Dysfunction Of Dorsolateral Prefrontal Cortex Research Articles

Kynurenic acid inflammatory signaling expands in primates and impairs prefrontal cortical cognition.

Cognitive deficits from dorsolateral prefrontal cortex (dlPFC) dysfunction are common in neuroinflammatory disorders, including long-COVID, schizophrenia and Alzheimer's disease, and have been correlated with kynurenine inflammatory signaling. Kynurenine is further metabolized to kynurenic acid (KYNA) in brain, where it blocks NMDA and α7-nicotinic receptors (nic-α7Rs). These receptors are essential for neurotransmission in dlPFC, suggesting that KYNA may cause higher cognitive deficits in these disorders. The current study found that KYNA and its synthetic enzyme, KAT II, have greatly expanded expression in primate dlPFC in both glia and neurons. Local application of KYNA onto dlPFC neurons markedly reduced the delay-related firing needed for working memory via actions at NMDA and nic-α7Rs, while inhibition of KAT II enhanced neuronal firing in aged macaques. Systemic administration of agents that reduce KYNA production similarly improved cognitive performance in aged monkeys, suggesting a therapeutic avenue for the treatment of cognitive deficits in neuroinflammatory disorders.

The neuropsychology and neuroanatomy of reduplicative paramnesia

Reduplicative paramnesia refers to the delusional belief that there are identical places in different locations. In this case–control study we investigated the clinical, phenomenological, neuropsychological and neuroanatomical data of eleven patients with reduplicative paramnesia and compared them against a control group of eleven patients with severe spatial disorientation without signs of reduplicative paramnesia.We show that most patients with reduplicative paramnesia report that a current place is reduplicated and/or relocated to an other familiar place. Patients with reduplicative paramnesia show a higher prevalence of deficits in the executive functions compared to the control patients, while mnestic and visuo-spatial deficits were both frequent in patients with reduplicative paramnesia and the control group. Patients with reduplicative paramnesia mostly suffer from right hemispheric lesions with a maximal overlap in the dorsolateral prefrontal cortex. Using lesion network mapping we show that lesions causing reduplicative paramnesia are connected to bilateral anterior insula and the right cingulate cortex.We argue that patients with reduplicative paramnesia fail to integrate the actual context with visuo-spatial memories and personal relevant emotional information due to a disruption of the neural network within the anterior temporal lobe, the cingulate cortex and the anterior insula. Also patients with reduplicative paramnesia are not able to resolve this conflict due to the lesion of the dorsolateral prefrontal cortex and executive dysfunction.

The Nature of Prefrontal Cortical GABA Neuron Alterations in Schizophrenia: Markedly Lower Somatostatin and Parvalbumin Gene Expression Without Missing Neurons.

In schizophrenia, somatostatin (SST) and parvalbumin (PV) mRNA levels are lower in the dorsolateral prefrontal cortex (DLPFC), but it remains unclear whether these findings reflect lower transcript levels per neuron, fewer neurons, or both. Distinguishing among these alternatives has implications for understanding the pathogenesis of, and developing new treatments for, DLPFC dysfunction in schizophrenia. To identify SST and PV neurons in postmortem human DLPFC, the authors used fluorescent in situ hybridization to label cells expressing two transcripts not altered in schizophrenia: vesicular GABA transporter (VGAT; a marker of all GABA neurons) and SOX6 (a marker of only SST and PV neurons). In cortical layers 2 and 4, where SST and PV neurons, respectively, are differentially enriched, levels of SST and PV mRNA per neuron and the relative densities of SST-, PV-, and VGAT/SOX6-positive neurons were quantified. In individuals with schizophrenia, mRNA levels per positive neuron were markedly and significantly lower for SST in both layers (effect sizes >1.48) and for PV only in layer 4 (effect size=1.14) relative to matched unaffected individuals. In contrast, the relative densities of all SST-, PV-, or VGAT/SOX6-positive neurons were unaltered in schizophrenia. Novel multiplex fluorescent in situ hybridization techniques permit definitive distinction between cellular levels of transcripts and the presence of neurons expressing those transcripts. In schizophrenia, pronounced SST and PV mRNA deficits are attributable to lower levels of each transcript per neuron, not fewer neurons, arguing against death or abnormal migration of these neurons. Instead, these neurons appear to be functionally altered and thus amenable to therapeutic interventions.

Dorsolateral prefrontal cortex dysfunction caused by a go/no-go task in children with attention-deficit hyperactivity disorder: A functional near-infrared spectroscopy study.

