Left Inferior Prefrontal Cortex Research Articles

Affective dysfunction mediates the link between neuroimmune markers and the default mode network functional connectivity, and the somatic symptoms in somatic symptom disorder

ObjectiveSomatic symptom disorder (SSD) is characterized by physical symptoms and associated functional impairments that are often comorbid with depression and anxiety disorders. In this study, we explored relationships between affective symptoms and the functional connectivity of the default mode network (DMN) in SSD patients, as well as the impact of peripheral inflammation. We employed mediation analyses to investigate the potential pathways between these factors. MethodsWe recruited a total of 119 individuals (74 unmedicated SSD patients and 45 healthy controls), who were subjected to comprehensive psychiatric and clinical evaluations, blood tests, and resting-state functional magnetic resonance imaging scanning. We assessed neuroimmune markers (interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), tryptophan, serotonin, and 5-hydroxyindoleacetic acid (5-HIAA)), clinical indicators of somatic symptoms, depression, anxiety, anger, alexithymia, and functional connectivity (FC) within the DMN regions. Data were analyzed using correlation and mediation analysis, with a focus on exploring potential relations between clinical symptoms, blood indices, and DMN FCs. ResultsPatients with SSD had higher clinical scores as well as IL-6 and TNF-α levels compared with those in the control group (P < 0.05). The SSD group exhibited lower FC strength between the left inferior parietal lobule and left prefrontal cortex (Pfalse discovery rate (FDR) < 0.05). Exploratory correlation analysis revealed that somatic symptom scores were positively correlated with affective symptom scores, negatively correlated with the FC strength between the intra prefrontal cortex regions, and correlated with levels of IL-6, TNF- α, and tryptophan (uncorrected P < 0.01). Mediation analysis showed that levels of anxiety and trait anger significantly mediated the relations between DMN FC strength and somatic symptoms. In addition, the DMN FC mediated the level of trait anger with respect to somatic symptoms (all PFDR < 0.05). The levels of depression and trait anger exhibited significant mediating effects as suppressors of the relations between the level of 5-HIAA and somatic symptom score (all PFDR < 0.05). Further, the level of 5-HIAA had a mediating effect as a suppressor on the relation between DMN FC and state anger. Meanwhile, the levels of hs-CRP and IL-6 had full mediating effects as suppressors when explaining the relations of DMN FC strengths with the level of depression (all PFDR < 0.05). The patterns of valid mediation pathways were different in the control group. ConclusionsAffective symptoms may indirectly mediate the associations between DMN connectivity, somatic symptoms, and neuroimmune markers. Inflammatory markers may also mediate the impact of DMN connectivity on affective symptoms. These results emphasize the importance of affective dysregulation in understanding the mechanisms of SSD and have potential implications for the development of tailored therapeutic approaches for SSD patients with affective symptoms. Furthermore, in SSD research using DMN FC or neuroimmune markers, considering and incorporating such mediating effects of affective symptoms suggests the possibility of more accurate prediction and explanation.

N°186 – Partially dissociative role of the left inferior frontal gyrus and left dorsolateral prefrontal cortex in reasoning

N°186 – Partially dissociative role of the left inferior frontal gyrus and left dorsolateral prefrontal cortex in reasoning

Using graph convolutional network to characterize individuals with major depressive disorder across multiple imaging sites.

