Dorsolateral Prefrontal Activation Research Articles

Out-of-phase transcranial alternating current stimulation modulates the neurodynamics of inhibitory control

Transcranial alternating current stimulation (tACS) is an efficient neuromodulation technique that enhances cognitive function in a non-invasive manner. Using functional magnetic resonance imaging, we investigated whether tACS with different phase lags (0° and 180°) between the dorsal anterior cingulate and left dorsolateral prefrontal cortices modulated inhibitory control performance during the Stroop task. We found out-of-phase tACS mediated improvements in task performance, which was neurodynamically reflected as putamen, dorsolateral prefrontal, and primary motor cortical activation as well as prefrontal-based top-down functional connectivity. Our observations uncover the neurophysiological bases of tACS-phase-dependent neuromodulation and provide a feasible non-invasive approach to effectively modulate inhibitory control.

Dorsolateral prefrontal activity supports a cognitive space organization of cognitive control.

Cognitive control resolves conflicts between task-relevant and -irrelevant information to enable goal-directed behavior. As conflicts can arise from different sources (e.g., sensory input, internal representations), how a limited set of cognitive control processes can effectively address diverse conflicts remains a major challenge. Based on the cognitive space theory, different conflicts can be parameterized and represented as distinct points in a (low-dimensional) cognitive space, which can then be resolved by a limited set of cognitive control processes working along the dimensions. It leads to a hypothesis that conflicts similar in their sources are also represented similarly in the cognitive space. We designed a task with five types of conflicts that could be conceptually parameterized. Both human performance and fMRI activity patterns in the right dorsolateral prefrontal cortex support that different types of conflicts are organized based on their similarity, thus suggesting cognitive space as a principle for representing conflicts.

Dorsolateral prefrontal activity supports a cognitive space organization of cognitive control

Cognitive control resolves conflicts between task-relevant and -irrelevant information to enable goal-directed behavior. As conflicts can arise from different sources (e.g., sensory input, internal representations), how a limited set of cognitive control processes can effectively address diverse conflicts remains a major challenge. Based on the cognitive space theory, different conflicts can be parameterized and represented as distinct points in a (low-dimensional) cognitive space, which can then be resolved by a limited set of cognitive control processes working along the dimensions. It leads to a hypothesis that conflicts similar in their sources are also represented similarly in the cognitive space. We designed a task with five types of conflicts that could be conceptually parameterized. Both human performance and fMRI activity patterns in the right dorsolateral prefrontal cortex support that different types of conflicts are organized based on their similarity, thus suggesting cognitive space as a principle for representing conflicts.

Study protocol - elucidating the neural correlates of functional remediation for older adults with bipolar disorder.

Beyond mood abnormalities, bipolar disorder (BD) includes cognitive impairments that worsen psychosocial functioning and quality of life. These deficits are especially severe in older adults with BD (OABD), a condition expected to represent most individuals with BD in the upcoming years. Restoring the psychosocial functioning of this population will thus soon represent a public health priority. To help tackle the problem, the Bipolar and Depressive Disorders Unit at the Hospital Clínic of Barcelona has recently adapted its Functional Remediation (FR) program to that population, calling it FROA-BD. However, while scarce previous studies localize the neural mechanisms of cognitive remediation interventions in the dorsal prefrontal cortex, the specific mechanisms are seldom unknown. In the present project, we will investigate the neural correlates of FR-OABD to understand its mechanisms better and inform for potential optimization. The aim is to investigate the brain features and changes associated with FROA-BD efficacy. Thirty-two individuals with OABD in full or partial remission will undergo a magnetic resonance imaging (MRI) session before receiving FR-OABD. After completing the FR-OABD intervention, they will undergo another MRI session. The MRI sessions will include structural, diffusion-weighted imaging (DWI), functional MRI (fMRI) with working memory (n-back) and verbal learning tasks, and frontal spectroscopy. We will correlate the pre-post change in dorsolateral and dorsomedial prefrontal cortices activation during the n-back task with the change in psychosocial functioning [measured with the Functioning Assessment Short Test (FAST)]. We will also conduct exploratory whole-brain correlation analyses between baseline or pre-post changes in MRI data and other clinical and cognitive outcomes to provide more insights into the mechanisms and explore potential brain markers that may predict a better treatment response. We will also conduct separate analyses by sex. The results of this study may provide insights into how FROA-BD and other cognitive remediations modulate brain function and thus could optimize these interventions.