Children with attention-deficit hyperactivity disorder (ADHD) exhibit executive function deficits, which can be attributed to a dysfunction in the prefrontal region of the brain. Our study aims to evaluate the alteration of brain activity in children with ADHD during the administration of a go/no-go task using functional near-infrared spectroscopy (fNIRS) in comparison to a control group containing typically developing (TD) children. 32 children with ADHD and 31 of their TD peers were recruited and asked to perform a go/no-go task while undergoing measurements, with the aim of detecting changes in average oxygenated hemoglobin signaling (Δavg oxy-Hb) via fNIRS in the prefrontal lobe. fNIRS data showed significant differences between the left and right dorsolateral prefrontal cortices, with a lower Δavg oxy-Hb change in the ADHD group compared to the TD group. Our results indicate that brain dysfunction in children with ADHD is related to functional impairments in the dorsolateral prefrontal cortex. The go/no-go task paired with fNIRS represents a useful measurement tool to assess prefrontal brain dysfunction in children struggling with ADHD.

History and Future Directions of rTMS for Treatment of Depressive Disorders

History and Future Directions of rTMS for Treatment of Depressive Disorders

Left prefrontal transcranial direct-current stimulation reduces symptom-severity and acutely enhances working memory in schizophrenia

Recent studies indicated that left dorsolateral prefrontal cortex (DLPFC) transcranial direct current stimulation (tDCS) may improve clinical status and cognitive functioning in schizophrenia patients.The current study examined the effects of left prefrontal anodal tDCS on symptom-severity and on working memory performance in schizophrenia (SZ) patients. We conducted a double-blind, randomized sham-controlled parallel-group trial. Following baseline clinical and WM assessments, 19 chronic SZ patients were randomly assigned to receive 10 sessions of either active left dorsolateral prefrontal cortex (DLPFC) tDCS or sham DLPFC-tDCS across five consecutive days, followed by post-tDCS assessments every four weeks across 12 weeks. Active tDCS significantly alleviated symptom-severity versus baseline and versus sham tDCS. WM-performance improved versus baseline in the active tDCS group. Patients' symptom alleviation was maintained for four weeks after tDCS intervention. Patients' Post-tDCS WM scores were comparable to healthy controls' WM scores. The present findings highlight the benefits of left-prefrontal tDCS interventions and support the association between DLPFC dysfunction and symptom-severity in schizophrenia.

Prefrontal cortical alterations of glutamate and GABA neurotransmission in schizophrenia: Insights for rational biomarker development.

Certain cognitive deficits in schizophrenia, such as impaired working memory, are thought to reflect alterations in the neural circuitry of the dorsolateral prefrontal cortex (DLPFC). Gamma oscillations in the DLPFC appear to be a neural corollary of working memory function, and the power of these oscillations during working memory tasks is lower in individuals with schizophrenia. Thus, gamma oscillations represent a potentially useful biomarker to index dysfunction in the DLPFC circuitry responsible for working memory in schizophrenia. Postmortem studies, by identifying the cellular basis of DLPFC dysfunction, can help inform the utility of biomarker measures obtained in vivo. Given that gamma oscillations reflect network activity of excitatory pyramidal neurons and inhibitory GABA neurons, we review postmortem findings of alterations to both cell types in the DLPFC and discuss how these findings might inform future biomarker development and use.

Schizophrenia-related abnormalities in the triple network: a meta-analysis of working memory studies.

Previous meta-analyses found abnormal brain activations in schizophrenia patients compared with normal controls when performing working memory tasks. Although most studies focused on dysfunction of the working memory activation network in schizophrenia patients, deactivation abnormalities of the working memory in the default mode network have also been reported in schizophrenia but have received less attention. Our goal was to discover whether deactivation abnormalities can also be consistently found in schizophrenia during working memory tasks and, further, to consider both activation and deactivation abnormalities. Fifty-two English language peer-reviewed studies were included in this meta-analysis. Compared with normal controls, the schizophrenia patients showed activation dysfunction of the bilateral dorsolateral prefrontal cortex and posterior parietal cortex as well as the anterior insula, anterior cingulate cortex, and supplementary motor area, which are core nodes of the central executive and salience network. In addition to dysfunction of the activation networks, the patients showed deactivation abnormalities in the ventral medial prefrontal cortex and posterior cingulate cortex, which are core nodes of the default mode network. These results suggest that both activation and deactivation abnormalities exist in schizophrenia patients and that these abnormalities should both be considered when investigating the pathophysiological mechanism of schizophrenia.