SummaryBackgroundEstablishing objective and quantitative neuroimaging biomarkers at individual level can assist in early and accurate diagnosis of major depressive disorder (MDD). However, most previous studies using machine learning to identify MDD were based on small sample size and did not account for the brain connectome that is associated with the pathophysiology of MDD. Here, we addressed these limitations by applying graph convolutional network (GCN) in a large multi-site MDD dataset.MethodsResting-state functional MRI scans of 1586 participants (821 MDD vs. 765 controls) across 16 sites of Rest-meta-MDD consortium were collected. GCN model was trained with individual whole-brain functional network to identify MDD patients from controls, characterize the most salient regions contributing to classification, and explore the relationship between topological characteristics of salient regions and clinical measures.FindingsGCN achieved an accuracy of 81·5% (95%CI: 80·5–82·5%, AUC: 0·865), which was higher than other common machine learning classifiers. The most salient regions contributing to classification were primarily identified within the default mode, fronto-parietal, and cingulo-opercular networks. Nodal topologies of the left inferior parietal lobule and left dorsolateral prefrontal cortex were associated with depressive severity and illness duration, respectively.InterpretationThese findings based on a large, multi-site dataset support the feasibility and effectiveness of GCN in characterizing MDD, and also illustrate the potential utility of GCN for enhancing understanding of the neurobiology of MDD by detecting clinically-relevant disruption in functional network topology.FundingThis study was supported by the National Natural Science Foundation of China (Grant Nos. 81621003, 82027808, 81820108018).

Altered Brain Functional Asymmetry in Patients With Major Depressive Disorder Related to Gastrointestinal Symptoms

ObjectiveDisrupted brain functional asymmetry has been reported in major depressive disorder (MDD). The comorbidity may be a crucial factor to this functional asymmetry. It is quite common that gastrointestinal (GI) symptoms are comorbid with MDD, but limited evidence focuses on the effect of GI comorbidity on the neuropathology of MDD from a functional lateralization perspective.MethodsResting-state functional magnetic resonance imaging was obtained in 28 healthy controls (HCs), 35 MDD patients with GI symptoms (GI-MDD patients), and 17 patients with MDD without GI symptoms (nGI-MDD patients). The parameter of asymmetry (PAS) was used to analyze the imaging data and evaluate the changes of functional asymmetry.ResultsThe GI-MDD patients showed increased PAS scores in the left inferior frontal gyrus (IFG) and superior medial prefrontal cortex (MPFC) and decreased PAS scores in the right postcentral gyrus in comparison with nGI-MDD patients. The PAS scores of the left IFG and left superior MPFC were correlated with the severity of GI problems and could be applied to distinguish GI-MDD patients from nGI-MDD patients with an accuracy, a sensitivity, and a specificity of 92.31, 100, and 76.47%, respectively. Furthermore, GI-MDD and nGI-MDD patients both displayed increased PAS scores in the PCC/precuneus.ConclusionsThis study revealed the influence of concomitant GI symptoms on functional asymmetry in MDD patients. Increased PAS scores of the left IFG and superior MPFC might represent an unbalanced regulation of brain over GI function and had the potential to be regarded as distinctive features related to functional GI symptoms in MDD.

Similar neural networks respond to coherence during comprehension and production of discourse.

When comprehending discourse, listeners engage default-mode regions associated with integrative semantic processing to construct a situation model of its content. We investigated how similar networks are engaged when we produce, as well as comprehend, discourse. During functional magnetic resonance imaging, participants spoke about a series of specific topics and listened to discourse on other topics. We tested how activation was predicted by natural fluctuations in the global coherence of the discourse, that is, the degree to which utterances conformed to the expected topic. The neural correlates of coherence were similar across speaking and listening, particularly in default-mode regions. This network showed greater activation when less coherent speech was heard or produced, reflecting updating of mental representations when discourse did not conform to the expected topic. In contrast, regions that exert control over semantic activation showed task-specific effects, correlating negatively with coherence during listening but not during production. Participants who showed greater activation in left inferior prefrontal cortex also produced more coherent discourse, suggesting a specific role for this region in goal-directed regulation of speech content. Results suggest strong correspondence of discourse representations during speaking and listening. However, they indicate that the semantic control network plays different roles in comprehension and production.

The neural basis of compound word processing revealed by varying semantic transparency and morphemic neighborhood size

This study investigated the neural basis of compound word processing by using fMRI and Chinese two-character compounds for lexical decision. Semantic transparency and morphemic neighborhood size were manipulated to augment the processing profile for measurement. The behavioral results disclosed a semantic transparency effect and its interaction with the neighborhood size, which supported existence of a mechanism for compound processing. The fMRI results located a neural substrate in the left inferior prefrontal cortex (BA 45) which reacted in an interactive manner to the two variables. While its activities were lower when their neighborhood size was larger for processing transparent compounds, its activities became higher when their neighborhood size was larger for processing opaque compounds. When scaling to a larger scope, the function of this mechanism fitted well with the theoretical account of unification function of the left inferior frontal cortex for language processing.

