Acetylcholine and noradrenaline enhance foraging optimality in humans.

Foraging theory prescribes when optimal foragers should leave the current option for more rewarding alternatives. Actual foragers often exploit options longer than prescribed by the theory, but it is unclear how this foraging suboptimality arises. We investigated whether the upregulation of cholinergic, noradrenergic, and dopaminergic systems increases foraging optimality. In a double-blind, between-subject design, participants (N = 160) received placebo, the nicotinic acetylcholine receptor agonist nicotine, a noradrenaline reuptake inhibitor reboxetine, or a preferential dopamine reuptake inhibitor methylphenidate, and played the role of a farmer who collected milk from patches with different yield. Across all groups, participants on average overharvested. While methylphenidate had no effects on this bias, nicotine, and to some extent also reboxetine, significantly reduced deviation from foraging optimality, which resulted in better performance compared to placebo. Concurring with amplified goal-directedness and excluding heuristic explanations, nicotine independently also improved trial initiation and time perception. Our findings elucidate the neurochemical basis of behavioral flexibility and decision optimality and open unique perspectives on psychiatric disorders affecting these functions.

Neural representation of valenced and generic probability and uncertainty.

Representing the probability and uncertainty of outcomes facilitates adaptive behavior by allowing organisms to prepare in advance and devote attention to relevant events. Probability and uncertainty are often studied only for valenced (appetitive or aversive) outcomes, raising the question whether the identified neural machinery also processes the probability and uncertainty of motivationally neutral outcomes. Here, we aimed to dissociate valenced from valence-independent (i.e., generic) probability (p; maximum at p=1) and uncertainty (maximum at p=0.5) signals using human neuroimaging. In a Pavlovian task (n=41; 19 females), different cues predicted appetitive, aversive, or neutral liquids with different probabilities (p=0, p=0.5, p=1). Cue-elicited motor responses accelerated, and pupil sizes increased primarily for cues that predicted valenced liquids with higher probability. For neutral liquids, uncertainty rather than probability tended to accelerate cue-induced responding and decrease pupil size. At the neural level, generic uncertainty signals were limited to occipital cortex, while generic probability also activated anterior ventromedial prefrontal cortex. These generic probability and uncertainty signals contrasted with cue-induced responses that only encoded the probability and uncertainty of valenced liquids in medial prefrontal, insular and occipital cortices. Our findings show that the brain processes probability and uncertainty in a generic fashion. Moreover, the behavioral and neural dissociation of generic and valenced signals indicates that the brain keeps track of motivational charge and highlights the need and usefulness of characterizing the exact nature of learned representations.Significance Statement Encoding the probability and uncertainty of outcomes is important for adaptive behavior. Here we ask to what extent the brain represents probability and uncertainty regardless of whether the predicted outcomes are valenced (i.e. motivationally relevant) or generic (i.e., valence-independent). We dissociate generic from valenced variables by using not only cues that predict appetitive or aversive outcomes, but also cues that predict neutral outcomes. Our data reveal distinct behavioral effects and largely separate neural representations of valenced and generic variables. For example, valenced probability activated more proximal parts of medial prefrontal and occipital cortex whereas generic probability activated more distal parts. Thus, the representation of probability and uncertainty is multiplexed, allowing for tailored information processing according to computational needs.

Phasic, Event-Related Transcutaneous Auricular Vagus Nerve Stimulation Modifies Behavioral, Pupillary, and Low-Frequency Oscillatory Power Responses.