Prefrontal activation in response to a plantar contact task under open and closed eye conditions in patients with cerebral infarction.

This study investigates the effect of a bilateral (paralyzed side, healthy side) plantar contact task on dorsolateral prefrontal activation in patients recovering from cerebral infarction under open and closed eye conditions. We selected 10 patients with cerebral infarction, admitted to the neurorehabilitation center of Beijing Rehabilitation Hospital, affiliated with Capital Medical University, from January 2019 to July 2020, who met our established criteria. Under open-eye and closed-eye conditions, the paralyzed and healthy sides performed the plantar contact tasks separately. The dorsolateral prefrontal region was monitored simultaneously with functional near-infrared spectroscopy (fNIRS), and activation was analyzed according to the curve-type changes of oxyhemoglobin and deoxyhemoglobin changes in the dorsolateral prefrontal cortex with 560 near-infrared monitoring channels. After stratifying the data based on the eyes-open and eyes-closed conditions, some degree of heterogeneity was observed between the layers. Under the eyes-closed condition, the Pearson χ2 was 0.142, with a p value of 0.706, indicating no significant impact of the eyes-closed condition on the activation of the dorsolateral prefrontal cortex during the plantar task, whether performed on the paralyzed or the healthy side.In contrast, the Pearson χ2 value was 15.15 for the eyes-open condition, with a p value of 0.002. This suggests that carrying out the plantar task, either on the paralyzed or the healthy side, with eyes open significantly influenced the activation of the dorsolateral prefrontal cortex. Furthermore, activation of the dorsolateral prefrontal cortex was 1.55 times higher when the task was executed with the paralyzed side compared to the healthy side. This implies that the paralyzed side was more likely to activate the dorsolateral prefrontal lobe when performing the plantar contact task under eyes-open conditions. Observations via fNIRS revealed that the plantar contact task elicited dorsolateral prefrontal cortex activation. Moreover, the activation effect was intensified when performed on the paralyzed side under eyes-open conditions. Therapeutic methods that leverage these findings-namely cognitive-motor therapies that promote the recovery of motor functions by activating cognitive control brain regions via perception (information construction)-may hold promise.

What a difference timing makes: Cortisol effects on neural underpinnings of emotion regulation

The ability of emotion regulation under stress is of crucial importance to psychosocial health. Yet, the dynamic function of stress hormones for the cognitive control of emotions over time via non-genomic and genomic cortisol effects remains to be elucidated. In this randomized, double-blind, placebo-controlled neuroimaging experiment, 105 participants (54 men, 51 women) received 20 mg hydrocortisone (cortisol) or a placebo either 30min (rapid, non-genomic cortisol effects) or 90min (slow, genomic cortisol effects) prior to a cognitive reappraisal task including different regulatory goals (i.e., downregulate vs. upregulate negative emotions). On the behavioral level, cortisol rapidly reduced and slowly enhanced emotional responsivity to negative pictures. However, only slow cortisol effects improved downregulation of negative emotions. On the neural level, cortisol rapidly enhanced, but slowly reduced amygdala and dorsolateral prefrontal activation as well as functional connectivity between both structures in the down- minus upregulate contrast. This interaction speaks for an effortful but ineffective regulation of negative emotions during rapid cortisol effects and improved emotion regulation capacities during slow cortisol effects. Taken together, these results indicate a functional shift of cortisol effects on emotion regulation processes over time which may foster successful adaptation to and recovery from stressful life events.

8. Altered Associations Between Task Ability and Dorsolateral Prefrontal Activation During a Cognitive Control Task in Schizophrenia

8. Altered Associations Between Task Ability and Dorsolateral Prefrontal Activation During a Cognitive Control Task in Schizophrenia

Dorsolateral prefrontal activation in depressed young adults with and without suicidal ideation during an emotional autobiographical memory task: A fNIRS study