P 17. Multichannel tDCS on the left DLPFC in healthy children and adolescents: A behavioral study

Introduction. Transcranial direct current stimulation (tDCS) is a non-invasive method of modulating brain activity. Previous studies with common tDCS montages have shown that there are positive effects on the left inferior dorsolateral prefrontal cortex (lDLPFC) for both healthy and clinical population like improvement of the working memory. Nevertheless, there is still lack of clear guidelines and safety instructions, probably due to not specific enough simulation montages, especially when focusing on pediatric population. This study aims to investigate behavioral outcome of multichannel tDCS over the lDLPFC in healthy children and adolescents. Therefore, tDCS was coupled with a memory task, especially focusing on accuracy and reaction time changes. Methods. The study was approved by the Ethic Committee of the Faculty of Medicine of Kiel University. The study was conducted in a double-blinded, randomized, sham-controlled design. 28 healthy children and adolescents (Age range: 10–17 years, mean age = 14,18, SD = 2,23) were included in the analysis. In four separate sessions, they received multichannel 2 mA anodal or sham tDCS for 20 minutes over the left DLPFC before or during working memory task (2 back task). At the behavioral level response time and accuracy for N-back task were evaluated. Additionally, safety and tolerability of multichannel tDCS has been investigated by written questionnaires. For multichannel 2 mA tDCS over DLPFC we used a 6-channel solution (3.14 cm 2 circular electrodes; AF3 (897 μΑ), AF7 (284 μΑ), F3 (819 μΑ), Fp2 (−1000 μΑ) und T7 (−1000 μΑ)). Before, during and after stimulation 32 channel EEG was recorded in order to demonstrate neurophysiological changes. All materials required for the stimulations and EEG recording were obtained from Neuroelectrics (Barcelona, Spain). Results. All participants tolerated the stimulation well. Our preliminary behavioral results showed that there were no significant effects on accuracy (ACC) or reaction time (RT) compared tDCS to sham stimulation. There were also no significant effects on ACC and RT between online or offline stimulation and no significant effects in the interaction of these variables ( p > 0.05). Conclusion. In summary, our study demonstrates that multichannel tDCS over DLPFC with 2 mA intensity over 20 min is well tolerated, and thus may be used as an experimental and treatment method in the pediatric population. Based on preliminary behavioral data, we could not show any stimulation effect. In accordance to literature though, stimulation often shows bigger effects on clinical population rather than healthy participants. Possible reasons for null findings could be ceiling effects (e.g. Suitability of the Paradigm depending on age). Furthermore, individual differences like baseline activity, may have had an impact on stimulation effectivity. Additional EEG analysis may provide more specific insights into developmental aspects of working memory processing on the neural level.

Mapping the 'funny bone': neuroanatomical correlates of humor creativity in professional comedians.

What are the neuroanatomical correlates of expertise in a specific creative domain? Professional comedians, amateurs and controls underwent a T1 MRI anatomical scan. Measures of cortical surface area (gyrification and sulcal depth) and thickness were extracted for each participant. Compared to controls, professional comedians had a greater cortical surface area in the left inferior temporal gyrus, angular gyrus, precuneus and right medial prefrontal cortex. These regions have been previously implicated in abstract, divergent thinking and the default-mode network. The high degree of overlap between the regions of greater surface area in professional comedians with the regions showing greater activation in the same group during comedy improvisation in our previous work (particularly the temporal regions and angular gyrus) suggests that these regions may be specifically involved in humor creativity.

Anosognosia in Mild Cognitive Impairment: Lack of Awareness of Memory Difficulties Characterizes Prodromal Alzheimer's Disease.