Transcutaneous auricular vagus nerve stimulation (taVNS) has been proposed to activate the locus ceruleus-noradrenaline (LC-NA) system. However, previous studies failed to find consistent modulatory effects of taVNS on LC-NA biomarkers. Previous studies suggest that phasic taVNS may be capable of modulating LC-NA biomarkers such as pupil dilation and alpha oscillations. However, it is unclear whether these effects extend beyond pure sensory vagal nerve responses. Critically, the potential of the pupillary light reflex as an additional taVNS biomarker has not been explored so far. Here, we applied phasic active and sham taVNS in 29 subjects (16 female, 13 male) while they performed an emotional Stroop task (EST) and a passive pupil light reflex task (PLRT). We recorded pupil size and brain activity dynamics using a combined Magnetoencephalography (MEG) and pupillometry design. Our results show that phasic taVNS significantly increased pupil dilation and performance during the EST. During the PLRT, active taVNS reduced and delayed pupil constriction. In the MEG, taVNS increased frontal-midline theta and alpha power during the EST, whereas occipital alpha power was reduced during both the EST and PLRT. Our findings provide evidence that phasic taVNS systematically modulates behavioral, pupillary, and electrophysiological parameters of LC-NA activity during cognitive processing. Moreover, we demonstrate for the first time that the pupillary light reflex can be used as a simple and effective proxy of taVNS efficacy. These findings have important implications for the development of noninvasive neuromodulation interventions for various cognitive and clinical applications.SIGNIFICANCE STATEMENT taVNS has gained increasing attention as a noninvasive neuromodulation technique and is widely used in clinical and nonclinical research. Nevertheless, the exact mechanism of action of taVNS is not yet fully understood. By assessing physiology and behavior in a response conflict task in healthy humans, we demonstrate the first successful application of a phasic, noninvasive vagus nerve stimulation to improve cognitive control and to systematically modulate pupillary and electrophysiological markers of the noradrenergic system. Understanding the mechanisms of action of taVNS could optimize future clinical applications and lead to better treatments for mental disorders associated with noradrenergic dysfunction. In addition, we present a new taVNS-sensitive pupillary measure representing an easy-to-use biomarker for future taVNS studies.

Anticipatory energization revealed by pupil and brain activity guides human effort-based decision making.

An organism's fitness is determined by how it chooses to adapt to effort in response to challenges. Exertion of effort correlates with activity in dorsomedial prefrontal cortex (dmPFC) and noradrenergic pupil dilation, but little is known about the role of these neurophysiological processes for decisions about future efforts - they may provide anticipatory energization to help us accept the challenge or a cost representation that is weighted against the expected rewards. Here we provide evidence for the former, by measuring pupil and fMRI brain responses while 52 human participants (29 females) chose whether to exert efforts to obtain rewards. Both pupil-dilation rate and dMPFC fMRI activity increased with anticipated effort level, and these increases differ depending on the choice outcome: They were stronger when participants chose to accept the challenge compared to when the challenge was declined. Crucially, the choice-dependent modulation of pupil and brain-activity effort representations were stronger in participants whose behavioral choices were more sensitive to effort. Our results identify a process involving the peripheral and central human nervous system that simulates the required energization prior to overt response, suggesting a role in guiding effort-based decisions.SIGNIFICANCE STATEMENT:The brain's arousal system tracks the effort we engage in during strenuous activity. But much less is known about what role this effort signaling may play when we decide whether to exert effort in the future. Here we characterize pupil-linked arousal and brain signals that guide decisions whether to engage in effort to gain money. During such choices, increases in brain activity and pupil dilation correlated with the effort involved in the chosen option, and these increases were stronger when people decided to accept the effort compared to when they rejected it. These results suggest that the brain arousal system guides decisions by energizing the organism for the prospective challenge.

Brain Network Mechanisms Underlying Motor Enhancement by Transcranial Entrainment of Gamma Oscillations.

Gamma and beta oscillations are routinely observed in motor-related brain circuits during movement preparation and execution. Entrainment of gamma or beta oscillations via transcranial alternating current stimulation (tACS) over primary motor cortex (M1) has opposite effects on motor performance, suggesting a causal role of these brain rhythms for motor control. However, it is largely unknown which brain mechanisms characterize these changes in motor performance brought about by tACS. In particular, it is unclear whether these effects result from brain activity changes only in the targeted areas or within functionally connected brain circuits. Here we investigated this issue by applying gamma-band and beta-band tACS over M1 in healthy humans during a visuomotor task and concurrent functional magnetic resonance imaging (fMRI). Gamma tACS indeed improved both the velocity and acceleration of visually triggered movements, compared with both beta tACS and sham stimulation. Beta tACS induced a numerical decrease in velocity compared with sham stimulation, but this was not statistically significant. Crucially, gamma tACS induced motor performance enhancements correlated with changed BOLD activity in the stimulated M1. Moreover, we found frequency- and task-specific neural compensatory activity modulations in the dorsomedial prefrontal cortex (dmPFC), suggesting a key regulatory role of this region in motor performance. Connectivity analyses revealed that the dmPFC interacted functionally with M1 and with regions within the executive motor system. These results suggest a role of the dmPFC for motor control and show that tACS-induced behavioral changes not only result from activity modulations underneath the stimulation electrode but also reflect compensatory modulation within connected and functionally related brain networks. More generally, our results illustrate how combined tACS-fMRI can be used to resolve the causal link between cortical rhythms, brain systems, and behavior. SIGNIFICANCE STATEMENT: Recent research has suggested a causal role for gamma oscillations during movement preparation and execution. Here we combine transcranial alternating current stimulation (tACS) with functional magnetic resonance imaging (fMRI) to identify the neural mechanisms that accompany motor performance enhancements triggered by gamma tACS over the primary motor cortex. We show that the tACS-induced motor performance enhancements correlate with changed neural activity in the stimulated area and modulate, in a frequency- and task-specific manner, the neural activity in the dorsomedial prefrontal cortex. This suggests a regulatory role of this region for motor control. More generally, we show that combined tACS-fMRI can elucidate the causal link between brain oscillations, neural systems, and behavior.