ObjectivePrevious studies have proved that there is a strong association between dorsolateral prefrontal cortex and mood symptoms. This study aimed at using functional near-infrared spectroscopy technology to invest brain activity in dlPFC of depressed individuals with and without suicidal ideation during emotional autobiographical memory test, and to understand their differences in brain cognitive mechanisms. It is helpful to improve our ability to predict and subsequently to prevent suicide. Methods85 young adults participated in the study by a simple random sampling method, with health control (34participants), depression with suicidal ideation (17participants), and depression without suicidal ideation (34participants). The average oxyhemoglobin in dlPFC of subjects during EAMT was collected by a 53-channel fNIRS imaging device. ResultsA marginal significant difference was found between three groups in left dlPFC and right dlPFC. Post hoc analysis revealed that: (1) under negative emotion, depression without suicidal ideation group had higher activation than healthy control group in left dlPFC. (2) under positive emotion, depression with suicidal ideation group had lower activation than healthy control in right dlPFC. ConclusionsResults indicated that the depressed individuals with suicidal ideation had some deficits in executive function in right dlPFC, while the depressed adults without suicidal ideation may have mechanism of resource compensatory recruitment in left dlPFC and the dlPFC abnormality involved in the pathophysiology, may localize within left hemisphere. The depressed individuals with and without suicidal ideation had the different mechanisms in dlPFC and fNIRS can be a neuroimaging biomarker characterizing or predicting suicidality in depressed individuals.

Reduced left dorsolateral prefrontal activation in problematic smartphone users during the Stroop task: An fNIRS study.

The widespread use of smartphones has triggered concern over problematic smartphone use (PSPU), as well as the need to elucidate its underlying mechanisms. However, the correlation between cortical activation and deficient inhibitory control in PSPU remains unclear. This study examined inhibitory control using the color-word matching Stroop task and its cortical-activation responses using functional near-infrared spectroscopy (fNIRS) in college students with PSPU (n = 56) compared with a control group (n = 54). At the behavioral level, Stroop interference, coupled with reaction time, was significantly greater in the PSPU group than in the control group. Changes in oxygenated hemoglobin (Oxy-Hb) signals associated with Stroop interference were significantly increased in the left ventrolateral prefrontal cortex, left frontopolar area, and bilateral dorsolateral prefrontal cortex (DLPFC). Moreover, the PSPU group had lower Oxy-Hb signal changes associated with Stroop interference in the left-DLPFC, relative to controls. These results provide first behavioral and neuroscientific evidence using event-related fNIRS method, to our knowledge, that college students with PSPU may have a deficit in inhibitory control associated with lower cortical activation in the left-DLPFC.

Spatio-temporal dynamics of oscillatory brain activity during the observation of actions and interactions between point-light agents.

Predicting actions from non-verbal cues and using them to optimise one's response behaviour (i.e. interpersonal predictive coding) is essential in everyday social interactions. We aimed to investigate the neural correlates of different cognitive processes evolving over time during interpersonal predictive coding. Thirty-nine participants watched two agents depicted by moving point-light stimuli while an electroencephalogram (EEG) was recorded. One well-recognizable agent performed either a 'communicative' or an 'individual' action. The second agent either was blended into a cluster of noise dots (i.e. present) or was entirely replaced by noise dots (i.e. absent), which participants had to differentiate. EEG amplitude and coherence analyses for theta, alpha and beta frequency bands revealed a dynamic pattern unfolding over time: Watching communicative actions was associated with enhanced coupling within medial anterior regions involved in social and mentalising processes and with dorsolateral prefrontal activation indicating a higher deployment of cognitive resources. Trying to detect the agent in the cluster of noise dots without having seen communicative cues was related to enhanced coupling in posterior regions for social perception and visual processing. Observing an expected outcome was modulated by motor system activation. Finally, when the agent was detected correctly, activation in posterior areas for visual processing of socially relevant features was increased. Taken together, our results demonstrate that it is crucial to consider the temporal dynamics of social interactions and of their neural correlates to better understand interpersonal predictive coding. This could lead to optimised treatment approaches for individuals with problems in social interactions.

Comparing the functional neuroanatomy of proactive and reactive control between patients with schizophrenia and healthy controls.

Cognitive control deficits are associated with impaired executive functioning in schizophrenia. The Dual Mechanisms of Control framework suggests that proactive control requires sustained dorsolateral prefrontal activity, whereas reactive control marshals a larger network. However, primate studies suggest these processes are maintained by dual-encoding regions. To distinguish between these theories, we compared the distinctiveness of proactive and reactive control functional neuroanatomy. In a reanalysis of data from a previous study, 47 adults with schizophrenia and 56 controls completed the Dot Pattern Expectancy task during an fMRI scan examining proactive and reactive control in frontoparietal and medial temporal regions. Areas suggesting specialized control or between-group differences were tested for association with symptoms and task performance. Elastic net models additionally explored these areas' predictive abilities regarding performance. Most regions were active in both reactive and proactive control. However, evidence of specialized proactive control was found in the left middle and superior frontal gyri. Control participants showed greater proactive control in the left middle and right inferior frontal gyri. Elastic net models moderately predicted task performance and implicated various frontal gyri regions in control participants, with additional involvement of anterior cingulate and posterior parietal regions for reactive control. Elastic nets for patient participants implicated the inferior and superior frontal gyri, and posterior parietal lobe. Specialized cognitive control was unassociated with either performance or schizophrenia symptomatology. Future work is needed to clarify the distinctiveness of proactive and reactive control, and its role in executive deficits in severe psychopathology.

