Early Immune Initiation by Porcine Cells following Toxoplasma gondii Infection versus TLR Ligation

Containment of acute Toxoplasma gondii infection is dependent on an efficient interferon gamma response. However, the earliest steps of immune response initiation immediately following exposure to the parasite have not been previously characterized in pigs. Murine and human myeloid cells produce large quantities of interleukin (IL)-12 during early T. gondii infection. We therefore examined IL-12 expression by porcine peripheral blood monocytes and dendritic cell (DC) subsets following toll-like receptor (TLR) ligation and controlled T. gondii tachyzoite infection. We detected IL-12p40 expression by porcine plasmacytoid DC, but not conventional or monocyte-derived DC following TLR ligation. Unexpectedly, we also observed considerable IL-12p40 production by porcine CD3– NKp46+ cells—a classical natural killer cell phenotype—following TLR ligation. However, in response to T. gondii exposure, no IL-12 production was observed by either DC or CD3– NKp46+ cells. Despite this, IL-18 production by DC-enriched peripheral blood mononuclear cells was detected following live T. gondii tachyzoite exposure. Only combined stimulation of porcine peripheral blood mononuclear cells with recombinant IL-12p70 and IL-18 induced innate interferon gamma production by natural killer cells, while T cells and myeloid cells did not respond. Therefore, porcine CD3– NKp46+ cells serve as important IL-12 producers following TLR ligation, while IL-18 likely plays a prominent role in early immune response initiation in the pig following T. gondii infection.

An fMRI study of initiation and inhibition of manual responses in people who stutter

Developmental stuttering is a speech motor disorder characterised by difficulties initiating speech and frequent interruptions to the speech flow. Previous work suggests that people who stutter (PWS) have an overactive response suppression mechanism. Imaging studies of speech production in PWS consistently reveal greater activity of the right inferior frontal cortex, an area robustly implicated in inhibitory control of both manual and spoken responses. Here, we used a manual response version of the stop-signal task during fMRI to investigate neural differences related to response initiation and inhibition in PWS. Behaviourally, PWS were slower to respond to ‘go’ stimuli than people who are typically fluent (PWTF), but there was no difference in stop-signal reaction time. Our fMRI results were consistent with these behavioural results. The fMRI analysis revealed the expected networks associated with manual response initiation and inhibition in both groups. However, all contrasts between the two groups were characterised by overactivity in PWS relative to PWTF. This overactivity was significantly different for the initiation of responses (i.e. the ‘go’ trials) but not for response inhibition (i.e. the ‘stop’ trials). One explanation of these results is that PWS are consistently in a heightened inhibition state, i.e. areas of the inhibition network are more active, generally. This interpretation is consistent with predictions from the global response suppression hypothesis.

Understanding the dual-task costs of walking: a StartReact study

The need to perform multiple tasks more or less simultaneously is a common occurrence during walking in daily life. Performing tasks simultaneously typically impacts task performance negatively. Hypothetically, such dual-task costs may be explained by a lowered state of preparation due to competition for attentional resources, or alternatively, by a ‘bottleneck’ in response initiation. Here, we investigated both hypotheses by comparing ‘StartReact’ effects during a manual squeezing task under single-task (when seated) and dual-task (when walking) conditions. StartReact is the acceleration of reaction times by a startling stimulation (a startling acoustic stimulus was applied in 25% of trials), attributed to the startling stimulus directly releasing a pre-prepared movement. If dual-task costs are due to a lowered state of preparation, we expected trials both with and without an accompanying startling stimulus to be delayed compared to the single-task condition, whereas we expected only trials without a startling stimulus to be delayed if a bottleneck in response initiation would underlie dual-task costs. Reaction times of the manual squeezing task in the flexor digitorum superficialis and extensor carpi radialis muscle were significantly delayed (approx. 20 ms) when walking compared to the seated position. A startling acoustic stimulus significantly decreased reaction times of the squeezing task (approx. 60 ms) both when walking and sitting. Dual-task costs during walking are, therefore, likely the result of lowered task preparation because of competition for attentional resources.

Response initiation and inhibition and the relationship with fluid intelligence across the adult lifespan

Background Cognitive processes associated with frontal lobe functioning are often termed “executive functions.” Two such processes are initiation and inhibition or the starting and stopping of responses. It has recently been claimed dysfunction of executive abilities can be explained by a single measure of fluid intelligence. Here, we test this claim, specifically for the executive abilities of response initiation and inhibition, across the healthy lifespan. Method In a cohort of 336 healthy adults (18–89 years), initiation and inhibition were assessed with the Hayling test, Stroop test, and phonemic and semantic verbal fluency. All participants also completed a measure of fluid intelligence. The relationship between fluid intelligence and executive measures was explored across the lifespan using a continuous approach. Mediation models were computed to assess whether age-related decline across the four initiation/inhibition tasks could be fully explained by a single measure of fluid intelligence. Results Age was negatively correlated with response initiation/inhibition and fluid intelligence. The mediation analyses identified only partial mediation of fluid intelligence for age and Hayling performance. By contrast, fluid intelligence did not mediate performance on the Stroop test or phonemic and semantic verbal fluency. Conclusions Response initiation/inhibition are not able to be explained by fluid intelligence. The results support a multifactorial theory of executive functions and provide evidence for the inclusion of multiple specific executive measures in a thorough neuropsychological assessment of age-related cognitive decline.