Sensory perceptions of individuals exposed to the static field of a 7T MRI: A controlled blinded study.

PURPOSE: To determine the subjective experience of subjects undergoing 7T magnetic resonance imaging (MRI) compared to a mock scanner with no magnetic field. METHODS AND MATERIALS: In all, 44 healthy subjects were exposed to both the B0 field of a 7T whole-body MRI and a realistic mock scanner with no magnetic field. Subjects were blinded to the actual field strength and no scanning was performed. After exposure, subjects rated their experience of potential sensory perceptions. RESULTS: The most frequently observed side effect was vertigo while entering the gantry, which was reported by 38.6% (n = 17). Other frequent side effects were the appearance of phosphenes (18.2%, n = 8), thermal heat sensation (15.9%), unsteady gait after exposure (13.6%, n = 6), and dizziness (13.6%). All side effects were reported significantly more often after 7T exposure. Nine subjects (20.5%) did not report any sensory perceptions at all, ie, neither in the 7T scanner nor in the mock scanner. CONCLUSION: Light, acute, and transient sensory perceptions can occur in subjects undergoing ultrahighfield MRI, of which vertigo seems to be the most frequently reported. Possible psychological effects might contribute to the emergence of such sensory perceptions, as some subjects also reported them to appear in a realistic mock scanner with no magnetic field.

Fast construction of voxel-level functional connectivity graphs.

BACKGROUND: Graph-based analysis of fMRI data has recently emerged as a promising approach to study brain networks. Based on the assessment of synchronous fMRI activity at separate brain sites, functional connectivity graphs are constructed and analyzed using graph-theoretical concepts. Most previous studies investigated region-level graphs, which are computationally inexpensive, but bring along the problem of choosing sensible regions and involve blurring of more detailed information. In contrast, voxel-level graphs provide the finest granularity attainable from the data, enabling analyses at superior spatial resolution. They are, however, associated with considerable computational demands, which can render high-resolution analyses infeasible. In response, many existing studies investigating functional connectivity at the voxel-level reduced the computational burden by sacrificing spatial resolution. METHODS: Here, a novel, time-efficient method for graph construction is presented that retains the original spatial resolution. Performance gains are instead achieved through data reduction in the temporal domain based on dichotomization of voxel time series combined with tetrachoric correlation estimation and efficient implementation. RESULTS: By comparison with graph construction based on Pearson's r, the technique used by the majority of previous studies, we find that the novel approach produces highly similar results an order of magnitude faster. CONCLUSIONS: Its demonstrated performance makes the proposed approach a sensible and efficient alternative to customary practice. An open source software package containing the created programs is freely available for download.

Investigating heart rate variability measures during pregnancy as predictors of postpartum depression and anxiety: an exploratory study.

Perinatal affective disorders are common, but standard screening measures reliant on subjective self-reports might not be sufficient to identify pregnant women at-risk for developing postpartum depression and anxiety. Lower heart rate variability (HRV) has been shown to be associated with affective disorders. The current exploratory study aimed to evaluate the predictive utility of late pregnancy HRV measurements of postpartum affective symptoms. A subset of participants from the BASIC study (Uppsala, Sweden) took part in a sub-study at pregnancy week 38 where HRV was measured before and after a mild stressor (n = 122). Outcome measures were 6-week postpartum depression and anxiety symptoms as quantified by the Edinburgh Postnatal Depression Scale (EPDS) and the Beck Anxiety Inventory (BAI). In total, 112 women were included in a depression outcome analysis and 106 women were included in an anxiety outcome analysis. Group comparisons indicated that lower pregnancy HRV was associated with depressive or anxious symptomatology at 6 weeks postpartum. Elastic net logistic regression analyses indicated that HRV indices alone were not predictive of postpartum depression or anxiety outcomes, but HRV indices were selected as predictors in a combined model with background and pregnancy variables. ROC curves for the combined models gave an area under the curve (AUC) of 0.93 for the depression outcome and an AUC of 0.83 for the anxiety outcome. HRV indices predictive of postpartum depression generally differed from those predictive of postpartum anxiety. HRV indices did not significantly improve prediction models comprised of psychological measures only in women with pregnancy depression or anxiety.

