Cognitive flexibility in 12-month-old preterm and term infants is associated with neurobehavioural development in 18-month-olds

There is growing evidence that preterm children are at an increased risk of poor executive functioning, which underlies behavioural and attention problems. Previous studies have suggested that early cognitive flexibility is a possible predictor of later executive function; however, how it develops in infancy and relates to the later neurobehavioural outcomes is still unclear in the preterm population. Here, we conducted a longitudinal study to investigate oculomotor response shifting in 27 preterm and 25 term infants at 12 months and its relationship with general cognitive development and effortful control, which is a temperamental aspect closely associated with executive function, at 18 months. We found that moderate to late preterm and term infants significantly inhibited previously rewarded look responses, while very preterm infants did not show significant inhibition of perseverative looking at 12 months. Moreover, lower inhibition of perseverative looking was significantly associated with lower general cognitive development and attentional shifting at 18 months. These findings suggest that the early atypical patterns of oculomotor response shifting may be a behavioural marker for predicting a higher risk of negative neurobehavioural outcomes, including attention-related problems in preterm children.

Visual, delay and oculomotor timing and tuning in macaque dorsal pulvinar during instructed and free choice memory saccades

Causal perturbation studies suggest that the primate dorsal pulvinar (dPul) plays a crucial role in target selection and saccade planning, but many of its basic visuomotor neuronal properties are unclear. While some functional aspects of dPul and interconnected frontoparietal areas - such as ipsilesional choice bias after inactivation - are similar, it is not known if dPul neurons share oculomotor response properties of cortical circuitry. In particular, the delay period and choice-related activity have not been explored. Here we investigated visuomotor timing and tuning in macaque dPul during instructed and free choice memory saccades using electrophysiological recordings. Most units (80%) showed significant visual (16%), visuomotor (29%) or motor-related (35%) responses. Visual cue responses were mainly contralaterally-tuned; motor responses showed weak contralateral bias. Saccade-related responses (enhancement and suppression) were more common (64%) than cue-driven responses (45%). Pre-saccadic enhancement was less frequent (9-15% depending on the definition), and only few units exhibited classical visuomotor patterns such as a combination of cue and continuous delay period activity up to the saccade onset, or pre-saccadic ramping. Instead, activity was often suppressed during movement planning (30%) and execution phases (19%). Interestingly, most spatially-selective neurons did not encode the upcoming decision during the delay in free choice trials. Thus, in absence of a visible goal, the dorsal pulvinar has only a limited role in the prospective motor planning, with response patterns partially complementary to its frontoparietal cortical partners. Conversely, prevalent cue and post-saccadic responses imply that the dorsal pulvinar participates in integrating spatial goals with processing across saccades.

Chemogenetic inactivation reveals the inhibitory control function of the prefronto-striatal pathway in the macaque brain

The lateral prefrontal cortex (LPFC) has a strong monosynaptic connection with the caudate nucleus (CdN) of the striatum. Previous human MRI studies have suggested that this LPFC-CdN pathway plays an important role in inhibitory control and working memory. We aimed to validate the function of this pathway at a causal level by pathway-selective manipulation of neural activity in non-human primates. To this end, we trained macaque monkeys on a delayed oculomotor response task with reward asymmetry and expressed an inhibitory type of chemogenetic receptors selectively to LPFC neurons that project to the CdN. Ligand administration reduced the inhibitory control of impulsive behavior, as well as the task-related neuronal responses observed in the local field potentials from the LPFC and CdN. These results show that we successfully suppressed pathway-selective neural activity in the macaque brain, and the resulting behavioral changes suggest that the LPFC-CdN pathway is involved in inhibitory control.

Confirmation of age-related alterations in inhibitory control using a modified minimally delayed oculomotor response (MDOR) task