While anosognosia is often present in Alzheimer's disease, the degree of awareness of cognitive difficulties in the earlier stages, such as Mild Cognitive Impairment (MCI), is less clear. Using a questionnaire and Feeling-of-Knowing tasks, the aims of this study were (1) to test the hypothesis that anosognosia is present specifically in prodromal AD stage in patients that, owing to a more severe AD neuropathology, will rapidly progress to overt dementia and (2) to assess the neural bases of self-awareness for memory functioning. A group of 44 patients with amnestic MCI and a group of 29 healthy older participants (CTRL) performed two Feeling-of-Knowing tasks (episodic and semantic FOK) and responded to the Functional Memory Scale (MARS), also completed by one of their relatives. They underwent FDG-PET and structural MRI. The participants were followed clinically for 4 years. At the end of follow-up, 23 patients with MCI developed Alzheimer's disease (converters) and 21 patients still presented symptoms of MCI without progression (non-converters). The analyses focused on the data from inclusion stratified according to clinical status 4 years later (converters, non-converters, CTRL). On the episodic FOK task, converters patients overestimated their ability to later recognize unrecalled words and they showed prediction accuracy (Hamann coefficient) at the level of chance. No difficulty was observed in any group with the semantic FOK task. On the MARS, converters patients had a higher anosognosia score than non-converters patients and CTRL, which did not differ from each other. Correlations between self-awareness scores and neuroimaging data using small volume correction analyses in a priori regions of interest in converters indicated that inaccurate episodic FOK judgments was related to changes in brain areas that might support interpretation of retrieved content for judging the likelihood of recognition. For the MARS, the association between anosognosia and decreased gray matter density of the left inferior prefrontal cortex in converters might indicate poor inhibition over outdated personal knowledge. In amnestic MCI, anosognosia could be an early sign of neurodegeneration in brain areas that would support control mechanisms over memory representations.

Retrieval of semantic knowledge in language pre-surgical mapping. A MEG study.

Retrieval of semantic knowledge in language pre-surgical mapping. A MEG study.

Imaging of semantic association judgements reveals areas of functional disruption and compensation remote from lesion in chronic Wernicke's aphasia

Imaging of semantic association judgements reveals areas of functional disruption and compensation remote from lesion in chronic Wernicke's aphasia

Electrical stimulation of the left IFG improves category fluency in primary progressive aphasia: far-transfer effects and their neural mechanisms

Electrical stimulation of the left IFG improves category fluency in primary progressive aphasia: far-transfer effects and their neural mechanisms

Changes in morning salivary melatonin correlate with prefrontal responses during working memory performance.

Humans demonstrate a circadian rhythm of melatonin production that closely tracks the daily light/dark cycle, with profound increases in circulating levels during the night-time and nearly nonexistent levels during daylight hours. Although melatonin is known to play a role in preparing the brain and body for sleep, its effects on cognition and brain function are not well understood. We hypothesized that declines in morning melatonin would be associated with increased functional activation within cortical regions involved in alertness, attention, and executive function. We measured the change in salivary melatonin from mid-morning to late-morning in 26 healthy young adults who were also exposed to a 30-min period of blue or amber light followed by functional MRI during a working memory task (N-back). Brain activation was regressed on the change in melatonin scores from the mid-morning to late-morning saliva samples and the role of light exposure was also assessed. Although overall melatonin levels did not change significantly over the morning at the group level, individual declines in salivary melatonin were associated with significant increases in activation within the left dorsomedial and right inferior lateral prefrontal cortex during the 2-back condition (P<0.05, cluster corrected). Medial prefrontal activation also correlated modestly with better vigilance performance during the 0-back (P<0.05), but not the 1-back or 2-back conditions. The light condition did not affect the outcomes. These findings suggest declining melatonin levels in the morning are associated with increased prefrontal cortex functioning and may play a role in the increased frontal activation that occurs following awakening.

Longer Fixation Times During Reading Are Correlated With Decreased Connectivity in Cognitive-Control Brain Regions During Rest in Children.

