Specific mechanisms underlying executive and emotional apathy: A phenotyping study.

Apathy is a behavioral symptom prevalent both in neuropsychiatric pathologies and in the healthy population. However, the knowledge of the cognitive and neural mechanisms underlying apathy is still very limited, even if clinical and fMRI data support the existence of three forms of apathy (executive, emotional, initiative). These forms could be explained by the alteration of specific mechanisms. This present study's aim is to specify the cognitive and neuronal mechanisms of executive and emotional apathy. We used an EEG study conducted on 68 subjects comprising two groups of young people with specific executive or emotional phenotypes of apathy and one group with no apathy. Despite having symptom of apathy, participants were free of any neurological, metabolic, or psychiatric diagnoses and with high education. Two tasks were used: the DPX for cognitive control and the MID for motivation. Our results showed that distinct mechanisms underlie these two forms of apathy, and, for the first time, we specified these mechanisms. A deficit of the proactive control mode, reflected by a reduced probe-N2 amplitude in AY trials, underlies the executive form of apathy (p < .03), whereas liking motivational blunting, highlighted by a reduced LPP amplitude for financial loss, characterizes the emotional form (p < .04). The main limit of the results is that generalizability to the general population may be reduced since the apathetic samples were chosen for having a specific form of apathy. To conclude, better knowledge of these mechanisms informs new, more targeted treatments, both pharmacological and non-pharmacological, necessary for reducing the debilitating consequences of apathy.

Initiative apathy trait underlies individual differences in the ability to anticipate and expend cognitive effort in cost-benefit decision-making tasks.

Initiative apathy is the most disabling form of apathy, prevalent both in neuropsychiatric pathologies and in the healthy population. This apathy has been specifically associated with functional abnormalities of the anterior cingulate cortex, a key structure underlying Effort-based Decision-Making (EDM). The main aim of the present study was to explore, for the first time, the cognitive and neural effort mechanisms of initiative apathy, by distinguishing the steps of effort anticipation and effort expenditure and the potential modulating effect of motivation. We conducted an EEG study in 23 subjects with specific subclinical initiative apathy and 24 healthy subjects with no apathy. The subjects had to complete two effort tasks. The analysis of behavioral choices, CNV, and mPFC theta power highlighted that initiative apathy is associated with effort avoidance and impairments of effort anticipation and effort expenditure that suggest EDM deficits. Better knowledge of these impairments should aid the development of new, more targeted therapeutic interventions necessary for reducing the debilitating consequences of initiative apathy.

Conjoint fluctuations of PFC-mediated processes and behavior: An investigation of error-related neural mechanisms in relation to sustained attention.

The ability to detect errors, which derives from the medial prefrontal cortex (mPFC), is crucial to maintain attention over a long period of time. While impairment of this ability has been reported in patients with sustained attention disruption, the role mPFC-mediated processes play in the intra-individual fluctuation of sustained attention remains an open question. In this context, we computed the variance time course of reaction time (RT) of 42 healthy individuals to distinguish intra-individual periods of low and high performance instability, assumed to represent optimal and suboptimal attentional states, when performing a sustained Go/NoGo task. Analysis of the neurophysiological mechanisms of response monitoring revealed a specific reduction in the error-related negativity (ERN) amplitude and frontal midline theta power during periods of high compared to low RT variability, but only in individuals with a higher standard deviation of reaction time (SD-RT). Concerning post-error adaptation, an increase in the correct-related negativity (CRN) amplitude as well as the frontal lateral theta power on trials following errors was observed in individuals with lower SD-RT but not in those with higher SD-RT. Our results thus show that individuals with poor sustained attention ability exhibit altered post-error adaptation and attentional state-dependent efficiency of error monitoring. Conversely, individuals with good sustained attention performances retained their post-error adaptation and response monitoring regardless of the attentional periods. These findings reveal the critical role of the action-monitoring system in intra-individual behavioral stability and highlight the importance of considering attentional states when studying mPFC-mediated processes, especially in subjects with low sustained attention ability.

Investigation of electrophysiological precursors of attentional errors in schizophrenia: Toward a better understanding of abnormal proactive control engagement.

Impaired cognitive control has been associated with the occurrence of attentional errors in those with schizophrenia. However, the extent of altered proactive or reactive control underlying such errors is still unknown. Twenty-two patients with schizophrenia and 21 healthy matched controls performed a detection task (i.e., the continuous temporal expectancy task). Electrophysiological measures of proactive and reactive control were based on two periods of interest: during the target presentation (the critical window) and four trials before the critical window. Regarding the proactive mode, patients with schizophrenia exhibited a specific decrease in frontal midline theta power during the critical window before a miss compared to a correct detection. In contrast, the contingent negative variation amplitude was altered regardless of the response type, four trials before the critical window. Regarding the reactive mode, a reduced P3 amplitude was revealed later before a miss than a correct detection with differences apparent only two trials before the critical window in patients with schizophrenia, whereas it was observable up to four trials prior in healthy controls. Moreover, only the P3 amplitude reduction in patients with schizophrenia predicted the miss rate and was anti-correlated with the clinical symptoms. Thus, our results revealed a specific impairment of the proactive goal-updating process before an error and an altered implementation of the endogenous proactive mode engagement regardless of the response type. The results also highlighted the strong relationship between the disrupted reactive mode and the increased rate of attentional errors and severity of the clinical symptoms of schizophrenia.