Relationships between dietary nutrients intake and lipid levels with functional MRI dorsolateral prefrontal cortex activation.

BackgroundDorsolateral prefrontal cortex (DLPFC) is a key node in the cognitive control network that supports working memory. DLPFC dysfunction is related to cognitive impairment. It has been suggested that dietary components and high-density lipoprotein cholesterol (HDL-C) play a vital role in brain health and cognitive function.PurposeThis study aimed to investigate the relationships between dietary nutrient intake and lipid levels with functional MRI (fMRI) brain activation in DLPFC among older adults with mild cognitive impairment.Participants and methodsA total of 15 community-dwelling older adults with mild cognitive impairment, aged ≥60 years, participated in this cross-sectional study at selected senior citizen clubs in Klang Valley, Malaysia. The 7-day recall Diet History Questionnaire was used to assess participants’ dietary nutrient intake. Fasting blood samples were also collected for lipid profile assessment. All participants performed N-back (0- and 1-back) working memory tasks during fMRI scanning. DLPFC (Brodmann’s areas 9 and 46, and inferior, middle, and superior frontal gyrus) was identified as a region of interest for analysis.ResultsPositive associations were observed between dietary intake of energy, protein, cholesterol, vitamins B6 and B12, potassium, iron, phosphorus, magnesium, and HDL-C with DLPFC activation (P<0.05). Multivariate analysis showed that vitamin B6 intake, β=0.505, t (14)=3.29, P=0.023, and Digit Symbol score, β=0.413, t (14)=2.89, P=0.045; R2=0.748, were positively related to DLPFC activation.ConclusionIncreased vitamin B6 intake and cognitive processing speed were related to greater activation in the DLPFC region, which was responsible for working memory, executive function, attention, planning, and decision making. Further studies are needed to elucidate the mechanisms underlying the association.

Environmental dependency phenomena in schizophrenia: a pilot study

ABSTRACTIntroduction: Environmental dependency phenomena refer to the enslavement of patients’ performances under the characteristics of the tasks and were first described in case of prefrontal lobe damage. Two forms of environmental dependency, executive and social, may be dissociated, which involve respectively dorsolateral and orbital prefrontal cortex (PFC) dysfunction. Schizophrenia is widely considered to be caused by PFC dysfunction, but no study to date has addressed environmental dependency in this pathology.Methods: We compared patients (N = 17) and healthy controls (N = 28) on a task dedicated to the study of environmental dependency.Results: Our results demonstrate the presence of environmental dependency in schizophrenia. Each form of environmental dependency can be highlighted independently, as previously demonstrated by studies with prefrontal patients.Conclusions: These findings suggest specific prefrontal dysfunction for each subgroup of patients and demonstrate a dissociation between socio-cognitive and neurocognitive performance in schizophrenia. Additionally, we found relationships between symptomatology and environmental dependency. This pilot study supports the relevance of studying environmental dependency to highlight specific patterns of prefrontal disorders in schizophrenia, which may contribute to a better understanding of PFC dysfunction in schizophrenia.

Chapter 25 - Mapping pathologic circuitry in schizophrenia

Schizophrenia is a complex disorder lacking an effective treatment option for the pervasive and debilitating cognitive impairments experienced by patients. Working memory is a core cognitive function impaired in schizophrenia that depends upon activation of distributed neural network, including the circuitry of the dorsolateral prefrontal cortex (DLPFC). Accordingly, individuals diagnosed with schizophrenia show reduced DLPFC activation while performing working-memory tasks. This lower DLPFC activation appears to be an integral part of the disease pathophysiology, and not simply a reflection of poor performance. Thus, the cellular and circuitry alterations that underlie lower DLPFC neuronal activity in schizophrenia must be determined in order to identify appropriate therapeutic targets. Studies using human postmortem brain tissue provide a robust way to investigate and characterize these cellular and circuitry alterations at multiple levels of resolution, and such studies provide essential information that cannot be obtained either through in vivo studies in humans or through experimental animal models. Studies examining neuronal morphology, protein expression and localization, and transcript levels indicate that a microcircuit composed of excitatory pyramidal cells and inhibitory interneurons containing the calcium-binding protein parvalbumin is altered in the DLPFC of subjects with schizophrenia and likely contributes to DLPFC dysfunction.

