Biology subjects

Mamelak, A.

Publications and source records attributed to Mamelak, A..

5 recordsLinked to original sources

bioRxiv2026

Microstimulation of the human dopaminergic midbrain causally reshapes value-based decision-making and happiness

Midbrain circuits are thought to govern reward-guided behavior and momentary happiness, yet causal evidence in humans remains scarce. Here, we show that focal microstimulation of the substantia nigra pars compacta alters both decision making and momentary happiness in patients undergoing awake deep-brain stimulation surgery for Parkinsons disease. During a gambling task with interleaved momentary happiness ratings, stimulation delivered at outcome reduced risk-seeking in the loss domain without increasing overall gambling probability. Stimulation improved choice efficiency, guiding behavior toward gambles with higher expected value and thereby increasing cumulative earnings. Computational modeling revealed selective changes in loss processing, with reduced loss weighting and more linear loss utility, while gain processing remained unchanged. In parallel, stimulation did not tonically elevate happiness but selectively amplified outcome-related happiness changes, scaling with decision value and reward prediction errors. These results provide causal evidence that localized perturbation of human midbrain circuits reshapes valuation, choice, and momentary well-being.

neuroscience↗

bioRxiv2026

Autonomous error detection is enabled by conflict-dependent forward models in human medial frontal cortex

Learning from mistakes is fundamental for survival. Humans can monitor their behavior to detect action errors without external feedback, utilizing error information for adaptation and learning. How such errors are detected remains unknown. We investigated single neurons recorded from human medial frontal cortex while subjects performed a task in which conflict between target and distractor increases control demands and error likelihood. Population activity in presupplementary motor area (preSMA), but not dorsal anterior cingulate, encoded target and distractor responses distinctly and only in conflict trials. These representations were insensitive to response accuracy, indicating they reflect forward predictive models. Geometric alignment between target and actual response representations covaried with error commission, supporting the mismatch theory of error monitoring. Artificial neural networks trained to detect errors developed similar neural geometries. These findings identify a mechanism for detecting errors without external feedback and show that all signals required for this computation are present in preSMA.

neuroscience↗

bioRxiv2023

Encoding of predictive associations in human prefrontal and medial temporal neurons during Pavlovian conditioning

Pavlovian conditioning is thought to involve the formation of learned associations between stimuli and values, and between stimuli and specific features of outcomes. Here we leveraged human single neuron recordings in ventromedial prefrontal, dorsomedial frontal, hippocampus and amygdala neurons while patients performed a sequential Pavlovian conditioning task containing both stimulus-value and stimulus-stimulus associations. Neurons in the ventromedial prefrontal cortex encoded predictive value along with the amygdala, but also encoded predictions about the identity of stimuli that would subsequently be presented, suggesting a role for neurons in this region in encoding predictive information beyond value. Unsigned error signals were found in dorsomedial prefrontal areas and hippocampus, potentially supporting learning of non-value related outcome features. Our findings implicate distinct human prefrontal and medial temporal neuronal populations in mediating predictive associations which could partially support model-based mechanisms during Pavlovian conditioning. Significance statementPavlovian conditioning is a fundamental form of learning, allowing organisms to associate stimuli and outcomes. Recent Pavlovian work suggests that phenomena such as devaluation sensitivity and sensory preconditioning can be explained by a model-based learning framework. How human neurons perform model-based learning during Pavlovian conditioning is still an open question. We recorded single neurons from epilepsy patients during a two-step Pavlovian conditioning task and found that ventromedial prefrontal neurons encoded expected rewards along with amygdala neurons, but also predicted the identity of upcoming stimuli as required for model-based cognition. Additionally, medial frontal neurons were found to encode error signals that could be used for stimulus-outcome learning. This is the first study mapping model-based computations during Pavlovian conditioning in human neurons.

neuroscience↗

bioRxiv2021

Cognitive boundary signals in the human medial temporal lobe shape episodic memory representation

While experience unfolds continuously, memories are organized as a set of discrete events that bind together the "where", "when", and "what" of episodic memory. This segmentation of continuous experience is thought to be facilitated by the detection of salient environmental or cognitive events. However, the underlying neural mechanisms and how such segmentation shapes episodic memory representations remain unclear. We recorded from single neurons in the human medial temporal lobe while subjects watched videos with different types of embedded boundaries and were subsequently evaluated for memories of the video contents. Here we show neurons that signal the presence of cognitive boundaries between subevents from the same episode and neurons that detect the abstract separation between different episodes. The firing rate and spike timing of these boundary-responsive neurons were predictive of later memory retrieval accuracy. At the population level, abrupt neural state changes following boundaries predicted enhanced memory strength but impaired order memory, capturing the behavioral tradeoff subjects exhibited when recalling episodic content versus temporal order. Successful retrieval was associated with reinstatement of the neural state present following boundaries, indicating that boundaries structure memory search. These findings reveal a neuronal substrate for detecting cognitive boundaries and show that cognitive boundary signals facilitate the mnemonic organization of continuous experience as a set of discrete episodic events.

neuroscience↗

bioRxiv2019

Flexible recruitment of memory-based choice representations by human medial-frontal cortex

Decisions in complex environments rely on flexibly utilizing past experience as required by context and instructions1. This process depends on the medial frontal cortex (MFC) and the medial temporal lobe (MTL)2-5, but it remains unknown how these structures jointly implement flexible memory retrieval6,7. We recorded single neurons in MFC and MTL while human subjects switched8 between making memory- and categorization-based decisions9,10. Here we show that MFC rapidly implements changing task demands by utilizing different subspaces of neural activity during different types of decisions. In contrast, no effect of task demands was seen in the MTL. Choices requiring memory retrieval selectively engaged phase-locking of MFC neurons to field potentials in the theta-frequency band in the MTL. Choice-selective neurons in MFC signaled abstract yes-no decisions independent of behavioral response modality (button press or saccade). These findings reveal a novel mechanism for flexibly and selectively engaging memory retrieval11-14 and show that unlike perceptual decision-making15, memory-related information is only represented in frontal cortex when choices require it.

neuroscience↗