Evidence of impaired proactive control under positive affect.

If it can be assumed that positive affect modulates cognitive control, the underlying mechanisms remain unclear. The main aim of this study was to investigate how positive affect influences proactive and reactive modes of control and to explore the temporal dynamic of this influence, in terms of its transient and/or sustained effects. We used the AX-continuous performance task, combined with event-related potentials (ERP) recording. The results showed that positive affect impaired proactive control. More specifically, response preparation was weaker, as highlighted by a decreased contingent negative variation (CNV), prior to the target. As a consequence, conflict detection, as reflected by the N2 component, was decreased under positive affect. The P3a, associated with conflict resolution, remained unaffected by positive emotion, suggesting a lack of reactive control modulation. These effects were diffuse and did not appear on a transient timescale, highlighting the importance of positive emotion's time course for how it influences cognitive control processes.

fMRI working memory hypo-activations in schizophrenia come with a coupling deficit between arousal and cognition.

Cognition has become a target for therapeutic intervention and favoring arousal could be a way to help patients. Working memory is an arousal dependent cognitive function. This study used functional MRI (fMRI) as a surrogate marker of working memory to evaluate the sensitivity of patients' hypoactive regions to arousal in a subpopulation of rehabilitated patients. Are hypoactive regions sensitive to arousal? Does the deficit result from arousal deficit or improper coupling with cognitive activity? Eighteen patients and matched controls were recruited. Participants performed a working memory task during combined electroencephalographic (EEG) and fMRI measurements. Cortical regions sensitive to arousal were defined as those which were inversely correlated with low EEG frequencies. Overlap between the arousal-sensitive and hypoactive regions was assessed by mutual information. Arousal-cognitive coupling was evaluated by the correlation between the arousal effect and the task effect. In the patient group, most hypoactive voxels were sensitive to arousal and corresponded to the prefronto-parietal network. But patients had no arousal deficit. Although arousal seems to improve cognitive activity in most of the patients' cortical areas, this coupling appears to be specifically disturbed in their hypoactive regions. In conclusion, although increasing arousal may help cognition, it may do so in an unspecific way.

Correcting for the echo-time effect after measuring the cerebral blood flow by arterial spin labeling.

PURPOSE: To take into account the echo time (TE) influence on arterial spin labeling (ASL) signal when converting it in regional cerebral blood flow (rCBF). Gray matter ASL signal decrease with increasing TE as a consequence of the difference in the apparent transverse relaxation rates between labeled water in capillaries and nonlabeled water in the tissue (δR 2*). We aimed to measure ASL/rCBF changes in different parts of the brain and correct them. MATERIALS AND METHODS: Fifteen participants underwent ASL measurements at TEs of 9.7-30 ms. Decreases in ASL values were localized by statistical parametric mapping. The corrections assessed were a subject-per-subject adjustment, an average δR 2* value adjustment, and a two-compartment model adjustment. RESULTS: rCBF decreases associated with increasing TEs were found for gray matter and were corrected using an average δR 2* value of 20 s(-1) . Conversely, for white matter, rCBF values increased with increasing TEs (δR 2* = -23 s(-1)). CONCLUSION: Our correction was as good as using a two-compartment model. However, it must be done separately for the gray and white matter rCBF values because the capillary R 2* values are, respectively, larger and smaller than those of surrounding tissues.

Evidence for a role of the parafascicular nucleus of the thalamus in the control of epileptic seizures by the superior colliculus.

PURPOSE: The aim of this study was to investigate whether the nucleus parafascicularis (Pf) of the thalamus could be a relay of the control of epileptic seizures by the superior colliculus (SC). The Pf is one of the main ascending projections of the SC, the disinhibition of which has been shown to suppress seizures in different animal models and has been proposed as the main relay of the nigral control of epilepsy. METHODS: Rats with genetic absence seizures (generalized absence epilepsy rat from Strasbourg or GAERS) were used in this study. The effect of bilateral microinjection of picrotoxin, a gamma-aminobutyric acid (GABA) antagonist, in the SC on the glutamate and GABA extracellular concentration within the Pf was first investigated by using microdialysis. In a second experiment, the effect of direct activation of Pf neurons on the occurrence of absence seizures was examined with microinjection of low doses of kainate, a glutamate agonist. RESULTS: Bilateral injection of picrotoxin (33 pmol/side) in the SC suppressed spike-and-wave discharges for 20 min. This treatment resulted in an increase of glutamate but not GABA levels in the Pf during the same time course. Bilateral injection of kainate (35 pmol/side) into the Pf significantly suppressed spike-and-wave discharges for 20 min, whereas such injections were without effects when at least one site was located outside the Pf. CONCLUSIONS: These data suggest that glutamatergic projections to the Pf could be involved in the control of seizures by the SC. Disinhibition of these neurons could lead to seizure suppression and may be involved in the nigral control of epilepsy.