Dyslexia, or reading difficulty (RD), is characterized by slow, inaccurate reading and accompanied by deficit in executive functions (EF) and altered functional connectivity (FC) in the related networks (i.e., cingulo-opercular). Individuals with RD also present with altered oculomotor gaze patterns that include longer fixation times. The researchers examined the relationship between fixation times and FC of neural circuits related to EF during rest in children with RD and typical readers. Nineteen children participated in a 10-min resting-state scan. FC analysis was performed with the anterior cingulate cortex (ACC), related to cognitive control, chosen as a seed. Fixation time during word reading was used as a covariate of interest. Results demonstrated that FC between the ACC and the left inferior frontal cortex pars triangularis and left inferior prefrontal cortex during rest were negatively correlated with fixation times during word reading. These exploratory results support the critical role for the cingulo-opercular network, which is related to cognitive control, in the reading process, and likely also in reading impairment.

Task-based and resting-state fMRI reveal compensatory network changes following damage to left inferior frontal gyrus

Damage to left inferior prefrontal cortex in stroke aphasia is associated with semantic deficits reflecting poor control over conceptual retrieval, as opposed to loss of knowledge. However, little is known about how functional recruitment within the semantic network changes in patients with executive-semantic deficits. The current study acquired functional magnetic resonance imaging (fMRI) data from 14 patients with semantic aphasia, who had difficulty with flexible semantic retrieval following left prefrontal damage, and 16 healthy age-matched controls, allowing us to examine activation and connectivity in the semantic network. We examined neural activity while participants listened to spoken sentences that varied in their levels of lexical ambiguity and during rest. We found group differences in two regions thought to be good candidates for functional compensation: ventral anterior temporal lobe (vATL), which is strongly implicated in comprehension, and posterior middle temporal gyrus (pMTG), which is hypothesized to work together with left inferior prefrontal cortex to support controlled aspects of semantic retrieval. The patients recruited both of these sites more than controls in response to meaningful sentences. Subsequent analysis identified that, in control participants, the recruitment of pMTG to ambiguous sentences was inversely related to functional coupling between pMTG and anterior superior temporal gyrus (aSTG) at rest, while the patients showed the opposite pattern. Moreover, stronger connectivity between pMTG and aSTG in patients was associated with better performance on a test of verbal semantic association, suggesting that this temporal lobe connection supports comprehension in the face of damage to left inferior prefrontal cortex. These results characterize network changes in patients with executive-semantic deficits and converge with studies of healthy participants in providing evidence for a distributed system underpinning semantic control that includes pMTG in addition to left inferior prefrontal cortex.

Effects of subclinical depression, anxiety and somatization on brain structure in healthy subjects

BackgroundDimensional approaches in highly prevalent psychiatric disorders like depression or anxiety could lead to a better understanding of pathogenesis and advantages in early detection and prevention. In an effort to better understand associations of brain structural variation across the depression/anxiety spectra, we investigated minor subclinical symptoms in a non-clinical healthy population. MethodsWe studied 177 healthy subjects from the community, who underwent high-resolution T1-weighted 3T MRI and completed the symptom-checklist-90 (SCL-90-R). Using voxel-based morphometry (VBM) analysis with CAT12 software, we correlated SCL-90-R-subscales for depression, anxiety, and somatization with gray matter across the brain. ResultsSignificant positive gray matter correlations emerged across all three scales in different areas: the depression subscale correlated positively with gray matter in the Rolandic operculum, superior temporal gyrus (left) and postcentral gyrus (bilateral), the anxiety subscale correlated positively with middle temporal gyrus, Rolandic operculum, middle cingular gyrus and precuneus bilaterally, and the somatization subscale with left inferior prefrontal cortex. Somatization also showed negative correlations with cerebellar vermis and right supplementary motor area. LimitationsOur study is limited to VBM and does not include surface-based measures. It also only contains subjects with very small psychological distress by partly overlapping symptoms. ConclusionOur findings are consistent with a non-linear relationship between symptom severity and cortical volume in several brain areas involved in both emotion regulation as well as altered in clinically manifest depressive/anxiety disorders.