Causal phase-dependent control of non-spatial attention in human prefrontal cortex.

Non-spatial attention is a fundamental cognitive mechanism that allows organisms to orient the focus of conscious awareness towards sensory information that is relevant to a behavioural goal while shifting it away from irrelevant stimuli. It has been suggested that attention is regulated by the ongoing phase of slow excitability fluctuations of neural activity in the prefrontal cortex, a hypothesis that has been challenged with no consensus. Here we developed a behavioural and non-invasive stimulation paradigm aiming at modulating slow excitability fluctuations of the inferior frontal junction. Using this approach, we show that non-spatial attention can be selectively modulated as a function of the ongoing phase of exogenously modulated excitability states of this brain structure. These results demonstrate that non-spatial attention relies on ongoing prefrontal excitability states, which are probably regulated by slow oscillatory dynamics, that orchestrate goal-oriented behaviour.

BOLD responses in human V1 to local structure in natural scenes: Implications for theories of visual coding.

In this study we tested predictions of two important theories of visual coding, contrast energy and sparse coding theory, on the dependence of population activity level and metabolic demands on spatial structure of the visual input. With carefully calibrated displays we find that in humans neither the V1 blood oxygenation level dependent (BOLD) response nor the initial visually evoked fields in magnetoencephalography (MEG) are sensitive to phase perturbations in photographs of natural scenes. As a control, we quantitatively show that the applied phase perturbations decrease sparseness (kurtosis) of our stimuli but preserve their root mean square (RMS) contrast. Importantly, we show that the lack of sensitivity of the V1 population response level to phase perturbations is not due to a lack of sensitivity of our methods because V1 responses were highly sensitive to variations of image RMS contrast. Our results suggest that the transition from a sparse to a distributed neural code in the early visual system induced by reducing image sparseness has negligible consequences for population metabolic cost. This result imposes a novel and important empirical constraint on quantitative models of sparse coding: Population metabolic rate and population activation level is sensitive to second order statistics (RMS contrast) of the input but not to its spatial phase and fourth order statistics (kurtosis).

Individual risk attitudes arise from noise in neurocognitive magnitude representations.

Humans are generally risk averse, preferring smaller certain over larger uncertain outcomes. Economic theories usually explain this by assuming concave utility functions. Here, we provide evidence that risk aversion can also arise from relative underestimation of larger monetary payoffs, a perceptual bias rooted in the noisy logarithmic coding of numerical magnitudes. We confirmed this with psychophysics and functional magnetic resonance imaging, by measuring behavioural and neural acuity of magnitude representations during a magnitude perception task and relating these measures to risk attitudes during separate risky financial decisions. Computational modelling indicated that participants use similar mental magnitude representations in both tasks, with correlated precision across perceptual and risky choices. Participants with more precise magnitude representations in parietal cortex showed less variable behaviour and less risk aversion. Our results highlight that at least some individual characteristics of economic behaviour can reflect capacity limitations in perceptual processing rather than processes that assign subjective values to monetary outcomes.

Functional Coupling of the Locus Coeruleus Is Linked to Successful Cognitive Control.

The locus coeruleus (LC) is a brainstem structure that sends widespread efferent projections throughout the mammalian brain. The LC constitutes the major source of noradrenaline (NE), a modulatory neurotransmitter that is crucial for fundamental brain functions such as arousal, attention, and cognitive control. This role of the LC-NE is traditionally not believed to reflect functional influences on the frontoparietal network or the striatum, but recent advances in chemogenetic manipulations of the rodent brain have challenged this notion. However, demonstrations of LC-NE functional connectivity with these areas in the human brain are surprisingly sparse. Here, we close this gap. Using an established emotional stroop task, we directly compared trials requiring response conflict control with trials that did not require this, but were matched for visual stimulus properties, response modality, and controlled for pupil dilation differences across both trial types. We found that LC-NE functional coupling with the parietal cortex and regions of the striatum is substantially enhanced during trials requiring response conflict control. Crucially, the strength of this functional coupling was directly related to individual reaction time differences incurred by conflict resolution. Our data concur with recent rodent findings and highlight the importance of converging evidence between human and nonhuman neurophysiology to further understand the neural systems supporting adaptive and maladaptive behavior in health and disease.