Depression Symptoms in Chronic Left Hemisphere Stroke Are Related to Dorsolateral Prefrontal Cortex Damage.

Damage to the brain's mood regulation systems may contribute to poststroke depression. This study examines relationships between depression symptoms and psychosocial factors and then uses multivariate lesion-symptom mapping to localize depression symptoms in people with chronic left hemisphere stroke. Depression symptoms relate inversely to education and directly to physical disability. Damage in the left dorsolateral prefrontal cortex is associated with greater depression symptoms. These results demonstrate a neurological contribution to depression symptoms in chronic left hemisphere stroke and provide evidence of convergent biological mechanisms for poststroke depression symptoms and major depression with regard to left dorsolateral prefrontal cortex dysfunction.

Mechanisms of Working Memory Impairment in Schizophrenia

BackgroundThe neural correlates of working memory (WM) impairment in schizophrenia remain a key puzzle in understanding the cognitive deficits and dysfunction of dorsolateral prefrontal cortex observed in this disorder. We sought to determine whether patients with schizophrenia exhibit an alteration in the inverted-U relationship between WM load and activation that we recently observed in healthy individuals and whether this could account for WM deficits in this population. MethodsMedicated (n = 30) and unmedicated (n = 21) patients with schizophrenia and healthy control subjects (n = 45) performed the self-ordered WM task during functional magnetic resonance imaging. We identified regions exhibiting an altered fit to an inverted-U relationship between WM load and activation that were also predictive of WM performance. ResultsA blunted inverted-U response was observed in left dorsolateral prefrontal cortex in patients and was associated with behavioral deficits in WM capacity. In addition, suppression of medial prefrontal cortex during WM was reduced in patients and was associated with poorer WM capacity in patients. Finally, activation of visual cortex in the cuneus was elevated in patients and associated with improved WM capacity. Together, these findings explained 55% of the interindividual variance in WM capacity when combined with diagnostic and medication status, which alone accounted for only 22% of the variance in WM capacity. ConclusionsThese findings identify a novel biomarker and putative mechanism of WM deficits in patients with schizophrenia, a reduction or flattening of the inverted-U relationship between activation and WM load observed in healthy individuals in left dorsolateral prefrontal cortex.

Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia

Alterations in cortical parvalbumin (PV)-containing neurons, including a reduced density of detectable neurons and lower PV levels, have frequently been reported in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia subjects. Most PV neurons are surrounded by perineuronal nets (PNNs) and the density of PNNs, as detected by Wisteria floribunda agglutinin (WFA) labeling, has been reported to be lower in schizophrenia. However, the nature of these PNN alterations, and their relationship to disease-related changes in PV neurons, has not been assessed. Using confocal microscopy, we quantified the densities and fluorescence intensities of PV neurons and PNNs labeled with WFA or immunoreactive for the major PNN protein, aggrecan, in the DLPFC from schizophrenia and matched comparison subjects. In schizophrenia, the densities of PV cells and of PNNs were not altered; however, the fluorescence intensities of PV immunoreactivity in cell bodies and of WFA labeling and aggrecan immunoreactivity in individual PNNs around PV cells were lower. These findings indicate that the normal complements of PV cells and PNNs are preserved in schizophrenia, but the levels of PV protein and of individual PNN components, especially the carbohydrate moieties on proteoglycans to which WFA binds, are lower. Given the roles of PV neurons in regulating DLPFC microcircuits and of PNNs in regulating PV cellular physiology, the identified alterations in PV neurons and their PNNs could contribute to DLPFC dysfunction in schizophrenia.

Neurophysiological, psychological and behavioural correlates of rTMS treatment in alcohol dependence

BackgroundAddiction is associated with dorso-lateral prefrontal cortex (DLPFC) dysfunction and altered brain-oscillations. High frequency repetitive transcranial magnetic stimulation (HFrTMS) over DLPFC reportedly reduces drug craving. Its effects on neuropsychological, behavioural and neurophysiological are unclear. MethodsWe assessed psychological, behavioural and neurophysiological effects of 4 sessions of 10-min adjunctive HFrTMS over the left DLPFC during two weeks during a residential programme for alcohol detoxification. Participants were randomized to active HFrTMS (10Hz, 100% motor threshold) or sham. Immediately before the first and after the last session, 32-channels EEG was recorded and alcohol craving Visual Analogue Scale, Symptom Check List-90-R, Numeric Stroop task and Go/No-go task administered. Tests were repeated at 1-month follow-up. Results17 subjects (mean age 44.7 years, 4 F) were assessed. Active rTMS subjects performed better at Stroop test at end of treatment (p=0.036) and follow up (p=0.004) and at Go-NoGo at end of treatment (p=0.05) and follow up (p=0.015). Depressive symptoms decreased at end of active treatment (p=0.036). Active-TMS showed an overall decrease of fast EEG frequencies after treatment compared to sham (p=0.026). No significant modifications over time or group emerged for craving and number of drinks at follow up. Conclusion4 HFrTMS sessions over two weeks on the left DLPFC can improve inhibitory control task and selective attention and reduce depressive symptoms. An overall reduction of faster EEG frequencies was observed. Nonetheless, this schedule is ineffective in reducing craving and alcohol intake.

