Facing successfully high mental workload and stressors: An fMRI study.

The present fMRI study aimed at highlighting patterns of brain activations and autonomic activity when confronted with high mental workload and the threat of auditory stressors. Twenty participants performed a complex cognitive task in either safe or aversive conditions. Our results showed that increased mental workload induced recruitment of the lateral frontoparietal executive control network (ECN), along with disengagement of medial prefrontal and posterior cingulate regions of the default mode network (DMN). Mental workload also elicited an increase in heart rate and pupil diameter. Task performance did not decrease under the threat of stressors, most likely due to efficient inhibition of auditory regions, as reflected by a large decrement of activity in the superior temporal gyri. The threat of stressors was also accompanied with deactivations of limbic regions of the salience network (SN), possibly reflecting emotional regulation mechanisms through control from dorsal medial prefrontal and parietal regions, as indicated by functional connectivity analyses. Meanwhile, the threat of stressors induced enhanced ECN activity, likely for improved attentional and cognitive processes toward the task, as suggested by increased lateral prefrontal and parietal activations. These fMRI results suggest that measuring the balance between ECN, SN, and DMN recruitment could be used for objective mental state assessment. In this sense, an extra recruitment of task-related regions and a high ratio of lateral versus medial prefrontal activity may represent a relevant marker of increased but efficient mental effort, while the opposite may indicate a disengagement from the task due to mental overload and/or stressors.

Incongruent object/context relationships in visual scenes: where are they processed in the brain?

Rapid object visual categorization in briefly flashed natural scenes is influenced by the surrounding context. The neural correlates underlying reduced categorization performance in response to incongruent object/context associations remain unclear and were investigated in the present study using fMRI. Participants were instructed to categorize objects in briefly presented scenes (exposure duration=100ms). Half of the scenes consisted of objects pasted in an expected (congruent) context, whereas for the other half, objects were embedded in incongruent contexts. Object categorization was more accurate and faster in congruent relative to incongruent scenes. Moreover, we found that the two types of scenes elicited different patterns of cerebral activation. In particular, the processing of incongruent scenes induced increased activations in the parahippocampal cortex, as well as in the right frontal cortex. This higher activity may indicate additional neural processing of the novel (non experienced) contextual associations that were inherent to the incongruent scenes. Moreover, our results suggest that the locus of object categorization impairment due to contextual incongruence is in the right anterior parahippocampal cortex. Indeed in this region activity was correlated with the reaction time increase observed with incongruent scenes. Representations for associations between objects and their usual context of appearance might be encoded in the right anterior parahippocampal cortex.

Neural correlates of the continuous Wagon Wheel Illusion: a functional MRI study.

After prolonged viewing of a continuous periodic motion stimulus at frequencies around 10 Hz, observers experience a fleeting impression of reversed motion: the continuous Wagon Wheel Illusion (c-WWI). To account for this phenomenon it has been proposed that attentional mechanisms discretely sample motion information. Alternative accounts argue that the illusion relies on the spurious activation of motion detectors, which under the effect of adaptation could trigger a reversed percept. We investigated the neural correlates of the c-WWI using fMRI (3T). Subjects viewed a vertically bisected ring containing a radial grating unambiguously rotating at 10 Hz; they continuously reported the perceived motion direction within each half of the ring. The two halves always rotated in opposite directions, allowing us to separately explore illusory reversals occurring within each hemifield. Comparing BOLD activity during illusory (c-WWI) or real perceptual periods revealed systematic differences in right parietal regions, in addition to the right motion complex MT+. This activation pattern did not depend on the side on which the illusion occurred, and could not be accounted for by purely perceptual switch-related activity-known to encompass parietal regions during other bistable effects. This first characterization of the fMRI correlates of the c-WWI may have implications for the different theoretical explanations of the phenomenon.

A Reproducible New Model of Focal Ischemic Injury in the Marmoset Monkey: MRI and Behavioural Follow-Up.