Pupil dilation predicts individual self-regulation success across domains.

Multiple theories have proposed that increasing central arousal through the brain's locus coeruleus-norepinephrine system may facilitate cognitive control and memory. However, the role of the arousal system in emotion regulation is less well understood. Pupil diameter is a proxy to infer upon the central arousal state. We employed an emotion regulation paradigm with a combination of design features that allowed us to dissociate regulation from emotional arousal in the pupil diameter time course of 34 healthy adults. Pupil diameter increase during regulation predicted individual differences in emotion regulation success beyond task difficulty. Moreover, the extent of this individual regulatory arousal boost predicted performance in another self-control task, dietary health challenges. Participants who harnessed more regulation-associated arousal during emotion regulation were also more successful in choosing healthier foods. These results suggest that a common arousal-based facilitation mechanism may support an individual's self-control across domains.

Sources of confidence in value-based choice.

Confidence, the subjective estimate of decision quality, is a cognitive process necessary for learning from mistakes and guiding future actions. The origins of confidence judgments resulting from economic decisions remain unclear. We devise a task and computational framework that allowed us to formally tease apart the impact of various sources of confidence in value-based decisions, such as uncertainty emerging from encoding and decoding operations, as well as the interplay between gaze-shift dynamics and attentional effort. In line with canonical decision theories, trial-to-trial fluctuations in the precision of value encoding impact economic choice consistency. However, this uncertainty has no influence on confidence reports. Instead, confidence is associated with endogenous attentional effort towards choice alternatives and down-stream noise in the comparison process. These findings provide an explanation for confidence (miss)attributions in value-guided behaviour, suggesting mechanistic influences of endogenous attentional states for guiding decisions and metacognitive awareness of choice certainty.

Neuro-Computational Foundations of Moral Preferences.

Moral preferences pervade many aspects of our lives, dictating how we ought to behave, whom we can marry, and even what we eat. Despite their relevance, one fundamental question remains unanswered: Where do individual moral preferences come from? It is often thought that all types of preferences reflect properties of domain-general neural decision mechanisms that employ a common "neural currency" to value choice options in many different contexts. This view, however, appears at odds with the observation that many humans consider it intuitively wrong to employ the same scale to compare moral value (e.g., of a human life) with material value (e.g., of money). In this paper, we directly test if moral subjective values are represented by similar neural processes as financial subjective values. In a study combining fMRI with a novel behavioral paradigm, we identify neural representations of the subjective values of human lives or financial payoffs by means of structurally identical computational models. Correlating isomorphic model variables from both domains with brain activity reveals specific patterns of neural activity that selectively represent values in the moral (rTPJ) or financial (vmPFC) domain. Intriguingly, our findings show that human lives and money are valued in (at least partially) distinct neural currencies, supporting theoretical proposals that human moral behavior is guided by processes that are distinct from those underlying behavior driven by personal material benefit.

Real-world stress resilience is associated with the responsivity of the locus coeruleus.

Individuals may show different responses to stressful events. Here, we investigate the neurobiological basis of stress resilience, by showing that neural responsitivity of the noradrenergic locus coeruleus (LC-NE) and associated pupil responses are related to the subsequent change in measures of anxiety and depression in response to prolonged real-life stress. We acquired fMRI and pupillometry data during an emotional-conflict task in medical residents before they underwent stressful emergency-room internships known to be a risk factor for anxiety and depression. The LC-NE conflict response and its functional coupling with the amygdala was associated with stress-related symptom changes in response to the internship. A similar relationship was found for pupil-dilation, a potential marker of LC-NE firing. Our results provide insights into the noradrenergic basis of conflict generation, adaptation and stress resilience.

Role of the locus coeruleus arousal system in cognitive control.