Distinctive transcriptome alterations of prefrontal pyramidal neurons in schizophrenia and schizoaffective disorder.

Schizophrenia is associated with alterations in working memory that reflect dysfunction of dorsolateral prefrontal cortex (DLPFC) circuitry. Working memory depends on the activity of excitatory pyramidal cells in DLPFC layer 3, and to a lesser extent in layer 5. Although many studies have profiled gene expression in DLPFC gray matter in schizophrenia, little is known about cell type-specific transcript expression in these two populations of pyramidal cells. We hypothesized that interrogating gene expression specifically in DLPFC layer 3 or 5 pyramidal cells would reveal new and/or more robust schizophrenia-associated differences that would provide new insights into the nature of pyramidal cell dysfunction in the illness. We also sought to determine the impact of other variables, such as a diagnosis of schizoaffective disorder or medication use at time of death, on the patterns of gene expression in pyramidal neurons.Individual pyramidal cells in DLPFC layers 3 or 5 were captured by laser microdissection from 36 subjects with schizophrenia or schizoaffective disorder and matched normal comparison subjects. The mRNA from cell collections was subjected to transcriptome profiling by microarray followed by qPCR validation.Expression of genes involved in mitochondrial (MT) or ubiquitin-proteasome system (UPS) functions were markedly down-regulated in the patient group (p values for MT-related and UPS-related pathways were <10−7 and <10−5 respectively). MT-related gene alterations were more prominent in layer 3 pyramidal cells, whereas UPS-related gene alterations were more prominent in layer 5 pyramidal cells. Many of these alterations were not present, or found to a lesser degree, in samples of DLPFC gray matter from the same subjects, suggesting that they are pyramidal cell-specific. Furthermore, these findings principally reflected alterations in the schizophrenia subjects, were not present or present to a lesser degree in the schizoaffective disorder subjects (diagnosis of schizoaffective disorder was the most significant covariate, p<10−6), and were not attributable to factors frequently comorbid with schizophrenia.In summary, our findings reveal expression deficits in MT- and UPS-related genes specific to layer 3 and/or layer 5 pyramidal cells in the DLPFC of schizophrenia subjects. These cell type-specific transcriptome signatures are not characteristic of schizoaffective disorder, providing a potential molecular-cellular basis of differences in clinical phenotypes.

Short-Term Memory Impairment and Left Dorsolateral Prefrontal Cortex Dysfunction in the Orthostatic Position: A Single Case Study of Sinking Skin Flap Syndrome.

We describe the case of a patient who underwent craniectomy for hemorrhage of the left parietal lobe. Three weeks later, orthostatic memory impairment was detected as initial symptom of sinking skin flap syndrome (SSFS). This deficit was examined by neuropsychological testing and associated with a posture-dependent increase in the delta/alpha ratio at the F3 electrode, an electroencephalographic (EEG) index related to brain hypoperfusion. This EEG spectral alteration was detected in a brain region that includes the left dorsolateral prefrontal cortex, an area known to be involved in memory processing; therefore we hypothesize that SSFS induced reversible hypoperfusion of this otherwise undamaged cortical region. Neither of these findings was present after cranioplasty. This case suggests that SSFS may induce neuropsychological deficits potentially influencing outcome in the postacute phase and is further evidence supporting the clinical benefits of early cranioplasty.

Cognitive deterioration and functional compensation in ALS measured with fMRI using an inhibitory task.

Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of upper and lower motor neurons, resulting in progressive weakness and muscle atrophy. Recent studies suggest that nondemented ALS patients can show selective cognitive impairments, predominantly executive dysfunction, but little is known about the neural basis of these impairments. Oculomotor studies in ALS have described deficits in antisaccade execution, which requires the implementation of a task set that includes inhibition of automatic responses followed by generation of a voluntary action. It has been suggested that the dorsolateral prefrontal cortex (DLPFC) contributes in this process. Thus, we investigated whether deterioration of executive functions in ALS patients, such as the ability to implement flexible behavior during the antisaccade task, is related to DLPFC dysfunction. While undergoing an fMRI scan, 12 ALS patients and 12 age-matched controls performed an antisaccade task with concurrent eye tracking. We hypothesized that DLPFC deficits would appear during the antisaccade preparation stage, when the task set is being established. ALS patients made more antisaccade direction errors and showed significant reductions in DLPFC activation. In contrast, regions, such as supplementary eye fields and frontal eye fields, showed increased activation that was anticorrelated with the number of errors. The ALS group also showed reduced saccadic latencies that correlated with increased activation across the oculomotor saccade system. These findings suggest that ALS results in deficits in the inhibition of automatic responses that are related to impaired DLPFC activation. However, they also suggest that ALS patients undergo functional changes that partially compensate the neurological impairment.

Disorder-dissociated effects of fluoxetine on brain function of working memory in attention deficit hyperactivity disorder and autism spectrum disorder.

Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are often co-morbid and share performance and brain dysfunctions during working memory (WM). Serotonin agonists modulate WM and there is evidence of positive behavioural effects in both disorders. We therefore used functional magnetic resonance imaging (fMRI) to investigate shared and disorder-specific brain dysfunctions of WM in these disorders, and the effects of a single dose of the selective serotonin reuptake inhibitor (SSRI) fluoxetine. Age-matched boys with ADHD (n=17), ASD (n=17) and controls (n=22) were compared using fMRI during an N-back WM task. Patients were scanned twice, under either an acute dose of fluoxetine or placebo in a double-blind, placebo-controlled randomized design. Repeated-measures analyses within patients assessed drug effects on performance and brain function. To test for normalization effects of brain dysfunctions, patients under each drug condition were compared to controls. Under placebo, relative to controls, both ADHD and ASD boys shared underactivation in the right dorsolateral prefrontal cortex (DLPFC). Fluoxetine significantly normalized the DLPFC underactivation in ASD relative to controls whereas it increased posterior cingulate cortex (PCC) deactivation in ADHD relative to control boys. Within-patient analyses showed inverse effects of fluoxetine on PCC deactivation, which it enhanced in ADHD and decreased in ASD. The findings show that fluoxetine modulates brain activation during WM in a disorder-specific manner by normalizing task-positive DLPFC dysfunction in ASD boys and enhancing task-negative default mode network (DMN) deactivation in ADHD.

Dissociable patterns in the control of emotional interference in adults with attention-deficit/hyperactivity disorder (ADHD) and in adults with alcohol dependence.

ObjectivesTo effectively manage current task demands, attention must be focused on task-relevant information while task-irrelevant information is rejected. However, in everyday life, people must cope with emotions, which may interfere with actual task demands and may challenge functional attention allocation. Control of interfering emotions has been associated with the proper functioning of the dorsolateral prefrontal cortex (DLPFC). As DLPFC dysfunction is evident in subjects with ADHD and in subjects with alcohol dependence, the current study sought to examine the bottom-up effect of emotional distraction on task performance in both disorders.MethodsMale adults with ADHD (n = 22), male adults with alcohol dependence (n = 16), and healthy controls (n = 30) performed an emotional working memory task (n-back task). In the background of the task, we presented neutral and negative stimuli that varied in emotional saliency.ResultsIn both clinical groups, a working memory deficit was evident. Moreover, both clinical groups displayed deficient emotional interference control. The n-back performance of the controls was not affected by the emotional distractors, whereas that of subjects with ADHD deteriorated in the presence of low salient distractors, and that of alcoholics did not deteriorate until high salient distractors were presented. Subsequent to task performance, subjects with ADHD accurately recognized more distractors than did alcoholics and controls. In alcoholics, picture recognition accuracy was negatively associated with n-back performance, suggesting a functional association between the ability to suppress emotional distractors and successful task performance. In subjects with ADHD, performance accuracy was negatively associated with ADHD inattentive symptoms, suggesting that inattention contributes to the performance deficit.ConclusionsSubjects with ADHD and alcoholics both display an emotional interference control deficit, which is especially pronounced in subjects with ADHD. Beyond dysfunctional attention allocation processes, a more general attention deficit seems to contribute to the more pronounced performance deficit pattern in ADHD.