Ischemic stroke mostly affects the primary motor cortex and descending motor fibres, with consequent motor impairment. Pre-clinical models of stroke with reproducible and long-lasting sensorimotor deficits in higher-order animals are lacking. We describe a new method to induce focal brain damage targeting the motor cortex to study damage to the descending motor tracts in the non-human primate. Stereotaxic injection of malonate into the primary motor cortex produced a focal lesion in middle-aged marmosets (Callithrix jacchus). Assessment of sensorimotor function using a neurological scale and testing of forelimb dexterity and strength lasted a minimum of 12 weeks. Lesion evolution was followed by magnetic resonance imaging (MRI) at 24 h, 1 week, 4 and 12 weeks post-injury and before sacrifice for immunohistochemistry. Our model produced consistent lesions of the motor cortex, subcortical white matter and caudate nucleus. All animals displayed partial spontaneous recovery with long lasting motor deficits of force (54% loss) and dexterity (≈ 70% loss). Clearly visible T2 hypointensity in the white matter was observed with MRI and corresponded to areas of chronic gliosis in the internal capsule and lenticular fasciculus. We describe a straightforward procedure to reproducibly injure the motor cortex in the marmoset monkey, causing long-lasting motor deficits. The MRI signature reflects Wallerian degeneration and remote injury of corticospinal and corticopontine tracts, as well as subcortical motor loops. Our model may be suitable for the testing of therapies for post-stroke recovery, particularly in the chronic phase.

Influences of age, mental workload, and flight experience on cognitive performance and prefrontal activity in private pilots: a fNIRS study.

The effects of aging on cognitive performance must be better understood, especially to protect older individuals who are engaged in risky activities (e.g. aviation). Current literature on executive functions suggests that brain compensatory mechanisms may counter cognitive deterioration due to aging, at least up to certain task load levels. The present study assesses this hypothesis in private pilots engaged in two executive tasks from the standardized CANTAB battery, namely Spatial Working Memory (SWM) and  One Touch Stockings of Cambridge (OTS). Sixty-one pilots from three age groups (young, middle-aged, older) performed these two tasks from low to very high difficulty levels, beyond those reported in previous aging studies. A fNIRS headband measured changes in oxyhemoglobin (HbO2) in the prefrontal cortex. Results confirmed an overall effect of the difficulty level in the three age groups, with a decline in task performance and an increase in prefrontal HbO2 signal. Performance of older relative to younger pilots was impaired in both tasks, with the greatest impairment observed for the highest-load Spatial Working Memory task. Consistent with this behavioral deficit in older pilots, a plateau of prefrontal activity was observed at this highest-load level, suggesting that a ceiling in neural resources was reached. When behavioral performance was either equivalent between age groups or only slightly impaired in the older group, there were not any age-related differences in prefrontal activity. Finally, older pilots with extensive flying experience tend to show better preserved spatial working memory performance when compared to mildly-experienced of the same age group. The present findings are discussed in the frames of HAROLD and CRUNCH theoretical models of cognitive and neural aging, evoking the possibility that piloting expertise may contribute to preserve executive functions throughout adulthood.

Acquisition of a new bimanual coordination pattern modulates the cerebral activations elicited by an intrinsic pattern: an fMRI study.