Cognitive control lies at the core of human adaptive behaviour. Humans vary substantially in their ability to execute cognitive control with respect to optimally facing environmental challenges, although the neural origins of this heterogeneity are currently not well understood. Recent theoretical frameworks implicate the locus coeruleus noradrenergic arousal system (LC-NE) in that process. Invasive neurophysiological work in rodents has shown that the LC-NE is an important homeostatic control centre of the body. LC-NE innervates the entire neocortex and has particularly strong connections with the cingulate gyrus. In the present study, using a response conflict task, functional magnetic resonance imaging and concurrent pupil dilation measures (a proxy for LC-NE firing), we provide empirical evidence for a decisive role of the LC-NE in cognitive control in humans. We show that the level of individual behavioural adjustment in cognitive control relates to the level of functional coupling between LC-NE and the dorsomedial prefrontal cortex, as well as dorsolateral prefrontal cortex. Moreover, we show that the pupil is substantially more dilated during conflict trials requiring behavioural adjustment than during no conflict trials. In addition, we explore a potential relationship between pupil dilation and neural activity during choice conflict adjustments. Our data provide novel insight into arousal-related influences on cognitive control and suggest pupil dilation as a potential external marker for endogenous neural processes involved in optimising behavioural control. Our results may also be clinically relevant for a variety of pathologies where cognitive control is compromised, such as anxiety, depression, addiction and post-traumatic stress disorder.

Emotional conflict adaptation predicts intrusive memories.

Why do some individuals experience intrusive emotional memories following stressful or traumatic events whereas others do not? Attentional control may contribute to the development of such memories by shielding attention to ongoing tasks from affective reactions to task-irrelevant emotional stimuli. The present study investigated whether individual differences in theability to exert cognitive control are associated with experiencing intrusive emotional memories after laboratory trauma. Sixty-one healthy women provided self-reported and experimentally derived measures of attentional control. They then viewed a trauma film in the laboratory and recorded intrusive memories for one week using a diary. Gaze avoidance during trauma film exposure was associated with more intrusive memories. Greater attentional control over emotion prior to film viewing, as assessed with the experimental task, predicted fewer intrusive memories while self-reported attentional control was unrelated to intrusive memories. Preexisting capacity to shield information processing from distraction may protect individuals from developing intrusive emotional memories following exposure to stress or trauma. These findings provide important clues for prevention and intervention science.

How stress affects sleep and mental health: nocturnal heart rate increases during prolonged stress and interacts with childhood trauma exposure to predict anxiety.

STUDY OBJECTIVES: Stress can adversely impact sleep health by eliciting arousal increase and a cascade of endocrine reactions that may impair sleep. To date, little is known regarding continuous effects of real-world stress on physiological sleep characteristics and potential effects on stress-related psychopathology. We examined effects of stress on heart rate (HR) during sleep and total sleep time (TST) during prolonged real-world stress exposure in medical interns. Moreover, we investigated the influence of previous stress and childhood trauma exposure on HR during sleep, TST, and its interaction in predicting anxiety. METHODS: We examined a sample of 50 medical students prior to and during their first internship, a well described real-world stressor. HR and TST were continuously collected over 12 weeks non-invasively by a wrist-worn activity monitor. Prior to starting the internship, at baseline, participants reported on their sleep, anxiety, and childhood trauma exposure. They also tracked stress exposure during internship and reported on their anxiety symptoms 3 months after this professional stress. RESULTS: Mean HR during sleep increased over time, while TST remained unchanged. This effect was more pronounced in interns exposed to childhood trauma exposure. In multilevel models, childhood trauma exposure also moderated the relation between individual HR increase and development of anxiety. CONCLUSIONS: Prolonged stress may lead to increased HR during sleep, whereas individuals with childhood trauma exposure are more vulnerable. Childhood trauma exposure also moderated the relation between individual HR increase and development of anxiety. These findings may inform prevention and intervention measures.

Causal contributions of human frontal eye fields to distinct aspects of decision formation.

Several theories propose that perceptual decision making depends on the gradual accumulation of information that provides evidence in favour of one of the choice-options. The outcome of this temporally extended integration process is thought to be categorized into the 'winning' and 'losing' choice-options for action. Neural correlates of corresponding decision formation processes have been observed in various frontal and parietal brain areas, among them the frontal eye-fields (FEF). However, the specific functional role of the FEFs is debated. Recent studies in humans and rodents provide conflicting accounts, proposing that the FEF either accumulate the choice-relevant information or categorize the outcome of such evidence integration into discrete actions. Here, we used transcranial magnetic stimulation (TMS) on humans to interfere with either left or right FEF activity during different timepoints of perceptual decision-formation. Stimulation of either FEF affected performance only when delivered during information integration but not during subsequent categorical choice. However, the patterns of behavioural changes suggest that the left-FEF contributes to general evidence integration, whereas right-FEF may direct spatial attention to the contralateral hemifield. Taken together, our results indicate an FEF involvement in evidence accumulation but not categorization, and suggest hemispheric lateralization for this function in the human brain.