed in autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), depression, and schizotypy. Participants (N=744 in session one; N=584 in session two) were recruited online, enriched for self-reported ASD diagnoses, and matched for sex at birth. We identified qualitatively unique strategies related to goal-directed attention and short-term memory, such as a focused goal-directed strategy and a frequency-based strategy that relied on attending to all the stimulus features. The goal-directed strategy was associated with lower behavioral rigidity, while the frequency-based strategy was associated with elevated behavioral rigidity, despite showing the highest task performance. Strategy membership was substantially stable across sessions. Although transitions from the random-like strategy to the frequency-based strategy occurred less often than expected by chance, the subset of individuals who made this transition showed elevated behavioral rigidity and inattention-related symptoms consistent with the broader frequency-based profile. These findings demonstrate that individuals vary substantially in the cognitive strategies used to solve the same task and highlight the importance of measuring inter-individual variation in computational strategy rather than relying solely on aggregate performance metrics. More broadly, our results support a framework for linking psychiatric phenotypes to interpretable patterns of attention and learning, advancing efforts toward computational phenotyping and precision psychiatry.

Adaptive behavior under threat requires balancing reward pursuit against the risk of harm. During approach-avoidance conflict, animals often pause at decision points, but whether these pauses reflect a unified process or distinct decision states remains unclear. Here, we replicate and extend findings from Calvin et al.1 by analyzing hippocampal activity in rats performing a predator-based foraging task across two cohorts. We compared three behaviors: mid-track aborts (MTAs), mid-track continues (MTCs), and attack-triggered retreats. Behaviorally, MTAs and MTCs emerged from a shared pause state but led to different outcomes, whereas retreats reflected rapid, reactive escape following attack. Despite similar behavioral endpoints (return to safety), retreats and MTAs differed markedly in movement dynamics and neural activity. During retreats, hippocampal representations remained biased toward the attack location, consistent with ongoing encoding of immediate threat. In contrast, MTAs showed a shift in representation toward safe locations following the decision to abort. During pauses, hippocampal activity differentiated future behavioral outcomes before movement diverged: pauses preceding MTAs showed stronger representation of threat-related locations, whereas pauses preceding MTCs emphasized goal-related locations. These representational biases were already present during the outbound approach, indicating that decision-related processes emerged at the beginning of the outbound journey. Across experience, representations of threat and goal locations became increasingly differentiated when encountering an attacking robot, diminished during extinction, and re-emerged when the attack was introduced again. Together, these findings extend prior work by dissociating hippocampal representations associated with reactive escape from those underlying anticipatory, anxiety-like decision-making, suggesting that the hippocampus dynamically tracks behaviorally relevant features to guide decisions under threat.

Cortical neurons continuously change their spatial tuning properties over days and weeks, yet how this representational drift is coordinated across distributed cortical networks remains unknown. Using a robotic cranial exoskeleton for chronic widefield calcium imaging with cellular resolution, we tracked over 110,000 unique layer 2/3 neurons across retrosplenial, visual, somatosensory, and motor cortices in mice navigating a figure-8 maze spanning 47 days. Single-neuron spatial tuning properties followed a posterior-to-anterior gradient, with retros- plenial and visual cortices containing the highest proportions of spatially tuned neurons. This was dissociated from local functional coupling, which was strongest in somatosensory cortex. Population activity formed a low-dimensional manifold whose geometry mirrored the structure of the maze. Despite these regional differences, all four regions decorrelated with similar exponential timescales, and session-specific deviations from each region’s decay trajectory were correlated across all pairwise region combinations, suggesting that drift was coordinated rather than independent across the dorsal cortex. This coordination persisted after controlling for shared behavioral fluctuations. Furthermore, drift was consistent with an orthogonal trans- formation of the population code that preserved the geometric relationships between spatial representations across sessions despite continuous drift in single-neuron tuning.