Pramipexole modulates fronto-subthalamic pathway in sequential working memory

Brain dopamine may regulate the ability to maintain and manipulate sequential information online. However, the precise role of dopamine remains unclear. This pharmacological fMRI study examined whether and how the dopamine D2/3 receptor agonist pramipexole modulates fronto-subthalamic or fronto-striatal pathways during sequential working memory. This study used a double-blind, randomized crossover design. Twenty-two healthy male volunteers completed a digit ordering task during fMRI scanning after receiving a single oral dose of 0.5-mg pramipexole or placebo. The pramipexole effects on task performance, regional activity, activity pattern similarity, and functional connectivity were analyzed. Pramipexole impaired task performance, leading to less accurate and slower responses in the digit ordering task. Also, it downregulated the maintenance-related subthalamic and dorsolateral prefrontal activity, increasing reaction times for maintaining sequences. In contrast, pramipexole upregulated the manipulation-related subthalamic and dorsolateral prefrontal activity, increasing reaction time costs for manipulating sequences. In addition, it altered the dorsolateral prefrontal activity pattern similarity and fronto-subthalamic functional connectivity. Finally, pramipexole reduced maintenance-related striatal activity, which did not affect the behavior. This study confirms the role of the fronto-subthalamic pathway in sequential working memory. Furthermore, it shows that D2 transmission can regulate sequential working memory by modulating the fronto-subthalamic pathway.

Dorsolateral Prefrontal Activation in Emotional Autobiographical Task in Depressed and Anxious College Students: An fNIRS Study.

The dorsolateral prefrontal cortex (dlPFC) is strongly associated with mood symptoms. This study used functional near-infrared spectroscopy (fNIRS) technology to explore the features of brain neural activity in the dlPFC of anxious and depressed college students, during an emotional autobiographical memory task, and to understand the differences in brain cognitive mechanisms caused by anxiety and depression. A simple random sampling method was used to test 440 college students at a university with a healthy control group (HC, 220 participants), a pure depression group (PD, 92 participants), and a pure anxiety group (PA, 128 participants). The average oxyhemoglobin in the dlPFC of the subjects during the emotional autobiographical memory task was collected by a 53-channel functional near-infrared spectroscopy imaging device. The activation of the left dlPFC (ch13) in the pure depression group was significantly higher than in the pure anxiety group. The activation of the right dlPFC (ch48) was significantly higher under positive emotions than under negative emotions. The interaction between emotion valence and group was marginally significant, and the activation of the right dlPFC (ch41) in the pure depression group was significantly higher under positive emotion than in negative emotion. The activation of the pure depression group under positive emotions was significantly higher than that of the pure anxiety group. In comparison, the activation of the pure depression group under negative emotions was significantly lower than that of the healthy control group. The results of correlation analysis showed that the activation of the left dlPFC (ch13) was significantly negatively correlated with anxiety in positive emotions, but the activation of the right dlPFC (ch34, ch42) was significantly positively correlated with anxiety in positive and negative emotions. The right dlPFC was insensitive to positive emotions in college students with high-anxiety symptoms, whereas this region was insensitive to negative emotions in college students with high depressive symptoms, which might be one of the critical differences in the cognitive mechanisms of anxiety and depression. Furthermore, left and right dlPFC activation correlated differently with anxiety. The higher the anxiety level, the lower the activation on the left side, and the higher the activation on the right side. The results suggested that anxiety might reduce the function of the left dlPFC.

