Inflammation-induced reorientation of reward versus punishment sensitivity is attenuated by minocycline.

BACKGROUND: Inflammation rapidly reorients motivational state, mood is impaired, pleasurable activities avoided and sensitivity to negative stimuli enhanced. When sustained, this can precipitate major depressive episodes. In humans, this has been linked to opposing actions of inflammation on striatal/insula reward/punishment learning signals while in rodents, motivational impairments can be attenuated with minocycline, implicating a mechanistic role for microglia. Here we investigated whether minocycline also inhibits the reorienting effects of lipopolysaccharide (LPS) on reward/punishment sensitivity in humans. Methods Using a crossover design, fifteen healthy volunteers underwent two experimental sessions in which they each received LPS (1 ng/kg) and placebo. Half (N = 8) received minocycline (100 mg bd) and half (N = 7) an identical looking placebo for 3½ days before each session. Six hours post-injection participants completed a probabilistic instrumental learning task in which they had to learn to select high probability reward (win £1) and avoid high probability punishment (lose £1) stimuli to maximise their gains and minimize losses. Physiological and sickness responses were sampled hourly and blood sampled at baseline, 3 and 6 h post-injection. Results LPS induced robust peripheral physiological: temperature, heart rate and immune: differential white cell, IL-6, TNF-α, IL-8, IL-10 responses (all condition × time interactions: p < 0.005), none were significantly modulated by minocycline (p > 0.1). LPS also biased behavior, enhancing punishment compared with reward sensitivity (F(1,13) = 6.10, p = 0.028). Minocycline significantly attenuated this inflammation-induced shift in reward versus punishment sensitivity (F(1,13) = 4.28, p = 0.033). Conclusions These data replicate the previous finding that systemic inflammation rapidly impairs sensitivity to rewards versus punishments in humans and extend this by implicating activated microglia in this acute motivational reorientation with implications for the development of microglial-targeted immune-modulatory therapies in depression.

Sensory representations in primary visual cortex are not sufficient for subjective imagery.

The contemporary definition of mental imagery is characterized by two aspects: a sensory representation that resembles, but does not result from, perception, and an associated subjective experience. Neuroimaging demonstrated imagery-related sensory representations in primary visual cortex (V1) that show striking parallels to perception. However, it remains unclear whether these representations always reflect subjective experience or if they can be dissociated from it. We addressed this question by comparing sensory representations and subjective imagery among visualizers and aphantasics, the latter with an impaired ability to experience imagery. Importantly, to test for the presence of sensory representations independently of the ability to generate imagery on demand, we examined both spontaneous and voluntary imagery forms. Using multivariate fMRI, we tested for decodable sensory representations in V1 and subjective visual imagery reports that occurred either spontaneously (during passive listening of evocative sounds) or in response to the instruction to voluntarily generate imagery of the sound content (always while blindfolded inside the scanner). Among aphantasics, V1 decoding of sound content was at chance during voluntary imagery, and lower than in visualizers, but it succeeded during passive listening, despite them reporting no imagery. In contrast, in visualizers, decoding accuracy in V1 was greater in voluntary than spontaneous imagery (while being positively associated with the reported vividness of both imagery types). Finally, for both conditions, decoding in precuneus was successful in visualizers but at chance for aphantasics. Together, our findings show that V1 representations can be dissociated from subjective imagery, while implicating a key role of precuneus in the latter.

Mental imagery and visual attentional templates: A dissociation.

There is a growing interest in the relationship between mental images and attentional templates as both are considered pictorial representations that involve similar neural mechanisms. Here, we investigated the role of mental imagery in the automatic implementation of attentional templates and their effect on involuntary attention. We developed a novel version of the contingent capture paradigm designed to encourage the generation of a new template on each trial and measure contingent spatial capture by a template-matching visual feature (color). Participants were required to search at four different locations for a specific object indicated at the start of each trial. Immediately prior to the search display, color cues were presented surrounding the potential target locations, one of which matched the target color (e.g., red for strawberry). Across three experiments, our task induced a robust contingent capture effect, reflected by faster responses when the target appeared in the location previously occupied by the target-matching cue. Contrary to our predictions, this effect remained consistent regardless of self-reported individual differences in visual mental imagery (Experiment 1, N = 216) or trial-by-trial variation of voluntary imagery vividness (Experiment 2, N = 121). Moreover, contingent capture was observed even among aphantasic participants, who report no imagery (Experiment 3, N = 91). The magnitude of the effect was not reduced in aphantasics compared to a control sample of non-aphantasics, although the two groups reported substantial differences in their search strategy and exhibited differences in overall speed and accuracy. Our results hence establish a dissociation between the generation and implementation of attentional templates for a visual feature (color) and subjectively experienced imagery.