Distinct Contributions of Ventromedial and Dorsolateral Subregions of the Human Substantia Nigra to Appetitive and Aversive Learning.

The role of neurons in the substantia nigra (SN) and ventral tegmental area (VTA) of the midbrain in contributing to the elicitation of reward prediction errors during appetitive learning has been well established. Less is known about the differential contribution of these midbrain regions to appetitive versus aversive learning, especially in humans. Here we scanned human participants with high-resolution fMRI focused on the SN and VTA while they participated in a sequential Pavlovian conditioning paradigm involving an appetitive outcome (a pleasant juice), as well as an aversive outcome (an unpleasant bitter and salty flavor). We found a degree of regional specialization within the SN: Whereas a region of ventromedial SN correlated with a temporal difference reward prediction error during appetitive Pavlovian learning, a dorsolateral area correlated instead with an aversive expected value signal in response to the most distal cue, and to a reward prediction error in response to the most proximal cue to the aversive outcome. Furthermore, participants' affective reactions to both the appetitive and aversive conditioned stimuli more than 1 year after the fMRI experiment was conducted correlated with activation in the ventromedial and dorsolateral SN obtained during the experiment, respectively. These findings suggest that, whereas the human ventromedial SN contributes to long-term learning about rewards, the dorsolateral SN may be particularly important for long-term learning in aversive contexts. SIGNIFICANCE STATEMENT: The role of the substantia nigra (SN) and ventral tegmental area (VTA) in appetitive learning is well established, but less is known about their contribution to aversive compared with appetitive learning, especially in humans. We used high-resolution fMRI to measure activity in the SN and VTA while participants underwent higher-order Pavlovian learning. We found a regional specialization within the SN: a ventromedial area was selectively engaged during appetitive learning, and a dorsolateral area during aversive learning. Activity in these areas predicted affective reactions to appetitive and aversive conditioned stimuli over 1 year later. These findings suggest that, whereas the human ventromedial SN contributes to long-term learning about rewards, the dorsolateral SN may be particularly important for long-term learning in aversive contexts.

A compact and cost-effective laser-powered speckle visibility spectroscopy (SVS) device for measuring cerebral blood flow.

In the realm of cerebrovascular monitoring, primary metrics typically include blood pressure, which influences cerebral blood flow (CBF) and is contingent upon vessel radius. Measuring CBF non-invasively poses a persistent challenge, primarily attributed to the difficulty of accessing and obtaining signal from the brain. This study aims to introduce a compact speckle visibility spectroscopy (SVS) device designed for non-invasive CBF measurements, offering cost-effectiveness and scalability while tracking CBF with remarkable sensitivity and temporal resolution. The wearable hardware has a modular design approach consisting solely of a laser diode as the source and a meticulously selected board camera as the detector. They both can be easily placed on a subject's head to measure CBF with no additional optical elements. The SVS device can achieve a sampling rate of 80 Hz with minimal susceptibility to external disturbances. The device also achieves better SNR compared with traditional fiber-based SVS devices, capturing about 70 times more signal and showing superior stability and reproducibility. It is designed to be paired and distributed in multiple configurations around the head, and measure signals that exceed the quality of prior optical CBF measurement techniques. Given its cost-effectiveness, scalability, and simplicity, this laser-centric tool offers significant potential in advancing non-invasive cerebral monitoring technologies.

Neural correlates of specific and general Pavlovian-to-Instrumental Transfer within human amygdalar subregions: a high-resolution fMRI study.

It is widely held that the interaction between instrumental and Pavlovian conditioning induces powerful motivational biases. Pavlovian-Instrumental Transfer (PIT) is one of the key paradigms demonstrating this effect, which can further be decomposed into a general and specific component. Although these two forms of PIT have been studied at the level of amygdalar subregions in rodents, it is still unknown whether they involve different areas of the human amygdala. Using a high-resolution fMRI (hr-fMRI) protocol optimized for the amygdala in combination with a novel free operant task designed to elicit effects of both general and specific PIT, we demonstrate that a region of ventral amygdala within the boundaries of the basolateral complex and the ventrolateral putamen are involved in specific PIT, while a region of dorsal amygdala within the boundaries of the centromedial complex is involved in general PIT. These results add to a burgeoning literature indicating different functional contributions for these different amygdalar subregions in reward-processing and motivation.

Assessing depth sensitivity in laser interferometry speckle visibility spectroscopy (iSVS) through source-to-detector distance variation and cerebral blood flow monitoring in humans and rabbits.

Recently, speckle visibility spectroscopy (SVS) was non-invasively applied on the head to monitor cerebral blood flow. The technique, using a multi-pixel detecting device (e.g., camera), allows the detection of a larger number of speckles, increasing the proportion of light that is detected. Due to this increase, it is possible to collect light that has propagated deeper through the brain. As a direct consequence, cerebral blood flow can be monitored. However, isolating the cerebral blood flow from the other layers, such as the scalp or skull components, remains challenging. In this paper, we report our investigations on the depth-sensitivity of laser interferometry speckle visibility spectroscopy (iSVS). Specifically, we varied the depth of penetration of the laser light into the head by tuning the source-to-detector distance, and identified the transition point at which cerebral blood flow in humans and rabbits starts to be detected.

Neural signatures of social inferences predict the number of real-life social contacts and autism severity.

We regularly infer other people's thoughts and feelings from observing their actions, but how this ability contributes to successful social behavior and interactions remains unknown. We show that neural activation patterns during social inferences obtained in the laboratory predict the number of social contacts in the real world, as measured by the social network index, in three neurotypical samples (total n = 126) and one sample of autistic adults (n = 23). We also show that brain patterns during social inference generalize across individuals in these groups. Cross-validated associations between brain activations and social inference localize selectively to the right posterior superior temporal sulcus and were specific for social, but not nonsocial, inference. Activation within this same brain region also predicts autism-like trait scores from questionnaires and autism symptom severity. Thus, neural activations produced while thinking about other people's mental states predict variance in multiple indices of social functioning in the real world.

Evidence for model-based encoding of Pavlovian contingencies in the human brain.

Prominent accounts of Pavlovian conditioning successfully approximate the frequency and intensity of conditioned responses under the assumption that learning is exclusively model-free; that animals do not develop a cognitive map of events. However, these model-free approximations fall short of comprehensively capturing learning and behavior in Pavlovian conditioning. We therefore performed multivoxel pattern analysis of high-resolution functional MRI data in human participants to test for the encoding of stimulus-stimulus associations that could support model-based computations during Pavlovian conditioning. We found that dissociable sub-regions of the striatum encode predictions of stimulus-stimulus associations and predictive value, in a manner that is directly related to learning performance. Activity patterns in the orbitofrontal cortex were also found to be related to stimulus-stimulus as well as value encoding. These results suggest that the brain encodes model-based representations during Pavlovian conditioning, and that these representations are utilized in the service of behavior.