Intensive practice of a new complex motor skill results in progressive improvement of performance. This induces neuroplastic changes, reflecting the transition from attention-demanding to more automatic performance throughout the learning. In the present fMRI study, learning-related cerebral activation changes during the acquisition of a new complex bimanual coordination pattern were examined, i.e., the 90 degrees out-of-phase pattern (90Phi). Furthermore, we investigated whether practice of this new pattern influenced the neural correlates associated with performance of a preferred intrinsic pattern. Twelve young healthy subjects were intensively trained on the 90Phi task, and underwent two fMRI scanning sessions in early (PRE) and late (POST) learning. Scanning sessions included performance of the trained 90Phi pattern, as well as the nontrained intrinsic in-phase pattern (InPhi). Kinematics registered during training and scanning experiments showed that the new 90Phi pattern was acquired successfully, resulting in learning-related brain activation changes. Activation decreases were observed in the right prefrontal cortex (DLPFC and dorsal premotor), in the right middle temporal and occipital cortices and in the posterior cerebellum. Conversely, increases were found in the basal ganglia and hippocampus. Interestingly, activity elicited by the InPhi task also evidenced within-subjects PRE/POST differences (although kinematics InPhi performance was equivalent in both sessions). In particular, the learning-related decreases found for the 90Phi pattern in the cerebellum, the occipital and temporal gyri were similarly observed for the intrinsic InPhi pattern. Moreover, InPhi performance induced PRE/POST increases of activity in the left superior frontal gyrus. Our fMRI results suggest that intensive practice of a new complex coordination pattern impacted, at least temporarily, on the neural correlates of preferred intrinsic coordination patterns. Additional neural recruitment might reflect increased mental effort to prevent negative transfer from the learned mode onto the intrinsic coordination mode.

Long Term Memory for Noise: Evidence of Robust Encoding of Very Short Temporal Acoustic Patterns.

Recent research has demonstrated that humans are able to implicitly encode and retain repeating patterns in meaningless auditory noise. Our study aimed at testing the robustness of long-term implicit recognition memory for these learned patterns. Participants performed a cyclic/non-cyclic discrimination task, during which they were presented with either 1-s cyclic noises (CNs) (the two halves of the noise were identical) or 1-s plain random noises (Ns). Among CNs and Ns presented once, target CNs were implicitly presented multiple times within a block, and implicit recognition of these target CNs was tested 4 weeks later using a similar cyclic/non-cyclic discrimination task. Furthermore, robustness of implicit recognition memory was tested by presenting participants with looped (shifting the origin) and scrambled (chopping sounds into 10- and 20-ms bits before shuffling) versions of the target CNs. We found that participants had robust implicit recognition memory for learned noise patterns after 4 weeks, right from the first presentation. Additionally, this memory was remarkably resistant to acoustic transformations, such as looping and scrambling of the sounds. Finally, implicit recognition of sounds was dependent on participant's discrimination performance during learning. Our findings suggest that meaningless temporal features as short as 10 ms can be implicitly stored in long-term auditory memory. Moreover, successful encoding and storage of such fine features may vary between participants, possibly depending on individual attention and auditory discrimination abilities. Significance Statement Meaningless auditory patterns could be implicitly encoded and stored in long-term memory.Acoustic transformations of learned meaningless patterns could be implicitly recognized after 4 weeks.Implicit long-term memories can be formed for meaningless auditory features as short as 10 ms.Successful encoding and long-term implicit recognition of meaningless patterns may strongly depend on individual attention and auditory discrimination abilities.

Neural and psychophysiological correlates of human performance under stress and high mental workload.

In our anxiogenic and stressful world, the maintenance of an optimal cognitive performance is a constant challenge. It is particularly true in complex working environments (e.g. flight deck, air traffic control tower), where individuals have sometimes to cope with a high mental workload and stressful situations. Several models (i.e. processing efficiency theory, cognitive-energetical framework) have attempted to provide a conceptual basis on how human performance is modulated by high workload and stress/anxiety. These models predict that stress can reduce human cognitive efficiency, even in the absence of a visible impact on the task performance. Performance may be protected under stress thanks to compensatory effort, but only at the expense of a cognitive cost. Yet, the psychophysiological cost of this regulation remains unclear. We designed two experiments involving pupil diameter, cardiovascular and prefrontal oxygenation measurements. Participants performed the Toulouse N-back Task that intensively engaged both working memory and mental calculation processes under the threat (or not) of unpredictable aversive sounds. The results revealed that higher task difficulty (higher n level) degraded the performance and induced an increased tonic pupil diameter, heart rate and activity in the lateral prefrontal cortex, and a decreased phasic pupil response and heart rate variability. Importantly, the condition of stress did not impact the performance, but at the expense of a psychophysiological cost as demonstrated by lower phasic pupil response, and greater heart rate and prefrontal activity. Prefrontal cortex seems to be a central region for mitigating the influence of stress because it subserves crucial functions (e.g. inhibition, working memory) that can promote the engagement of coping strategies. Overall, findings confirmed the psychophysiological cost of both mental effort and stress. Stress likely triggered increased motivation and the recruitment of additional cognitive resources that minimize its aversive effects on task performance (effectiveness), but these compensatory efforts consumed resources that caused a loss of cognitive efficiency (ratio between performance effectiveness and mental effort).