Neural circuitry involved in conditioned inhibition via safety signal learning is sensitive to trauma exposure

Exposure to trauma throughout the lifespan is prevalent and increases the likelihood for the development of mental health conditions such as anxiety and post-traumatic stress disorder (PTSD). Safety signal learning (SSL)––a form of conditioned inhibition that involves reducing fear via conditioned safety––has been shown to effectively attenuate fear responses among individuals with trauma exposure, but the association between trauma exposure and the neural mechanisms of SSL remains unknown. Adults with varied prior exposure to trauma completed a conditioned inhibition task during functional MRI scanning and collection of skin conductance response (SCR). Conditioned safety signals reduced psychophysiological reactivity (i.e., SCR) in the overall sample. Although exposure to a higher number of traumatic events was associated with elevated SCR across all task conditions, SCR did not differ between threat in the presence of conditioned safety (i.e., SSL) relative to threat alone in a trauma-related manner. At the neural level, however, higher levels of trauma exposure were associated with lower hippocampal, amygdala, and dorsolateral prefrontal cortical activation during SSL. These findings suggest that while conditioned safety signals can reduce fear in the presence of threat even among individuals exposed to higher degrees of trauma, the neural circuitry involved in SSL is in fact sensitive to trauma exposure. Future research investigating neural processes during SSL among individuals with PTSD or anxiety can further elucidate the ways in which SSL and its neural correlates may reduce fear and link trauma exposure with later mental health conditions.

Angiotensin II Regulates the Neural Expression of Subjective Fear in Humans: A Precision Pharmaco-Neuroimaging Approach

BackgroundRodent models and pharmacological neuroimaging studies in humans have been used to test novel pharmacological agents to reduce fear. However, these strategies are limited with respect to determining process-specific effects on the actual subjective experience of fear, which represents the key symptom that motivates patients to seek treatment. In this study, we used a novel precision pharmacological functional magnetic resonance imaging approach based on process-specific neuroaffective signatures to determine effects of the selective angiotensin II type 1 receptor (AT1R) antagonist losartan on the subjective experience of fear. MethodsIn a double-blind, placebo-controlled, randomized pharmacological functional magnetic resonance imaging design, healthy participants (N = 87) were administered 50 mg losartan or placebo before they underwent an oddball paradigm that included neutral, novel, and fear oddballs. Effects of losartan on brain activity and connectivity as well as on process-specific multivariate neural signatures were examined. ResultsAT1R blockade selectively reduced neurofunctional reactivity to fear-inducing visual oddballs in terms of attenuating dorsolateral prefrontal activity and amygdala-ventral anterior cingulate communication. Neurofunctional decoding further demonstrated fear-specific effects in that AT1R blockade reduced the neural expression of subjective fear but not of threat or nonspecific negative affect and did not influence reactivity to novel oddballs. ConclusionsThese results show a specific role of the AT1R in regulating the subjective fear experience and demonstrate the feasibility of a precision pharmacological functional magnetic resonance imaging approach to the affective characterization of novel receptor targets for fear in humans.

Evidence accumulation, not ‘self-control’, explains dorsolateral prefrontal activation during normative choice

What role do regions like the dorsolateral prefrontal cortex (dlPFC) play in normative behavior (e.g., generosity, healthy eating)? Some models suggest that dlPFC activation during normative choice reflects controlled inhibition or modulation of default hedonistic preferences. Here, we develop an alternative account, showing that evidence accumulation models predict trial-by-trial variation in dlPFC response across three fMRI paradigms and two self-control contexts (altruistic sacrifice and healthy eating). Using these models to simulate a variety of self-control dilemmas generated a novel prediction: although dlPFC activity might typically increase for norm-consistent choices, deliberate self-regulation focused on normative goals should decrease or even reverse this pattern (i.e., greater dlPFC response for hedonistic, self-interested choices). We confirmed these predictions in both altruistic and dietary choice contexts. Our results suggest that dlPFC response during normative choice may depend more on value-based evidence accumulation than inhibition of our baser instincts.

Shedding Light on the Effects of Orienteering Exercise on Spatial Memory Performance in College Students of Different Genders: An fNIRS Study.

Objective: To investigate the intervention effect of orienteering exercises on the spatial memory ability of college students of different genders and its underlying mechanism. Methods: Forty-eight college students were randomly screened into experimental and control groups, 12 each of male and female, by SBSOD scale. The effects of 12 weeks of orienteering exercises on the behavioral performance and brain activation patterns during the spatial memory tasks of college students of different genders were explored by behavioral tests and the fNIRS technique. Results: After the orienteering exercise intervention in the experimental group, the male students had significantly greater correct rates and significantly lower reaction times than the female students; left and right dorsolateral prefrontal activation was significantly reduced in the experimental group, and the male students had a significantly greater reduction in the left dorsolateral prefrontal than the female students. The degree of activation in the left and right dorsolateral prefrontals of the male students and the right dorsolateral prefrontals of the female students correlated significantly with behavioral performance, and the functional coupling between the brain regions showed an enhanced performance. Discussion: Orienteering exercises improve the spatial memory ability of college students, more significantly in male students. The degree of activation of different brain regions correlated with behavioral performance and showed some gender differences.