Considerable effort has been made to measure and understand the effects of ageing on inhibitory control using a range of behavioural tasks. In the minimally delayed oculomotor response (MDOR) task, participants are presented with a simple visual target step with variable target display duration (TDD), and instructed to saccade to the target not when it appears (a prosaccade response), but when it disappears (i.e., on target offset). Using this task, we recently found higher error rates and longer latencies for correct responses in older compared to younger participants. Here we have used a modified MDOR task, in which participants were presented with static placeholders identifying potential target positions (increasing spatial information), and three TDDs rather than two (reducing temporal predictability). We found that the yield of analysable trials was generally higher with this modified task and in 28 older (mean ± SD age: 65 ± 7 y) and 25 younger (26 ± 7 y) participants the total overall error rate was again higher in the older group (30 ± 18% vs. 16 ± 11%). An analysis of the temporal distribution of responses demonstrated a pronounced peak in error production around 150 ms (young) or 200 ms (old) after target onset. When we recalculated the error rate focusing on these errors, it was again significantly higher in the older group. The latency of correct responses (to offsets) was significantly increased in the older group, although much of this increase was accounted for by expected age-related visuomotor slowing. However, both latency and distribution data suggested that while older participants could generate increased levels of inhibition, they could not maintain these levels as efficiently as the younger participants. In 24 participants (15 old, 9 young) who completed both versions of the MDOR task, neither latency nor error rates differed significantly between versions. These results confirm an inhibitory control deficit in healthy older participants, and suggest that the dynamics of inhibitory control are also affected by ageing. The modified MDOR task yields more data while not altering basic performance parameters.

Oculomotor response to images in primary school children with mild intellectual disability

Oculomotor activity (eye movements) is an essential component of visual data acquisition, analysis and use. The aim of this study was to determine the characteristics of oculomotor response to static images in primary school children with mild intellectual disability (ID). Our sample included a total of 49 schoolers (23 children with mild ID and 26 typically developing children). Oculomotor activity was evaluated using a GP3 Gazepoint eye tracker. The participants were presented with 15 visual stimuli: 10 pictorial and 5 mixed (pictures + text) static color images. Children with mild ID generated significantly fewer fixations (р = 0.038) than typically developing children. So, learning materials containing both pictorial and textual images are ineffective because textual elements are completely ignored by children with mild ID. The total duration of gaze fixations was significantly longer (р = 0.029) in typically developing children than in children with mild ID. However, the average duration of a single gaze fixation was longer in children with mild ID. The identified features of oculomotor response can help to optimize the format of instructional materials for primary school children with mild ID.

Effector-Specific Characterization of Brain Dynamics in Manual vs. Oculomotor Go/NoGo Tasks

Motor inhibitory control (IC), the ability to suppress unwanted actions, has been previously shown to rely on domain-general IC processes that are involved in a wide range of IC tasks. Nevertheless, the existence of effector-specific regions and activation patterns that would differentiate manual vs. oculomotor response inhibition remains unknown. In this study, we investigated the brain dynamics supporting these two response effectors with the same IC task paradigm. We examined the behavioral performance and electrophysiological activity in a group of healthy young people (n = 25) with a Go/NoGo task using the index finger for the manual modality and the eyes for the oculomotor modality. By computing topographic analysis of variance, we found significant differences between topographies of scalp recorded potentials of the two response effectors between 250 and 325 ms post-stimulus onset. The source estimations localized this effect within the left precuneus, a part of the superior parietal lobule, showing stronger activity in the oculomotor modality than in the manual modality. Behaviorally, we found a significant positive correlation in response time between the two modalities. Our collective results revealed that while domain-general IC processes would be engaged across different response effectors in the same IC task, effector-specific activation patterns exist. In this case, the stronger activation of the left precuneus likely accounts for the increased demand for visual attentional processes in the oculomotor Go/NoGo task.

Recurrent circuit dynamics underlie persistent activity in the macaque frontoparietal network

During delayed oculomotor response tasks, neurons in the lateral intraparietal area (LIP) and the frontal eye fields (FEF) exhibit persistent activity that reflects the active maintenance of behaviorally relevant information. Despite many computational models of the mechanisms of persistent activity, there is a lack of circuit-level data from the primate to inform the theories. To fill this gap, we simultaneously recorded ensembles of neurons in both LIP and FEF while macaques performed a memory-guided saccade task. A population encoding model revealed strong and symmetric long-timescale recurrent excitation between LIP and FEF. Unexpectedly, LIP exhibited stronger local functional connectivity than FEF, and many neurons in LIP had longer network and intrinsic timescales. The differences in connectivity could be explained by the strength of recurrent dynamics in attractor networks. These findings reveal reciprocal multi-area circuit dynamics in the frontoparietal network during persistent activity and lay the groundwork for quantitative comparisons to theoretical models.