White matter disruption at the prodromal stage of Alzheimer's disease: relationships with hippocampal atrophy and episodic memory performance.

White matter tract alterations have been consistently described in Alzheimer's disease (AD). In particular, limbic fronto-temporal connections, which are critical to episodic memory function, may degenerate early in the course of the disease. However the relation between white matter tract degeneration, hippocampal atrophy and episodic memory impairment at the earliest stages of AD is still unclear. In this magnetic resonance imaging study, white matter integrity and hippocampal volumes were evaluated in patients with amnestic mild cognitive impairment due to AD (Albert et al., 2011) (n = 22) and healthy controls (n = 15). Performance in various episodic memory tasks was also evaluated in each participant. Relative to controls, patients showed a significant reduction of white matter fractional anisotropy (FA) and increase of radial diffusivity (RD) in the bilateral uncinate fasciculus, parahippocampal cingulum and fornix. Within the patient group, significant intra-hemispheric correlations were notably found between hippocampal grey matter volume and FA in the uncinate fasciculus, suggesting a relationship between atrophy and disconnection of the hippocampus. Moreover, episodic recognition scores were related with uncinate fasciculus FA across patients. These results indicate that fronto-hippocampal connectivity is reduced from the earliest pre-demential stages of AD. Disruption of fronto-hippocampal connections may occur progressively, in parallel with hippocampal atrophy, and may specifically contribute to early initial impairment in episodic memory.

Cleaved lymphocytes in chronic lymphocytic leukemia: a detailed retrospective analysis of diagnostic features.

Through a global analysis of diagnostic features, the aim was to profile CLL patients with circulating cleaved lymphocytes at diagnosis, a controversial prognostic factor. Although some of them could have been considered today as having Non-Hodgkin's lymphoma, all 106 patients of our retrospective series have had CLL treatments. Slide review distinguished seven lymphocyte morphotypes. With minimal a priori assumptions, excluding in particular clinical staging systems, forty-five diagnostic features were analyzed in 37 patients. CORICO (Correlations Iconography), a purely geometric method, deciphered the multidimensional structure of the raw data. Probabilistic monoparametric tests were made on the 106 patients. In ten patients (Binet stages: 3A, 6B, 1C), at least 8% of the lymphocytes were cleaved. Unrelated to the prolymphocytes, this morphotype had neither links with the CD5+CD23+ (9/10 vs 80/86), FMC7+ (5/10 vs 22/62), CD38 (1/7 vs 7/64) markers nor with any major CLL laboratory values; only three links characterized it: no cases of mixed marrow infiltrate (nodular: 1, interstitial: 6, diffuse: 3; ns), a lower percentage of eosinophils (ns), and predominance of CD11c (7/10 vs 20/66, p < 0.02). In conclusion, in contrast to the PLL morphotype, or to the lactic dehydrogenase (LDH) activity, which was a strong prognostic factor in this series, an independent detrimental value of the cleaved morphotype has not yet been found. Our study shows that free of modeling constraints, this method makes possible a rapid and objective insight into variable interrelations. If further explored in a prospective study, this approach may contribute to the understanding of discrepancies in the literature.

Mental calculation impairment in Alzheimer's disease: a functional magnetic resonance imaging study.