Neurofunctional Abnormalities during Sustained Attention in Severe Childhood Abuse.

Childhood maltreatment is associated with adverse affective and cognitive consequences including impaired emotion processing, inhibition and attention. However, the majority of functional magnetic resonance imaging (fMRI) studies in childhood maltreatment have examined emotion processing, while very few studies have tested the neurofunctional substrates of cognitive functions and none of attention. This study investigated the association between severe childhood abuse and fMRI brain activation during a parametric sustained attention task with a progressively increasing load of sustained attention in 21 medication-naïve, drug-free young people with a history of childhood abuse controlling for psychiatric comorbidities by including 19 psychiatric controls matched for psychiatric diagnoses, and 27 healthy controls. Behaviorally, the participants exposed to childhood abuse showed increased omission errors in the task which correlated positively trend-wise with the duration of their abuse. Neurofunctionally, the participants with a history of childhood abuse, but not the psychiatric controls, displayed significantly reduced activation relative to the healthy controls during the most challenging attention condition only in typical attention regions including left inferior and dorsolateral prefrontal cortex, insula and temporal areas. We therefore show for the first time that severe childhood abuse is associated with neurofunctional abnormalities in key ventral frontal-temporal sustained attention regions. The findings represent a first step towards the delineation of abuse-related neurofunctional abnormalities in sustained attention, which may help in the development of effective treatments for victims of childhood abuse.

Auditory Brain Development in Children with Hearing Loss – Part Two

Auditory Brain Development in Children with Hearing Loss – Part Two

Inferior Prefrontal Cortex Mediates the Relationship between Phosphatidylcholine and Executive Functions in Healthy, Older Adults.

Objectives: This study examines the neural mechanisms that mediate the relationship between phosphatidylcholine and executive functions in cognitively intact older adults. We hypothesized that higher plasma levels of phosphatidylcholine are associated with better performance on a particular component of the executive functions, namely cognitive flexibility, and that this relationship is mediated by gray matter structure of regions within the prefrontal cortex (PFC) that have been implicated in cognitive flexibility.Methods: We examined 72 cognitively intact adults between the ages of 65 and 75 in an observational, cross-sectional study to investigate the relationship between blood biomarkers of phosphatidylcholine, tests of cognitive flexibility (measured by the Delis–Kaplan Executive Function System Trail Making Test), and gray matter structure of regions within the PFC. A three-step mediation analysis was implemented using multivariate linear regressions and we controlled for age, sex, education, income, depression status, and body mass index.Results: The mediation analysis revealed that gray matter thickness of one region within the PFC, the left inferior PFC (Brodmann’s Area 45), mediates the relationship between phosphatidylcholine blood biomarkers and cognitive flexibility.Conclusion: These results suggest that particular nutrients may slow or prevent age-related cognitive decline by influencing specific structures within the brain. This report demonstrates a novel structural mediation between plasma phosphatidylcholine levels and cognitive flexibility. Future work should examine the potential mechanisms underlying this mediation, including phosphatidylcholine-dependent cell membrane integrity of the inferior PFC and phosphatidylcholine-dependent cholinergic projections to the inferior PFC.

Transcranial stimulation over the left inferior frontal gyrus increases false alarms in an associative memory task in older adults.

Transcranial direct current stimulation (tDCS) is a potential tool for alleviating various forms of cognitive decline, including memory loss, in older adults. However, past effects of tDCS on cognitive ability have been mixed. One important potential moderator of tDCS effects is the baseline level of cognitive performance. We tested the effects of tDCS on face-name associative memory in older adults, who suffer from performance deficits in this task relative to younger adults. Stimulation was applied to the left inferior prefrontal cortex during encoding of face-name pairs, and memory was assessed with both a recognition and recall task. Face-name memory performance was decreased with the use of tDCS. This result was driven by increased false alarms when recognizing rearranged face-name pairs. This result suggests that tDCS can lead to increased false alarm rates in recognition memory, and that effects of tDCS on a specific cognitive task may depend upon cognitive capability for that task.