Differential neural sensitivity to social inclusion and exclusion in adolescents in foster care

ObjectivesAdolescents in foster care may exhibit differential patterns of brain functioning that contribute to their pervasive socioemotional challenges. However, there has been limited investigation of implicated neural processes, particularly in the social domain. Thus, the current study investigated neural responses to exclusionary and inclusionary peer interactions in adolescents in foster-care. MethodsParticipants comprised adolescents aged 11–18 years in foster care (N = 69) and a community sample (N = 69). They completed an fMRI adaptation of Cyberball, a virtual ball-throwing paradigm, that included periods of exclusion and over-inclusion. To investigate neural sensitivity to peer social experiences, we quantified neural responses that scaled with consecutive inclusionary and exclusionary interactions (using parametric modulators). ResultsRelative to the community sample, adolescents in foster care exhibited increasing response to consecutive exclusionary events in lateral prefrontal regions and decreasing response to consecutive inclusionary events in the intraparietal sulcus and temporo-occipital cortex. Further, exploratory analyses revealed that dorsolateral prefrontal activation to exclusion was related to externalizing problems, particularly in the foster care sample. ConclusionsFindings highlight greater neural sensitivity to exclusionary, and lesser sensitivity to inclusionary, peer interactions in adolescents in foster care. Engagement of prefrontal clusters may reflect greater salience and emotion regulatory processes during exclusion, while parietal and temporal clusters may reflect reduced attention and behavioural engagement during inclusion. Thus foster care involvement is associated with broad changes in neural responses during peer interactions, and further these potentially relate to externalizing problems that have been identified in this vulnerable population.

Neural and self-reported responses to antisocial news stories: Entertaining versus traditional news introduction

Recently, as entertainment programs have become more prevalent in the news media, there is a growing need to understand how entertainment appeal influences viewers' sociomoral evaluation of news content. We investigated neural and self-reported moral evaluation of antisocial news content in college students who viewed real-life news reports featuring moral violations inside a functional magnetic resonance imaging (fMRI) brain scanner. Each news report was preceded by a traditional or entertaining style of introduction. The behavioral results showed that antisocial severity was reduced for antisocial news content that was presented following entertaining news introductions versus traditional news introductions. The fMRI results showed that entertainment news introductions tax more cognitive control resources than traditional news introductions during news processing, as indicated by greater activation in the dorsolateral prefrontal region; however, they diminish moral saliency, as suggested by the reduced activation in the medial prefrontal region. We also found that greater dorsolateral prefrontal activation during the early phase of news reports was associated with more lenient moral acceptability ratings in the entertainment condition. Furthermore, reduced functional connectivity of the mentalizing brain network was observed in the entertainment condition when compared with the traditional condition. These results suggest that entertainment appeal may increase resource depletion, diminish moral sensitivity, and reduce functional integration of relevant social information during news processing, thus hindering viewers' moral scrutiny. This novel study contributes to a better understanding of how entertainment features influence viewers’ sociomoral evaluation of news stories.

Nucleus basalis stimulation enhances working memory by stabilizing stimulus representations in primate prefrontal cortical activity.

SUMMARYAcetylcholine plays a critical role in the neocortex. Cholinergic agonists and acetylcholinesterase inhibitors can enhance cognitive functioning, as does intermittent electrical stimulation of the cortical source of acetylcholine, the nucleus basalis (NB) of Meynert. Here we show in two male monkeys how NB stimulation affects working memory and alters its neural code. NB stimulation increases dorsolateral prefrontal activity during the delay period of spatial working memory tasks and broadens selectivity for stimuli but does not strengthen phasic responses to each neuron’s optimal visual stimulus. Paradoxically, despite this decrease in neuronal selectivity, performance improves in many task conditions, likely indicating increased delay period stability. Performance under NB stimulation does decline if distractors similar to the target are presented, consistent with reduced prefrontal selectivity. Our results indicate that stimulation of the cholinergic forebrain increases prefrontal neural activity, and this neuromodulatory tone can improve cognitive performance, subject to a stability-accuracy tradeoff.