This functional MRI study investigates cerebral activations during mental arithmetic performance, in patients diagnosed with probable Alzheimer's disease (with mild to moderate severity) and age-matched healthy controls. The arithmetic task consisted in three-digit addition and subtraction problems. The task elicited bilateral parietal and prefrontal activations in the control group, in agreement with previous imaging studies of mental arithmetic. In the Alzheimer group, inferior parietal and lateral prefrontal activations were significantly reduced when compared to controls (corrected P < 0.05 ). This important reduction of activity was likely responsible for the patients' poor performance in the task. These results confirm the deficit in calculation abilities, which occurs early in Alzheimer's disease, and provide additional knowledge of the neural mechanisms underlying this impairment.

Dual-task interference during initial learning of a new motor task results from competition for the same brain areas.

Cerebral patterns of activity elicited by dual-task performance throughout the learning of a complex bimanual coordination pattern were addressed. Subjects (N=12) were trained on the coordination pattern and scanned using fMRI at early (PRE) and late (POST) learning stages. During scanning, the coordination pattern was performed either as a single task or in concurrence with a simultaneous visual search task (i.e. dual task). Kinematics data revealed a significant performance improvement as a result of learning. In PRE-scanning, the dual-task condition induced deterioration of motor performance, relative to the single-task condition. Activity in lateral frontal and parietal regions involved in both visual search and motor coordination tasks (i.e. 'overlapping' regions) was reduced when the tasks were performed simultaneously. In POST-scanning, kinematics performance was equivalent under single- and dual-task conditions, suggesting automaticity of the coordination pattern. Furthermore, overlap between regions involved in visual search and motor tasks was reduced, and dual-task performance was no longer associated with reduction of frontal and parietal activity. Our results suggest that behavioral interference between a complex motor coordination task and a simple simultaneous visual search task occurs when both tasks recruit overlapping regions in the frontal and parietal cortices. This may provide a neural basis for dissipation of dual-task interference following extensive motor practice, which is a traditional behavioral marker of motor automaticity.

Verbal episodic memory impairment in Alzheimer's disease: a combined structural and functional MRI study.

Anatomical and functional MRI images were acquired in a group of healthy elderly subjects (n = 11) and a group of patients diagnosed with probable Alzheimer's disease, from mild to moderate severity (n = 8). During functional sessions, verbal episodic Encoding and Recognition tasks were presented to subjects. Both groups were compared in terms of gray matter volume and cerebral activation. Furthermore, in the AD group, correlations between hippocampal gray matter volume and whole-brain activations were examined. When compared to healthy controls, AD patients presented significant gray matter atrophy as well as reduced activations during Encoding and Recognition in the medial temporal lobes and inferior parietal/superior temporal associative areas. In the same regions, the fMRI activity elicited by the Recognition task was positively correlated with hippocampal gray matter volume. Moreover, an increase of left prefrontal activity during Encoding and Recognition was observed in AD patients relative to controls and was correlated with memory performance. This additional activity elicited by episodic memory processes was not found to correlate with the degree of medial temporal atrophy in our group of patients. Our study shows that function in brain regions critical to episodic memory is altered in AD. During episodic Recognition, these functional changes may closely correlate with the progressive structural changes observed in the hippocampal region.

Pain modulates cerebral activity during cognitive performance.

The present study investigates how pain modulates brain activity during the performance of a semantic cognitive task. Based on previous observations, we hypothesized that a simultaneous painful stimulus will induce an activation increase in brain regions engaged in the cognitive task. High-field BOLD-fMRI experiments were conducted on 12 young healthy subjects, using a 2 x 2 factorial design. Painful stimuli were induced by thermal hot stimulation (46-49 degrees C) on the palmar surface of the hand, using a contact thermode. Cognitive tasks consisted of either word generation (category fluency) or word repetition. Brain activity owing to the semantic tasks in the group was highly consistent with previous neuroimaging studies. When the painful stimulus was added to the cognitive task, activity in brain regions involved in semantic cognition, such as Broca's area, was increased (P < 0.01). Pain also modulated activity in brain areas not directly engaged in cognition. A positive modulation effect was observed in the midcingulate and the dorsomedial prefrontal cortex (P < 0.05). A negative modulation effect was observed in perigenual cingulate cortex, insula, and medial thalamus (P < 0.05).